Long-term Intraocular Pressure Fluctuation and Progressive Visual Field Deterioration in Patients With Glaucoma and Low Intraocular Pressures After a Triple ProcedureHong, Samin;Seong, Gong Je;Hong, Young Jae
2007 Archives of Ophthalmology
doi: 10.1001/archopht.125.8.1010pmid: 17698746
Abstract Objective To evaluate the association of long-term intraocular pressure (IOP) fluctuation and visual field (VF) progression in patients with glaucoma and low IOP. Methods Four hundred eight eyes with IOPs below 18 mm Hg after a triple procedure (phacoemulsification, posterior chamber intraocular lens implantation, and trabeculectomy) were included in this study. Measurements of IOP and VF were taken for at least 3 years after surgery. Based on the SD in postoperative IOPs, the sample was split into 2 groups (group 1: SD ≤2; group 2: SD >2). Change in VF at each test location was defined as a change in threshold sensitivity of 1 dB per year or higher, with P≤.01; pointwise linear regression analysis was applied. Main Outcome Measures Intraocular pressure and VF progression. Results The groups showed no differences in IOPs through the follow-up period and in the VF defect score 3 months after surgery. After 13 years, more patients with progressive VF deterioration were detected in group 2 than in group 1. Conclusion Our results showed that larger long-term IOP fluctuation was associated with a progressive increase in the VF deterioration even though patients with glaucoma maintained their IOPs after the triple procedure. Application to Clinical Practice The SD of long-term IOP should be less than 2 in patients with glaucoma, even if their IOPs drop below 18 mm Hg. Trial Registration clinicaltrials.gov Identifier: LOCATOR="http://clinicaltrials.gov/show/NCT00428740">NCT00428740 Prevention of further visual field (VF) deterioration is a goal of glaucoma therapy. Previous studies reported that lowering intraocular pressure (IOP)slowed the advancement of VF damage in patients with glaucoma.1-9 However, even if the IOP can be substantially lowered, reduction of mean and peak IOP does not always prevent progressive VFdeterioration.10-12 Several studies have reported that diurnal IOP variation is a risk factor for glaucoma.13-15 However, we believe that long-term IOP fluctuation may play a significant role in VF deterioration in patients with glaucoma and low IOPs. Moreover, few reports appear in the literature regarding long-term IOP control and long-term progressive VF deterioration after a triple procedure (phacoemulsification, foldable posterior chamber intraocular lens implantation, and trabeculectomy).16,17 The aim of this study was to evaluate the association of long-term IOP fluctuation and progressive VF deterioration in patients with glaucoma and low IOPs after a triple procedure. Methods Subjects The patients who underwent triple procedure for primary open-angle glaucoma (POAG) or chronic primary angle-closure glaucoma (CPACG) at Severance Hospital,Yonsei University College of Medicine (Seoul, Korea), between January 1, 1990, and September 30, 2002, were retrospectively identified from a patient database. From the originalpatient sample, 408 eyes of 408 patients meeting the following criteria were selected for this study: (1) at least 3 years of follow-up; (2) IOP less than 18 mm Hg at eachpostoperative visit; (3) a minimum of 5 VF examinations; (4) a reference VF defect score of 16 or less; and (5) good reliability indices (fixation loss of <20%, false-positiveand false-negative rate of <15%). One eye of each patient was randomly selected for the study, even if both eyes satisfied the entry criteria. In addition, patients with any other significant ocular diseases or intraocular surgical histories, diseases that may affect VF, or diabetes mellitus were excluded. Surgical procedure All operations were performed by the same glaucoma specialist (Y.J.H.) with the patient under peribulbar anesthesia. In some cases, separate surgical sites were used for the phacoemulsification and trabeculectomy procedures, and in others a single site was used. In cases in which separate surgical sites were used, a fornix- or limbus-based conjunctival flap was created, and a rectangular half-thickness scleral flap measuring 4 × 4 mm was made. A continuous-tear capsulorrhexis was created, which was followed by hydrodissection and hydrodelineation. Phacoemulsification was accomplished through a corneal incision at a site separate from where the trabeculectomy was performed. Following implantation of a foldable posterior chamber intraocular lens, a sponge soaked in mitomycin, 0.04%, was applied under the scleral flap and subconjunctival space for 1 to 4 minutes (in cases of mitomycin application). After rinsing with isotonic sodium chloride solution, a trabeculectomy and peripheral iridectomy were performed. The scleral flap was closed with two to five 10-0 nylon sutures. The tenon and conjunctiva were sutured to be watertight. When a single surgery site was used, phacoemulsification was performed through a scleral tunnel beneath a fornix-based conjunctival flap, followed by a trabeculectomy in which the scleral tunnel was used to create the half-thickness scleral flap. Data collection and analysis Preoperative and postoperative data were collected retrospectively. Patient follow-up occurred on the first postoperative day, and then according to clinical needs thereafter. During these visits, best-corrected visual acuity (as determined using the standard Snellen chart), IOP (measured using the Goldmann applanation tonometer), anterior segment examination, and fundoscopic examination (including cup-disc ratio) were evaluated. Based on the SD value of the postoperative IOP, the sample was split into 2 groups (group 1: SD ≤2; group 2: SD >2). Postoperative VF tests were conducted with a Humphrey field analyzer II (Carl Zeiss Meditec Inc, Dublin, California) using the 30-2 Swedish interactive threshold algorithm standard strategy 3 months after surgery, and every 6 months thereafter. Scores of VF defect ranged from 0 (no defect) to 20 (advanced loss).18 A statistical software package (SPSS version 13.0; SPSS Inc, Chicago, Illinois) was used to perform pointwise linear regression analysis. Our method for definition of change vs stability at each test location, the 2-omitting regression algorithm, is described in detail elsewhere.19-21 In summary, a point was considered to be progressing or improving during the follow-up period only if the regression slope was significant (as defined later) in the following regression analyses: (1) after omitting the last threshold in a series and (2) after censoring the threshold before last for the same series. Regression slopes were considered significant if they measured −1 dB per year or less (progression) or 1 dB per year or more (improvement), with P≤.01. The change in a VF series was defined when at least 2 test locations belonging to the same glaucoma hemifield test cluster showed a change in the same direction.20,21 The VF defect score 3 months after surgery and at last follow-up and the proportion of patients with progressive VF loss were compared between the 2 groups. Results A total of 408 eyes of 408 patients with glaucoma (246 eyes with POAG and 162 eyes with CPACG) were included in this study. The mean ± SD postoperative follow-up period was 9.21 ± 3.64 years. Mean ± SD age at the time of surgery was 66.5 ± 10.3 years, and 126 patients (30.9%) were male. The mean ± SD best-corrected visual acuity was 0.67 ± 0.45 logMAR before surgery and 0.44 ± 0.55 logMAR at last follow-up. The mean ± SD numbers of postoperative topical antiglaucoma medications used were 1.35 ± 0.74 (group 1) and 1.40 ± 0.92 (group 2) in patients with POAG (P = .70), and 1.10 ± 0.77 (group 1) and 1.14 ± 0.84 (group 2) in patients with CPACG (P = .76). Preoperative and postoperative IOPs are shown in Table 1. The preoperative and postoperative IOP through the follow-up period did not differ between group 1 and group 2. Patients with POAG and CPACG showed a similar tendency. Table 2 shows the data on VFs at the 3-month postoperative follow-up and at last follow-up. In group 1, the VF defect score at both follow-up times showed no significant difference (P = .75 for POAG; P >.99 for CPACG). However, the VF defect score at last follow-up was significantly worse than that at the 3-month postoperative follow-up in group 2 (P<.001 for POAG and CPACG). The number of patients with progressive VF loss was significantly higher in group 2 (30.0% for POAG; 28.6% for CPACG) than in group 1 (9.7% for POAG; 10.0% for CPACG). A similar tendency was observed in patients with both types of glaucoma. Comment Long-term IOP fluctuation was significantly associated with the progression of glaucomatous VF loss, even in patients in whom IOPs were maintained at lowlevels after a triple procedure, an effective approach for patients with coexisting glaucoma and visually significant cataracts. This study included patients with POAG and CPACGwhose IOPs were maintained below 18 mm Hg after a triple procedure. The patients were split into 2 groups based on the SD value of the postoperative IOP (group 1: SD ≤2; group2: SD >2). The VF defect score was significantly worse in group 2 than in group 1. More patients in group 2 showed progression of VF loss during the postoperative follow-upperiod than in group 1. Similar tendencies were noted in patients with POAG and CPACG. The Advanced Glaucoma Intervention Study trial presented the relationship between IOP and progression in VF loss.3 Itincluded patients with POAG whose IOPs remained uncontrolled despite maximum-tolerated medical therapy. They performed an argon laser trabeculoplasty or trabeculectomy, with thegoal of maintaining an IOP lower than 18 mm Hg. Progression of VF was the primary study outcome. They classified eyes by the percentage of IOPs measuring lower than 18 mm Hgduring the first 6 years of the postoperative follow-up period. Those eyes in which the IOP was lower than 18 mm Hg at all study visits had minimal mean change in VF status for 6to 8 years. However, the other groups had substantial mean VF losses throughout the follow-up period. These differences were considered statistically significant beyond the first5 years of follow-up, and the effect was greater in the following years. The Advanced Glaucoma Intervention Study trial showed that the patients with POAG whose IOPs were maintained below 18 mm Hg did not experience a progressionof their VF damage. Despite that finding, however, some patients apparently continued to lose portions of their VF after filtering surgery, even at IOP that are always considered excellent (<18 mm Hg). In our study, group 1 patients, who had little long-term IOP fluctuation, had very little progression in VF loss during the 13 years after the triple procedure. Our results suggest that glaucomatous VF damage cannot be stabilized by only lowering the postoperative IOP but also requires reducing the long-term fluctuation of the postoperative IOP. If the diurnal variation of IOP were considered a risk factor for glaucomatous VF loss,13-15 thelong-term fluctuation of IOP may play a significant role in VF deterioration even in those patients with glaucoma who have always maintained low IOPs. However, our long-termretrospective study did not consider the diurnal variation. In conclusion, our study suggests that reducing the long-term fluctuation of IOP after glaucoma surgery is effective in slowing or preventing VF loss in patients with glaucoma. Correspondence: Young Jae Hong, MD, PhD, Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, 120-752 Korea ([email protected]). Submitted for Publication: August 30, 2006; final revision received December 3, 2006; accepted January 8, 2007. Financial Disclosure: None reported. References 1. Mao LKStewart WCShields MB Correlation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma. Am J Ophthalmol 1991;111 (1) 51- 55PubMedGoogle Scholar 2. Bergeå BBodin LSvedbergh B Impact of intraocular pressure regulation on visual fields in open-angle glaucoma. Ophthalmology 1999;106 (5) 997- 1005PubMedGoogle ScholarCrossref 3. The AGIS Investigators, The Advanced Glaucoma Intervention Study (AGIS), 7: the relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol 2000;130 (4) 429- 440PubMedGoogle ScholarCrossref 4. Heijl ALeske MCBengtsson BHyman LBengtsson BHussein MEarly Manifest Glaucoma Trial Group, Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120 (10) 1268- 1279PubMedGoogle ScholarCrossref 5. Brogliatti BRigault RPalanza L et al. Intraocular pressure and progression of visual field damage. Acta Ophthalmol Scand Suppl 2002;23626- 27PubMedGoogle ScholarCrossref 6. Leske MCHeijl AHussein MBengtsson BHyman LKomaroff EEarly Manifest Glaucoma Trial Group, Factors for glaucoma progression and the effect of treatment: the Early Manifest Glaucoma Trial. Arch Ophthalmol 2003;121 (1) 48- 56PubMedGoogle ScholarCrossref 7. Nouri-Mahdavi KHoffman DColeman AL et al. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology 2004;111 (9) 1627- 1635PubMedGoogle ScholarCrossref 8. Ehrnrooth PPuska PLehto ILaatikainen L Progression of visual field defects and visual loss in trabeculectomized eyes. Graefes Arch Clin Exp Ophthalmol 2005;243 (8) 741- 747PubMedGoogle ScholarCrossref 9. Nakagami TYamazaki YHayamizu F Prognostic factors for progression of visual field damage in patients with normal-tension glaucoma. Jpn J Ophthalmol 2006;50 (1) 38- 43PubMedGoogle ScholarCrossref 10. Kass MAKolker AEBecker B Prognostic factors in glaucomatous visual field loss. Arch Ophthalmol 1976;94 (8) 1274- 1276PubMedGoogle ScholarCrossref 11. Werner EBDrance SM Progression of glaucomatous field defects despite successful filtration. Can J Ophthalmol 1977;12 (4) 275- 280PubMedGoogle Scholar 12. Chauhan BCDrance SM The relationship between intraocular pressure and visual field progression in glaucoma. Graefes Arch Clin Exp Ophthalmol 1992;230 (6) 521- 526PubMedGoogle ScholarCrossref 13. Smith J Diurnal intraocular pressure: correlation to automated perimetry. Ophthalmology 1985;92 (7) 858- 861PubMedGoogle ScholarCrossref 14. Rota-Bartelink AMPitt AStory I Influence of diurnal variation on the intraocular pressure measurement of treated primary open-angle glaucoma during office hours. J Glaucoma 1996;5 (6) 410- 415PubMedGoogle ScholarCrossref 15. Saccà SCRolando MMarletta AMacri ACerqueti PCiurlo G Fluctuations of intraocular pressure during the day in open-angle glaucoma, normal-tension glaucoma and normal subjects. Ophthalmologica 1998;212 (2) 115- 119PubMedGoogle ScholarCrossref 16. Caporossi ACasprini FTosi GMBalestrazzi A Long-term results of combined 1-way phacoemulsification, intraocular lens implantation, and trabeculectomy. J Cataract Refract Surg 1999;25 (12) 1641- 1645PubMedGoogle ScholarCrossref 17. Kuroda SMizoguchi TTerauchi HNagata M Trabeculectomy combined with phacoemulsification and intraocular lens implantation. Semin Ophthalmol 2001;16 (3) 168- 171PubMedGoogle ScholarCrossref 18. Advanced Glaucoma Intervention Study, 2: visual field test scoring and reliability. Ophthalmology 1994;101 (8) 1445- 1455PubMedGoogle ScholarCrossref 19. Gardiner SKCrabb DP Examination of different pointwise linear regression methods for determining visual field progression. Invest Ophthalmol Vis Sci 2002;43 (5) 1400- 1407PubMedGoogle Scholar 20. Nouri-Mahdavi KCaprioli JColeman ALHoffman DGaasterland D Pointwise linear regression for evaluation of visual field outcomes and comparison with the advanced glaucoma intervention study methods. Arch Ophthalmol 2005;123 (2) 193- 199PubMedGoogle ScholarCrossref 21. Manassakorn ANouri-Mahdavi KKoucheki BLaw SKCaprioli J Pointwise linear regression analysis for detection of visual field progression with absolute versus corrected threshold sensitivities. Invest Ophthalmol Vis Sci 2006;47 (7) 2896- 2903PubMedGoogle ScholarCrossref
Chromosome 3 Analysis of Uveal Melanoma Using Fine-Needle Aspiration Biopsy at the Time of Plaque Radiotherapy in 140 Consecutive Cases: The Deborah Iverson, MD, LectureshipShields, Carol L.;Ganguly, Arupa;Materin, Miguel A.;Teixeira, Luiz;Mashayekhi, Arman;Swanson, Lori Ann;Marr, Brian P.;Shields, Jerry A.
2007 Archives of Ophthalmology
doi: 10.1001/archopht.125.8.1017pmid: 17698747
Abstract Objective To evaluate the feasibility of genetic testing of uveal melanoma using fine-needle aspiration biopsy (FNAB). Methods We reviewed the clinical records of all patients of the Ocular Oncology Service at Wills Eye Hospital with the diagnosis of uveal melanoma who underwent FNAB for genetic testing for chromosome 3 status between November 1, 2005, and March 1, 2006. The FNAB was performed immediately before plaque radiotherapy. The specimens underwent genetic analysis using DNA amplification and microsatellite assay to determine the presence of monosomy 3. Results A total of 140 eyes of 140 patients with uveal melanoma were sampled for chromosome 3 abnormalities using FNAB. Monosomy 3 was found in 44 cases (31%), disomy 3 was found in 76 cases (54%), and the genomic DNA yield was insufficient for genetic analysis in 20 cases (14%). Monosomy 3 was found in 16 of 61 small melanomas (26%), 24 of 67 medium melanomas (36%), and 4 of 12 large melanomas (33%). Adequate DNA was achieved in 97% of cases using a 27-gauge needle via the transvitreal tumor apex approach and in 75% of cases using a 30-gauge needle via the transscleral tumor base approach. Factors predictive of monosomy 3 included greater tumor basal dimension (P = .02) and greater distance from the optic disc (P = .02). Transient localized vitreous hemorrhage was found in 46% of eyes. No cases of diffuse vitreous hemorrhage, retinal detachment, or tumor recurrence along the biopsy tract were found. Conclusion We found that in most cases, FNAB provides adequate DNA for genetic analysis of uveal melanoma using microsatellite assay. The search for information on host, environmental, and genetic factors in uveal melanoma is well under way.1-12 Most of the published work on genetic testing of uveal melanoma has been performed on enucleated eyes in which a macroscopic sample of tumor was retrieved and studied using 1 of several techniques.3-10 However, enucleation is typically reserved for eyes with large tumors or those with circumpapillary tumor location, extrascleral tumor extension, secondary glaucoma, extensive retinal detachment, or poor visual prognosis. Currently, most eyes with uveal melanoma are managed with nonenucleation measures, such as plaque radiotherapy or charged particle radiotherapy. Tissue sampling for genetic testing in this cohort of patients has preliminarily been investigated in a series of 8 patients using transscleral fine-needle aspiration biopsy (FNAB) and fluorescence in situ hybridization (FISH).13 In this report, we evaluate the feasibility of genetic testing of uveal melanoma in a large cohort of 140 patients using microscopic sampling with FNAB immediately before plaque radiotherapy as well as DNA amplification and microsatellite assay. Methods We reviewed the clinical records of all patients of the Ocular Oncology Service at Wills Eye Hospital with the diagnosis of uveal melanoma who underwent FNAB for genetic testing for chromosome 3 status between November 1, 2005, and March 1, 2006. The Wills Eye Hospital institutional review board issued approval for this retrospective study. Data were gathered regarding clinical and genetic features of the tumor. The clinical data at initial examination included age, race (African American, Hispanic, Asian, or white), sex (female or male), affected eye (right or left), visual acuity, and symptoms. The tumor data included location (iris, ciliary body, or choroid), quadrant location (inferior, temporal, superior, nasal, or macula), anteroposterior location (macula, macula-equator, equator-ora, ciliary body, or iris), distance to the optic nerve (in millimeters), distance to the foveola (in millimeters), tumor basal dimension (in millimeters), tumor thickness (in millimeters by ultrasonography), subretinal fluid, orange pigment on the tumor surface, and previous documented tumor growth. The FNAB parameters included needle gauge, route (transscleral tumor base approach or transvitreal tumor apex approach), and fundus findings immediately after biopsy. Follow-up data included needle biopsy complications and recurrence at the site of biopsy. Fnab technique After obtaining informed patient consent for FNAB and genetic testing, tissue sampling was performed. A 3-mL blood sample in a purple-top EDTA tube at room temperature was obtained for isolation of constitutional DNA to be used as a control for comparison with microsatellite alleles detected in tumor DNA. The intraocular tumor sample was obtained at the time of plaque radiotherapy using retrobulbar anesthesia. After localization of the intraocular tumor and placement of intrascleral nylon sutures before securing the plaque, FNAB was performed (Figure 1). If the tumor was posterior to the equator of the eye, sampling was done via the trans pars plana transvitreal approach using a 27-gauge long needle on a connector tube and a 10-mL syringe.14,15 If the tumor was anterior to the equator of the eye, sampling was performed via the transscleral approach using a 30-gauge short needle on a connector tube and a 10-mL syringe. For the pars plana approach, the needle was entered along the meridian of the tumor 4 mm posterior to the limbus and directed into the extrafoveal apical portion of the tumor using indirect ophthalmoscopic guidance. For the transscleral approach, the tumor transillumination shadow was outlined on the sclera, and the needle was entered nearly perpendicular to the sclera at the tumor base, but with a slight bevel to make the wound self-sealing. The depth of penetration through the sclera depended on the measured tumor thickness, and the needle was aimed to sample the tumor base or midportion. In both approaches, the needle was held securely for the 10-mL syringe aspiration, and after needle withdrawal, pressure was applied to the globe puncture site with a cotton-tipped applicator. The microscopic cells were aspirated up the needle tip into the syringe using Hank solution and then flushed into a test tube and refrigerated until analysis by the genetic laboratory. The radioactive plaque was then applied to the eye using a standard technique, and the remainder of the procedure was completed. Genetic testing technique DNA extractions from blood and the FNAB samples were performed using commercially available isolation kits (Qiagen, Valencia, California) following manufacturer-suggested protocols. Polymerase chain reaction–based diagnosis for monosomy of chromosome 3 was performed by evaluating 10 polymorphic microsatellite markers on chromosome 3. These markers (ABI human genome mapping kit V2.5; Applied Biosystems, Foster City, California; http://www.appliedbiosystems.com) were used according to the manufacturer's instructions. The amplification products were analyzed on an ABI 3100 fragment analyzer, and the data analysis was performed with ABI GeneMapper software V3.0 (Applied Biosystems). Statistical analysis The clinical data were then analyzed with regard to the single outcome of presence of monosomy 3. The effect of each clinical variable on this outcome was analyzed using the Fisher exact test and logistic regression analysis. All variables were analyzed as discrete variables except for patient age, tumor base, tumor thickness, proximity to optic disc, and proximity to foveola, which were analyzed as continuous variables. The average age, tumor base, and tumor thickness in eyes with monosomy 3 vs disomy 3 were compared using an independent sample t test. The distributions of proximity to optic disc and proximity to foveola were compared using the Wilcoxon rank sum test. Statistical significance was assigned at P<.05. Results A total of 140 eyes of 140 patients with uveal melanoma were sampled for chromosome 3 abnormalities using FNAB. The patient and tumor findings are listed in Table 1. The median patient age at FNAB was 59 years (range, 24-93 years). A total of 139 patients were white (99%), 1 was Hispanic (<1%), 75 were male (54%), and 65 were female (46%). Preoperative visual acuity was 20/20 to 20/50 in 106 eyes (76%), 20/60 to 20/100 in 15 (11%), and 20/200 or worse in 19 (14%). Patient symptoms included blurred vision in 54 cases (39%), flashes or floaters in 17 (12%), metamorphopsia in 4 (3%), visual field loss in 10 (7%), color vision loss in 1 (<1%), and pain in 1 (<1%); 53 patients were asymptomatic (38%). The tumor was located predominantly in the choroid in 129 eyes (92%), ciliary body in 9 (6%), and iris in 2 (1%). The median largest tumor basal dimension measured with ophthalmoscopy, transillumination, and ultrasonography was 11 mm (mean, 10.6 mm; range, 3-20 mm), and the median tumor thickness according to ultrasonography was 3.9 mm (mean, 4.6 mm; range, 1.6-11.6 mm). The FNAB approach was transscleral at the site of the tumor into the tumor base in 73 cases (52%) and trans pars plana through the vitreous into the tumor apex in 67 cases (48%). Localized vitreous or subretinal blood at the biopsy site occurred immediately at the time of FNAB in 64 cases (46%) and resolved in all cases. In no case was there extensive intraocular hemorrhage or retinal detachment. There have been no cases of tumor recurrence at the needle biopsy site during a median of 8 months of follow-up. On the basis of tumor size, adequate yield was found in 49 of 61 small melanomas 3 mm thick or less (80%), in 62 of 67 medium melanomas between 3 and 8 mm thick (93%), and in 9 of 12 large melanomas 8 mm thick or more (75%). On the basis of the biopsy approach, adequate yield was found in 55 of 73 cases using the transscleral tumor base approach (75%) and 65 of 67 cases using the transvitreal tumor apex approach (97%). In all cases, the yield was microscopic and no cells were visible after aspiration with the exception of a large necrotic melanoma that yielded visible cellular debris, but because of extensive tumor necrosis, genetic studies were not possible. According to tumor size, monosomy 3 was found in 16 of 61 small melanomas (26%), 24 of 67 medium melanomas (36%), and 4 of 12 large melanomas (33%) (Figure 2 and Figure 3). On the basis of melanoma quadrant location, monosomy 3 was found in 7 of 13 tumors in the macular region (54%), 13 of 37 inferiorly (35%), 10 of 39 temporally (26%), 11 of 41 superiorly (27%), and 3 of 9 nasally (33%) (Table 1). According to the anteroposterior location of the melanoma, monosomy 3 was found in 7 of 13 tumors in the macular region (54%), 18 of 75 between the macular area and equator (24%), and 19 of 52 anterior to the equator (37%). Melanomas with monosomy 3 were a median of 4.0 mm from the foveola and 4.8 mm from the optic disc compared with those with disomy 3, which were a median of 3.0 mm from the foveola and 2.0 mm from the optic disc. Melanomas with monosomy 3 had a median basal diameter of 12 mm and a median thickness of 4.1 mm relative to those with disomy 3, which had a median basal diameter of 9.5 mm and a median thickness of 3.8 mm. Statistical analysis of the impact of each clinical variable on the single outcome of presence of monosomy 3 revealed a significant factor of greater basal dimension (odds ratio [OR], 1.17 per every 1-mm increase; P = .02) (Table 2). A trend toward presence of monosomy 3 was found with melanoma location anterior to the equator (OR, 4.54; P = .05) and within the macular region (OR, 3.18; P = .06) (compared with location at macula-equator). The median distance to optic disc was also found to be greater among those with monosomy 3 (P = .02; Wilcoxon rank sum test). The only complication of needle biopsy was localized transient vitreous hemorrhage at the tumor site in 64 eyes (46%). No cases of diffuse vitreous hemorrhage, retinal detachment, or tumor recurrence along the biopsy tract were found. Comment In 1990, Sisley et al5 in England published cytogenetic findings in 6 eyes with posterior uveal melanoma that showed monosomy 3 and 8q abnormalities (n = 3, 50%), chromosome 1 abnormality (n = 2, 33%), and chromosome 6 abnormality (n = 4, 67%). Two years later, Sisley et al6 analyzed 10 cases of uveal melanoma, and abnormalities of chromosomes 3, 6, and 8 were found in 5 cases (50%), chromosome 11 in 3 cases (30%), and chromosome 13 in 2 cases (20%). One tumor showed normal chromosome complement.6 In 1992, Horsthemke et al3 from Germany found loss of chromosome 3 alleles and multiplication of chromosome 8 alleles in uveal melanoma. Later, Prescher et al,4 from the same laboratory in Germany, published the prognostic implications of monosomy 3. They evaluated 54 patients who underwent enucleation for uveal melanoma and found monosomy 3 in 30 tumors (56%) and disomy 3 in 24 tumors (44%). By 3 years, 50% of the patients with monosomy 3 showed metastasis, whereas those with disomy 3 showed no metastatic disease. They concluded that monosomy 3 was a significant predictor of poor life prognosis. Similar findings were published in 1997 by Sisley et al,7 who discovered that monosomy 3 and additional copies of 8q statistically correlated with reduced patient survival. Three years later, they recognized that the amount of chromosomal abnormalities increased with increasing tumor size.8 More refined global gene expression patterns of uveal melanoma have been recently studied by Onken et al9 from the United States with fresh tumor samples obtained at the time of enucleation. They performed gene expression microarray analysis of 3075 significant genes in 25 enucleated eyes and found a distinctive separation of uveal melanoma, which they classified into 2 groups: class 1 (low-grade tumor) in 14 cases (56%) and class 2 (high-grade tumor) in 11 cases (44%). They found that class 2 tumors displayed down-regulated gene clusters on chromosome 3 and up-regulated clusters on chromosome 8q. These findings paralleled those of Sisley et al.7 Onken and colleagues further evaluated prognostic implications of the 2 classes and found that 95% of class 1 patients and 31% of class 2 patients were still alive at 8 years. These studies have been performed on fresh or paraffin-embedded tissue from eyes with melanoma after enucleation. Most of these studies have concluded that loss (monosomy) or down-regulation of chromosome 3 is the most important genetic factor related to prognosis of patients with uveal melanoma. In our analysis, we specifically focused on our ability to detect abnormalities of chromosome 3 with only an FNAB sample of the tumor and without a solid tissue sample. We were able to harvest adequate cells for analysis in 86% of cases, despite the fact that 61 of 140 tumors (44%) were 3 mm thick or less. Of the 20 cases in which genetic testing was not feasible, most tumors (12) were 3 mm thick or less. Of the 61 tumors that were 3 mm thick or less, genetic testing was feasible in 49 cases (80%). We suspect that failure to obtain adequate samples in 20 of our cases occurred because of 1 or more reasons, including small tumor size, small needle bore, tightly cohesive spindle cells not yielding to aspiration, necrotic cells without intact DNA, or loss of cells during transfer to the test tube. Of the 79 melanomas that measured more than 3 mm in thickness, adequate aspirate was obtained in 71 (90%). Naus et al16 validated that FISH analysis for uveal melanoma obtained by needle aspirate was reliable. They evaluated 40 eyes with uveal melanoma managed with enucleation. The mean tumor thickness was not evaluated, but the mean tumor diameter was 12.9 mm. After eye removal, a 25-gauge needle attached to a 10-mL syringe was inserted through the sclera into the tumor (transscleral approach), and cells were aspirated. In 39 of 40 eyes (98%), the FISH results of both chromosomes 3 and 8 could be analyzed. In 11 of 249 hybridizations (4%), discrepancies between the results of FNAB and the solid tumor were detected, but the overall weighted κ was 0.95, indicating good agreement between the FNAB and solid tumor results. Such discrepancies included mostly differences in the extent of chromosome or subclone abnormality on FNAB vs solid tumor analysis. These authors concluded that FNAB of uveal melanoma provided sufficient samples and was reliable for FISH analysis for chromosome 3 or 8 abnormalities. Sisley et al17 found similar accurate correlation of cytogenetic analysis in FNAB compared with solid tumor samples after enucleation in 10 cases. In our series of 140 consecutive cases, we used FNAB at the time of plaque radiotherapy rather than enucleation. In 67 cases (48%) the route was transvitreal using indirect ophthalmoscopy guidance with a 27-gauge needle, whereas in 73 cases (52%) the route was transscleral, directly through the sclera into the tumor base after transillumination using a 30-gauge needle. We preferred the small needle bore for the transscleral route to minimize possible tumor seeding through the site of scleral perforation. Results were obtained in 65 of 67 melanomas with the transvitreal route (97%) and 55 of 73 melanomas with the transscleral route (75%). Most uveal melanomas are currently treated with radiotherapy rather than enucleation, so genetic analysis of FNAB specimens provides a method of obtaining important genetic information on all patients with uveal melanoma. For eyes that undergo enucleation, fresh tissue can be harvested for the same genetic studies. In this analysis, greater basal dimension and greater distance from the optic disc were factors associated with monosomy 3. Monosomy 3 was noted in 26% of small melanomas, 36% of medium melanomas, and 33% of large melanomas. These findings could indicate that monosomy 3 mutation develops during tumor enlargement, but further analysis is warranted because this could reflect the difficulty in obtaining sufficient DNA in the smaller tumors. We used a microsatellite assay rather than FISH analysis for our FNAB specimens. The microsatellite assay is more refined and provides more information on chromosomal segments than does FISH analysis.18,19 The microsatellite-based assay is more robust from the inherent amplification of signals owing to polymerase chain reaction. The main advantage of this assay is ready adaptability of this test in any molecular biology laboratory. In contrast, FISH requires access to specialized microscopy and operator skills to correctly identify and quantify the signals that infer monosomy vs disomy. For microsatellite-based assays, the analysis software aids in making automated calls for loss of heterozygosity and infers monosomy vs disomy. A drawback of the latter assay might be the inability to distinguish between loss of heterozygosity and copy neutral amplification (loss of heterozygosity followed by reduplication of the lost allele). There has been only 1 report, to our knowledge, of an alternate form of chromosome 3 abnormality for uveal melanoma; thus, this concern is minimal.20 Percutaneous biopsy for prognostication via genetic testing has been found feasible and is used in other fields of medicine. Teixeira et al21 found that genomic analysis of prostate carcinoma obtained using ultrasonography-guided needle biopsy was possible in 34 of 35 cases with chromosome banding analysis and comparative genomic hybridization. They found aberrations in 69% of samples and noted that specific imbalances, such as 16q and 8q abnormalities, imparted a worse prognosis. Hoffer et al22 found that percutaneous needle biopsy in 21 children with neuroblastoma provided genetic prognostic information in 95%, DNA index (ploidy) in 90%, and N-myc gene expression in 70%. They concluded that percutaneous biopsy of advanced neuroblastoma was a feasible alternative to open biopsy. Our study has shown that FNAB of uveal melanoma for genetic information is possible, and this finding, combined with previous knowledge that needle biopsy specimens correlate with open biopsy specimens, suggests that this technique may be useful in assessing ultimate patient prognosis. Correspondence: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Hospital, 840 Walnut St, Philadelphia, PA 19107 ([email protected]). Submitted for Publication: October 5, 2006; final revision received December 12, 2006; accepted January 8, 2007. Author Contributions: Dr C. L. Shields has full access to all of the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Financial Disclosure: None reported. Funding/Support: Support was provided by the Retina Research Foundation Award of the Retina Society (Dr C. L. Shields), the Paul Kayser International Award of Merit in Retina Research (Dr J. A. Shields), a donation from Michael, Bruce, and Ellen Ratner (Drs J. A. Shields and C. L. Shields), Mellon Charitable Giving from the Martha W. Rogers Charitable Trust (Dr C. L. Shields), the LuEsther Mertz Retina Research Foundation (Dr C. L. Shields), and the Eye Tumor Research Foundation (Drs C. L. Shields and J. A. Shields). Previous Presentations: Presented in part at the Retina Research Foundation Award/Charles L. Schepens Lecture at the Combined Retina Society/Gonin Society Meeting; October 17, 2006; Capetown, South Africa (Dr C. L. Shields); and at the Deborah Iverson, MD Lectureship; November 1, 2006; Detroit, Michigan (Dr C. L. Shields). Additional Contributions: Statistical analysis was provided by Rishita Nutheti, MSc, International Centre for Advancement of Rural Eye Care, L.V. Prasad Eye Institute, Hyderabad, India. References 1. Weis EShah CPLajous M et al. The association between host susceptibility factors and uveal melanoma: a meta-analysis. Arch Ophthalmol 2006;124 (1) 54- 60PubMedGoogle ScholarCrossref 2. Shah CPWeis ELajous M et al. Intermittent and chronic ultraviolet light exposure and uveal melanoma: a meta-analysis. Ophthalmology 2005;112 (9) 1599- 1607PubMedGoogle ScholarCrossref 3. Horsthemke BPrescher GBornfeld N et al. Loss of chromosome 3 alleles and multiplication of chromosome 8 alleles in uveal melanoma. Genes Chromosomes Cancer 1992;4 (3) 217- 221PubMedGoogle ScholarCrossref 4. Prescher GBornfeld NHirche H et al. Prognostic implications of monosomy 3 in uveal melanoma. Lancet 1996;347 (9010) 1222- 1225PubMedGoogle ScholarCrossref 5. Sisley KRennie IGCottam DW et al. Cytogenetic findings in six posterior uveal melanomas: involvement of chromosomes 3, 6, and 8. Genes Chromosomes Cancer 1990;2 (3) 205- 209PubMedGoogle ScholarCrossref 6. Sisley KCottam DWRennie IG et al. Non-random abnormalities of chromosomes 3, 6, and 8 associated with posterior uveal melanoma. Genes Chromosomes Cancer 1992;5 (3) 197- 200PubMedGoogle ScholarCrossref 7. Sisley KRennie IGParsons MA et al. Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes Chromosomes Cancer 1997;19 (1) 22- 28PubMedGoogle ScholarCrossref 8. Sisley KParsons MAGarnham J et al. Association of specific chromosome alteration with tumour phenotype in posterior uveal melanoma. Br J Cancer 2000;82 (2) 330- 338PubMedGoogle ScholarCrossref 9. Onken MDWorley LAEhlers JPHarbour JW Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer Res 2004;64 (20) 7205- 7209PubMedGoogle ScholarCrossref 10. Hughes SDamato BEGiddings IHiscott PSHumphreys JHoulston RS Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3. Br J Cancer 2005;93 (10) 1191- 1196PubMedGoogle ScholarCrossref 11. Harbour JW Eye cancer: unique insights into oncogenesis: the Cogan Lecture. Invest Ophthalmol Vis Sci 2006;47 (5) 1736- 1745PubMedGoogle ScholarCrossref 12. Ehlers JPHarbour JW Molecular pathobiology of uveal melanoma. Int Ophthalmol Clin 2006;46 (1) 167- 180PubMedGoogle ScholarCrossref 13. Midena EBonaldi LParrozzani RTebaldi EBoccassini BVujosevic S In vivo detection of monosomy 3 in eyes with medium-sized uveal melanoma using transscleral fine needle aspiration biopsy. Eur J Ophthalmol 2006;16 (3) 422- 425PubMedGoogle Scholar 14. Augsburger JJShields JA Fine needle aspiration biopsy of solid intraocular tumors. Trans Pa Acad Ophthalmol Otolaryngol 1983;36 (2) 169- 172PubMedGoogle Scholar 15. Shields JAShields CLEhya HEagle RC JrDe Potter P Fine-needle aspiration biopsy of suspected intraocular tumors: the 1992 Urwick Lecture. Ophthalmology 1993;100 (11) 1677- 1684PubMedGoogle ScholarCrossref 16. Naus NCVerhoeven ACvan Drunen E et al. Detection of genetic prognostic markers in uveal melanoma biopsies using fluorescence in situ hybridization. Clin Cancer Res 2002;8 (2) 534- 539PubMedGoogle Scholar 17. Sisley KNichols CParsons MAFarr RRees RCRennie IG Clinical applications of chromosome analysis, from fine needle aspiration biopsies, of posterior uveal melanomas. Eye 1998;12 (pt 2) 203- 207PubMedGoogle ScholarCrossref 18. Cross NAGanesh AParpia MMurray AKRennie IGSisley K Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma. Eye 2006;20 (4) 476- 481PubMedGoogle ScholarCrossref 19. Häusler TStang AAnastassiou G et al. Loss of heterozygosity of 1p in uveal melanomas with monosomy 3. Int J Cancer 2005;116 (6) 909- 913PubMedGoogle ScholarCrossref 20. White VAMcNeil BKHorsman DE Acquired homozygosity (isodisomy) of chromosome 3 in uveal melanoma. Cancer Genet Cytogenet 1998;102 (1) 40- 45PubMedGoogle ScholarCrossref 21. Teixeira MRRibeiro FREknaes M et al. Genomic analysis of prostate carcinoma specimens obtained via ultrasound-guided needle biopsy may be of use in preoperative decision-making. Cancer 2004;101 (8) 1786- 1793PubMedGoogle ScholarCrossref 22. Hoffer FAChung TDiller L et al. Percutaneous biopsy for prognostic testing of neuroblastoma. Radiology 1996;200 (1) 213- 216PubMedGoogle Scholar
A look at the past . . .2007 Archives of Ophthalmology
doi: 10.1001/archopht.125.8.1024
Forty years ago it was difficult to find a prominent American ophthalmologist, or even a professor of ophthalmology, who had any real knowledge of such basic subjects asphysiologic optics or ophthalmic pathology. On the other hand, on the European Continent it was difficult to find any ophthalmologist who did not have suchknowledge. . . . And almost equally as widespread ignorance of physiologic optics also still prevails. Reference: Verhoeff FH.American ophthalmology during the past century. Arch Ophthalmol. 1948;39:460.
In Vivo Corneal High-Speed, Ultra–High-Resolution Optical Coherence TomographyChristopoulos, Viki;Kagemann, Larry;Wollstein, Gadi;Ishikawa, Hiroshi;Gabriele, Michelle L.;Wojtkowski, Maciej;Srinivasan, Vivek;Fujimoto, James G.;Duker, Jay S.;Dhaliwal, Deepinder K.;Schuman, Joel S.
2007 Archives of Ophthalmology
doi: 10.1001/archopht.125.8.1027pmid: 17698748
Abstract Objective To introduce new corneal high-speed, ultra–high-resolution optical coherence tomography (hsUHR-OCT) technology that improves the evaluation of complicated and uncomplicated cataract, corneal, and refractive surgical procedures. Design This case series included a control subject and 9 eyes of 8 patients who had undergone phacoemulsification, Descemet membrane stripping endokeratoplasty, corneal implantation for keratoconus, and complicated and uncomplicated laser in situ keratomileusis. These eyes underwent imaging using a prototype ophthalmic hsUHR-OCT system. All the scans were compared with conventional slitlamp biomicroscopy. Results Cross-sectional hsUHR-OCT imaging allowed in vivo differentiation of corneal layers and existing pathologic abnormalities at ultrahigh axial image resolution. These images illustrate the various incisional and refractive interfaces created with corneal procedures. Conclusions The magnified view of the cornea using hsUHR-OCT is helpful in conceptualizing and understanding basic and complicated clinical pathologic features; hsUHR-OCT has the potential to become a powerful, noninvasive clinical corneal imaging modality that can enhance surgical management. Trial Registration clinicaltrials.gov Identifier: LOCATOR="http://clinicaltrials.gov/show/NCT00343473">NCT00343473 The cornea is routinely examined using slitlamp biomicroscopy at magnifications of ×10 to ×25 (and up to ×100) in the clinic setting. Several in vivo imaging devices are currently available that provide high magnification and detailed information regarding the ocular anterior segment. Confocal scanning laser microscopy has good transverse resolution capability1 but does not provide a cross-sectional view of the cornea with contiguous reference to neighboring corneal layers. Ultrasound biomicroscopy has good anterior segment penetration (4 mm) but requires an immersion bath and has an overall axial resolution of 20 to 60 μm.2 Commercially available time-domain anterior segment optical coherence tomographs (OCTs) (Optical Coherence Pachymetry; Heidelberg Engineering, Heidelberg, Germany; and Visante; Carl Zeiss Meditec Inc, Dublin, California) allow noncontact viewing of the cornea.3,4 Both OCT devices use a 1310-nm light source, resulting in an axial resolution of 11 and 18 μm, respectively.3,4 This wavelength allows better penetration into anterior structures, revealing structures internal to the sclera, including the angle. The latest iteration of OCT technology uses Fourier domain (spectral) signal analysis. This OCT version acquires images with an axial resolution of 3.4 μm and increases scanning speed to 24 000 A-scans per second compared with the 2000 A-scans per second with the commercially available technology.3 The diagnostic benefits of high-speed, ultra–high-resolution OCT (hsUHR-OCT) in glaucoma5 and in the retina6 have been reported. The aim of this hsUHR-OCT imaging case series is to examine the utility of hsUHR-OCT in the management of corneal surgical patients. Methods Participants Data on a variety of corneal abnormalities were retrospectively collected from a prospective study of hsUHR-OCT evaluation. All the participants underwent comprehensive anterior segment ocular examination by cornea specialists that defined the clinical diagnosis. Qualified individuals had good-quality corneal photographs and hsUHR-OCT scans acquired at the same visit. The study was approved by the University of Pittsburgh institutional review board/ethics committee and adhered to the Declaration of Helsinki and Health Insurance Portability and Accountability Act regulations. Informed consent was obtained from all of the participants. Instrumentation All of the participants underwent digital corneal photography using a camera (Nikon D1X; Nikon Corp, Tokyo, Japan) mounted on a slitlamp (Topcon 8Z; Topcon Medical Systems Inc, Paramus, New Jersey). Detailed information on the hsUHR-OCT device has previously been published.7,8 Briefly, anterior segment hsUHR-OCT was based on Fourier domain (spectral) OCT technology. Infrared light is focused on the cornea using a condensing lens, and the back-reflected light from the cornea creates an interference pattern with light returning from a stationary reference arm. These interference data points are measured by means of low-coherence interferometry at a fast rate to yield high-resolution, cross-sectional tomographic corneal images. For this study, a prototype device of anterior segment hsUHR-OCT was used with a broadband (mean ± SD) 840 ± 50-nm super-luminescent diode laser that was projected onto the cornea at a distance of 25 mm. The optical power scanning across the eye was 750 μW, within the American National Standards Institute maximum permissible exposure limit for continuous exposure at that wavelength.9 The sample arm (camera head) was mounted on a standard slitlamp stand. Light reflected from the cornea was coupled with light from the reference arm, and the interference pattern was quantified by a spectrometer equipped with a linear charge-coupled device camera. The spectrogram was analyzed using a computer with advanced signal processing software and hardware. Two scan patterns were used in the study. Raster scans of the cornea were acquired by an experienced operator (L.K.) and contained 180 consecutive frames covering a volume of 3 × 3 × 1.4 mm. Each frame contained 501 A-scan lines, and each A-scan contained 1024 points sampling reflectance in a 1.4-mm-thick window. Total acquisition time for raster scans was 3.8 seconds per scan. The second scan pattern consisted of 3 line scans, 2 vertical and 1 horizontal. Each 3-mm line scan contained 8000 A-scans, and the total scan time for all 3 line scans was 1 second. Anterior segment imaging using a commercially available device (Visante) was also performed in a control subject. Visante and hsUHR-OCT images were acquired at the same visit. A high-resolution scan was acquired using Visante that was constructed from 4 repeated line scans, each with 512 A-scans, to cover a 10 × 3-mm window. The high-resolution scan time was 0.5 seconds. Results Nine eyes of 8 patients who had undergone surgical cataract, corneal, or refractive procedures and a representative control subject were included in this case series. Case 1: control subject A healthy 45-year-old man with 20/20 uncorrected visual acuity had normal findings on clinical corneal examination, including keratometry, central corneal pachymetry, and corneal topography. Comparison of the conventional time-domain OCT (Visante) (Figure 1A) and hsUHR-OCT (Figure 1B) images showed a markedly enhanced view of the corneal structure and delineation of the various layers in the hsUHR-OCT image. This hsUHR-OCT image was used as a reference for interpreting the results of the other patients with corneal procedures or abnormalities. Three of the cornea's 5 individual layers were visualized as distinct entities: the epithelium, Bowman layer, and stroma. The Descemet membrane and the endothelial layer, for the most part, are seen as 1 complex. The centralmost aspect of the image shows more optical backscattered light than the adjacent cornea owing to the approximately tangential orientation of the tissue relative to the scanning beam. The central tear-epithelial interface has more reflectivity owing to the large difference in index of refraction between air and the tear film compared with differences between subsequent tissue layers. Case 2: uncomplicated and complicated laser in situ keratomileusis A 44-year-old man with best-corrected visual acuity of 20/15 OU who had undergone uncomplicated bilateral myopic laser in situ keratomileusis (LASIK) 3 years earlier sustained an injury during a hunting mishap that resulted in a thorn becoming embedded in his left cornea. The thorn was successfully removed, and the ensuing diffuse lamellar keratitis was resolved with medication. A few weeks later, a resultant epithelial ingrowth was removed surgically. Three weeks after the removal, a small iron foreign body from a welding accident lodged on the surface of the LASIK flap, inciting a second episode of diffuse lamellar keratitis (Figure 2A). The hsUHR-OCT image showed a highly reflective region underneath the overlying focal epithelial defect (Figure 2B). The adjacent LASIK interface was highly reflective owing to the inflammatory response (Figure 2C). Case 3: complicated lasik A 52-year-old man who had undergone bilateral myopic LASIK 5 years earlier returned for further myopic LASIK enhancement of his left eye. Five days after an uncomplicated procedure, the patient sustained eye trauma with resultant epithelial ingrowth (Figure 3A). The hsUHR-OCT image of the eye showed the resultant ingrowth as a highly reflective, well-circumscribed area in the stromal LASIK flap interface (Figure 3B). Eight weeks after surgical removal of the epithelial ingrowth, there was no further evidence of this finding either clinically or by means of hsUHR-OCT (Figure 3C and D). Case 4: lasik fluid cleft syndrome A 54-year-old woman had undergone uncomplicated LASIK for bilateral −4.00-diopter spherical myopia 4 months earlier. She had episodic, recurring diffuse corneal haze in her left eye (visual acuity, 20/60) that was thought to be diffuse lamellar keratitis (Figure 4A). Lifting and irrigation of the LASIK flap 2 months earlier had not resolved the problem. The patient was referred to the University of Pittsburgh Medical Center Eye Center for further evaluation. On slitlamp biomicroscopy (Figure 4B), there was diffuse corneal stromal haze and a subtle discontinuous fluid pocket at the level of the LASIK flap that was clearly observed on the hsUHR-OCT scan (Figure 4C). The finding of the fluid cleft between the LASIK flap and the stroma triggered a retrospective medical record review that revealed a discrepancy between the pre-LASIK pachymetry values of the 2 eyes (581 μm OD and 651 μm OS). The 70-μm difference in central corneal thickness between the patient's 2 eyes and the fluid cleft suggested that her persistent, recurring corneal stromal haze was primarily due to endothelial dysfunction after LASIK, manifesting as fluid cleft syndrome.10 Pre-LASIK and post-LASIK intraocular pressures were normal. She was administered a topical hyperosmotic agent and an aqueous suppressant to reduce endothelial stress, with moderate clearing of her corneal haze. Case 5: uncomplicated descemet stripping endokeratoplasty A 72-year-old woman experienced a reduction in visual acuity in her right eye secondary to Fuchs endothelial dystrophy. A Descemet stripping endokeratoplasty (DSEK) was performed (Figure 5A), and high slitlamp magnification showed a hyperreflective donor-host interface (Figure 5B). The hsUHR-OCT confirmed a well-delineated, highly reflective horizontal line representing the donor-host interface (Figure 5C). The patient's edematous anterior stroma appeared hyperreflective, possibly owing to edema and proximity to the entering light signal. The transplanted posterior graft (stroma–Descemet membrane–endothelial complex) was from an otherwise healthy 20-year-old cadaveric eye and appeared considerably less reflective in comparison. The donor Descemet membrane transplant was entirely adherent to the posterior corneal surface with the aid of an air bubble in the anterior chamber. Case 6: complex dsek An 81-year-old woman with Fuchs endothelial dystrophy underwent an otherwise uncomplicated DSEK, although an iridocorneal adhesion to a previous clear-corneal cataract wound was present temporally. On postoperative day 1, it was impossible to assess whether the transplant was fully adherent inferiorly on slitlamp examination because of the patient's dense corneal arcus (Figure 6A and B). The hsUHR-OCT image, unaffected by the dense corneal arcus, demonstrated the known iridocorneal adhesion and a hyporeflective space between the transplant interface, confirming that there was subtle nonadherence of the donor transplant inferiorly (Figure 6C). Case 7: keratoconus and corneal implants A 42-year-old man with bilateral keratoconus underwent corneal implantation (Intacs; Addition Technology Inc, Des Plaines, Illinois) (Figure 7A). The hsUHR-OCT obtained 6 weeks after corneal implant placement confirms the intended placement at two-thirds corneal thickness (Figure 7B). The highly reflective stroma adjacent to the corneal implant channels is secondary to distortion of normal stromal intralamellar architecture (stress lines), with resultant increased light scattering. Case 8: corneal ectasia A 59-year-old man had undergone radial keratotomy 14 years earlier. A subsequent LASIK procedure 7 years earlier for consecutive hyperopia ultimately resulted in corneal ectasia (Figure 8A). High, irregular astigmatism required either penetrating or deep anterior lamellar keratoplasty. The hsUHR-OCT was performed to ensure that a suggestive radial keratotomy scar was not actually full thickness, which would obviate the more desirable lamellar keratoplasty procedure (Figure 8B). The hsUHR-OCT revealed an intact Descemet membrane–endothelial complex. None of the radial keratotomy scars were found to be full thickness intraoperatively, and a deep lamellar keratoplasty was successfully performed. Case 9: descemet membrane detachment A 53-year-old man had 20/70 preoperative visual acuity in an eye with a long-standing traumatic cataract. He underwent phacoemulsification with posterior chamber intraocular lens implantation and capsular tension ring placement for zonular dehiscence. On the first postoperative day his vision was only hand motions, and slitlamp findings showed unexpected, dramatic 4+ microcystic corneal edema for which intensive topical corticosteroid treatment was initiated. On postoperative day 4 there was persistent microcystic corneal edema. He was referred to an experienced cornea/anterior segment surgeon who diagnosed possible endothelial failure and continued the intensive topical corticosteroid treatment with the addition of a hyperosmolar ointment. One month later his vision had improved to 20/70, but he had persistent central bullous corneal edema (Figure 9A). Although a small Descemet membrane detachment was noted nasally (Figure 9B), no obvious Descemet membrane abnormality was noted more centrally on slitlamp examination. A hsUHR-OCT image showed a bullous epithelium (Figure 9C) and a detached and missing Descemet membrane centrally (Figure 9D and E). This patient's topical corticosteroid treatment was reduced, and he was referred for a definitive DSEK. Comment In this study, we reported the hsUHR-OCT surgical corneal findings in cases in which the enhanced imaging capabilities provided by hsUHR-OCT affected clinical and surgical management compared with slitlamp examination alone. The hsUHR-OCT images confirmed slitlamp biomicroscopic findings and affected surgical and postoperative decision making. The cornea, on average, is 540 μm thick and is made up of 5 layers.11 Each layer reflects light differently according to variable indices of refraction. Findings from time-based corneal OCT images were found to be in good agreement with those of histologic sections.12 The hsUHR-OCT case images delineated 4 layers of the cornea and showed good correlation with well-known histologic features. Unlike the commercially available anterior segment OCT, hsUHR-OCT does not compensate for refraction at the surface of the cornea, so there may also be geometric errors at the anterior and posterior surfaces. Nevertheless, findings from these hsUHR-OCT cornea images are in good agreement with anatomical corneal norms and provide substantially improved detailed information compared with the commercially available time-domain OCT images (Figure 1). The epithelium (approximately 50 μm), Bowman layer (approximately 10-15 μm), stroma (approximately 460 μm), and Descemet membrane (approximately 10 μm) were easily identifiable using hsUHR-OCT, whereas the endothelium usually appeared as a complex with the Descemet membrane. The endothelium, 5 to 6 μm thick, approaches the image resolution of the prototype hsUHR-OCT, which makes it difficult to differentiate as a separate entity. These findings seem to agree with those of a study by Kaluzny et al8 that examined various corneal abnormalities using hsUHR-OCT. When the scanning beam is perpendicular to the tissue structures, reflectivity is very high. Tissue orientation combined with the large difference in refractive index between air and the tear film creates the high level of reflectivity observed centrally in the tear film.11 The varying nuclear to cytoplasmic ratio and shape of the superficial epithelial cells compared with the epithelial basal cells may also affect variable reflectivity in this layer. An increase in light reflectivity in the hsUHR-OCT images corresponded to all surgical and refractive corneal incisions, scarring, dense inflammation, corneal edema, ectopic epithelial cells, and fibrosis. All of the cases illustrated the highly reflective interfaces of LASIK, DSEK, and corneal implantation procedures. A decrease in light scattering or reflectivity was due to fluid in interface potential spaces, clear intrastromal appliances (corneal implants) (Figure 7B), bullous epithelial edema (Figure 9C), and shadowing. In the case of the interface fluid cleft syndrome, the fluid in the potential space appeared hyporeflective (Figure 4C). Although the finding of the fluid cleft could be viewed using the slitlamp, it was initially missed by an experienced refractive surgeon on multiple examinations. The hsUHR-OCT, which instigated retrospective pachymetric review, highlighted the importance of additional information provided by the device. If hsUHR-OCT had been performed early on, the patient most likely would not have undergone an unnecessary second procedure to lift the flap for presumed diffuse lamellar keratitis. The hsUHR-OCT in this case study provided excellent visualization of various surgical and refractive corneal interfaces. Confluent abnormalities in refractive corneal interfaces (eg, epithelial in-growth after LASIK trauma) were clearly delineated (Figure 3B). The high-resolution capability of hsUHR-OCT was an advantage in case 4, the LASIK interface cleft, where the subtle fluid cleft between the LASIK flap and the underlying stroma was visualized and could be monitored (Figure 4C). Monitoring the light-scattering properties of certain corneal conditions will be useful in assessing disease progression or regression.8 In case 6, hsUHR-OCT imaging guided postoperative management. Because of the nonadherence of the inferior DSEK transplant (Figure 6C), which was otherwise not easily visualized behind the dense corneal arcus senilis, the patient was instructed to remain in a supine, chin-up position for 1 more day. By staying flat longer, the remaining air bubble positioned in the anterior chamber resulted in complete adhesion of the transplant during the next 24 hours. Similarly, in case 9, clinical and slitlamp examination findings inferred corneal endothelial dysfunction. The hsUHR-OCT image revealed a small nasal Descemet membrane detachment and a larger, central missing Descemet membrane that were not detected clinically (Figure 9D and E). Although this prototype OCT technology has successfully captured high-quality corneal images, it does have limitations. Dense corneal opacities will result in shadowing of structures posterior to the lesion. In conclusion, hsUHR-OCT improves visualization of structures and their relationship to incisional and refractive corneal procedures. The hsUHR-OCT images of corneal abnormalities enhanced slitlamp biomicroscopic examination. Corneal hsUHR-OCT imaging can be useful in the preoperative and postoperative clinical treatment of patients undergoing corneal and refractive surgery. Correspondence: Gadi Wollstein, MD, UPMC Eye Center, Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St, Suite 827, Pittsburgh, PA 15213 ([email protected]). Submitted for Publication: September 29, 2006; final revision received January 24, 2007; accepted January 29, 2007. Author Contributions: Mr Kagemann had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Christopoulos and Mr Kagemann participated equally in the preparation of this article. Financial Disclosure: None reported. Funding/Support: Supported in part by grants RO1-EY013178-7, R01-EY011289-20, and P30-EY008098 from the National Institutes of Health; grants FA9550-040-1-0046 and FA9550-040-1-0011 from the Air Force Office of Scientific Research; grant BES-0522845 from the National Science Foundation; The Eye and Ear Foundation; and an unrestricted grant from Research to Prevent Blindness Inc. Role of the Sponsor: The sponsors did not participate in the study at any stage other than providing the funding. Previous Presentation: This study was presented in part at the Fourth Annual Meeting of the International Society for Imaging of the Eye; March 28, 2006; Fort Lauderdale, Florida. References 1. Masters BRThaer AA Real-time scanning slit confocal microscopy of the in vivo human cornea. Appl Opt 1994;33 (4) 695- 701Google ScholarCrossref 2. Hoerauf HWirbelauer CScholz C et al. Slit-lamp–adapted optical coherence tomography of the anterior segment. Graefes Arch Clin Exp Ophthalmol 2000;238 (1) 8- 18PubMedGoogle ScholarCrossref 3. Visante OCT. Dublin, California Carl Zeiss Meditec Inc 2006; Publication 000000-1376-265 4. Müller MHoerauf HGeerling G et al. Filtering bleb evaluation with slit-lamp–adapted 1310-nm optical coherence tomography. Curr Eye Res 2006;31 (11) 909- 915PubMedGoogle ScholarCrossref 5. Wollstein GPaunescu LAKo TH et al. Ultrahigh-resolution optical coherence tomography in glaucoma. Ophthalmology 2005;112 (2) 229- 237PubMedGoogle ScholarCrossref 6. Ko THFujimoto JGSchuman JS et al. Comparison of ultrahigh-and standard-resolution optical coherence tomography for imaging macular pathology. Ophthalmology 2005;112 (11) 1922- 1935PubMedGoogle ScholarCrossref 7. Bouma BETearney GJ Handbook of Optical Coherence Tomography. New York, NY Informa Healthcare 2001; 8. Kaluzny BJKaluzny JJSzkulmowska A et al. Spectral optical coherence tomography: a new imaging technique in contact lens practice. Ophthalmic Physiol Opt 2006;26 (2) 127- 132PubMedGoogle ScholarCrossref 9. Z136 Committee, Laser Institute of America, American National Standards Institute for Safe Use of Lasers. New York, NY American National Standards Institute 1993; 10. Wirbelauer CPham DT Imaging interface fluid after laser in situ keratomileusis with corneal optical coherence tomography. J Cataract Refract Surg 2005;31 (4) 853- 856PubMedGoogle ScholarCrossref 11. Maurice DM The structure and transparency of the cornea. J Physiol 1957;136 (2) 263- 268PubMedGoogle Scholar 12. Wirbelauer CWinkler JBastian GO et al. Histopathological correlation of corneal diseases with optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 2002;240 (9) 727- 734PubMedGoogle ScholarCrossref
Evaluation of the Relationship Between Ablation Diameter, Pupil Size, and Visual Function With Vision-Specific Quality-of-Life Measures After Laser In Situ KeratomileusisSchmidt, Gregory W.;Yoon, Michael;McGwin, Gerald;Lee, Paul P.;McLeod, Stephen D.
2007 Archives of Ophthalmology
doi: 10.1001/archopht.125.8.1037pmid: 17698749
Abstract Objective To evaluate the relationship between ablation diameter, pupil size, and visual function as measured by a vision-specific quality-of-life instrument after undergoing laser in situ keratomileusis. Methods Of 300 patients eligible for this study, 97 (32.3%) responded to a mailed study questionnaire, the National Eye Institute Refractive Error Quality of Life (RQL) Instrument. The RQL Instrument was administered in all 97 patients after laser in situ keratomileusis. Spearman correlation coefficients were calculated for the association between RQL subscale scores and characteristics including pupil diameter and uncorrected visual acuity. Results Positive correlations between larger mesopic and scotopic pupil diameter and higher RQL satisfaction scores (0.12 and 0.19, respectively) were not statistically significant at the P = .05 level. As uncorrected visual acuity in the better eye improved, patients reported significantly less worry (−0.22; P = .03), more satisfaction (−0.25; P = .01), clearer vision (−0.25; P = .01), and better far vision (−0.24; P = .02). Conclusion Larger pupil diameter is not significantly associated with postoperative satisfaction and visual function as measured with the RQL. Rather, postoperative uncorrected visual acuity is confirmed as a strong predictor of patient satisfaction after refractive surgery. Laser in situ keratomileusis (LASIK) is effective in treating a wide variety of refractive errors and has become the most commonly performed refractive procedure in the United States. There is, therefore, a need for greater understanding of the factors that directly affect visual function after this procedure. After LASIK, a subset of patients reported nighttime glare, halo, and vision disturbance,1-5 and these symptoms may be a source of less patient satisfaction.6 A difference of opinion exists among refractive surgeons. The role of pupil size in the appropriate selection of patients for refractive surgery insofar as risk of visual disturbances under low-light conditions remains controversial. The effect of increased spherical aberration after LASIK to treat myopia is thought to be partially dependent on pupil size as well as attempted correction. This is supported by clinical findings of increasing incidence of glare, halo, and disturbances in night vision with smaller ablation diameter7,8 as well as larger pupil size8,9 and attempted correction.10 Seiler et al11 described an increase in spherical aberration with pupil dilation in corneas that have undergone photorefractive keratectomy but not in healthy corneas, and O’Brart and colleagues7,12 showed that a pupil diameter greater than 7.0 mm and large corrections are associated with reports of large-diameter halo. Furthermore, Oliver et al13 calculated modulation transfer functions after photorefractive keratectomy and concluded that the contour change induced substantial optical aberrations, particularly for large-diameter pupils. Several recent articles, however, refute an association between pupil size and night vision disturbances.14-16 Most of the literature that has attempted to address this relationship has reported no demonstrable association. In a recent study of substantial sample size, not pupil size but attempted degree of spherical correction, optical zone, patient age, and postoperative spherical equivalent were major risk factors for glare and halo symptoms.14 It has been difficult to define pupil diameter and treatment zone dimensions that minimize the risk for subjective visual function compromise after surgery. This can be attributed in part to the difficulty in formally assessing subjective visual function in patients after surgical correction of refractive error. The National Eye Institute (NEI) has recognized the need to “study quality of life and functional status as perceived by the patient . . . to assess the full impact of a treatment or disease process.”17(p331) Though questionnaires to determine visual acuity have been developed to measure disease-specific18,19 and generic20 outcomes, few standardized questionnaires have been designed specifically for preoperative and postoperative use in patients undergoing surgery to correct refractive error. Vitale et al21 and Schein et al22 have developed an instrument specific to refractive error and its correction, the Refractive Status and Vision Profile, that enables detection of clinically relevant changes in functional status and quality of life after refractive surgery and shows promise in evaluating interventions for correction of refractive error. Another such tool that has recently been developed is the NEI Refractive Error Quality of Life (NEI-RQL) Instrument. Like the Refractive Status and Vision Profile, the NEI-RQL has been specifically designed to assess the subjective visual and functional effects of refractive error and its correction, with contact lenses, eyeglasses, or surgery. The NEI-RQL is accurate and sensitive in providing information about patient status that is not reflected by traditional clinical ophthalmic measures.23,24 This study retrospectively evaluated the relationship between pupil diameter and excimer laser treatment zone dimension as they relate to subjective outcomes self-reported on the NEI-RQL. We specifically examined the patients' perception of glare and halo symptoms and visual performance after LASIK and report on the relationship between satisfaction scores, performance scores, and pupil size, in an effort to illuminate whether larger pupil size is associated with poor visual function after LASIK. Methods Study design This study was performed under the supervision of the Committee on Human Research at the University of California, San Francisco, from which institutional review board approval was obtained. A retrospective study of 97 patients was performed to assess the relationship between pupil diameter, excimer laser treatment zone size, and visual results, along with patient satisfaction after LASIK for the treatment of myopia. All treatments were performed at the University of California, San Francisco by one of us (S.D.M.), and all patients gave informed consent to the study. Patient selection Subjects included adults of either sex who underwent refractive surgery at the University of California, San Francisco between January 1, 1999, and December 31, 2002. All patients enrolled in the study were 23 years or older and had myopia of −1.00 to −11.50 diopters (D) (manifest refraction spherical equivalent). Refractive astigmatism of 3.5 D or less was allowed. In addition, a calculated minimal residual corneal stromal bed thickness greater than 250 μm was required. Preoperatively, patients gave a complete ophthalmic history and underwent examination including measurement of refractive error, slitlamp examination, Goldmann applanation tonometry, and dilated fundus examination. Pupil size was measured using the Colvard pupilometer (Oasis Medical Inc, Glendora, California) under mesopic and scotopic conditions. Before the preoperative examination, contact lens wear was discontinued for at least 3 weeks in rigid lens wearers and at least 1 week in soft contact lens wearers. Inclusion criteria were uneventful LASIK for treatment of myopia performed by one of us (S.D.M.). Patients were excluded if both eyes were not operated on using the LASIK procedure (n = 8). Patients who underwent monovision treatment or those in whom any surgical or postoperative complication developed that was judged to affect postoperative visual quality were excluded from the study (n = 13). Lasik procedure One of us (G.W.S.) determined which eye was to be treated first. Laser treatments were performed with an excimer laser system (VISX Inc, Santa Clara, California). For procedures performed before June 2001, the VISX Star S2 laser with software version 3.30 was used, and after that, the VISX Star S3 laser with software version 4.52 was used. Before introduction of the 8.0-mm blend zone included in the Star S3 software package, the upper limit of scotopic pupil diameter allowed for treatment with the excimer laser was 6.5 mm. (An EC-5000 excimer laser [Nidek Co Ltd, Gamagori, Japan] that provided enlarged treatment zones was also available in the center.) The default treatment zone on the excimer laser was set at 6.5 mm and, when an attempt was made to limit treatment depth, the treatment zone was not reduced to 6.0 mm unless the scotopic pupil diameter, as measured with the Colvard pupilometer, was 6.0 mm or smaller. After introduction of the blend zone included in the Star S3 software package, the upper limit of scotopic pupil diameter allowed for treatment with the excimer laser was increased to 8.0 mm and a blend zone of 8.0 mm was included in all procedures in which the scotopic pupil diameter was larger than 6.5 mm at Colvard pupilometry. The Moria Carriazo-Barraquer manual microkeratome was used to prepare a corneal flap with a superiorly located hinge. The flap was then retracted, laser ablation performed, and the flap carefully repositioned and smoothed. Postoperative management After LASIK, a combination of a fluoroquinolone antibiotic and corticosteroid eyedrop were administered 4 times daily, then the treatment was discontinued after 1 to 2 weeks. Patients were followed up postoperatively at 1 day, 1 week, 3 months, and 6 months, and then as needed. Patient questionnaires The NEI-RQL Instrument was used to assess patient satisfaction and function after LASIK. Three hundred patients who had undergone LASIK with at least 6 months of follow-up, selected in reverse consecutive order, were asked to complete this self-administered questionnaire. Ninety-seven patients returned questionnaires; a response rate of 32.3%. In general, questionnaires were completed without assistance; however, explanations of questions were given by study personnel if requested by a patient. We performed analyses to determine that those who answered the questionnaire did not differ significantly from those who did not. Clinical records data acquisition Along with demographic data, pertinent objective factors including pupil diameter under mesopic and scotopic conditions, preoperative and postoperative uncorrected and best corrected visual acuity, manifest refraction, and ablation data were collected. Subjective scores Satisfaction with correction, glare, symptoms, clarity of vision, worry, and quality of far vision scores were assessed by and compiled from RQL responses. So that the subscales would operate the same regardless of category, higher scores were assigned to a more favorable outcome (eg, a higher “worry” score to represent a better outcome, or less worry). The RQL is written so that certain questions refer specifically to defined areas including satisfaction with correction, glare, symptoms, clarity of vision, worry, and quality of far vision. The mean of questions 23, 37, 39, and 40 from the NEI-RQL Instrument measure clarity of vision; the mean of questions 21 and 22 assess worry; question 26 measures satisfaction with correction; glare is quantified by responses to questions 17 and 38; symptoms such as pain, itching, dryness, and fatigue are measured by questions 18, 19, 24, 25, 36, 41, and 42; and far vision score is the mean of questions 4, 5, 6, 9, and 10. In examining and evaluating RQL responses in a defined area, study personnel referenced component questions and evaluated the specific scores of the component questions. Performance scores Three-month, 6-month, and most recent postoperative refractive error and uncorrected visual acuity (UCVA) constituted objective performance scores in this study. Data analysis Data were initially entered on an Excel spreadsheet (Microsoft Corp, Redmond, Washington) and were transferred to StataView software (SAS Institute Inc, Cary, North Carolina) for statistical analysis. Spearman correlations (rank correlation coefficients) were calculated to evaluate the distribution of values from the norm. Results Of the 300 patients contacted who were eligible for the study, 97 (32.3%) completed a postoperative RQL questionnaire. The baseline characteristics of those completing vs those not completing the RQL were compared. There were no significant between-group differences in scotopic pupil size or preoperative and postoperative refractive error and UCVA. In addition, no demographic differences existed between the groups. Mean (±SD) patient age was 43.7 (± 9.7) years (age range, 23-67 years). The mean (±SD) preoperative manifest refraction in the right eye was −5.15 (± 2.24) D (range, −11.00 to −1.00 D), and in the left eye was −5.13 (± 2.35) D (range, −11.5 to −1.25 D; Table 1). There was a significant percentage of patients with moderate to severe myopia (33.3% with −6.0 to −9.9 D and 1.71% with −10.0 D or higher in the right eye, and 31.6% with −6.0 to −9.9 D and 3.42% with −10.0 D or higher in the left eye). The ablation zone diameter was between 6 and 8 mm in all patients. Table 2 gives postoperative residual refractive error (spherical equivalent values) and UCVA results in study participants. Three months postoperatively, 95.8% of patients had UCVA of 20/40 or better in their better eye. Three months postoperatively, 74.4% of worse eyes were within ±1.0 D of emmetropia and 96.3% were within ±2.0 D. Satisfaction Despite a good outcome reflected by Snellen UCVA, a certain subset of patients indicated occasional untoward symptoms. However, RQL responses demonstrate that 81 patients (83.5%) were either completely or very satisfied with LASIK correction (Table 3). One patient (1.0%) was very dissatisfied with correction, primarily because of symptoms of glare, dryness, and blurry vision. Glare Distortion of vision in the form of glare is a major concern after LASIK and typically is more symptomatic at night, when the pupil dilates. Seventy-six patients (78.4%) reported little or no nighttime glare; 10 patients (10.3%) reported glare some of the time; 5 patients (5.15%) reported nighttime glare most of the time; and 6 patients (6.19%) reported nighttime glare all of the time. In patients who reported nighttime glare, 14 (60.9%) reported the symptom as only a little bothersome. Other symptoms after lasik Other patient-reported symptoms measured by the NEI-RQL included pain, discomfort, dryness, tearing, itching, soreness, and headaches related to vision. Commonly reported symptoms included eye soreness in 43 patients (44.3%), tearing in 20 (20.8%), itching in 38 (39.6%), and moderate dryness or worse in 28 (20.8%). Most patients indicated pain or discomfort infrequently (n = 35 [36.1%]) or never (n = 46 [47.4%]). In 5 of these patients (5.21%), pain or discomfort was moderate, and was severe in only 1 patient. Few patients reported headaches related to vision: 71 patients (73.2%) never experienced a headache related to vision and 8 (8.25%) reported only occasional headaches they considered to be related to vision. Clarity of vision Most patients reported excellent clarity of vision postoperatively, with 50 patients (52.1%) reporting perfectly clear vision and 40 (41.7%) indicating nearly clear vision. Nonetheless, not all patients indicated consistent, perfect clarity of vision, and 24 patients (25%) reported episodes of some degree of distorted vision, 33 (34.4%) indicated episodes of some degree of blurry vision, and 31 (32.3%) reported occasional episodes of some degree of trouble seeing. Worry A small percentage of patients in this study worry about their postoperative vision. Sixty-eight (70.1%) respondents never or rarely worry about vision, 18 (18.6%) reported occasional worry, 7 (7.22%) indicated some degree of worry, and 4 (4.12%) reported worrying about vision all of the time. The RQL responses to question 22 indicate that 41 patients (43.4%) never or rarely think about their eyesight or vision, 35 (36.1%) occasionally think about their eyesight or vision, 12 (12.8%) sometimes think about eyesight or vision, and 8 (8.3%) think about eyesight or vision all of the time. Spearman correlations Table 4 gives Spearman correlations. Contrary to the notion that larger scotopic and mesopic pupil diameter is correlated with lower satisfaction, the correlations between mesopic and scotopic pupil diameter and the RQL satisfaction score were 0.12 and 0.19, respectively, indicating greater satisfaction with larger pupil diameter; however, neither association was statistically significant at the P = .05 level. With respect to the RQL clarity and far vision scores, the correlations were 0.06 and 0.13, respectively, for mesopic pupil diameter and 0.01 and 0.17, respectively, for scotopic pupil diameter (not statistically significant at the P = .05 level). Therefore, larger pupil diameter is not significantly associated with postoperative satisfaction with vision, clarity of vision, or far vision as measured with the NEI-RQL Instrument. However, there was a significant association between better eye UCVA and RQL satisfaction scores, which serves to confirm postoperative UCVA as a strong predictor of patient satisfaction after refractive surgery. So that the subscales operated in the same manner (higher scores representing a more favorable outcome), higher worry values indicated a better outcome, or less worry. Therefore, as postoperative UCVA in the better eye improved (with better visual acuity represented by a smaller value), patients reported significantly less worry (−0.22; P = .03), more satisfaction (−0.25; P = .01), clearer vision (−0.25; P = .01), and better far vision (−0.24; P = .02), according to the respective RQL subscale scores. As UCVA in the worse eye improved, patients reported significantly less worry (−0.23; P = .02), clearer vision (−0.20; P = .049), and better far vision (−0.24; P = .02). Comment Although the outcome of LASIK is satisfying for most patients, optical sequelae such as glare, halo, and night vision disturbance are troubling adverse effects in some. The effect of increased spherical aberration after LASIK for treatment of myopia may be partially dependent on pupil size and attempted correction. However, in this study, preoperative scotopic and mesopic pupil diameters were not significantly associated with less postoperative satisfaction and visual function as measured with the NEI-RQL Instrument. We found that a larger scotopic pupil diameter was correlated with higher satisfaction and far vision scores, although statistical significance was not met (Table 4). This study demonstrates that large pupil size, matched to the ablation zones of today's excimer lasers, is not strongly associated with night vision disturbance. Clinical findings of increasing incidence of glare, halo, and disturbance of night vision with smaller ablation diameter7,8 and larger pupil diameter8,9 have implicated pupil size in earlier studies. However, this study and other recent reports14-16 demonstrate no correlation between larger pupil size and subjective visual outcomes after LASIK. Pop and Payette14 reported that attempted degree of spherical correction, optical zone, patient age, and postoperative spherical equivalent, and not pupil size, were major risk factors for glare and halo symptoms in their patient population. While these authors obtained responses for a large sample size, their study design is vulnerable in that an unvalidated instrument was used to assess subjective visual disturbances. To our knowledge, our study is the first independent application of the validated NIE-RQL Instrument in evaluating the relationship between pupil size and quality of vision after LASIK. It must be acknowledged that our study population represents only those who chose to respond to a mailed solicitation for participation (32.3% of the eligible population) and, thus, introduces the confounding element of selection bias. It cannot be predicted whether patients who might be more or less satisfied with their visual outcomes might be more or less inclined to respond to an outcomes questionnaire. However, the demographic and physiologic characteristics were similar between participants and nonparticipants. Sample size limitations cannot be ruled out as a potential explanation for the lack of statistically significant findings in some measures examined. This study does not confirm previous reports that suggest visual performance may demonstrate a decline in function related to clearance zones compromised by large pupil diameter. A type II error is one of several explanations of why this study did not find a significant result. However, because observed correlations are generally low (<0.15), the magnitude of the associations suggests that any true association between larger pupil diameter and postoperative satisfaction scores would be weak at best. It is important to recognize that in this study, while patients with scotopic pupil diameter up to 7.0 mm were included, routinely patients were selected and ablation zones chosen so that the ablation zone would match or exceed the scotopic pupil diameter as measured with the Colvard pupilometer. Moreover, at the time these procedures were performed, it was the practice of the operating surgeon to discourage surgery if the pupil diameter in daytime ambient light was greater than 6.5 mm. Thus, this study describes the outcomes in a patient cohort in which the pupil diameter in daytime ambient light was consistently 6.5 mm or less and in which the ablation zone diameter including transition zones was chosen to match or exceed the measured scotopic pupil diameter. Results of this study must be interpreted in that context and indicate that in patients in whom scotopic pupil diameter does not exceed treatment zone area including the transition zone, a larger pupil is not more strongly associated with less postoperative satisfaction with visual outcome. It is acknowledged that high degrees of spherical aberration can be introduced by smaller treatment zones in substantially larger pupils, but this study did not include treatments that fit such a description and, therefore, we cannot comment on the risk of patient dissatisfaction under those circumstances. With the exponential increase in patients undergoing refractive surgery, an increase in patient dissatisfaction with scotopic or mesopic vision disturbances, regardless of cause, has the potential to become an important public health issue. As new methods and technology continue to advance refractive surgery practice, there is a parallel need to accurately assess such potential complications and to identify appropriate surgical candidates. High-contrast distance visual acuity and decreased residual refractive error are correlated with overall patient visual function and satisfaction after surgery25; however, high-contrast visual acuity fails to identify a significant percentage of patients with visual disturbances after LASIK. Historically, high-contrast distance visual acuity measures (eg, Snellen chart) have been accepted as standards for assessing quality of vision. However, the limits of high-contrast distance visual acuity measures arise when considering the types of complications that occur after refractive surgery. By developing a consistent measure that takes a more nuanced account of various visual functioning (ie, glare disability, contrast sensitivity, and image degradation), we reach a better understanding of specific visual disturbances. As described herein, the NEI-RQL Instrument seems to be a valuable tool in better assessing subjective visual function. In determining specific factors through a standardized means of measurement, patient characteristics can be categorized, quantified, and, with the aid of instruments such as the NEI-RQL, ultimately analyzed to determine risk factors for poor outcome and design procedures to circumvent these limitations. This study indicates that scotopic pupil diameter (in this case, that does not exceed treatment zone area including the blend zone) does not seem to be a strong risk factor for poor outcome or to be associated with less postoperative satisfaction with visual outcome. Correspondence: Stephen D. McLeod, MD, Department of Ophthalmology, University of California, San Francisco, 10 Koret Way, Room K-301, San Francisco, CA 94143 ([email protected]). Submitted for Publication: July 18, 2006; final revision received December 12, 2006; accepted December 17, 2006. Financial Disclosure: None reported. Funding/Support: This study was supported in part by unrestricted grants from That Man May See and by Research to Prevent Blindness. References 1. el Danasoury AM Prospective bilateral study of night glare after laser in situ keratomileusis with single zone and transition zone ablation. J Refract Surg 1998;14 (5) 512- 516PubMedGoogle Scholar 2. O’Brart DPSLohmann CPFitzke FW et al. Disturbances in night vision after excimer laser photorefractive keratectomy. Eye 1994;8 (pt 1) 46- 51PubMedGoogle ScholarCrossref 3. Gartry DSKerr Muir MGMarshall J Excimer laser photorefractive keratectomy: 18-month follow-up. Ophthalmology 1992;99 (8) 1209- 1219PubMedGoogle ScholarCrossref 4. Pop MPayette Y Photorefractive keratectomy versus laser in situ keratomileusis: a control-matched study. Ophthalmology 2000;107 (2) 251- 257PubMedGoogle ScholarCrossref 5. Hersh PSSteinert RFBrint SFSummit PRK-LASIK Study Group, Photorefractive keratectomy versus laser in situ keratomileusis: a comparison of optical side effects. Ophthalmology 2000;107 (5) 925- 933PubMedGoogle ScholarCrossref 6. Hersh PSSchwartz-Goldstein BHSummit Photorefractive Keratectomy Topography Study Group, Corneal topography of phase III excimer laser photorefractive keratectomy: characterization of clinical effects. Ophthalmology 1995;102 (6) 963- 978PubMedGoogle ScholarCrossref 7. O’Brart DPSGartry DSLohmann CPKerr Muir MGMarshall J Excimer laser photorefractive keratectomy for myopia: comparison of 4.00- and 5.00-millimeter ablation zones. J Refract Corneal Surg 1994;10 (2) 87- 94PubMedGoogle Scholar 8. Roberts CWKoester CJ Optical zone diameters for photorefractive corneal surgery. Invest Ophthalmol Vis Sci 1993;34 (7) 2275- 2281PubMedGoogle Scholar 9. Maloney RK Corneal topography and optical zone location in photorefractive keratectomy. Refract Corneal Surg 1990;6 (5) 363- 371PubMedGoogle Scholar 10. Halliday BL Refractive and visual results and patient satisfaction after excimer laser photorefractive keratectomy for myopia. Br J Ophthalmol 1995;79 (10) 881- 887PubMedGoogle ScholarCrossref 11. Seiler TReckmann WMaloney RK Effective spherical aberration of the cornea as a quantitative descriptor in corneal topography. J Cataract Refract Surg 1993;19 ((suppl)) 155- 165PubMedGoogle ScholarCrossref 12. O’Brart DPSLohmann CPFitzke FW et al. Discrimination between the origins and functional implications of haze and halo at night after photorefractive keratectomy. J Refract Corneal Surg 1994;10 (2) ((2 suppl)) S281PubMedGoogle Scholar 13. Oliver KMHemenger RPCorbett MC et al. Corneal optical aberrations induced by photorefractive keratectomy. J Refract Surg 1997;13 (3) 246- 254PubMedGoogle Scholar 14. Pop MPayette Y Risk factors for night vision complaints after LASIK for myopia. Ophthalmology 2004;111 (1) 3- 10PubMedGoogle ScholarCrossref 15. Lee YCHu FRWang IJ Quality of vision after laser in situ keratomileusis: influence of dioptric correction and pupil size on visual function. J Cataract Refract Surg 2003;29 (4) 769- 777PubMedGoogle ScholarCrossref 16. Schallhorn SCKaupp SETanzer DJTidwell JLaurent JBourque L Pupil size and quality of vision after LASIK. Ophthalmology 2003;110 (8) 1606- 1614PubMedGoogle ScholarCrossref 17. National Advisory Eye Council, National Eye Institute, National Institutes of Health, Vision Research: A National Plan—1994-1998. Washington, DC US Dept of Health and Human Services1993;331NIH Publication 93-3186 18. Barber BLStrahlman ERLaibovitz R et al. Validation of a questionnaire for comparing the tolerability of ophthalmic medications. Ophthalmology 1997;104 (2) 334- 342 [published correction appears in Ophthalmology. 1997;104(5):736, 890-893]PubMedGoogle ScholarCrossref 19. Wu AWColeson LCHolbrook JJabs DAStudies of Ocular Complication of AIDS Research Group, Measuring visual function and quality of life in patients with cytomegalovirus retinitis: development of a questionnaire. Arch Ophthalmol 1996;114 (7) 841- 847PubMedGoogle ScholarCrossref 20. Mangione CMLee PPPitts JGutierrez PBerry SHays RDNEI-VFQ Field Test Investigators, Psychometric properties of the National Eye Institute Visual Function Questionnaire (NEI-VFQ). Arch Ophthalmol 1998;116 (11) 1496- 1504PubMedGoogle ScholarCrossref 21. Vitale SSchein ODMeinert CLSteinberg EP The Refractive Status and Vision Profile: a questionnaire to measure vision-related quality of life in persons with refractive error. Ophthalmology 2000;107 (8) 1529- 1539PubMedGoogle ScholarCrossref 22. Schein ODVitale SCassard SDSteinberg EP Patient outcomes of refractive surgery: the Refractive Status and Vision Profile. J Cataract Refract Surg 2001;27 (5) 665- 673PubMedGoogle ScholarCrossref 23. Hays RDMangione CMEllwein LLindblad ASSpritzer KLMcDonnell PJ Psychometric properties of the National Eye Institute Refractive Error Quality of Life (NEI-RQL) Instrument. Ophthalmology 2003;110 (12) 2292- 2301PubMedGoogle ScholarCrossref 24. McDonnell PJLee PBerry S et al. Responsiveness of the National Eye Institute Refractive Error Quality of Life (NEI-RQL) Instrument to surgical correction of refractive error. Ophthalmology 2003;110 (12) 2302- 2309PubMedGoogle ScholarCrossref 25. Bourque LBCosand BBDrews CWaring GO IIILyn MCartwright C Reported satisfaction, fluctuation of vision, and glare among patients one year after surgery in the Prospective Evaluation of Radial Keratotomy (PERK) Study. Arch Ophthalmol 1986;104 (3) 356- 363PubMedGoogle ScholarCrossref
Severe Loss of Central Vision in Patients With Advanced Glaucoma Undergoing TrabeculectomyLaw, Simon K.;Nguyen, Anne M.;Coleman, Anne L.;Caprioli, Joseph
2007 Archives of Ophthalmology
doi: 10.1001/archopht.125.8.1044pmid: 17698750
Abstract Objective To evaluate the visual outcomes in patients with advanced visual field (VF) loss undergoing trabeculectomy with mitomycin C. Methods The records of patients with severe preoperative VF defects undergoing trabeculectomy from June 1, 1998, through October 31, 2005, were retrospectively reviewed. Severe loss of central vision was defined as visual acuity (VA) of 20/200 or less in the affected eye, counting fingers or less if preoperative VA was less than 20/200, or more than a 4-line reduction in Snellen VA. Results Central vision loss occurred in 7 of 117 patients (eyes) (6%) because of hypotony maculopathy (3 cases), uncontrolled elevated intraocular pressures (2 cases), posterior subcapsular cataract increase (1 case), and inflammatory reaction (1 case). A statistically significant mean VA reduction after surgery from −0.32 to −0.39 (logMAR, P = .01) was found. Differences in VF parameters before and after surgery were not statistically significant. Patients who had severe loss of central vision had statistically significantly higher mean ± SD preoperative intraocular pressures (27.1 ± 8.8 mm Hg vs 19.7 ± 8.1 mm Hg; P = .04) and higher rates of surgical complications (43% vs 4%; P = .001) compared with those who did not. Conclusions Severe loss of central vision after a trabeculectomy with mitomycin C occurred in 6% of patients who had glaucoma with marked VF loss. These patients had higher preoperative intraocular pressures and higher rates of surgical complications. Unexplained severe loss of central vision (snuff-out) was rare. Patients with advanced glaucomatous optic neuropathy have a high risk of further disease progression, which may affect the central vision. Large clinical trials have shown that successfully lowering intraocular pressures (IOPs) is associated with a decrease in visual field (VF) progression.1-5 Although glaucoma procedures such as trabeculectomies are often required to effectively reduce or stabilize IOP, surgeons may be hesitant to recommend intraocular procedures in patients with glaucoma who have severely constricted VFs that involve central fixation because of concerns about the possibility of a loss or “snuff-out” of central vision after surgery. This belief probably stems from early reports that suggested that patients with advanced glaucoma were at high risk for loss of central vision after surgery.6-8 However, the exact reasons for sudden loss of central vision were unclear, and some ophthalmologists have suggested that surgery should be performed despite the risk of snuff-out.9-11 Early studies7-9,12 that evaluated different types of glaucoma surgery, such as full-thickness sclerectomy, thermal sclerostomy, iridencleisis, and Scheie procedures, may have limited applicability to current practice. In the 5 studies6,10,11,13,14 that evaluated the rate of severe loss of central vision after trabeculectomy, the rate ranged from 0% to 7.7%. This variability may be secondary to the small sample sizes in these studies. For example, the 2 prospective studies by Aggarwal and Hendeles6 and Topouzis et al11 had 26 and 21 patients enrolled, respectively, and 2 of the 21 patients in the latter study had a combined trabeculectomy and cataract extraction. Two retrospective reviews on the incidence of central vision loss after trabeculectomy by Martinez et al10 and Langerhorst et al13 had larger sample sizes (50 eyes of 42 patients and 54 eyes of 44 patients, respectively); however, both studies did not take into account the correlation of 2 eyes for a patient being enrolled in the analysis. In another retrospective study, Costa et al14 identified 4 cases of central vision loss after a trabeculectomy; however, advanced VF defects were not an inclusion criterion for the study. Because the decision to proceed with trabeculectomy in patients with advanced glaucomatous VF loss remains controversial, we performed a comprehensive review, taking advantage of the practice environment of a tertiary glaucoma referral center with a large proportion of patients with advanced glaucoma, to evaluate the outcomes of visual acuity (VA) and perimetry in patients with advanced VF defects undergoing trabeculectomy with mitomycin C. Methods Institutional review board approval was obtained through the University of California, Los Angeles, to conduct this retrospective review. The medical records of all patients who underwent trabeculectomy performed by 2 surgeons (S.K.L. and J.C.) from June 1, 1998, through October 31, 2005 (89 months), were reviewed. Patients who had severe preoperative glaucomatous VF defects were enrolled. The requirement for automated VF tests in recently published studies6,10,13 includes VF defects that encroached on the central 10°, which corresponds to the central 8 test points (or 15% of the test points, excluding the foveal test point) of standard automated perimetry with a 24-2 program. To be comparable with previous studies in identifying patients with advanced VF defects, severe VF defects were defined as those with a sensitivity of 5 dB or less either in more than 85% of test points, excluding the central 4 test points, or in more than 75% of test points, including 3 of the central 4 test points with threshold automated perimetry (full threshold or Swedish Interactive Threshold Algorithm [SITA] standard 24-2 program of the Humphrey Field Analyzer-750; Carl Zeiss Meditec, Dublin, California), with consistent optic nerve cupping. Patients were excluded if they had uveitic glaucoma, neovascular glaucoma, nonglaucomatous optic neuropathy, corneal or retinal disease, or aphakia or had undergone a concurrent procedure with a trabeculectomy. One eye of each patient was enrolled. If both eyes of a patient qualified, the eye with the greater VF damage was selected. Medical data collected in this review included general medical diagnoses and systemic medications. Ocular data collected included ocular history, diagnoses, ocular examination results, ophthalmic medications used before and after the operation, surgical technique, and surgical complications. Surgical complications were defined as complications that resulted in decreased VA or required additional surgical intervention. Complications included, but were not limited to, hypotony maculopathy, flat anterior chamber that needed reformation, choroidal hemorrhage, and retrobulbar hemorrhage. Hypotony maculopathy was considered to be present if chorioretinal folds were noted in the macular area according to slitlamp examination with a noncontact fundus lens and with a decrease in VA. Information collected from the ophthalmic examination included VA, VF test results, anterior segment slitlamp examination results, IOP, gonioscopy findings, and fundus examination findings. Preoperative VA and IOP were recorded from the closest visit before surgery, and postoperative VA and IOP were recorded at 1 day, 1 week, 1 month, 3 months, and 6 months after the operation. The VA at 3 months postoperatively was used for analysis to allow enough time for recovery of vision after surgery and avoid transient vision decreases related to the surgery. The VA was measured with a Snellen chart and was converted to the logMAR VA scale for comparison. LogMAR values of −1.40, −2.70, and −4.70 were assigned to counting fingers, hand motions, and light perception, respectively.14 Severe loss of central vision was defined as best-corrected VA of 20/200 or less in the affected eye, counting fingers or less if preoperative vision was less than 20/200, or a reduction of more than 4 lines of Snellen VA at 3 months postoperatively. Medical records were carefully reviewed to determine if any evident cause was responsible when there was a severe loss of central vision. Anesthesia consisted of a peribulbar injection of a 1-to-1 mixture of 2% lidocaine hydrochloride and 0.75% bupivacaine hydrochloride without epinephrine. Two milliliters of the solution was injected into the inferior lateral orbit and 2 mL into the superior orbit with a 23-gauge 38-mm Atkinson needle (Eagle Laboratories, Rancho Cucamonga, California). Monitored anesthesia care was provided by an anesthesiologist, and no general anesthesia was required. A topical anesthetic supplement was used (0.5% tetracaine hydrochloride) as needed during surgery to enhance patient comfort. The dissection of the conjunctiva was performed with either a fornix-based or limbus-based approach according to the preference and discretion of the surgeon. A 4.0 × 3.0–mm scleral flap was outlined with a surgical blade at the 12-o’clock position. Pieces of cut Weck-cel (Medtronic Xomed, Inc, Jacksonville, Florida) soaked in 0.3 mg/mL of mitomycin C were placed under the Tenon capsule and conjunctiva, covering an area of approximately 4.0 × 8.0 mm on the sclera at the outlined flap area for 1 minute. The Weck-cel pieces were removed, followed by thorough irrigation of the area exposed to mitomycin C with balanced salt solution. Then a partial-thickness, 4.0 × 3.0–mm rectangular sclera flap was dissected. A block of trabecular section was removed anterior to the scleral spur with a Kelly punch or No. 75 microsurgery blade and Vannas scissors, and a peripheral iridectomy was performed. The scleral flap was sutured at its 2 corners with interrupted 10-0 nylon sutures to ensure a slight egression of aqueous, and yet they were tied tight enough to maintain a deep anterior chamber. Finally, the limbus-based conjunctiva and Tenon capsule incision was sutured with a continuous 9-0 polyglactin suture, or the fornix-based peritomy incision was sutured to the limbus with an interrupted 9-0 polyglactin suture. Postoperatively, patients received a 4- to 6-week tapering dose of 1% prednisolone acetate ophthalmic drops starting at 4 times daily. Suture lysis was performed with an argon laser for inadequate IOP control or a low filtering bleb 1 to 4 weeks after surgery. The target IOP before laser suture lysis or the addition of ocular hypotensive therapy was in the low teens or less, with the goal of preventing further progression of functional visual loss. Statistical analysis was performed with SPSS statistical software, version 13.0, for Windows (SPSS Inc, Chicago, Illinois). Descriptive statistics were used to report the incidence of loss of VA after the surgery. The VAs in logMAR values and the VF test results before and after surgery were compared with the t test. The VF test results within 6 months before and after surgery were used for comparison. Forty-six patients had reliable VF test results before and after the trabeculectomy for analysis, which provided an 80% power level to detect a difference of 2 dB of average mean deviation (MD) or a 3-dB difference in the central 4-point mean before and after trabeculectomy at an α level of .05. A logistic regression model was used to compare patients who had severe loss of vision with the remaining group of patients who did not lose vision. Statistical significance was defined as P<.05. Results The medical records of 1304 patients who underwent trabeculectomy with mitomycin C were retrospectively reviewed. A total of 117 patients (117 eyes, 9%) had severe VF defects without other exclusion criteria. The MD ± SD of the preoperative VF was 25.2 ± 5.1 dB. Figure 1 and Figure 2 display the IOP and VA levels during 1 year of follow-up, respectively. Seven patients (6%) had severe loss of central vision after surgery; causes of vision loss included hypotony maculopathy (3 cases), uncontrolled elevated IOPs (2 cases), increase in a posterior subcapsular cataract (1 case), and a severe noninfectious inflammatory reaction (1 case). The patient with increase in posterior subcapsular cataract recovered vision to 20/50 in the affected eye after cataract surgery, but the other 6 patients did not. Table 1 summarizes the demographic and clinical data of the 7 patients. Eighty-five patients (73%) had a VA better than 20/200 in the affected eye before the trabeculectomy. In these 85 patients, a small but statistically significant reduction in mean VA was found after surgery from −0.32 to −0.39 (logMAR), corresponding to a reduction from approximately 20/40 to 20/50 Snellen VA (P = .01). Figure 3 represents the frequency distribution of VA changes in the 85 patients. Sixteen of the 85 patients (19%) had a decrease of more than 1 line of Snellen VA at 3 months postoperatively. Table 2 ranks the reasons for the decreased VA in the 16 patients. Eleven of the 16 patients (69%) were phakic before the trabeculectomy. Seven of the 11 patients (64%) had an increase in their cataracts that was determined to be the cause of their VA decease if it was documented on clinical examination in the absence of other causes of VA decrease (3 patients) or on the basis that the VA improved to or was better than baseline after subsequent cataract surgery (4 patients). The 3 patients with cataracts documented on clinical examination as the cause of their VA decrease chose not to receive the cataract surgery. One of the 16 patients had no identifiable cause of the decrease of more than 1 line of Snellen VA. This patient had a preoperative VA of 20/50 in the affected eye that decreased to 20/60 at 1 month and to 20/70 at 3 months postoperatively, despite IOP reduction from 19 mm Hg preoperatively to 12 mm Hg postoperatively. Not every patient underwent VF testing after the trabeculectomy in this retrospective study. Forty-six of 85 patients (39%) had reliable VF test results before and after the trabeculectomy. The average MD ± SD was –24.8 ± 4.1 dB. No statistically significant differences were found between the VF test results before and after trabeculectomy for the mean value of all test points, mean value of the central 4 test points, MD, pattern standard deviation, and area under the curve of the VF (sum of thresholds in decibels of all test points, P = .80, .99, .07, and .67, respectively. Table 3 and Table 4 summarize the comparison with a logistic regression model between the 7 patients who had severe loss of central vision after surgery and the 110 patients who did not. Patients who experienced a severe loss of central vision had statistically significantly higher preoperative IOP (mean ± SD, 27.1 ± 8.8 mm Hg vs 19.7 ± 8.1 mm Hg; P = .04) and higher rates of surgical complications (43% vs 4%; P = .001) compared with patients without severe loss of central vision. No statistically significant differences were found between the 2 groups with regard to different surgeons, age, race, sex, diagnosis, lens status, prior operations, preoperative VA, medical conditions (such as hypertension, diabetes mellitus, and cardiovascular disease), use of systemic anticoagulation therapy, and fornix- vs limbus-based surgical techniques. Reanalysis with preoperative IOP and surgical complications entered as covariates in a multivariate logistic regression model showed surgical complications to be the only statistically significant factor in association with severe loss of central vision in patients with advanced glaucomatous VF defects undergoing trabeculectomy with mitomycin C (odds ratio, 15.32; 95% confidence interval, 2.38-98.63; P = .004). Comment We have found that unexplained snuff-out or loss of central vision after a trabeculectomy with mitomycin C is rare. Existing data on the occurrence of severe loss of vision are limited.6-14 Although a few studies6,10,11,13,14 have evaluated glaucoma surgery with more current surgical techniques, the inclusion of trabeculectomy with and without an antimetabolite as adjuvant, trabeculectomy with concurrent procedures such as cataract extraction, anterior vitrectomy, Molteno implantation, and even cataract extraction in the analysis render the interpretation and application of the results difficult. Table 5 summarizes the available studies in the English literature on the incidence of severe loss of central vision after glaucoma surgery. Reasons for severe loss of central vision are listed, and the rates of unexplained severe loss of central vision are reported separately. Of the 9 published studies, 2 prospective studies6,11 had small sample sizes. Aggarwal and Hendeles6 prospectively studied 26 patients (eyes) whose VF had only a central island remaining or had a defect that was encroaching on the central 10° who were undergoing trabeculectomy without antimetabolites. Four patients (15.4%) were reported to have a loss of central vision. One patient developed cystoid macular edema, and another had a shallow anterior chamber after surgery. The remaining 2 patients (7.7%) had no explainable cause for the vision loss. The authors concluded that there was a considerable risk of sudden loss of VF in patients with small residual VFs undergoing trabeculectomy.6 In another prospective study by Topouzis et al,11 in which 21 patients (eyes) who had advanced glaucomatous VF defects on automated perimetry with scores of more than 16 (of 20) on the VF scoring system of the Advanced Glaucoma Intervention Study,2 no patient experienced severe loss of central vision with trabeculectomy with mitomycin C, with or without cataract extraction and intraocular lens implantation. Among the studies that reported cases of severe loss of central vision, most cases had explainable causes. In the review by Costa et al14 of 508 eyes of 440 patients, who underwent trabeculectomy with or without postoperative subconjunctival injection of fluorouracil or with concurrent anterior vitrectomy or Molteno implantation, 9.3% of the patients had reduction of more than 1 line of Snellen VA at 3 months after the procedure. Reasons for vision loss included hypotony maculopathy, cystoid macular edema, cataract, posterior capsule opacity, vitreous hemorrhage, choroidal hemorrhage, retinal detachment, and uncontrolled IOP. Four eyes (0.95%) had postoperative VA decreased to 20/200 or less. These 4 cases were described as having a “snuff-out” or “wipe-out” of vision. However, it is uncertain if the postoperative occurrence of IOP greater than 22 mm Hg at 1 day postoperatively, hyphema, encapsulated bleb, and choroidal detachment in these 4 cases were the actual causes for the vision loss.14 In our review, in which only trabeculectomy with mitomycin C was studied, all patients who had severe loss of central vision had an explainable cause. This is consistent with the overall impression summarized in Table 5 that unexplained severe loss of central vision from trabeculectomy is rare, even in patients with advanced VF defects that involve central fixation. Although all patients who had severe loss of central vision had an explainable cause, a rate of 6% with severe loss of central vision after trabeculectomy in this group of patients with advanced glaucomatous optic neuropathy still represents a significant risk and should dictate appropriate caution in planning this procedure. In our retrospective review, patients who had severe loss of vision after trabeculectomy with mitomycin C had higher rates of surgical complications and higher preoperative IOPs. Although patients with severe loss of central vision had greater reductions in IOP after surgery (mean ± SD preoperative IOP minus postoperative IOP, 17.1 ± 18.2 mm Hg) than patients without severe loss of vision (9.6 ± 11.0 mm Hg), this difference was not statistically significant, probably because of the small number of patients. Three of the 7 patients who had central vision loss in our study had hypotony maculopathy. This finding is consistent with the review by Costa et al,14 in which severe postoperative hypotony was associated with severe loss of vision (snuff-out) after glaucoma surgery. Hypotony maculopathy and flat anterior chamber that required reformation were probably the result of overfiltration, which should be carefully avoided in performing glaucoma procedures. Planned argon laser suture lysis to allow a gradual reduction of IOP after trabeculectomy may lower the rate of overfiltration. In our subgroup analysis of the 85 patients who had preoperative Snellen VA better than 20/200, a small but statistically significant reduction in acuity was found. Sixteen patients (19%) had a decrease of more than 1 line of Snellen VA 3 months postoperatively. Seven of 11 patients (64%) who were phakic preoperatively had a vision decrease secondary to an increase in cataract. Cataract development or progression is a common cause of VA reduction after trabeculectomy. The Advanced Glaucoma Intervention Study15 reported an increased risk of 78% for cataract formation. Limitations of this study are its retrospective design and short-term follow-up. In addition, our findings may not be generalizable to patients who are younger than those in this study. Although no statistically significant changes in VF test results were found after trabeculectomy in this study, the small proportion of patients (46 patients, 39%) with reliable preoperative and postoperative VF test results available for analysis makes it difficult to draw any conclusion. In summary, approximately 6% of patients who had glaucoma with advanced preoperative VF defects who underwent trabeculectomy with intraoperative mitomycin C had a severe reduction in their central VA. Patients who lost central vision had statistically significantly higher rates of surgical complications and higher preoperative IOPs. Unexplained snuff-out or loss of central vision was not observed. Correspondence: Simon K. Law, MD, 100 Stein Plaza 2-235, Jules Stein Eye Institute, Los Angeles, CA 90095 ([email protected]). Submitted for Publication: November 1, 2006; final revision received January 4, 2007; accepted January 22, 2007. Author Contributions: Dr Law has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Financial Disclosure: None reported. Previous Presentation: Presented in part as a poster at the Association for Research in Vision and Ophthalmology meeting; May 4, 2006; Fort Lauderdale, Florida. References 1. Migdal CGregory WHitchings R Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma. Ophthalmology 1994;101 (10) 1651- 1656PubMedGoogle ScholarCrossref 2. The AGIS Investigators, The Advanced Glaucoma Intervention Study (AGIS) 4: comparison of treatment outcomes within race: seven-year results. Ophthalmology 1998;105 (7) 1146- 1164PubMedGoogle ScholarCrossref 3. Collaborative Normal-Tension Glaucoma Study Group, Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol 1998;126 (4) 487- 497PubMedGoogle ScholarCrossref 4. Lichter PRMusch DCGillespie BW et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology 2001;108 (11) 1943- 1953PubMedGoogle ScholarCrossref 5. Heijl ALeske MCBengtsson BHyman LBengtsson BHussein MEarly Manifest Glaucoma Trial Group, Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120 (10) 1268- 1279PubMedGoogle ScholarCrossref 6. Aggarwal SPHendeles S Risk of sudden visual loss following trabeculectomy in advanced primary open-angle glaucoma. Br J Ophthalmol 1986;70 (2) 97- 99PubMedGoogle ScholarCrossref 7. Kolker AE Visual prognosis in advanced glaucoma: a comparison of medical and surgical therapy for retention of vision in 101 eyes with advanced glaucoma. Trans Am Ophthalmol Soc 1977;75539- 555PubMedGoogle Scholar 8. Levene RZ Central visual field, visual acuity, and sudden visual loss after glaucoma surgery. Ophthalmic Surg 1992;23 (6) 388- 394PubMedGoogle Scholar 9. Lichter PRRavin JG Risks of sudden visual loss after glaucoma surgery. Am J Ophthalmol 1974;78 (6) 1009- 1013PubMedGoogle Scholar 10. Martinez JABrown RHLynch MGCaplan MB Risk of postoperative visual loss in advanced glaucoma. Am J Ophthalmol 1993;115 (3) 332- 337PubMedGoogle Scholar 11. Topouzis FTranos PKoskosas A et al. Risk of sudden visual loss following filtration surgery in end-stage glaucoma. Am J Ophthalmol 2005;140 (4) 661- 666PubMedGoogle ScholarCrossref 12. O'Connell EJKarseras AG Intraocular surgery in advanced glaucoma. Br J Ophthalmol 1976;60 (2) 124- 131PubMedGoogle ScholarCrossref 13. Langerhorst CTde Clercq Bvan den Berg TJ Visual field behavior after intra-ocular surgery in glaucoma patients with advanced defects. Doc Ophthalmol 1990;75 (3-4) 281- 289PubMedGoogle ScholarCrossref 14. Costa VPSmith MSpaeth GLGandham SMarkovitz B Loss of visual acuity after trabeculectomy. Ophthalmology 1993;100 (5) 599- 612PubMedGoogle ScholarCrossref 15. AGIS (Advanced Glaucoma Intervention Study) Investigators, The Advanced Glaucoma Intervention Study 8: risk of cataract formation after trabeculectomy. Arch Ophthalmol 2001;119 (12) 1771- 1779PubMedGoogle ScholarCrossref
High-Frequency Ultrasound Characteristics of 24 Iris and Iridociliary Melanomas: Before and After Plaque BrachytherapyFinger, Paul T.;Reddy, Shantan;Chin, Kimberly
2007 Archives of Ophthalmology
doi: 10.1001/archopht.125.8.1051pmid: 17698751
Abstract Objective To evaluate size, characteristics, and regression of iris and iridociliary melanomas on high-frequency ultrasound images before and after plaque brachytherapy. Methods Retrospective review of high-frequency ultrasound characteristics of 24 consecutive iris and iridociliary melanomas before and after radiation therapy. Results The median tumor thickness before radiation therapy was 2.3 mm (range, 1.4-4.3 mm). Nineteen iris melanomas (79%) involved the ciliary body, 18 (75%) involved the iris pigment epithelium, 11 (46%) were club shaped, and 4 (17%) caused disinsertion of the iris root. At a median follow-up of 30 months after plaque brachytherapy, the mean tumor thickness had diminished to 1.2 mm (median, 1.2 mm; range, 0.9-1.9 mm). While all tumors exhibited a reduction in thickness, no tumors showed additional regression after 30 months past treatment. Fourteen tumors (58%) were noted to have increases in internal reflectivity. There was 1 failure of local control (at 6 years), successfully treated by a second application of plaque brachytherapy. Conclusion High-frequency ultrasonography revealed unique tumor characteristics, quantified tumor size, and demonstrated tumor response to radiation therapy. High-frequency ultrasonography allows for evaluation of the size, occult margins, internal reflectivity, and growth of iris and iridociliary melanomas. It is an invaluable tool for initial diagnosis and for subsequent treatment. High-resolution cross-sectional ultrasound images allow visualization of a tumor's surface characteristics, interstitial borders, and reflectivity.1-4 Histopathologic correlations of high-frequency ultrasound images of anterior segment tumors have confirmed its usefulness.4-6 High-frequency ultrasonography is used to identify tumor growth, vascularity, sector cataract, and disturbance of the iris pigment epithelium (IPE).3-5 Although findings from studies2,5 suggest that changes in internal reflectivity and tumor size predict malignancy, the usefulness of evaluating involvement of the IPE needs to be proven. Although iridectomy or iridocyclectomy previously was the procedure of choice for iris and ciliary body melanomas, ophthalmic plaque radiation therapy offers the advantages of larger treatment margins and retained iris function.7-10 As an extraocular procedure, plaque radiation therapy is associated with little risk of hyphema, infection, or retinal detachment.11,12 Although iridociliary plaque radiation therapy is likely to cause cataract, it is unlikely to induce radiation maculopathy.10,11 High-frequency ultrasound tumor measurements facilitate plaque radiation therapy dose calculations and assist in planning for surgical resection.5,10,13 Ultrasound characteristics of iris and ciliary body melanomas have been described.2-6,13-15 Most recently, the high-frequency ultrasound features of 4 anterior melanomas before and after brachytherapy were reported.14 The objective of our study was to evaluate the high-frequency ultrasound characteristics of 24 iris and iridociliary melanomas before and after plaque radiation therapy. Methods We conducted a retrospective review of 24 patients diagnosed as having iris (n = 5) and iridociliary (n = 19) melanomas and subsequently treated with palladium 103 plaque brachytherapy. Patients selected for this study were consecutive cases with at least 4 months of follow-up. All patients were referred to The New York Eye Cancer Center, New York, where a detailed medical history was followed by an ophthalmic examination. These evaluations included but were not limited to best-corrected visual acuity (Early Treatment of Diabetic Retinopathy Study chart), slitlamp biomicroscopy with photography, Goldmann tonometry, gonioscopy, scleral transillumination, ultrasonography, and indirect ophthalmoscopy. Phakic patients were examined for the presence of sector cataract. This study adhered to the tenets of the Declaration of Helsinki and the Health Insurance Portability and Accountability Act of 1996. High-frequency (20-, 35-, or 50-MHz) ultrasonography was typically performed at the initial visit, during periods of observation for tumor growth, and every 4 months after plaque brachytherapy. Within the framework of The New York Eye Cancer Center, we used 3 commercially available units. Early scans were performed using a 50-MHz transducer (Paradigm Medical Industries, Salt Lake City, Utah). This highest-frequency ultrasound transducer provides the greatest resolution and the least intraocular penetration. Examinations of larger lesions typically required the examiner to tape together sequential images (to include the entire lesion). Subsequently, an ophthalmic 20-MHz transducer (Innovative Imaging, Inc, Sacramento, California) became available. This lower-frequency unit provides a larger field, integrated calipers, and ease of use through a miniature water-filled latex condom. Our most recently acquired 35-MHz transducer-based machine (Ophthalmic Technologies Inc, Toronto, Ontario) requires the use of an isotonic sodium chloride solution–filled eye cup (water bath). However, the newer machines have the advantage of computerization. This allows for recording of the examination as a video, with subsequent image capture, magnification, and measurement (with integrated calipers). In addition to tumor evaluations, we routinely examine all 360° of the anterior segment to rule out additional tumors (eg, ring melanoma). In this study, we evaluated the initial and subsequent ultrasonograms. There may have been some variation in tumor size related to the capability and resolution of the 3 high-frequency ultrasound instruments. However, all reported tumor sizes represent the best possible measurements (by P.T.F.). In comparing serial ultrasonograms for the same patient using different machines, every effort was made to account for the inherent instrument-related differences in analyzing ultrasound features. Regardless of the instrument used, tumor thicknesses were measured at the thickest portion of the tumor, whether in the ciliary body or in the iris. Width was typically determined by evaluation of adjacent tissues for tumor invasion. Longitudinal and transverse tumor diameters were measured (Figure 1). The largest transverse dimension was recorded in the iris or in the ciliary body (depending on its location). Other high-frequency ultrasound characteristics evaluated included the tumor shape, scleral invasion, involvement of the IPE, internal tumor reflectivity, disinsertion of the iris root, angle morphological features, and presence of intratumoral hypoechoic spaces. In this study, there were 3 types of melanomas: (1) ciliary body tumor with iris displacement or extension, (2) diffuse iris melanoma that extended into the supraciliary space, and (3) pure iris melanomas that did not extend posterior to the iris root. Assessment of tumor growth was used to help determine the stage of malignancy for all 3 types of melanomas. However, because the metastatic potential for focal iris melanomas is low, criteria for treating these tumor were growth suggestive of malignancy or biopsy-proven malignant melanoma. Tumor shapes were defined as club, dome, or irregular. The internal reflectivity was graded as low, moderate, or high. The iris was evaluated for attachment to the ciliary body at the iris root or for disinsertion by the tumor. The IPE was determined to be involved if it was displaced or eroded by the tumor. Ultrasonographic evidence of subjacent cataract (lens hyperreflectivity) was noted. Tumor thickness was evaluated by serial high-frequency ultrasound examinations every 4 months after plaque brachytherapy. Results Analysis of 24 iris and iridociliary melanomas revealed that their median follow-up was 30 months (mean, 35.5 months; range, 4 months to 10 years). The median patient age was 63.5 years (mean age, 60 years; age range, 29-90 years) (Table 1). Fourteen patients (58%) were female, and 10 patients (42%) were male. Clinical data were available for all 24 patients. Eleven melanomas (46%) were present in the right eye, and 13 melanomas (54%) were present in the left eye. Eleven of 24 irises (46%) exhibited corectopia. Nine of 24 irises (38%) had tumor-associated ectropion uveae (Figure 2). Before plaque brachytherapy, 6 patients had biopsy-proven malignant melanoma, 1 by surgical iridectomy and 5 by the minimally invasive iridectomy technique described by Finger et al.16 After healing for 3 weeks, tumors were remeasured by high-frequency ultrasonography for radiation dosimetry planning. Postoperative findings Evaluation of visual acuity revealed that 19 patients (79%) retained visual acuity within 1 line of their preoperative visual acuity on the Early Treatment of Diabetic Retinopathy Study chart (Table 2). Of 5 patients who did not, 1 had age-related macular degeneration, 2 had cataracts, and 2 required enucleation for melanomalytic glaucoma. Fourteen patients (58%) were noted to have cataract formation following surgery, 11 of whom underwent cataract surgery at a mean of 34.5 months (range, 9-68 months) after brachytherapy. Four patients (17%) required other postsurgical procedures (1 each required endolaser, argon laser trabeculoplasty, and enucleation, and 1 patient required both cyclocryotherapy with subsequent enucleation). Two patients (8%) developed iris neovascularization. Seven patients (29%) had elevated intraocular pressure secondary to pigment dispersion alone (n = 5) or to a combination of neovascularization of the angle (n = 2). Three patients had glaucoma before brachytherapy. High-frequency ultrasound findings On high-frequency ultrasonography, the initial mean ± SD tumor thickness before radiation therapy was 2.6 ± 0.8 mm (median, 2.3 mm; range, 1.4-4.3 mm) (Table 3). Nineteen melanomas (79%) involved the ciliary body, and 5 tumors (21%) were confined to the iris (Figure 3). Eighteen tumors (75%) had low reflectivity, and 6 tumors (25%) had moderate reflectivity. Eleven iris melanomas(46%) were club shaped, 7 (29%) were dome shaped, and 6 (25%) were irregularly shaped (Figure 4). Four tumors (17%) caused disinsertion of the iris root (Figure 5), 18 tumors (75%) involved the IPE (Figure 6), and 12 tumors (50%) caused blunting of the angle (Figure 7). Two tumors (8%) had intratumoral hypoechoic spaces, and no tumors had invaded the sclera. Follow-up ultrasonography and clinical course After analysis of comparative intraocular dosimetry, we chose to use palladium 103 plaques (vs iodine 125).12,17-19 In every case, comparative dosimetric analysis (palladium 103 vs iodine 125 plaques) revealed that the use of palladium 103 resulted in less or decreased irradiation of the optic disc and macula. Therefore, all patients were treated with palladium 103 plaques. At a median of 30 months after plaque brachytherapy, the mean ± SD tumor thickness was reduced to 1.2 ± 0.4 mm (median, 1.2 mm; range, 0.9-1.9 mm) (Table 2). The mean ± SD change in thickness of an iris or iridociliary melanoma was 1.4 ± 0.9 mm (median, 1.3 mm; range, 0.1-3.3 mm). All tumors were reduced in thickness after treatment. Of 5 tumors that were followed up beyond 3 years (mean follow-up, 84.4 months; median follow-up, 74 months; follow-up range, 72-120 months), no tumor showed additional regression after 30 months. Fourteen tumors were followed up beyond 2 years (mean follow-up, 50.4 months; median follow-up, 36 months; follow-up range, 26-120 months), and 8 melanomas did not show additional regression after 2 years. Six tumors continued to regress at between 24 and 36 months. The mean rate of reduction in tumor thickness during the first 30 months was 0.4 mm (median, 0.3 mm; range, 0.1-1.7 mm) per 6-month interval. Seventeen tumors (71%) were reduced by at least 33% of the initial thickness by 24 months (Figure 8). Fourteen tumors (58%) increased in internal reflectivity after therapy (Figure 1), while 10 tumors (42%) exhibited no change in reflectivity (Figure 9). One patient (4%) died of metastatic disease within 3 years of radiation therapy, and 1 patient (4%) was found to have local recurrence 6 years after initial treatment. The latter tumor was irregularly shaped, involved the ciliary body and the IPE, caused blunting of the angle and iris root disinsertion, and exhibited an increase in reflectivity after therapy. It was initially considered a local cure, having decreased in thickness by 0.6 mm (30%), with an increase in internal reflectivity. When the tumor enlarged, it was treated by an additional application of palladium 103 plaque radiation therapy (8800 rad [88 Gy]). Although the tumor was subsequently controlled for 48 months, the patient died of myocardial infarction. Comment The diagnosis and treatment of malignant iris and iridociliary melanomas are important because the tumors can metastasize and induce secondary glaucoma.20-22 Before the advent of high-frequency ultrasonography, these tumors were evaluated using slitlamp photography, gonioscopy, and conventional B-scan ultrasonography. High-frequency ultrasonography has expanded our capability to serially evaluate various tumor characteristics. Subtle interstitial areas of ciliary body invasion of an iris melanoma can be detected by high-frequency ultrasonography (Figure 3). Decreased internal tumor reflectivity can help discriminate an iris melanoma from a nevus.5 High-frequency ultrasonography can visualize IPE and iris root involvement that may be missed using older diagnostic modalities (Figures 3 and 4). Furthermore, high-frequency ultrasonography has shown usefulness in delineating the borders of a tumor by helping distinguish benign scleral pigmentation from invasive melanoma.14 Investigators have reported on the high-frequency ultrasound characteristics of iris melanomas and the usefulness of this imaging modality in showing tumor growth.2,4,5,14,15 Conway et al15 used high-frequency ultrasonography to demonstrate that a high percentage (81%) of iris melanomas distorted surrounding structures, such as the ciliary body and posterior iris plane. Other reports evaluated the frequency of cavitations within iris tumors detected by high-frequency ultrasonography and found them to be present in up to 8.4% of cases.23-25 To our knowledge, only 1 previous study14 reported on the high-frequency ultrasound features of anterior uveal melanomas after plaque brachytherapy, and Torres et al found a mean reduction in thickness of 1.12 mm after a median follow-up of 23 months in 4 tumors. In this series of 24 iris and iridociliary melanomas, most tumors were club shaped (11 of 24 [46%]), involved the ciliary body (19 of 24 [79%]), distorted the IPE (18 of 24 [75%]), and caused blunting of the angle (12 of 24 [50%]). Four tumors (17%) had disinserted the iris root, and no melanomas had invaded the sclera. We observed 2 patients (8%) who had iridociliary melanomas with intratumoral hypoechoic spaces, which may represent cystic degeneration or vascularity. Tumors in this study were clinically diagnosed uveal melanomas, exhibited growth while under observation, or were biopsy-proven malignant melanoma.16 Plaque brachytherapy provided local control in 23 patients (96%) and preservation of initial visual acuity in 19 patients (79%). In comparison, there was 90% local control in an iridocyclectomy series, with 57% of eyes achieving 20/50 visual acuity or better.9 Our increased control may be explained by the use of larger tumor margins and shorter follow-up. However, since plaque brachytherapy is an extraocular procedure, it all but eliminates the risks inherent to intraocular surgery (as well as pupil deformation).7,8,12 Following therapy, high-frequency ultrasonography was a valuable tool for documenting regression. In our study of 24 iris and iridociliary melanomas treated with plaque brachytherapy during a median follow-up of 30 months, there was a mean reduction in tumor thickness of 1.4 mm. In addition, tumor regression occurred during 30 months by a mean 0.25 mm for every 6 months of follow-up, and one-third of the tumors had regressed to normal iris and ciliary body thickness by the first year after treatment. Fourteen tumors (58%) in our study increased in reflectivity after treatment. A similar tendency was reported by Torres et al.14 Pavlin et al2 suggested that high reflectivity was histopathologically correlated with poorly cohesive cells with resultant large intercellular spaces. Therefore, our finding of increased internal reflectivity after plaque brachytherapy may represent a decrease in the density and cohesion of the uveal melanoma cells within treated tumors. We found that changes in reflectivity did not always correlate with reductions in tumor thickness. Therefore, tumor response to plaque brachytherapy should be monitored by observation for a decrease in tumor size (thickness and width) and for changes in internal reflectivity. As noted in our 1 case of failure of local control despite an initial response to therapy (shrinkage and an increase in reflectivity), the potential for recurrence continues and underscores the need for follow-up vigilance. Our study findings demonstrate that the diagnosis and classification of iris and iridociliary melanomas can be obtained by observation of their visually apparent and high-frequency ultrasound characteristics. High-frequency ultrasound characteristics include involvement of the ciliary body, IPE distortion, disinsertion of the iris root, and tumor shape and growth. After plaque brachytherapy, this imaging modality should again be used to serially document a tumor's response to therapy (shrinkage and reflectivity). High-frequency ultrasonography revealed unique tumor characteristics, quantified tumor size, and demonstrated tumor response to radiation therapy. Correspondence: Paul T. Finger, MD, The New York Eye Cancer Center, 115 E 61st St, New York, NY 10065 ([email protected]). Submitted for Publication: July 17, 2006; final revision received December 8, 2006; accepted December 11, 2006. Financial Disclosure: None reported. Funding/Support: This study was supported by The EyeCare Foundation, Inc. References 1. Pavlin CJHarasiewicz KSherar MDFoster FS Clinical use of ultrasound biomicroscopy. Ophthalmology 1991;98 (3) 287- 295PubMedGoogle ScholarCrossref 2. Pavlin CJMcWhae JAMcGowan HDFoster FS Ultrasound biomicroscopy of anterior segment tumors. Ophthalmology 1992;99 (8) 1220- 1228PubMedGoogle ScholarCrossref 3. Marigo FAFinger PT Anterior segment tumors: current concepts and innovations. Surv Ophthalmol 2003;48 (6) 569- 593PubMedGoogle ScholarCrossref 4. Katz NRFinger PTMcCormick SA et al. Ultrasound biomicroscopy in the management of malignant melanoma of the iris. Arch Ophthalmol 1995;113 (11) 1462- 1463PubMedGoogle ScholarCrossref 5. Marigo FAFinger PTMcCormick SA et al. Iris and ciliary body melanomas: ultrasound biomicroscopy with histopathologic correlation. Arch Ophthalmol 2000;118 (11) 1515- 1521PubMedGoogle ScholarCrossref 6. Maberly DAPavlin CJMcGowan HDFoster FSSimpson ER Ultrasound biomicroscopy imaging of the anterior aspect of peripheral choroidal melanomas. Am J Ophthalmol 1997;123 (4) 506- 514PubMedGoogle Scholar 7. Harbour JWAugsburger JJEagle RC Jr Initial management and follow-up of melanocytic iris tumors. Ophthalmology 1995;102 (12) 1987- 1993PubMedGoogle ScholarCrossref 8. Geisse LJRobertson DM Iris melanomas. Am J Ophthalmol 1985;99 (6) 638- 648PubMedGoogle Scholar 9. Memmen JEMcLean IW The long-term outcome of patients undergoing iridocyclectomy. Ophthalmology 1990;97 (4) 429- 432PubMedGoogle ScholarCrossref 10. Finger PT Plaque radiation therapy for malignant melanoma of the iris and ciliary body. Am J Ophthalmol 2001;132 (3) 328- 352PubMedGoogle ScholarCrossref 11. Finger PT Tumour location affects the incidence of cataract and retinopathy after ophthalmic plaque radiation therapy. Br J Ophthalmol 2000;84 (9) 1068- 1070PubMedGoogle ScholarCrossref 12. Finger PT Radiation therapy for choroidal melanoma. Surv Ophthalmol 1997;42 (3) 215- 232PubMedGoogle ScholarCrossref 13. Torres VLAllemann NErwenne CM Ultrasound biomicroscopy features of iris and ciliary body melanomas before and after brachytherapy. Ophthalmic Surg Lasers Imaging 2005;36 (2) 129- 138PubMedGoogle Scholar 14. Weisbrod DJPavlin CJEmara KMandell MAMcWhae JSimpson ER Small ciliary body tumors: ultrasound biomicroscopy assessment and follow-up of 42 patients. Am J Ophthalmol 2006;141 (4) 622- 628PubMedGoogle ScholarCrossref 15. Conway RMChew TGolchet PDesai KLin SO'Brien J Ultrasound biomicroscopy: role in diagnosis and management in 130 consecutive patients evaluated for anterior segment tumours. Br J Ophthalmol 2005;89 (8) 950- 955PubMedGoogle ScholarCrossref 16. Finger PTLatkany PKurli MIacob C The Finger iridectomy technique: small incision biopsy of anterior segment tumors. Br J Ophthalmol 2005;89 (8) 946- 949PubMedGoogle ScholarCrossref 17. Finger PTLu DBuffa ADeBlasio DMBosworth JL Palladium-103 versus iodine-125 for ophthalmic plaque radiotherapy. Int J Radiat Oncol Biol Phys 1993;27 (4) 849- 854PubMedGoogle ScholarCrossref 18. Finger PTBerson ANg TSzechter A Palladium-103 plaque radiotherapy for choroidal melanoma: an 11-year study. Int J Radiat Oncol Biol Phys 2002;54 (5) 1438- 1445PubMedGoogle ScholarCrossref 19. Astrahan MA Improved treatment planning for COMS eye plaques. Int J Radiat Oncol Biol Phys 2005;61 (4) 1227- 1242PubMedGoogle ScholarCrossref 20. van Klink Fde Keizer RJJager MJKakebeeke-Kemme HM Iris nevi and melanomas: a clinical follow-up study. Doc Ophthalmol 1992;82 (1-2) 49- 55PubMedGoogle ScholarCrossref 21. Brown DBoniuk MFont RL Diffuse malignant melanoma of the iris with metastasis. Surv Ophthalmol 1990;34 (5) 357- 364PubMedGoogle ScholarCrossref 22. Shields CLShields JAMaterin MGershenbaum ESingh ADSmith A Iris melanoma: risk factors for metastasis in 169 consecutive patients. Ophthalmology 2001;108 (1) 172- 178PubMedGoogle ScholarCrossref 23. Lois NShields CLShields JAEagle RC JrDe Potter P Cavitary melanoma of the ciliary body: a study of eight cases. Ophthalmology 1998;105 (6) 1091- 1098PubMedGoogle ScholarCrossref 24. Augsburger JJAffel LLBenarosh DA Ultrasound biomicroscopy of cystic lesions of the iris and ciliary body. Trans Am Ophthalmol Soc 1996;94259- 274PubMedGoogle Scholar 25. Kennedy RE Cystic malignant melanoma of the uveal tract. Am J Ophthalmol 1948;31 (2) 159- 167Google Scholar
Six-Year Incidence of Visual Loss in African Americans With Type 1 Diabetes Mellitus: The New Jersey 725Roy, Monique S.;Skurnick, Joan
2007 Archives of Ophthalmology
doi: 10.1001/archopht.125.8.1061pmid: 17698752
Abstract Objective To report the 6-year incidence of visual loss and associated risk factors in African Americans with type 1 diabetes mellitus. Methods African Americans with type 1 diabetes (n = 483) who participated in the New Jersey 725 study were reexamined as part of a 6-year follow-up. Best-corrected visual acuity, a structured clinical interview, fundus photographs, and blood pressure measurements were obtained. The biological evaluation included blood and urine assays. Any visual loss was defined as a visual acuity of 20/40 or worse in the better eye, blindness as a visual acuity of 20/200 or worse in the better eye, and doubling of the visual angle (DVA) as the loss of 15 or more letters between the first and second visits. Results Over 6 years, 19 of 440 patients (4.3%) developed visual loss in the better eye, 3 of 472 patients (0.6%) became blind, 47 of 481 patients (9.8%) developed DVA in the better eye, and 65 of 481 (13.5%) developed DVA in either eye. Baseline older age, high glycosylated hemoglobin level, retinopathy severity, and proteinuria were characteristics significantly (P<.001 for all) and independently associated with DVA in either eye at follow-up. Conclusions The 6-year incidence of DVA in either eye (13.5%) is high in African Americans with type 1 diabetes. Baseline poor glycemic control, diabetic retinopathy severity, proteinuria, and older age are predictors of visual loss in this population. Diabetic retinopathy (DR) remains the leading cause of new cases of legal blindness in Americans aged 20 to 64 years.1 Whether African Americans with type 1 diabetes mellitus are at a higher risk for visual loss than their white counterparts is unclear. Self-reported blindness in the 1970 Model Reporting Area registry indicated that nonwhite diabetic women were 3 times more likely to be blind from diabetes than either nonwhite diabetic men or diabetic whites.2 A large cohort of type 1 diabetic African Americans (the New Jersey 725) was previously examined,3 and the frequency of visual impairment (11%)—visual acuity (VA) of 20/40 or worse in the better eye—was higher than the 7.8% reported in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) for type 1 diabetic whites.4 Among the African American patients, the frequency of visual impairment was higher in women than in men (13.3% vs 7.7%).3 However, the frequency of blindness—VA of 20/200 or worse in the better eye—was similar in African American men and women (3.0% vs 3.1%), and was also similar in the African American patients compared with type 1 diabetic whites in the WESDR (3.1% vs 3.2%).3,4 The incidence of visual loss has been reported for whites with type 1 diabetes.5-7 To our knowledge, however, there are no published incidence data for large populations of African Americans with type 1 diabetes. We have reexamined the African American patients who participated in the New Jersey 725 study as part of a 6-year follow-up, which provides a unique opportunity to examine the incidence of visual loss in this population. The purpose of the present study was to determine the 6-year incidence of visual loss in and associated risk factors for African Americans with type 1 diabetes. Methods Study population Details regarding patients who had baseline examinations were previously reported.3 Patients diagnosed as having diabetes and treated with insulin before the age of 30 years and currently taking insulin were identified from a random review of 13 615 medical records.3 Excluded were patients with type 2 diabetes, those diagnosed as having diabetes after the age of 30 years, and patients with maturity-onset diabetes of youth.3 Of the 725 patients, 508 (70.1%) were available for the 6-year follow-up, 44 (6.0%) could not be located, 34 (4.7%) refused examination, and 139 (19.2%) had died within the 6-year interval. (Percentages do not total 100 because of rounding.) Of the 508 available patients, 25 (4.9%) were no longer taking insulin at the 6-year follow-up. Compared with those receiving insulin, patients not receiving insulin had, at baseline, a shorter duration of diabetes (mean ± SD, 7.0 ± 6.5 vs 10.4 ± 8.6 years; P < .02), a lower glycosylated hemoglobin level (mean ± SD, 10.9% ± 4.7% vs 13.5% ± 4.3%; P < .01), and higher C-peptide levels (mean ± SD, 2.91 ± 1.69 vs 1.06 ± 1.16 ng/mL [to convert C-peptide level to nanomoles per liter, multiply by 0.331]; P < .001), and more had a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater (88.0% vs 57.1%; P < .002).8 There were no significant differences at baseline between patients receiving and those not receiving insulin for sex (P=.69), age (P=.78), visual impairment in the better eye (P=.12), DR severity (P=.09), systemic hypertension (P=.10), macroangiopathy (P=.56), or renal disease (P=.32). Because these 25 patients not taking insulin may not be truly insulin dependent, they were excluded, leaving 483 patients (95.1%) for analysis. Details about those who were deceased, who were not located, or who refused a second examination were previously reported.8 Among the 483 participants, 195 (40.4%) were men and 288 (59.6%) were women. At baseline, their mean ± SD age was 27.5 ± 10.8 years and the mean ± SD duration of diabetes was 10.4 ± 8.6 years.8 The mean ± SD follow-up was 6.1 ± 0.5 years (median, 5.96 years). Procedures Examinations at both visits followed a similar protocol, which had been approved by the institutional review board of the University of Medicine & Dentistry of New Jersey, New Jersey Medical School. Patients were examined in the Eye Clinic of University Hospital in Newark. On arrival, informed written consent was obtained from each patient. Patients underwent a detailed examination that included best-corrected VA using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol9; measurement of intraocular pressure by applanation; dilation of the pupil and 7 standard stereoscopic Diabetic Retinopathy Study retinal photographs10; height and weight measurements; blood pressure measurements (twice in the sitting and standing positions)11; a structured clinical interview with medical and ophthalmologic histories, sociodemographic factors, and lifestyle variables; measurement of total glycosylated hemoglobin and total and high- and low-density lipoprotein cholesterol; and 4-hour timed urine collection for measurement of albumin excretion rate. Visual Acuity For each eye, best-corrected VA was recorded as the number of letters read—0 (≤20/250) to 70 (20/10). For eyes with a best-corrected VA of 20/250 or worse, a level of VA was assigned: −5, −10, −25, −40, −55, and −70 for VAs of 20/320, 20/400, 20/800, hand motions, light perception, and no light perception, respectively.5 Any visual loss was defined as a VA of 20/40 or worse in the better eye. Blindness was defined as a VA of 20/200 or worse in the better eye. Doubling of the visual angle (DVA) was defined as the loss of 15 letters or more on the ETDRS chart between the first and second visits (eg, VA change from 20/20 to 20/40) in the better eye or in either eye. The 6-year incidence of any visual loss was calculated for all patients (n = 440) who had a VA of better than 20/40 in the better eye at baseline. Patients who developed any visual loss were those in this group who had a VA of 20/40 or worse in the better eye at follow-up. The 6-year incidence of blindness (VA of 20/200 or worse in the better eye) was calculated for all patients (n = 472) who were not blind at baseline. Patients who became blind were those in this group who had become blind in the better eye by follow-up. The 6-year incidence of DVA in the better eye or in either eye was calculated for all patients, excluding those with no light perception in either eye at baseline (n = 481): patients who developed DVA in the better eye were those in this group who developed DVA in the eye that was the better eye at baseline; patients who developed DVA in either eye were those in this group who developed DVA in either eye at follow-up. DR Severity Color fundus photographs obtained at baseline and follow-up were graded for DR severity in a masked fashion by the Wisconsin Fundus Photograph Reading Center in Madison. The modified ETDRS Airlie House classification of DR was used.12,13 Level 10 indicates no DR; levels 20 to 35, mild nonproliferative DR; levels 43 to 53, moderate nonproliferative DR; and levels 61 to 85, proliferative DR (PDR) of increasing severity.13 For each eye, the maximum grade in any of the 7 standard photographic fields was used to define the retinopathy level according to the ETDRS severity scale.13 For each patient, the retinopathy level was determined from the severity level of the worse eye. If the retinopathy severity could not be graded in 1 eye, the subject was considered to have a score equivalent to that in the gradable eye. Macular edema (ME) was considered present if there was thickening of the retina with or without partial loss of retinal transparency within 1 disc diameter from the center of the macula and/or focal laser photocoagulation scars in the macular area and a documented history of ME.14 Eyes that could not be graded because of opacities of the media, phthisis, or enucleation were initially classified as “cannot grade.” For such persons, review of all previous medical records was done by one of us (M.S.R.). When a history of panretinal photocoagulation for PDR or pars plana vitrectomy for complications of PDR was documented via medical record review, then the DR level was scored as 85. Persons who had an ETDRS grading of less than 61 at examination and had previously received laser photocoagulation for PDR, as documented by medical record review, were classified as having a grade of 61. Definitions A patient's age was defined as the age at the baseline examination. Age at diagnosis of diabetes was defined as the age at which the diagnosis of diabetes was first recorded in the patient's medical record by a physician. The duration of diabetes was defined as the time between the age at diagnosis and the age at baseline. Systemic hypertension was defined as present if, at baseline, the systolic reading was 140 mm Hg or higher, the diastolic reading was 90 mm Hg or higher, or the patient was taking antihypertensive medication. Microproteinuria was defined as present if the baseline albumin excretion rate was 20 to 200 μg/min. Overt proteinuria was considered present if the baseline albumin excretion rate was greater than 200 μg/min. Macroangiopathy was considered present if, at baseline, the patient reported having undergone foot or leg amputation for a circulatory problem (excluding amputation secondary to an infection) or having had a myocardial infarction or a stroke, and if the patient's report was confirmed using standardized criteria by review of the medical records of all previous hospital admissions. Socioeconomic factors included patients' level of education (for those aged ≥25 years), personal annual income (for those aged ≥18 years), and family annual income. Patients' socioeconomic status was classified according to the Goldthorpe and Hope Social Grading of Occupations.15 Smoking was defined as “pack-years smoked,” obtained by dividing the number of cigarettes smoked per day by 20, multiplied by the number of years smoked until the baseline examination. Patients were categorized into those without myopia (spherical equivalent <−2 diopters) and those with significant myopia (spherical equivalent ≥−2 diopters). Ocular perfusion pressure was calculated as follows: 2/3{[Diastolic Blood Pressure + (Systolic Blood Pressure − Diastolic Blood Pressure)/3] − Intraocular Pressure}. Statistical analyses Statistical analyses were performed using SAS statistical software, version 9.1 (SAS Institute Inc, Cary, North Carolina). Incidence rates with 95% binomial confidence intervals (CIs) were calculated for the following end points: (1) any visual loss, (2) DVA in the better eye at baseline, and (3) DVA in either eye. The criterion for statistical significance was P < .05. For analysis of systemic risk factors, DVA in either eye was used. For analysis of ocular risk factors, DVA in right and left eyes was used. Relationships of incidence of DVA in either eye with binary risk factors (eg, sex, history of drug abuse, and educational level) were examined using the Fisher exact test. Relationships of incidence of DVA in either eye with ordinal risk factors (eg, categories of baseline age, duration of diabetes, DR severity level, and proteinuria) were examined using the Mantel-Haenszel trend test. Univariate logistic regression modeling was applied to selected variables to estimate the odds ratio and 95% CI to predict DVA in either eye. Risk factors significant in univariate analyses were entered into multiple logistic regression models to examine independent associations between risk factors and 6-year incidence of DVA in either eye. Forward regression was used first, with an entry criterion of P < .25. Because some of the risk factors were highly correlated with each other, alternative models included hypertension, proteinuria, or cholesterol levels only. Final models were selected with attention to variables' consistency of significance across alternative risk factor choices and the Akaike information criterion. Results Six-year incidence of any visual loss, blindness, and dva Of the 483 patients who participated in the 6-year follow-up, 19 of 440 (4.3%; 95% CI, 2.6%-6.7%) developed visual loss in the better eye, 3 of 472 (0.6%; 95% CI, 0.1%-1.9%) became blind in the better eye, 47 of 481 (9.8%; 95% CI, 7.3%-12.8%) developed DVA in the better eye, and 65 of 481 (13.5%; 95% CI, 10.6%-16.9%) developed DVA in either eye (Table 1). At the 6-year follow-up examination, visual loss was determined to be because of the following causes: (1) PDR, either alone (17 in the right eye and 12 in the left eye) or in combination with lens changes and/or glaucoma (6 in the right eye and 5 in the left eye); (2) lens opacities (6 in the right eye and 10 in the left eye); and (3) miscellaneous, ie, optic neuropathy, corneal opacities, and central retinal vein occlusion (3 in the right eye and 3 in the left eye). Relationship between 6-year incidence of visual loss and baseline age, duration of diabetes, and sex The incidences of visual loss in the better eye and of DVA in the better eye or in either eye increase significantly with increasing age at baseline (Figure 1). The incidence of DVA in either eye increases from 5.1% in patients aged 10 to 14 years to 30.6% in those 45 years or older at baseline (P < .001). The 3 patients who developed blindness during the 6-year period were aged 16, 20, and 33 years at baseline (Figure 1). The 6-year incidences of visual loss in the better eye and of DVA in the better eye or in either eye also increase with increasing duration of diabetes at baseline (Figure 2). The incidence of DVA in either eye increases from 1.3% in those with less than 5 years of diabetes at baseline to 33.3% in those with 30 years or more of diabetes (P < .001). The 3 patients who developed blindness at follow-up had durations of 7, 12, and 14 years of diabetes at baseline. When baseline age and duration of diabetes are examined simultaneously, only age is significantly associated with incidence of DVA in either eye (P < .03). There is no significant sex difference for incidence of any of the end points (P=.48 for any visual loss, P>.99 for blindness, and P=.27 for DVA in the better eye). Among the 287 women, 42 (14.6%) developed DVA in either eye at the 6-year follow-up compared with 23 (11.8%) of 194 men (P = .42). Relationship between 6-year incidence of visual loss and baseline severity of dr Table 2 shows that 6-year incidence of any visual loss, blindness, and DVA in right and left eyes increases significantly with increasing severity of DR, presence of ME, or presence of hard exudates. Of the patients with PDR in the right eye at baseline, 28.0% developed visual loss, 31.1% developed DVA, and 13.9% developed blindness in that eye at the 6-year follow-up. Relationship between 6-year incidence of dva in either eye and baseline characteristics Because of the low incidence of any visual loss, DVA in the better eye, and blindness, analyses of the risk factors are provided for DVA in either eye. Baseline characteristics of patients with and without DVA in either eye at the 6-year follow-up are provided in Table 3. Univariate analysis Six-year incidence of DVA in either eye was significantly associated with age at diagnosis of 13 years or older (P = .046), higher glycosylated hemoglobin levels (P = .008), higher systolic (P = .003) and diastolic (P = .01) blood pressure measurements, presence of proteinuria (P < .001), macroangiopathy (P = .006), and total and low-density lipoprotein cholesterol levels (P = .009 and P = .01, respectively) (Table 4). There were no significant associations between DVA in either eye and level of education (P=.36), socioeconomic status (P=.91), marital status (P>.99), employment status (P=.16), family (P=.16) or personal (P=.52) annual income, body mass index (P=.89), diuretic use (P=.27), smoking (P=.79), alcohol consumption (P=.14), illicit drug use (P=.31), or eye insurance coverage (P=.88). Doubling of the visual angle in either eye was significantly associated with severity of retinopathy, ME, hard exudates (Table 2), and ocular perfusion pressure (P < .10 and P = .001 for the right and left eyes, respectively). There was no significant association between DVA in either eye and myopia (P=.84 and .16 for right and left eyes, respectively) or intraocular pressure (P>.99 and .52 for right and left eyes, respectively). Multivariate analysis Older age, higher glycosylated hemoglobin level, and presence of proteinuria at baseline were significantly and independently associated with 6-year incidence of DVA in either eye (Table 5). When baseline DR severity and ME were included in the multiple logistic model, higher glycosylated hemoglobin level and DR severity at baseline were the risk factors significantly and independently associated with incidence of DVA in either eye at the 6-year follow-up (Table 5). Comment Data from the present study indicate that during the 6-year period, 19 (4.3%) of our study group of type 1 diabetic African Americans became visually impaired in the better eye, 3 (0.6%) became blind, 47 (9.8%) developed DVA in the better eye, and 65 (13.5%) developed DVA in either eye. In our African American patients, baseline older age, poor glycemic control, DR severity, and presence of proteinuria were factors significantly and independently associated with the 6-year incidence of DVA in either eye. The few published studies5-7,16-19 of incidence of visual loss in persons with type 1 diabetes have been for primarily white populations. In the WESDR, the 4-year incidence of DVA in the better eye (5.9%) is lower than the 9.8% found in our African American patients at our 6-year follow-up.5 However, the 6-year incidence of any visual loss in the better eye in our African American patients is remarkably similar to the 4-year incidence of visual loss in the type 1 diabetic whites in the WESDR (4.3% vs 4.7%, respectively).5 In the present study, the 6-year incidence of blindness (0.6%) is much lower than rates reported for white type 1 diabetic populations (1.5% at 4 years in the WESDR,5 7.6% at 8 years in the Danish study by Sjolie and Green,18 3% at 5 years in an English study,16 and 3.7% at 1 year in the Danish study by Nielsen17), albeit similar to the 5-year 0.5% reported by Agardh et al19 in type 1 Swedish patients. There are a number of probable reasons for this low incidence of blindness in our cohort. First, our African American patients were recruited more recently than were patients in the WESDR (1993-1998 vs 1980-1982), when photocoagulation treatment for PDR had become universally available. Moss et al7 previously noted that there was a decrease in the annual incidence of blindness during the 14-year follow-up of the WESDR cohort. Second, in the study by Sjolie and Green,18 patients who became blind and died during the follow-up were included in the calculation of the incidence data, unlike that which was done in the present study. Finally, our low incidence of blindness may be related to selective mortality of African American patients with severe visual impairment at baseline, because 13 of the 139 patients (9.4%) who died before the 6-year follow-up were already legally blind and an additional 18 (12.9%) were blind in 1 eye. Thus, the incidence of blindness among our 6-year survivors may have underestimated the incidence of blindness among the 725 patients in the original cohort. In the present study, we found that baseline DR severity—particularly PDR—was a strong predictor of visual loss. Others5-7,20-23 have reported similar findings. For example, in the Diabetic Retinopathy Study,23 untreated eyes with PDR at baseline had a 6-year 37% incidence of severe visual loss. In the WESDR study,5 30% of patients with PDR at baseline became blind at the 4-year follow-up. These incidence rates are higher than the 13.9% reported herein for our African American patients with PDR at baseline (Table 2). Differences in incidence rates between studies may again be explained by the availability of photocoagulation and its effectiveness in reducing severe visual loss from PDR.23 For instance, in the present study, 21 of the 28 patients (75.0%) who, at baseline, required laser photocoagulation for PDR in at least 1 eye had received panretinal photocoagulation at follow-up. However, only 5 of the 29 patients (17.2%) with clinically significant ME at baseline had received focal laser therapy when examined at follow-up. This suggests that, unlike PDR, ME—whose 6-year incidence (15.9%) is high in our patients—may not have been diagnosed or adequately treated in this group.8 We cannot exclude, however, that ME may have resolved in patients who received diuretics or underwent dialysis. We also found that poor glycemic control was significantly associated with the 6-year incidence of DVA in either eye in our African American patients. Poor glycemic control is a well-established risk factor for visual loss as a result of its deleterious effect on progression of DR.5,20,22,24 It has previously been shown that glycemic control at baseline was poor among an African American population and remained poor at follow-up.8,25 Furthermore, among African American patients, those in the upper quartile of glycosylated hemoglobin values at baseline had 8 to 20 times the odds for progression to PDR at the 6-year follow-up than did patients in the lowest quartile.8 Thus, improving glycemic control in this population is critical for reducing visual loss. In the present study, the presence of proteinuria was another baseline characteristic significantly associated with incidence of visual loss, a finding similar to that found for white type 1 diabetic patients.5,21,22 However, as also noted by others, DR severity at baseline was a stronger predictor of visual loss than was proteinuria, as we demonstrated when both characteristics were entered into the logistic regression model (Table 4).21 In our African American patients, microproteinuria, which is detected within a few years of the diagnosis of diabetes, seems to precede retinopathy and is a major predictor of mortality, particularly in men.26,27 Thus, African American patients diagnosed as having PDR should be evaluated for the presence of proteinuria. In our African American patients, the 6-year incidence of DVA in either eye was significantly and positively associated with baseline older age and longer duration of diabetes, as found in some, but not all, other studies.5-7,16-19 In our study, older age was a more powerful predictor of incidence of visual loss than was duration of diabetes. While the number of African American patients who became blind (n = 3) is small, all 3 cases occurred among patients who, at baseline, were young (aged 16-33 years) and had a relatively short duration (7-14 years) of diabetes. It is difficult to make exact comparisons between studies of type 1 diabetic African Americans and their white counterparts. For example, compared with studies of type 1 diabetic white patients, our study population was smaller than some but larger than others.5,19,21 Other possible confounding factors in comparing our studies with similar studies of the white population are differences in the time points at which patients were enrolled, changes in treatments, and/or socioeconomic status. Finally, the higher mortality among African American patients compared with type 1 diabetic whites could lead to underestimation of the incidence of visual loss in the former population.27 In summary, data from this study indicate that the 6-year incidence of DVA in either eye (13.5%) is particularly high in African Americans with type 1 diabetes and that baseline older age, poor glycemic control, severity of DR, and presence of proteinuria are significant and independent predictors of visual loss. Correspondence: Monique S. Roy, MD, The Institute of Ophthalmology and Visual Science, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, 90 Bergen St, Room 6164, Newark, NJ 07101-1709 ([email protected]). Submitted for Publication: September 12, 2006; final revision received December 13, 2006; accepted December 16, 2006. Financial Disclosure: None reported. Funding/Support: This study was supported by grant RO1 EY 09860 from the National Eye Institute; a Lew Wasserman Merit Award; and an unrestricted grant from Research to Prevent Blindness. References 1. Klein RKlein BE Vision disorders in diabetes. Diabetes in America 2nd Bethesda, MD National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health1995;293- 338NIH publication 95-1468Google Scholar 2. Kahn HMoorhead H Statistics on Blindness in the Model Reporting Area, 1969-1970. Washington, DC US Government Printing Office1973; NIH publication 73-427 3. Roy MS Diabetic retinopathy in African Americans with type 1 diabetes: the New Jersey 725. Arch Ophthalmol 2000;118 (1) 97- 104PubMedGoogle ScholarCrossref 4. Klein RKlein BMoss S Visual impairment in diabetes. Ophthalmology 1984;91 (1) 1- 9PubMedGoogle ScholarCrossref 5. Moss SEKlein RKlein BE The incidence of vision loss in a diabetic population. Ophthalmology 1988;95 (10) 1340- 1348PubMedGoogle ScholarCrossref 6. Moss SEKlein RKlein BE Ten-year incidence of visual loss in a diabetic population. Ophthalmology 1994;101 (6) 1061- 1070PubMedGoogle ScholarCrossref 7. Moss SEKlein RKlein BE The 14-year incidence of visual loss in a diabetic population. Ophthalmology 1998;105 (6) 998- 1003PubMedGoogle ScholarCrossref 8. Roy MSAffouf M Six-year progression of retinopathy and associated risk factors in African American patients with type 1 diabetes mellitus: the New Jersey 725. Arch Ophthalmol 2006;124 (9) 1297- 1306PubMedGoogle ScholarCrossref 9. Early Treatment of Diabetic Retinopathy Study (ETDRS), Manual of Operations. Baltimore, MD ETDRS Coordinating Center, Dept of Epidemiology and Preventive Medicine, University of Maryland1985; 10. Diabetic Retinopathy Study Research Group, Report number 7: a modification of the Airlie House classification of diabetic retinopathy. Invest Ophthalmol Vis Sci 1981;21 (1) ((pt 2)) 210- 226Google Scholar 11. Canner PLBorhani NOOberman A et al. The Hypertension Prevention Trial. Am J Epidemiol 1991;134 (4) 379- 392PubMedGoogle Scholar 12. Early Treatment Diabetic Retinopathy Study Research Group, Grading diabetic retinopathy from stereoscopic color fundus photographs: an extension of the modified Airlie House classification. Ophthalmology 1991;98 (5) ((suppl)) 786- 806PubMedGoogle ScholarCrossref 13. Early Treatment Diabetic Retinopathy Study Research Group, Fundus photographic risk factors for progression of diabetic retinopathy: ETDRS Report Number 12. Ophthalmology 1991;98 (5) ((suppl)) 823- 833PubMedGoogle ScholarCrossref 14. Early Treatment Diabetic Retinopathy Study Research Group, Photocoagulation for diabetic macular edema. Arch Ophthalmol 1985;103 (12) 1796- 1806PubMedGoogle ScholarCrossref 15. Goldthorpe JHope K The Social Grading of Occupations: A New Approach and Scale. New York, NY Oxford University Press 1974;134- 143 16. Caird F Diabetic retinopathy as a cause of visual impairment. Diabetes and the Eye Oxford, England Blackwell1968;41- 46Google Scholar 17. Nielsen NV Diabetic retinopathy 1: the course of retinopathy in insulin-treated diabetics. Acta Ophthalmol (Copenh) 1984;62 (2) 256- 265PubMedGoogle ScholarCrossref 18. Sjolie AKGreen A Blindness in insulin-treated diabetic patients with age at onset <30 years. J Chronic Dis 1987;40 (3) 215- 220PubMedGoogle ScholarCrossref 19. Agardh EAgardh CDHansson-Lundblad C The five-year incidence of blindness after introducing a screening programme for early detection of treatable diabetic retinopathy. Diabet Med 1993;10 (6) 555- 559PubMedGoogle ScholarCrossref 20. Davis MDFisher MRGangnon RE et al. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18. Invest Ophthalmol Vis Sci 1998;39 (2) 233- 252PubMedGoogle Scholar 21. Rand LIPrud’homme GJEderer FCanner PL Factors influencing the development of visual loss in advanced diabetic retinopathy: Diabetic Retinopathy Study (DRS) report No. 10. Invest Ophthalmol Vis Sci 1985;26 (7) 983- 991PubMedGoogle Scholar 22. Kaufman SCFerris FL IIISeigel DGDavis MDDeMets DL Factors associated with visual outcome after photocoagulation for diabetic retinopathy: Diabetic Retinopathy Study Report #13. Invest Ophthalmol Vis Sci 1989;30 (1) 23- 28PubMedGoogle Scholar 23. Diabetic Retinopathy Study Research Group, Photocoagulation treatment of proliferative diabetic retinopathy. Ophthalmology 1981;88 (7) 583- 600PubMedGoogle ScholarCrossref 24. Diabetes Control and Complications Trial Research Group, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329 (14) 977- 986PubMedGoogle ScholarCrossref 25. Roy MS Diabetic retinopathy in African Americans with type 1 diabetes: the New Jersey 725, II: risk factors. Arch Ophthalmol 2000;118 (1) 105- 115PubMedGoogle ScholarCrossref 26. Roy MS Proteinuria in African Americans with type 1 diabetes. J Diabetes Complications 2004;18 (1) 69- 77Google ScholarCrossref 27. Roy MRendas-Baum RSkurnick J Mortality in African-Americans with type 1 diabetes: the New Jersey 725. Diabet Med 2006;23 (6) 698- 706PubMedGoogle ScholarCrossref
Superior Oblique Tendon Incarceration SyndromeKushner, Burton J.
2007 Archives of Ophthalmology
doi: 10.1001/archopht.125.8.1070pmid: 17698753
Abstract Objective To describe the clinical features, etiology, and management of superior oblique tendon incarceration syndrome. Methods This series consists of all patients I treated between September 15, 1974, and March 1, 2006, for restrictive hypertropia in which the superior oblique tendon was found scarred to the superior rectus muscle insertion after prior surgery. Results Twenty eyes in 18 patients were included in this series. The mean ± SD hypertropia of the affected eye was 15.4 ± 9.0 prism diopters, and the mean ± SD incyclotropia was 15.0° ± 3.5°. Causes of superior oblique tendon incarceration syndrome included prior superior rectus muscle resection, recession, plication, or transposition; superior oblique tendon recession, disinsertion, or posterior tenectomy; and scleral buckling surgery. The syndrome was difficult to treat and required a mean ± SD of 1.9 ± 0.7 additional surgical procedures to correct. Conclusions Superior oblique tendon incarceration syndrome is a complication of surgery on the superior rectus muscle or superior oblique tendon that can result in restrictive hypertropia and incyclotropia. Proper handling of the connection between the superior oblique tendon and superior rectus muscle at the time of surgery may prevent this complication, which can be difficult to treat. The superior oblique muscle has a triple function that causes intorsion, depression, and to a lesser degree, abduction. The specific location of the insertion of the superior oblique tendon and the angle made by the course of the tendon and the anterior-posterior axis of the globe determine how the muscle's force is distributed among these 3 functions. Any substantial anterior displacement of the tendon's insertion will greatly increase the intorsional force vector,1,2 and any movement nasal and anterior to the center of rotation of the globe may restrict depression.3,4 Several iatrogenic clinical situations exist in which the superior oblique tendon may become scarred to the nasal corner of the superior rectus muscle insertion.3,5 This occurrence has been referred to as superior oblique inclusion syndrome; however, I believe the name superior oblique tendon incarceration syndrome is more appropriately descriptive. To my knowledge, no reports have described this syndrome in detail, including its characteristic findings, etiology, prevention, or management. A search of the PubMed database for the keywords superior oblique inclusion or superior oblique incarceration found only 2 references to this clinical entity. One was a 4-case series by Metz and Norris6 of patients who developed torsional diplopia after scleral buckling. It included 1 patient in whom the torsion was caused by the superior oblique tendon becoming scarred anteriorly to the encircling band. The other was a report of different weakening procedures of the superior oblique tendon by Castanera de Molina et al3 in which they reported 2 cases of superior oblique tendon incarceration syndrome. In addition, Jampolsky5 mentioned the existence of this entity in published transactions of the New Orleans Academy of Ophthalmology. None of these reports described the syndrome in detail. I have observed and treated many patients with this syndrome. The purpose of this study is to provide information regarding the characteristics, etiology, prevention, and management of superior oblique tendon incarceration syndrome. Methods This is a retrospective review of all patients I operated on who were found at surgery to have the superior oblique tendon scarred to the nasal corner of the superior rectus muscle insertion. This review was accomplished by searching my patient database to identify patients in whom I observed that clinical finding between September 15, 1974, and March 1, 2006. For patients in whom prior surgery was performed by other ophthalmologists, the operative reports from the prior surgical procedures were obtained and studied to help determine the cause of this complication. My preoperative examination included alternate prism and cover testing at 6 m in the primary position, in the secondary fields (gazes right, left, up, and down), and with the patient's head tilted 30° to the right and left (Bielschowsky head tilt test).7 Measurements were also made at one-third meter. In most patients the misalignment at 6 m in the tertiary (oblique) fields was also quantified, unless the patient was too young to allow for this additional testing. Subjective torsion was tested in all sufficiently cooperative patients with double Maddox rods. Ductions and versions were also assessed. Surgery was always performed under general anesthesia with the patients being pharmacologically paralyzed to permit accurate assessment of intraoperative passive ductions. After 1981 all patients underwent exaggerated passive duction testing to assess the oblique muscles, as described by Guyton.8 In addition, after 1985, patients underwent rotary passive duction testing at the time of surgery to determine if there was a torsional restriction. This test is performed by fixating the eye at the 6-o’clock and 12-o’clock positions with forceps and rotating the eye counterclockwise and clockwise until resistance is felt. If the eye could be passively intorted further than it could be extorted, a restriction to excyclorotation was present (Figure 1). All patients were followed up for at least 6 months after their last surgical procedure. This study was approved by the University of Wisconsin institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Results The review identified 20 eyes in 18 patients who were treated for superior oblique tendon incarceration syndrome. Their characteristics are presented in the Table. All patients in this series had hypertropia of the affected eye (mean ± SD, 15.7 ± 8.7 prism diopters [PD]; range, 8-35 PD), except the 2 who had bilateral superior oblique tendon inclusion. All patients had some limitation of depression, but it was variable, ranging from −1 to −4 (on a 5-point scale of 0 to −4); consequently, the hypertropia increased in downgaze in all patients. In most the limitation was moderate (−2 to −3). In some patients depression was more limited in adduction and in others in abduction. Because of the overall complexity of these patients and the presence of other findings (eg, slipped muscles, restrictions secondary to Graves orbitopathy, or underacting muscles due to prior large recessions), one could not attribute all the limitation of depression to the incarceration of the superior oblique tendon. This can also explain the wide range observed with respect to downgaze limitation. All but 2 patients could be tested for subjective torsion, and they all had incyclotropia of the affected eye (mean ± SD, 15.1° ± 3.5°; range, 10°-20°). Results of the Bielschowsky head tilt test were inconsistent. In some patients no substantial increase in hypertropia on head tilt to either side was found, and in others a small to moderate increase on ipsilateral head tilt was found. Only 2 patients showed a small increase on head tilt to the contralateral side. In general, the test was not useful diagnostically. Vertical passive duction test results tended to be abnormal for depression, and they seemed to correlate with the size of the primary position hypertropia; the larger the deviation, the greater the restriction of passive ductions. All of the patients with unilateral involvement who underwent exaggerated forced duction testing had substantially more prominent tightness of the superior oblique tendon in the affected than in the contralateral eye. All patients who underwent rotary passive duction testing had a notable restriction of excyclorotation in the affected eye, which was abnormal to a greater degree than the exaggerated passive duction test results. I had performed prior surgery in 1 of the patients (case 3) who had undergone 3 prior strabismus surgical procedures. Two of them involved surgery on her right superior rectus muscle before my caring for her. I advanced her right superior rectus muscle from 14 to 7 mm from the limbus, which resulted in superior oblique tendon incarceration syndrome. In the remaining 17 patients, someone else had performed the prior surgery. I was able to obtain previous operative reports for all 17, and thus I was able to tell what surgical procedure predisposed patients to superior oblique tendon incarceration syndrome. However, only 1 of the 17 reports indicated any unusual findings at the time of surgery that suggested the superior oblique tendon might have gotten scarred to the superior rectus muscle insertion. In that case (case 12), unique findings were observed. This patient had previously undergone a right superior oblique tenectomy and right inferior oblique muscle myectomy to treat oscillopsia secondary to superior oblique myokymia by another pediatric ophthalmologist. These procedures eliminated his oscillopsia but left him with a 45-PD right hypotropia and an inability to elevate his right eye. He underwent additional surgery by the same physician, at which time his right superior rectus muscle was discovered to have been avulsed. The surgeon thought that there were 2 separate slips of muscle: a larger temporal slip and a smaller nasal slip. They were both sutured to the original superior rectus muscle insertion site, and the right inferior rectus muscle was recessed using an adjustable suture. After surgery the patient had no vertical misalignment in the primary position but had 15° of right incyclotropia with markedly limited elevation and depression of the right eye. His symptoms of oscillopsia had returned. I operated on him 3 months later and found the right superior oblique tendon scarred to the nasal corner of the superior rectus muscle insertion (Figure 2). Presumably, what was thought to be a nasal slip of superior rectus muscle at the time of his second surgical procedure was in fact the remaining superior oblique tendon, which was purposefully sutured to the superior rectus muscle insertion. After I performed a tenectomy of the remaining superior oblique tendon, he manifested 12° to 15° of right excyclotropia and still had limited elevation and depression of the right eye. During a subsequent operation, I found that the proximal end of his myectomized right inferior oblique muscle was tight and scarred to the temporal corner of the right inferior rectus muscle. Presumably, it had been inadvertently hooked and incorporated with the right inferior rectus muscle at the time of his right inferior rectus muscle recession. This condition was treated with an additional myectomy of the right inferior oblique muscle. In addition, a simultaneous posterior fixation of the contralateral left inferior rectus muscle was performed to treat a right hypertropia in downgaze. Although this patient's findings are presented in the Table, I did not include them in calculations of the mean amount of hypertropia and incyclotropia in this series because he had the unique situation of having incarceration of both the superior oblique tendon and the inferior oblique muscle in the respective adjacent vertical rectus muscle insertion. I similarly excluded the 2 patients with bilateral superior oblique tendon incarceration from the calculation of the mean hypertropia in the primary position; however, I included them in the calculation of the mean amount of incyclotropia with each eye entered as a separate data point. My approach for treating this entity is still in a state of evolution and is not fully satisfactory. Also, in addition to surgery on the incarcerated superior oblique tendon, many patients underwent simultaneous surgery on other vertical or horizontal muscles, which was dependent on the magnitude of the deviation, the presence of restriction that persisted after the incarcerated tendon was freed up, and their incomitant pattern. Consequently, I cannot provide a standard treatment approach for all patients with this syndrome. This confirms the idea that complex strabismus may begin with a specific cause (eg, a restriction) and then become multifactorial as other muscles become contractured. In this series, the most common manifestation of this fact was the presence of contracture of the superior rectus muscle in the affected eye. When that was found, the contractured muscle was recessed. Despite the heterogeneity of these patients, some general treatment principles have evolved. Initially, I simply tried to free the incarcerated tendon; however, in 3 of the 4 patients on whom I tried this approach, the adherence recurred shortly thereafter. This treatment was successful only in case 4 (Figure 3). Castanera de Molina described a similar lack of success in treating the syndrome by simply freeing the incarcerated tendon (written communication, August 22, 2006). In the subsequent 2 patients, I fashioned a sling of 6-0 polyglactin suture material and used that to hold the tendon approximately 5 mm posterior to the nasal corner of the superior rectus muscle insertion. In these patients the tendon scarred to the sclera at the site of the sling, resulting in further symptoms and abnormalities of motility. Both tenectomy and recession of the tendon to the superior nasal quadrant in the manner described by Prieto-Díaz9 proved successful in eliminating the symptoms of incarceration syndrome. However, depending on the patient's history and findings, this treatment often resulted in the clinical picture of a fourth cranial nerve palsy. In many of the cases in which I either freed and mobilized the tendon or recessed the tendon, I had to disinsert the superior rectus muscle to complete the dissection of the superior oblique tendon. The Table indicates the patients in whom this was necessary. In general, I needed to do this if the prior surgical procedure did not involve recessing or disinserting the superior oblique tendon. In patients on whom either of those procedures were performed, the original insertional end of the tendon ended up at the nasal border of the superior rectus muscle, thus making it unnecessary to detach the superior rectus muscle to visualize the entire superior oblique tendon. Most recently, I have been performing a split tendon lengthening procedure in a manner similar to the one reported by Bardorf and Baker10 and leaving the distal end of the tendon attached where I found it. Although this approach appears successful in eliminating the findings of superior oblique tendon incarceration syndrome, it still necessitated additional surgery in some patients to treat an ipsilateral fourth nerve palsy. Despite this fact, this approach is currently my preferred method of treating this condition. In many cases in this series, other muscles were also operated on simultaneously in addition to the superior oblique tendon. Most often this involved recession of the ipsilateral superior rectus muscle, and sometimes it included surgery to correct horizontal deviations. Overall, the patients in this series needed to undergo a mean ± SD of 1.8 ± 0.7 surgical procedures (range, 1-3) to correct this entity and its sequelae; however, all but 1 were visually comfortable and found their cosmetic appearance acceptable as of their last examination. Although this number includes the operation at which the superior oblique tendon incarceration was diagnosed and initially treated, it does not include any previous surgical procedures. One patient (case 8) had initially undergone bilateral superior oblique tendon recessions using a suspension technique (“hang-back”) by another ophthalmologist to treat marked overdepression in adduction, which resulted in a worsening of his findings. When I operated on this patient, I found superior oblique tendon incarceration syndrome bilaterally and treated him with split tendon lengthening in each eye, which only slightly improved his symptoms. Subsequent dynamic magnetic resonance imaging suggested that he had lateral rectus instability, as described by Oh et al.11 His lateral rectus muscles slipped superiorly on abduction, which may have been the cause of his initial overdepression in adduction. Further surgery is planned to stabilize the lateral rectus muscles inferiorly; however, it has not yet been performed. Case 4 is unique in that the cause of the patient's problem is somewhat unclear. She was born with left hypotropia associated with monocular elevation deficiency. Another pediatric ophthalmologist treated her initially with a 3-mm recession of her left inferior rectus muscle combined with a transposition of her left medial rectus muscle and left lateral rectus muscle to the left superior rectus muscle (Knapp procedure)12 at 8 months of age. He positioned the transposed horizontal rectus muscles to keep their new insertions on the spiral of Tillaux. This approach resulted in an overcorrection characterized by a 20-PD left hypertropia and limited depression of her left eye. Four months later the same surgeon recessed the left superior rectus muscle 5.5 mm. At the time of this second operation, the surgeon described substantial scarring around the superior rectus muscle and the transposed medial rectus muscle. This second operation had essentially no effect on the hypertropia. When I examined her at 18 months of age, she had 18 PD of left hypertropia with a markedly limited ability to depress her left eye (Figure 3A). An alternate cover test confirmed that this was not dissociated vertical divergence, since an even larger right hypotropia was noticed when she was made to fixate with her left eye. At surgery 1 month later, I found the left superior oblique tendon scarred to the nasal corner of the left superior rectus muscle insertion and the superior corner of the transposed left medial rectus muscle insertion in 1 confluent mass of tissue (Figure 3B). I freed the superior oblique tendon and reposited it in its normal position and infraplaced the left medial and lateral rectus muscles, returning them to their original muscle insertion site. After surgery she had a negligible left hypertropia, which has been stable for 8½ years (Figure 3C). In this patient it is impossible to tell which prior surgical procedure caused the incarceration of the superior oblique tendon. It may have occurred during the recession of the superior rectus. Alternatively, at the time of the medial rectus transposition superiorly, the surgeon may have inadvertently hooked the superior oblique tendon and incorporated it in the suturing. Comment Superior oblique tendon incarceration syndrome is a complicated iatrogenic disorder of ocular motility that can occur after surgery on the superior rectus muscle or superior oblique tendon or after scleral buckling surgery. Treatment can be difficult and often requires multiple subsequent surgical procedures. The superior oblique tendon is adherent to the undersurface of the superior rectus muscle by tenuous areolar tissue,13 which Jampolsky5,14 called frenulum. He pointed out that when the superior rectus muscle is recessed, this frenulum will cause the superior oblique tendon to retract with the superior rectus muscle, as long as the frenulum is left intact. Prieto-Díaz15 reported similar observations. If the frenulum is severed, the superior oblique tendon will not retract and can scar to the superior rectus muscle insertion if the superior rectus muscle is recessed. Jampolsky therefore advocated preserving the frenulum when recessing the superior rectus muscle. This advice seems prudent to me. However, he also indicated that the frenulum may prevent the superior rectus muscle from taking up the slack if a recession of greater than 10 mm is desired using a suspension technique. In that circumstance, Jampolsky advocates cutting the frenulum. It seems to me that separating this connection between the superior rectus muscle and the superior oblique tendon could predispose the patient to superior oblique tendon incarceration syndrome, particularly because a recession of approximately 10 mm would place the new insertion directly over the superior oblique tendon. Prieto-Díaz15 observed that this does occur. However, Castanera de Molina has indicated that perhaps the adverse effects of superior oblique tendon incarceration might not be severe if it occurs close to the equator of the globe because the vector forces would not be as disadvantageous in that position (written communication, June 28, 2006). It is not clear from prior operative records if the frenulum had been severed in my 3 patients who developed superior oblique tendon incarceration syndrome after prior ipsilateral superior rectus muscle recession. However, in all 3 the recession was performed using a suspension technique. Conversely, the frenulum will cause the superior oblique tendon to be drawn forward if the superior rectus muscle is resected and the frenulum is left intact. Transposition of the superior rectus muscle temporally, as is performed to treat sixth cranial nerve palsy, can drag the superior oblique tendon with it if the frenulum is not severed. I am similarly unclear as to how the frenulum was handled in my patients who had prior superior rectus muscle resection or transposition temporally. It is also possible that in my patients who had prior recession, resection, or transposition of the superior rectus muscle, the superior oblique tendon was inadvertently hooked when the superior rectus muscle was identified and was inadvertently incorporated in the sutures. The normal anatomical course of the superior oblique tendon has its functional origin (the trochlea) anterior to its insertion. Consequently, the distance between the superior rectus muscle insertion and the superior oblique tendon is shorter along the nasal edge of the superior rectus muscle than along the temporal edge. Thus, if the superior oblique tendon is recessed following its normal anatomical course, the insertional end will move forward and be closer to the superior rectus muscle insertion. Any recession procedure that does not fix the superior oblique tendon to the sclera at the desired point may result in this restrictive syndrome. Seven eyes in 5 of my patients developed this complication after prior surgical procedures on the superior oblique tendon, either in the form of a disinsertion or recession using a suspension technique. I know of no way to prevent this syndrome with either of those surgical procedures, unless there is minimal stripping of the frenulum at the time of surgery. However, if the frenulum is left essentially intact, the tendon will be constrained and unable to effect the desired recession. This is consistent with Parks' observations reported in his Doyne Memorial Lecture.13 He stated that complete disinsertion of the superior oblique tendon will have a minimal weakening effect unless the anterior and posterior connective tissue around the tendon are incised, in which case the weakening effect is profound. Interestingly, Castanera de Molina et al3 compared different superior oblique weakening procedures and found the highest incidence of persistent overdepression in the infra-adducted position with disinsertion (62.5%), which they referred to as an uncontrolled procedure. They also reported cases of superior oblique tendon incarceration syndrome with that procedure, which is consistent with my observations. According to Castanera de Molina et al, in 1974 Prieto-Díaz reported in a transaction of the Consejo Latino-Americana de Estrabismo (CLADE) Congress that superior oblique tendon inclusion syndrome can occur after a variety of surgical procedures on the superior oblique tendon or superior rectus muscle. In the 3 patients who developed this complication after scleral buckling surgery, I found that the encircling band had been placed posterior to the superior oblique tendon insertion. This approach had the effect of tucking the tendon and drawing it anteriorly. Obviously, care must be taken to avoid this situation during placement of the encircling band. These cases are somewhat different from the one described by Metz and Norris.6 In their patient, the superior oblique tendon was scarred to the posterior edge of the encircling silicone band, which in turn was posterior to the superior rectus muscle insertion. Their patient was successfully treated with freeing of the scarred tendon. In my patients, the superior oblique tendon was incarcerated between the superior rectus muscle insertion and the encircling band, which in effect tucked the tendon (Figure 4). It was impossible to simply mobilize the tendon without removing the silicone band, and the tendon beneath the band was atrophic. In this series, I excluded patients who had the findings at surgery described by Metz (eg, the superior oblique tendon scarred to the posterior edge of the buckle) because I believe that represents a somewhat different entity. The lack of uniform response to the Bielschowsky head tilt test is not surprising given the heterogeneity of the initial strabismic conditions in this patient group. Some had dissociated vertical divergence, suspected superior oblique muscle palsy, partial third cranial nerve palsy, Graves orbitopathy, and comitant primary vertical strabismus. Many had undergone prior surgery on multiple vertical muscles. These factors can all result in misleading findings with the 3-step test, which is designed to identify isolated vertical muscle palsy.7,16,17 This study needs to be viewed in light of its limitations. Being retrospective in nature, measurements were not obtained in a masked manner or with the rigor that is inherent in prospective studies. Nevertheless, I believe the qualitative descriptions are sufficiently accurate to provide the ophthalmic surgeon with the information needed to recognize this entity. Also, it can be hard to extrapolate meaningful treatment protocols from this series because the patients had such complex and heterogeneous histories and findings. In addition, because this series represents my experience during a period of more than 30 years, there was presumably a learning curve in my ability to identify and strategically treat this condition. I believe that this study justifies some conclusions. Superior oblique tendon incarceration syndrome should be suspected in any patient who had prior superior rectus muscle surgery of any type or a scleral buckling procedure and in whom there is hypertropia of the affected eye, incyclotropia of 10° or more, and limitation of depression. Rotary passive ductions and exaggerated passive ductions at the time of surgery can be helpful in diagnosing this complication. It can be difficult to treat and may require more than 1 additional surgical procedure. Simply freeing the incarcerated tendon is often unsuccessful. Recession, tenectomy, or split lengthening of the tendon can eliminate the syndrome but may result in subsequent motility problems that require treatment. Until further studies are performed to clarify the behavior of the superior oblique frenulum during different surgical procedures, the following guidelines (based on theoretical considerations) seem prudent for prevention of superior oblique tendon incarceration syndrome: (1) do not separate the superior oblique frenulum when recessing the superior rectus muscle up to 10 mm; (2) separate the frenulum for superior rectus muscle resections or transpositions; (3) to prevent superior oblique tendon incarceration syndrome caused by superior oblique tendon disinsertions or recessions with a suspension technique, strip the frenulum to effect the desired recession; and (4) whenever surgery is performed on the superior rectus muscle, identify the superior oblique tendon and confirm that it is not inadvertently incorporated in the sutures. Correspondence: Burton J. Kushner, MD, Department of Ophthalmology and Visual Sciences, University of Wisconsin Hospital and Clinics, 2870 University Ave, Suite 206, Madison, WI 53705 ([email protected]). Submitted for Publication: December 8, 2006; final revision received January 15, 2007; accepted January 21, 2007. Financial Disclosure: None reported. Funding/Support: This study was supported by an unrestricted grant from Research to Prevent Blindness, Inc. References 1. Harada MIto Y Surgical correction of cyclotropia. Jpn J Ophthalmol 1964;888- 96Google Scholar 2. Kushner BJ Surgery with respect to cyclotropia. Ocular Ther Surg 1980;144- 54Google Scholar 3. Castanera de Molina AFabiani RGiner MG Downshoot in infra-adduction following selected superior oblique surgical weakening procedures for A-pattern strabismus. Binocul Vis Strabismus Q 1998;13 (1) 17- 28PubMedGoogle Scholar 4. Prieto-D Jaz JSouza-Dias C A- and V-pattern deviations. 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