Performing corneal crosslinking under local anaesthesia in patients with Down syndrome

Performing corneal crosslinking under local anaesthesia in patients with Down syndrome Int Ophthalmol (2018) 38:917–922 https://doi.org/10.1007/s10792-017-0535-1 ORIGINAL PAPER Performing corneal crosslinking under local anaesthesia in patients with Down syndrome . . Nienke Soeters Esme ´e Bennen Robert P. L. Wisse Received: 2 November 2016 / Accepted: 10 April 2017 / Published online: 19 April 2017 The Author(s) 2017. This article is an open access publication Abstract Keywords Down syndrome  Keratoconus  Corneal Purpose To report on the ability to perform corneal crosslinking  CXL  Local anaesthesia crosslinking (CXL) under local anaesthesia for the treatment of keratoconus in patients with Down Introduction syndrome. Methods Nine eyes of seven patients with both Keratoconus has long since been linked with Down keratoconus and Down syndrome were scheduled for syndrome [1]. Reports show a 0.5–15% incidence of an epithelium-off CXL procedure under local anaes- keratoconus in patients with Down syndrome, which is thesia. Exclusion criteria were a corneal thickness much higher than in the general population (1:2000) under 400 lm and the presence of corneal scars. A [2–6]. Keratoconus can be detected at earlier stages standardized clinical decision tool was used to with corneal topography, a reliable instrument for estimate patient cooperation and the likelihood for a screening and diagnosis in patients with Down successful procedure under local rather than general syndrome [7–9]. anaesthesia. The role of trisomy 21 in developing keratoconus Results In seven eyes, the CXL was completed remains somewhat unclear. A nonparametric linkage successfully. The treatment was aborted in two eyes analysis suggested that a gene on chromosome 21 due to insufficient corneal thickness (\400 lm) prior could be related to keratoconus, but this finding was to ultraviolet-A irradiation, even after employing never confirmed [10]. Genetic studies have not yet hypoosmolar riboflavin. No adverse events occurred deciphered the complex genetic architecture of kera- post-operatively, except for one case of delayed toconus. This is perhaps in part due to differential epithelial healing (23 days). distribution of the risk loci among ethnic populations Conclusions With a proper patient selection, CXL or the relatively low contribution of genetic variants in under local anaesthesia can be achieved in patients developing keratoconus [11]. with Down syndrome. Patients with Down syndrome often do not complain about their vision. Instead, the ailment is typically noticed by others in their environment, resulting in a N. Soeters (&)  E. Bennen  R. P. L. Wisse Utrecht Cornea Research Group, Department of diagnosis in a more advanced disease state. The Ophthalmology, University Medical Center Utrecht, HP management of keratoconus in patients with Down E03.136, Heidelberglaan 100, 3508 GX Utrecht, The syndrome varies, depending on the severity of kerato- Netherlands conus and the degree of Down syndrome characteristics. e-mail: nsoeters@umcutrecht.nl 123 918 Int Ophthalmol (2018) 38:917–922 Performing a corneal transplantation in patients with Germany), slit-lamp examination, and dilated fun- Down syndrome entails considerable risks, and this doscopy. All patients were asked to remove their surgery has a worse prognosis than other patients with contact lenses for 2 week prior to the measurements. keratoconus [12, 13]. Therefore, it is desirable to halt Exclusion criteria for CXL treatment were a corneal keratoconus progression in an earlier stage and greatly thickness \400 lm prior to UV irradiation and the minimize the need for corneal surgery. Corneal presence of a corneal scar. crosslinking (CXL) is a minimally invasive procedure The diagnosis of Down syndrome was apparent in that has the potential to slow keratoconus progression all cases. Furthermore, a semi-structured approach and prevent the development of keratoconus into stages was used to assess patient compliance based on items where patients become dependent on rigid (scleral) covering three domains. The decision tool was com- contact lenses or corneal grafting procedures for an pleted by both the optometrist and ophthalmologist adequate visual acuity and quality of life [14, 15]. CXL and discussed together after the patient underwent a has an attractive safety profile: it is easy to perform trial-position in the treatment room. The first domain under local anaesthesia, it has few side effects, and it has of the decision tool comprised a general assessment: a low rate of vision threatening complications such as are spectacles tolerated, is eye contact being made, is keratitis or corneal haze formation [16]. there verbal communication, are slit-lamp examina- Patients with Down syndrome show higher risks tion and topography possible? The second domain assessed ability of patients to undergo the treatment: during general anaesthesia (bradycardia, natural air- way obstruction, difficult intubation, post-intubation are there abrupt movements of the head or body, can croup, and bronchospasm); therefore, it is preferred to anaesthetic eye drops be tolerated, can eyelid touch be perform CXL under local anaesthesia [17–19]. tolerated, is there the ability to be placed in a supine Here, we report on the potential to perform CXL position and fixate on a light for 5 min? The third procedures under local anaesthesia in patients with domain estimated post-procedure compliance: can the Down syndrome, our standardized clinical decision patient follow instructions adequately, can they refrain tool, and the outcomes of these treatments. from eye rubbing, are parents or institutional care- givers competent and supporting of treatment? See the standardized clinical decision tool in Table 1. Patients and methods Procedure The study was a prospective case series of patients with Down syndrome and keratoconus scheduled for An epithelium-off CXL was performed following the epithelium-off CXL under local anaesthesia at the ‘Dresden protocol’ [15, 20]. After local anaesthetics University Medical Centre, Utrecht. The study was (oxybuprocaine 0.4% and tetracaine 1%) were admin- approved by the University Medical Center Utrecht istered, the epithelium was removed with a blunt Ethics Review Board, who judged that our research spatula at the central 9 mm of the cornea. Isotonic (which was the collection of data of an already riboflavin drops (0.1%, Innocross-R) with 20% dextran scheduled procedure, not performed in a trial) inferred were applied to the cornea every 3 min for 30 min. no additional risks for the patient and waived the need After this phase, pachymetry measurements were for a written informed consent. All patients and their taken. When pachymetry was\400 lm, hypoosmolar riboflavin drops were added every 20 s for 5 min and parents/legal representatives were properly informed by their medical specialist, and they consented with repeated twice when necessary to reach 400 lm. the CXL procedure. The treatments were performed During the 30 min of ultraviolet-A (UVA) irradiation according to the highest standards of care and in (UV-X 1000, Peschke Meditrade GmbH, Switzerland), accordance with the Declaration of Helsinki and local riboflavin was applied on the cornea every 5 min. A laws regarding research using human subjects. bandage contact lens was placed (Purevision, Bausch A full ophthalmic evaluation was done, including & Lomb). Antibiotic eye drops (chloramphenicol the assessment of uncorrected (UDVA) and corrected preservative free 4 mg/ml, BID for 1 month) and pain (CDVA) distance visual acuity, manifest refraction, medication were prescribed (paracetamol 1000 mg corneal topography (Pentacam HR; Oculus, Wetzlar, QID, diclofenac 50 mg TID). After the epithelium was 123 Int Ophthalmol (2018) 38:917–922 919 Table 1 Standardized clinical decision tool to judge the subject suitability of Down syndrome patients for a corneal crosslinking treatment under local anaesthesia General (preop) assessment Spectacle tolerance Yes No Eye contact Yes No Verbal communicaon Yes No Adequate Pentacam measurement Yes No Treatment assessment Abrupt movements With head No Yes With legs No Yes With arms No Yes Passes 5-min supine posion and fixaon test Yes No Can tolerate anaesthec eye drop Yes No Can tolerate eyelid touch Yes No Aer-care assessment Eye rubbing No Yes Follows instrucons adequately Yes No Cooperave parents/care givers Yes No General impression Good Bad healed and the bandage contact lens was removed, keratoconus between 2011 and 2015. Mean age at the topical steroids (fluorometholone 1 mg/ml, BID) were time of treatment was 24 years (range 15–34), 29% started and continued for 3 weeks. Follow-up mea- were male, and mean follow-up was 26 months (range surements were taken after 2 days and 1 week to 12–48). On average, the UDVA was 0.3 Snellen confirm epithelial healing, and then after 1, 3, decimal (measured in 3 out of 9 eyes), the CDVA 6 months, and 1 year. A visit included assessment of (Snellen decimal) was 0.35 ± 0.18, and refractive UDVA/CDVA, manifest refraction, corneal topogra- astigmatism was -3.00 D ± 2.2. The mean maximal phy, and slit-lamp examination. keratometry (K ) value was 55.6 ± 5.0 D. The max mean amount of corneal astigmatism was 3.2 ± 1.7 D, and the mean pre-CXL pachymetry was Results 447 ± 52 lm. Slit-lamp examinations were feasible in all subjects and revealed no signs of ocular allergies A total of nine eyes of seven patients with Down of atopic conjunctivitis. Table 2 gives a detailed syndrome were scheduled for CXL for the treatment of overview of the baseline characteristics per patient 123 920 Int Ophthalmol (2018) 38:917–922 and post-CXL outcomes. All patients scored ‘positive’ on all items of the standardized clinical decision tool in Table 1, except for patient 6 who had an inadequate Pentacam measurement. All patients were scheduled for CXL under local anaesthesia. Two patients were treated bilaterally, with a 3-month interval. In the other five patients, the fellow eye was unsuitable for CXL due to the presence of a hydrops (patient 3 and 5), the absence of keratoconus (patient 6 and 7), or a cornea of insuffi- cient thickness (patient 2). All patients were examined within a week after treatment. No short-term post- operative complications occurred in any patient, except for a delayed epithelial healing in patient 2 (23 days). In three eyes, the corneal thickness was \400 lm after isotonic riboflavin instillation and additional hypoosmolar riboflavin drops were applied. Two of these eyes remained too thin before the start of UVA radiation and the procedure was aborted. In patient 6, Pentacam measurements were unreliable and neither keratometry readings nor pachymetry were interpretable. During treatment, pachymetry was 414 lm prior to UVA irradiation in this patient. Patient 5 showed a K increase from 51.8 to 56.1 D max after 1 year, which decreased to 50.6 D at the 3-year follow-up. For patient 4, a 16-year-old girl, fixating on the blue light in the UVA-lamp proved to be very tough. To solve this problem, her father held his tablet showing a video behind the UVA-lamp to effectively maintain fixation and prevent abrupt eye movements. Discussion This study reports the feasibility of a crosslinking procedure in patients with Down syndrome under local rather than general anaesthesia. Lack of cooperation was not an issue in any of the cases and the treatment was completed in 7 of 9 eyes. No adverse events were encountered during treatment or in the follow-up period, apart from one case of delayed epithelial healing. A semi-structured assessment to aid in patient selection is therefore proposed. A few case reports describe CXL in patients with Down syndrome. Two case reports show the results of CXL performed under general anaesthesia and in both eyes simultaneously: one by Koppen et al. [21] and one by Faschinger et al. [22]. Unfortunately, these Table 2 Patient characteristics (Down syndrome and corneal crosslinking for keratoconus) Pt Eye Age (years) Sex Optical correction Keratoconus stage CXL completed Visual acuity (decimal) Thinnest Maximal keratometry (D) pachymetry (lm) Preop 6 Mo 12 Mo Preop 12 Mo Preop 1 Mo 6 Mo 12 Mo 1 OD 20 F Scleral lenses 2 No 0.5? cc n/a n/a 384 264 59.6 n/a n/a 85.5 OS 2 Yes 0.30 cc 0.40 cc 0.30 cc 390 386 61.1 59.6 60.3 60.5 2 OS 31 F Spectacles 2 No 0.30= sc 0.30 cc n/a 419 404 51.3 n/a 51.0 n/a 3 OD 20 M Spectacles 2 Yes 0.30 ec 0.10 cc 0.03 cc 434 414 63.3 63.1 61.2 61.0 4 OD 15 F Spectacles 2 Yes 0.50 ec 0.50 cc 0.60 cc 519 505 53.5 n/a 53.1 52.0 OS 2 Yes 0.50 ec 0.55 cc 0.55 cc 498 484 53.5 52.5 n/a 52.0 5 OS 34 M None 1 Yes 0.60 sc 0.50 sc 0.65 sc 434 443 51.8 54.3 52.8 56.1 6 OS 21 F Spectacles n/a Yes n/a n/a n/a n/a n/a n/a n/a n/a n/a 7 OD 24 F Scleral lenses 1 Yes 0.20 cc 0.20 cc 0.20 cc 498 464 50.5 49.9 50.2 50.8 Pt patient, CXL corneal crosslinking, Mo months, F female, M male, cc with refraction, sc without correction, ec with spectacles, n/a not available Based on Amsler Krumeich classification Int Ophthalmol (2018) 38:917–922 921 treatments resulted in severe corneal complications convincingly stabilize disease progression [25]. The including corneal melting, corneal ulcer, and compli- main drawbacks with the epithelium-off technique are cated healing. A 4-year-old patient with Down abrasion-related complications such as delayed wound syndrome was successfully treated by CXL under healing and infectious keratitis. This is especially the general anaesthesia unilaterally; the keratoconus case in mentally disabled patients who have an remained stable for 3 years [23]. A specific CXL increased likelihood of rubbing their eyes [26]. project for patients with Down syndrome, called In conclusion, this case series shows promising ‘Light for sight 21’, was founded in 2011 by Dr. results of CXL under local anaesthesia in patients with Hafezi and offers a platform for research on the effects keratoconus and Down syndrome. CXL should be and efficacy of CXL in this patient group [24]. considered in an early stage of keratoconus to avoid The likelihood for a successful CXL treatment in safety problems and premature termination of the this specific patient group is dependent on the treatment. A standardized clinical decision tool can be observed behaviour of the patient. To our knowledge, used for a proper patient selection to perform CXL there’s no general staging of Down syndrome avail- under local anaesthesia. able. However, a valid method to estimate patient Acknowledgements Robert PL Wisse was supported for cooperation and the likelihood for a successful CXL research by the Dr. F.P. Fischer Stichting, the Netherlands, by procedure under local anaesthesia in this patient group an unrestricted grant. There is no financial interest for any of the would be valuable. Therefore, we proposed a semi- authors, their families, or direct business associates. The structured decision tool to help the practitioner manuscript was presented in public as a poster at the 11th International Congress of Corneal Cross-linking 2015, 05 selecting patients with Down syndrome for a CXL December, 2015, Boston, USA, presented as a paper at the treatment. Some of the items, for instance ‘abrupt Nederlands Contactlens Congres, 14 March, 2016, Veldhoven, movements’, are considered to be a greater contraindi- the Netherlands, and presented as a paper at the Nederlands cation for CXL under local anaesthesia. Therefore, we Oogheelkundig Gezelschap, 06 April, 2016, Maastricht, the Netherlands. assessed per individual patient whether CXL under local anaesthesia could be possible. Our decision tool Compliance with ethical standards aids in this decision. Alternatively, patients with a low score during the pre-CXL assessment could be offered Conflict of interest The authors declare that there is no con- flict of interest regarding the publication of this paper. the treatment under general anaesthesia. In this case series, a prospectively selected group of Open Access This article is distributed under the terms of the patients with Down syndrome was shown. The authors Creative Commons Attribution 4.0 International License (http:// are aware that only a selection of the patients visiting creativecommons.org/licenses/by/4.0/), which permits unre- stricted use, distribution, and reproduction in any medium, our outpatient clinic were shown; one other patient provided you give appropriate credit to the original with Down syndrome was treated under general author(s) and the source, provide a link to the Creative Com- anaesthesia due to non-cooperation during the pre- mons license, and indicate if changes were made. CXL assessment and another patient with mental disability received CXL under general anaesthesia. The number of dismissed CXL treatments based on a References low score on the decision tool assessment in our outpatient clinic is unknown. Although the prevalence 1. Hofmann H (1956) Acute keratoconus with mongoloid of keratoconus in patients with Down syndrome is idiocy. Klin Monbl Augenheilkd Augenarztl Fortbild much higher than in the general keratoconus popula- 129:756–762 2. Shapiro MB, France TD (1985) The ocular features of tion, the percentage of CXL treatments in our kera- Down’s syndrome. Am J Ophthalmol 99:659–663 toconus centre is much lower in this group. 3. Hestnes A, Sand T, Fostad K (1991) Ocular findings in Performing CXL to stop the progression of kera- Down’s syndrome. J Ment Defic Res 35:194–203 toconus and prevent a future corneal transplantation is 4. Woodward MA, Blachley TS, Stein JD (2016) The associ- ation between sociodemographic factors, common systemic valuable to this patient group to maintain vision and diseases, and keratoconus: an analysis of a nationwide heath ability to function. However, an epithelial abrasion is care claims database. Ophthalmology 123(457–65):e2 currently still regarded essential for adequate uptake 5. Van Splunder J, Stilma JS, Bernsen RMD, Evenhuis HM (2004) Prevalence of ocular diagnoses found on screening of riboflavin, since transepithelial CXL has failed to 123 922 Int Ophthalmol (2018) 38:917–922 1539 adults with intellectual disabilities. Ophthalmology 17. Borland LM, Colligan J, Brandom BW (2004) Frequency of 111:1457–1463 anesthesia-related complications in children with Down 6. Krachmer JH, Feder RS, Belin MW (1984) Keratoconus and syndrome under general anesthesia for noncardiac proce- related noninflammatory corneal thinning disorders. Surv dures. Paediatr Anaesth 14:733–738 Ophthalmol 28:293–321 18. Santamaria LB, Di Paola C, Mafrica F, Fodale V (2007) 7. Vincent AL, Weiser BA, Cupryn M et al (2005) Comput- Preanesthetic evaluation and assessment of children with erized corneal topography in a paediatric population with Down’s syndrome. Sci World J 7:242–251 Down syndrome. Clin Exp Ophthalmol 33:47–52 19. Lewanda AF, Matisoff A, Revenis M et al (2016) Preop- 8. Doyle SJ, Bullock J, Gray C et al (1998) Emmetropisation, erative evaluation and comprehensive risk assessment for axial length, and corneal topography in teenagers with children with Down syndrome. Paediatr Anaesth Down’s syndrome. Br J Ophthalmol 82:793–796 26:356–362 9. Aslan L, Aslankurt M, Aksoy A, Gu¨mu¨s¸alan Y (2014) 20. Spoerl E, Mrochen M, Sliney D et al (2007) Safety of UVA- Differences of the anterior segment parameters in children riboflavin cross-linking of the cornea. Cornea 26:385–389 with down syndrome. Ophthalmic Genet 35:74–78 21. Faschinger C, Kleinert R, Wedrich A (2010) Corneal 10. Rabinowitz YS, Zu L, Yang H et al (1999) Keratoconus: melting in both eyes after simultaneous corneal cross-link- non-parametric linkage analysis suggests a gene locus near ing in a patient with keratoconus and Down syndrome. the centromere of chromosome 21. Investig Ophthalmol Vis Ophthalmologe 107:951–952 Sci 40:S564 22. Koppen C, Leysen I, Tassignon M-J (2010) Riboflavin/ 11. Wisse RPL, Kuiper JJW, Gans R et al (2015) Cytokine UVA cross-linking for keratoconus in Down syndrome. expression in keratoconus and its corneal microenviron- J Refract Surg 26:623–624 ment: a systematic review. Ocul Surf 13:272–283 23. Sabti S, Tappeiner C, Frueh BE (2015) Corneal cross- 12. Frantz JM, Insler MS, Hagenah M et al (1990) Penetrating linking in a 4-year-old child with keratoconus and Down keratoplasty for keratoconus in Down’s syndrome. Am J syndrome. Cornea 34:1157–1160 Ophthalmol 109:143–147 24. Hafezi F (2015) Light for sight 21 raises awareness, pro- 13. Bodenmueller M, Frueh BE, Keratoplastik P (2003) Per- motes detection and treatment of keratoconus in children forierende Keratoplastik bei Trisomie 21. Klin Monbl with Down syndrome. Ocular Surgery News. Accessed 10 Augenheilkd 220:99–102 Aug 2015 14. Wittig-Silva C, Chan E, Islam FMA et al (2014) A ran- 25. Soeters N, Wisse RP, Godefrooij DA et al (2015) domized, controlled trial of corneal collagen cross-linking Transepithelial versus epithelium-off corneal cross-linking in progressive keratoconus: three-year results. Ophthal- for the treatment of progressive keratoconus: a randomized mology 121:812–821 controlled trial. Am J Ophthalmol 159:821–828 15. Wollensak G, Spoerl E, Seiler T (2003) Riboflavin/ultravi- 26. Ozcan AA, Ersoz TR (2007) Severe acute corneal hydrops olet-A-induced collagen crosslinking for the treatment of in a patient with Down syndrome and persistent eye rub- keratoconus. Am J Ophthalmol 135:620–627 bing. Ann Ophthalmol (Skokie) 39:158–160 16. Seiler TG, Schmidinger G, Fischinger I et al (2013) Com- plications of corneal cross-linking. Ophthalmologe 110:639–644 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Ophthalmology Springer Journals

Performing corneal crosslinking under local anaesthesia in patients with Down syndrome

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Abstract

Int Ophthalmol (2018) 38:917–922 https://doi.org/10.1007/s10792-017-0535-1 ORIGINAL PAPER Performing corneal crosslinking under local anaesthesia in patients with Down syndrome . . Nienke Soeters Esme ´e Bennen Robert P. L. Wisse Received: 2 November 2016 / Accepted: 10 April 2017 / Published online: 19 April 2017 The Author(s) 2017. This article is an open access publication Abstract Keywords Down syndrome  Keratoconus  Corneal Purpose To report on the ability to perform corneal crosslinking  CXL  Local anaesthesia crosslinking (CXL) under local anaesthesia for the treatment of keratoconus in patients with Down Introduction syndrome. Methods Nine eyes of seven patients with both Keratoconus has long since been linked with Down keratoconus and Down syndrome were scheduled for syndrome [1]. Reports show a 0.5–15% incidence of an epithelium-off CXL procedure under local anaes- keratoconus in patients with Down syndrome, which is thesia. Exclusion criteria were a corneal thickness much higher than in the general population (1:2000) under 400 lm and the presence of corneal scars. A [2–6]. Keratoconus can be detected at earlier stages standardized clinical decision tool was used to with corneal topography, a reliable instrument for estimate patient cooperation and the likelihood for a screening and diagnosis in patients with Down successful procedure under local rather than general syndrome [7–9]. anaesthesia. The role of trisomy 21 in developing keratoconus Results In seven eyes, the CXL was completed remains somewhat unclear. A nonparametric linkage successfully. The treatment was aborted in two eyes analysis suggested that a gene on chromosome 21 due to insufficient corneal thickness (\400 lm) prior could be related to keratoconus, but this finding was to ultraviolet-A irradiation, even after employing never confirmed [10]. Genetic studies have not yet hypoosmolar riboflavin. No adverse events occurred deciphered the complex genetic architecture of kera- post-operatively, except for one case of delayed toconus. This is perhaps in part due to differential epithelial healing (23 days). distribution of the risk loci among ethnic populations Conclusions With a proper patient selection, CXL or the relatively low contribution of genetic variants in under local anaesthesia can be achieved in patients developing keratoconus [11]. with Down syndrome. Patients with Down syndrome often do not complain about their vision. Instead, the ailment is typically noticed by others in their environment, resulting in a N. Soeters (&)  E. Bennen  R. P. L. Wisse Utrecht Cornea Research Group, Department of diagnosis in a more advanced disease state. The Ophthalmology, University Medical Center Utrecht, HP management of keratoconus in patients with Down E03.136, Heidelberglaan 100, 3508 GX Utrecht, The syndrome varies, depending on the severity of kerato- Netherlands conus and the degree of Down syndrome characteristics. e-mail: nsoeters@umcutrecht.nl 123 918 Int Ophthalmol (2018) 38:917–922 Performing a corneal transplantation in patients with Germany), slit-lamp examination, and dilated fun- Down syndrome entails considerable risks, and this doscopy. All patients were asked to remove their surgery has a worse prognosis than other patients with contact lenses for 2 week prior to the measurements. keratoconus [12, 13]. Therefore, it is desirable to halt Exclusion criteria for CXL treatment were a corneal keratoconus progression in an earlier stage and greatly thickness \400 lm prior to UV irradiation and the minimize the need for corneal surgery. Corneal presence of a corneal scar. crosslinking (CXL) is a minimally invasive procedure The diagnosis of Down syndrome was apparent in that has the potential to slow keratoconus progression all cases. Furthermore, a semi-structured approach and prevent the development of keratoconus into stages was used to assess patient compliance based on items where patients become dependent on rigid (scleral) covering three domains. The decision tool was com- contact lenses or corneal grafting procedures for an pleted by both the optometrist and ophthalmologist adequate visual acuity and quality of life [14, 15]. CXL and discussed together after the patient underwent a has an attractive safety profile: it is easy to perform trial-position in the treatment room. The first domain under local anaesthesia, it has few side effects, and it has of the decision tool comprised a general assessment: a low rate of vision threatening complications such as are spectacles tolerated, is eye contact being made, is keratitis or corneal haze formation [16]. there verbal communication, are slit-lamp examina- Patients with Down syndrome show higher risks tion and topography possible? The second domain assessed ability of patients to undergo the treatment: during general anaesthesia (bradycardia, natural air- way obstruction, difficult intubation, post-intubation are there abrupt movements of the head or body, can croup, and bronchospasm); therefore, it is preferred to anaesthetic eye drops be tolerated, can eyelid touch be perform CXL under local anaesthesia [17–19]. tolerated, is there the ability to be placed in a supine Here, we report on the potential to perform CXL position and fixate on a light for 5 min? The third procedures under local anaesthesia in patients with domain estimated post-procedure compliance: can the Down syndrome, our standardized clinical decision patient follow instructions adequately, can they refrain tool, and the outcomes of these treatments. from eye rubbing, are parents or institutional care- givers competent and supporting of treatment? See the standardized clinical decision tool in Table 1. Patients and methods Procedure The study was a prospective case series of patients with Down syndrome and keratoconus scheduled for An epithelium-off CXL was performed following the epithelium-off CXL under local anaesthesia at the ‘Dresden protocol’ [15, 20]. After local anaesthetics University Medical Centre, Utrecht. The study was (oxybuprocaine 0.4% and tetracaine 1%) were admin- approved by the University Medical Center Utrecht istered, the epithelium was removed with a blunt Ethics Review Board, who judged that our research spatula at the central 9 mm of the cornea. Isotonic (which was the collection of data of an already riboflavin drops (0.1%, Innocross-R) with 20% dextran scheduled procedure, not performed in a trial) inferred were applied to the cornea every 3 min for 30 min. no additional risks for the patient and waived the need After this phase, pachymetry measurements were for a written informed consent. All patients and their taken. When pachymetry was\400 lm, hypoosmolar riboflavin drops were added every 20 s for 5 min and parents/legal representatives were properly informed by their medical specialist, and they consented with repeated twice when necessary to reach 400 lm. the CXL procedure. The treatments were performed During the 30 min of ultraviolet-A (UVA) irradiation according to the highest standards of care and in (UV-X 1000, Peschke Meditrade GmbH, Switzerland), accordance with the Declaration of Helsinki and local riboflavin was applied on the cornea every 5 min. A laws regarding research using human subjects. bandage contact lens was placed (Purevision, Bausch A full ophthalmic evaluation was done, including & Lomb). Antibiotic eye drops (chloramphenicol the assessment of uncorrected (UDVA) and corrected preservative free 4 mg/ml, BID for 1 month) and pain (CDVA) distance visual acuity, manifest refraction, medication were prescribed (paracetamol 1000 mg corneal topography (Pentacam HR; Oculus, Wetzlar, QID, diclofenac 50 mg TID). After the epithelium was 123 Int Ophthalmol (2018) 38:917–922 919 Table 1 Standardized clinical decision tool to judge the subject suitability of Down syndrome patients for a corneal crosslinking treatment under local anaesthesia General (preop) assessment Spectacle tolerance Yes No Eye contact Yes No Verbal communicaon Yes No Adequate Pentacam measurement Yes No Treatment assessment Abrupt movements With head No Yes With legs No Yes With arms No Yes Passes 5-min supine posion and fixaon test Yes No Can tolerate anaesthec eye drop Yes No Can tolerate eyelid touch Yes No Aer-care assessment Eye rubbing No Yes Follows instrucons adequately Yes No Cooperave parents/care givers Yes No General impression Good Bad healed and the bandage contact lens was removed, keratoconus between 2011 and 2015. Mean age at the topical steroids (fluorometholone 1 mg/ml, BID) were time of treatment was 24 years (range 15–34), 29% started and continued for 3 weeks. Follow-up mea- were male, and mean follow-up was 26 months (range surements were taken after 2 days and 1 week to 12–48). On average, the UDVA was 0.3 Snellen confirm epithelial healing, and then after 1, 3, decimal (measured in 3 out of 9 eyes), the CDVA 6 months, and 1 year. A visit included assessment of (Snellen decimal) was 0.35 ± 0.18, and refractive UDVA/CDVA, manifest refraction, corneal topogra- astigmatism was -3.00 D ± 2.2. The mean maximal phy, and slit-lamp examination. keratometry (K ) value was 55.6 ± 5.0 D. The max mean amount of corneal astigmatism was 3.2 ± 1.7 D, and the mean pre-CXL pachymetry was Results 447 ± 52 lm. Slit-lamp examinations were feasible in all subjects and revealed no signs of ocular allergies A total of nine eyes of seven patients with Down of atopic conjunctivitis. Table 2 gives a detailed syndrome were scheduled for CXL for the treatment of overview of the baseline characteristics per patient 123 920 Int Ophthalmol (2018) 38:917–922 and post-CXL outcomes. All patients scored ‘positive’ on all items of the standardized clinical decision tool in Table 1, except for patient 6 who had an inadequate Pentacam measurement. All patients were scheduled for CXL under local anaesthesia. Two patients were treated bilaterally, with a 3-month interval. In the other five patients, the fellow eye was unsuitable for CXL due to the presence of a hydrops (patient 3 and 5), the absence of keratoconus (patient 6 and 7), or a cornea of insuffi- cient thickness (patient 2). All patients were examined within a week after treatment. No short-term post- operative complications occurred in any patient, except for a delayed epithelial healing in patient 2 (23 days). In three eyes, the corneal thickness was \400 lm after isotonic riboflavin instillation and additional hypoosmolar riboflavin drops were applied. Two of these eyes remained too thin before the start of UVA radiation and the procedure was aborted. In patient 6, Pentacam measurements were unreliable and neither keratometry readings nor pachymetry were interpretable. During treatment, pachymetry was 414 lm prior to UVA irradiation in this patient. Patient 5 showed a K increase from 51.8 to 56.1 D max after 1 year, which decreased to 50.6 D at the 3-year follow-up. For patient 4, a 16-year-old girl, fixating on the blue light in the UVA-lamp proved to be very tough. To solve this problem, her father held his tablet showing a video behind the UVA-lamp to effectively maintain fixation and prevent abrupt eye movements. Discussion This study reports the feasibility of a crosslinking procedure in patients with Down syndrome under local rather than general anaesthesia. Lack of cooperation was not an issue in any of the cases and the treatment was completed in 7 of 9 eyes. No adverse events were encountered during treatment or in the follow-up period, apart from one case of delayed epithelial healing. A semi-structured assessment to aid in patient selection is therefore proposed. A few case reports describe CXL in patients with Down syndrome. Two case reports show the results of CXL performed under general anaesthesia and in both eyes simultaneously: one by Koppen et al. [21] and one by Faschinger et al. [22]. Unfortunately, these Table 2 Patient characteristics (Down syndrome and corneal crosslinking for keratoconus) Pt Eye Age (years) Sex Optical correction Keratoconus stage CXL completed Visual acuity (decimal) Thinnest Maximal keratometry (D) pachymetry (lm) Preop 6 Mo 12 Mo Preop 12 Mo Preop 1 Mo 6 Mo 12 Mo 1 OD 20 F Scleral lenses 2 No 0.5? cc n/a n/a 384 264 59.6 n/a n/a 85.5 OS 2 Yes 0.30 cc 0.40 cc 0.30 cc 390 386 61.1 59.6 60.3 60.5 2 OS 31 F Spectacles 2 No 0.30= sc 0.30 cc n/a 419 404 51.3 n/a 51.0 n/a 3 OD 20 M Spectacles 2 Yes 0.30 ec 0.10 cc 0.03 cc 434 414 63.3 63.1 61.2 61.0 4 OD 15 F Spectacles 2 Yes 0.50 ec 0.50 cc 0.60 cc 519 505 53.5 n/a 53.1 52.0 OS 2 Yes 0.50 ec 0.55 cc 0.55 cc 498 484 53.5 52.5 n/a 52.0 5 OS 34 M None 1 Yes 0.60 sc 0.50 sc 0.65 sc 434 443 51.8 54.3 52.8 56.1 6 OS 21 F Spectacles n/a Yes n/a n/a n/a n/a n/a n/a n/a n/a n/a 7 OD 24 F Scleral lenses 1 Yes 0.20 cc 0.20 cc 0.20 cc 498 464 50.5 49.9 50.2 50.8 Pt patient, CXL corneal crosslinking, Mo months, F female, M male, cc with refraction, sc without correction, ec with spectacles, n/a not available Based on Amsler Krumeich classification Int Ophthalmol (2018) 38:917–922 921 treatments resulted in severe corneal complications convincingly stabilize disease progression [25]. The including corneal melting, corneal ulcer, and compli- main drawbacks with the epithelium-off technique are cated healing. A 4-year-old patient with Down abrasion-related complications such as delayed wound syndrome was successfully treated by CXL under healing and infectious keratitis. This is especially the general anaesthesia unilaterally; the keratoconus case in mentally disabled patients who have an remained stable for 3 years [23]. A specific CXL increased likelihood of rubbing their eyes [26]. project for patients with Down syndrome, called In conclusion, this case series shows promising ‘Light for sight 21’, was founded in 2011 by Dr. results of CXL under local anaesthesia in patients with Hafezi and offers a platform for research on the effects keratoconus and Down syndrome. CXL should be and efficacy of CXL in this patient group [24]. considered in an early stage of keratoconus to avoid The likelihood for a successful CXL treatment in safety problems and premature termination of the this specific patient group is dependent on the treatment. A standardized clinical decision tool can be observed behaviour of the patient. To our knowledge, used for a proper patient selection to perform CXL there’s no general staging of Down syndrome avail- under local anaesthesia. able. However, a valid method to estimate patient Acknowledgements Robert PL Wisse was supported for cooperation and the likelihood for a successful CXL research by the Dr. F.P. Fischer Stichting, the Netherlands, by procedure under local anaesthesia in this patient group an unrestricted grant. There is no financial interest for any of the would be valuable. Therefore, we proposed a semi- authors, their families, or direct business associates. The structured decision tool to help the practitioner manuscript was presented in public as a poster at the 11th International Congress of Corneal Cross-linking 2015, 05 selecting patients with Down syndrome for a CXL December, 2015, Boston, USA, presented as a paper at the treatment. Some of the items, for instance ‘abrupt Nederlands Contactlens Congres, 14 March, 2016, Veldhoven, movements’, are considered to be a greater contraindi- the Netherlands, and presented as a paper at the Nederlands cation for CXL under local anaesthesia. Therefore, we Oogheelkundig Gezelschap, 06 April, 2016, Maastricht, the Netherlands. assessed per individual patient whether CXL under local anaesthesia could be possible. Our decision tool Compliance with ethical standards aids in this decision. Alternatively, patients with a low score during the pre-CXL assessment could be offered Conflict of interest The authors declare that there is no con- flict of interest regarding the publication of this paper. the treatment under general anaesthesia. In this case series, a prospectively selected group of Open Access This article is distributed under the terms of the patients with Down syndrome was shown. The authors Creative Commons Attribution 4.0 International License (http:// are aware that only a selection of the patients visiting creativecommons.org/licenses/by/4.0/), which permits unre- stricted use, distribution, and reproduction in any medium, our outpatient clinic were shown; one other patient provided you give appropriate credit to the original with Down syndrome was treated under general author(s) and the source, provide a link to the Creative Com- anaesthesia due to non-cooperation during the pre- mons license, and indicate if changes were made. CXL assessment and another patient with mental disability received CXL under general anaesthesia. The number of dismissed CXL treatments based on a References low score on the decision tool assessment in our outpatient clinic is unknown. Although the prevalence 1. Hofmann H (1956) Acute keratoconus with mongoloid of keratoconus in patients with Down syndrome is idiocy. Klin Monbl Augenheilkd Augenarztl Fortbild much higher than in the general keratoconus popula- 129:756–762 2. Shapiro MB, France TD (1985) The ocular features of tion, the percentage of CXL treatments in our kera- Down’s syndrome. Am J Ophthalmol 99:659–663 toconus centre is much lower in this group. 3. Hestnes A, Sand T, Fostad K (1991) Ocular findings in Performing CXL to stop the progression of kera- Down’s syndrome. J Ment Defic Res 35:194–203 toconus and prevent a future corneal transplantation is 4. 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Paediatr Anaesth 14:733–738 Ophthalmol 28:293–321 18. Santamaria LB, Di Paola C, Mafrica F, Fodale V (2007) 7. Vincent AL, Weiser BA, Cupryn M et al (2005) Comput- Preanesthetic evaluation and assessment of children with erized corneal topography in a paediatric population with Down’s syndrome. Sci World J 7:242–251 Down syndrome. Clin Exp Ophthalmol 33:47–52 19. Lewanda AF, Matisoff A, Revenis M et al (2016) Preop- 8. Doyle SJ, Bullock J, Gray C et al (1998) Emmetropisation, erative evaluation and comprehensive risk assessment for axial length, and corneal topography in teenagers with children with Down syndrome. Paediatr Anaesth Down’s syndrome. Br J Ophthalmol 82:793–796 26:356–362 9. Aslan L, Aslankurt M, Aksoy A, Gu¨mu¨s¸alan Y (2014) 20. Spoerl E, Mrochen M, Sliney D et al (2007) Safety of UVA- Differences of the anterior segment parameters in children riboflavin cross-linking of the cornea. Cornea 26:385–389 with down syndrome. Ophthalmic Genet 35:74–78 21. Faschinger C, Kleinert R, Wedrich A (2010) Corneal 10. Rabinowitz YS, Zu L, Yang H et al (1999) Keratoconus: melting in both eyes after simultaneous corneal cross-link- non-parametric linkage analysis suggests a gene locus near ing in a patient with keratoconus and Down syndrome. the centromere of chromosome 21. Investig Ophthalmol Vis Ophthalmologe 107:951–952 Sci 40:S564 22. Koppen C, Leysen I, Tassignon M-J (2010) Riboflavin/ 11. Wisse RPL, Kuiper JJW, Gans R et al (2015) Cytokine UVA cross-linking for keratoconus in Down syndrome. expression in keratoconus and its corneal microenviron- J Refract Surg 26:623–624 ment: a systematic review. Ocul Surf 13:272–283 23. Sabti S, Tappeiner C, Frueh BE (2015) Corneal cross- 12. Frantz JM, Insler MS, Hagenah M et al (1990) Penetrating linking in a 4-year-old child with keratoconus and Down keratoplasty for keratoconus in Down’s syndrome. Am J syndrome. Cornea 34:1157–1160 Ophthalmol 109:143–147 24. Hafezi F (2015) Light for sight 21 raises awareness, pro- 13. Bodenmueller M, Frueh BE, Keratoplastik P (2003) Per- motes detection and treatment of keratoconus in children forierende Keratoplastik bei Trisomie 21. Klin Monbl with Down syndrome. Ocular Surgery News. Accessed 10 Augenheilkd 220:99–102 Aug 2015 14. Wittig-Silva C, Chan E, Islam FMA et al (2014) A ran- 25. Soeters N, Wisse RP, Godefrooij DA et al (2015) domized, controlled trial of corneal collagen cross-linking Transepithelial versus epithelium-off corneal cross-linking in progressive keratoconus: three-year results. Ophthal- for the treatment of progressive keratoconus: a randomized mology 121:812–821 controlled trial. Am J Ophthalmol 159:821–828 15. Wollensak G, Spoerl E, Seiler T (2003) Riboflavin/ultravi- 26. Ozcan AA, Ersoz TR (2007) Severe acute corneal hydrops olet-A-induced collagen crosslinking for the treatment of in a patient with Down syndrome and persistent eye rub- keratoconus. Am J Ophthalmol 135:620–627 bing. Ann Ophthalmol (Skokie) 39:158–160 16. Seiler TG, Schmidinger G, Fischinger I et al (2013) Com- plications of corneal cross-linking. Ophthalmologe 110:639–644

Journal

International OphthalmologySpringer Journals

Published: Apr 19, 2017

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