Purpose To evaluate the efficacy of half-dose photodynamic therapy (PDT) for the treatment of bullous retinal detachment. Methods Interventional prospective case series in six eyes from six consecutive patients with bullous retinal detachment. The effected eyes were treated with indocyanine green angiography (ICGA)-guided half-dose PDT with multifocal and large laser spots. Clinical evaluations included best-corrected visual acuity (BCVA), ophthalmoscopy, ophthalmic B scan, fundus fluores- cein angiography (FFA), optical coherence tomography (OCT), and ICGA at each scheduled visit at baseline; at 1, 3, and 6 months after PDT; and during follow-up after 6 months. Results All six eyes received half-dose verteporfin PDT with a mean number of therapeutic spots 2.83 ± 1.47 and a mean spot size of 4647 ± 996 μm in diameter. Three months after PDT, retinal reattachment was observed on B scans and resolution of sub- retinal fluid (SRF) was observed in OCT images for five eyes. There was no significant difference in the mean logMAR BCVA between the baseline and the value at 1 month after PDT (P = 0.477). At 3 months after PDT, the mean logMAR BCVA improved significantly from a baseline value of 1.02 to 0.54 (P = 0.044). At 6 months after PDT, the mean logMAR BCVA further improved to 0.46 (P = 0.025) and remained stable. One affected eye received a second half-dose PDT for SRF not reduced until the second month after PDT. Retinal reattachment and SRF resolution were observed at 1 and 3 months after the second therapy, respectively. BCVA improved from a baseline value of 20/63 to 20/20 at 1 month after the second PDT and remained stable until the sixth month after the second PDT. During follow-up after more than 6 months, recurrence occurred in no cases. Conclusions This study demonstrated half-dose PDT with multifocal and large laser spots was an effective treatment for bullous retinal detachment contributing to the retinal reattachment, a resolution of SRF, and an improvement of BCVA. Thus, PDT for the treatment of bullous retinal detachment is considered to be a worthwhile endeavor. . . . . Keywords Bullous retinal detachment Efficacy Photodynamic therapy Multifocal Large laser spot Introduction layer of the retina from the retinal pigment epithelium in the macular area [1, 2]. The detachment spontaneously resolves Chronic central serous chorioretinopathy (CSC) is a major within 2 to 3 months in two-thirds of affected individuals, threat to central vision in the working population and is main- which is defined as acute CSC . However, more than one- ly characterized by the serous detachment of the neurosensory third of patients experience chronic forms of CSC with per- sistent sub-retinal fluid (SRF) accumulation or recurrences leading to continuous visual impairment . The vascular leakage of chronic CSC results from the dysfunction of the * Mingwei Zhao retinal pigment epithelium (RPE) outer blood-retinal barrier, firstname.lastname@example.org most likely caused by choroidal vasodilatation and Department of Ophthalmology, Eye Diseases and Optometry hyperpermeability [5, 6]. Bullous retinal detachment, which Institute, Beijing Key Laboratory of Diagnosis and Therapy of can eventually lead to vision loss as a result of irreversible Retinal and Choroid Diseases, College of Optometry, Peking retinal damage, is an extremely rare manifestation of CSC. University People’s Hospital, Peking University Health Science However, the precise pathogenesis of why only a small subset Center, Xizhimen South Street 11, Xi Cheng District, Beijing 100044, China of eyes with CSC are complicated by bullous retinal detach- ment has remained unclear until now. In recent decades, the Department of Ophthalmology, 3rd People’s Hospital of Linyi, Linyi, China relationship between CSC and corticoid has been one of the 1430 Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 most intriguing aspects of the disease. A previous study re- were chosen according to abnormal vascular areas and a ported that glucocorticoids can reduce macular edema and total light energy of 50 J/cm for 83 s was used. Separate aggravate SRF accumulation in CSC patients . areas of choroidal hyperpermeability were treated separate- Additionally, in previous reports, the occurrence of bullous ly. If SRF was not reduced until the second month after retinal detachment was also associated with a history of glu- PDT, then the eye received another half-dose PDT. The cocorticoids [7, 8]. patients were instructed to avoid light for 48 h after PDT. Based on the currently available literature, the traditional BCVA, ophthalmoscopy, ophthalmic B scan, FFA, OCT, treatment of CSC consists of photodynamic therapy (PDT) and ICGA results were examined upon follow-up at 1, 3, and laser photocoagulation. However, there are limited clini- and 6 months after treatment. cal data on the therapy of patients with bullous retinal detach- ment thus far. In the present study, we present a series of cases Statistical analyses of bullous retinal detachment that responded favorably to half- dose PDT without any additional complications during the For statistical analyses, a paired-samples t test was used in follow-up period of more than 6 months. SPSS Statistics (version 20; IBM) to compare logMAR BCVA during each visit at baseline and 1, 3, and 6 months after PDT. The level of statistical significance was set at p < Methods 0.05. Patients Results Six eyes of six patients with bullous retinal detachment sec- ondary to CSC were included in this prospective study. The This study included six eyes from six consecutive patients. diagnosis of bullous retinal detachment was established by Table 1 summarizes the clinical characteristics of six patients ophthalmoscopy, ophthalmic B scan, fundus fluorescein angi- with bullous retinal detachment. The patients were five males ography (FFA), optical coherence tomography (OCT), and and one female with an average age of 40.5 ± 6.7 years (mean indocyanine green angiography (ICGA). Bullous retinal de- ± standard deviation). The disease affected a single eye in all tachment was designed as a neurosensory detachment (more six patients (100%). Regarding medical history, two patients than 10 disc diameters) with shifting SRF attributed to a leak (33.3%) had bullous retinal detachment associated with sys- or leaks at the level of the RPE with a bullous appearance that tematic corticosteroid therapy for initial nephritic syndrome extended to the inferior vascular arcades . All of the fol- and intravitreal injection of triamcinolone acetonide (TA) for lowing had to be present to diagnose bullous retinal detach- misdiagnosis of uveitis. Four patients (66.7%) presented with ment: exudative retinopathy observed by fundoscopy, retinal characteristics of classic CSC initially, followed by develop- detachment observed by B scan, SRF observed by OCT, vas- ment of bullous retinal detachment 3 months to 10 years later. cular leakage observed by FFA, and corresponding Except for one patient who lost vision in the fellow eye be- hyperfluorescence observed by ICGA. The patients were con- cause of glaucoma at a young age, the remaining five patients secutively enrolled from July 2015 to May 2017 in Peking had classic CSC in the fellow eyes. University People’s Hospital. The patients recruited received Bullous retinal detachment was invariable in the posterior PDT without other kind of treatments. The study protocol was pole and peripheral retina, characterized by accumulation of approved by the Ethical Committee and Institutional Review SRF shifting on different positions. Retinal detachment and Board of Peking University People’s Hospital (Beijing, macular SRF were observed in six eyes (100%). Peripheral China) and was in accordance with the Declaration of hyperfluorescent foci were observed by FFA in five eyes Helsinki. Written informed consent was obtained from the (83.3%). Sub-retinal fibrin occurred in three eyes (50%) as recruited bullous retinal detachment patients prior to PDT. observed by OCT. Two eyes (33.3%) were identified with retinal folds. Photodynamic therapy treatment and follow-up All six eyes received ICGA-guided half-dose verteporfin PDT. The mean number of PDT spots was 2.83 ± 1.47 (range Half-dose intravenous (3 mg/m ) verteporfin was infused over from 1 to 5) with a mean spot size of 4647 ± 996 μmin a period of 10 min. A contact glass was positioned on the diameter (range from 3000 to 6000 μm). Three months after affected eye, followed by delivery of 689 nm laser energy to PDT, retinal reattachment on B scan and resolution of sub- the target zone 15 min after infusion. Abnormal vascular areas retinal fluid (SRF) on an OCT image were observed in five selected based on hyperfluorescent zones observed by ICGA eyes. There was no significant difference in the mean of the mid-phase, corresponding to hyperfluorescent leakage logMAR BCVA between the baseline and 1 month after PDT (P = 0.477). At 3 months after PDT, the mean logMAR on FFA of the mid-phase were treated. For PDT, the spot sizes Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 1431 BCVA improved significantly from a baseline value of 1.02 to 0.54 (P = 0.044). At 6 months after PDT, the mean logMAR BCVA further improved to 0.46 (P = 0.025) and remained stable. The changes in BCVA of the five eyes at different time points are shown in Fig. 1. One affected eye (16.7%) received a second half-dose PDT, as SRF was not reduced until the second month after the first therapy. Next, we adjusted the therapeutic areas of PDT based on ICGA imaging. Retinal reattachment was observed 1 month after the second therapy, and SRF resolution was observed 3 months after the second therapy. BCVA improved from a baseline value of 20/63 to 20/20 1 month after the second PDT and remained stable until the 6th month after the second PDT. No major sequelae for PDT, such as persistent choroidal ischemia, macular hemorrhage, or severe chorioretinal degen- eration, were observed in any eyes during the follow-up pe- riods. During the follow-up more than 6 months, no recur- rence occurred. Case reports Case 1 A 35-year-old woman presented with blurred vision and photopsia in both eyes for 3 months. Her BCVA was 20/63 OU (in each eye). Ophthalmoscopy and ophthalmic B scan of the right eye revealed bullous retinal detachment in the poste- rior pole (Fig. 2a, b). The patient was treated with oral pred- nisone at 30 mg per day for over 6 years for nephritic syn- drome. FFA of the right eye revealed hyperfluorescent leakage in areas corresponding to exudative retinal detachment (Fig. 2c). OCT of the right eye disclosed neuro-retinal detach- ment (Fig. 2d). The left eye had focal retinal pigment epithelial detachment in the inferior retina. The right eye received a 50% dose of verteporfin PDT with a spot size of 5000 μmto cover the abnormal vascular area in indocyanine green angiography (Fig. 2e). One month later, the SRF was partly reduced (Fig. 2f, g), while 3 months later, there was retinal reattach- ment, and the complete absence of SRF was confirmed by ophthalmic B scan and OCT (Fig. 2h, i). At the 6-month examination after photodynamic therapy, the BCVA improved to 20/50 in the right eye, and a mottled appearance was ob- served in the fundus (Fig. 2j). FFA showed a mottled shape upon fluorescence transmission, and no fluorescein leakage was observed (Fig. 2k). ICGA showed hypofluorescence in the lesion area (Fig. 2l). Case 2 A 35-year-old man first noted visual loss in both eyes and was diagnosed with classic central serous chorioretinopathy; he received argon laser photocoagulation in the right eye at an- other hospital. Two years later at the age of 37, the patient Table 1 Clinical information of six patients with bullous retinal detachment Case no. Sex Age at onset, Eyes History of glucosteroid Treatments Total number Mean diameter Retinal reattachment Resolution of BCVA of BCVA of the Recurrence? year affected of PDT spots of spots, μm post-PDT on B scan, SRF on OCT, baseline 6th month months months after PDT 1 F 35 RE Oral prednisone 50% PDT 1 5000 3 3 20/63 20/50 No for 6 years 2 M 37 LE No 50% PDT 2 4500 3 3 20/200 20/40 No 3 M 38 RE No Twice 50% PDT 4 4500 1 month after 3 months after 20/63 20/20 No the 2nd PDT the 2nd PDT 4 M 48 LE Intravitreal injection of 50% PDT 3 4333 3 3 20/200 20/100 No TA a month before 5 M 50 RE No 50% PDT 5 4800 3 3 20/200 20/40 No 6 M 35 LE No 50% PDT 2 5000 3 3 20/800 20/80 No PDT photodynamic therapy, SRF sub-retinal fluid, RE right eye, LE left eye, TA triamcinolone acetonide 1432 Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 Fig. 1 Time course of changes in best-corrected visual acuity (logMAR) of five eyes received single 50% dose PDT. Error bars = standard errors. P <0.05 experienced severe blurring in the left eye, with a BCVA of (Fig. 3d). His left eye received a 50% dose of verteporfin PDT 20/80intherighteye and20/200 inthe left eye. with two spots of 6000 and 3000 μm under the guidance of Ophthalmoscopy of the left eye disclosed exudative lesions ICGA (Fig. 3e). One month after PDT, the SRF obviously in the macula and inferotemporal retina (Fig. 3a), which were decreased and sub-retinal fibrin disappeared based on ophthal- confirmed as bullous retinal detachment by ophthalmic B scan mic B scan and OCT (Fig. 3f, g). Three months later, ophthal- (Fig. 3b). FFA revealed hyperfluorescent leakage in areas of moscopy and ophthalmic B scan showed that the exudative exudative retinal detachment (Fig. 3c). OCT disclosed SRF, retinal detachment was resolved completely at the macula sub-retinal fibrin adjacent, and retinal folds in the lesion area (Fig. 3h, i). FFA revealed a mottled appearance of transmitted Fig. 2 Clinical examinations of the right eye in case 1. a Fundus at 1 month after PDT. g OCT image showing deposits at the area of photograph taken on the initial presentation illustrating bullous retinal detachment especially on RPE during the course of SRF reducing at detachment in the posterior pole. b Ophthalmic B scan revealing 1 month after PDT. h Ophthalmic B scan revealing reattachment of retina bullous retinal detachment at baseline. c FFA image demonstrating 3 months after PDT. i OCT image showing the disappearance of SRF hyperfluorescent leakage in areas corresponding to exudative retinal 3 months after PDT. j Fundus photograph obtained 6 months after PDT, detachment at baseline. d OCT image showing the neuro-retinal detach- illustrating the mottled appearance in the posterior pole. k FFA image ment in macula at baseline. e ICGA image illustrating hyperfluorescent showing a mottled shape in fluorescence transmission and no fluorescein leakage of choroid at baseline. White circle indicates the spot size of PDT. leakage 6 months after PDT. l ICGA image showing hypofluorescence in f Ophthalmic B scan revealing bullous retinal detachment partly resolved the lesion area 6 months after PDT Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 1433 Fig. 3 Clinical examinations of the left eye in patient 2. a Fundus reduction in SRF and disappearance of sub-retinal fibrin 1 month after photograph disclosing exudative lesions in the macula and PDT. h Fundus photograph taken 3 months after PDT illustrating the inferotemporal retina at baseline. b Ophthalmic B scan revealing disappearance of the exudative lesions. i Ophthalmic B scan revealing bullous retinal detachment at baseline. c FFA image revealing the retinal reattachment 3 months after PDT. j FFA revealing the mottled hyperfluorescent leakages in areas of exudative retinal detachment at appearance of transmitted fluorescence and no hyperfluorescent leakage baseline. d OCT image disclosing SRF, sub-retinal fibrin and retinal folds 3 months after PDT. k OCT showing complete resolution of SRF and the at baseline. e ICGA image illustrating several hyperfluorescent leakages disappearance of retinal folds 3 months after PDT. l ICGA image showing of the choroid at baseline. White circles indicate the spot sizes of PDT. f the disappearance of hyperfluorescent leakage and mottled appearance Ophthalmic B scan revealing obvious resolution of the bullous retinal remaining 3 months after PDT detachment 1 month after PDT. g OCT image disclosing obvious fluorescence and no hyperfluorescent leakage (Fig. 3j), and (Fig. 4c). OCT disclosed large amounts of SRF in the macular OCT showed the complete resolution of SRF and the disap- and temporal retinal areas (Fig. 4d). His right eye received a pearance of retinal folds (Fig. 3k). ICGA also disclosed the 50% dose of verteporfin PDT with three spots under the guid- disappearance of hyperfluorescent leakage and the mottled ance of ICGA (Fig. 4e). Ophthalmic B scan disclosed obvi- appearance that remained (Fig. 3l). At the 6-month examina- ously reduced bullous retinal detachment 1 month after PDT tion, his BCVA improved to 20/40 in the left eye and remained (Fig. 4f), and his BCVA improved to 20/25. However, the stable. SRF slowly resolved. Although the OCT image revealed a reduction in sub-retinal fibrin, the SRF remained and resolved Case 3 slowly until the second month after PDT (Fig. 4g). Considering the slow resolution of SRF, the patient received A 38-year-old man with a history of blurred vision in the right a second 50% dose of verteporfin PDT in the right eye. We eye for 1 year was diagnosed with CSC in the left eye, which adjusted the therapeutic area with a spot size of 5000 μm was treated with argon laser photocoagulation 10 years ago. under the guidance of ICGA. One month after the second His BCVA was 20/63 in the right eye and 20/200 in the left PDT (3 months after the first PDT), ophthalmoscopy of the eye. Ophthalmoscopy of the right eye revealed retinal detach- right eye revealed the disappearance of the yellowish, fibri- ment accompanied with yellowish, fibrinoid exudative lesions noid exudative lesions (Fig. 4h). Additionally, the reattached in the temporal macula (Fig. 4a). Ophthalmic B scan con- retina was observed on B scan, and SRF in the temporal area firmed bullous retinal detachment in the right eye (Fig. 4b). markedly decreased in the OCT image (Fig. 4i, j). OCT re- FFA disclosed multiple intense sub-retinal leakage in areas vealed nearly resolved SRF 2 months after the second PDT corresponding to exudative lesion and in the superior retina (Fig. 4k), and the SRF was completely resolved 3 months after 1434 Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 Fig. 4 Clinical examinations of the right eye in patient 3. a Fundus detachment 1 month after PDT. g OCT image revealing that the SRF photograph taken at the initial presentation revealing retinal detachment slowly resolved with reduced sub-retinal fibrin 2 months after PDT. h accompanied with yellowish, fibrinoid exudative lesions in the temporal One month after the second PDT (3 months after the first PDT), a fundus of macula. b Ophthalmic B scan revealing bullous retinal detachment at photograph revealed the disappearance of yellowish, fibrinoid exudative baseline. c FFA image revealing several hyperfluorescent leakages at lesions. i Ophthalmic B scan revealing the reattachment of retina 1 month baseline. d OCT image disclosing severe SRF and sub-retinal fibrin at after the second PDT. j OCT image showing markedly decreased SRF in baseline. e ICGA image illustrating several hyperfluorescent leakages of the temporal area 1 month after the second PDT. k OCT image revealing the choroid at baseline. White circles indicate the spot sizes of PDT. f nearly resolved SRF 2 months after the second PDT. l OCT image show- Ophthalmic B scan disclosing an obvious reduction in bullous retinal ing the complete resolution of SRF 3 months after the second PDT the second PDT (Fig. 4l). The patient’s BCVA of the right eye corresponding to exudative retinal detachment at baseline improved to 20/20 in the third month after the second PDTand (Fig. 5c). OCT disclosed SRF at the area of macula and tem- remained stable until the sixth month after the second PDT. poral retina (Fig. 5d). His left eye received a 50% dose of No recurrence occurred during the follow-up of more than verteporfin PDT with two spots of 5000 μm and one spot of 6 months after the second PDT. 3000 μmunder theguidance of ICGA (Fig. 5e). One month later, an ophthalmic B scan revealed obviously reduced bul- lous retinal detachment, and OCT disclosed the decreased Case 4 SRF (Fig. 5f, g). Three months after PDT, ophthalmoscopy and an ophthalmic B scan revealed the completely resolved A 48-year-old man presented with blurred vision in the left exudative retinal detachment (Fig. 5h, i). FFA showed eye for 2 weeks. He had a history of intravitreal injection of hypofluorescence, and ICGA revealed hypofluorescence triamcinolone acetonide (TA) for a misdiagnosis of uveitis in in the lesion area (Fig. 5j, k). SRF on the OCT image the left eye 1 month prior to examination. Additionally, his left disappeared, and the macula regained normal anatomic eye was treated with two periocular injections of dexametha- structure (Fig. 5l). At the 6-month examination, his vision sone, one intravitreal injection of conbercept and one applica- acuity improved to 20/100 in the left eye, and no recur- tion of laser photocoagulation within 1 month at other hospi- rence occurred. tal. However, there was with no improvement of visual acuity. His BCVA was 20/20 in the right eye and 20/200 in the left when he came to our outpatient facility. Ophthalmoscopy of Case 5 the left eye disclosed intraocular TA in the nasal retina and non-rhegmatogenous retinal detachment with multifocal exu- A 50-year-old man presented with blurred vision in the dative lesions in the posterior pole (Fig. 5a). An ophthalmic B right eye for a year. His BCVA was 20/200 in the right scan revealed retinal detachment in the left eye (Fig. 5b). FFA eye, while the left eye worsened to no light perception showed multiple hyperfluorescent leakage in areas because of glaucoma at an early age. Ophthalmoscopy of Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 1435 Fig. 5 Clinical examinations of the left eye in case 4. a Fundus Ophthalmic B scan revealing bullous retinal detachment partly resolved photograph illustrating TA in the nasal retina and non-rhegmatogenous 1 month after PDT. g OCT image revealing reduced SRF 1 month after retinal detachment with multifocal exudative lesions in the posterior pole PDT. h Fundus photograph revealing the disappearance of TA and bul- at baseline. b Ophthalmic B scan revealing bullous retinal detachment at lous retinal detachment 3 months after PDT. i Ophthalmic B scan reveal- baseline. c FFA image demonstrating hyperfluorescent leakages in areas ing the reattachment of the retina 3 months after PDT. j FFA image corresponding to exudative retinal detachment at baseline. d OCT image showing hypofluorescence in the lesion area 3 months after PDT. k showing SRF in the macular and temporal retinal areas at baseline. e ICGA image showing hypofluorescence in the lesion area 3 months after ICGA image illustrating hyperfluorescent leakages of the choroid around PDT. l OCT image showing the disappearance of SRF 3 months after the lesion area at baseline. White circles indicate the spot sizes of PDT. f PDT the right eye disclosed non-rhegmatogenous retinal detach- Case 6 ment in the posterior pole, and ophthalmic B scan con- firmed the bullous retinal detachment (Fig. 6a, b). FFA A 35-year-old man presented with blurred vision in the left revealed several hyperfluorescent leakages around the op- eye for near 3 months. His BCVA was 20/25 in the right eye tic disc corresponding to exudative lesions (Fig. 6c). OCT and 20/800 in the left eye. Ophthalmoscopy of the left eye of the right eye disclosed exudative retinal detachment revealed retinal detachment in the inferior retina (Fig. 7a). with serious SRF, sub-retinal fibrin, and retinal folds An ophthalmic B scan confirmed bullous retinal detach- (Fig. 6d). Five spots of 50% dose of verteporfin PDT were ment in the left eye (Fig. 7b). FFA disclosed multiple administered under the guidance of ICGA (Fig. 6e). One hyperfluorescent leakages in areas of temporal retina month after PDT, an ophthalmic B scan revealed obviously and hypofluorescent exudative retinal lesions correspond- reduced bullous retinal detachment (Fig. 6f). SRF and sub- ing to retinal detachment in the inferior retina (Fig. 7c). retinal fibrin decreased and the retinal folds disappeared OCT disclosed large amounts of SRF (Fig. 7d). His left from theOCT image(Fig. 6g). Three months after PDT, eye received a 50% dose of verteporfin PDT with two ophthalmoscopy and an ophthalmic B scan revealed that spots of 5000 μm under the guidance of ICGA (Fig. 7e). the bullous retinal detachment was completely resolved One month after PDT, the SRF was partly resolved based (Fig. 6h, i). A mottled shape was observed by fluorescence on an ophthalmic B scan and OCT (Fig. 7f, g). Three transmission, and no fluorescein leakage was found in months after PDT, SRF was completely resolved, as con- the FFA image (Fig. 6j). OCT showed normal macula firmed by ophthalmic B scan, OCT, and ophthalmoscopy structure in the right eye (Fig. 6k). ICGA disclosed (Fig. 7h–j). At the 6-month examination after photody- hypofluorescence in the lesion area (Fig. 6l). His BCVA im- namic therapy, his BCVA improved to 20/80 in the left proved to 20/40, with no recurrence during the follow-up of eye. An FFA image showed a mottled shape in fluores- more than 6 months. cence transmission, and no fluorescein leakage was found 1436 Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 Fig. 6 Clinical examinations of the right eye in patient 5. a Fundus after PDT. g OCT image revealing decreases in SRF and sub-retinal fibrin photograph taken at the initial presentation illustrating bullous retinal and the disappearance of retinal folds 1 month after PDT. h Fundus detachment. b Ophthalmic B scan confirming the bullous retinal photograph illustrating the disappearance of bullous retinal detachment detachment. c FFA image demonstrating several hyperfluorescent 3months after PDT. i Ophthalmic B scan revealing the reattachment of leakages around the optic disc corresponding to exudative lesions at the retina 3 months after PDT. j FFA image showing the mottled shape baseline. d OCT image showing exudative retinal detachment with detected by fluorescence transmission and no fluorescein leakage serious SRF and sub-retinal fibrin. Retinal folds can be revealed at base- 3months after PDT. k OCT image showing the complete resolution of line. e ICGA image illustrating hyperfluorescent leakages of the choroid SRF and sub-retinal fibrin 3 months after PDT. l ICGA image showing at baseline. White circles indicate the spot sizes of PDT. f Ophthalmic B hypofluorescence in the lesion area 3 months after PDT scan revealing an obvious reduction in bullous retinal detachment 1 month (Fig. 7k). An ICGA image showed the disappearance of In fact, the treatment for bullous retinal detachment has not hyperfluorescence leakage in the lesion area (Fig. 7l). been well established. In past decades, laser photocoagulation was the traditional treatment for extrafoveal leakage area . The rapid resolution of bullous retinal detachment was Discussion reported after photocoagulation of the areas of RPE de- tachment . However, there have been only a limited In this study, we evaluated the efficacy of half-dose number of case reports on the use of PDT for bullous retinal detachment [17, 18]. verteporfin PDT with multifocal and large laser spots in the In 1973, Gass first reported a group of patients with bullous treatment of bullous retinal detachment. Although PDT is gen- exudative detachment . Bullous retinal detachment is a erally considered a common therapy for classic CSC , it rare sub-type of CSC characterized by multifocal posterior has not been popularized among the treatment of bullous ret- inal detachment, a severe variant of CSC. exudations with shifting SRF . CSC is a common maculopathy mainly affecting working-age populations and Besides PDT, studies suggested that laser photocoagulation may be of benefit in reducing SRF and oral administration of is observed more frequently in men than in women . In a previous study, Balaratnasingam et al.  reported a group mineralocorticoid receptor antagonist eplerenone or intravit- real antiangiogenic drugs may be helpful to improve visual of bullous retinal detachment patients with a mean age of 53.8 years, and 50% of patients were bilaterally affected, acuity [11, 12]. Some cases also indicated that transpupillary thermotherapy seemed to be effective for the treatment of while Otsuka et al. reported25 patients—21 men and 4 women—with a mean age at disease onset of 43.1 years. Our bullous variant of CSC in the short term and internal drainage study showed that the mean age was 40.5 ± 6.7 years and the could lead to anatomical and functional improvement [13, 14]. Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 1437 Fig. 7 Clinical examinations of the left eye in patient 6. a Fundus indicate the spot sizes of PDT. f Ophthalmic B scan revealing a photograph taken at the initial presentation illustrating bullous retinal reduction in bullous retinal detachment 1 month after PDT. g OCT detachment in the inferior retina. b Ophthalmic B scan confirming the image revealing a decrease in SRF 1 month after PDT. h Ophthalmic B bullous retinal detachment at baseline. c FFA image demonstrating scan revealing the reattachment of the retina 3 months after PDT. i OCT hyperfluorescent leakages in temporal retinal areas and hypofluorescent image showing the complete resolution of SRF 3 months after PDT. j exudative retinal lesions corresponding to retinal detachment in the Fundus photograph illustrating a normal fundus 3 months after PDT. k inferior retina at baseline. d OCT image disclosing exudative retinal FFA image showing a mottled shape in fluorescence transmission and no detachment with serious SRF at baseline. e ICGA image illustrating fluorescein leakage 6 months after PDT. l ICGA image showing hyperfluorescent leakages of the choroid at baseline. White circles hypofluorescence in the lesion area 6 months after PDT male-to-female ratio was 5:1, which was similar to previous progression and visual loss. This disease can also occur spon- reports. However, the disease affected a single eye in all six taneously without any history of corticosteroid use. The re- patients, accounting for 100% in our group, which was differ- maining four patients, accounting for 66.7% in the present ent from the results of previous studies [9, 23]. case series, initially presented with characteristics of classic Previous studies have shown an association between retinal CSC, followed by the development of bullous retinal detach- disease and retinal or cardiac transplantation with the bullous ment 3 months to 10 years later. A previous study reported that variant of CSC [24, 25]. Corticosteroids also have been impli- patients with classic CSC developed the severe variant after cated in the pathogenesis of bullous retinal detachment [7, 26]. 7 months to 9 years . A patient in the present study Balaratnasingam et al.  reported that 50% of patients had progressed to bullous retinal detachment in the shortest time corticosteroid use in the bullous retinal detachment group. In of 3 months from the stage of acute CSC, which, to our knowl- the present study, two patients, accounting for 33.3%, had edge, has seldom been reported. The new findings in the pres- undergone corticosteroid therapy: one (patient 1) for initial ent study will aid the exploration of the pathophysiology of disease of nephritic syndrome and the other (patient 4) for bullous retinal detachment. We suggest that bullous retinal intravitreal injection of TA. The latter patient was initially detachment is not a single pathogenic risk factor but may be misdiagnosed with uveitis by another ophthalmologist and a result of interactions between environmental, genetic, and was subsequently administered various treatments, including individual conditions. corticosteroids, prior to visiting our hospital. Although CSC is Peripheral hyperfluorescent foci were observed on FFA a self-limiting condition in the majority of patients, the recog- in 83.3% of eyes in the present study. We also observed nition of this atypical form is important. Failure to differentiate sub-retinal fibrin on OCT in 50% of affected eyes. this condition from inflammatory disease may result in the Hooymans  reported fibrotic scar formation in the de- inappropriate use of corticosteroids, leading to disease velopment of CSC to severe variants of bullous retinal 1438 Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 Funding Beijing Municipal Science and Technology Commission pro- detachment during systematic treatment with corticoste- vided financial support in the form of Science and Technology Program roids. Balaratnasingam et al. described a more frequent of Beijing (No. Z171100002217081, Z161100000516037). National occurrence of sub-retinal fibrin in the eyes of the bullous Natural Science Foundation of China provided financial support in the CSC group than in the eyes of the non-bullous CSC group form of National Natural Science Foundation of China (Grant NO. 81470651, 81770943). This work was supported by National key re- . Retinal folds were observed in 33.3% of eyes with search and development program (2016YFC0904801, bullous retinal detachment in the present case series. We 2017YFC0111204). The sponsor had no role in the design or conduct inferred the folds were association with retinal edema and of this research. choroidal vasodilatation. In the present case series, all affected eyes received Compliance with ethical standards half-dose PDT, including five eyes that received single PDT, accounting for 83.3%, and one eye that received a Conflict of interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or second PDT, accounting for 16.7%. The second PDT was non-financial interest in the subject matter or materials discussed in this administered when SRF accumulation was not reduced manuscript. until 2 months after the first therapy. After adjustment of the therapeutic area guided by ICGA, retinal reattachment Ethical approval All procedures performed in studies involving human was acquired 1 month later. Studies have shown that vas- participants were in accordance with the ethical standards of the institu- tional and/or national research committee and with the 1964 Helsinki cular damage and cytotoxicity associated with PDT are declaration and its later amendments or comparable ethical standards. dosage-dependent . Considering the dosage- dependent administration of verteporfin and the results of Informed consent Informed consent was obtained from all individual a previous study on the efficacy of PDT in the treatment of participants included in the study. Additional informed consent was ob- CSC, we used half-dose PDT in the present study . tained from all individual participants for whom identifying information is included in this article. The PDT treatment was guided by ICGA, which has be- come the mainstream procedure to guide PDT to target Open Access This article is distributed under the terms of the Creative hyperfluorescent areas in mid-phase [30, 31]. The entire Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, area of abnormal choroidal vessels could be covered by distribution, and reproduction in any medium, provided you give appro- ICGA-guided PDT to prevent further leakage. The spot priate credit to the original author(s) and the source, provide a link to the sizes in the present study ranged from 3000 to 6000 μm Creative Commons license, and indicate if changes were made. with a mean size of 4647 ± 996 μmindiameter. The success rate of half-dose PDT in the present study was defined as the reattachment of retina on ophthalmol- References ogy B scan. These data showed a success rate of 100% after PDT treatment for bullous retinal detachment, with 1. Liew G, Quin G, Gillies M et al (2013) Central serous an absence of SRF on OCT. The recurrence rate was as chorioretinopathy: a review of epidemiology and pathophysiology. low as zero during the follow-up of more than 6 months. Clin Exp Ophthalmol 41:201–214 Remarkably, the visual results were significantly improved 2. Quin G, Liew G, Ho IVet al (2013) Diagnosis and interventions for 3 and 6 months after half-dose PDT compared to the base- central serous chorioretinopathy: review and update. Clin Exp Ophthalmol 41:187–200 line. Similar results in case series of bullous retinal de- 3. Gergely R, Kovács I, Schneider M et al (2017) Mineralocorticoid tachment have not previously been reported. The present receptor antagonist treatment in bilateral chronic central serous study provides clinical evidence for the treatment of bul- chorioretinopathy: a comparative study of exudative and lous retinal detachment with PDT. nonexudative fellow eyes. Retina 37:1084–1091 Since the present sample size was small and the follow-up 4. Ross A, Ross AH, Mohamed Q (2011) Review and update of cen- tral serous chorioretinopathy. Curr Opin Ophthalmol 22:166–173 time was short, a prospective randomized control study in- 5. van Dijk EHC, Dijkman G, Boon CJF (2017) Photodynamic therapy volving a large number of patients with long-term follow-up in chronic central serous chorioretinopathy with subretinal fluid out- is needed for further investigation of the advantage of PDT. side the fovea. Graefes Arch Clin Exp Ophthalmol 255:2029–2035 In conclusion, this study has demonstrated the effective 6. Daruich A, Matet A, Dirani A et al (2015) Central serous treatment of half-dose PDT with multifocal and large laser chorioretinopathy: recent findings and new physiopathology hy- pothesis. Prog Retin Eye Res 48:82–118 spots in bullous retinal detachment, leading to significant 7. Gao X, Li X (2011) Development of bullous retinal detachment visual and anatomic improvement in all affected eyes in the during systematic corticosteroid treatment. Graefes Arch Clin Exp present case series. We are currently performing a multi- Ophthalmol 249:1905–1907 center prospective randomized controlled trial to explore 8. Cebeci Z, Oray M, Bayraktar S et al (2017) Atypical central serous the efficacy of PDT for bullous retinal detachment. chorioretinopathy. Turk J Ophthalmol 47:238–242 Graefes Arch Clin Exp Ophthalmol (2018) 256:1429–1439 1439 9. Balaratnasingam C, Freund KB, Tan AM et al (2016) Bullous var- 21. Tsai DC, Chen SJ, Huang CC et al (2013) Epidemiology of idio- pathic central serous chorioretinopathy in Taiwan, 2001-2006: a iant of central serous chorioretinopathy: expansion of phenotypic features using multimethod imaging. Ophthalmology 123:1541– population-based study. PLoS One 8:e66858 1552 22. Otsuka S, Ohba N, Nakao K (2002) A long-term follow-up study of severe variant of central serous chorioretinopathy. Retina 22:25–32 10. Tsng CC, Chen SN (2015) Long-term efficacy of half-dose photo- 23. Sahu DK, Namperumalsamy P, Hilton GF, de Sousa NF (2000) dynamic therapy on chronic central serous chorioretinopathy. Br J Bullous variant of idiopathic central serous chorioretinopathy. Br Ophthalmol 99:1070–1077 J Ophthalmol 84:485–492 11. Nicholson B, Noble J, Forooghian F et al (2014) Central serous 24. Gass JD (1992) Bullous retinal detachment and multiple retinal chorioretinopathy: update on pathophysiology and treatment. Surv pigment epithelial detachments in patients receiving hemodialysis. Ophthalmol 58:103–126 Graefes Arch Clin Exp Ophthalmol 230:454–458 12. Cakir B, Fischer F, Ehlken C et al (2016) Clinical experience with 25. Fawzi AA, Holland GN, Kreiger AE et al (2006) Central serous eplerenone to treat chronic central serous chorioretinopathy. chorioretinopathy after solid organ transplantation. Ophthalmology Graefes Arch Clin Exp Ophthalmol 254:2151–2157 113:805–813 13. John VJ, Mandelcorn ED, Albini TA (2014) Internal drainage for 26. Gass JD, Little H (1995) Bilateral bullous exudative retinal detach- chronic macula-involving serous retinal detachment in idiopathic ment complicating idiopathic central serous chorioretinopathy dur- central serous chorioretinopathy. Int Ophthalmol 34:91–95 ing systemic corticosteroid therapy. Ophthalmology 102:737–747 14. Kawamura R, Ideta H, Hori H et al (2012) Transpupillary 27. Hooymans JM (1998) Fibrotic scar formation in central serous thermotherapy for atypical central serous chorioretinopathy. Clin chorioretinopathy developed during systematic treatment with cor- Ophthalmol 6:175–179 ticosteroids. Graefes Arch Clin Exp Ophthalmol 236:876–879 15. Robertson DM (1986) Argon laser photocoagulation treatment in 28. Schlötzer-Schrehardt U, Viestenz A, Naumann GO et al (2002) central serous chorioretinopathy. Ophthalmology 93:972–974 Dose-related structural effects of photodynamic therapy on choroi- 16. Chen JC, Lee LR (2005) Central serous choriorenopathy and bul- dal and retinal structures of human eyes. Graefes Arch Clin Exp lous retinal detachment: a rare association. Clin Exp Optom 88: Ophthalmol 240:748–757 248–252 29. Zhao M, Zhang F, Chen Y et al (2015) A 50% versus 30% dose of 17. Kuroyanagi K, Sakai T, Kasai K, Tsuneoka H (2013) Spectral do- verteporfin (photodynamic therapy) for acute central serous main optical coherence tomography and angiographic findings in chorioretinopathy: one-year results of a randomized clinical trial. multifocal posterior pigment epitheliopathy treated with low- JAMA Ophthalmol 133:333–340 fluence photodynamic therapy. Clin Exp Optom 96:126–129 30. Breukink MB, Mohr JK, Ossewaarde-van Norel A et al (2016) 18. Ng WW, Wu ZH, Lai TY (2011) Half-dose verteporfin photody- Half-dose photodynamic therapy followed by diode micropulse namic therapy for bullous variant of central serous laser therapy as treatment for chronic central serous chorioretinopathy: a case report. J Med Case Rep 5:208 chorioretinopathy: evaluation of a prospective treatment protocol. 19. Gass JD (1973) Bullous retinal detachment. An unusual manifesta- Acta Ophthalmol 94:187–197 tion of idiopathic central serous choroidopathy. Am J Ophthalmol 31. Rouvas A, Nikita E, Chatziralli I et al (2015) Long-term follow-up 75:810–812 of standard photodynamic therapy with standardized small spot size 20. Otsuka S, Ohba N, Nakao K (2002) A long-term follow up study of for diffuse retinal pigment epitheliopathy. Eur J Ophthalmol 25: severe variant of central serous chorioretinopathy. Retina 22:25–32 229–234
Graefe's Archive for Clinical and Experimental Ophthalmology – Springer Journals
Published: Jun 4, 2018
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera