A Multicenter Study on the Long-Term Outcomes of Half-Dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy

A Multicenter Study on the Long-term Outcomes of Half-dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy

FRANK H.P. LAI, DANNY S. NG, MALINI BAKTHAVATSALAM, VESTA C.K. CHAN, ALVIN L. YOUNG, FIONA O.J. LUK, CHI WAI TSANG, AND MA˚ RTEN E. BRELE´N

PURPOSE: To investigate long-term efficacy and prog- CONCLUSIONS: Chronic CSCR patients treated with nostic factors of half-dose photodynamic therapy (PDT) half-dose PDT can achieve long-term stable visual acuity in chronic central serous chorioretinopathy (CSCR). and resolution of SRD. Patients with chronic CSCR are DESIGN: Retrospective multicenter interventional case recommended to undergo half-dose PDT before they series. have significant visual deterioration. Patients with bilat- METHODS: Patients with chronic CSCR undergoing eral CSCR are more likely to develop CSCR recurrence half-dose PDT between 2005 and 2011 were reviewed. after half-dose PDT. (Am J Ophthalmol 2016;170: Main outcome measures included resolution of serous 91–99. Ó 2016 Elsevier Inc. All rights reserved.) retinal detachment (SRD) with single PDT, change in best-corrected visual acuities (BCVAs), and recurrence rate of CSCR at 36 months after PDT. Prognostic factors ENTRAL SEROUS CHORIORETINOPATHY (CSCR) IS of visual outcome and recurrence of CSCR after PDT characterized by 1 or more serous detachments of were identified with multivariate regression analysis. C the neurosensory retina commonly associated RESULTS: A total of 136 eyes of 123 patients were with retinal pigment epithelium (RPE) detachments. 1,2 followed up for 57.7 ± 16.2 months. At 36 months after There is a broad spectrum of clinical presentations. PDT, 132 eyes (97.1%) achieved complete resolution of Although the visual prognosis is usually good in acute SRD with single PDT and 4 eyes (2.9%) had CSCR manifestations, chronic CSCR can be associated with recurrence. The mean logMAR BCVA improved from complications such as RPE loss, geographic atrophy, 0.36 ± 0.29 (Snellen equivalent 20/46; range: 0.1–1.2) chronic cystic retinal changes, subretinal fibrinous at baseline to 0.15 ± 0.23 at 36 months (Snellen equiva- accumulation, subretinal fibrosis, and secondary choroidal 3,4 lent 20/28; range: 0.1–1.5; P < .001) and 0.16 ± 0.24 neovascularization (CNV). These complications can be (Snellen equivalent: 20/29; range: 0.1–1.5; P < .001) associated with permanent visual loss. at final follow-up. Forty-four eyes (32.4%) had ‡3 lines The pathogenesis of CSCR is poorly understood but is of BCVA gain while 5 eyes (3.7%) had ‡3 lines of believed to be related to an abnormal choroidal circulation, BCVA loss at 36 months after PDT. Nine eyes (6.6%) as demonstrated by indocyanine green angiography 5–7 developed CSCR recurrence at final follow-up. Baseline (ICGA). Congested and dilated choroidal vessels, BCVA was significantly associated with the BCVA choroidal staining, and hyperfluorescence have been (P [ .009) and the improvement in BCVA shown in the middle and late phases of ICGA in CSCR 8 (P < .001) at final follow-up. History of bilateral patients. In recent years, photodynamic therapy (PDT) CSCR was significantly associated with CSCR recur- has been reported as an effective treatment option for 9–11 rence at final follow-up (P [ .036; odds ratio [ 15.84, CSCR. PDT works by causing short-term choriocapilla- 95% confidence interval [ 1.20–208.32). Eight eyes ris hypoperfusion and long-term choroidal vascular remod- (5.9%) had complications related to PDT. eling, which reduces choroidal congestion, vascular hyperpermeability, and extravascular leakage.12,13 However, PDT has the potential of causing RPE tear and subretinal or sub-RPE hemorrhage, a particular concern in eyes with good pretreatment visual acuity.14–17 Some Supplemental Material available at AJO.com. Accepted for publication Jul 30, 2016. studies have reported treating CSCR with modified PDT 2 From the Department of Ophthalmology and Visual Sciences, Prince of parameters, including reduced dose (3 mg/m )of Wales Hospital, (F.H.P.L., V.C.K.C., A.L.Y., M.Brelen), and Department verteporfin or reduced fluence (25 J/cm2) of irradiation, of Ophthalmology and Visual Sciences, Hong Kong Eye Hospital (D.S.N., 18,19 M.Bakthavatsalam, F.O.J.L., C.W.T., M.Brelen), the Chinese University which can minimize side effects. Despite the short- of Hong Kong, Kowloon, Hong Kong. term success of PDT on persistent CSCR, there have Inquiries to Ma˚rten E. Breleń, Department of Ophthalmology and been few studies about the long-term efficacy and safety Visual Sciences, Chinese University of Hong Kong, 4/F, Hong Kong Eye 20,21 Hospital, 147K Argyle St, Kowloon, Hong Kong; e-mail: brelen. of PDT in treating CSCR. The aim of this study is to [email protected] evaluate the long-term outcomes and identify predictors

0002-9394/$36.00 © 2016 ELSEVIER INC.ALL RIGHTS RESERVED. 91 http://dx.doi.org/10.1016/j.ajo.2016.07.026 of visual outcome and disease recurrence in patients with with chronic CSCR in all involved centers. All chronic chronic CSCR treated with half-dose PDT. CSCR patients would receive half-dose PDT. The area of irradiation was set to cover the area of choroidal dilation and hyperpermeability in ICGA.9 The total light energy delivered to the area of hyperpermeability was 50 J/cm2 METHODS over 83 seconds. If multifocal, nonconfluent lesions were responsible for the subretinal fluid, consecutive, nonover- THIS RETROSPECTIVE MULTICENTER REVIEW WAS lapping laser spots (83 seconds for each spot) were used ac- approved by the Clinical Ethics Committees of New Terri- cording to the lesion size in ICGA (Figure 1). tories East Cluster and Kowloon Central Cluster. The Patients’ records during their follow-up visits at the near- research adhered to the tenets of the Declaration of est time points from the first, third, sixth, and twelfth Helsinki. Consecutive patients with chronic CSCR under- month after PDT and every 6 months thereafter were going half-dose PDT at Hong Kong Eye Hospital, Prince of reviewed. At the follow-up visits, Snellen BCVA, slit- Wales Hospital, and Alice Ho Miu Ling Hospital between lamp examination, fundus examination, and macular January 1, 2005 and December 31, 2011 were studied retro- OCT were performed. The same OCT machine was used spectively. at pre-PDT and all post-PDT time points for the same pa- Chronic CSCR was defined as idiopathic serous retinal tient to measure the central foveal thickness (CFT).26 The detachments (SRD) in the macular area associated with CFT obtained with Stratus 3 OCT was converted to corre- RPE changes or leakage on fluorescein angiography (FA) sponding measurement with Spectralis OCT using the con- with associated visual symptoms for at least 3 months. version formula previously reported.27 The inclusion criteria included (1) patient who received half-dose photodynamic therapy; (2) presence of SRD OUTCOMES AND STATISTICAL ANALYSIS: The primary involving the fovea in the optical coherence topography outcomes included change in BCVA and proportion of (OCT) images; (3) patient with age of 18 years or older; eyes with complete resolution of SRD after single PDT at (4) absence of spontaneous resolution or improvement 36 months after treatment. Secondary outcome measures induced by empirical treatment such as acetazolamide or included change in CFT, number of PDT treatments, any ketoconazole.22,23 Exclusion criteria included (1) recurrence of CSCR, and the time to a recurrence. A recur- previous treatment with PDT or focal thermal laser rence was defined as the appearance of a new SRD in the photocoagulation before the first time point of PDT for OCT images after disappearance following the initial CSCR; (2) follow-up period less than 3 years; (3) iatrogenic half-dose PDT. Complications of PDT were also recorded. CSCR caused by systemic corticosteroids; (4) FA or ICGA The Snellen visual acuity was converted to logarithm of findings of CNV or polypoidal choroidal vasculopathy the minimum angle of resolution (logMAR) units for statis- (PCV); (5) other maculopathy on clinical examination; tical analysis. Comparisons of categorical variables be- (6) media opacity such as cataract that could interfere tween 2 groups were performed using the x2 test or the with adequate acquisition of OCT, FA, and ICGA images. Fisher exact test. Continuous variables were compared Patients’ age, sex, first episode or recurrence of CSCR, using a 2-tailed t test for parametric distribution or and duration of the latest onset at their initial visits were Mann-Whitney U test for nonparametric distribution. As- recorded. At baseline, all patients had a complete ophthal- sociation between clinical parameters and the BCVA as mologic examination, including measurements of best- well as improvement in BCVA in patients’ final follow- corrected visual acuity (BCVA) and intraocular pressure up visits after PDT were analyzed with a multiple linear (IOP) by Goldmann tonometry, slit-lamp examination, regression model. A multiple logistic regression model FA (TRC-50IX; Topcon Corp, Tokyo, Japan), ICGA was used to identify the independent predictors of recur- (TRC-50IX; Topcon Corp), and OCT with 1 of 2 OCT sys- rence of CSCR in patients’ final follow-up. Statistical anal- tems including Stratus 3 OCT (Carl Zeiss, Dublin, Califor- ysis was performed using SPSS version 20.0 (SPSS, Inc, nia, USA) or Spectralis OCT (Spectralis; Heidelberg Chicago, Illinois, USA). A P value of <.05 was considered Engineering Inc, Heidelberg, Germany). Enhanced depth as statistically significant. imaging (EDI) was not used for any of the patients in this study. ICGA findings during the middle phase (around 10 minutes after the ICG injection) were classified as intense or intermediate hyperfluorescence or as having no RESULTS hyperfluorescence according to previous studies.24,25 PDT was performed using half-dose verteporfin (Visu- ONE HUNDRED FORTY-FOUR EYES OF 131 PATIENTS WITH dyne; Novartis AG, Bu¨lach, Switzerland). In brief, chronic CSCR were included in the study. Six eyes of 6 pa- 3 mg/m2 of verteporfin was infused over 10 minutes, and tients were excluded owing to follow-up period less than 3 5 minutes thereafter the laser treatment was applied.25 years. Two eyes of 2 patients with associated CNV or PCV Half-dose PDT was the standard of treatment for patients were excluded. One hundred thirty-six eyes of 123 patients

92 AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER 2016 FIGURE 1. Photodynamic therapy in multifocal chronic central serous chorioretinopathy. (Left) Multifocal leakage points were demonstrated by ﬂuorescein angiography in a patient with chronic central serous chorioretinopathy. (Right) Consecutive, nonover- lapping laser spots (83 seconds for each spot) were delivered to the areas of hyperpermeability in indocyanine green angiography (white dashed circles).

were eventually included in the study. The mean age of the baseline to 244.23 6 53.74 mm at 36 months post PDT. patients was 49.4 6 9.0 years (range: 29–80 years). There The CFT at 3, 6, 12, 24, and 36 months and at patients’ were 94 (76.4%) male and 29 (23.6%) female subjects. final follow-up after PDT treatment were all significantly The mean duration of follow-up was 57.7 6 16.2 months (P < .001) better than at baseline (Table 1). Multiple (range: 36–96 months). The mean duration of symptoms linear regression model showed that baseline BCVA was was 8.53 6 6.96 months (range: 3–52 months). Twenty- positively associated with BCVA at patients’ final follow three patients (18.7%) had history of bilateral CSCR. up (P ¼ .009, standardized b ¼ 0.662; Table 2). Baseline Nineteen eyes (14.0%) had history of recurrent CSCR BCVA was also negatively associated with improvement before PDT. The mean baseline logMAR BCVA was in BCVA at patients’ final follow-up (P < .001, standard- 0.36 6 0.29 (Snellen equivalent 20/46; range: 0.1–1.2). ized b ¼0.609; Table 3). Age, sex, duration of symptom, Presence of subretinal fluid (SRF) was found in all eyes at PDT spot size, baseline CFT, history of recurrent CSCR, presentation. Pigment epithelial detachment (PED) was history of bilateral CSCR, FA pattern, grade of ICGA in- found in 55 eyes (40.4%). The mean baseline CFT was tensity, coexistent PED, resolution of SRD after first 387.70 6 105.45 mm. The pattern of leakage on FA PDT, and CSCR recurrence were not significantly associ- was an inkblot pattern in 128 eyes (94.1%) and 8 eyes ated with BCVA and change in BCVA at patients’ last (5.9%) had a smoke-stack pattern. The ICGA intensity follow-up. Duration of symptoms was significantly corre- was intermediate hyperfluorescence in 80 eyes (58.8%), lated with baseline BCVA (r ¼ 0.309, P < .001, Pearson intense hyperfluorescence in 49 eyes (36.0%), and no correlation). Eyes with baseline Snellen BCVA of 20/40 hyperfluorescence in 6 eyes (4.4%). The ICGA of 1 eye or better (28 of 83 eyes) were significantly more likely was missing in the clinical records. than eyes with worse than 20/40 baseline vision (5 of 53 The mean spot size of the first PDT was 3773.5 6 eyes) to achieve BCVA of 20/20 or better at the final 1084.5 mm (range: 1500–6400 mm). At 36 months after follow-up after PDT (P ¼ .001; odds ratio [OR] ¼ 4.89, the PDT treatment, 132 eyes (97.1%) achieved complete 95% confidence interval [CI] ¼ 1.75–13.65, Fisher exact SRD resolution with a single PDT treatment. Three eyes test). (2.2%) of 3 patients received second half-dose PDT for persistent SRD and all these eyes achieved complete CLINICAL CHARACTERISTICS OF EYES WITH AND SRD resolution after repeat treatment. The remaining WITHOUT RECURRENCE OF CHRONIC CENTRAL SEROUS eye had spontaneous resolution of SRD after 36 months CHORIORETINOPATHY POST PHOTODYNAMIC THERAPY: and did not receive further PDT until the final follow-up. Nine eyes (6.6%) of 8 patients developed recurrence of The logMAR BCVA significantly improved from 0.36 6 CSCR at their final follow-up (Figure 2). Four eyes 0.29 (Snellen equivalent 20/46; range: 0.1–1.2) to 0.15 6 (2.9%) of 3 patients had recurrence within 36 months af- 0.23 at 36 months after PDT (Snellen equivalent 20/28; ter PDT. Five cases received a second PDT treatment range: 0.1–1.5; P < .001). Forty-four eyes (32.4%) had >_3 while the remaining 4 cases of recurrent CSCR resolved lines of BCVA gain while 5 eyes (3.7%) had >_3 lines of spontaneously. The mean time to recurrence of CSCR BCVA loss at 36 months after PDT. The BCVA at 3, 6, was 43.6 6 33.7 months (range 10–93 months). The clin- 12, 24, and 36 months and at patients’ last follow-up ical characteristics of eyes with and without recurrence of were all significantly (P < .001) better than that at baseline CSCR at their final follow-up after PDT treatment were (Table 1). The CFT improved from 387.70 6 105.45 mmat shown in Table 4. Four patients with failed resolution of

VOL. 170 PHOTODYNAMIC THERAPY FOR CENTRAL SEROUS CHORIORETINOPATHY 93 TABLE 1. Treatment Results of Half-dose Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

Characters Results P Value

Pretreatment BCVA (logMAR) 0.36 6 0.29 Posttreatment BCVA (logMAR) 3 months 0.24 6 0.32 <.001a 6 months 0.20 6 0.30 <.001a 12 months 0.17 6 0.26 <.001a 24 months 0.19 6 0.26 <.001a 36 months 0.15 6 0.23 <.001a Final follow-up 0.16 6 0.24 <.001a Subgroup of BCVA Pretreatment >_20/30 42 (30.9%) 20/40–20/80 70 (51.5%) <_20/100 24 (17.6%) 36 months >_20/30 116 (85.3%) 20/40–20/80 18 (13.2%) <_20/100 2 (1.5%) Final follow-up >_20/30 114 (83.8%) 20/40–20/80 15 (11.0%) <_20/100 7 (5.1%) Pretreatment central foveal thickness (mm) 387.70 6 105.45 Posttreatment central foveal thickness (mm) 3 months 239.61 6 52.50 <.001a 6 months 238.28 6 41.82 <.001a 12 months 237.43 6 44.83 <.001a 24 months 236.45 6 39.96 <.001a 36 months 244.23 6 53.74 <.001a Final follow-up 237.78 6 44.10 <.001a Complete SRD resolution with single PDT at 36 months Yes 132 (97.1%) No 4 (2.9%) Number of PDT required at ﬁnal follow-up 1 128 (94.1%) 2 8 (5.9%) Recurrence of CSCR at ﬁnal follow-up Yes 9 (6.6%) No 127 (93.4%) Time of recurrence 43.6 6 33.7 (10–93 months) Ocular complications RPE atrophy 5 (3.7%) CNV 1 (0.7%) RPE rip 1 (0.7%) Macular scar 1 (0.7%)

BCVA ¼ best-corrected visual acuity; CNV ¼ choroidal neovascularization; CSCR ¼ central serous chorioretinopathy; PDT ¼ photodynamic therapy; RPE ¼ retinal pigment epithelium; SRD ¼ serous retinal detachment. aPaired t test.

SRD with single PDT were excluded from the analysis. For history of recurrent CSCR, and resolution of CSCR patients who had both eyes treated with PDT, only the with single PDT between 2 groups. However, eyes with right eye was included in the analysis. There were no sig- recurrent CSCR post PDT had a signiﬁcantly higher pro- niﬁcant differences in the age, sex distribution, duration of portion of history of bilateral CSCR (P ¼ .004, Fisher symptoms, PDT spot size, baseline BCVA, proportion of exact test). A multiple logistic regression model coexistent PED, FA pattern, grade of ICGA intensities, (Table 5) with the above parameters showed that history

94 AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER 2016 TABLE 2. Multiple Linear Regression for Predictors of Visual Acuity at Patients’ Final Follow-up After Photodynamic Therapy

Predictors b Standard Error Standardized b 95% CI for b P Value

Age (y) 0.002 0.002 0.073 0.006 to 0.002 .321 Male 0.074 0.042 0.127 0.157 to 0.009 .081 Duration of symptom (mo) 0.001 0.003 0.033 0.005 to 0.008 .663 Pretreatment BCVA (logMAR) 0.560 0.067 0.662 0.427 to 0.694 .009* History of recurrent CSCR before PDT 0.067 0.051 0.093 0.035 to 0.169 .197 History of bilateral CSCR 0.019 0.46 0.033 0.110 to 0.72 .685 PDT spot size (mm) <0.001 <0.001 0.005 - .944 Baseline CFT (mm) <0.001 <0.001 0.152 0.001 to <0.001 .057 Inkblot pattern in FA 0.009 0.068 0.010 0.144 to 0.125 .892 Grade of ICGA intensity 0.003 0.033 0.007 0.062 to 0.069 .921 Coexistent PED 0.007 0.037 0.013 0.067 to 0.080 .860 Resolution of SRD with single PDT 0.079 0.136 0.043 0.191 to 0.350 .561 Post-PDT CSCR recurrence 0.022 0.075 0.022 0.170 to 0.126 .767

TABLE 3. Multiple Linear Regression for Predictors of Improvement in Visual Acuity at Patients’ Final Follow-up After Photodynamic Therapy

Predictors b Standard Error Standardized b 95% CI for b P Value

Age (y) 0.002 0.002 0.086 0.006 to 0.002 .321 Male 0.074 0.042 0.150 0.157 to 0.009 .081 Duration of symptom (mo) 0.001 0.003 0.039 0.005 to 0.008 .663 Pretreatment BCVA (logMAR) 0.440 0.067 0.609 0.573 to 0.306 <.001* History of recurrent CSCR before PDT 0.067 0.051 0.110 0.035 to 0.169 .197 History of bilateral CSCR 0.019 0.46 0.039 0.110 to 0.72 .685 PDT spot size (mm) <0.001 <0.001 0.006 - .944 Baseline CFT (mm) <0.001 <0.001 0.178 0.001 to <0.001 .057 Inkblot pattern in FA 0.009 0.068 0.011 0.144 to 0.125 .892 Grade of ICGA intensity 0.003 0.033 0.009 0.062 to 0.069 .921 Coexistent PED 0.007 0.037 0.015 0.067 to 0.080 .860 Resolution of SRD with single PDT 0.079 0.136 0.051 0.191 to 0.350 .561 Post-PDT CSCR recurrence 0.022 0.075 0.026 0.170 to 0.126 .767

Asterisk indicates P value is statistically significant (P < .05). BCVA ¼ best-corrected visual acuity; CFT ¼ central foveal thickness; CSCR ¼ central serous chorioretinopathy; FA ¼ fluorescein angiography; ICGA ¼ indocyanine green angiography; PDT ¼ photodynamic therapy; PED ¼ pigment epithelial detachment; SRD ¼ serous retinal detachment. of bilateral CSCR was significantly associated with recur- ment found before PDT. There was 1 eye (0.7%) with rence of CSCR after PDT (P ¼ .036; odds ratio ¼ 15.84, subretinal fibrotic macular scar (0.7%) that did not show 95% CI ¼ 1.20–208.32). any CNV in FA and ICGA.

SAFETY ASSESSMENTS: Eight eyes (5.9%) were found to have complications related to half-dose PDT at 36 months after PDT. There were 5 eyes (3.7%) with enlarged RPE at- DISCUSSION rophy in the serial follow-up after the PDT. One eye had CNV (0.7%), which developed 12 months after the PDT. CHRONIC CSCR, CHARACTERIZED BY PERSISTENT NEURO- RPE rip was found in 1 eye (0.7%) at 3 months after the sensory retinal detachment or RPE atrophy, can be a debil- PDT. The RPE rip occurred in an eye with RPE detach- itating condition, especially in the working population.2

VOL. 170 PHOTODYNAMIC THERAPY FOR CENTRAL SEROUS CHORIORETINOPATHY 95 tients’ last follow-up. This shows that patients with worsepresentingvisualacuityhadalargerroomforvi- sual improvement after half-dose PDT. On the other side, baseline BCVA was positively associated with the BCVA at the last follow-up after PDT. Eyes with baseline Snellen BCVA of 20/40orbetterweremore likely to achieve BCVA of 20/20 or better at the final follow-up after PDT. Previous studies have also reported this association.28,37 Eyes with prolonged duration of symptoms of more than 9 months have been reported to be associated with foveal atrophy and worse final visual outcome after full-dose PDT.37 In the current study, duration of symptoms was not significantly corre- lated with post-treatment BCVA after half-dose PDT. This may be attributable to a higher proportion of our patients with early treatment or better preservation of RPE function long-term after half-dose PDT. FIGURE 2. Kaplan-Meier survival curve for disease recurrence Standard-dose PDT was reported to have complication 20 free after half-dose photodynamic therapy of chronic central se- ratesrangingfrom0to13.4%. The reported complica- 18, 21 rous chorioretinopathy. tion rate from half-dose PDT was generally low, and this was also found in the current study. Given how safe half-dose PDT has been shown to be, patients with chronic CSCR should be considered for PDT has been shown to be an effective therapy for chronic half-dose PDT early and well before they experience vi- CSCR.20,21 PDT can result in visual improvement, sual deterioration in order to avoid irreversible visual shortened duration of symptoms, and reduced recurrence loss. rates, with a good safety profile.20 The drug dosage, fluence, The long-term recurrence rate of untreated CSCR was and irradiation time of PDT can be modified to reduce the reported to be 40%–50%.2 This study demonstrated a adverse effects of PDT and provide good treatment effi- significant reduction in recurrence rate of CSCR after cacy.28 Nevertheless, there are limited studies with large half-dose PDT at 3 years and beyond. Only 9 eyes sample size and long-term follow-up to provide evidence (6.6%) developed recurrence of CSCR after a mean regarding the long-term efficacy and safety of PDT in follow-up of 57.7 months. The recurrence rate chronic CSCR.29–34 of CSCR after PDT was reported to be between The current study showed that half-dose PDT was an 2% and 20% in other studies, with a mean follow-up effective and safe treatment for chronic CSCR patients period ranging from 25 to 80 months.29–32,34 In with a minimum follow-up of 3 years. A single PDT treat- this study, the mean time to CSCR recurrence was ment achieved complete SRD resolution in 97.1% of eyes 43.6 6 33.7 months. The longest time to recurrence in at 36 months post treatment. Previous publications this study was 8 years after PDT treatment. Such reported the rate of SRD resolution to be between 85% findings suggested that more studies with even longer and 100% at 1 year.19,25,34–36 Silva and associates follow-up are needed to investigate the longer-term reported the 4-year outcomes of standard PDT in 46 recurrence rate of CSCR after PDT. eyes with chronic CSCR.31 Complete SRF resolution Themultiplelogisticregressionmodelshowedthat was achieved in 93.4% of eyes, with a mean of 1.08 6 history of bilateral CSCR was associated with recur- 0.3 sessions of PDT. Karakus and associates reported rence of CSCR at the patients’ final follow-up after that 91.7% of 27 eyes treated with half-dose PDT were PDT. To our knowledge, this association has not been free of SRF at an average follow-up period of previously reported. It might be possible that those 25.3 months.29 Inanotherseriesof55eyestreatedwith patients with bilateral CSCR were prone to a more half-dose PDT, 100% of SRF resolution was obtained after aggressive course of CSCR that was refractory to half- a mean follow-up of 55.5 months.32 Theanatomicsuccess dose PDT. Patients with unilateral CSCR have rate in our study was comparable to these studies. The been shown to have increased choroidal thickness in mean BCVA improved gradually and stabilized at the contralateral disease-free eye.38 Recently, patholog- 6–12 months after PDT until the follow-up of 3 years. ically dilated deep choroidal vessels referred to as This pattern of visual improvement was also observed in pachychoroidal changes have been described.39 They other studies.29–32 have been associated with focal disruptions in In the current study, worse baseline BCVA was asso- the RPE and Bruch membrane.39,40 With the advance ciated with greater improvement of BCVA at the pa- of noninvasive in vivo imaging using OCT, abnormal

96 AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER 2016 TABLE 4. Comparison of Features Between Patients With and Without Recurrence of Chronic Central Serous Chorioretinopathy at Patients’ Final Follow-up

Features Eyes Without Recurrence Eyes With Recurrence P Value

No. of patients 114 5 Age (y) 49.4 6 8.7 50.7 6 12.1 .749a Sex, male: female 86:28 5:0 .590b Duration of symptoms (mo) 7.9 6 5.7 12.6 6 8.8 .301a PDT spot size (mm) 3764.0 6 1044.8 4140.0 6 1467.3 .600a BCVA at baseline (logMAR) 0.37 6 0.29 0.44 6 0.35 .651a Coexistent PED, yes: no 42:72 4:1 .073b FA pattern, inkblot: smoke stack 107:7 5:0 1.000b Grade of ICGA intensity: no/intermediate/intense 6/66/41 0/3/2 .867c History of bilateral CSCR, yes: no 18:96 4:1 .004b* History of recurrent CSCR, yes: no 16:98 0:5 1.000b

Asterisk indicates P value is statistically signiﬁcant (P < .05). BCVA ¼ best-corrected visual acuity; CSCR ¼ central serous chorioretinopathy; FA ¼ ﬂuorescein angiography; ICGA ¼ indocyanine green angiography; PDT ¼ photodynamic therapy; PED ¼ pigment epithelial detachment; SRD ¼ serous retinal detachment. at test. bFisher exact test. cx2 test.

be studied and might identify a difference in choroidal TABLE 5. Multiple Logistic Regression for Predictors of vascular condition between patients with unilateral or Recurrence of Central Serous Chorioretinopathy at Patients’ bilateral CSCR. Last Follow-up After Photodynamic Therapy The limitations of our study included retrospective analysis and lack of control group. Because enhanced depth im- Odds Ratio (95% Predictors Confidence Interval) P Value aging and autofluorescence were not available in all patients, especially those with long follow-up duration, Age (y) 0.99 (0.87–1.12) .834 we did not analyze data on choroidal thickness and RPE Female - .998 Duration of symptoms (mo) 1.03 (0.91–1.16) .651 function that has been previously reported to be associated 41 PDT spot size (mm) 1.00 (1.00–1.00) .943 with the success rate of PDT. The good efficacy of half- BCVA at baseline (logMAR) 5.20 (0.04–718.02) .512 dose PDT implied a low number of CSCR recurrence, Coexistent PED 3.56 (0.26–48.39) .341 which led to a skewed distribution in comparing the nonre- Inkblot pattern in FA - .999 current and recurrent cases. This study was nevertheless Grade of ICGA intensity 1.67 (0.22–12.80) .621 one of the largest (136 eyes) investigations on long-term History of bilateral CSCR 15.84 (1.20–208.32) .036* (more than 3 year) treatment outcomes of half-dose PDT History of recurrent CSCR - .998 in chronic CSCR to date. In conclusion, the current study demonstrated a good Asterisk indicates P value is statistically significant (P < .05). BCVA ¼ best-corrected visual acuity; CSCR ¼ central serous long-term anatomic and visual success rate after half- chorioretinopathy; FA ¼ fluorescein angiography; ICGA ¼ indoc- dose PDT for chronic CSCR. Patients with good base- yanine green angiography; PDT ¼ photodynamic therapy; PED ¼ line visual acuity were more likely to achieve good final pigment epithelial detachment; SRD ¼ serous retinal detachment. visual acuity outcome. Therefore, patients should consider half-dose PDT before chronic CSCR causes irreversible visual deterioration. The history of bilateral choroidal morphology of choroidal vasculature has been CSCR was also shown to be associated with higher observed even in the asymptomatic fellow eyes in recurrence of CSCR after PDT. Further studies are CSCR patients.39 Whether these changes are more required to identify the optimal treatment regime of prominent in patients with bilateral CSCR remains to PDT in bilateral disease.

FUNDING/SUPPORT: NO FUNDING OR GRANT SUPPORT. FINANCIAL DISCLOSURES: THE FOLLOWING AUTHORS HAVE NO ﬁnancial disclosures: Frank H.P. Lai, Danny S. Ng, Malini Bakthavatsalam, Vesta C.K. Chan, Alvin L. Young, Fiona O.J. Luk, Chi Wai Tsang, and Ma˚rten Brelen. All authors attest that they meet the current ICMJE criteria for authorship.

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