Purpose
To compare the efficacy of half-dose vs half-time photodynamic therapy (PDT) guided by fluorescein angiography (FA) for the treatment of central serous chorioretinopathy (CSC).
Design
Two-center, retrospective, comparative case series.
Methods
Sixty-one eyes with acute or chronic CSC involving fovea were recruited; 35 eyes received half-dose PDT and 26 eyes received half-time PDT. Improvement in best-corrected visual acuity (BCVA), resolution of subretinal fluid (SRF) demonstrated by optical coherence tomography (OCT), and recurrence of CSC after PDT were compared between the 2 groups.
Results
The mean follow-up time after PDT was 14.8 ± 13.3 months. Both groups showed significant improvement in BCVA at months 1, 3, 6, and 12 after PDT ( P < .05 for all times). Multiple regression analysis showed that PDT type was not correlated with visual improvement ( P > .05 for all times). All eyes that received half-time PDT showed complete resolution of SRF within 6 months after PDT, but 3 eyes that received half-dose PDT had persistent SRF before loss to follow-up at months 5, 7, and 8 ( P = .21 between 2 groups). Three of 32 eyes in the half-dose group and 2 of 26 eyes in the half-time group had recurrence of CSC during follow-up; all recurrent cases had complete SRF resolution after another PDT treatment. No adverse systemic or ocular side effects were observed in any cases.
Conclusions
Half-dose and half-time FA-guided PDT were both effective and safe in treating CSC and showed similar efficacy in visual improvement and SRF resolution.
Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neurosensory retina with or without serous detachment of the retinal pigment epithelium (RPE) at the posterior pole caused by increased permeability of the choroidal vessels. Although CSC mainly is self-limiting and generally has a good visual prognosis, persistent foveal detachment or recurrence can result in damage to the RPE and choroidal neovascularization (CNV). Photodynamic therapy (PDT) has been shown to be effective against both acute and chronic CSC. Although PDT has yielded favorable results, post-PDT complications have been reported, including RPE atrophy, RPE tear, choriocapillaris ischemia, and secondary CNV.
During the past decade, various modifications of the PDT regimen adopted reduced irradiance, exposure time, or verteporfin dose in an effort to maintain efficacy while reducing the risk of complications. Both half-fluence and half-dose PDT were shown to be effective for treating acute or chronic CSC with fewer complications. In fact, fluence is composed of irradiance and exposure time. To the best of our knowledge, the so-called half-fluence PDT used in the majority of previous studies was carried out by halving the irradiance instead of the exposure time. Half-time PDT, which was performed by halving the laser exposure time using standard irradiance, has also been reported to be effective and safe in the treatment of CSC. A previous study compared the safety and efficacy of half-irradiance vs half-dose PDT, but no comparative study has reported comparative data for half-time PDT. In this study, we retrospectively collected data and compared the efficacy and safety of half-dose fluorescein angiography (FA)-guided PDT vs half-time FA-guided PDT for the treatment of acute or chronic CSC.
Methods
Retrospective review of medical records of 61 patients who had received half-dose or half-time PDT for treatment of CSC at the Department of Ophthalmology, National Taiwan University Hospital, or at the Department of Ophthalmology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, from January 1, 2008 to March 31, 2014 was conducted. This study followed the tenets of the Declaration of Helsinki, and Institutional Review Board (IRB) approval was obtained prospectively from the National Taiwan University Hospital (IRB approval number: 201508025RINB) and the Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (IRB approval number: 03-X09-024). Inclusion criteria included the following: (1) symptoms of blurred vision or central scotoma for at least 1 month; (2) CSC with subfoveal or juxtafoveal active leakage documented by FA; and (3) persistent subfoveal subretinal fluid (SRF) and/or retinal pigmented epithelium detachment documented by optical coherence tomography (OCT) during at least 2 successive clinical visits before PDT treatment. Exclusion criteria included: (1) suspected CNV or polypoidal vasculopathy on FA or OCT; (2) previous PDT; and (3) loss to follow-up within 3 months of PDT. For patients who received treatment in both eyes, only the eyes that were treated first were recruited.
PDT was performed in the following manner: verteporfin (Novartis, Basel, Switzerland) was infused intravenously over 10 minutes, followed by administration of diode laser (693 nm) 15 minutes after the start of the infusion. Each patient received either the half-dose regimen (irradiance of 600 mW/cm 2 , laser time of 83 seconds, and verteporfin 3 mg/m 2 ) regimen or the half-time regimen (irradiance of 600 mW/cm 2 , laser time of 42 seconds, and verteporfin 6 mg/m 2 ). The treatment area was based on the area of active leakage documented by FA. All PDT treatments were performed by retinal specialists.
Best-corrected visual acuity (BCVA) was measured at baseline and during post-PDT visits using Snellen charts and was converted into the logarithm of the minimal angle of resolution (logMAR). Patients were examined with OCT (Cirrus HD-OCT 400; Carl Zeiss Meditec, Dublin, California, USA) at baseline, 1 month after PDT, and as needed thereafter, according to their clinical conditions. Two clinical markers were defined for evaluating the efficacy of PDT treatment: complete SRF resolution and recurrence. Complete SRF resolution was defined as the absence of SRF determined by 6 × 6 mm 2 OCT scanning. Recurrence was defined as the reappearance of SRF within the 6 × 6 mm 2 OCT scan after complete SRF resolution. The times for complete SRF resolution and recurrence documented by OCT were recorded. All patients received indirect funduscopic examinations at each follow-up visit.
Statistical Analysis
Paired t tests were used to compare the logMAR of BCVA before and after PDT, and t tests were used to compare the changes in the logMAR of BCVA after PDT between the half-dose group and the half-time group. Linear regression analysis was used to evaluate the correlating factors for logMAR changes after PDT. Proportions of complete SRF resolution and recurrence after PDT in the 2 groups were compared using Fisher exact tests and Kaplan-Meier log-rank tests. Cox regression analysis was used to evaluate the correlating factors for complete SRF resolution and recurrence after PDT. Age, sex and baseline BCVA were adjusted in all linear regression models and Cox regression models. A P value < .05 was considered statistically significant. SAS 9.4 (SAS Institute, Cary, North Carolina, USA) was used for all statistical analyses.
Results
Among the 61 eyes included in this study, 35 eyes received half-dose PDT and 26 eyes received half-time PDT. The baseline demographic data of both groups are shown in Table 1 . No significant differences in baseline characteristics were noted between these 2 groups. The mean follow-up period was 14.8 ± 13.3 months (range, 3–69 months). All patients received follow-up examinations at months 1 and 3, but only 75% and 44% of patients received follow-up at months 6 and 12, respectively.
| Half-dose PDT | Half-time PDT | P Value | |
|---|---|---|---|
| Case number | 35 | 26 | – |
| Age (y) | 44.5 ± 10.0 | 46.4 ± 7.8 | .44 |
| Sex (female, %) | 14% | 35% | .06 |
| LogMAR of baseline BCVA | 0.39 ± 0.32 | 0.29 ± 0.20 | .13 |
| Duration of symptoms (mo) | 5.9 ± 5.6 | 7.5 ± 5.5 | .27 |
Best-Corrected Visual Acuity
At baseline, the mean logMAR BCVA was 0.39 ± 0.32 in the half-dose PDT group and 0.29 ± 0.20 in the half-time PDT group. After PDT treatment, patients in both groups showed significant improvement in BCVA at each follow-up at months 1, 3, 6, and 12 compared with baseline ( P < .001 for all). Patients in the half-dose group had greater visual improvement at months 1 and 3 than those in the half-time group ( P = .0004 and P = .026, respectively), but not at months 6 and 12 ( P = .11 for both) ( Table 2 ). No eyes in the half-time group experienced a loss of BCVA during the follow-up periods. In the half-dose group, however, 1 eye experienced a loss of BCVA from 20/200 at baseline to 20/400 at month 5; this patient was lost to follow-up at month 5, and persistent SRF was noted during the follow-up visits before the patient dropped out.
| Half-dose PDT | P Value | Half-time PDT | P Value | P Value for Comparison Between 2 Groups | |
|---|---|---|---|---|---|
| Month 1 | −0.19 ± 0.16 | <.0001 | −0.07 ± 0.09 | .0005 | .0004 |
| Month 3 | −0.23 ± 0.24 | <.0001 | −0.12 ± 0.12 | <.0001 | .026 |
| Month 6 | −0.23 ± 0.21 | <.0001 | −0.14 ± 0.14 | .0005 | .11 |
| Month 12 | −0.25 ± 0.19 | .0002 | −0.15 ± 0.09 | <.0001 | .11 |
Table 3 shows the results of linear regression analysis for prognostic factors for visual improvement at month 3. In simple regression analysis, a poorer BCVA at baseline ( P < .0001) and half-dose regimen ( P = .040) were found to correlate with better visual improvement following PDT. After adjustment for age, sex, and baseline BCVA, a poorer BCVA was still significantly correlated with greater visual improvement ( P < .0001); PDT type, however, no longer correlated with changes in BCVA ( P = .18). Age, sex, duration of symptoms, and treatment spot size also were not correlated with visual improvement at month 3 after PDT ( P > .05 for all).
| Simple Regression | Adjusted for Age, Sex, and LogMAR of Baseline BCVA | |||
|---|---|---|---|---|
| Coefficient | P Value | Coefficient | P Value | |
| Age (y) | −0.003 | .27 | 0.0007 | .78 |
| Sex (F:0, M:1) | −0.018 | .77 | −0.035 | .52 |
| LogMAR of baseline BCVA | −0.387 | < .0001 | −0.399 | < .0001 |
| Half-time (0) vs half-dose (1) | −0.107 | .040 | −0.066 | .18 |
| Duration of symptoms (mo) | 0.052 | .48 | 0.090 | .17 |
| Treatment spot size (mm) | 0.008 | .89 | 0.002 | .97 |
Complete Subretinal Fluid Resolution
Table 4 shows the proportions of eyes with complete resolution of SRF at months 1, 3, 6, and 12 after PDT. Sixty percent of patients in the half-dose group and 81% in the half-time group had complete SRF resolution within 1 month after PDT ( P = .10). All patients in the half-time group had complete SRF resolution at month 6. In the half-dose group, 3 patients had persistent SRF at their last follow-up visits at months 5, 7, and 8, respectively. Figure 1 shows the cumulative probability for complete SRF resolution in the 2 groups: Patients in the half-time group had faster SRF resolution than did those in the half-dose group, according to a Kaplan-Meier log-rank test ( P = .024). According to Cox regression, however, complete SRF resolution was not affected by PDT type (half-dose vs half-time) or other baseline characteristics such as age, sex, BCVA at baseline, duration of symptoms, or treatment spot size ( P > .05 for all) ( Table 5 ).
| Half-dose PDT | Half-time PDT | P Value | |
|---|---|---|---|
| 1 month after PDT | 21/35 (60%) | 21/26 (81%) | .10 |
| 3 months after PDT | 27/35 (77%) | 25/26 (96%) | .065 |
| 6 months after PDT | 31/35 (89%) a | 26/26 (100%) | .13 |
| 12 months after PDT | 32/35 (91%) b | 26/26 (100%) | .25 |
a One case in the half-dose group was lost to follow-up at month 5 and showed persistent subretinal fluid at the last visit.
b Three cases in the half-dose group were lost to follow-up at months 5, 7, and 8; all presented with persistent subretinal fluid at the last visit.
| Simple Regression | Adjusted for Age, Sex, and LogMAR of Baseline BCVA | |||
|---|---|---|---|---|
| Hazard Ratio | P Value | Hazard Ratio | P Value | |
| Age (y) | 0.983 | .27 | 0.984 | .33 |
| Sex (F:0, M:1) | 0.725 | .31 | 0.685 | .23 |
| LogMAR of baseline BCVA | 0.668 | .38 | 0.758 | .58 |
| Half-time (0) vs. half-dose (1) | 0.681 | .16 | 0.686 | .21 |
| Duration of symptoms (mo) | 1.300 | .48 | 1.209 | .62 |
| Treatment spot size (mm) | 1.158 | .62 | 1.223 | .51 |
Recurrence
Among the 32 eyes with complete SRF resolution after 1 session of PDT treatment in the half-dose group, 3 eyes (9.4%) experienced SRF recurrence at months 3, 20, and 22, respectively. All 3 eyes had leakage points at the same locations as those before PDT demonstrated by FA ( Figure 2 ). In these 3 cases, patients received another half-dose or full-dose PDT, and complete resolution of SRF was noted within 1 month in 2 cases and within 4 months in 1 case. In the half-time group, 2 eyes out of the total of 26 eyes (7.7%) had recurrence of SRF at months 4 and 17, respectively. However, in both eyes the locations of the leakage points were different from those before PDT treatment ( Figure 3 ). Both eyes received another half-time PDT after recurrence, and complete resolution of SRF was noted in both cases within 1 month. No significant difference in the recurrence rate was noted between the 2 groups ( P = .93 by Kaplan-Meier log-rank test), as shown in Figure 4 . None of the variables, including age, sex, BCVA at baseline, duration of symptoms, types of PDT, and treatment spot size, was shown to be significantly correlated with the recurrence of SRF after PDT treatment ( P > .05 for all) ( Table 6 ).
