To determine the efficacy of half-dose photodynamic therapy (PDT) in relation to indocyanine green angiography (ICGA) and optical coherence tomography (OCT) findings for treating chronic central serous chorioretinopathy (CSC).
Observational case series.
Thirty-eight eyes of 37 patients with chronic CSC and symptoms for at least 6 months were recruited. PDT was performed using half the normal dose of verteporfin. A total light energy of 50 J/cm 2 over 83 seconds was delivered to the area of choroidal hyperfluorescence as observed on ICGA. The resolution of the subretinal fluid and recurrence rates were assessed in relation to the different degrees of choroidal hyperfluorescence and the distribution of fluid in the neuroepithelium, namely subretinal fluid or posterior retinal cystoid degeneration.
After half-dose PDT a dry macula was obtained in 86.8% and 92.1% of the eyes at 1 month and at the last follow-up (14.2 ± 5.8 months) respectively. ICGA at baseline showed intermediate and intense hyperfluorescence in 39.4% and 60.5% of the eyes respectively. All eyes with intermediate hyperfluorescence had only subretinal fluid at OCT and a dry macula was obtained in 87% and 100% at 1 month and at the last follow-up after half-dose PDT. In the intense hyperfluorescence group, 82.6% and 17.4% of the eyes had subretinal fluid only or both subretinal fluid and posterior retinal cystoid degeneration respectively. In the intense hyperfluorescence group with subretinal fluid only, a dry macula was obtained in 89.5% and 100% of the eyes at 1 month and at the last follow-up respectively. In the intense hyperfluorescence group with both subretinal fluid and posterior retinal cystoid degeneration, a dry macula was obtained in 75% and 25% of the eyes at 1 month and at the last follow-up respectively. Overall, of the 23 eyes with intense hyperfluorescence, 20 eyes (87%) had a dry macula starting from 1 month for the entire follow-up period.
The half-dose PDT success rate in eyes with chronic CSC depends also on the distribution of fluid in the neuroepithelium. Half-dose PDT might not be effective or the recurrence rate might be high in eyes with posterior retinal cystoid degeneration.
Central serous chorioretinopathy (CSC) is characterized by the development of serous neurosensory retinal detachment at the posterior pole. In the majority of patients, CSC is self-limiting and patients usually have a good visual prognosis. However, in cases of chronic CSC with persistent serous retinal detachment and chronic decompensation of the retinal pigment epithelium (RPE), progressive visual loss attributable to photoreceptor disruption and cystoid edema of the neurosensory retina might develop. The increasing use of indocyanine green angiography (ICGA) in CSC has improved the understanding of the pathogenesis of CSC and has demonstrated that during CSC choroidal circulation in addition to RPE is primarily affected, resulting in multifocal areas of choroidal vascular hyperpermeability.
Treatment options for chronic CSC are thermal laser photocoagulation and photodynamic therapy. As direct thermal laser has the disadvantages of causing RPE damage and iatrogenic choroidal neovascularization (CNV), more effective and less harmful treatment modalities have been proposed. Photodynamic therapy (PDT) for CSC is reported to be efficacious in reducing subretinal fluid and increasing visual acuity in most patients. One of the strengths of PDT lies in its security and the assumed absence of side effects, although standard PDT can have some significant negative implications such as RPE atrophy, choriocapillaris ischemia, and secondary CNV.
In order to avoid PDT-related complications, half-dose or low-fluence PDT has been suggested by different authors. Half-dose or low-fluence PDT with verteporfin is effective in inducing reabsorption of subretinal or intraretinal fluid with some beneficial visual outcomes in the majority of patients with CSC. Retinal sensitivity increases in patients with CSC treated with half-dose PDT, showing a high safety profile of this treatment.
The exact mechanism of PDT in treating chronic CSC is not conclusive, but it is thought to be caused by short-term choriocapillaris hypoperfusion and long-term choroidal vascular remodeling, leading to a reduction in choroidal congestion, vascular hyperpermeability, and extravascular leakage. Previous studies, focusing on the ICGA findings, showed a high correlation between choroidal hyperpermeability and the efficacy of PDT. However, it is not clear if there might be factors other than ICGA findings that could influence the outcome after PDT. In chronic CSC fluid usually accumulates under the retina, though in some cases it can also infiltrate the neuroepithelium to form posterior cystoid retinal degeneration. The current study is focused on baseline ICGA findings as well as OCT findings in eyes with chronic CSC and the associations between such findings and the efficacy of long-term results after half-dose PDT has been evaluated.
This study was a retrospective, interventional case series conducted in the Department of Neuroscience, Ophthalmology and Genetics of the University of Genova, Italy. Patients were offered treatment if they had persistent fluid involving the macula. Inclusion criteria were: 1) a 6-month history of CSC; 2) best-corrected visual acuity (BCVA) of 20/200 or better; 3) presence of subretinal fluid involving the fovea with or without posterior cystoid retinal degeneration on OCT; and 4) presence of active angiographic leakage on fluorescein angiography (FA) caused by CSC but not CNV or other diseases.
Indocyanine green angiography was performed on all patients in order to outline choroidal hyperpermeability areas. Patients who had received focal thermal laser photocoagulation for the treatment of CSC prior to this study were included, whereas patients previously treated with anti–vascular endothelial growth factor or steroid intraocular injections were excluded. Snellen BCVA was measured at the baseline and post-PDT visits. Evaluation of macular detachment was performed using a spectral-domain optical coherence tomography (OCT) machine (Topcon 3D OCT-1000; Topcon, Capelle a/d IJssel, the Netherlands). Central foveal thickness was measured by way of the 12-radial scan protocols at baseline, at 1 month, and at the last follow-up visit. FA and ICGA were performed in all patients at baseline and at the last follow-up visit after PDT. Additional FA and ICGA were carried out on patients with persisting or recurring CSC during follow-up. PDT was performed by administering half the normal dose of verteporfin (Visudyne; Novartis AG, Lausanne, Switzerland) as previously described. Verteporfin was infused over 10 minutes followed by delivery of laser at 693 nm after 5 minutes from the commencement of infusion to target the area of choroidal hyperpermeability. A total light energy of 50 J/cm 2 over 83 seconds was delivered to the area of choroidal hyperfluorescence as observed in ICGA. Areas of choroidal vascular abnormality that were supposed to cause the serous detachment were considered to be treated.
In order to classifiy ICGA findings according to the criteria previously reported, 1 of the authors (M.N.) reviewed all baseline middle-phase ICG angiograms about 10 minutes after ICG injection. Revisions were masked with regard to outcomes in order to enhance objectivity. After treatment, patients were given protective glasses and instructed to avoid strong light for 2 days. The main outcome measures of the study included the percentage of patients with a dry macula at 1 month and at the last follow-up visit, BCVA, and central foveal thickness.
A total of 38 eyes of 37 patients with chronic CSC received half-dose PDT. The mean ± SD age of patients was 48.5 ± 10.3 years (range 31–70) and 34 of the patients (91.8%) were male. Baseline mean ± standard deviation (SD) BCVA was 0.74 ± 0.19 (range 0.3–1.0). Mean follow-up was 14.2 ± 5.8 months (median 12, range 8–30). Baseline mean ± SD central foveal thickness was 345.61 ± 101.00 μm.
At baseline, 34 of the 38 eyes (89.5%) had subretinal fluid alone and 4 eyes (10.5%) had combined subretinal fluid and posterior cystoid retinal degeneration. Baseline FA showed 5 eyes (13.1%) with focal leakage and 33 eyes (86.8%) with diffuse leakage. On ICGA, choroidal hyperfluorescence was identified in all patients. Fifteen eyes (39.4%) showed an intermediate hyperfluorescence and 23 eyes (60.5%) showed an intense hyperfluorescence. All 15 eyes (100%) in the intermediate choroidal hyperfluorescence group had subretinal fluid only at OCT. Of the 23 eyes in the intense hyperfluorescence group, 19 (82.6%) had subretinal fluid only, while the remaining 4 (17.4%) also had posterior cystoid retinal degeneration.
At 1 month from PDT, the resolution of the fluid was complete, partial, or absent in 86.8% (33/38), 10.5% (4/38), and 2.6% (1/38) of eyes respectively. At the last follow-up visit the resolution of the fluid was complete, partial, or absent in 92.1% (35/38), 2.6% (1/38), and 5.3% (2/38) of the eyes respectively. Overall, there was a significant ( P < .001) decrease of the central foveal thickness ( Table 1 ). BCVA was unchanged or had improved by 3 lines in 57.8% (22/38) and 39.5% (15/38) of the eyes respectively. Only 1 eye lost 3 lines at the last follow-up visit. Overall BCVA improved significantly (0.83 ± 0.2, P = .001). The rates of resolution of subretinal fluid based on ICGA and OCT findings are reported in Table 2 . In the intermediate hyperfluorescence group, subretinal fluid recovered completely in 87% (13/15) and 100% (15/15) of eyes at 1 month and at last follow-up respectively. In the intense hyperfluorescence group with subretinal fluid only, a dry macula was obtained in 89.5% (17/19) and 100% (19/19) of the eyes at 1 month and at the last follow-up respectively. In the intense hyperfluorescence group with posterior cystoid retinal degeneration, a dry macula was obtained in 75% (3/4) and 25% (1/4) of the eyes at 1 month and at last follow-up visit respectively. Overall, in the intense hyperfluorescence group, 87% (13/15) of eyes had a dry macula starting from 1 month after treatment and lasting throughout the follow-up period ( Figures 1 through 3 ) .
|Central Foveal Thickness ± SD||Resolution of Fluid|
|Baseline||345.61 ± 101.00 μm|
|1 month||—||86.8% (n = 33)||10.5% (n = 4)||2.6% (n = 1)|
|Last follow-up (14 months)||213.07 ± 47.20 μm a||92.1% (n = 35)||2.6% (n = 1)||5.3% (n = 2)|
a P value was significant at the last follow-up ( P = < .001).
|Baseline ICGA Findings||Baseline VA (Range)||No. Eyes||Baseline OCT Findings||Resolution of Subretinal Fluid||Resolution of Posterior Cystoid Retinal Degeneration||VA at Last Follow-up (Range)|
|At 1 Month||At Last Follow-up||At 1 Month||At Last Follow-up|
|Intense hyperfluorescence||0.7 (0.3–1)||23||Subretinal fluid in 19 eyes; posterior cystoid retinal degeneration in 4 eyes||17 of 19 eyes (89.5%)||19 of 19 eyes (100%)||3 of 4 eyes (75%)||1 of 4 eyes (25%)||0.28 (0.3–1)|
|Intermediate hyperfluorescence||0.7 (0.6–1)||15||Subretinal fluid in 15 eyes; posterior cystoid retinal degeneration in 0 eyes||13 of 15 eyes (87%)||15 of 15 eyes (100%)||—||—||1 (0.6–1)|