To determine the efficacy of photodynamic therapy (PDT) and indocyanine green angiography (ICGA) findings for treating chronic central serous chorioretinopathy (CSC).
Observational case series.
Thirty-two eyes of 27 patients with chronic CSC and symptoms for at least 6 months were recruited. The minimum follow-up was 1 year. The total PDT energy was reduced to about 36 to 42 mJ/cm 2 . The baseline middle-phase ICGA findings were classified as intense, intermediate, or no hyperfluorescence depending on the degree of hyperfluorescence. The resolution of the subretinal fluid and recurrence rates were assessed in relation to each ICGA finding at baseline.
ICGA before PDT showed intense hyperfluorescence in 23 eyes (72%), intermediate hyperfluorescence in 6 eyes (19%), and no hyperfluorescence in 3 eyes (9%). The subretinal fluid resolved completely 3 months after 1 application of PDT in 23 eyes (100%) with intense hyperfluorescence, 6 eyes (100%) with intermediate hyperfluorescence, and no eyes (0%) with no hyperfluorescence. In the last group, the subretinal fluid did not resolve throughout the follow-up period despite additional applications of PDT. The subretinal fluid recurred in 7 of 29 eyes (24%) in which the subretinal fluid resolved at 3 months; recurrence was frequent in eyes with intermediate hyperfluorescence (5 eyes; 83%).
The PDT success rate in eyes with chronic CSC depends on the degree of hyperpermeability on ICGA. PDT is not effective or the recurrence rate is predicted to be high in eyes without intense hyperfluorescence.
Central serous chorioretinopathy (CSC) is commonly seen in young or middle-aged adults as localized detachment of the neurosensory retina. CSC is a self-limiting disease that usually is associated with good visual prognosis. However, in cases of chronic CSC with persistent serous retinal detachment, the retinal pigment epithelium (RPE) may decompensate, leading to eventual visual loss. The pathogenic factors of CSC are thought to be related to abnormal choroidal circulation. Indocyanine green angiography (ICGA) has shown congested and dilated choroidal vein and capillaries, choroidal staining, and leakage into the extracellular space that appears as areas of hyperfluorescence seen in the middle and late phases in eyes with CSC.
The conventional management options for CSC have been observation or thermal laser photocoagulation applied to the site of fluorescein leakage. However, because laser photocoagulation causes RPE damage, it cannot be applied to the subfoveal region. Moreover, laser photocoagulation itself is not specific enough for tackling the fundamental choroidal vascular problem.
Photodynamic therapy (PDT) for CSC has been reported to be efficacious in reducing subretinal fluid and increasing visual acuity (VA) in most patients. The proposed therapeutic mechanism of PDT is hypoperfusion of the choriocapillaris in the short term and choroidal vascular remodeling over time, which reduces choroidal congestion and vascular permeability. Thus, PDT for CSC is desirable for eyes with hyperfluorescence in middle- or late-phase ICGA. However, ICGA does not necessarily show hyperfluorescence in eyes with chronic CSC. In the current study, we focused on the baseline ICGA findings in eyes with chronic CSC and evaluated the associations between each ICGA finding and the efficacy of the long-term results after PDT.
Patients and Methods
We prospectively studied eyes with chronic symptomatic CSC for at least 6 months. The patients were recruited from October 28, 2005 to June 22, 2007 at Osaka University Medical School Hospital. All subjects provided informed consent for research. The minimum follow-up period after the initial application of PDT was 1 year.
The inclusion criteria were the presence of visual symptoms such as visual disturbance, distortion, or metamorphopsia; the presence of subretinal fluid involving the fovea on optical coherence tomography (OCT); the presence of active angiographic leakage at the level of the RPE on fluorescein angiography (FA) caused by CSC but no other diseases; and abnormal dilation of the choroidal vasculature, no apparent choroidal neovascularization, and no polypoidal choroidal vasculopathy masquerading as CSC on ICGA. Patients were excluded if they were taking steroids or had been treated with PDT previously.
PDT with verteporfin (Visudyne; QLT Phototherapeutics, Vancouver, Canada) infusion and laser application were performed according to the protocol of the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) study. All patients received a 6-mg/m 2 infusion of verteporfin over 10 minutes followed by laser delivery at 689 nm 15 minutes after the start of the infusion. Using the standard light intensity of 600 mW/cm 2 , the irradiation time was shortened to about 60 to 70 seconds, which is equivalent to reducing the energy to about 36 to 42 mJ/cm 2 . The area of irradiation was set to hyperfluorescence during the middle phase of ICGA, which indicated the area of leakage on FA. The spot size was adequate to cover the extent of choroidal hyperpermeability as it appeared about 10 minutes after the ICGA injection. If hyperpermeability was not seen during the middle phase on ICGA, the spot size was set to a minimum of 800 μm to areas of leakage on FA, in which the subretinal fluid seemed to originate from reference areas showing dilated choroidal abnormalities on ICGA.
Patients were assessed at baseline and followed at 1, 3, 6, 9, and 12 months after PDT. The best-corrected visual acuity (BCVA) in decimal equivalent was measured and OCT images (Stratus OCT; Carl Zeiss Meditec, Inc, Dublin, California, USA) were obtained at every visit. FA and ICGA (TRC-50IX; Topcon, Tokyo, Japan) were performed at baseline in all study eyes. Additional or periodic FA and ICGA were performed in eyes with persistent or recurrent subretinal fluid during the follow-up period.
We examined the ICGA findings before PDT was applied to overlying areas of RPE leakage on FA. ICGA findings during the middle phase about 10 minutes after the ICG injection were classified as intense or intermediate hyperfluorescence or as having no hyperfluorescence by three authors (R.I., M.S., F.G.) masked to the details of the study. Intense hyperfluorescence appeared as a well-defined homogeneous hyperfluorescent area that was brighter than the background fluorescence. Intermediate hyperfluorescence was less defined, with less significant fluorescence than intense hyperfluorescence, but slightly brighter than the background fluorescence. The absence of hyperfluorescence appeared as an area of no distinct hyperfluorescence and slightly decreased fluorescence compared with the background fluorescence. The ICGA findings that were selected required agreement by 2 or 3 authors (R.I., M.S., F.G.).
We evaluated the associations between each ICGA finding at baseline and the resolution of subretinal fluid on OCT after PDT. We also examined any associations between each ICGA finding at baseline and recurrence after PDT, and any associations between each baseline ICGA finding and fluorescein leakage when there was a recurrence. Analysis was performed using SigmaStat Ver. 2.0 (SPSS Inc, Chicago, Illinois, USA), with a statistical significance of P < .05.
A total of 32 eyes of 27 patients (20 men, 7 women) with chronic CSC were recruited. The mean ± standard deviation patient age was 56 ± 9 years (range, 32–75 years). The duration of CSC ranged from 6 months to 15 years. The mean follow-up period after the initial PDT was 15.5 months (range, 12–29 months). The mean BCVA before PDT was 0.49 (range, 0.08–1.2). In addition to subretinal fluid in the macula, 5 eyes had a small pigment epithelial detachment; no eyes had subretinal fibrin deposition in the fundus on OCT examination. The baseline FA showed focal leakage including single or multiple pinpoints of leakage in 26 eyes and diffuse leakage, so-called oozing, in 6 eyes. The mean spot size on the initial PDT was 1829 μm (range, 850–3500 μm).
Overall, the subretinal fluid resolved completely in 19 eyes (59%) at 1 month, 29 eyes (91%) at 3 months, and 28 eyes (88%) at 12 months. The mean VAs at each time point within 1 year are summarized in Table 1 .
|Visit||Mean Visual Acuity a (Range)||P Value b|
|Month 1||0.55 (0.08–1.5)||.021|
|Month 3||0.59 (0.1–1.5)||<.001|
|Month 12||0.60 (0.08–1.5)||.008|
To determine the efficacy of PDT for resolving subretinal fluid, we analyzed the association with the baseline ICGA findings. Findings during the middle phase of ICGA overlying the area of leakage at baseline included intense hyperfluorescence in 23 eyes (72%), intermediate hyperfluorescence in 6 eyes (19%), and no hyperfluorescence in 3 eyes (9%) ( Figure , Table 2 ). The initial rates of resolution of the subretinal fluid after 1 application of PDT were as follows. In 23 eyes with intense hyperfluoresence on the baseline ICGA, the subretinal fluid completely resolved in 16 eyes (70%) at 1 month and in 23 eyes (100%) at 3 months. In 6 eyes with intermediate hyperfluorescence at baseline, the subretinal fluid resolved completely in 3 eyes (50%) at 1 month and in 6 eyes (100%) at 3 months. In 3 eyes with no hyperfluorescence at baseline, the subretinal fluid did not resolve at 3 months in any eyes. Although additional PDT was applied in 2 of those eyes, the subretinal fluid did not resolve throughout the follow-up period in any eyes with no hyperfluorescence.
|Baseline ICGA Finding||No. Eyes||Age, Years (Range)||Baseline VA (Range)||Leakage Pattern on FA||Resolution of Subretinal Fluid||VA at 12 Months (Range)|
|At 1 Month||At 3 Months||At 12 Months|
|Intense hyperfluorescence||23 eyes (22 patients a )||56 (32–71)||0.51 (0.08–1.2)||Focal in 20 eyes Diffuse in 3 eyes||16 eyes (70%)||23 eyes (100%)||23 eyes (100%)||0.66 (0.08–1.5)|
|Intermediate hyperfluorescence||6 eyes (4 patients a )||57 (53–66)||0.33 (0.15–1.0)||Focal in 6 eyes||3 eyes (50%)||6 eyes (100%)||5 eyes (83%)||0.44 (0.2–1.2)|
|No hyperfluorescence||3 eyes (2 patients)||57 (48–75)||0.86 (0.8–1.0)||Diffuse in 3 eyes||0 eyes (0%)||0 eyes (0%)||0 eyes (0%)||0.63 (0.4–0.8)|