Aims To compare clinical outcomes for patients with central serous chorioretinopathy (CSC) undergoing either focal laser photocoagulation or photodynamic therapy (PDT).
Methods 26 eyes of 26 patients with symptomatic CSC underwent focal laser photocoagulation or half-dose PDT, as appropriate. Best-corrected visual acuity, optical coherence tomography and multifocal electroretinography were assessed prospectively prior to treatment and at 1, 3 and 6 months after treatment.
Results 12 eyes in the focal laser group and 14 eyes in the PDT group were evaluated. One month after PDT, all eyes, except one, showed complete absorption of subretinal fluid, whereas five eyes in the focal laser group showed residual subretinal fluid (p=0.022). Visual acuity and parameters of multifocal electroretinography improved from baseline at 1, 3 and 6 months after treatment, without any significant differences between the two groups. However, compared with those in the PDT group at 1 month after treatment, P1 latencies in the first annuli of the focal laser group were delayed (40.1±5.5 ms and 34.9±2.5 ms, respectively; p=0.047).
Conclusions Compared with focal laser, half-dose PDT may facilitate earlier resolution of macular detachment and earlier recovery of central retinal function. However, at 3 months after treatment and thereafter, no difference in anatomical and functional recovery was noted between the two modalities of treatment.
- Central serous chorioretinopathy
- focal laser photocoagulation
- multifocal electroretinography
- photodynamic therapy
- Treatment Lasers
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- Central serous chorioretinopathy
- focal laser photocoagulation
- multifocal electroretinography
- photodynamic therapy
- Treatment Lasers
Central serous chorioretinopathy (CSC) is characterised by development of serous neurosensory retinal detachment at the posterior pole.1 2 Traditionally, the major treatment options for CSC have included observation or thermal laser photocoagulation.3 4 With the advent of indocyanine green angiography, it has been demonstrated that CSC primarily affects the choroidal circulation and causes multifocal areas of choroidal vascular hyperpermeability.5 On the basis of indocyanine green angiographic findings, photodynamic therapy (PDT) with verteporfin, a new option, has also been adopted for treatment of CSC. Beneficial visual outcomes after PDT have also been demonstrated in the majority of patients.6–11 Reduction in the dose of verteporfin has been advocated for enhancement of the safety profile of the therapy.12–15 However, until recently, no studies comparing outcomes of PDT and laser photocoagulation in treatment of CSC have been conducted. In this study, we longitudinally studied disease prognosis and macular function in patients with CSC treated with focal laser photocoagulation or half-dose PDT.
This study was a prospective, comparative case series conducted in the Department of Ophthalmology at Samsung Medical Center. The protocol was approved by the institutional review board of the hospital (IRB file number no 2008-05-030), and was registered at Clinical trial.gov (ID: NCT00803517).
From March 2008 to August 2008, patients at Samsung Medical Center with symptomatic CSC of 3 months duration or longer were recruited for this study. The inclusion criteria were as follows: (1) CSC with subretinal fluid and/or serous pigmentary epithelial detachment involving the fovea, as demonstrated by clinical examination and optical coherence tomography (OCT); (2) choroidal vascular dilation and hyperpermeability on indocyanine green angiography; and (3) with symptom duration of 3 months or more, and worsening of symptoms, or no subjective improvement since the onset of CSC. Patients who had evidence of ocular trauma, uveitis, retinal vasculopathies, choroidal neovascularisation, polypoidal choroidal vasculopathy or other maculopathies capable of causing macular exudation, such as age-related macular degeneration, pathological myopia, and angioid streaks were excluded. Patients with a history of intraocular surgery or vitreoretinal intervention, including retinal laser therapy, were also excluded.
All patients underwent a thorough ophthalmological examination, including slit-lamp biomicroscopy, intraocular pressure measurement, fluorescein and indocyanine angiography (HRA; Heidelberg Engineering, Heidelberg, Germany) at baseline. Best-corrected visual acuity (BCVA), OCT (Model 3000; Carl Zeiss Meditec, Dublin, California) and multifocal electroretinography (Retiport and RETIscan; software version 3.15; Roland Consult., Wiesbaden, Germany) were assessed at baseline and 1, 3 and 6 months after treatment. BCVA was measured using a Snellen chart and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis.
Multifocal electroretinography was obtained with reference to guidelines from the International Society for Clinical Electrophysiology of Vision.16 All patients were able to maintain steady central fixation. No participants had a refractive error of more than −4.0 dioptres or +2.5 dioptres. The stimulus, consisting of 103 hexagons, was presented on a high-resolution black and white monitor with a frame rate of 75 Hz. Once the pupils were dilated, multifocal electroretinography of each eye was recorded using the same Burian–Allen electrode. The response was analysed using regional averages derived from six concentric rings: ring 1 (central hexagon), 3°; ring 2, 3 to 6°; ring 3, 6 to 10°; ring 4, 10 to 15°; ring 5, 15 to 22°; and ring 6, 22 to 28°.
A single physician (SWK) performed treatment procedures in all cases according to our protocol. Eyes presenting with extrafoveal focal leakage on fluorescein angiography were treated by focal laser photocoagulation. Focal laser photocoagulation was applied (150 μm, 0.15 s) to produce a light grey burn at the leaking point. Eyes exhibiting no definite focal leakage or subfoveal or juxtafoveal focal leakage on fluorescein angiography were treated by PDT. PDT was performed according to the safety-enhanced PDT protocol for CSC using half the normal dose of verteporfin (Visudyne, Novartis AG, Bulach, Switzerland), that is, 3 mg/m2 infusion with a rationale that using lower dosage has less collateral damaging effects on the retina and choroid.12–15 Verteporfin was infused over a period of 8 min, followed by delivery of the laser (689 nm) at 10 min from commencement of infusion to target the area of choroidal dilation and hyperpermeability. Earlier laser application allowed less drug accumulation at the RPE layer and less drug less toxicity at the RPE. A fluence of 50 J/cm2, a light dose rate of 600 mW/cm2 and a time of photosensitisation of 83 s were applied.
Following treatment, macular status as assessed by OCT was classified into one of two types: with fluid or without fluid. ‘With fluid’ was defined as the presence of subretinal fluid or retinal pigmentary epithelial detachment by OCT. ‘Without fluid’ was defined as total absorption of subretinal fluid and resolution of retinal pigmentary epithelial detachment.
Comparison of data was performed using the Wilcoxon two-sample test or the Fisher exact test with Bonferroni correction, as appropriate. Multivariate linear regression analyses were undertaken using BCVA and multifocal electroretinography as dependent variables. Statistical analysis was performed using SPSS software version 12.0 for Windows (SPSS, Chicago, Illinois). A p value of less than 0.05 was considered significant.
A total of 26 eyes from 26 patients with central serous chorioretinopathy who fulfilled inclusion and exclusion criteria were enrolled in this study. The mean age of the patients was 45.6±7.3 years (range 37–56). Twenty-three of 26 patients were male, and three were female. The mean logMAR BCVA at baseline was 0.18±0.17 (range 0–0.5). The mean central foveal thickness at baseline was 350.1±100.3 μm (range 210–517). Twelve eyes were treated by focal laser photocoagulation, and 14 eyes were treated by PDT. All 12 eyes treated by focal laser photocoagulation exhibited extrafoveal focal leakage on fluorescein angiography. Among fourteen eyes in the PDT group, 10 eyes showed diffuse oozing, and the remaining four eyes showed subfoveal or juxtafoveal focal leakage. Demographic data on gender, age, laterality of the eye, baseline visual acuity and baseline central retinal thickness were not significantly different between the two groups. All patients completed the 6-month follow-up. None of the patients presented with recurrence of disease or required further treatment during the follow-up period. No systemic or ocular adverse events were observed during the study. Baseline characteristics are shown in table 1.
The mean logMAR BCVA of the focal laser group and the PDT group was 0.22±0.18, and 0.14±0.16, respectively (p=0.641) at baseline. In both groups, BCVA had improved when measured 1 month after treatment (0.04±0.07, 0.07±0.13, respectively; p=0.044 in the focal laser group, p=0.059 in the PDT group), and BCVA showed gradual improvement when measured at 3 and 6 months after treatment, without any significant differences between the two groups. At the final follow-up, all eyes had a Snellen BCVA better than 20/25. All eyes showed the same or better visual acuity after treatment. Changes in mean BCVA after treatment are shown in figure 1.
At baseline OCT, 22 (80.7%) eyes had subretinal fluid alone without serous pigmentary epithelial detachment at the macula, five (15.4%) eyes had combined subretinal fluid and retinal pigmentary epithelial detachment, and one (3.8%) eye had isolated retinal pigmentary epithelial detachment involving the fovea. Baseline incidence of retinal pigmentary epithelial detachment was not different between the focal laser and PDT groups (p=0.346). According to the OCT classification of the macular status 1 month after treatment, the PDT group showed the without-fluid type in 12 (92.3%) eyes and the with-fluid type in one (7.7%) eye. However, the focal laser group showed the without fluid type in seven eyes (58.3%), and the with-fluid type in five (41.6%) eyes. The difference in the distribution of OCT types between the two groups at 1 month after treatment was significant (p=0.022). Retinal pigmentary epithelial detachment was completely resolved 1 month after treatment in all eyes. At 3 and 6 months after treatment, all eyes of both groups exhibited a without-fluid status. OCT findings after treatment are shown in table 2.
After 1 month, central retinal thickness of the focal laser group was 200.6±64.2 μm, and that of the PDT group was 197.6±58.1 μm(p=0.249). Central retinal thickness in each group was significantly decreased from baseline thickness (p=0.011, p=0.008, respectively). Central retinal thickness was stabilised when measured at 3 and 6 months after treatment, without any significant differences between the two groups.
At baseline, the amplitude and latency of both N1 and P1 waves in all six ring areas showed no difference between the two groups. At 1 month after treatment, P1 latency in the ring 1 area of the focal laser group (40.1±3.5 ms) was delayed, compared with that of the PDT group (34.9±2.3 ms; p=0.047). In addition, statistical significance was maintained even after correction for the difference in the post-treatment OCT state 1 month after treatment (multivariate regression analysis, p=0.002). When compared with the PDT group, P1 latency in the other ring areas also tended to be delayed in the focal laser group, but not significantly. P1 and N1 amplitude in all six ring areas showed a tendency to increase from baseline values; however, the difference was not significant (p>0.05). No difference in amplitude was observed between the two groups, and N1 latencies in all the ring areas were not different between the two groups. At 3 and 6 months after treatment, the amplitude and latency in both N1 and P1 waves in all six ring areas showed no differences between the two groups. When compared with baseline, multifocal electroretinography in all six ring areas showed a tendency towards gradual improvement at each follow-up visit.
After 1 month, the P1 latency in the ring 1 area in 20 eyes of the with-fluid type was 39.2±4.5 ms and 36.2±2.5 ms in eyes of the without-fluid type (p=0.161), and the other parameters of multifocal electroretinography showed no difference, either. Longitudinal changes of N1 and P1 waves in the ring 1 and 2 area from multifocal electroretinography for these patients are presented in table 3.
CSC has a favourable natural course and typically results in spontaneous resolution of the detachment and improvement of visual function.1 17 18 The high spontaneous remission rate favours conservative management as a first-line therapeutic option. However, in some cases of CSC, patients may develop progressive visual loss resulting from persistent serous retinal detachment, cystoid macular degeneration or retinal pigment epithelium decompensation.2 17 Thus, active intervention should be considered in CSC with a symptom duration lasting longer than 3 months, as with the eyes included in the current study. Compared with sham photocoagulation, argon laser photocoagulation to the area of angiographic leakage has been reported to shorten the duration of detachment and reduce recurrence.3 4 19 A potential benefit of focal laser treatment may be mediated by lowering the rate of retinal pigment epithelium degeneration due to earlier resolution of CSC. The inherent energy of focal laser light is converted to heat in the retinal pigment epithelium, causing thermal damage primarily to the retinal pigment epithelium and choriocapillaris, which results in debridement of the diseased retinal pigment epithelium and permits growth of the surrounding healthy retinal pigment epithelium, and eventually results in resolution of CSC. Although focal laser treatment is inexpensive, simple and convenient, possible complications of laser photocoagulation include choroidal neovasculisation, conversion of metamorphopsia to scotoma and inadvertent foveal damage.19 20 Therefore, the point of leakage should be at least 500 μm from the centre of the fovea avascular zone,19 and focal laser treatment is not suitable for CSC with a subfoveal or juxtafoveal leaking point. Also, in this study, we performed focal laser treatment primarily for eyes exhibiting extrafoveal focal leakage on fluorescein angiography. For this reason, conducting a randomised trial comparing the treatment effect of PDT and focal laser on CSC is difficult. In this study, the PDT group included the eyes with diffuse angiographic leakage, in contrast to the focal laser group which included only the eyes with focal leakage. Although there are few reports regarding the outcomes of CSC according to the angiographic leakage pattern, CSCs with diffuse oozing might have a different natural course and response to treatments from those with focal leakage. Thus, further study on this issue will be useful to validate our results.
Despite the reported efficacy of a standard dose (6 mg/m2) of verteporfin PDT,6–11 potential adverse events, such as a transient reduction in retinal function or secondary changes in retinal pigmentary epithelium may develop after treatment.21–23 This may limit the usefulness of PDT for CSC, because the involved eyes generally have fair vision. Because it has been reported as a safer and equally effective regimen, half-dose PDT was applied in the current study.12–15
Results of the current study indicate that there is no significant difference in visual recovery between patients treated with focal laser and patients treated with PDT. However, it was interesting to note that subretinal fluid absorbed more rapidly in the PDT group than in the focal laser group. At 1 month after treatment, complete absorption of intraretinal and subretinal fluid on OCT was noted in 13 (92.8%) of 14 eyes in the PDT group, however, in seven (58.3%) of 12 eyes in the focal laser group. Several studies have reported on temporary hypoperfusion of choriocapillaris and reduction in vascular permeability within 1 week after PDT treatment.9–11 Direct action of PDT on the choriocapillaris may lead to relatively rapid resolution of subretinal fluid accumulation. In contrast, laser photocoagulation induces resolution of CSC via remodelling of retinal pigmentary epithelium.24 With closure of the microrip after formation of a laser scar, subretinal fluid was gradually absorbed by the retinal pigment epithelium pump. This may perhaps explain differences in the speed of subretinal fluid absorption.
Only a subtle difference between the two treatment groups was noted in multifocal electroretinography examination. Compared with the PDT group, the focal laser group showed a delay in P1 latency in the central fovea at 1 month. Lai et al15 reported that multifocal electroretinography in patients with chronic CSC revealed no significant changes from baseline in mean N1 and P1 amplitude and latency at 1 month after PDT. A reduction in mean central P1 amplitude for eyes with retinal pigmentary epithelial detachment only was observed at 4 days after PDT. We also observed no significant change in N1 and P1 amplitude and latency 1 month after PDT. However, amplitude and latency showed a continuous improvement during 6 months of follow-up in both the focal laser group and the PDT group.
It is noteworthy that no previous studies have addressed multifocal electroretinography results after focal laser treatment in CSC. Increased amplitude and no difference in the implicit time were demonstrated 3 months after focal laser treatment for diabetic macular oedema.25 However, the result of multifocal electroretinography after focal laser treatment for CSC is expected to be different from that for other diseases, because it may reflect a more localised mild burn and recovery of retinal function with resorption of subretinal fluid. In the current study, we interpreted the delayed latency in multifocal electroretonography as the result of delayed absorption of subretinal fluid and cone photoreceptor damage. Alternatively, other factors, such as residual oedema, postlaser reactive oedema, progression of retinopathy or retinal hypoxia may have contributed to transient impairment of central retinal function.
Limitations of our study include a small sample size and short follow-up period. This might limit the statistical power in detecting the differences in treatment outcome or the factors which would influence the outcomes. Nevertheless, our results comparing the treatment effect between focal laser photocoagulation and PDT on CSC, utilising OCT and multifocal electroretinography, would be meaningful for clinicians to determine treatment modality.
In conclusion, when compared with focal laser photocoagulation, half-dose PDT may facilitate earlier absorption of subretinal fluid and earlier recovery of central macular function. However, 3 months afterwards, no difference was noted between the two modalities of treatment.
Competing interests None.
Ethics approval Ethics approval was provided by the the institutional review board of the Samsung Medical Center (IRB file number # 2008-05-030).
Provenance and peer review Not commissioned; externally peer reviewed.
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