Purpose
To evaluate the effect of low-fluence photodynamic therapy (PDT) on central retinal sensitivity and fixation stability as compared with standard-fluence PDT for treating chronic central serous chorioretinopathy (CSC).
Design
Prospective longitudinal follow-up of patients enrolled in a nonrandomized clinical trial of standard-fluence vs low-fluence PDT in chronic CSC.
Methods
Forty-two eyes (42 patients) with chronic CSC were enrolled; 19 eyes received indocyanine green angiography–guided standard-fluence PDT (50 J/cm 2 ) and 23 received indocyanine green angiography–guided low-fluence PDT (25 J/cm 2 ). Retinal sensitivity in the central 12 degrees and fixation stability were evaluated by MP-1 microperimeter at baseline and at 3 and 12 months after PDT.
Results
Mean central retinal sensitivity improved significantly at all time points (at 12 months vs baseline P < .01, Tukey-Kramer test), in the standard- fluence group from 11.9 to 14.4 at 12 months, and in the low-fluence-group from 11.8 to 16.3, with a significant difference between the 2 groups ( P = .04, t test). Fixation stability did not change in either group (not significant, analysis of variance). At 12 months’ follow-up the retinal sensitivity significantly correlated with best-corrected visual acuity in both groups (standard-fluence, r = −0.52, P = .02; low-fluence, r = −0.54, P = .01).
Conclusions
The study shows a significant improvement in macular sensitivity after PDT in eyes with chronic CSC, with greater efficacy in low-fluence-treated eyes. Microperimetry data suggest that low-fluence PDT may be a good treatment option in patients with chronic CSC.
Chronic central serous chorioretinopathy (CSC) is a disease characterized by long-standing serous detachment of the neurosensory retina at the posterior pole, in combination with diffuse retinal pigment epithelium (RPE) decompensation, leading to damage to the photoreceptors and resulting in vision loss.
Treatment with indocyanine green angiography (ICGA)-guided photodynamic therapy (PDT) with verteporfin has been shown to be effective in chronic CSC by improving visual acuity and reducing subretinal fluid. However, complications such as secondary choroidal neovascularization, persistent choriocapillaris hypoperfusion, and pigmentary RPE changes in the treated zone have been reported. It has been suggested that modified PDT protocols, in terms of verteporfin dosage, fluence rate, and/or the time course of delivery, may be more appropriate.
Recently, we showed that low-fluence-rate PDT was effective for treatment of chronic CSC in terms of best-corrected visual acuity (BCVA) and central retinal thickness, with a lower incidence of choroidal hypoperfusion, as compared to standard-fluence PDT.
BCVA testing, although an established modality, assesses only foveal function and poorly describes the functional impact of chorioretinal diseases involving the posterior pole. Therefore, it would be useful to evaluate macular function, in addition to visual acuity, to better determine the efficacy of PDT in eyes with CSC.
The MP-1 microperimeter (Nidek, Vigonza, Italy) provides exact localization and quantification of retinal sensitivity in the entire macular region and automatic eye tracking for evaluating the fixation pattern. Thus, it has been shown that more detailed information about a patient’s visual function can be gathered with microperimetry than with visual acuity measurement alone, and that distance visual acuity underestimates the functional benefit of treatment as compared with microperimetry.
Limited information is available on retinal sensitivity after PDT for CSC. In 2 eyes with long-standing chronic CSC with severe macular damage (foveal and gravitational atrophy) we reported that retinal sensitivity and fixation stability improved after low-fluence-rate PDT.
As an extension of the previously reported study, we evaluated the effect of standard and low-fluence PDT on retinal sensitivity and fixation stability in eyes with chronic CSC over a course of 12 months.
Methods
This analysis was part of a prospective, multicenter, nonrandomized, investigator-masked clinical study performed at the Department of Ophthalmology of the universities of Bari and Catania, Italy, between January 9, 2006 and May 26, 2008. Full details of the study methods and subjects have been published.
Briefly, the study enrolled 42 consecutive eyes with chronic CSC. In each center, the eligible patients were offered either standard-fluence PDT or low-fluence PDT. The rationale of the 2 treatments, the benefits, and the possible risks were fully explained. Only 1 treatment was given, as determined by the protocol. In cases of bilateral chronic CSC involving the macula, only the eye with the worse BCVA was treated. Standard-fluence PDT was performed in 19 eyes, and 23 eyes received low-fluence PDT. In standard-fluence PDT a total light energy of 50 J/cm 2 , a light dose rate of 600 mW/cm 2 , and a photosensitization time of 83 seconds were used. In low-fluence PDT we used a fluence of 25 J/cm 2 , a light dose rate of 300 mW/cm 2 , and a photosensitization time of 83 seconds.
Inclusion criteria were: 1) BCVA between 0.2 and 1 logarithm of the minimal angle of resolution (logMAR) units; 2) presence of subretinal fluid in the foveal region persisting for 3 months or more, with or without serous pigment epithelial detachment, on optical coherence tomography (OCT); 3) macular RPE decompensation with subtle or diffuse leaks, eventually with gravitational RPE atrophy, pigment epithelial detachment, or both, on fluorescein angiography (FA); and 4) abnormal dilated choroidal vasculature and choroidal vascular hyperpermeability with an active leakage area of less than 3500 μm in greatest linear dimension on ICGA.
Exclusion criteria were: 1) previous focal laser or PDT treatment for CSC; 2) any medical care for CSC in the last year; 3) evidence of choroidal neovascularization; 4) a branching network under the RPE, with aneurysm-like enlargements from polypoidal vasculopathy on ICGA; 5) cystic degeneration; 6) other chorioretinal disorders; 7) treatment with steroids for a systemic disease in the previous 12 months; 8) cataract or media opacities that could significantly interfere with OCT imaging, image analysis, or other diagnostic procedures; and 9) systemic contraindications to verteporfin or angiography dyes.
Microperimetry was performed at baseline and at 3 and 12 months after treatment. BCVA and central foveal thickness were evaluated in all patients at baseline and at 1, 3, 6, 9, and 12 months. For this analysis all parameters recorded at baseline and at 3 and 12 months were considered.
BCVA was measured by certified operators with the modified Early Treatment Diabetic Retinopathy Study charts at 4 m. Vision results were quantified as logMAR units. Central foveal thickness was measured by certified operators with OCT (Stratus OCT; Carl Zeiss Meditec, Dublin, California, USA), by using the fast macular thickness program, in which 6 low-resolution scans (128 A-scans per diagonal), centered on the fovea, are performed simultaneously.
In all patients, macular sensitivity and fixation stability were measured by fundus-related microperimetry with the MP-1 microperimeter. The examinations were done by the same experienced ophthalmologists in each center (M.R., F.B.).
Both participating centers used the same MP-1 software version (version 1.4.2.). To avoid bias resulting from instrument variability, all microperimeters were calibrated accurately by the same experienced technician, and parameters were standardized at all centers.
After the pupils were dilated (1% tropicamide), a reference frame was obtained with the integrated infrared camera. We used a standardized macular scan pattern with a 4-2-1 double staircase test strategy. Then a grid of 45 stimuli with a Goldmann III stimulus size and a projection time of 200 ms was projected onto the central 12 degrees. A bright red cross of 2 degrees in size was used for the fixation target. White background illumination was 4 apostilbs, and the starting stimulus light attenuation was set at 10 dB. For assessment of fixation, the fundus movements were tracked during examination. Fixation stability was calculated as the percentage of fixation points inside the 2-degree-diameter circle. Each patient underwent microperimetry twice on 2 different days before baseline testing, and a brief training at the beginning of each repeat microperimetry was performed during follow-up. All subjects underwent microperimetry after 5 minutes of visual adaptation.
In each group, the values of central retinal sensitivity and fixation stability detected before and after treatment were compared by analysis of variance (ANOVA), and if the difference was significant, multiple comparisons were performed with the Tukey-Kramer test. Central retinal sensitivity and fixation stability values detected in the 2 groups at each measurement were compared by t test. The number of eyes with an increase of sensitivity greater than 2.5 dB in 2 groups was evaluated by χ 2 test. The correlation between central retinal sensitivity and BCVA, and between central retinal sensitivity and central foveal thickness, in each group at 12 months of follow-up was tested by linear regression analysis. A P value less than .05 was considered statistically significant. The statistical analyses were performed with SPSS, version 16.0 (SPSS Inc, Chicago, Illinois, USA).
Results
At baseline, no difference in age, sex, duration of symptoms, central retinal sensitivity, fixation stability, BCVA, or central foveal thickness was seen between the 2 treatment groups ( Table 1 ). Mean BCVA and central foveal thickness in the 2 groups at baseline and at 3 and 12 months after treatment are shown in Table 2 . Compared with baseline, significant BCVA improvement and central foveal thickness decrease were seen in both groups on all measurements ( P < .01, Tukey-Kramer test), with no significant difference between the 2 groups at any time point . Complete resolution of subretinal fluid was observed at 12 months in 15 of 19 eyes in the standard-fluence group and 21 of 23 eyes in the low-fluence group (79% vs 91%; P = not significant, χ 2 ).
| Standard-Fluence Group (n = 19) | Low-Fluence Group (n = 23) | P Value a | |
|---|---|---|---|
| Mean ± SD age (years) | 48 ± 8 | 50 ± 6 | NS |
| Mean ± SD BCVA (logMAR) | 0.43 ± 0.1 | 0.46 ± 0.2 | NS |
| Mean ± SD central foveal thickness (μm) | 324 ± 83 | 315 ± 95 | NS |
| Mean ± SD central retinal sensibility (dB) | 11.9 ± 3.3 | 11.8 ± 3.2 | NS |
| Mean ± SD fixation stability ( % ) | 85.1 ± 9.2 | 84.2 ± 10.2 | NS |
| Mean duration of symptoms ± SD (months) | 8.5 ± 7.3 | 8.9 ± 7.8 | NS |
| Standard-Fluence Group (n = 19) | Low-Fluence Group (n = 23) | P Value a | |
|---|---|---|---|
| Mean ± SD BCVA (logMAR) | |||
| Baseline | 0.43 ± 0.1 | 0.46 ± 0.2 | NS |
| 3 months | 0.27 ± 0.1 | 0.22 ± 0.2 | NS |
| 12 months | 0.25 ± 0.2 | 0.16 ± 0.2 | NS |
| P value b | <.01 c , d | <.01 c , d | – |
| Mean ± SD central foveal thickness (μm) | |||
| Baseline | 324 ± 83 | 315 ± 95 | NS |
| 3 months | 194 ± 81 | 168 ± 40 | NS |
| 12 months | 173 ± 81 | 161 ± 34 | NS |
| P value b | <.01 c , d | <.01 c , d | – |
| Mean ± SD 12 degrees retinal sensitivity (dB) | |||
| Baseline | 11.9 ± 3.3 | 11.8 ± 3.2 | NS |
| 3 months | 14.0 ± 3.0 | 15.1 ± 3.0 | NS |
| 12 months | 14.4 ± 2.9 | 16.3 ± 3.0 | .04 |
| P value b | <.05 c | <.01 c | – |
| P value b | <.01 d | <.01 d | – |
| Mean ± SD fixation stability (%) | |||
| Baseline | 85.1 ± 9.2 | 84.2 ± 10.2 | NS |
| 3 months | 86.7 ± 9.5 | 86.5 ± 9.2 | NS |
| 12 months | 86.8 ± 9.1 | 86.9 ± 9.6 | NS |
| P value e | NS | NS | – |
At baseline, functional macular mapping showed a mean retinal sensitivity (standard deviation [SD]) in the central 12 degrees of 11.9 (3.3) dB in the standard-fluence group and 11.8 (3.2) dB in the low-fluence group. After the treatment, retinal sensitivity improved significantly in both groups (standard-fluence P = .04, ANOVA; low-fluence P < .001, ANOVA) ( Table 2 ): at 12 months after PDT, the mean value (SD) was 14.4 (2.9) dB in the standard-fluence group and 16.3 (3.0) dB in the low-fluence group (vs baseline P < .01, Tukey-Kramer test ), with a significant difference between the 2 groups ( P = .04, t test). At 12 months retinal sensitivity of central 2 degrees improved more than 2.5 dB in 12 of 19 eyes (63%) and 19 of 23 eyes (83%) in the standard and low-fluence group, respectively ( P = not significant, χ 2 test).
Fixation stability had not changed in either group at 3 and 12 months after PDT compared with baseline values ( P = not significant, ANOVA), with no significant difference between the 2 groups at any time point ( P = not significant, t test) ( Table 2 ). Examples of the serial changes in FA, ICGA, OCT, and microperimetry findings of the patients in the standard-fluence and low-fluence groups are displayed in Figures 1 and 2 .
