Reduced-fluence Photodynamic Therapy for Subfoveal Serous Pigment Epithelial Detachment With Choroidal Vascular Hyperpermeability




Purpose


To evaluate the efficacy of reduced-fluence photodynamic therapy (PDT) for treating symptomatic subfoveal serous pigment epithelial detachments (PEDs) with hyperfluorescence on late-phase indocyanine green angiography (ICGA) without choroidal neovascularization (CNV).


Design


Retrospective, interventional case series.


Methods


Fifteen eyes of 15 patients (mean age, 55.3 years) with a serous PED were included. Baseline ICGA showed hyperpermeable choroidal vessels but no CNV in any eyes. Reduced-fluence PDT was applied and included treatment of hyperfluorescent areas on late-phase ICGA. We evaluated changes in the PEDs and hyperfluorescence on late-phase ICGA at baseline and 3 months after PDT. We compared the subfoveal choroidal thickness and best-corrected visual acuity (BCVA).


Results


The baseline ICGA showed mild to intense hyperfluorescence at the PED with hyperpermeable choroidal vessels. One month after reduced-fluence PDT, the PED resolved in 14 eyes (93%) and decreased in height in 1 eye. The PED flattening continued for more than 3 months. The baseline hyperfluorescence on ICGA decreased at month 3 except for 1 eye. The subfoveal choroidal thickness decreased significantly ( P < .0001) from 297 to 238 μm; the BCVA significantly ( P = .019) improved from 0.08 to −0.01 between baseline and month 3. The month-3 BCVA was significantly associated with the baseline BCVA and the duration and size of the PED. No PEDs recurred or complications developed, such as secondary CNV or retinal pigment epithelial tears.


Conclusion


Serous PEDs accompanying hyperfluorescence on ICGA are considered a variant of central serous chorioretinopathy. Reduced-fluence PDT is beneficial for resolving PEDs.


Idiopathic serous pigment epithelial detachment (PED) is often observed unilaterally or sometimes bilaterally in both elderly and younger subjects. The mechanism of serous PED in elderly patients is presumed to be that the accumulation of lipid in the Bruch membrane affects a hydrophobic barrier to normal movement of fluid and ions by the retinal pigment epithelium (RPE) into the choroid, inducing serous detachment of the RPE. The PED larger than 1 disc diameter is reported to increase the risk of choroidal neovascularization and visual deterioration. In elderly Asians, it has been presumed to be a manifestation of exudative age-related macular degeneration regardless of the presence of soft drusen. On the other hand, serous PED in younger patients is frequently associated with choroidal hyperpermeability on indocyanine green angiography (ICGA) and regarded as a variant of central serous chorioretinopathy (CSC). The visual prognosis of serous PED is relatively good; however, in eyes with PED involving the fovea, vision is sometimes affected because of the persistent RPE abnormalities after the resolution of the original PED.


In recent years, photodynamic therapy (PDT) for CSC with subfoveal leakage has been reported to be safe and efficacious in reducing subretinal fluid (SRF) and increasing visual acuity (VA) in most patients. The PDT protocol using a half dose of verteporfin to treat CSC was reported to be as effective as conventional PDT and more minimizing of the deleterious effect on choriocapillaris perfusion. We previously reported that the reduced-fluence PDT for CSC was highly effective in eyes with intense leakage on late-phase ICGA; however, in eyes with less or no leakage, it resulted in limited or no efficacy to obtain the dry macula.


Because there are eyes with serous PED without SRF showing intense hyperfluorescense in the late phase on ICGA at the PED lesion, we hypothesized that reduced-fluence PDT is similarly effective to treat PED associated with choroidal vascular hyperpermeability.


The purpose of this study was to determine the efficacy of reduced-fluence PDT for symptomatic subfoveal serous PED with choroidal hyperfluorescence in late-phase ICGA and without SRF and choroidal neovascularization (CNV).


Materials and Methods


We retrospectively studied the efficacy of reduced-fluence PDT for eyes with symptomatic subfoveal PED without SRF or any choroidal vascular abnormalities such as CNV or polypoidal choroidal vasculopathy (PCV). All eyes were treated from February 20, 2009 to September 20, 2011 at Osaka University Hospital. The minimum follow-up period after the initial application of PDT was 4 months.


The inclusion criteria of the study were as follows: 1) the presence of PED involving the fovea without SRF confirmed on optical coherence tomography (OCT); 2) the presence of visual symptoms such as visual disturbance, distortion, or metamorphopsia; 3) the presence of hyperfluorescence in late-phase ICGA with matched part of PED; 4) no evidence of choroidal neovascularization or polypoidal choroidal vasculopathy on fluorescein angiography (FA) and ICGA; 5) no leakage at the level of RPE on FA. Patients were excluded if they had previous PDT treatment for the macular diseases.


The protocol of reduced-fluence PDT with verteporfin (Visudyne; Novartis, Basel, Switzerland) was reported previously. Briefly, 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 68 seconds, which is equivalent to reducing the energy to 40 mJ/cm 2 . The area of irradiation was set to cover the hyperfluorescent area during the middle to late phase of ICGA, which indicated the area of the whole PED and, if any, surrounding hyperpermeable choroidal vessels.


All patients were assessed at baseline and followed at 1 and 3 months after PDT. The best-corrected visual acuity (BCVA) using the Landolt charts, OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Inc, Dublin, California, USA; Heidelberg Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany; or prototype high-penetration OCT; Topcon, Tokyo, Japan), and fundus observations were obtained at every visit. FA and ICGA were performed at baseline and 3 months after PDT (TRC-50IX; Topcon, Tokyo, Japan). To exclude the possibilities of any choroidal vascular abnormalities, baseline ICGA was taken using confocal scanning laser ophthalmoscopy (HRA2; Heidelberg Engineering, Heidelberg, Germany) simultaneously.


We evaluated the changes of the PED and the hyperfluorescence on late-phase ICGA before and after PDT. In addition, the subfoveal choroidal thickness and the BCVA were compared. The height of the PED was defined as the distance between the upper surface of the detached RPE and the inner surface of the choroid, possibly corresponding to the Bruch membrane, and the subfoveal choroidal thickness was measured from the inner surface of the choroid to the inner surface of the sclera using the included measurement software in each OCT apparatus. Those measurements were performed by 2 of the authors (S.G. and C.U.) and the values were within 5% of differences, and therefore, all values were averaged together for analysis. The hyperfluorescence on late ICGA was classified into 3 grades in the order of fluorescein intensity. We also evaluated any disruptions in the lines of the presumed boundary of the photoreceptor inner and outer segments (IS/OS line) and the third line, presumed to be a continuous cone outer segment tips (COST) line, above the originally detached RPE on OCT at 3 months after the PDT.


The BCVA was converted to logMAR (logarithm of the minimal angle of resolution) for the analysis. We compared the BCVA and subfoveal choroidal thickness before and after PDT using a paired t test. To understand the associating factors with the posttreatment BCVA, we performed stepwise regression analysis using covariates such as baseline age, BCVA, duration of PED, the size of PED, and baseline subfoveal choroidal thickness. All statistical analysis was carried out using JMP software version 9.0 (SAS Inc, Cary, North Carolina, USA), with a statistical significance of P < .05.




Results


A total of 15 eyes of 15 patients (13 men, 2 women) with symptomatic PED including the fovea were treated. The demographic details of 15 eyes are displayed in the Table . The mean age of the patients was 55.3 ± 9.0 years (range, 41–68 years). One eye was highly myopic with spherical error of −7.5 diopters and the others were approximately emmetropic within ±1.5 diopters. The mean duration of symptoms was 21.6 ± 30.5 months (range, 2–120 months) and 5 eyes had been diagnosed as having CSC previously. In 7 eyes, PED was initially confirmed on OCT more than 3 years before. Two eyes had multiple PEDs and the others showed single PED. In 1 fellow eye, PED was observed at the nasal area from the fovea without symptoms. The mean (± standard deviation) logMAR BCVA before PDT was 0.08 ± 0.19 (range, 0.22 to −0.17). Two eyes had been treated with ranibizumab for the PED and showed no obvious changes. The mean follow-up duration after the PDT was 6.1 ± 3.6 months (range, 3–12 months).



TABLE

Demographic and Clinical Data of Patients With Serous Pigment Epithelial Detachment


























































































































































































































































































































Case Age (years) Sex Eye Symptom Duration (months) Baseline PED PED at Month 3 BCVA (logMAR) Subfoveal Choroidal Thickness (μm) Degree of Hyperfluorescence on ICGA Disruption of Outer Retinal Layer at Month 3 Change in Subjective Symptoms
Diameter (μm) Height (μm) Baseline Month 3 Baseline Baseline of Fellow Eye Month 3 Baseline Month 3 IS/OS COST
1 62 F L 9 1300 142 0.15 −0.08 186 105 158 +++ Improved
2 50 M R 22 940 146 Reduced 0.1 0.22 206 204 181 + + + + No change
3 68 M L 52 2300 349 0.1 −0.08 237 239 186 +++ Improved
4 43 M R 6 1000 164 0.15 0.1 356 323 335 +++ + No change
5 66 M R 6 1800 292 0.22 0.15 304 207 210 +++ + Improved
6 57 M L 10 1700 253 −0.08 −0.08 166 178 166 +++ + No change
7 60 M R 12 1800 400 0.15 0.15 355 372 253 +++ + + Improved
8 55 M L 120 1200 202 0.22 0.15 330 290 311 +++ + + + No change
9 45 M R 5 1800 437 −0.18 −0.18 440 405 385 +++ Improved
10 45 M L 2 2000 321 −0.18 −0.18 302 372 208 +++ Improved
11 62 M L 20 2000 563 0.52 0.05 356 227 259 +++ + + + Improved
12 41 M R 5 1900 371 −0.18 −0.18 380 304 255 +++ + Improved
13 52 F R 10 830 371 −0.08 −0.08 221 175 186 ++ + Improved
14 67 M R 7 1930 181 0.05 −0.08 302 230 221 +++ + + Improved
15 57 M R 38 1200 378 0.22 0.15 315 240 250 ++ + + No change

BCVA = best-corrected visual acuity; COST = cone outer segment tips; ICGA = indocyanine green angiography; IS/OS = inner/outer segment junction; L = left; logMAR = logarithm of the minimal angle of resolution; PED = pigment epithelial detachment; R = right.

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Jan 12, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Reduced-fluence Photodynamic Therapy for Subfoveal Serous Pigment Epithelial Detachment With Choroidal Vascular Hyperpermeability
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