To evaluate subfoveal choroidal thickness changes in cases with recurrent polypoidal choroidal vasculopathy (PCV) after combination therapy with intravitreal ranibizumab and photodynamic therapy (PDT).
Retrospective observational case series study.
We measured subfoveal choroidal thickness in PCV using optical coherence tomography (OCT) before and after PDT. In recurrent cases, the choroidal thickness was measured at the time of the recurrence. In nonrecurrent cases, choroidal thickness was measured 1 year after PDT.
Combination therapy was performed in 27 eyes (27 patients). Polypoidal lesions regressed within 3 months after initial treatment in all eyes. Retreatment was needed in 10 of 27 eyes (37.0%) after more than 3 months of follow-up. In recurrent cases, subfoveal choroid decreased from 188 μm at baseline to 157 μm 3 months after PDT ( P < .01); however, choroidal thickness increased to 179 μm with recurrence ( P = .54 compared to baseline; average, 8.0 months). In nonrecurrent cases, subfoveal choroid decreased from 257 μm at baseline to 210 μm 3 months after PDT and 212 μm 1 year after PDT ( P < .01, respectively).
Subfoveal choroidal thickness in PCV at the time of recurrence returned to the baseline level after choroidal thinning as a result of PDT treatment. Choroidal thickness changes after PDT examined using OCT may reflect disease activity in PCV.
Polypoidal choroidal vasculopathy (PCV), a subtype of neovascular age-related macular degeneration (AMD), is characterized by elevated orange-red lesions with exudation and hyperfluorescent aneurysmal lesion(s) on indocyanine green angiography (ICGA). PCV is more common in Asians, especially the Japanese, than in whites. Photodynamic therapy (PDT) with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) is a major treatment option for PCV, because anti–vascular endothelial growth factor (VEGF) therapy for PCV does not cause regression of polypoidal lesions. The efficacy of combination therapy with anti-VEGF drugs and PDT for PCV has recently been reported.
Spectral-domain optical coherence tomography (SDOCT) noninvasively detects morphologic changes in a variety of macular diseases. Spaide and associates recently reported a new technique, enhanced depth imaging SDOCT (EDI-OCT), for evaluating the choroidal status. Using EDI-OCT, we previously reported that subfoveal choroidal thickness in the eyes with PCV decreased 1 month after PDT either with or without intravitreal ranibizumab. We also suggested that choroidal thickness changes might reflect the activity of PCV. However, our previous study had not included long-term follow-up or data of recurrent cases. In the current study, we retrospectively evaluated subfoveal choroidal thickness changes after combination therapy with intravitreal ranibizumab and PDT in PCV cases with or without lesion recurrence.
Materials and Methods
This is a retrospective observational case series study. The institutional review board at Fukushima Medical University School of Medicine approved OCT observation of eyes with macular and retinal disorders, the observational study for AMD at treatment and follow-up, and the retrospective comparative analysis performed in this study. The tenets of the Declaration of Helsinki were followed.
Indirect ophthalmoscopy, slit-lamp biomicroscopy with a contact lens or noncontact lens, digital fluorescein angiography (FA), and ICGA were performed to diagnose PCV. We used a digital imaging system with an infrared camera and a standard fundus camera (TRC-50 IX/IMAGEnet H1024 system; Topcon, Tokyo, Japan), as well as a confocal laser scanning system (HRA-2; Heidelberg Engineering, Heidelberg, Germany). The best-corrected visual acuity (BCVA) was measured with a Japanese standard decimal VA chart and converted to the logarithm of the minimal angle of resolution (logMAR) scale for analysis. All eyes were examined with the Spectralis OCT (Heidelberg Engineering).
The diagnostic criteria for PCV were proposed based on ICGA findings, which imaged the hyperfluorescent characteristic aneurysmal lesions. All patients with PCV had choroidal neovascularization on FA, which was identified as PCV on ICGA. Area of choroidal vascular hyperpermeability in eyes with PCV is defined as hyperfluorescence of abnormal choroidal staining on middle- or late-phase ICGA, which is usually larger than the area of the polypoidal lesions and branching vascular network (BVN). The judgment of choroidal vascular hyperpermeability from ICGA was made by 3 coauthors (I.M., H.O., Y.S.). Recurrence of PCV was defined as the reappearance of polypoidal lesions on ICGA (polyp type) or new exudative changes from BVN vessels on FA and OCT despite complete regression of the polypoidal lesions on ICGA (BVN type).
All patients were treated with PDT (6 mg/m 2 ) according to the protocol of the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy studies, except for the greatest linear dimension (GLD). The GLD in the current study was measured on ICGA including BVN and polyps. The diameter of the PDT treatment spot size was the GLD plus 1 mm. We administered combination therapy with intravitreal ranibizumab (Lucentis; Genentech, South San Francisco, California, USA) and PDT for PCV from July 2009. Combination therapy was performed by injecting ranibizumab 1 or 2 days before application of PDT. Intravitreal ranibizumab (0.5 mg/0.05 mL) was injected 3.5-4.0 mm posterior to the corneal limbus into the vitreous cavity using a 30-gauge needle after topical anesthesia was applied. Consecutive monthly intravitreal ranibizumab injections were administered for 3 months.
We measured choroidal thickness (defined as the area between the outer surface of retinal pigment epithelium and the inner surface of sclera) using EDI-OCT, in which the Spectralis OCT device is positioned close to the eye to obtain an inverted image. Each section was obtained using eye tracking, and 100 scans were averaged to improve the signal-to-noise ratio.
The subfoveal choroidal thicknesses were measured using EDI-OCT on the horizontal and vertical OCT lines passing through the center of the fovea before treatment (baseline) and after application of PDT on months 1 and 3. In cases with recurrent PCV during follow-up (recurrent cases), the choroidal thickness was measured at the time of the recurrence. In the PCV cases without recurrence (nonrecurrent cases), the choroidal thickness was measured after PDT on months 6 and 12. The central retinal thickness including retinal detachment also was measured at the same time.
The measurements obtained from the OCT images represented the averages of all measurements performed by 3 coauthors (I.M., H.O., Y.S.). All examiners were masked to the treatment status. The VAs are expressed in decimal and logMAR equivalents. The choroidal and retinal thicknesses were analyzed using the Wilcoxon signed rank test (SPSS, version 17.0; SPSS Inc, Chicago, Illinois, USA). P = .05 or less was considered significant.
Twenty-seven eyes of 27 patients treated with combination therapy of intravitreal ranibizumab and PDT for newly diagnosed PCV were included. Baseline characteristics, including retinal and choroidal thickness changes during follow-up period, are shown in the Table . Mean spot size of PDT was 4113 μm (GLD was 3102 μm). In all eyes of the combination therapy, 10 eyes (37.0%) had a recurrence more than 3 months after initial treatment. The average time to recurrence was 8.0 months (range, 6-13 months). Recurrence was divided into polyp type (5 eyes) and BVN type (5 eyes). Typical cases in the recurrent and nonrecurrent cases are shown in Figures 1-4 . The choroid at baseline was significantly thicker in 15 eyes with choroidal vascular hyperpermeability than that in 12 eyes without hyperpermeability on the middle- or late-phase ICGA images (mean, 294 ± 110 μm vs 154 ± 46 μm at baseline, P < .001, Mann-Whitney U test).
|Recurrent Cases||Sex||Age (y)||Eye||BCVA at Baseline (logMAR)||BCVA at Recurrence (logMAR)||Permeability a||Recurrence Type b||Central Retinal Thickness (μm) c||Subfoveal Choroidal Thickness (μm) d||Time to Recurrence|
|Baseline||M 1||M 3||Recurrence||Baseline||M 1||M 3||Recurrence|
|1||M||67||OS||0.4 (0.40)||0.5 (0.30)||−||Polyp||260||253||230||374||111||95||98||110||6|
|2||M||75||OS||0.3 (0.52)||0.3 (0.52)||−||Polyp||414||232||124||499||106||82||87||122||12|
|3||M||83||OS||0.6 (0.22)||0.3 (0.52)||−||Polyp||116||102||90||361||114||113||108||126||8|
|4||F||80||OD||0.4 (0.40)||1.0 (0.00)||−||Polyp||327||196||157||173||88||86||70||90||9|
|5||M||61||OD||0.3 (0.52)||0.2 (0.70)||−||Polyp||108||88||110||214||183||181||181||206||6|
|6||M||67||OD||0.5 (0.30)||1.0 (0.00)||−||BVN||464||257||165||245||185||149||148||185||13|
|7||M||82||OD||0.3 (0.52)||0.2 (0.70)||−||BVN||377||256||159||230||132||88||88||98||6|
|8||F||74||OD||0.1 (1.00)||0.15 (0.71)||−||BVN||266||119||106||232||206||183||165||191||6|
|9||M||63||OD||0.6 (0.22)||0.8 (0.10)||+||BVN||98||65||75||157||300||248||256||268||6|
|10||F||54||OS||0.9 (0.05)||0.9 (0.05)||+||BVN||336||186||150||310||459||413||369||393||8|
|Mean||70.6||0.38 (0.42)||0.43 (0.37)||277||175||137||280||188||164||157||179||8.0|
|Nonrecurrent Cases||Sex||Age (y)||Eye||BCVA at Baseline (logMAR)||BCVA at 1 Year (logMAR)||Permeability a||Recurrence||Central Retinal Thickness (μm) c||Subfoveal Choroidal Thickness (μm) d|
|Baseline||M 1||M 3||M 6||Y 1||Baseline||M 1||M 3||M 6||Y 1|
|11||M||77||OS||0.3 (0.52)||0.9 (0.05)||−||−||454||229||191||191||199||224||205||164||176||158|
|12||F||84||OD||0.5 (0.30)||0.4 (0.40)||−||−||245||193||202||186||201||175||158||150||117||116|
|13||M||69||OS||0.09 (0.81)||0.3 (0.52)||−||−||467||232||243||222||235||126||116||122||108||129|
|14||M||75||OD||0.2 (0.70)||0.3 (0.52)||−||−||196||181||152||150||121||199||106||96||98||101|
|15||M||55||OS||0.5 (0.30)||0.9 (0.05)||+||−||273||121||129||129||126||604||508||505||508||516|
|16||F||67||OS||0.5 (0.30)||1.2 (−0.08)||+||−||430||393||227||168||183||292||262||248||272||271|
|17||F||74||OS||0.5 (0.30)||1.2 (−0.08)||+||−||191||144||152||170||175||344||311||323||383||375|
|18||F||72||OD||0.3 (0.52)||0.7 (0.15)||+||−||400||222||150||152||155||208||169||145||114||122|
|19||F||84||OD||0.01 (2.00)||0.05 (1.30)||+||−||668||456||382||449||420||250||205||173||155||167|
|20||M||73||OS||0.6 (0.22)||1.0 (0.00)||+||−||263||229||147||142||147||266||237||210||219||210|
|21||M||84||OS||0.4 (0.40)||0.6 (0.22)||+||−||214||168||152||155||155||224||170||169||179||160|
|22||F||86||OS||0.5 (0.30)||0.7 (0.15)||+||−||210||145||159||167||163||247||242||207||214||186|
|23||M||77||OS||0.3 (0.52)||0.6 (0.22)||+||−||198||170||137||145||150||157||120||129||129||139|
|24||M||86||OD||0.6 (0.22)||0.8 (0.10)||+||−||268||188||188||186||191||260||237||229||232||240|
|25||F||82||OD||0.4 (0.40)||0.9 (0.05)||+||−||243||183||155||176||163||235||206||181||201||194|
|26||M||73||OD||0.6 (0.22)||1.0 (0.00)||+||−||674||325||212||212||209||310||274||268||277||263|
|27||F||76||OD||0.6 (0.22)||0.6 (0.22)||+||−||353||183||188||188||193||255||250||251||248||258|
|Mean||76.1||0.32 (0.50)||0.60 (0.22)||338||221||186||188||187||257||222||210||213||212|
b Recurrence type: Polyp type was defined as re-polypoidal lesions appearance on indocyanine green angiography, BVN (branching vascular network) type was defined as new exudative changes from BVN vessels on fluorescein angiography and optical coherence tomography without polypoidal lesion on indocyanine green angiography.