Choroidal Thickness Changes After Intravitreal Ranibizumab and Photodynamic Therapy in Recurrent Polypoidal Choroidal Vasculopathy




Purpose


To evaluate subfoveal choroidal thickness changes in cases with recurrent polypoidal choroidal vasculopathy (PCV) after combination therapy with intravitreal ranibizumab and photodynamic therapy (PDT).


Design


Retrospective observational case series study.


Methods


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.


Results


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).


Conclusion


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.




Results


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).



Table

Baseline Characteristics and Changes in the Retinal and Choroidal Thicknesses After Combination Therapy With Intravitreal Ranibizumab and Photodynamic Therapy for Polypoidal Choroidal Vasculopathy

















































































































































































































































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
SD 132 76 45 106 114 103 93 94



































































































































































































































































































































































































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
SD 156 90 60 72 67 104 94 96 106 106

Baseline = before treatment; BCVA = best-corrected visual acuity; logMAR = logarithm of the minimal angle of resolution; M 1 = 1 month after photodynamic therapy; M 3 = 3 months after photodynamic therapy; M 6 = 6 months after photodynamic therapy; Y 1 = 1-year after photodynamic therapy.

a Choroidal vascular hyperpermeability.


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.


c Retinal thickness including retinal detachment at the fovea.


d Choroidal thickness measured using enhanced depth imaging spectral-domain optical coherence tomography.




Figure 1


Case 6. A case of recurrent polypoidal choroidal vasculopathy in a 67-year-old man. (Top row) Gray-scale fundus photograph (FP), fluorescein angiography (FA), and early- and late-phase indocyanine green angiography (ICGA) at baseline. FP shows a round whitish lesion corresponding to a serous retinal detachment (SRD). FA shows the hyperfluorescence of active leakage at the upper fovea and a retinal pigment epithelium (RPE) detachment temporal to the fovea. Early-phase ICGA shows a polypoidal lesion at the foveal center, and late-phase ICGA does not show hyperfluorescence representative of choroidal vascular hyperpermeability. (Middle row) FP, FA, and ICGA images 3 months after photodynamic therapy (PDT). FP shows subretinal yellow deposits at the macula. FA indicates no leakage at the macula, and both ICGAs show no polypoidal lesion. (Bottom row) At recurrence: FP, FA, ICGA images about 1 year after PDT treatment. FP shows whitish exudates temporal to the fovea. FA shows hyperfluorescence of active leakage and RPE degeneration in the temporal macular area. Early- and late-phase ICGA show an abnormal vascular network at the temporal macular area without polypoidal lesions.

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Jan 9, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Choroidal Thickness Changes After Intravitreal Ranibizumab and Photodynamic Therapy in Recurrent Polypoidal Choroidal Vasculopathy

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