Introduction

Although multiple studies1, 2, 3, 4, 5, 6 and the pivotal ANCHOR and MARINA trials7, 8 have shown high efficacy in the treatment of choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD) with anti-vascular endothelial growth factor (anti-VEGF) therapy, analysis of the responses based on specific lesion subtypes (ie, pigment epithelial detachments (PEDs)) was not performed. Previous studies have shown suboptimal and inconsistent outcome for the treatment of vascularized pigment epithelial detachment (vPED).7, 8, 9, 10 Although conventional doses of anti-VEGF therapy may reduce associated haemorrhage and intraretinal or subretinal fluid, the vPED does not typically resolve10 and residual visual disturbance may persist. Herein, we report three cases of rapid resolution of the vPED after only a single high dose (2 mg/0.05 ml) of ranibizumab. Approval by the respective institutional boards for this study and a full informed consent from all patients were obtained.

Case reports

Case 1

An 86-year-old man reported a 6-month history of metamorphopsia affecting the left eye (LE). Best-corrected VA was 20/30 in the right eye (RE) and 20/100 in the LE. Fundus examination showed nonexudative ARMD in the RE, and a large PED with a neovascular focus, consistent with vPED, in the LE, which was confirmed by fluorescein angiography (FA) and optical coherent tomography (OCT) imaging (Figures 1a–c). Baseline indocyanine-green (ICG) angiography showed no evidence of polypoidal choroidal vasculopathy (PCV) in the LE. Following a single injection of high-dose (2 mg) ranibizumab (Genentech Inc., San Francisco, CA, USA), resolution of subretinal fluid and collapse of the vPED were noted by day 10 post treatment visit (Figures 1d–f). Repeat high-dose injections were performed for the LE on a monthly basis. The vPED remained flat with improved vision (RE: 20/30, LE: 20/30) at the 12-month follow-up examination.

Figure 1
figure 1

(a) Pre-treatment FP, (b) FA, and (c) OCT show a large vPED with a subfoveal choroidal neovascular focus. (d) FP, (e) FA, and (f) OCT 10 days after a single injection of 2 mg ranibizumab show collapse of the vPED.

Full size image

Case 2

A 60-year-old woman reported vision loss in both eyes for 3 months. The best-corrected VA was 20/30 in the RE and 20/100 in the LE. Macular atrophy was noted in the LE and subfoveal vPED in the RE, confirmed by FA and OCT (Figures 2a–c). Baseline ICG angiography showed absence of PCV in the RE. After a single injection of 2 mg ranibizumab, there was resolution of most of the subretinal fluid, hard exudates, and collapse of the vPED 1 month after the injection (Figures 2d–f). Injections were repeated for the RE on a monthly basis. Twelve months later, the vPED remained flat without leakage and associated with stable vision (RE: 20/20, LE: 20/100).

Figure 2
figure 2

(a) A subfoveal vPED was noted in the RE on pre-treatment FP, (b) FA, and (c) OCT. (d) Resolution of most of the subretinal fluid and the vPED was noted on FP, (e) FA, and (f) OCT 1 month after a single intravitreal injection of 2-mg ranibizumab.

Full size image

Case 3

An 85-year-old man presented with a 7-month history of progressive metamorphopsia affecting both eyes. Best-corrected VA was 20/60 in the RE and 20/400 in the LE. The posterior-segment examination showed a subfoveal vPED with hard exudates in the RE. There was an irregular vPED associated with diffuse subretinal fluid in the LE. FA showed CNV associated with a retinochoroidal anastomosis at the margin of the vPED in the RE (Figures 3a–c), and occult CNV associated with the vPED in the LE. Baseline ICG angiography did not show PCV in both eyes. He received 2 mg of ranibizumab, RE, initially, which was repeated on a monthly basis. His LE received 0.5 mg ranibizumab monthly. After a single injection, there was resolution of the subretinal fluid and exudates and flattening of the vPED in the RE 1 month after the injection (Figures 3d–f). After a follow-up of 12 months, there was no recurrent leakage, and the VA was 20/40 in the RE and 20/100 in the LE.

Figure 3
figure 3

(a) Baseline FP and (b) FA of the RE showed a retinochoroidal anastomosis within a vPED. (c) Baseline OCT also confirmed the diagnosis of PED in the RE. His RE received 2 mg ranibizumab, and the LE also received conventional 0.5 mg ranibizumab injections. (d) After a single 2mg ranibizumab injection, there was resolution of the subretinal fluid and flattening of the vPED in the RE, as shown on follow-up FP, (e) FA, and (f) OCT 1 month later.

Full size image

Discussion

The highly favourable outcomes on treatment of combined subtypes of neovascular AMD with conventional doses of ranibizumab shown by the pivotal clinical trials (ie, ANCHOR, MARINA, FOCUS, and SAILOR)5, 6, 11, 12 are not consistently achieved for vPED, a difficult-to-treat subtype of neovascular AMD. The aetiology of the slow and inconsistent response of vPED to conventional doses of anti-VEGF therapy is unknown.10 Rapid flattening of the PED with high-dose therapy may be explained by the greater concentration of ranibizumab that penetrates the RPE barrier and suppresses CNV and resolves the associated fluid and haemorrhage.

For our 3 cases, monthly maintenance injections were performed for 12 months. Patients were monitored on a prospective basis for ocular and systemic adverse events, and none of them developed any cardiovascular, neurological, or thromboembolic complications. However, further monitoring is needed to analyse potential ocular adverse events, such as RPE tears. The preliminary 1-year results of HARBOR, a large multicenter randomized trial, showed no dose–response safety signals relating to ocular or systemic adverse events (A Ho, unpublished data, AAO subspecialty day presentation, Orlando, October 2011).

In conclusion, this case series shows that high-dose ranibizumab may rapidly resolve vPED without complications. Further prospective analysis of a larger cohort of eyes is necessary to validate these outcomes.