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David M Brown, Avner Ingerman, Shawn Patrick Shearn, Jason S Slakter; CNV lesion characteristics as a predictor of visual outcome in wet AMD patients receiving combination therapy of intravitreal anti-VEGF therapy and topical Squalamine lactate ophthalmic solution.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4419.
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© ARVO (1962-2015); The Authors (2016-present)
Neovascular age-related macular degeneration (AMD) is currently treated by intravitreal (IVT) injections of anti-VEGF agents. Multiple, frequent anti-VEGF IVT injections are required, and improvement in visual function is often sub-optimal. Squalamine lactate 0.2% solution is administered topically, and functions by blocking intracellular signaling pathways common to VEGF, PDGF, and bFGF. An exploratory Phase II study examined the safety and efficacy of treatment with topical Squalamine, administered BID for 9 months, in combination with PRN (as-needed) IVT ranibizumab injections.
142 patients enrolled in a phase II, double masked, placebo controlled study. All patients received a single IVT injection of ranibizumab at baseline, followed by criteria-based PRN ranibizumab IVT injections monthly to month 9. Patients were randomized 1:1 to receive either placebo eye drops or Squalamine eye drops BID to month nine. 128 patients (63 in the placebo/Ranibizumab monotherapy group and 65 patients in the Squalamine/combination group) completed the month 9 endpoint. Patients with total lesion area ≤ 12 disc areas, choroidal neovascularization (CNV) affecting > 50% of the total lesion area, and all angiographic lesion types (occult and classic) were included in the study. Best Corrected Visual Acuity (BCVA) was assessed monthly and compared to baseline. An analysis of visual outcome as a function of lesion characteristics (presence and size of classic and occult CNV) was performed.
At month 9, the mean BCVA gain from baseline was 7.8 letters for all patients in the Combination group (N=65), compared to 5.3 letters for all patients in the ranibizumab monotherapy group (N=63) (P=0.25). An analysis of visual acuity outcome as a function of the occult CNV size demonstrated a strong correlation in the combination therapy group (p=<0.0001) but not with ranibizumab monotherapy (Table).
Angiographic CNV lesion characteristics were predictive of visual acuity outcomes in combination therapy. Baseline occult CNV area shows the highest correlation to visual outcome in combination treatment with IVT anti-VEGF and topical Squalamine. Patients with occult CNV <10 mm2 represent an optimal target population for combination therapy in clinical trials.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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