Another kinase inhibitor, regorafenib (Stivarga, Bayer), showed positive results in two studies as a potential topical therapy for AMD and related disorders (Beottger MK. IOVS. 2015;56:ARVO E-Abstract 2294; Klar J. IOVS. 2015;56:ARVO E-Abstract 246). Oral docosahexaenoic acid supplements protected against neovascularization and retinopathy in rat models of AMD (Ogami S. IOVS. 2015;56:ARVO E-Abstract 2350), and a new RNAi-based agent appears to inhibit both angiogenesis and fibrosis promoted by periostin (Nakama T. IOVS. 2015;56:ARVO E-Abstract 2280).
The variety of new agents showing promise in preclinical studies bodes well for future improvements in retinal proliferative disease.
The 1-year results of a phase I/II combination therapy of low-dose, proton beam irradiation and anti-VEGF therapy were presented (Osmanovic S. IOVS. 2015;56:ARVO E-Abstract 4906). This study was based on observed synergism of VEGF inhibitors and proton beam therapy in patients receiving radiotherapy. Though this was only an interim analysis, results are encouraging, with fewer injections needed in the group receiving radiation treatment.
Dry AMD continues to be one of the main ocular disorders without significant, FDA-approved therapies. In the clinic, BAM114341, a therapy designed to block formation of β-amyloid deposits seen in Alzheimer’s disease, is being tested in a phase II study in geographic atrophy secondary to AMD (Shearn SP. IOVS. 2015;56:ARVO E-Abstract 2840). Though this presentation only covered results from the 4-month run-in period in which endpoint criteria values were established, it will be exciting to see the efficacy results of this study given the emerging link between β-amyloid formation in AMD and other neurodegenerative disorders.
Retinal branch occlusion and diabetic macular edema (DME) were both the focus of important clinical trial results. First-year results from the VIBRANT study—a trial in which monthly intravitreal aflibercept (Eylea, Regeneron) injections were compared with laser therapy for retinal branch occlusion—were presented (BoyerDS. IOVS. 2015;56:ARVO E-Abstract 3749). Using the proportion of patients with a ≥15 letter gain in best-corrected visual acuity (BCVA) as primary endpoint, intravitreal aflibercept injection therapy was superior to control at both 24 weeks (52.7% versus 26.7%, p = 0.0003) and at 52 weeks (57.1% versus41.1%, p = 0.0296).
Another trial involved head-to-head comparison of the VEGF inhibitor, bevacizumab, with a depot form of dexamethasone (Ozurdex, Allergan) for treatment of DME (Gillies MC. IOVS. 2015;56:ARVO E-Abstract 3144). Improvements of 10 or more letters at 24 months were similar in both groups (Avastin 45% versus Ozurdex 43%), but more subjects (5/46 versus 1/42) in the Ozurdex group showed a decline of ≥0 letters in BCVA, and a significant number in the Ozurdex group showed a progression in cataract formation. (43% versus 8).
Progress in gene-based therapy for inherited disease was demonstrated in study of corneal clouding associated with MPS1, a condition known historically as Hurler’s syndrome (Hirsch M. IOVS.2015;56:ARVO E-Abstract 260). The study tested a viral-based expression of a replacement for the affected gene product in patient fibroblasts, mouse cornea, and human cornea. Optimization of the adeno-associated viral vector for corneal expression was demonstrated in all three test tissues, providing hope for therapeutic intervention for corneal clouding in children with MPS 1 and other variants of mucopolysacharride-associated disorders.