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Purpose To assess changes in retinal nonperfusion (RNP) in patients with retinal vein occlusion (RVO) treated with ranibizumab (RBZ) Design Secondary outcome measure in randomized double-masked controlled clinical trial Subjects Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO) Methods Subjects were randomized to 0.5mg or 2.0mg RBZ every month for 6 months and then re-randomized to pro re nata (prn) groups RBZ+scatter photocoagulation (laser) or RBZ alone for an additional 30 months. Main Outcome Measures Comparison of percentage of patients with increased or decreased area of RNP in patients with RVO treated with 0.5mg versus 2.0mg RBZ, during monthly injections versus prn RBZ, and in patients treated with prn RBZ versus prn RBZ+laser. Results In RVO patients given monthly injections of 0.5mg or 2.0mg RBZ for 6 months there was no significant difference in the percentage who showed reduction or increase in area of RNP. However, regardless of dose, during the 6 month period of monthly injections, a higher percentage of patients showed a reduction in area of RNP and a lower percentage showed an increase in area of RNP compared to subsequent time periods of prn RBZ treatment. After the 6 month period of monthly injections, BRVO, but not CRVO patients randomized to prn RBZ+laser showed significantly less progression of RNP compared to patients treated with prn RBZ. Conclusions Regardless of dose of ranibizumab (0.5mg or 2.0mg), monthly injections promote improvement and reduce progression of RNP compared to prn injections. Addition of scatter photocoagulation to prn RBZ may reduce progression of RNP in patients with BRVO, but a statistically significant reduction was not seen in patients with CRVO.

Purpose The Diabetic Macular Edema Treated with Ozurdex (DMEO) Trial measured aqueous pro-permeability factors (PPFs) in diabetic macular edema (DME) patients before and after injection of dexamethasone implant or vascular endothelial growth factor (VEGF)-neutralizing protein and correlated changes in levels with changes in excess foveal thickness (EFT) to identify potential PPFs contributing to DME. Design Prospective, randomized cross-over clinical trial Methods Twenty DME patients randomized to dexamethasone implant or VEGF-neutralizing protein had aqueous taps and spectral domain-optical coherence tomography (SD-OCT) at baseline and every 4 weeks for 28 weeks. Aqueous levels of 55 vasoactive proteins were measured with protein array. Cross-over at week 16 provided changes in protein levels after each intervention in all 20 patients. Results After dexamethasone implant there was significant correlation between changes in levels of 13 vasoactive proteins with changes in EFT, including three known PPFs, angiopoietin-2 (r=0.40, p=0.001), hepatocyte growth factor (HGF, r=0.31, p=0.02), and endocrine gland-VEGF (EG-VEGF, r=0.43, p<0.001). Reduction of prolactin, insulin-like growth factor binding protein-3, and matrix metalloproteinase-9 correlated with edema reduction after injection of a VEGF-neutralizing protein as well as dexamethasone implant suggesting their modulation is likely secondary to changes in edema rather than causative. Conclusions Correlation of edema reduction with reduction in the PPFs angiopoietin-2, HGF, and EG-VEGF provides potential insight into the multi-factorial molecular mechanism by which dexamethasone implants reduce edema and suggest that additional study is needed to investigate the contributions of these 3 factor to chronic DME.

Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development.

ImportanceIt is important to establish reliable outcome measures to detect progression in retinitis pigmentosa (RP).BackgroundTo evaluate progression of RP using multimodal imaging, including spectral‐domain optical coherence tomography (SD‐OCT), fundus autofluorescence (FAF) and microperimetry (MP).DesignRetrospective longitudinal study at a tertiary teaching hospital.Participants205 eyes of 106 patients with RP with 1 to 5 y of follow‐up.MethodsDemographics and visual acuity (VA) were recorded, and each modality was graded at baseline and every annual follow‐up. SD‐OCT was graded for the width of ellipsoid zone (EZ), FAF was graded for the diameter and area of the hyperautofluorescent ring (if present), and MP was graded for mean, central and paracentral sensitivity. Spearman's correlation was used to measure correlations at baseline. Mixed effects models were used to estimate the annual change of each parameter, adjusted for disease duration.Main Outcome MeasuresRate of progression.ResultsThe median VA at baseline was 75 letters and was positively correlated with mean and central sensitivity (r: 0.372 and 0.394; P = 0.01 for both). All parameters (except paracentral sensitivity) were strongly correlated with each other (r: 0.673‐0.991; P < 0.001 for all). The annual rates of change for each parameter were as follows: VA, −2.3 letters (P < 0.001); EZ, −151 μm (P < 0.001); ring diameter, −132 μm (P < 0.001); ring area, −0.4 mm2 (P < 0.001); mean sensitivity, −0.3 dB (P < 0.001); central sensitivity, −0.7 dB (P < 0.001); paracentral sensitivity, −0.4 dB (P < 0.001).Conclusions and RelevanceStructural and functional measures are well correlated in RP and can reliably measure disease progression within the course of a year.