Retinal and choroidal neovascularization are a major cause of significant visual impairment, worldwide. Understanding the various factors involved in the accompanying physiopathology is vital for development of novel treatments, and most important, for preserving patient vision. The intraocular use of anti-vascular endothelial growth factor therapeutics has improved management of the retinal and choroidal neovascularization but some patients do not respond, suggesting other vascular mediators may also contribute to ocular angiogenesis. Several recent studies examined possible new targets for future anti-angiogenic therapies. Potential targets of retinal and choroidal neovascularization therapy include members of the platelet-derived growth factor family, vascular endothelial growth factor sub-family, epidermal growth factor family, fibroblast growth factor family, transforming growth factor-β superfamily (TGF-β1, activins, follistatin and bone morphogenetic proteins), angiopoietin-like family, galectins family, integrin superfamily, as well as pigment epithelium derived factor, hepatocyte growth factor, angiopoietins, endothelins, hypoxia-inducible factors, insulin-like growth factors, cytokines, matrix metalloproteinases and their inhibitors and glycosylation proteins. This review highlights current antiangiogenic therapies under development, and discusses future retinal and choroidal pro- and anti-angiogenic targets as wells as the importance of developing of new drugs.

To evaluate the concentration of vascular endothelial growth factor (VEGF) in aqueous humor after a single intravitreal injection of bevacizumab (IVB) in eyes with neovascular age-related macular degeneration (AMD). In this prospective interventional case series study, 24 eyes of 24 patients with types 1 and 2 choroidal neovascularization secondary to neovascular AMD were treated with a single intravitreal injection of bevacizumab. Aqueous humor samples were obtained before the intravitreal injection and at one week, one month, and three months follow-up periods. Best-corrected visual acuity (BCVA) and three spectral-domain optical coherence tomography parameters (central retinal thickness, macular volume and macular area) were also analyzed and correlated with VEGF expression at the baseline and each follow-up period. All of the ninety-six aqueous humor study taps were well tolerated by the study patients without adverse events. Increased VEGF levels (mean ± SD = 179.7 ± 88.3 pg/mL) were observed in the aqueous humor of all study patients before the intravitreal injection of bevacizumab. At all follow-up periods, compared to baseline, levels of VEGF significantly reduced (P < 0.0001), and BCVA significantly improved (P < 0.005). The lowest VEGF expression was observed at 1 week, and the greatest BCVA improvement occurred 1 month after treatment. At 1 month, central retinal thickness (CRT), macular volume (MV), and macular area (MA) significantly reduced compared to baseline (P < 0.0001, P = 0.0005, P = 0.007, P = 0.009, respectively). At 1 week and 3 months, although without statistical significance (P > 0.005), CRT, MV and MA also reduced in comparison to baseline. Single intravitreal bevacizumab injection in eyes with neovascular AMD resulted in a substantial decrease of aqueous VEGF levels 1 week after treatment with the greatest improvement of clinical outcomes occurring at 1 month follow-up.

To determine the safety and efficacy of poly-N-isopropylacrylamide, a thermoresponsive adhesive, for sutureless sclerotomy closure in rabbits. Eight rabbits were randomized into three groups: short-term acute, mid-term chronic, and long-term chronic studies. A corresponding control group in which the scleral wounds were sutured by 6–0 vicryl sutures was assigned for each study group. A 20-gauge sclerotomy was performed following a core vitrectomy and 0.1 mL of 50 % liquid poly-N-isopropylacrylamide was applied to the scleral wounds. Before the polymer application, the scleral surface was raised above 32 °C using a halogen bulb lamp. Follow-up exams included color external and fundus photography, fundus fluorescein angiography, optical coherence tomography, and electroretinography. After the last follow-up assessment, the rabbits were sacrificed and histopathological studies on the scleral incision sites were performed. Scleral wound healing was observed in the long-term chronic study rabbits. Histological studies were able to identify poly-N-isopropylacrylamide polymer at the sclerotomy site in the mid-term chronic study rabbits. Besides iatrogenic cataracts due to mechanical instrument touch in 2 rabbits, no other ocular abnormalities were identified in any of the eyes in the perioperative setting or during the follow-up period. Cornea, retina, and vitreous remained unaffected, and no abnormal inflammatory reaction or endophthalmitis was noticed in the 3 study groups. Filtering blebs indicative of leakage through the sclerotomies were not observed during the follow-up period. Poly-N-isopropylacrylamide may provide effective in vitro scleral adhesion above 32 °C. Clinical studies are required to evaluate its utility in patients undergoing pars plana vitrectomy.

Autoimmune retinopathy (AIR) is a rare but potentially blinding condition that is often underdiagnosed. Common features in AIR presentation include rapidly progressive vision loss with abnormal electrophysiological responses of the retina associated with positive anti-retinal antibodies. AIR is also challenging to treat, and thus, the introduction of new potential therapeutic agents is welcomed. The goal of this communication is to assess the effects of rituximab infusions on electroretinogram (ERG) responses and visual function outcomes in patients with non-paraneoplastic autoimmune retinopathy (npAIR). Following infusion(s), three out of five patients showed no evidence of disease progression or improved, while two patients continued to progress on ERG. One patient demonstrated improvement in visual acuity (2 lines) in both eyes. ERG responses provided objective monitoring of patients’ visual function and response to immunosuppression over time. These findings suggest that patients with npAIR unresponsive to other immunosuppression therapies may benefit from rituximab infusion, although stabilization rather than improvement was more frequently the outcome in our case series. Furthermore, regularly scheduled ERG follow-up examinations are recommended for monitoring patients’ progression during treatment.

Retinitis pigmentosa (RP) is a category of inherited retinal dystrophies that is best prognosticated using electroretinography (ERG). In this retrospective cohort study of 25 patients with RP, we evaluated the correlation between 30 Hz flicker ERG and structural parameters in the retina. Internationally standardized 30 Hz flicker ERG recordings, short-wavelength autofluorescence (SW-AF), and spectral domain–optical coherence tomography (SD-OCT) were acquired at two visits at least one year apart. Vertical and horizontal hyperautofluorescent ring diameter measurements with SW-AF, as well as ellipsoid zone (EZ) line width measurements with SD-OCT, were used as structural parameters of disease progression. The 30 Hz flicker ERG amplitude decreased by 2.2 ± 0.8 µV/year (p = 0.011), while implicit times remained unchanged. For SD-OCT, the EZ line decreased by 204.1 ± 34.7 µm/year (p < 0.001). Horizontal and vertical hyperautofluorescent ring diameters decreased by 161.9 ± 25.6 µm/year and 146.9 ± 34.6 µm/year, respectively (p = 0.001), with SW-AF. A correlation was found between the progression rates of the 30 Hz flicker amplitude recorded with Burian–Allen electrodes and both the horizontal ring diameter (p = 0.020) and EZ line (p = 0.044). SW-AF and SD-OCT, two readily available imaging techniques, may be used to prognosticate disease progression because of the reliability of their measurements and correlation with functional outcome.