Purpose: To investigate the changes in the retinal microvasculature during the course of anti-VEGF therapy in eyes with macular edema due to retinal vein occlusion (RVO) and their association with visual outcomes. Methods: The vessel density (VD) and foveal avascular zone (FAZ) area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were quantitatively measured by optical coherence tomography angiography (OCTA) in 48 consecutive eyes with RVO before and 1, 3, 6, 9, and 12 months after anti-VEGF therapy. Anti-VEGF therapy was performed either with ranibizumab or aflibercept following a pro re nata (PRN) regimen. The correlation between post-treatment best-corrected visual acuity (BCVA) and changes in the retinal microvasculature evaluated by OCTA were assessed. Results: The BCVA improved significantly at 12 months (P < 0.001). Better BCVA at 12 months was significantly associated with a better VD in the SCP and DCP both at baseline (R² = 0.524, P < 0.001 and R² = 0.457, P < 0.001, respectively) and at 12 months (R² = 0.521, P < 0.001 and R² = 0.662, P < 0.001, respectively). Overall, both VD and FAZ did not change significantly during the 12 months. However, the progression of nonperfusion was observed in the SCP in 6 (13%) eyes and in the DCP in 10 (21%) eyes. The number of macular edema recurrence was significantly associated with a decrease in the VD (P = 0.006 [SCP] and P < 0.001 [DCP]) and less visual gain (P = 0.02) after treatment. Conclusions: Anti-VEGF therapy maintains retinal perfusion in most patients with RVO. Preserving retinal perfusion is crucial for better visual outcomes.

We investigated changes in retinal vascular area and the foveal avascular zone (FAZ) after intravitreal aflibercept in diabetic macular edema (DME) and the association of these changes with visual outcomes. The retinal vascular area in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) and the FAZ area were measured using optical coherence tomography angiography (OCTA) in 23 eyes of 23 patients with DME, before and after intravitreal aflibercept. Overall, there was no significant change in retinal vascular area or FAZ. Better BCVA after treatment was significantly associated with larger retinal vascular area in the SCP and the DCP, both at baseline (R² = 0.512, P < 0.001 and R² = 0.361, P = 0.002, respectively) and after intravitreal aflibercept (R² = 0.717, P < 0.001 and R² = 0.618, P < 0.001, respectively). MAs were observed in the DCP in 20 eyes (87%), but only detected in four eyes (17%) in the SCP before treatment. The number of eyes with MAs in the DCP significantly decreased to 13 (57%) after treatment (P = 0.049). The persistence of DME was associated with persistent MAs (P = 0.019) and less visual gain (P = 0.031) following treatment. Thus, preserving retinal perfusion and the resolution of MAs are associated with better vision and resolution of the DME after intravitreal aflibercept.

To investigate vascular perfusion and foveal avascular zone area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) after intravitreal aflibercept therapy in central retinal vein occlusion eyes and their association with best-corrected visual acuity. Thirty-five subjects with central retinal vein occlusion and macular edema were evaluated. After macular edema resolution following intravitreal aflibercept, subjects underwent optical coherence tomography angiography to measure SCP and DCP perfusion and the foveal avascular zone within a 3 × 3-mm area. Correlations between best-corrected visual acuity and optical coherence tomography angiography measurements were examined. After intravitreal aflibercept therapy, mean retinal vascular area was 3.41 ± 0.74 mm2 in the SCP and 3.25 ± 0.91 mm2 in the DCP. Foveal avascular zone area was 1.03 ± 1.04 mm2 in the SCP and 1.78 ± 1.73 mm2 in the DCP. Improved best-corrected visual acuity was significantly associated with better SCP and DCP perfusion (both P < 0.001) and with smaller SCP and DCP foveal avascular zone areas (both P < 0.001). Additionally, SCP and DCP perfusion were negatively correlated with macular edema before treatment (P < 0.05) and ischemia (determined via pretreatment fluorescein angiography, P < 0.05), and positively correlated with photoreceptor integrity (P < 0.001). Patients with better retinal perfusion and less retinal ischemia are associated with better visual outcomes after aflibercept in eyes with central retinal vein occlusion.

The corneal endothelium, which originates from the neural crest via the periocular mesenchyme (PM), is crucial for maintaining corneal transparency. The development of corneal endothelial cells (CECs) from the neural crest is accompanied by the expression of several transcription factors, but the contribution of some of these transcriptional regulators to CEC development is incompletely understood. Here, we focused on activating enhancer-binding protein 2 (TFAP2, AP-2), a neural crest–expressed transcription factor. Using semiquantitative/quantitative RT-PCR and reporter gene and biochemical assays, we found that, within the AP-2 family, the TFAP2B gene is the only one expressed in human CECs in vivo and that its expression is strongly localized to the peripheral region of the corneal endothelium. Furthermore, the TFAP2B protein was expressed both in vivo and in cultured CECs. During mouse development, TFAP2B expression began in the PM at embryonic day 11.5 and then in CECs during adulthood. siRNA-mediated knockdown of TFAP2B in CECs decreased the expression of the corneal endothelium–specific proteins type VIII collagen alpha 2 (COL8A2) and zone pellucida glycoprotein 4 (ZP4) and suppressed cell proliferation. Of note, we also found that TFAP2B binds to the promoter of the COL8A2 and ZP4 genes. Furthermore, CECs that highly expressed ZP4 also highly expressed both TFAP2B and COL8A2 and showed high cell proliferation. These findings suggest that TFAP2B transcriptionally regulates CEC-specific genes and therefore may be an important transcriptional regulator of corneal endothelial development and homeostasis.

To demonstrate the utility of optical coherence tomography angiography (OCTA) in visualizing the choroidal vasculature in bilateral diffuse uveal melanocytic proliferation (BDUMP), so as to elucidate pathophysiology and also aid in diagnosis. Additionally, to recommend autofluorescence (AF) over traditional angiography for purposes of noninvasive diagnosis. Three BDUMP cases are examined using AF, and two are examined using OCTA. Additionally, the cases vary in etiology and include a case with iris cysts, which we believe to have only been recorded once before in scientific literature, steroids were successfully used to treat two cases and anti-tumor drugs were used to treat the third case. OCTA revealed altered choroidal vasculature in the two cases tested, and AF was successfully used to diagnose all three cases regardless of etiology. We believe the OCTA findings are potentially elucidative regarding the pathophysiology at the choroidal layer, where BDUMP lesions primarily exist. Given the limited number of recorded BDUMP cases and relatively unknown pathophysiology, OCTA may prove to be invaluable in visualizing disease progression. Also we were able to use AF to diagnose all three cases ranging from extremely rare iris cysts to a more conventional presentation, indicating its utility regardless of etiology.