Late neuroprogenitors contribute to normal retinal vascular development in a Hif2a-dependent manner.

In the adult central nervous system, endothelial and neuronal cells engage in tight cross-talk as key components of the so-called neurovascular unit. Impairment of this important relationship adversely affects tissue homeostasis, as observed in neurodegenerative conditions including Alzheimer's and Parkinson's disease. In development, the influence of neuroprogenitor cells on angiogenesis is poorly understood. Here, we show in mouse that these cells interact intimately with the growing retinal vascular network, and we identify a novel regulatory mechanism of vasculature development mediated by hypoxia-inducible factor 2a (Hif2a). By Cre-lox gene excision, we show that Hif2a in retinal neuroprogenitor cells upregulates the expression of the pro-angiogenic mediators vascular endothelial growth factor and erythropoietin, whereas it locally downregulates the angiogenesis inhibitor endostatin. Importantly, absence of Hif2a in retinal neuroprogenitor cells causes a marked reduction of proliferating endothelial cells at the angiogenic front. This results in delayed retinal vascular development, fewer major retinal vessels and reduced density of the peripheral deep retinal vascular plexus. Our findings demonstrate that retinal neuroprogenitor cells are a crucial component of the developing neurovascular unit.

RETINAL SURFACE WRINKLING AS AN INDICATOR FOR INTERNAL LIMITING MEMBRANE PEELING DURING VITRECTOMY FOR RETINAL DETACHMENT.

PURPOSE: To assess the validity of retinal surface wrinkling (RSW) as an indicator to select patients relevant for internal limiting membrane peeling during vitrectomy for rhegmatogenous retinal detachment, to prevent postoperative visual decline due to epiretinal membrane growth. METHODS: This was a prospective, interventional case series of 78 consecutive eyes that underwent initial vitrectomy to repair rhegmatogenous retinal detachments and were followed for 6 months. The presence/absence of RSW was evaluated presurgically on en face optical coherence tomographic images. The internal limiting membrane was peeled if RSW was identified. The main outcome measure was the prevalence of postsurgical epiretinal membrane growth that caused a visual decline of 0.2 or more in logarithm of the minimum angle of resolution unit. RESULTS: The internal limiting membrane was peeled for RSW appearance in 22 eyes (28.2%). Mild epiretinal membranes developed in 8 of the 56 internal limiting membrane-unpeeled eyes (10.3% of total, 6 eyes at stage 1 in the classification of Govetto); however, visual decline occurred in none of them with the mean visual acuity of these 8 eyes maintained at -0.08 ± 0.11 in logarithm of the minimum angle of resolution (≈20/16). CONCLUSION: Visual decline due to epiretinal membrane growth after rhegmatogenous retinal detachment repair was entirely prevented by peeling the internal limiting membrane in about 30% of cases selected for the presence of RSW.

Light-dark changes in iris thickness and anterior chamber angle width in eyes with occludable angles.

BACKGROUND: The purpose of this study was to investigate and measure light-dark changes in iris thickness (IT) and anterior chamber angle width in eyes with occludable angles and open angles by using anterior segment optical coherence tomography (AS-OCT). METHODS: We examined 153 eyes of 153 Japanese patients with primary angle closure suspect, primary angle closure, primary angle closure glaucoma, or primary open angle glaucoma. AS-OCT was used to determine pupil diameter, IT, angle opening distance at 500 µm (AOD500), and trabecular-iris space area at 500 µm (TISA500) in each quadrant of the anterior chamber angle (superior, inferior, temporal, and nasal) under light and dark conditions. RESULTS: In the angle closure cases, IT, AOD500 and TISA500 in the dark varied significantly among the four quadrants (P < 0.05, analysis of variance). In contrast, in the open angle cases, IT, AOD500 and TISA500 in the dark did not differ significantly among the four quadrants. In the angle closure cases and the open angle cases, significant negative associations were found between IT difference [IT(light)-IT(dark)] and AOD500 difference [AOD500(light)-AOD500(dark)] (R = -0.411, P < 0.001 and R = -0.501, P = 0.001, respectively) and between IT difference and TISA500 difference [TISA500(light)-TISA500(dark)] (R = -0.475, P < 0.001 and R = -0.462, P = 0.002, respectively). CONCLUSION: Our results suggest that thickening of the iris root under dark conditions is related to the mechanism of primary angle closure. It is important to analyze both the angle structure and peripheral IT in each quadrant.

Comparison of Mydriatic Provocative and Dark Room Prone Provocative Tests for Anterior Chamber Angle Configuration.

PURPOSE: To investigate the relationship between angle configuration and diagnostic provocation tests such as the mydriatic provocative test (MPT) and the dark room prone provocative test (DRPPT). MATERIALS AND METHODS: Seventy eyes of 70 consecutive patients with primary angle closure suspect, primary angle closure, or primary angle closure glaucoma were included. The anterior chamber depth, angle opening distance 500, trabecular-iris space area 500, and iris thickness (IT) were quantitatively determined by anterior segment optical coherence tomography, and the MPT and DRPPT were used to investigate intraocular pressure variations. RESULTS: Seven eyes were positive and 3 eyes were suspected positive, using the MPT, whereas 10 eyes were positive and 7 eyes were suspected positive using the DRPPT. The anterior chamber depth and angle opening distance 500 of the positive and suspected positive groups (positive group), using the MPT, were significantly less than those of the negative group (P=0.013, P=0.013, respectively). IT of the positive group, using the MPT, was significantly greater than the negative group, using the same test (P=0.003). The trabecular-iris space area 500 of the positive group was significantly less than the negative group, using both the MPT (P<0.001) and the DRPPT (P=0.004). CONCLUSIONS: Eyes from the positive group, using the MPT, contained a shallower anterior chamber, narrower angle, and greater IT than those from the negative group. These results suggested that the MPT results better correlated with the anterior chamber angle configuration in eyes with primary angle closure, than the results using the DRPPT.

Influence of anterior segment biometric parameters on the anterior chamber angle width in eyes with angle closure.

PURPOSE: To predict angle narrowing in eyes with angle closure in a Japanese population using anterior segment optical coherence tomography (AS-OCT) quantitative parameters. PATIENTS AND METHODS: AS-OCT was used to examine 118 eyes of 118 patients with angle closure and 40 eyes of 40 patients with open angle under dark conditions. After measuring the angle opening distance 500 (AOD500), anterior chamber depth, iris thickness (IT), iris convexity (IC), pupil diameter, anterior chamber width, and crystalline lens rise, multivariate regression analyses were performed for the AOD500 in each group. RESULTS: With the exception of IT, significant differences were observed between the AS-OCT parameters for the angle closure and open-angle groups. Anterior chamber depth, IT, and IC were the explanatory variables associated with AOD500 for each group (P≤0.001). A significant negative association was found between IT and IC only in the angle-closure group (P<0.001). CONCLUSIONS: This study quantitatively confirmed that shallow anterior chamber depth was a major mechanism of angle narrowing, and that both IT and IC had a strong impact on angle narrowing. Moreover, the negative association found between IT and IC in only the angle closure group indicated the existence of the stretch force placed on the iris by relative pupillary block.

The significance of cone outer segment tips as a prognostic factor in epiretinal membrane surgery.

PURPOSE: To evaluate the prognostic value of the cone outer segment tips (COST) and other features using spectral-domain optical coherence tomography (SD-OCT) in patients undergoing epiretinal membrane (ERM) surgery. DESIGN: Retrospective observational case series. METHODS: Fifty eyes of 49 patients that underwent vitrectomy for idiopathic ERM were studied. Best-corrected visual acuity (BCVA) and SD-OCT images were examined preoperatively and at 1 and 6 months postoperatively. The SD-OCT features evaluated included central foveal thickness (CFT) and the status and defect diameter of the external limiting membrane (ELM), the photoreceptor inner/outer segment (IS/OS) junction, and the COST line. The associations between SD-OCT parameters and BCVA were analyzed. RESULTS: There was no ELM disruption found, and thus the eyes were categorized into 3 groups: Group A, with a continuous IS/OS and COST line; Group B, with a continuous IS/OS but disrupted COST line; and Group C, with a disrupted IS/OS and COST line. At 6 months, Group A showed a significantly better BCVA than Group B (P<.005), and poorer BCVA was noted in Group C (P=.034). Defect diameters of IS/OS and COST line were also significantly correlated with BCVA postoperatively. The BCVA at 6 months was better in order of Group A, B, and C as assigned at baseline (P<.05) or 1 month (P<.001). There was no significant correlation between CFT and BCVA. CONCLUSIONS: The status of the COST line, in conjunction with the IS/OS junction, is a useful prognostic factor after ERM surgery.

Remission and dropout rate of anti-VEGF therapy for age-related macular degeneration.

PURPOSE: Anti-vascular endothelial growth factor (VEGF) therapy is a first-line treatment for age-related macular degeneration (AMD) but frequent visits and injections can be a burden for patients. The purpose of this study is to estimate the remission rate and tolerability of anti-VEGF therapy for AMD in a clinical setting. METHODS: We investigated 90 eyes of 87 patients with AMD who underwent anti-VEGF therapy and were followed for more than 6 months. Ranibizumab and pegaptanib were used as anti-VEGF agents. Initial therapy was any of the following: a single injection, 3 consecutive monthly injections, or combination therapy with verteporfin. Additional injections were given as-needed during follow-up. An injection-free period greater than 6 months at the final observation was regarded as cessation; the reason for cessation was studied for each patient. Clinical characteristics were compared between patents with and without cessation. RESULTS: The mean follow-up period was 12.8 months. Mean logMAR before and 6 months after the treatment was 0.89 and 0.83, respectively. Cessation was noted in 32 eyes of 31 patients (35.6%). Remission was achieved in 13 (40.6%) of these eyes. The other cases either did not wish to undergo further treatment or dropped out. Poor baseline visual acuity (VA) was associated with cessation. CONCLUSIONS: With current anti-VEGF therapy, remission was achieved in a limited number of AMD cases. The high frequency of voluntary cessation warrants consideration of an alternative treatment and/or supportive care for those with poor baseline VA.