Childhood blindness incidence and aetiologies trends in Israel 2014-2020: what should we focus on?

OBJECTIVES: Analyse trends in incidence and aetiologies of childhood blindness (CHB) in Israel during 2014-2020, with comparison to the previous decade. METHODS: Descriptive, retrospective population-based trend study using Poisson regression. Data retrieved from the Israeli National Registry of the Blind included demographics, registration-years, and aetiologies. Primary and secondary outcomes were incidence of new certified blindness cases and its comparison with the previous decade, respectively. RESULTS: In total, 4.19 new CHB certificates per 100,000 were issued in Israel during 2014-2020, with a slight non-significant increase (p = 0.31). Males and younger children had higher incidence rates (p = 0.0008 and p = 0.0002, respectively). Leading causes were optic nerve anomalies (ONA), retinal dystrophies (RDYS), other retinal disorders (ORD) and cerebral visual impairment (CVI) (16.9%, 15.1%, 12.4% and 10.5%, respectively). Compared with the previous decade: ONA rates remained unchanged (p = 0.13) as did some other main aetiologies (i.e., albinism, CVI and nystagmus), while rates of RDYS and ORD increased (by 21.9%, p = 0.001 and 9.9% p = 0.02, respectively). Rates of retinopathy of prematurity (ROP), glaucoma, cataract and amblyopia remained very low (weighted average of 0.15, 0.14, 0.09 and 0.03 per 100,000, respectively). CONCLUSIONS: The incidence of CHB certifications in Israel remained stable with a slight increase, stemming chiefly from RDYS resurgence and an increase in ORD. Main causes remained ONA and RDYS. The most common avoidable cause, ROP, remained scarce, maintaining the reduction seen in the earlier decade, as did cataract, glaucoma, and amblyopia. This may support future nationwide prevention policies to decrease the incidence of RDYS and ORD.

Time Trends of Etiologies of Blindness in Israel 2009-2020:Have Methods to Decrease Leading Causes of Blindness Been Exhausted?

PURPOSE: To perform a nationwide analysis of trends in the incidence of etiologies for legal blindness in Israel during 2009-2020, and to compare the results with those of the previous decade. DESIGN: Descriptive, retrospective population-based trend study. METHODS: Data were retrieved from the Israeli National Registry of the Blind during 2009-2020. Data obtained included demographics, years of registration, and causes. Primary and secondary outcomes were the incidence of new certified blindness cases and its comparison with that of the previous decade, respectively. RESULTS: The age-standardized incidence rate of blindness in Israel decreased from 15.76 per 100,000 residents in 2009 to 11.83 in 2020, a 24.9% drop. The mean annual decline was evident until 2013 (P < .001, 6.15%), but subsequently flattened (P = .71, 0.42%). Age-related macular degeneration (AMD), glaucoma, optic atrophy, and cataract decreased until 2014, and reached a plateau that was maintained until the end of the study period. Diabetic retinopathy (DR) incidence rates diminished throughout the decade (P < .001, 9.2%), with attenuation of the rate of decline after 2014. CONCLUSIONS: The impact of efforts to reduce the incidence of preventable causes of blindness may have nearly reached saturation for most of the leading causes of blindness in Israel, namely, AMD, glaucoma and cataract. The incidence of DR has been maintained; however, attenuation has been observed. New modalities to detect and treat these causes may have to emerge before a resurgence of improvement can occur.

Comparative analysis of induced vs. spontaneous models of autoimmune uveitis targeting the interphotoreceptor retinoid binding protein.

Animal models of autoimmunity to the retina mimic specific features of human uveitis, but no model by itself reproduces the full spectrum of human disease. We compared three mouse models of uveitis that target the interphotoreceptor retinoid binding protein (IRBP): (i) the "classical" model of experimental autoimmune uveitis (EAU) induced by immunization with IRBP; (ii) spontaneous uveitis in IRBP T cell receptor transgenic mice (R161H) and (iii) spontaneous uveitis in Autoimmune Regulator (AIRE)(-/-) mice. Disease course and severity, pathology and changes in visual function were studied using fundus imaging and histological examinations, optical coherence tomography and electroretinography. All models were on the B10.RIII background. Unlike previously reported, IRBP-induced EAU in B10.RIII mice exhibited two distinct patterns of disease depending on clinical scores developed after onset: severe monophasic with extensive destruction of the retina and rapid loss of visual signal, or lower grade with a prolonged chronic phase culminating after several months in retinal degeneration and loss of vision. R161H and AIRE(-/-) mice spontaneously developed chronic progressive inflammation; visual function declined gradually as retinal degeneration developed. Spontaneous uveitis in R161H mice was characterized by persistent cellular infiltrates and lymphoid aggregation, whereas AIRE(-/-) mice characteristically developed multi-focal infiltrates and severe choroidal inflammation. These data demonstrate variability and unique distinguishing features in the different models of uveitis, suggesting that each one can represent distinct aspects of uveitis in humans.

Cellular Resolution Panretinal Imaging of Optogenetic Probes Using a Simple Funduscope.

PURPOSE: To acquire and characterize cellular-resolved in vivo fluorescence images of optogenetic probes expressed in rodent retinal ganglion cells, by adapting a low-cost and simple fundus system based on a topical endoscope. METHODS: A custom endoscope-based fundus system was constructed (adapted from the design of Paques and colleagues). Bright field and fluorescence images were acquired from head-fixed transgenic mice expressing Channelrhodopsin2-eYFP, and Sprague Dawley rats virally transfected with the optogenetic probe GCaMP3. Images were compared to in vitro images of the same structures and were analyzed. RESULTS: The fundus system provides high-quality, high-resolution fluorescence images of the eye fundus that span the whole retina. The images allow resolving individual cells and axon bundles in the Channelrhodopsin2-eYFP mice and cellular-scale structures in the GCaMP3 expressing rats. The resolution in mouse eyes was estimated to be better than 20 µm (full width at half maximum) and is only marginally dependent on movement-related blurring. CONCLUSIONS: The fluorescence-endoscopy fundus system provides a powerful yet simple and widely accessible tool for obtaining cellular resolved fluorescent images of optogenetic and other fluorescent probes. TRANSLATIONAL RELEVANCE: The new system could prove to be a basic tool for non-invasive in vivo small animal retinal imaging in a wide array of translational vision applications, including the tracking of fluorescently tagged cells and the expression of gene-therapy and optogenetic vectors.