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Purpose To report 15-year incidence rate of visual loss (blindness and visual impairment [VI]), causes, and risk factors for participants in Andhra Pradesh Eye Disease Study III (APEDS III). Design Population-based cohort study. Methods From 2012 to 2016, all rural participants were interviewed and underwent a comprehensive eye examination, including dilated fundus examination and imaging. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) were measured using a standard logarithm of Minimum Angle of Resolution chart at 3 meters. World Health Organization (WHO) and United States of America (USA) categories of VI and blindness were used. Incident visual loss was defined as the development of or worsening of visual loss of one or more categories. Results In APEDS I, 7,771 rural participants were examined using stratified, random-cluster systematic sampling; in APEDS III, 5,395 participants (69.4% of rural or 52.4% of total participants) were re-examined. Using WHO categories, the crude incidence rate of any visual loss based on PVA and BCVA were 14.6 (95% confidence interval [CI]:13.6-15.7) and 6.3 (95% CI: 6.1-6.4) per 100 person-years, respectively. Using USA criteria, the values were 22.6 (95% CI: 22.3-23.0) and 10.6 (95% CI: 10.3-10.8) per 100 person-years, respectively. More than 90% of visual loss was attributable to cataract and uncorrected refractive error. Using WHO categories, significant independent risk factors for the incident visual loss were increasing age, female gender, illiteracy, past or current smoker, and current use of alcohol. Using the USA definition, an additional risk factor was lower level of education. Conclusions The high incidence likely reflects poor access to eye care in this population, which needs to be taken into account when planning eye care programs.

Purpose To report 15-year incidence rate and associated risk factors of pterygium among people aged 30 years and above at baseline in the rural clusters of longitudinal Andhra Pradesh Eye Disease Study (APEDS III). Methods The baseline APEDS I included 7771 participants of which 6447 (83%) were traced and 5395 (83.7%) were re-examined in APEDS III. To estimate the incidence of pterygium, we selected participants who were 30 years and above at baseline (4188), of which 2976 were traced and 2627 (88.3%) were examined, and based on inclusion criteria, 2290 participants were included in the study. The incidence rate of pterygium was defined as the proportion of people free of pterygium at baseline who had developed the condition at 15-year follow-up (range 13–17 years). Univariate and multivariable analyses for risk factors were undertaken. Results The sex-adjusted incidence rate of pterygium was 25.2 per 100 person-years (95% CI 24.8 to 25.7) which was significantly higher for men than women (26.3 per 100 person-years (95% CI 25.6 to 27.0) and 24.7 (95% CI 24.1 to 25.3) respectively). At the multivariable analysis, male gender (RR: 1.35, 95% CI 1.0 to 1.83), no formal education (RR: 2.46, 95% CI 1.22 to 4.93), outdoor occupation (RR: 1.47, 95% CI 1.14 to 1.9) and lower body mass index (BMI) ( Conclusions The overall incidence rate of pterygium was high in this rural population, especially in men and those engaged in outdoor activities, lack of formal education and with lower BMI. It is likely that greater exposure to ultraviolet light is a major contributing factor, thus warranting preventive strategies.

To report the 15-year incidence rate of pseudo-exfoliation (PXF), PXF glaucoma and regional variation among rural participants in the Andhra Pradesh Eye Disease Study (APEDS) III.This population-based longitudinal study was carried out at three rural study sites. Individuals of all ages who participated at baseline with a mean 15-year follow-up visit were included. Detailed Comprehensive ophthalmic examination was performed on all participants. The main outcome measure was development of PXF during the follow-up period in participants who were phakic in one or both eyes without PXF at baseline.Among 5395 participants, 5108 (94.6%) met the inclusion criteria. There were 93 (1.82%; 95% confidence interval (CI), 1.47-2.22) cases of incident PXF. Their median baseline age (1st, 3rd quartiles) was 51 (44, 59) years and the male: female ratio was 1.3:1. There was no case of incident PXF in participants aged30 years at baseline. The incidence rate per 100 person years (95% CI) among all ages and those aged ≥30 years at baseline was 1.73 (1.64-1.82) and 3.73 (3.53-3.93), respectively. PXF material was located on iris as well as anterior surface of lens and it was often bilateral. Participants living in two study sites and increasing age were associated with the incidence of PXF. The 15-year incidence of PXF glaucoma (95% CI) in participants ≥30 years of age at baseline was 0.33% (0.14-0.66).There is significant regional variation in incidence of PXF in south India which warrants further investigation.

Our previous research showed that increased phosphorylation of connexin (Cx)36 indicated extended coupling of AII amacrine cells (ACs) in the rod-dominant mouse myopic retina. This research will determine whether phosphorylation at serine 276 of Cx35-containing gap junctions increased in the myopic chicken, whose retina is cone-dominant. Refractive errors and ocular biometric dimensions of 7-days-old chickens were determined following 12 h and 7 days induction of myopia by a −10D lens. The expression pattern and size of Cx35-positive plaques were examined in the early (12 h) and compensated stages (7 days) of lens-induced myopia (LIM). At the same time, phosphorylation at serine 276 (functional assay) of Cx35 in strata 5 (S5) of the inner plexiform layer was investigated. The axial length of the 7 days LIM eyes was significantly longer than that of non-LIM controls (P

Myopia is a substantial public health problem worldwide. In the myopic retina, distant images are focused in front of the photoreceptors. The cells and mechanisms for retinal signaling that account either for emmetropization (i.e., normal refraction) or for refractive errors have remained elusive. Gap junctions play a key component in enhancement of signal transmission in visual pathways. AII amacrine cells (ACs), coupled by connexin36, segregate signals into ON and OFF pathways. Coupling between AII ACs is actively modulated through phosphorylation at serine 293 via dopamine in the mouse retina. In this study, form deprivation mouse myopia models were used to evaluate the expression patterns of connexin36-positive plaques (structural assay) and the state of connexin36 phosphorylation (functional assay) in AII ACs, which was green fluorescent protein-expressing in the Fam81a mouse line. Single-cell RNA sequencing showed dopaminergic synapse and gap junction pathways of AII ACs were downregulated in the myopic retina, although Gjd2 mRNA expression remained the same. Compared with the normal refractive eye, phosphorylation of connexin36 was increased in the myopic retina, but expression of connexin36 remained unchanged. This increased phosphorylation of Cx36 could indicate increased functional gap junction coupling of AII ACs in the myopic retina, a possible adaptation to adjust to the altered noisy signaling status.

Primary congenital glaucoma (PCG) is a severe autosomal recessive ocular disorder associated with considerable clinical and genetic heterogeneity. Recently, rare heterozygous alleles in the angiopoietin receptor-encoding gene TEK were implicated in PCG. We undertook this study to ascertain the second mutant allele in a large cohort (n = 337) of autosomal recessive PCG cases that carried heterozygous TEK mutations. Our investigations revealed 12 rare heterozygous missense mutations in TEK by targeted sequencing. Interestingly, four of these TEK mutations (p.E103D, p.I148T, p.Q214P, and p.G743A) co-occurred with three heterozygous mutations in another major PCG gene CYP1B1 (p.A115P, p.E229K, and p.R368H) in five families. The parents of these probands harbored either of the heterozygous TEK or CYP1B1 alleles and were asymptomatic, indicating a potential digenic mode of inheritance. Furthermore, we ascertained the interactions of TEK and CYP1B1 by co-transfection and pull-down assays in HEK293 cells. Ligand responsiveness of the wild-type and mutant TEK proteins was assessed in HUVECs using immunofluorescence analysis. We observed that recombinant TEK and CYP1B1 proteins interact with each other, while the disease-associated allelic combinations of TEK (p.E103D)::CYP1B1 (p.A115P), TEK (p.Q214P)::CYP1B1 (p.E229K), and TEK (p.I148T)::CYP1B1 (p.R368H) exhibit perturbed interaction. The mutations also diminished the ability of TEK to respond to ligand stimulation, indicating perturbed TEK signaling. Overall, our data suggest that interaction of TEK and CYP1B1 contributes to PCG pathogenesis and argue that TEK-CYP1B1 may perform overlapping as well as distinct functions in manifesting the disease etiology.

Humans preferentially match arbitrary words containing higher- and lower-frequency phonemes to angular and smooth shapes, respectively. Here, we investigated the role of visual experience in the development of audiovisual and audiohaptic sound–shape associations (SSAs) using a unique set of five groups: individuals who had suffered a transient period of congenital blindness through congenital bilateral dense cataracts before undergoing cataract-reversal surgeries (CC group), individuals with a history of developmental cataracts (DC group), individuals with congenital permanent blindness (CB group), individuals with late permanent blindness (LB group), and controls with typical sight (TS group). Whereas the TS and LB groups showed highly robust SSAs, the CB, CC, and DC groups did not—in any of the modality combinations tested. These results provide evidence for a protracted sensitive period during which aberrant vision prevents SSA acquisition. Moreover, the finding of a systematic SSA in the LB group demonstrates that representations acquired during the sensitive period are resilient to loss despite dramatically changed experience.