Changing trends in barriers to accessing eye care services in rural South India: results from the longitudinal Andhra Pradesh Eye Disease Study III (APEDS III) cohort.

PURPOSE: To assess the changing trends in barriers towards accessing eye care in a rural population cohort from Southern India. METHODS: This is a population-based longitudinal cohort of participants (the Andhra Pradesh Eye Disease study [APEDS]) from three rural regions of Telangana and Andhra Pradesh who were evaluated at baseline (APEDS I; 1996-2000), along with follow-ups at 10 years (APEDS II; 2009-10) and 15 years (APEDS III; 2012-2016). At follow-up, all participants 30 years and above were administered a structured questionnaire on barriers to uptake of eye care services. RESULTS: Of 3810 participants, 1449 had visual impairment (VI). Among them, 1302 noticed a reduction in vision over last five years and 722 sought treatment, a significant improvement from baseline (P < 0.001). Participants were more likely to seek treatment if they were educated (OR = 1.43, 95%CI: 1.07-1.89), had hypertension (OR = 1.36, 95%CI: 1.04-1.77), had VI from causes other than cataract and refractive error (OR = 2.49, 95%CI: 1.56-3.99) and were residents of Adilabad (OR = 2.21; 95%CI: 1.58-3.08) and Mahbubnagar (OR = 3.55; 95%CI: 2.48-5.08) districts. Those with moderate or worse VI were less likely to seek treatment (moderate VI: OR = 0.56; 95%CI: 0.42-0.75, severe VI: OR = 0.34; 95%CI: 0.19-0.57, blindness: OR = 0.38; 95%CI: 0.2-0.73). The most important barriers to uptake of services were, not perceiving loss of vision as a serious problem (25.9%), accepting it an aging process (21.4%) or due to economic reasons (16.0%). CONCLUSION: Personal and economic elements accounted for considerable amounts of barriers for utilization of eye care services. The uptake of services could be improved by addressing these specific barriers and risk factors for non-compliance.

The Quantitative Impact of Visual Function on Accelerometer-measured Physical Activity in Older United States Adults: A Nationwide Cross-sectional Analysis.

Purpose: To explore the impact of objective vision measures on novel metrics of objectively-measured physical activity (PA) in a nationally representative sample of United States (US) older adults. Design: Cross-sectional analysis using data from the National Health and Aging Trends Study. Participants: Adults had their distance and near visual acuity (VA) and contrast sensitivity (CS) tested. Any objective vision impairment (VI), defined as any VI in distance VA, near VA, or CS, was the primary exposure. Physical activity data were collected using the Actigraph CentrePoint Insight Watch worn for 7 days. Methods: Multivariable regression models were used to investigate the association between vision and PA measures. All analyses accounted for the survey design and models were adjusted for age, sex, race, living arrangement, education, and comorbidities. Main Outcome Measures: Physical activity metrics included (1) total daily activity (active minutes per day, number of active bouts, and mean length of active bouts), (2) activity fragmentation, and (3) time until 75% activity. An active bout was defined as ≥ 1 consecutive active minute. Activity fragmentation was defined as the probability of an active minute being followed by a sedentary minute, with higher values indicating more fragmented activity. Time until 75% activity was defined as the time taken to complete 75% of daily PA starting from their first active bout. Results: Among 723 participants, sampled from 10 443 338 older adults in the US, 30% had any objective VI. Any objective VI was significantly associated with lower number of active minutes per day (7.8% fewer [95% confidence interval {CI}: -13.6% to -1.7%]), shorter active bouts (7.0% shorter [95% CI: -12.3% to -1.4%]), and greater activity fragmentation (2.5% [95% CI: 0.8% to 4.2%]), while no associations were found with number of active bouts. Time until 75% activity did not significantly differ between adults with any objective VI and those without (P = 0.34). Conclusions: Older US adults with any objective VI displayed lower total daily activity, as well as more fragmented, shorter periods of PA, despite having a similar number of active bouts compared to their normally sighted counterparts. Implementing interventions that increase bout duration may help promote PA in adults with VI. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Visual Impairment and Real-World Home Physical Activity With Home Environment in an Older Population.

Importance: Physical activity levels are lower in visual impairment. However, additional factors, such as home environmental features, which can modify physical activity in this group, are unknown. Objective: To investigate the association between home environment features and home physical activity in patients with visual impairment. Design, Setting, and Participants: This cross-sectional study of clinical patients included participants with glaucoma suspect and primary glaucoma who were 60 years or older with varying degrees of visual field damage. Study participants were recruited from the Johns Hopkins Wilmer Eye Institute Glaucoma Clinic, Baltimore, Maryland, from September 2013 through March 2015. Data were analyzed from December 19, 2022, through December 25, 2022. Main Outcomes and Measures: Total in-home steps taken per day was the primary outcome measure; time in daily home physical activity and nonsedentary activity were secondary outcomes. Results: A total of 153 participants were included in analyses with mean age of 71 (SD, 7.8) years and 71 were female (46%). Sixty percent had more than 1 comorbid illness, about one-third took 5 or more prescription drugs, and median daily home steps were 1137. Median integrated visual field sensitivity was 28 dB. Better-eye median visual acuity in logMAR was 0.05 (20/22 Snellen equivalent). For every 0.1-log unit increment in average measured home lighting, participants took 5% more daily steps (rate ratio [RR], 1.05; 95% CI, 1.00-1.10; P = .04) and had a 3% faster average daily peak cadence (RR, 1.03; 95% CI, 1.01-1.05; P = .01). The average number of nonsedentary activity minutes (RR, 1.04; 95% CI, 1.00-1.07; P = .06), average bout duration (ß = 0.03; 95% CI, 0.00-.07; P = .06), and activity fragmentation (ß = -0.06; 95% CI, -0.13 to 0.00; P = .06) showed associations with home lighting. The number of hazards was not associated with any activity metric (steps: RR, 1.14; 95% CI, 0.96-1.34; P = .13; peak cadence: RR, 1.00; 95% CI, 0.93-1.08; P = .98; and nonsedentary time: RR, 1.11; 95% CI, 0.98-1.26; P = .11), nor was the frequency of hazards. Conclusions and Relevance: In this study, results demonstrated that home environment features, particularly lighting, may influence home activity metrics in older adults with visual impairment. Further prospective studies would be needed to confirm if home modifications can improve at-home activity.

Incidence of primary open angle glaucoma in the Andhra Pradesh Eye Disease Study (APEDS).

BACKGROUND: To report 15-year incidence rate of primary open angle glaucoma (POAG) in the Andhra Pradesh Eye Disease Study (APEDS). METHODS: A population-based longitudinal study was carried out at three rural study sites. Phakic participants aged ≥40 years who participated at baseline (APEDS I) and the mean 15-year follow-up visit (APEDS III) were included. A comprehensive ophthalmic examination was performed on all participants. Mean intraocular pressure (IOP) was average of IOPs of right and left eyes. The definition of glaucoma was based on the International Society of Geographical and Epidemiological Ophthalmology (ISGEO) classification. The main outcome measure was incidence of POAG during the follow-up period in participants without glaucoma or suspicion of glaucoma at baseline. RESULTS: Data from the available and eligible participants from the original cohort (1241/2790; 44.4%) were analysed. The mean age (standard deviation) of participants at baseline was 50.2 (8.1) years; 580 (46.7%) were men. Thirty-six participants developed POAG [bilateral in 17 (47.2%)] over 15 years. The incidence rate of POAG per 100-person years (95% confidence interval) was 2.83 (2.6, 3.08). Compared to baseline, the reduction in mean IOP [median (range) mm Hg] was -0.75 (-7.5, 9) in participants with incident POAG and -2.5 (-14.5, 14.5) in those without. The inter-visit difference in mean IOP was a significant risk factor on logistic regression analysis. CONCLUSION: We report the long-term incidence of POAG in rural India. A longitudinal change in IOP, specifically a less pronounced reduction in IOP with increasing age, was a novel risk factor.

Retinal ganglion cells encode differently in the myopic mouse retina?

The etiology of myopia remains unclear. This study investigated whether retinal ganglion cells (RGCs) in the myopic retina encode visual information differently from the normal retina and to determine the role of Connexin (Cx) 36 in this process. Generalized linear models (GLMs), which can capture stimulus-dependent changes in real neurons with spike timing precision and reliability, were used to predict RGCs responses to focused and defocused images in the retinas of wild-type (normal) and Lens-Induced Myopia (LIM) mice. As the predominant subunit of gap junctions in the mouse retina and a plausible modulator in myopia development, Cx36 knockout (KO) mice were used as a control for an intact retinal circuit. The kinetics of excitatory postsynaptic currents (EPSCs) of a single αRGC could reflect projection of both focused and defocused images in the retinas of normal and LIM, but not in the Cx36 knockout mice. Poisson GLMs revealed that RGC encoding of visual stimuli in the LIM retina was similar to that of the normal retina. In the LIM retinas, the linear-Gaussian GLM model with offset was a better fit for predicting the spike count under a focused image than the defocused image. Akaike information criterion (AIC) indicated that nonparametric GLM (np-GLM) model predicted focused/defocused images better in both LIM and normal retinas. However, the spike counts in 33% of αRGCs in LIM retinas were better fitted by exponential GLM (exp-GLM) under defocus, compared to only 13% αRGCs in normal retinas. The differences in encoding performance between LIM and normal retinas indicated the possible amendment and plasticity of the retinal circuit in myopic retinas. The absence of a similar response between Cx36 KO mice and normal/LIM mice might suggest that Cx36, which is associated with myopia development, plays a role in encoding focused and defocused images.

Visual impairment and blindness due to retinitis pigmentosa in India: 15-year follow-up of the Andhra Pradesh Eye Disease Study cohort.

Purpose: To assess the incidence, visual impairment, and blindness due to retinitis pigmentosa (RP) in a rural southern Indian cohort. Methods: This is a population-based longitudinal cohort study of participants with RP from the Andhra Pradesh Eye Disease Study (APEDS) cohorts I and III, respectively. The study included participants with RP of APEDS I who were followed until APEDS III. Their demographic data along with ocular features, fundus photographs, and visual fields (Humphrey) were collected. Descriptive statistics using mean ± standard deviation with interquartile range (IQR) were calculated. The main outcome measures were RP incidence, visual impairment, and blindness as per the World Health Organization (WHO) definitions. Results: At baseline (APEDS I), 7771 participants residing in three rural areas were examined. There were nine participants with RP with a mean age at baseline of 47.33 ± 10.89 years (IQR: 39-55). There was a male preponderance (6:3), and the mean best-corrected visual acuity (BCVA) of 18 eyes from nine participants with RP was 1.2 ± 0.72 logarithm of minimum angle of resolution (logMAR; IQR: 0.7-1.6). Over a mean follow-up duration of 15 years, 5395/7771 (69.4%) were re-examined, which included seven RP participants from APEDS 1. Additionally, two new participants with RP were identified; so, the overall incidence was 370/ million in 15 years (24.7/million per year). The mean BCVA of 14 eyes of seven participants with RP who were re-examined in APEDS III was 2.17 ± 0.56 logMAR (IQR: 1.8-2.6), and five of these seven participants with RP developed incident blindness during the follow-up period. Conclusion: RP is a prevalent disease in southern India that warrants appropriate strategies to prevent this condition.

Regional variation in the incidence of pseudo-exfoliation in the Andhra Pradesh Eye Disease Study (APEDS).

BACKGROUND: 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. METHODS: 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. RESULTS: 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 aged <30 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). CONCLUSION: There is significant regional variation in incidence of PXF in south India which warrants further investigation.

The Effect of Low-Dose Atropine on Alpha Ganglion Cell Signaling in the Mouse Retina.

Low-dose atropine helps to control myopia progression with few side effects. However, the impact of atropine, a non-selective muscarinic Acetylcholine (ACh) receptor antagonist, on retinal ganglion cells (RGCs) remains unclear. After immersing the cornea and adjacent conjunctiva of enucleated eyes in 0.05% (approximately 800 µM) atropine solution for 30 min, the atropine concentration reached in the retina was below 2 µM. After direct superfusion of the retina with 1 µM atropine (considering that the clinical application of 0.05% atropine eye drops will be diluted over time due to tear flow for 30 min), no noticeable changes in the morphology of ON and OFF alpha RGCs (αRGCs) were observed. Atropine affected the light-evoked responses of ON and OFF αRGCs in a dose- and time-dependent fashion. Direct application of less than 100 µM atropine on the retina did not affect light-evoked responses. The time latency of light-induced responses of ON or OFF αRGCs did not change after the application of 0.05-100 µM atropine for 5 min. However, 50 µM atropine extended the threshold of joint inter-spike interval (ISI) distribution of the RGCs. These results indicated that low-dose atropine (<0.5 µM; equal to 1% atropine topical application) did not interfere with spike frequency, the pattern of synchronized firing between OFF αRGCs, or the threshold of joint ISI distribution of αRGCs. The application of atropine unmasked inhibition to induce ON responses from certain OFF RGCs, possibly via the GABAergic pathway, potentially affecting visual information processing.

Functional connexin35 increased in the myopic chicken retina.

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 < 0.05). Anti-phospho-Ser276 (Ser276-P)-labeled plaques were significantly increased in LIM retinas at both 12 h and 7 days. The density of Ser276-P of Cx35 was observed to increase after 12 h LIM. In the meanwhile, the areas of existing Cx35 plaques did not change. As there was more phosphorylation of connexin35 at Ser276 at both the early and late stages (12 h) and 7 days of LIM chicken retinal activity, the coupling with ACs could be increased in myopia development of the cone-dominated chicken retina.

Fifteen-Year Incidence Rate of Primary Angle Closure Disease in the Andhra Pradesh Eye Disease Study.

PURPOSE: To report on the 15-year incidence of primary angle closure disease (PACD) among participants aged ≥40 years in rural southern India DESIGN: Population-based longitudinal incidence rate study METHODS: Setting: 3 rural study centres. STUDY POPULATION: Phakic participants aged ≥40 years who participated in both examination time points. OBSERVATION PROCEDURES: All participants at the baseline and at the mean 15-year follow-up visit underwent a detailed interview, anthropometry, blood pressure measurement, and comprehensive eye examination. Automated perimetry was attempted based on predefined criteria. Main outcome measures included development of any form of PACD, as defined by the International Society for Geographical and Epidemiological Ophthalmology (ISGEO), during the follow-up period in phakic participants, who did not have the disease at baseline. RESULTS: We analyzed data obtained from 1,197 (81.4% out of available 1,470) participants to calculate the incidence of the disease. The mean age (standard deviation) of the study participants at the baseline was 50.2 (8.1) years, with 670 male (45.5%) and 800 female (54.4%) participants. The incidence rate per 100 person-years (95% confidence interval) for primary angle closure suspect, primary angle closure, and primary angle closure glaucoma was 8.8 (8.4, 9.2), 6.2 (5.9, 6.6), and 1.6 (1.4, 1.8), respectively. Thus, the incidence of all forms of PACD was 16.4 (15.9, 17) per 100 person-years. On logistic regression analysis, female gender was a significant risk factor whereas presence of myopia was protective. CONCLUSIONS: This study reports long-term incidence of PACD from rural India. It has implications for eye health care policies, strategies, and planning.

Incidence, Incident Causes, and Risk Factors of Visual Impairment and Blindness in a Rural Population in India: 15-Year Follow-up of the Andhra Pradesh Eye Disease Study.

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.

Fifteen-year incidence rate and risk factors of pterygium in the Southern Indian state of Andhra Pradesh.

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) (<18.5) (RR: 1.25, 95% CI 1.02 to 1.55) were associated with increased risk of pterygium. 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.

Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model.

All neurodegenerative diseases involve a relatively long period of timeframe from the onset of the disease to complete loss of functions. Extending this timeframe, even at a reduced level of function, would improve the quality of life of patients with these devastating diseases. The retina, as the part of the central nervous system and a frequent site of many distressing neurodegenerative disease, provides an ideal model to investigate the feasibility of extending the functional timeframe through pharmacologic intervention. Retinitis Pigmentosa (RP) is a group of blinding diseases. Although the rate of progression and degree of visual loss varies, there is usually a prolonged time before patients totally lose their photoreceptors and vision. It is believed that inhibitory mechanisms are still intact and may become relatively strong after the gradual loss of photoreceptors in RP patients. Therefore, it is possible that light-evoked responses of retinal ganglion cells and visual information processes in retinal circuits could be "unmasked" by blocking these inhibitory mechanisms restoring some level of visual function. Our results indicate that if the inhibition in the inner retina was unmasked in the retina of the rd10 mouse (the well-characterized RP mimicking, clinically relevant mouse model), the light-evoked responses of many retinal ganglion cells can be induced and restore their normal light sensitivity. GABA A receptor plays a major role in this masking inhibition. ERG b-wave and behavioral tests of spatial vision partly recovered after the application of PTX. Hence, removing retinal inhibition unmasks signalling mediated by surviving cones, thereby restoring some degree of visual function. These results may offer a novel strategy to restore the visual function with the surviving cones in RP patients and other gradual and progressive neurodegenerative diseases.

Increased Connexin36 Phosphorylation in AII Amacrine Cell Coupling of the Mouse Myopic Retina.

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.

Defocused Images Change Multineuronal Firing Patterns in the Mouse Retina.

Myopia is a major public health problem, affecting one third of the population over 12 years old in the United States and more than 80% of people in Hong Kong. Myopia is attributable to elongation of the eyeball in response to defocused images that alter eye growth and refraction. It is known that the retina can sense the focus of an image, but the effects of defocused images on signaling of population of retinal ganglion cells (RGCs) that account either for emmetropization or refractive errors has still to be elucidated. Thorough knowledge of the underlying mechanisms could provide insight to understanding myopia. In this study, we found that focused and defocused images can change both excitatory and inhibitory conductance of ON alpha, OFF alpha and ON-OFF retinal ganglion cells in the mouse retina. The firing patterns of population of RGCs vary under the different powers of defocused images and can be affected by dopamine receptor agonists/antagonists' application. OFF-delayed RGCs or displaced amacrine cells (dACs) with time latency of more than 0.3 s had synchrony firing with other RGCs and/or dACs. These spatial synchrony firing patterns between OFF-delayed cell and other RGCs/dACs were significantly changed by defocused image, which may relate to edge detection. The results suggested that defocused images induced changes in the multineuronal firing patterns and whole cell conductance in the mouse retina. The multineuronal firing patterns can be affected by dopamine receptors' agonists and antagonists. Synchronous firing of OFF-delayed cells is possibly related to edge detection, and understanding of this process may reveal a potential therapeutic target for myopia patients.

Color vision in sight recovery individuals.

BACKGROUND: Color vision has been consistently shown to be unaffected in animals that are raised in dark or in color-deprived environments. However, there are only a few studies that directly addressed the effect of congenital visual deprivation in color perception in humans. OBJECTIVE: The goal of the current study was to assess the effect of congenital visual deprivation on color vision using a panel based color arrangement test. METHODS: We investigated the recovery of color vision using the Farnsworth D15 test in a group of individuals who had experienced visual deprivation since birth due to bilateral dense congenital cataracts before undergoing cataract-reversal surgery (Congenital cataract, CC, n = 12). In addition, we tested two groups of control participants: (1) individuals who had had non-dense congenital cataract or developed cataract later in their childhood (Developmental cataract, DC, n = 10), and (2) sighted controls with normal or corrected to normal vision (n = 14). Based on the methods proposed by Vingrys and King-Smith (1988), we derived the following metrics of color vision performance: (1) total error score, (2) confusion index, (3) confusion angle, and (4) selectivity index. RESULTS: All of the measured indices of color vision performance were unaltered by a period of congenital visual deprivation. CONCLUSIONS: Our results support the view that, development of visual functions such as color discrimination and color arrangement does not depend on typical visual experience during a sensitive phase in early childhood.

A Protracted Sensitive Period Regulates the Development of Cross-Modal Sound-Shape Associations in Humans.

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.

Angiopoietin receptor TEK interacts with CYP1B1 in primary congenital glaucoma.

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.

Population-Based Assessment of Unilateral Visual Impairment in the South Indian State of Andhra Pradesh: Rapid Assessment of Visual Impairment (RAVI) Project.

PURPOSE: To assess the prevalence and causes of unilateral visual impairment (VI) in the South Indian state of Andhra Pradesh. METHODS: A population-based cross-sectional study was conducted among individuals aged ≥40 years in one urban and two rural locations, using rapid assessment methodology. A 2-stage cluster random sampling method was used to select 7800 individuals from 156 clusters. Distance visual acuity (VA) was assessed using a standard Snellen chart at a distance of 6 m. Eye examinations were conducted using a torchlight and distance direct ophthalmoscopy. Unilateral VI was defined as presenting VA <6/18 in one eye and presenting VA ≥6/18 in the other, and included moderate unilateral VI (<6/18 to 6/60) and unilateral blindness (<6/60). RESULTS: In total, 7378 individuals (94.6%) were examined. After excluding 918 individuals with VI in the better eye, data were analyzed for the remaining 6460 individuals. Among those included in the analysis, mean age was 50 years (standard deviation 9.6 years), 46.7% were male, 58.9% had no education, and 34.1% were urban residents. The prevalence of unilateral VI was 11.3% (95% confidence interval 10.5-12.1%; n = 730). Uncorrected refractive error was found to be the leading cause (44%; n = 321) of unilateral VI followed by cataract (39.7%; n = 290). CONCLUSIONS: Unilateral VI is common in the South Indian state of Andhra Pradesh. As most of this VI can be addressed with interventions such as cataract surgery and spectacles, service models need to be streamlined to address this need.