Identifying genetic defects in oculocutaneous albinism patients of West Bengal, Eastern India.

BACKGROUND: Oculocutaneous albinism (OCA) is a congenital heterogeneous group of autosomal recessive disorders characterized by the absence or loss of melanin in the skin, eyes and hair of the affected individuals. Based on the mutated gene, OCA has been classified into eight sub-types (OCA1-8) with overlapping clinical phenotypes. Mutations in the TYR gene cause OCA1, the most prevalent OCA worldwide including India. Mutations in OCA2 and SLC45A2, both of which regulate melanosomal pH that is critical to TYR activity, cause OCA2 and OCA4 respectively, the other common OCA subtypes in India. METHODS: In the present study, we have included 54 OCA-affected cases from 41 unrelated families representing 16 different marriage/ethnic groups from 17 districts of West Bengal, India. We pursued a PCR-sequencing based approach followed by bioinformatic analysis to identify mutations in TYR, OCA2 and SLC45A2 genes. RESULTS: Mutations were detected in 27 of the 54 (50%) OCA patients from 18 unrelated families, representing 9 different marriage/ethnic groups from 11 districts of West Bengal. Three TYR variants: NM_000372.4: c.391 A > G, NP_000363.1: p. Lys131Glu; NM_000372.4: c.1037G > T; NP_000363.1: p. Gly346Val, NM_000372.4: c.715 C > T; NP_000363.1:p.Arg239Trp was identified for the first time in Eastern Indian OCA cases. A novel nonsense variant: NM_016180.5: c.389 T > A, NP_057264.4: p. Leu130* and a novel synonymous variation NM_016180.5: c.1092 A > G; NP_057264.4: p.364E = were identified in SLC45A2. Additionally, NM_016180.5: c.904A > T; NP_057264.4: p. Thre302Ser was identified for the first time in any Eastern Indian OCA case. We identified 2 previously reported mutations in OCA2. In concordance with previous reports, NM_000372.4: c.832C > T, NP_000363.1: p. (Arg278*) was the commonest TYR mutation. CONCLUSION: The results of our study enrich the mutational spectrum of the known OCA causing genes in Eastern India, which would facilitate accurate diagnosis, familial screening, carrier detection and containment of the disease load.

Design and delivery of the Refractive Errors Among Children (REACH) school-based eye health programme in India.

CLINICAL RELEVANCE: Optimisation of vision screening programmes can result the detection of refractive anomalies in a high proportion of school children. BACKGROUND: The Refractive Errors Among Children (REACH) programme aims to optimise outcomes of school-based vision screening in India by collaborating with hospitals and monitoring eye care throughout school attendance. METHODS: REACH delivers school vision screening using pocket vision screeners (cards presenting rows of seven 0.2 logMAR Sloan letters at a 3 m viewing distance) in five states across India. Children who fail screening are referred for detailed evaluation including refraction, those requiring cycloplegic refraction are referred to partner hospitals. Spectacles are dispensed as needed and compliance is assessed. All data are recorded electronically. RESULTS: Out of 2,240,805 children aged 5 to 18 (mean 11.5; SD ±3.3) years, 2,024,053 have undergone REACH screening in 10,309 schools predominantly in rural locations (78.7%) and government-funded (76%). Of those screened, 174,706 (8.6%) underwent detailed evaluation. A higher proportion of children in private or urban schools (11.8% and 10.4% respectively) were referred for detailed evaluation than those in government-funded or rural schools (5.9% and 7.2%, respectively; p < 0.001). The proportion referred for detailed evaluation differed by state (p < 0.001), from 4.0% in West Bengal to 14.4% in Kerala. CONCLUSION: The REACH programme screened a high proportion of school children, providing further care and follow-up to optimise visual outcomes.

The economic and social costs of visual impairment and blindness in India.

Purpose: To provide a current estimate of the economic and social costs (or welfare costs) of visual impairment and blindness in India. Methods: Using evidence from the recently conducted Blindness and Visual Impairment Survey across India, the Lancet Global Health Commission on Global Eye Health and other sources, we developed an economic model that estimates the costs of reduced employment, elevated mortality risk, education loss for children, productivity loss in employment, welfare loss for the unemployed, and caregiver costs associated with moderate and severe visual impairment (MSVI) and blindness. Probabilistic sensitivity analyses were also conducted by varying key parameters simultaneously. Results: The costs of MSVI and blindness in India in 2019 are estimated at INR 1,158 billion (range: INR 947-1,427 billion) or $54.4 billion at purchasing power parity exchange rates (range: $44.5-67.0 billion), accounting for all six cost streams. The largest cost was for the loss of employment, whereas the the second largest cost was for caregiver time. A more conservative estimate focusing only on employment loss and elevated mortality risk yielded a cost of INR 504 billion (range: INR 348-621 billion) or $23.7 billion (range: $16.3-29.2 billion). Conclusion: Poor eye health imposes a non-trivial recurring cost to the Indian economy equivalent to 0.47% to 0.70% of GDP in the primary scenario, a substantial constraint on the country's growth aspirations. Furthermore, the absolute costs of poor eye health will increase over time as India ages and becomes wealthier unless further progress is made in reducing the prevalence of MSVI and blindness.

Strategies for cataract and uncorrected refractive error case finding in India: Costs and cost-effectiveness at scale.

Background: India has the largest number of individuals suffering from visual impairment and blindness in the world. Recent surveys indicate that demand-based factors prevent more than 80% of people from seeking appropriate eye services, suggesting the need to scale up cost-effective case finding strategies. We assessed total costs and cost-effectiveness of multiple strategies to identify and encourage people to initiate corrective eye services. Methods: Using administrative and financial data from six Indian eye health providers, we conduct a retrospective micro-costing analysis of five case finding interventions that covered 1·4 million people served at primary eye care facilities (vision centers), 330,000 children screened at school, 310,000 people screened at eye camps and 290,000 people screened via door-to-door campaigns over one year. For four interventions, we estimate total provider costs, provider costs attributable to case finding and treatment initiation for uncorrected refractive error (URE) and cataracts, and the societal cost per DALY averted. We also estimate provider costs of deploying teleophthalmology capability within vision centers. Point estimates were calculated from provided data with confidence intervals determined by varying parameters probabilistically across 10,000 Monte Carlo simulations. Findings: Case finding and treatment initiation costs are lowest for eye camps (URE: $8·0 per case, 95% CI: 3·4-14·4; cataracts: $13·7 per case, 95% CI: 5·6-27·0) and vision centers (URE: $10·8 per case, 95% CI: 8·0-14·4; cataracts: $11·9 per case, 95% CI: 8·8-15·9). Door-to-door screening is as cost-effective for identifying and encouraging surgery for cataracts albeit with large uncertainty ($11·3 per case, 95% CI: 2·2 to 56·2), and more costly for initiating spectacles for URE ($25·8 per case, 95% CI: 24·1 to 30·7). School screening has the highest case finding and treatment initiation costs for URE ($29·3 per case, 95% CI: 15·5 to 49·6) due to the lower prevalence of eye problems in school aged children. The annualized cost of operating a vision center, excluding procurement of spectacles, is estimated at $11,707 (95% CI: 8,722-15,492). Adding teleophthalmology capability increases annualized costs by $1,271 per facility (95% CI: 181 to 3,340). Compared to baseline care, eye camps have an incremental cost-effectiveness ratio (ICER) of $143 per DALY (95% CI: 93-251). Vision centers have an ICER of $262 per DALY (95% CI: 175-431) and were able to reach substantially more patients than any other strategy. Interpretation: Policy makers are expected to consider cost-effective case finding strategies when budgeting for eye health in India. Screening camps and vision centers are the most cost-effective strategies for identifying and encouraging individuals to undertake corrective eye services, with vision centers likely to be most cost-effective at greater scale. Investment in eye health continues to be very cost-effective in India. Funding: The study was funded by the Seva Foundation.

Compliance of spectacle wear among school children.

Purpose: In India, school eye screening is an important component of the National Programme for the Control of Blindness providing spectacles free of cost to children from primary section. The primary aim of this study was to know the compliance of wearing spectacles provided during school screening program and to find out reasons for noncompliance. The secondary aim of this study was to get information regarding the types of modifications required in the school eye screening program to improve the compliance level. Methods: It was a cross-sectional follow-up study involving school children of age group 10-16 years, class 5-9 from different parts of the country. Public or private schools were randomly selected based on their distance from the base hospitals/partner organizations. Data were collected by standard format directly from the students after informed written consent from school principal or class teacher. Results: The utilization of spectacles was found to be only 29.8% (n = 289) within 2 years of receiving the spectacles. Thirty-five percent (n = 108) students were using spectacles with less than 0.75 D. Appearance of the frame was a deciding factor. It was observed that the frames provided by the DBCS were especially not liked by the children. Twenty-five percent (n = 79) children were found to be wearing adult frames. Conclusion: Less than a third of the students were compliant with their spectacle prescription in this study. To improve the compliance, children should not be prescribed spectacles for nonsignificant refractive errors, should be given choices for frames and quality of work being conducted under school screening program needs a review.

Mapping the TYR gene reveals novel and previously reported variants in Eastern Indian patients highlighting preponderance of the same changes in multiple unrelated ethnicities.

Oculocutaneous albinism (OCA) is a group of congenital autosomal recessive disorders with seven known subtypes (OCA1-OCA7) characterized by loss or absence of pigmentation in the skin, hair, and eyes. OCA1, caused by pathogenic variations in the tyrosinase (TYR) gene, has been documented to be the most prevalent subtype across the world including India. In the present study, we recruited 53 OCA-affected individuals from 45 unrelated families belonging to 20 different marriage groups/ethnicities of 15 different districts of West Bengal. We took a targeted sequencing-based approach to find the causal variations in the TYR gene. We report here identification of two novel potentially pathogenic variations [NM_000372.4:c.614C>T, NP_000363.1:p.(Pro205Leu), and NM_000372.4:c.1036+1=/G>T], one novel synonymous TYR variant [NM_000372.4:c.204=/A>G, NP_000363.1:p.(Gln68=)], two pathogenic variations documented for the first time in Indian OCA cases [NM_000372.4:c.1147G>A, NP_000363.1:p.(Asp383Asn), and NM_000372.4:c.585G>A, NP_000363.1:p.(Trp195*)], along with nine previously reported pathogenic variants in 36 out of 53 (∼68%) patients recruited. We report common haplotype backgrounds for the two most prevalent variations [NM_000372.4:c.124G>A, NM_000372.4:c.832C>T] in cases belonging to different marriage/ethnic groups, suggesting a possible founder effect. To our knowledge, this is the most comprehensive genetic study on OCA1 from India, firmly establishing OCA1 as the commonest form of albinism in this part of the world.

Primary eye care in India - The vision center model.

The World Health Organization (WHO) Global Action Plan (GAP) 2014-19 emphasize providing Comprehensive Eye Care (CEC) using the health system approach to achieve Universal Eye Health Coverage (UEHC). An important aspect of CEC is Primary Eye Care (PEC). The scope of PEC varies significantly with primary health workers providing PEC in most parts of the developing world, whereas in developed nations PEC is provided by specialized personnel such as optometrists. This article focuses on delivery of PEC models in India, specifically through the vision center (VC) approach. VCs are part of a larger eye care network and provide PEC in remote rural areas of the country. The authors describe the how PEC is delivered in more than 300 VCs operated by six mentor hospitals in India under the Global Sight Initiative (GSI). Key factors compared include: The role of leadership; human resource planning, including recruitment and retention; service delivery; leveraging technology for planning and reaching key populations; financial sustainability; supply chain management; and quality and monitoring. It also discusses issues to be considered to strengthen VCs as we move ahead towards our collective goal of achieving UEHC and eliminating avoidable blindness.

Prevalence and causes of avoidable blindness and visual impairment, including the prevalence of diabetic retinopathy in Siwan district of Bihar, India: A population-based survey.

Purpose: The aim of this study was to estimate the prevalence and causes of visual impairment (VI) and blindness and diabetic retinopathy (DR) in Siwan district, Bihar. Methods: A population-based cross-sectional study was done from January to March 2016 using the Rapid Assessment of Avoidable Blindness 6 (RAAB 6, incorporating DR module) methodology. All individuals aged ≥50 years were examined in 57 randomly selected clusters within the district. Results: A total of 3476 individuals were enumerated and 3189 (92%) completed examination. The overall prevalence of blindness and severe VI was 2.2% (95% confidence interval (CI): 1.6-2.8) and 3.4% (95% CI: 2.6-4.3), respectively. Untreated cataract was the leading cause of blindness (73%) and severe VI (93%). The cataract surgical coverage (CSC) at <3/60 was 71.5% for eyes and 89.3% for persons in this sample and the CSC was similar between the genders. Refractive error (71%) was the primary cause of early VI. The overall prevalence of known and newly diagnosed diabetes was 6.3% (95% CI, 5.4-7.2%). Prevalence of any DR, maculopathy, and sight-threatening DR was 15, 12.4, and 6%, respectively. Conclusion: To conclude, as compared to previous reports, the prevalence of blindness and DR in Siwan district of Bihar was found to be lower and the CSC was higher. However, the problem of avoidable blindness remains a major problem in this region.

First Rapid Assessment of Avoidable Blindness Survey in the Maldives: Prevalence and Causes of Blindness and Cataract Surgery.

PURPOSE: A nationwide rapid assessment of avoidable blindness survey was undertaken in the Maldives among people aged 50 years or more to assess the prevalence and causes of blindness and visual impairment, cataract surgical coverage, cataract surgery outcome, and barriers to uptake of cataract surgical services. DESIGN: Prospective population-based study. METHODS: In the cluster sampling probability proportionate to size method, 3100 participants in 62 clusters across all 20 atolls were enrolled through house-to-house visits. They were examined in clusters by an ophthalmologist-led team. Data was recorded in mRAAB version 1.25 software on a smartphone. RESULTS: The age-sex standardized prevalence of blindness was 2.0% [95% confidence interval (CI), 1.5-2.6]. Cataract was the leading cause of blindness (51.4%) and uncorrected refractive error was the leading cause of visual impairment (50.9%). Blindness was more prevalent in higher age groups and women (16.3%). Cataract surgical coverage was 86% in cataract blind eyes and 93.5% in cataract blind persons. Good visual outcome in cataract operated eyes was 67.9% (presenting) and 76.6% (best corrected visual acuity). In this study, 48.1% of people had received cataract surgery in neighboring countries. Important barriers for not using the services were "did not feel the need" (29.7%) and "treatment deferred" (33.3%). CONCLUSIONS: Cataract surgical coverage is good, though nearly half the people received surgery outside the Maldives. Cataract surgery outcomes are below World Health Organization standards. Some barriers could be overcome with additional human resources and training to improve cataract surgical outcomes, which could encourage greater uptake of services within the country.

Spectrum of candidate gene mutations associated with Indian familial oculocutaneous and ocular albinism.

PURPOSE: Albinism is a group of genetic disorders, showing a broad spectrum of different phenotypes. The purpose of this study was to screen known candidate genes for oculocutaneous albinism (OCA) and ocular albinism (OA) mutations in Indian patients. METHODS: Blood samples were collected from 23 probands and 13 affected family members from 23 genetically unrelated Indian families (22 diagnosed as OCA and 1 diagnosed as OA) and analyzed by bidirectional DNA sequencing of the classic OCA genes--tyrosinase (TYR, or oculocutaneous albinism IA), pink eyed dilution (P; or oculocutaneous albinism II (OCA2]), tyrosinase-related protein 1 (TYRP1), solute carrier family 45, member 2 (SLC45A2; or membrane-associated transporter protein [MATP])--and the OA1 gene, G protein-coupled receptor 143 (GPR143). RESULTS: Three missense mutations, c. 715 C>T (R239W), c. 896 G>A (R299H), c.1255 G>A (G419R), and one termination c. 832 C>T (R278X), were identified in TYR, as well as one novel mutation, c.1453 G>A (G485R) in P. One novel single nucleotide polymorphism (SNP) was identified in both TYR and P; few reported SNPs were identified. The G>A base substitution caused relatively conservative amino acid changes, which altered glycine to arginine residues within the topological domain. The novel OCA2 mutation was not present in 100 control samples. This study identified two probands carrying mutations alone, 16 probands carrying SNPs alone, 4 probands carrying both mutations and SNPs and only one proband carrying neither mutations nor SNPs. CONCLUSIONS: Although sequence analysis was performed with all five candidate genes, only four (17.39%) of the 23 probands showed mutations in TYR and 2 probands (8.69%) showed an unreported novel mutation in P. Genetic counseling for phenotypical diagnosis and genetic mutation screening of these genes will help to minimize the incidence of OCA and OA in future generations.

Genetic analysis of oculocutaneous albinism type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR Gene.

PURPOSE: Oculocutaneous albinism type 1 (OCA1) patients demonstrate a partial or total lack of melanin in the skin, hair and eye. OCA1 is an autosomal recessive genetic disorder caused by mutations in the TYR gene located at chromosome band 11q14-q25. The purpose of this study was to carry out genetic analysis of OCA1 in Indian families. METHODS: Genomic DNA was isolated from blood leukocytes of all the individuals in this study. Haplotype analysis was performed at the TYR locus using informative microsatellite markers. Eight sets of primers were used to amplify the entire coding region of the TYR gene for bidirectional direct sequencing mutation analysis. RESULTS: Two novel deletions (c.937del8, c.1379del2) and a previously known nonsense mutation (R278X) in the TYR gene were identified from a total of 8 oculocutaneous albinism patients in India. CONCLUSIONS: Our study reports the distribution of two novel frameshift and a previously reported nonsense mutations in four OCA1 families from the Indian population. These findings will contribute to the development of a diagnostic method for OCA1 carrier status and genetic counseling for OCA1 affected families.