Identification of a novel locus on 2q for autosomal dominant high-grade myopia.

PURPOSE. Myopia, or nearsightedness, is a visual disorder of high and growing prevalence in the United States and in other countries. Pathologic high myopia, or myopia of ≤-6.00 D, predisposes individuals to retinal detachment, macular degeneration, cataracts, and glaucoma. Autosomal dominant (AD) nonsyndromic high-grade myopia has been mapped to loci on 18p11.31, 12q21-q23, 17q21-q23, and 7q36. This is the report of significant linkage to a novel locus on the long arm of chromosome 2 in a large, multigenerational family with AD high-grade myopia. METHODS. The family contains 31 participating members (14 affected). The average spherical refractive error for affected individuals was -14.46 D (range, -7.25 to -27.00). Before a genome screening was undertaken, linkage to intragenic or flanking markers for the myopic genetic syndromes of Stickler syndrome types I, II, and III; Marfan syndrome; and juvenile glaucoma were ruled out. In addition, no linkage was found to the known AD high-grade myopia loci listed above. A full genome screen of the family was performed with 382 microsatellite markers with an average intermarker distance of 10 cM. SimWalk2 software was used for multipoint linkage analysis based on an AD model with a penetrance of 90% and a disease allele frequency of 0.01. RESULTS. Fine-point mapping with an additional nine custommade and five commercial markers yielded a maximum two-point lod score of 5.67 at marker D2S2348. Results of multipoint analysis indicate that the 1-unit support intervals for this new locus spans approximately 9.1 cM from (238.7 to 247.8 cM) on the chromosome 2 genetic map at q37.1. CONCLUSIONS. A novel locus for AD high-grade myopia has been determined, providing further evidence of genetic heterogeneity for this disorder

Genetic linkage study of high-grade myopia in a Hutterite population from South Dakota

PURPOSE: Myopia is a common, complex disorder, and severe forms have implications for blindness due to increased risk of premature cataracts, glaucoma, retinal detachment, and macular degeneration. Autosomal dominant (AD) non-syndromic high-grade myopia has been mapped to chromosomes 18p11.31, 12q21-23, 17q21-23, 7q36, 2q37.1, 7p15.3, 15q12-13, 3q26, 4q12, 8p23, 4q22-q27, 1p36, and Xq23-q25. Here, we demonstrate evidence of linkage for AD non-syndromic high-grade myopia in a large Hutterite family to a locus on chromosome 10q21.1. METHODS: After clinical evaluation, genomic DNA was genotyped from 29 members of a Hutterite family from South Dakota (7 affected). The average refractive error of affected individuals was -7.04 diopters. Microsatellite markers were used to exclude linkage to the known AD nonsyndromic high-grade myopia loci as well as to syndromic high-grade myopia loci. A genome screen was then performed using 382 markers with an average inter-marker distance of 10 cM followed by fine-point mapping in all regions of the genome that gave positive LOD scores. SimWalk2 software was used for multipoint linkage based on AD and autosomal recessive (AR) models with a penetrance of 90% and a disease allele frequency of 0.001. RESULTS: A maximum multipoint LOD score of 3.22 was achieved under an AD model at microsatellite marker D10S1643. Fine point mapping and haplotype analysis defined a critical region of 2.67 cM on chromosome 10q21.1. Haplotype analysis demonstrated two distinct haplotypes segregating with high-grade myopia, indicative of two distinct mutations occurring in the same gene. CONCLUSIONS: We have identified a presumptive myopia locus for high-grade myopia based on linkage and haplotype analysis

Survey of Childhood Blindness and Visual Impairment in Botswana

Background/aims In terms of blind-person years, the worldwide burden of childhood blindness is second only to cataracts. In many developing countries, 30–72% of childhood blindness is avoidable. The authors conducted this study to determine the causes of childhood blindness and visual impairment (VI) in Botswana, a middle-income country with limited access to ophthalmic care. Methods This study was conducted over 4 weeks in eight cities and villages in Botswana. Children were recruited through a radio advertisement and local outreach programmes. Those ≤15 years of age with visual acuity \u3c6/18 in either eye were enrolled. The WHO/Prevention of Blindness Eye Examination Record for Children with Blindness and Low Vision was used to record data. Results The authors enrolled 241 children, 79 with unilateral and 162 with bilateral VI. Of unilateral cases, 89% were avoidable: 23% preventable (83% trauma-related) and 66% treatable (40% refractive error and 31% amblyopia). Of bilateral cases, 63% were avoidable: 5% preventable and 58% treatable (33% refractive error and 31% congenital cataracts). Conclusion Refractive error, which is easily correctable with glasses, is the most common cause of bilateral VI, with cataracts a close second. A nationwide intervention is currently being planned to reduce the burden of avoidable childhood VI in Botswana

Reliability of telemedicine for real-time paediatric ophthalmology consultations

Background/aimsTo assess the accuracy of real-time telemedicine to diagnose and manage paediatric eye conditions.MethodsDesign: Prospective, non-inferiority study analysing agreement in diagnoses and management plans between telemedicine and in-person examinations. Setting: Paediatric ophthalmology clinic. Population: Children 0-17 years, English-speaking or Spanish-speaking, able to participate in age-appropriate manner, either previously seen by the optometrist and required ophthalmology referral or newly referred from outside source. Procedures: Paediatric optometrist conducted examinations using digital equipment and streamed live to a paediatric ophthalmologist who recorded diagnoses and management plans, then re-examined patients in-person. Subjects were masked to the fact they would see the ophthalmologist in-person, same-day. Main outcome measures: Discrepancy in management plan or diagnosis between telemedicine and in-person examinations. Non-inferiority threshold was <1.5% for management plan or <15% for diagnosis discrepancies.Results210 patients participated in 348 examinations. 131 (62.4%) had strabismus as primary diagnosis. In these patients, excellent and almost perfect agreement was observed for angle measurements (intraclass correlation coefficients=0.98-1.00) and disease categorisation (kappa=0.94-1.00) (p<0.0001 in all cases). No primary diagnoses changed, and no management plans changed following in-person examination. 54/55 patients who consented for surgery at the initial visit did so while masked to receiving an in-person examination. Families felt comfortable with the quality of the telemedicine examination (98.5%) and would participate in another in the future (97.1%).ConclusionPaediatric ophthalmic conditions can be reliably diagnosed and managed via telemedicine. Access for underserved populations may be improved by collaboration between ophthalmologists and optometrists using this technology