Establishing a Pediatric Ophthalmology Service in Malawi: Developments in Childhood Cataract Surgery.

PURPOSE: The purpose of this study is to report on the establishment of a Pediatric Ophthalmology Service for Malawi using childhood cataract surgery as a surrogate measure of its effectiveness. MATERIALS AND METHODS: A retrospective review of pediatric cataract surgery at Lions Sight First Eye Hospital, Blantyre, between 2011 and 2016. The paucity of comprehensive records allowed for the sampling of a maximum of 25 cases/year (n = 150) for comparison. Theatre records and population statistics were used to calculate childhood cataract surgical rates (CCSR). RESULTS: A total of 949 cataract operations were performed during the six years studied - 55.8% of these were boys. The number of operations per year remained generally stable. Of the 150 cases reviewed, the mean age at presentation was 6.01 years, with a trend toward a slightly younger age over the period. Over the years studied, the geographical distribution of referrals became more reflective of the population's distribution. Where the logarithm of the minimum angle of resolution (LogMAR) visions were available, these demonstrated a mean improvement from 2.008 (n = 43) preoperatively to 0.613 (n = 51) postoperatively. The mean follow-up was 106 days (0 days-3.25 years). Complication rates were low. The CCSR was 9.2/million population. CONCLUSIONS: A Pediatric Ophthalmology Service has been established in Malawi delivering safe, effective surgery on a country-wide scale for childhood cataract. Over the period studied, the age at presentation reduced, and there was an improvement in the geographical distribution of patients, likely due to an improvement in referral systems throughout Malawi.

Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy.

BACKGROUND: Flash visual evoked potentials (VEPs) were abnormal in a cohort of 100 neonates exposed to maintenance methadone in utero. This prospective cohort study now describes clinical visual and electrophysiological outcomes at 6 months. METHODS: Visual assessment included modified Atkinson test battery; strabismus, nystagmus, reduced visual acuity, delayed visual maturation or refractive error (>3 dioptres) defined a fail. Pattern-onset VEPs were recorded to 120', 60' and 15' checks. RESULTS: 81 drug-exposed and 26 comparison infants (79% and 52% of the original cohorts) were assessed at a median age of 27 weeks (range 26-30). 90% of drug-exposed infants had been additionally exposed to illicit drugs and 41% to excess alcohol in utero. 40% of the drug-exposed cohort failed clinical visual assessment: the relative risk of abnormal assessment was 5.1 (95% CI 1.3 to 20; p=0.02). Nystagmus was particularly common. VEP peak times were slower and amplitudes smaller in drug-exposed infants, of whom 70% had one or more abnormal VEP parameter. Abnormal visual outcome at 6 months was not associated with the pattern of additional drug exposure or a history of neonatal abstinence. CONCLUSIONS: Abnormal visual electrophysiology in infants born to drug-misusing mothers prescribed maintenance methadone persists to 6 months of age, and is associated with abnormal clinical visual assessment.

Sensitivity and specificity of the step VEP in suspected functional visual acuity loss.

BACKGROUND/AIM: Early and accurate diagnosis of functional visual loss (FVL) allows optimum management. Visual evoked potentials (VEPs) offer a means of objectively estimating acuity and therefore could assist with early and accurate diagnosis. The aim of this study was to assess the sensitivity and specificity of the step VEP in diagnosing FVL. METHODS: A retrospective audit was conducted in 36 school-aged children presenting with reduced visual acuity and clinical suspicion of FVL. All had undergone step VEP testing as part of their investigation. Medical notes were reviewed, and where necessary, referring centres, general practitioners or electronic clinical portals were consulted to obtain longer-term outcome data. RESULTS: Twenty-seven of the 36 patients (75%) were classified as having had FVL: all had a normal step VEP spatial threshold. Nine patients (25 %) had an organic cause for their acuity loss, of whom seven had abnormal step VEP spatial thresholds: the other two patients had some functional overlay to their organic disease. The step VEP sensitivity was 78% (95% confidence interval 40-96%), and specificity was 100% (95% confidence interval 84-100%). CONCLUSION: The high specificity of the step VEP for FVL warrants increased suspicion of an organic cause should the step VEP spatial threshold be abnormal.

Heritability of strabismus: genetic influence is specific to eso-deviation and independent of refractive error.

Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent ('phoria') and manifest ('tropia') strabismus using cover-uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a genetic role (p = .003). There was no significant difference in polychoric correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation (p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50-0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and unravel their mechanisms of action.

Associations of birth weight with ocular biometry, refraction, and glaucomatous endophenotypes: the Australian Twins Eye Study.

PURPOSE: To examine the relationship of birth weight with ocular measures in a Caucasian twin population. DESIGN: Cross-sectional study of 1498 twins (308 monozygotic and 441 dizygotic pairs) aged between 5 to 80 years participating in the Australian Twins Eye Study. METHODS: All participants underwent ophthalmic examination including bilateral cycloplegic autorefraction, keratometry, interpupillary distance (IPD), central corneal thickness, intraocular pressure (IOP), and retinal photography. Birth weight and gestation were obtained from a self-administered questionnaire. A subset of the twins also participated in the Tasmanian Infant Health Study (288) and the Childhood Blood Pressure Study (184), which collected data on birth parameters allowing for verification of data. Linear mixed models were used for the main analysis. RESULTS: Both the within-pair (ß(w) 0.27, 95% confidence interval [CI] 0.15, 0.38 mm per kg increase in birth weight, P < .001) and between-pair associations (ß(B) 0.22, 95% CI 0.08, 0.35, P = .002) of birth weight with axial length were significant and of similar magnitude (difference in effect, P = .56), after adjusting for relevant confounders. In contrast, birth weight was negatively associated with corneal curvature (ß(w) -0.82, 95% CI -1.09, -0.55 diopters per kg increase; ß(B) -0.69, 95% CI -0.98, -0.41, both P < .001). These associations remained significant within dizygotic and monozygotic pairs. Refraction, anterior chamber depth, IPD, IOP, and optic disc parameters are unrelated to birth weight. CONCLUSIONS: Consistent with previous studies in singleton children, lower birth weight is associated with shorter axial length and more curved corneas in this twin study. This also adds new insights into the emmetropization process.

Twins eye study in Tasmania (TEST): rationale and methodology to recruit and examine twins.

Visual impairment is a leading cause of morbidity and poor quality of life in our community. Unravelling the mechanisms underpinning important blinding diseases could allow preventative or curative steps to be implemented. Twin siblings provide a unique opportunity in biology to discover genes associated with numerous eye diseases and ocular biometry. Twins are particularly useful for quantitative trait analysis through genome-wide association and linkage studies. Although many studies involving twins rely on twin registries, we present our approach to the Twins Eye Study in Tasmania to provide insight into possible recruitment strategies, expected participation rates and potential examination strategies that can be considered by other researchers for similar studies. Five separate avenues for cohort recruitment were adopted: (1) piggy-backing existing studies where twins had been recruited, (2) utilizing the national twin registry, (3) word-of-mouth and local media publicity, (4) directly approaching schools, and finally (5) collaborating with other research groups studying twins.

Effect of birth parameters on retinal vascular caliber: the Twins Eye Study in Tasmania.

Recent studies reported an association between smaller birth size and narrower retinal vascular caliber, but it remains unclear whether this association is attributed to confounding by shared environment or genetic factors. At a mean age of 9.3 years, 266 twins (49 monozygotic and 84 dizygotic pairs) in the Twins Eye Study in Tasmania underwent an ophthalmic examination including retinal photography. Retinal vascular caliber was measured using a validated protocol. The majority of these twins were also in the Tasmanian Infant Health Study, which prospectively collected data on birth parameters and antenatal maternal factors. We conducted the main analysis using linear mixed models, accounting for birth set clustering. Both the within-pair (-9.73; 95% CI: -14.68 to -4.77 microm per 5-cm decrease in birth length) and between-pair associations (-7.15; 95% CI: -11.54 to -3.01) with retinal arteriolar caliber were significant and of similar magnitude (difference in effect, P=0.61), after adjusting for age, sex, maternal smoking, mean arterial blood pressure, and other confounders. These associations remained within dizygotic and monozygotic pairs. Analyses of head circumference and retinal arteriolar caliber were similar to those of birth length (within-pair regression coefficient: -2.41; 95% CI: -5.09 to 0.28; between-pair regression coefficient: -2.60; 95% CI: -5.00 to -0.19). For birth weight, only a between-pair association was evident (-7.28; 95% CI: -13.07 to -1.48). This study demonstrates a consistent association between smaller birth size and narrower retinal arterioles in twins. The independent effect of shorter birth length on retinal arteriolar caliber supports a role for twin-specific supply line factors affecting fetal growth on vascular structure.

Genetic dissection of myopia: evidence for linkage of ocular axial length to chromosome 5q.

PURPOSE: To estimate heritability and locate quantitative trait loci influencing axial length. DESIGN: Classic twin study of monozygotic and dizygotic twins reared together. PARTICIPANTS: Eight hundred ninety-three individuals from 460 families were recruited through the Twin Eye Study in Tasmania and the Brisbane Adolescent Twin Study (BATS) and had ocular axial length measured. METHODS: Structural equation modeling on the entire sample was used to estimate genetic and environmental components of variation in axial length. Analysis of existing microsatellite marker genomewide linkage scan data was performed on 318 individuals from 142 BATS families. MAIN OUTCOME MEASURE: Ocular axial length. RESULTS: The heritability estimate for axial length, adjusted for age and sex, in the full sample was 0.81. The highest multipoint logarithm of the odds (LOD) score observed was 3.40 (genomewide P = 0.0004), on chromosome 5q (at 98 centimorgans [cM]). Additional regions with suggestive multipoint LOD scores were also identified on chromosome 6 (LOD scores, 2.13 at 76 cM and 2.05 at 83 cM), chromosome 10 (LOD score, 2.03 at 131 cM), and chromosome 14 (LOD score, 2.84 at 97 cM). CONCLUSION: Axial length, a major endophenotype for refractive error, is highly heritable and is likely to be influenced by one or more genes on the long arm of chromosome 5.

Familial transmission risk of infantile glaucoma in Australia.

PURPOSE: Primary infantile glaucoma (PIG) is predominantly inherited as a recessive disease, whereas anterior segment dysgenesis (ASD) is usually dominantly inherited. The purpose of this study was to determine the likelihood of a person who has infantile glaucoma to produce a child who also manifests the disease. METHODS: A retrospective cross-sectional design was utilized. The pedigrees of probands from south-eastern Australia diagnosed with infantile glaucoma since 1980 were reviewed. Cases were subdivided into two groups according to the presence or absence of ASD. Exclusion criteria included incomplete pedigree phenotype information or aphakic glaucoma following congenital cataract surgery. Fisher's exact test was used to compare the parent-offspring phenotype transmission between ASD-associated infantile glaucoma and PIG. RESULTS: A total of 67 probands were identified; however, three pedigrees were excluded due to incomplete phenotype information. Direct parent-offspring transmission of phenotype was statistically significantly more common in ASD-associated infantile glaucoma (2/8) than in PIG (1/56) pedigrees (p = 0.039). CONCLUSIONS: Although this study reveals that Australian patients with ASD-associated infantile glaucoma are at greater risk of having children with infantile glaucoma than patients with PIG, the number of ASD pedigrees with direct transmission of infantile glaucoma is lower than expected. Based on our population frequency analysis and the results of our study, the risk of PIG, if one parent is affected by PIG and the other is normal, is less than 2%.

Central corneal thickness is highly heritable: the twin eye studies.

PURPOSE: A classic twin study was performed to determine the heritability of central corneal thickness (CCT), an important parameter in glaucoma assessment. METHODS: The concordance of CCT between monozygotic (MZ) and dizygotic (DZ) twins was compared. A total of 256 twin pairs (131 MZ and 125 DZ) were recruited from three centers: the Twin Eye Study in Tasmania, the Brisbane Adolescent Twin Study, and the Twins U.K. Adult Registry held at St. Thomas' Hospital in London. As part of an extensive ophthalmic evaluation, CCT was measured by ultrasound pachymetry. Structural equation modeling with the Mx program (Department of Psychiatry, Medical College of Virginia, Richmond, VA) was used to determine the heritability of CCT. RESULTS: The mean age of subjects was 38 years (range, 8-81). The mean CCT of all eyes examined was 544.5 +/- 37.3 mum (SD). The CCT measurements correlated more highly in MZ twins than in DZ twins, with intraclass correlation coefficients of 0.95 and 0.52, respectively, suggesting a strong genetic influence. A model of additive genetic and unique environmental effects provided the best fit, yielding a heritability of 0.95 (95% confidence interval [CI], 0.93-0.96) with the remaining variation being attributable to unique environmental factors. CONCLUSIONS: In this study of Australian and U.K. twins, genetic factors were shown to be of major importance in CCT, with a heritability of 0.95.

Primary infantile glaucoma in an Australian population.

BACKGROUND: Primary infantile glaucoma presents rarely, but can be responsible for significant visual morbidity. There is little information on the clinical features and visual outcome of a pure population of primary infantile glaucoma, as opposed to a mixed population of primary and secondary glaucoma or combined group of those with trabeculodysgenesis and iridotrabeculodysgenesis. METHODS: We conducted a retrospective review of children with primary infantile glaucoma seen in south-eastern Australia between 1980 and 2000, using The Royal Children's Hospital ophthalmic diagnostic coding database. RESULTS: Fifty-one patients with primary infantile glaucoma were identified (83 eyes). This equates to an estimated incidence of approximately 1 in 30,000 births. The mean +/- SD age at presentation was 135 +/- 84 days. 'Burnt-out' disease (megalocornea without raised intraocular pressure) was diagnosed in 10.8%. Goniotomy was the most commonly performed surgical procedure (69.4% of 72 eyes). Surgical success with one or two goniotomies was achieved in 74% of eyes. Visual outcomes at final review were generally good with 61.8% reading 6/12 or better. There were a disproportionately high number of children having a final recorded acuity of <6/60 in the group diagnosed in the first 3 months of life. CONCLUSIONS: Primary infantile glaucoma is a rare ocular condition in this population that presents at a mean age of 4.4 months. Surgical and visual outcomes are generally favourable.

Toxocara canis: egg presence in Melbourne parks and disease incidence in Victoria.

PURPOSE: Toxocara canis can cause blinding eye disease. This study assessed the presence of T. canis eggs in soil from parks in Melbourne and also the incidence of presumed ocular toxocariasis in Victoria. METHODS: One hundred and eighty soil samples were collected from nine suburban locations in Melbourne, Australia. These were analyzed for the presence of T. canis eggs. A search of laboratory records of T. canis serology requests from Victorian patients over an 8-year period was performed. RESULTS: Only one soil sample was positive for T. canis eggs. Positive T. canis serology was reported in 13 samples from patients. These patients all had ocular features suggestive of T. canis infection. CONCLUSION: Toxocara canis eggs are rare in public parks in Melbourne and symptomatic ocular toxocariasis is uncommon in the Victorian population. The acquisition of the disease is unlikely to be from public parks.