Association of Polymorphisms in ZFHX1B and PAX6 With Anisometropia in Chinese Children: The Hong Kong Children Eye Genetics Study.

Purpose: To identify gene variants associated with anisometropia development in children. Methods: This is a population-based, cross-sectional, and longitudinal genetic association study involving 1057 children aged 6 to 10 years with both baseline and 3-year follow-up data. Six single nucleotide polymorphisms (SNPs), ZC3H11B rs4373767, ZFHX1B rs13382811, KCNQ5 rs7744813, SNTB1 rs7839488, PAX6 rs644242, and GJD2 rs524952 were analyzed in all children. Anisometropia was defined by an interocular difference in SE of ≥1 diopter (D) (Aniso-SE) and an interocular difference in axial length (AL) of ≥0.3 mm (Aniso-AL), respectively. Genetic associations of individual SNPs and joint SNP effects were analyzed. Results: ZFHX1B rs13382811 was associated nominally with Aniso-AL (odds ratio [OR], 1.66; P = 0.003) at baseline. At 3 years, rs13382811 was significantly associated with Aniso-AL (OR, 1.49; P = 0.001) and became nominally associated with Aniso-SE (OR, 1.40; P = 0.01). In addition, PAX6 rs644242 was significantly associated with Aniso-AL at 3 years (OR, 1.45; P = 0.002). At the 3-year follow-up, PAX6 rs644242 was associated significantly with Aniso-AL development (OR, 1.61; P = 0.0003) and nominally with Aniso-SE development (P = 0.03) in children who were not anisometropic at baseline, whereas ZFHX1B rs13382811 was associated nominally with Aniso-AL development (P = 0.02). An additive SNP analysis indicated children carrying the risk allele T of ZFHX1B rs13382811 and allele A of PAX6 rs644242 might have a 4.33- and 6.90-fold of increased risk of Aniso-SE and Aniso-AL development by 3 years, respectively. Conclusions: This study identified two susceptible gene variants, ZFHX1B rs13382811 and PAX6 rs644242, for anisometropia development in Hong Kong Chinese children, implicating their role in imbalanced refractive change and axial elongation between both eyes.

Mirror image hypermetropic anisometropia in a pair of monozygotic twins.

In monozygotic twins two embryos are formed from a single fertilized egg. In "mirror image twins" identical siblings have reverse asymmetric features in the right and left sides of the body. We report the case of twins with mirror-image hypermetropic anisometropia. They were referred to an ophthalmologist at the age of 3.5 years for amblyopia. Cycloplegic refraction of twin 1 was +1.00 in the right eye and +4.50 -0.75 ×180 in the left eye; of twin 2, +4.75 -1.00 ×180 and +1.25. Keratometry and axial length were measured with Lenstar LS 900 when the twins were 6 years of age. In twin 1, the axial length was 22.18 mm in the right eye and 20.97 in the left eye; in twin 2, 20.94 mm and 22.13. Keratomtry of both eyes of these twins was relatively equal.

Missense mutation in SLIT2 associated with congenital myopia, anisometropia, connective tissue abnormalities, and obesity.

BACKGROUND: SLIT2 is a protein ligand for the Roundabout (ROBO) receptor and was found to play a major role in repulsive midline axon guidance in central nervous system development. Based on studies utilizing knockout models, it has been postulated that SLIT2 is important for preventing inappropriate axonal routing during mammalian optic chiasm development. METHODS: Case report. RESULTS: Here, we report a case of congenital myopia, anisometropia, and obesity in a patient with a SLIT2 point mutation. Examination of the patient's skin biopsy revealed abnormalities in elastin and collagen fibrils that suggest an underlying connective tissue disorder. Structural modeling placed the novel mutation (p.D1407G) in the EGF-like domain 8 and was predicted to affect interactions with SLIT2 binding partners. CONCLUSIONS: To the authors' knowledge, this is the first report of a SLIT2 variant in the context of these ocular findings.

Exome sequencing identifies a novel UNC5D mutation in a severe myopic anisometropia family: A case report.

INTRODUCTION: Severe myopic anisometropia has been identified to have heritability, but the pathogenesis of anisometropia still remains obscure. CASE DESCRIPTION: Here, we presented a Chinese severe myopic anisometropia family with 5 members affected. Though using the exome sequencing, we identified a novel mutation in the UNC5D gene (c.1297C>T, p.R433C), which was predicted to have a damage effect on the protein function and kept highly conserved throughout evolution across species. As previously described, the UNC5D gene belongs to the UNC5 protein family and may have functions to regulate neuronal migration, axon guidance, and cell survival. The expression of UNC5D was also co-located at the visual areas of the mouse cortical regions at early postnatal ages. CONCLUSION: Our data provide the first evidence for involvement of UNC5D gene in the severe myopic anisometropia.

Anisometropia of ocular refractive and biometric measures among 66- to 79-year-old female twins.

PURPOSE: To examine the prevalence of anisometropia of spherical refraction (AnisoSR), astigmatism (AnisoAST) and spherical equivalent (AnisoSE) and their associations with spherical refraction (SR), refractive astigmatism (AST), spherical equivalent (SE) and interocular differences of ocular biometric parameters among elderly female twins. METHODS: Refraction of 117 monozygotic (MZ) and 116 dizygotic (DZ) female twin subjects aged 66-79 years was assessed with an auto-refractor (Topcon AT) and controlled by subjective refraction. Corneal refraction, anterior chamber depth and axial length were measured with a Zeiss IOL Master. Participants with eyes operated for cataract or glaucoma were excluded, but the grade of nuclear opacity was not recorded. The associations between the absolute values of AnisoSR, AnisoAST and AnisoSE with SR, AST, SE, corneal refractive power (CR), corneal astigmatism (CAST), anterior chamber depth (ACD) and axial length (AL) and with their interocular differences were calculated. When calculating the interdependencies of the differences, the real and absolute differences between the right and left eye were used. RESULTS: Means ± standard deviations for AnisoSR, AnisoAST and AnisoSE were 0.67 ± 0.92 D, 0.42 ± 0.41 D and 0.65 ± 0.71 D, respectively. AnisoSR, AnisoAST and AnisoSE >1.0 D were present in 14.7%, 4.2% and 17.7% of cases, respectively. Anisometropia of spherical refraction (AnisoSR), AnisoAST and AnisoSE were higher the more negative the values of SR or SE. Hyperopic ametropia did not increase these anisometropia values. The correlations of AnisoSR and AnisoSE with the absolute values of interocular differences in CR and AL were non-significant. Using the real values of the interocular differences, the respective correlations were significant. The correlation between the real interocular differences in CR and AL was negative (r = -0.258, p < 0.001). Thus, the combined effect of the real interocular differences in CR and AL was a decrease in AnisoSR and AnisoSE (emmetropization). CONCLUSION: Higher AnisoSR and AnisoSE were associated with more myopic refraction and longer AL. Higher AnisoAST was associated with more negative SR and higher AST and CAST. The negative correlation between real interocular differences in CR and AL indicated their influence of emmetropization in AnisoSR and AnisoSE.

[Amblyopia. Epidemiology, causes and risk factors]. / Amblyopie. Epidemiologie, Ursachen, Risikofaktoren.

BACKGROUND: Amblyopia is the main cause for mostly monocular, impaired vision in childhood. Treatment and prevention of amblyopia is only effective during childhood. Ophthalmological screening of children does not yet exist in Germany. EPIDEMIOLOGY: The prevalence of amblyopia in Germany is 5.6%, which is higher than in reports from studies in Australia; however, the prevalence of amblyopia is not comparable in these studies due to different definitions of amblyopia and the inclusion/exclusion criteria of the study cohorts. At present it is unknown at what age ophthalmological screening should be carried out to prevent amblyopia and the appropriate frequency of screening examinations. CAUSES: Amblyopia is a disorder of the visual cortex that is due to suppression and deprivation of one eye leading to unilateral visual impairment. Approximately 50% of cases of amblyopia are caused by anisometropia, 25% by strabismus and in every sixth person by a combination of both. Other causes, such as unilateral congenital cataracts are relatively rare. RISK FACTORS: A variety of factors, such as ocular pathologies, premature birth, familial disposition and general diseases are associated with an increased risk for amblyopia.

Severe anisometropic myopia in identical twins.

High anisometropic myopia is a rare condition in twins. Genetic factors have been implicated in its development and there may be an association with vision-threatening complications. A pair of 11-year-old twins presented with poor distance vision in both eyes. Detailed ocular examination was performed including slit lamp examination, dilated funduscopy, cycloplegic refraction, keratometry and axial length measurement. The objective refraction was -6.50 DS -2.00 DC × 180 (right eye), -1.00 DS (left eye) for the first twin; -13.75 DS -2.25 DC × 180 (right eye), -0.50 DS -0.75 DC × 04 (left eye) for the second twin. This case suggests an underlying genetic defect in the development of myopia.

Severe myopic anisometropia in a Chinese family.

PURPOSE: The aim of this study is to describe a Chinese four-generation family with severe myopic anisometropia and to explore the possible pathogenesis for this disease. METHODS: Eighteen individuals of a four-generation family participated in the study, including a pair of monozygotic (MZ) twins. A detailed family history and clinical data were recorded. All participants were subjected to ophthalmologic examinations including refractive error, slitlamp, and fundus examination. B-scan and A-scan ultrasonography were additionally ordered for each affected patient for further evaluation. Optical refractive correction was prescribed, and full-time occlusion therapy of 6 days weekly in right eye and 1 day weekly in left eye was prescribed for the MZ twins. RESULTS: Five individuals were affected with severe myopic anisometropia within this family, including the pair of MZ twins. In all affected individuals, the right eyes were more myopic than the left eyes, and axial length and anterior chamber depth measurements in the more myopic eyes were longer. After 6 months of therapy, the best corrected visual acuity in the amblyopic eye of the MZ twins improved significantly. CONCLUSIONS: The co-occurrence of severe myopic anisometropia in five individuals of the family supports a genetic basis for the disease. The successful therapeutic effect on anisometropic amblyopia highlights the importance of early detection and timely treatment.

Identical twins with "mirror image" anisometropia and esotropia.

INTRODUCTION: Identical twins account for 0.2% of the world population and 8% of all twins. A "mirror image" variation can be found in 25% of identical twins. Studies of twins assume a special place in human genetics due to the possibility of comparing genetic and other factors. We present two pairs of identical male twins with mirror-image astigmatism and esotropia. CASE OUTLINE: The first was a pair of twelve-year old identical twins with "mirror image" myopic astigmatism. The Twin 1 had myopic astigmatism in the right eye, while the Twin 2 was affected by the left eye myopic astigmatism. The second was a pair of six-year old identical twins with esotropia and hypermetropic astigmatism. The Twin 1 had esotropia in the left eye, while the right eye was affected in the Twin 2. Esotropia was surgically corrected. CONCLUSION: In this study we pointed to the role of genetic factors in the development of refractive error, as well as the type of strabismus. Refraction anomalies (myopia, hypermetropia and astigmatism) are complex heterogeneous disorders and ideal for genetic investigation. The knowledge of genetic mechanisms involved in refractive error susceptibility may allow treatment to prevent progression or to further examine gene-environment interactions. We hope that this paper will initiate further investigation of refraction anomalies in twins and future multicentre studies, which, to our knowledge, have not been conducted in our country so far.

One sister and brother with mirror image myopic anisometropia.

We report a case of one sister and brother with mirror image myopic anisometropia. One sister and brother complained visual disturbance. The sister was 10 years 11 months old, and brother was 8 years 4 months old. Full ophthalmic examinations were performed, including slit lamp examination, intraocular pressure, keratometry, anterior chamber depth, axial length, fundus examination and the cycloplegic refraction. The cycloplegic refractive power was -15.50 dpt cyl.+4.50 dpt Ax 85 degrees (right eye), -1.00 dpt cyl.+0.50 dpt Ax 90 degrees (left eye) in the sister; -1.75 dpt cyl.+2.25 dpt Ax 90 degrees (right eye), -9.50 dpt cyl.+4.00 dpt Ax 80 degrees (left eye) in the brother. The co-occurrence of severe myopic anisometropia in a sister and brother is extremely rare. The present case suggests that severe myopic anisometropia may be related by genetic inheritance.

Spontaneous axial myopia and emmetropization in a strain of wild-type guinea pig (Cavia porcellus).

PURPOSE: To describe a wild-type guinea pig strain with an incidence of spontaneous axial myopia, minimal pupil responses, lack of accommodation, and apparently normal spatial vision. Such a strain is of interest because it may permit the exploration of defective emmetropization and mapping of the underlying quantitative trait loci. METHODS: Twenty-eight guinea pigs were selected from 220 animals based on binocular myopia (exceeding -1.50 diopter [D]) or anisometropia (difference between both eyes exceeding 10 D) at 4 weeks of age. Refractions and pupil responses were measured with eccentric infrared photoretinoscopy, corneal curvature by modified conventional keratometer, and axial lengths by A-scan ultrasonography once a week. Twenty-one guinea pigs were raised under a normal 12-hour light/12-hour dark cycle. From a sample of 18 anisometropic guinea pigs, 11 were raised under normal light cycle and 7 were raised in the dark to determine the extent to which visual input guides emmetropization. Spatial vision was tested in an automated optomotor drum. RESULTS: In 10 guinea pigs with myopia in both eyes, refractive errors ranged from -15.67 D to -1.50 D at 3 weeks with a high interocular correlation (R = 0.82); axial length and corneal curvature grew almost linearly over time. Strikingly, two patterns of recovery were observed in anisometropic guinea pigs: in 12 (67%) anisometropia persisted, and in 6 (33%) it declined over time. These ratios remained similar in dark-reared guinea pigs. Unlike published strains, all guinea pigs of this strain showed weak pupil responses and no signs of accommodation but up to 3 cyc/deg of spatial resolution. CONCLUSIONS: This strain of guinea pigs has spontaneous axial refractive errors that may be genetically or epigenetically determined. Interestingly, it differs from other published strains that show no refractive errors, vivid accommodation, or pupil responses.

Ocular features of CHARGE syndrome.

PURPOSE: To detail the presence and severity of ocular and cranial nerve abnormalities found in individuals with CHARGE syndrome in a distinct geographic area. METHODS: Nine individuals with CHARGE syndrome from Maritime Canada identified from a Canadian database were prospectively examined. Structural and sensorial defects associated with functional visual deficits were defined with ophthalmic and neurological evaluation. RESULTS: Consistent with current diagnostic criteria and the literature, colobomas were the major ophthalmic manifestation. These were typically bilateral chorioretinal colobomas involving the optic nerve. All subjects had bilateral severe sensorineural deafness (cranial nerve VIII), and 8 of 9 (89%) had facial nerve (cranial nerve VII) involvement (7 of 9 had unilateral involvement; 1 of 9 had bilateral involvement). Unique to this group of participants were the findings of anisometropia in 8 of the 9 (89%) patients, severe myopic astigmatism in 13 of the 18 eyes (72%), and limited elevation in adduction in 3 of 9 (33%) participants. Associated findings were strabismus, cataracts, microcornea, keratopathy, staphyloma, reduced stereopsis, superior visual field defects, and reduced visual acuity. CONCLUSIONS: The presence of coloboma plus another CHARGE feature warrants further investigation, including genetic screening for the CHD7 gene. Early recognition and management of sensory problems (visual, auditory, and vestibular) are crucial to ensure best psychomotor and cognitive development.

Mirror image myopic anisometropia in two pairs of monozygotic twins.

Two sets of monozygotic twins with mirror image myopic anisometropia are reported. The first set were two boys aged 1 year 8 months. There was a right eye myopic anisometropia in one twin, and a left eye myopic anisometropia in the other. The differences in refractive power between both eyes were 11.6 and 7.6 dpt, respectively (spherical equivalent). The second set were two 6-year-old boys. The right eye had myopic anisometropia in one twin, while the left eye was affected in the other. The differences in refractive power between both eyes were 6.5 and 3.7 dpt, respectively (spherical equivalent). Exotropia was recognized in 3 cases. Previously only two sets of monozygotic twins with mirror image myopic anisometropia have been reported. Monozygotic twins with mirror image myopic anisometropia are extremely rare.

Mirror-image optic nerve dysplasia with associated anisometropia in identical twins.

BACKGROUND: Monozygotic (MZ) or "identical" twins arise from a single fertilized egg, which divides into two embryos at an early stage of development. As a result, MZ twins have identical genomes and are always of the same sex. METHODS: A case of optic nerve hypoplasia and anisometropia, in association with mirror-image presentation in a set of 12-year-old identical twins, is reported. The monozygotic twinning event responsible for identical twins--as well as the rare phenomenon of mirror imaging--is described. RESULTS: The combined occurrence of anisometropia and optic nerve hypoplasia in mirror-image presentation in a set of monozygotic twins provides a unique opportunity to study the genetic versus environmental influences on the development of optic nerve hypoplasia. CONCLUSIONS: Although the cause of optic nerve hypoplasia remains unclear, its associated mirror-image presentation in this case suggests a possible genetic predisposition.

[Video refraction measurement in the first year of life]. / Videorefraktionsmessung im ersten Lebensjahr.

BACKGROUND: 426 children were examined, using the isotropic photorefraction method (Atkinson et al. 1981). The aim of this study was to analyze whether the frequency of convergent strabismus and/or amblyopia would increase, particularly in cases of high ametropia, and whether the early prescription of spectacles would be beneficial. The preliminary results of this study are presented here. MATERIALS AND METHODS: 426 children aged between 5 and 12 months were examined. Family history, particularly involving strabismus, ametropia and amblyopia, was ascertained and taken into consideration. RESULTS: Spherical refraction: 92% of the children were emmetropic or slightly hyperopic (< or = +2.5 D). 3.4% were hyperopic (> +2.5 D spherical equivalent) and 4.6% were myopic (0.9 > or = -2.0 D). Astigmatism: 85% had no or mild (< or = 1.5 D) astigmatism. Values greater than 3.5 D were rarely seen. Anisometropia: 67% of the children had no side-difference and only 2.4% had anisometropia with values greater than 1.5 D. Family history/orthoptic findings: 2.6% of the examined population had strabismus. In 12.2% of all the cases one or more first degree relatives had strabismus. Hyperopia and strabismus were found more frequently in this latter group, namely hyperopia (> +2.5 D spherical equivalent) in 13.6% and strabismus in 11.5%. CONCLUSIONS: Refractive errors greater than 2.5 D were seldom seen in this study, and yet were more frequently detected in families with a history of strabismus. In our opinion, isotropic photorefraction is a method most suitable to screening these especially high-risk groups.

High symmetric anisometropia in monozygotic twins.

The first case in the literature of anisometropia of more than 20 dioptres in both left eyes of a pair of monozygotic 64-year-old twins is presented. The refractive parameters are given together with a short overview of the literature on anisometropia.