Optic Disc Features in Highly Myopic Eyes: The ZOC-BHVI High Myopia Cohort Study.

SIGNIFICANCE: Some studies reported that optic disc tilt and rotation might be risk factors for the susceptibility of high myopic eyes to develop glaucoma. However, data regarding optic disc manifestations in high myopia participants are few. It is crucial to characterize the features of optic disc manifestations among high myopes. PURPOSE: To describe optic disc characteristics of Chinese highly myopic eyes and to investigate associated factors. METHODS: This cross-sectional, observational study included 890 Chinese with bilateral high myopia (defined as ≤-6.00 diopters spherical power) in 2012. All subjects underwent cycloplegic autorefraction, ocular biometry, and fundus photography. The optic disc tilt ratio, degree of rotation, and ß-zone peripapillary atrophy area were measured from the 45°optic disc-centered fundus photographs. Optic disc tilt was defined as optic disc tilt ratio, the ratio of maximum to minimum diameter of optic disc, exceeding 1.3. The definition of optic disc rotation was using optic disc rotation degree, the angle from long diameter and the vertical meridian, of >15°. RESULTS: Among 890 participants, 2 were excluded by ungradable optic disc-centered fundus photographs. In the 888 studied right eyes, the mean spherical power was -9.36 ± 3.46 diopters with a mean axial length of 27.51 ± 1.63 mm. The proportion of optic disc tilting, rotation, and ß-zone peripapillary atrophy were 81.2%, 48.3%, and 92.8%, respectively. The mean ratio of optic disc tilting and rotation degree was 1.78 ± 0.53 and 21.08 ± 19.91°; the mean area of ß-zone peripapillary atrophy/optic disc head was 1.11 ± 1.22. A multiple linear regression showed that older age (P < .001), female (P = .02), and more myopic spherical equivalent (P = .005) were related to the greater optic disc tilting ratio. CONCLUSIONS: Beta-zone peripapillary atrophy, optic disc tilting, and rotation are very common in highly myopic eyes in Chinese population. Older age, female, and more myopic spherical equivalent are risk factors of higher degree of optic disc tilting.

ß-Zone Parapapillary Atrophy and Rates of Glaucomatous Visual Field Progression: African Descent and Glaucoma Evaluation Study.

Importance: ß-zone parapapillary atrophy (ßPPA) has been reported as a risk factor for glaucoma onset and progression. Previous studies have shown that the prevalence of ßPPA differs between individuals of African descent (AD) and European descent (ED). Objective: To test whether the association between the presence and progression of ßPPA vs visual field progression of glaucoma differs between these 2 ancestry groups. Design, Setting, and Participants: In a prospective, multicenter, longitudinal cohort study, 634 individuals (1090 eyes) enrolled in the African Descent and Evaluation Study (ADAGES) with a diagnosis of glaucomatous optic neuropathy (GON) or ocular hypertension (OHT) and at least 2 disc stereophotographs were included. Two graders masked to clinical and ancestry data reviewed and graded the baseline and last disc stereophotographs for the presence of ßPPA at baseline and ßPPA progression (development or enlargement). Mixed-effects linear models were tested with visual field mean deviation as a dependent variable and time (alone and with interaction terms) as independent variables. ADAGES enrollment began in January 2003 and ended in July 2006; follow-up ended in 2016. Exposures: Disc stereophotographs. Main Outcomes and Measures: Progression of ßPPA in AD and ED individuals. Results: In 634 patients, a total of 814 eyes of AD (395 eyes) and ED (419) patients with GON and 276 eyes of AD (106) and ED (170) patients with OHT who were enrolled in ADAGES were analyzed. There were 336 (53.0%) women in the study; mean (SD) age was 61.9 (12.7) years. In the OHT group, the association between ßPPA at baseline and visual field progression was not significantly different between AD and ED eyes (ß = 0.071; 95% CI, -0.016 to 0.158; P = .11), nor was the association between ßPPA progression and visual field progression (ß = 0.020; 95% CI, -0.465 to 0.506; P = .93). In the GON group, ED eyes with baseline ßPPA progressed faster than did AD eyes with baseline ßPPA (ß = -0.124; 95% CI, -0.241 to -0.007; P = .04), although the association between ßPPA progression and visual field progression did not differ significantly between race groups (ß = -0.101; 95% CI, -0.323 to 0.119; P = .37). Conclusions and Relevance: Race had a significant effect on the association between baseline ßPPA and rates of visual field progression in eyes with GON. Progression of ßPPA was not associated with faster visual field progression in either racial group.

Nerve conduction studies in spastic paraplegia, optic atrophy, and neuropathy (SPOAN) syndrome.

INTRODUCTION: SPOAN (spastic paraplegia, optic atrophy, and neuropathy) syndrome is an autosomal recessive neurodegenerative disorder identified in a large consanguineous Brazilian family. METHODS: Twenty-seven patients with SPOAN syndrome (20 women), aged 4-58 years, underwent nerve conduction studies (NCS) of the median, ulnar, tibial, and fibular nerves, and sensory NCS of the median, ulnar, radial, sural, and superficial fibular nerves. RESULTS: Sensory nerve action potentials were absent in the lower limbs and absent in >80% of upper limbs. Motor NCS had reduced amplitudes and borderline velocities in the upper limbs and absent compound muscle action potentials (CMAPs) in the lower limbs. CONCLUSIONS: The neuropathy in SPOAN syndrome is a severe, early-onset sensory-motor axonal polyneuropathy. Normal NCS seem to rule-out this condition.

Myopia-related fundus changes in Singapore adults with high myopia.

PURPOSE: To examine the pattern of myopia-related macular and optic disc changes in Singapore adults with high myopia (spherical equivalent ≤-6.00 diopters). DESIGN: Asian adults with high myopia from 3 population-based surveys. METHODS: Adults 40 years and older (n = 359) with high myopia were pooled from 3 population-based surveys in Singapore Asians: (1) the Singapore Prospective Study Program (SP2, n = 184); (2) the Singapore Malay Eye Study (SiMES, n = 98); and (3) the Singapore Indian Eye Study (SINDI, n = 77). All study participants underwent standardized refraction and fundus photography, and SiMES and SINDI subjects also completed ocular biometry measurements. Myopia-related macular (posterior staphyloma, lacquer cracks, Fuchs spot, myopic chorioretinal atrophy, and myopic choroidal neovascularization) and optic disc (optic nerve head tilt, optic disc dimensions, and peripapillary atrophy) changes were evaluated. RESULTS: The most common myopia-related macular finding in adults with high myopia was staphyloma (23%), followed by chorioretinal atrophy (19.3%). There were few cases of lacquer crack (n = 6, 1.8%), T-sign (n = 6, 1.8%), retinal hemorrhage (n = 3, 0.9%), active myopic choroidal neovascularization (n = 3, 0.9%), and no case of Fuchs spot. The most common disc finding associated with high myopia was peripapillary atrophy (81.2%), followed by disc tilt (57.4%). Staphyloma and chorioretinal atrophy increased in prevalence with increasing age, increasing myopic refractive error, and increasing axial length (all P < .001). Ethnicity comparisons demonstrated the highest proportion of staphyloma (P = .04) among Malays, the highest proportion of peripapillary atrophy (P = .01) and disc tilt (P < .001) among Chinese, and the largest cup-to-disc ratio (P < .001) among Indians. CONCLUSIONS: Staphyloma and chorioretinal atrophy lesions were the most common fundus findings among Asian adults with high myopia. In this population, tilted discs and peripapillary atrophy were also common, while choroidal neovascularization and Fuchs spot were rare. In contrast with Singapore teenagers, in whom tilted disc and peripapillary atrophy were common while staphyloma and chorioretinal atrophy were rare, pathologic myopia appears to be dependent on the duration of disease and, thus, age of the individual.

TMEM126A mutation in a Moroccan family with autosomal recessive optic atrophy.

PURPOSE: Nonsyndromic autosomal recessive optic atrophy (arOA) is extremely rare and its existence was disputed until a locus, optic atrophy 6 (OPA6), was mapped to 8q. Recently, a second locus, OPA7, was found on 11q in several families from North Africa, with one presumably ancestral mutation of transmembrane protein 126A (TMEM126A). Here we report an independently ascertained large consanguineous family of Moroccan descent with three siblings affected with nonsyndromic arOA. METHODS: Assuming autosomal recessive inheritance, we identified a locus on 11q with homozygosity mapping, with a multipoint logarithm of the odds score of 3.84, and sequenced two candidate genes. Direct sequencing of the complete coding sequence of TMEM126A revealed mutation p.Arg55X, homozygous in all affected siblings and heterozygous in both unaffected parents. RESULTS: This mutation was identical to that recently reported in families from North Africa, consistent with a single ancestral origin. In contrast to the recently reported patients, however, the siblings reported in this study had a relatively mild clinical course, with sudden onset in adolescence in the proband. Interestingly, the proband, but not the other affected siblings, had sensory-motor axonal neuropathy with electrophysiological data strongly suggestive of focal demyelinating abnormalities. An unaffected sibling had transient loss of vision after exercise, i.e., Uhthoff's sign of optic neuropathy, and was found to be a heterozygous carrier of the mutation. CONCLUSIONS: Our results confirm genetic heterogeneity in arOA, illustrate clinical variability between families with the p.Arg55X mutation including the description of a mild phenotype in a heterozygote, and underscore the implication of mitochondrial proteins in optic and peripheral neuropathy.

Association of beta zone of parapapillary atrophy with age-related macular degeneration in adult Chinese. The Beijing Eye Study.

BACKGROUND: Since parapapillary atrophy and age-related macular degeneration (AMD) share features of their ophthalmoscopic and histological appearance, such as irregular pigmentation, proliferation and loss of the retinal pigment epithelium, it was the purpose of the study to assess whether parapapillary atrophy, particularly beta zone of parapapillary atrophy, is associated with AMD in a population-based investigation. METHODS: The Beijing Eye Study included 4439 subjects out of 5324 subjects invited to participate (response rate 83.4%) with an age of 40 + years. The present investigation consisted of 3874 (82.3%) subjects for whom readable fundus photographs of at least one eye were available with normal intraocular pressure, a refractive error of >- 8 diopters, and no signs of glaucomatous optic neuropathy. RESULTS: In a multivariate analysis, beta zone of parapapillary atrophy was significantly associated with age (P < 0.001), optic disc size (P < 0.001) and myopic refractive error (P < 0.001). It was not significantly associated with presence of retinal pigment depigmentation (P = 0.20) or hyperpigmentation (P = 0.99), drusen size (P = 0.27), and presence of early AMD (P = 0.72) or late AMD (P = 0.99). CONCLUSIONS: Although beta zone of parapapillary atrophy and age-related macular degeneration have a similar histology with irregularities of the retinal pigment epithelium and eventual closure of the choriocapillaris and loss of retinal pigment epithelium cells, the entities are clinically not significantly associated with each other.

Retinal and optic disc atrophy associated with a CACNA1F mutation in a Japanese family.

OBJECTIVE: To describe retinal and optic disc atrophy and a progressive decrease of visual function in 2 Japanese brothers. Both had a mutation in the CACNA1F gene, the causative gene of incomplete congenital stationary night blindness (CSNB). METHODS: We studied observational case reports and performed comprehensive ophthalmologic examinations including best-corrected visual acuity, biomicroscopy, ophthalmoscopy, fundus photography, and electroretinography. Genomic DNA was extracted from the peripheral blood, and all 48 exons of the CACNA1F gene were directly sequenced. RESULTS: The 2 brothers had retinal and optic disc atrophy and a progressive reduction of visual acuity with increasing age. Although these clinical features are not typical of previous patients with incomplete CSNB, both patients had an in-frame mutation with deletion and insertion in exon 4 of the CACNA1F gene. In both patients, the bright-flash, mixed rod-cone electroretinogram had a negative configuration, a characteristic of incomplete CSNB. However, the full-field scotopic and photopic electroretinograms were nonrecordable, indicating severe, diffuse retinal malfunction, which is not typical in incomplete CSNB. CONCLUSION: These findings indicate that a mutation of the CACNA1F gene may be associated with retinal and optic disc atrophy with a progressive decline of visual function. Clinical Relevance In patients with retinal and optic disc atrophy associated with negative-type electroretinograms, a CACNA1F gene mutation should be considered.

OPA1 gene mutations in Japanese patients with bilateral optic atrophy unassociated with mitochondrial DNA mutations at nt 11778, 3460, and 14484.

PURPOSE: To report mutations in the OPA1 gene in Japanese patients with bilateral optic atrophy unassociated with mitochondrial DNA mutations at nt 11778, 3460, and 14484. METHODS: Twelve unrelated patients with bilateral optic atrophy and 100 healthy controls were examined. Each exon of the OPA1 gene was amplified by polymerase chain reaction (PCR). All PCR products were sequenced. RESULTS: Of the 12 patients, 2 had nonsense mutations of the OPA1 gene (nt 1039G --> T and nt 1096C --> T, leading to Glu347Stop and Arg366Stop, respectively). These nonsense mutations were not found in the 100 healthy controls. Two of the patients had silent mutations of OPA1 gene (nt 1177T --> G and nt 1923G --> A causing no amino acid change). CONCLUSIONS: The mutations (Glu347Stop and Arg366Stop) of the OPA1 gene are involved in the pathogenesis of bilateral optic atrophy in Japanese patients.

3-Methylglutaconic aciduria in the Iraqi-Jewish 'optic atrophy plus' (Costeff) syndrome.

Eleven new patients of Iraqi-Jewish origin with bilateral optic atrophy, neurological abnormalities ('optic atrophy plus' syndrome) and 3-methylglutaconic aciduria (type III) are described. Clinical abnormalities in decreasing order of frequency were bilateral optic atrophy, extrapyramidal signs, spasticity, ataxia, dysarthria and cognitive deficit. An association with age was found only for spasticity. Spasticity, extrapyramidal signs and optic atrophy frequently led to major disability, in contrast to ataxia, dysarthria and cognitive deficit. The combined excretion of 3-methylglutaconic and 3-methylglutaric acid ranged between 9 and 187 mmol/mol creatinine. The primary enzymatic defect possibly may reside in the mitochondrial respiratory chain.