Fundus Tessellation and Parapapillary Atrophy, as Ocular Characteristics of Spontaneously High Myopia in Macaques: The Non-Human Primates Eye Study.

Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.

Optic atrophy in prematurity: pathophysiology and clinical features.

Optic atrophy is an important cause of visual impairment in children, and the aetiological profile has changed over time. Technological advancements led by neuroimaging of the visual pathway and imaging of the optic nerve with optical coherence tomography have accelerated the understanding of this condition. In the new millennium, an increasing prevalence of prematurity as a cause of optic atrophy in children has been highlighted. This new shift has been linked with increasing rates of premature births and improved neonatal survival of preterm infants. The available literature is limited to hospital and registry-based cohorts with modest sample sizes, methodological heterogeneity and selection bias limitations. Larger studies that are better designed are required to better understand the contribution of prematurity to the disease burden. In addition to considering other life-threatening aetiologies, screening for premature birth should be covered as part of a comprehensive history when evaluating a child with paediatric optic atrophy.

Beta zone parapapillary atrophy in elderly Chinese.

PURPOSE: Assess the beta zone parapapillary atrophy in elderly Chinese. PATIENTS AND METHODS: The Beijing Eye Study 2011 is a population-based cross-sectional study, which includes 3468 patients with the average age of 64.5 ± 9.8 years. The beta zone of parapapillary atrophy was captured and analyzed morphometrically by using colour optic disc photographs. RESULTS: The beta zone was found in 1358 (39.9%) eyes, measuring 0.37 ± 0.84 mm2 in size, 203.5 ± 81.8° in circumferential angle, 0.36 ± 0.27 mm in the maximum radial extent, the most often and longest in the temporal peripapillary region, followed by the temporal inferior region and the temporal superior region, the nasal region at least. Beta zone has statistically significant association with male gender (P = 0.001), myopic refractive error (P = 0.003), thinner retinal nerve fiber layer thickness (P<0.001), thinner subfoveal choroidal thickness (P<0.001), bigger size of optic disc size (P<0.001). The size of beta zone has statistically significant association with longer axial length (P = 0.004)，increasing age (P<0.001), urban (P = 0.025), cardiovascular disease history (P = 0.025), with age related macular degeneration (P = 0.038), myopic ametropia (P<0.001), thinner retinal nerve fiber layer thickness (P = 0.001), thinner subfoveal choroidal thickness (P<0.001), bigger size of optic disc size (P = 0.001). CONCLUSION: The population prevalence of beta zone was 39.9% in elderly Chinese. The area of the beta zone has statistically significant association with age, urban, the thickness of retinal nerve fiber layer, age related macular degeneration, cardiovascular disease history, axial length, myopic refractive error, size of optic disc size, the thickness of subfoveal choroid.

Demographics and etiologic characteristics of non-glaucomatous optic atrophy: a single-center cross-sectional study from Turkey.

BACKGROUND: Optic atrophy is an end-stage pathology of optic nerve diseases that is characterized by optic nerve pallor and vision loss. Because of its sight-threatening effects, understanding its epidemiology and etiology is crucial. In this study, we aimed to determine the epidemiologic features of optic nerve pathologies which lead to optic atrophy. METHODS: This is a cross-sectional study in which, medical records of optic atrophy patients who were followed up in our clinic between 1999 and 2020 were evaluated. Three hundred and sixty eyes of 226 patients were included in the study. Demographic data were received from the patients' files. Patients with glaucomatous optic atrophy, consecutive optic atrophy and patients with less than a year follow-up were excluded from the study. RESULTS: The most frequent reason of optic atrophy was central nervous system diseases (27.43%) followed by secondary non-arteritic ischemic optic neuropathy (26.99%). The most frequent etiology of optic atrophy was non-arteritic ischemic optic neuropathy in males and central nerve system-related pathologies in females. The highest presentation age (mean 63.6 ± 17.85 years) was observed in arteritic ischemic optic neuropathy and central nerve system-related optic atrophy had the lowest presentation age (median 14 years, IQR [34]). CONCLUSION: Central nerve system diseases and non-arteritic ischemic optic neuropathies were the most common causes of non-glaucomatous and non-consecutive optic atrophy in Turkey. Better understanding of underlying etiologies of optic atrophy may lead us to take precautions timely for irreversible optic nerve dysfunction which is an important reason of blindness.

Prevalence and diagnostic ability of ß-zone parapapillary atrophy in open-angle glaucoma: a systematic review and meta-analysis.

BACKGROUND: ß-Zone parapapillary atrophy (ß-PPA) is a common sign in patients with open-angle glaucoma (OAG). Some studies have suggested that ß-PPA can aid in the diagnosis of OAG. We performed a systematic review and meta-analysis of the prevalence and diagnostic ability of ß-PPA in OAG. METHODS: We performed a literature search in PubMed, Web of Science, Embase and Google Scholar from inception to 1st November, 2021. Both hospital-based and population-based studies that reported details of ß-PPA in OAG were included. RESULTS: We screened 1404 articles from these databases and ultimately included 24 articles in our meta-analysis. The prevalence of ß-PPA in OAG was 0.73 (95% CI 0.67 to 0.78). The results of subgroup analysis by country revealed prevalence rates of 0.83 (95% CI 0.78 to 0.88) in Japan, 0.85 (95% CI 0.64 to 0.97) in Korea, 0.64 (95% CI 0.55 to 0.73) in the USA, 0.61 (95% CI 0.58 to 0.63) in Germany and 0.57 (95% CI 0.39 to 0.74) in China. Fundus photography, Heidelberg retina tomography (HRT), Heidelberg retina angiography (HRA) + indocyanine green angiography (ICGA), Spectral domain optical coherence tomography (SD-OCT)and Swept source optical coherence tomography(SS-OCT) values were 0.65 (95% CI 0.58 to 0.71), 0.70 (95% CI 0.50 to 0.86), 0.78 (95% CI 0.61 to 0.91), 0.77 (95% CI 0.65 to 0.88) and 0.99(95% CI 0.87 to 1.00) respectively. The sensitivity and specificity of ß-PPA as a diagnostic marker were 0.78 (95% CI 0.68 to 0.85) and 0.63 (95% CI 0.51 to 0.73), respectively. CONCLUSIONS: ß-PPA is a potential diagnostic marker for OAG. However, a more detailed understanding of ß-PPA characteristics is needed to improve the ability to predict OAG.

The association of myopia progression with the morphological changes of optic disc and ß-peripapillary atrophy in primary school students.

PURPOSE: To study the association of myopia progression with the morphological changes of optic disc and ß-peripapillary atrophy (ß-PPA) in 8-11 years old primary school students. METHODS: This study was a prospective, school-based investigation. This study included 610 children (1008 eyes) who were continuously observed and had data available from 2016 to 2017 in the Sanhe Cohort Study of the Risk Factors for Myopia (SCSRFM). The children underwent a comprehensive eye examination including measurement of visual acuity, autorefractometry, and posterior segment of the eye. ß-PPA regions and optic disc ovality index were identified and measured on the fundus photographs. RESULTS: The prevalence of myopia was 72.62% (732/1008) in 2016. In myopic children, the prevalence of the vertical ß-PPA, the horizontal ß-PPA, and the oval optic disc were 75.68% (554/732), 75.96% (556/732) and, 11.61% (85/732) respectively. From 2016 to 2017, with the progression of vertical ß-PPA, horizontal ß-PPA, area of ß-PPA, and optic disc ovality index, the myopic diopter and the axial length (AL) were increased. The progression of horizontal ß-PPA was significantly correlated with the progression of myopic diopter and AL (all p < 0.05). The analysis on the distribution of progression rate of parameters in different groups found that the progression rate of horizontal ß-PPA, area of ß-PPA, and optic disc ovality index increased with the increase of the progression of diopter and AL. The progression of horizontal ß-PPA, area of ß-PPA, optic disc ovality index, and diopter in girls were greater than that in boys, and the progression of optic disc ovality index and diopter had a statistical significance (all p < 0.05). CONCLUSIONS: The 1-year follow-up study of the third-grade primary school students showed that with the progression of myopia and the growth of AL, ß-PPA and optic disc ovality index also changed. There was a positive correlation between the change of ß-PPA and optic disc ovality index and the progression of myopia diopter and AL.

Homozygous TFG gene variants expanding the mutational and clinical spectrum of hereditary spastic paraplegia 57 and a review of literature.

In recent years, the tropomyosin-receptor kinase fused gene (TFG) has been linked to diverse hereditary neurodegenerative disorders, including a very rare complex hereditary spastic paraplegia, named spastic paraplegia type 57 (SPG57). Until now, four pathogenic homozygous variants of the TFG gene have been reported associated with SPG57. Two consanguineous Iranian families (1 and 2), the first one with two affected members and the second one with one, all with an early-onset progressive muscle weakness, spasticity, and several neurological symptoms were examined via the whole-exome sequencing. Two homozygous missense variants including c.41A>G (p.Lys14Arg) and c.316C>T (p.Arg106Cys) have been found in the related families. The candidate variants were confirmed by Sanger sequencing and found to co-segregate with the disease in families. The bioinformatics analysis showed the deleterious effects of these nucleotide changes and the variants were classified as pathogenic according to ACMG guidelines. A comparison of the clinical presentation of the patients harboring c.41A>G (p.Lys14Arg) with previously reported SPG57 revealed variability in the severity state and unreported clinical presentation, including, facial atrophy, nystagmus, hyperelastic skin, cryptorchidism, hirsutism, kyphoscoliosis, and pectus excavatum. The affected member of the second family carried a previously reported homozygous c.316C>T (p.Arg106Cys) variant and displayed a complex HSP including optic atrophy. Remarkable clinical differences were observed between the family 1 and 2 harboring the c.41A>G (p.Lys14Arg) and c.316C>T (p.Arg106Cys) variants, which could be attributed to the distinct affected domains (PB1 domains and coiled-coil domains), and therefore, SPG57 might have been representing phenotype vs. variant position correlation.

Martsolf syndrome with novel mutation in the TBC1D20 gene in a family from Iran.

Warburg Micro syndrome and Martsolf syndrome are phenotypically overlapping autosomal recessive conditions characterized by multiple organ abnormalities involving the ocular, nervous, and endocrine systems. Warburg Micro syndrome, the more severe of the two conditions, is caused by loss of function mutations in RAB3GAP1, RAB3GAP2, RAB18, and TBC1D20 genes, whereas Martsolf syndrome has been attributed to less damaging mutations in RAB3GAP1 and RAB3GAP2 genes. We report the clinical description and molecular characterization of a consanguineous Iranian family with two siblings, a male and a female, with dysmorphic features, bilateral congenital cataracts, optic nerve atrophy, congenital glaucoma, mild to moderate intellectual disability, seizures, hypogonadism, and mild osteoporosis. Spastic quadriplegia with contractures was observed in the male patient, while the female patient showed only mild hyperreflexia. Magnetic resonance imaging scans performed in the male patient showed a normal brain structure. Both siblings had neither microcephaly nor postnatal growth retardation. Whole exome sequencing identified a novel homozygous nonsense mutation [c.1060C>T; p.(Arg354Ter)] in the TBC1D20 gene in both siblings and confirmed the heterozygous carrier status of both parents. This report describes a novel mutation in the TBC1D20 gene in two Iranian patients with Martsolf syndrome, further extending the allelic heterogeneity and phenotypic spectrum of this rare condition. The genotype and phenotype of the patients are compared with those of Martsolf syndrome and Warburg Micro syndrome patients reported in the literature.

Ophthalmological changes in hereditary spastic paraplegia and other genetic diseases with spastic paraplegia.

Ophthalmological abnormalities may occur in specific subtypes of hereditary spastic paraplegia (HSP) and in genetic diseases that present with spastic paraplegia mimicking HSP. These ophthalmological changes may precede the motor symptoms and include pigmentary retinal degeneration, ophthalmoplegia, optic atrophy, cataracts and nystagmus. Some ophthalmological abnormalities are more prevalent in specific forms of HSP. Considering that the diagnosis of HSP is usually difficult and complex, specific ophthalmological changes may guide the genetic testing. There are other genetic diseases such as autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), X-linked adrenoleukodystrophy and spastic paraplegia, optic atrophy and neuropathy (SPOAN) that may mimic HSP and also may present with specific ophthalmological changes. In this article, we review the main ophthalmological changes observed in patients with HSP and HSP-like disorders.

Clinical Profile of Low Vision Patients Attending in Low Vision Clinic in a Tertiary Care Hospital.

The purpose of the study was to determine the disease profile of patients attending the low vision clinic of a tertiary eye care hospital at National Institute of Ophthalmology & Hospital (NIO&H), Dhaka, Bangladesh July 2016 to June 2017. Low vision and blindness are major causes of morbidity and an economic burden on the individual, family and the country. Low vision service has emerged as a major challenge faced by the developing countries .so prompt diagnosis; early treatment and early use of low vision devices can improve the quality of life. It was a prospective observational study conducted in low vision clinic at a tertiary care hospital in Bangladesh for one year. A total 419 patient, aged 6-60 years among them 267(63.7%) were male and 152(36.3%) were female. The leading causes of low vision in patient attending the low vision clinic were Retinitis pigmentosa (31.3%) macular dystrophy/stargards diseases & maculopathy (20.3%) and myopia with macular degeneration (14.8%). The percentage of visual impaired (6/18-6/60) were 38.3%, severely visual impaired (<6/60-3/60) were 24.4% & (<3/60) 37.3%. Almost all the patient was prescribed spectacles and Telescope for distant vision, Hand held magnifier and video magnifier were prescribed for near vision. Vision improved with low vision devices (6/18 or better) in 49.5%, (6/18-6/60) in 47.3%, (<6/60-3/60) in 2.8%, (<3/60) in 0.3% patient. Vision with low vision devices were significantly changes (p=0.001). The present study shows that hereditary ocular anomalies (Retinitis pigmentosa, macular dystrophy, myopic degeneration) and amblyopia were more common causes of low vision in this part of world.

Causes of childhood low vision and blindness in New Zealand.

IMPORTANCE: This is the first national study on childhood visual impairment in a developed nation, New Zealand, describing prevalence, aetiology and preventable causes of low vision and blindness in children. BACKGROUND: Causes of childhood blindness vary between regions. This study aimed to present region-specific data on epidemiology of childhood blindness affecting a developed nation, New Zealand. DESIGN: Retrospective data analysis. PARTICIPANTS: All children enrolled with the Blind and Low Vision Education Network New Zealand (BLENNZ) with best-corrected visual acuity ≤6/18, or binocular visual field <10°. METHODS: 1000 out of 1321 children with visual impairment enrolled with BLENNZ were included. The principal cause of visual loss was determined, and the severity of visual loss categorized as low vision, or blindness according to the World Health Organization criteria. MAIN OUTCOME MEASURES: Main outcome measures were degree of visual impairment, aetiology of visual impairment and treatment modalities for visual rehabilitation. RESULTS: The calculated prevalence of childhood blindness and low vision was 0.05% and 0.06%. Principle causes of blindness were cortical visual impairment (31.5%), optic nerve atrophy (16.5%) and optic nerve hypoplasia (9.0%). The main preventable causes of blindness were neonatal trauma/asphyxia (31.5%), retinopathy of prematurity (18.2%) and non-accidental injury (10.3%). CONCLUSIONS AND RELEVANCE: This is the first national report on prevalence of childhood low vision and blindness in New Zealand. The prevalence and leading causes of low vision and blindness found in this study were comparable to other developed nations; however, preventable causes of low vision and blindness appeared unique to New Zealand.

Spastic ataxias.

The presence of spasticity and pyramidal features is a hallmark of some of hereditary ataxias, such as autosomal-recessive spastic ataxia of Charlevoix-Saguenay, other primary spastic ataxias, Friedreich ataxia, or ataxia with isolated vitamin E deficiency. Certain spastic paraplegias, such as spastic paraplegia 7, may present as an ataxic phenotype and often share common pathophysiologic pathways with cerebellar ataxias. Because of the rarity and genetic heterogeneity of these conditions, their molecular diagnosis remains challenging and time consuming. Herein we review the clinical, epidemiologic, and genetic features of the best-defined spastic ataxias with a focus on autosomal-recessive spastic ataxia of Charlevoix-Saguenay, one of the most frequent ataxias worldwide, which presents with a unique early-onset spastic ataxia phenotype. We briefly discuss other genetic and metabolic multisystem disorders where spastic ataxia is a secondary feature. Emphasis is placed on their typical age of onset and key clinical and imaging features that enable discrimination between these complex diseases.

The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management.

Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients suggests that cochlear implantation may be effective in CAPOS patients.

Diabetes mellitus and optic atrophy: study of the Wolfram syndrome / Diabetes mellitus y atrofia óptica: estudio del síndrome de Wolfram

Background: Wolfram syndrome (WS), also known by the acronym DIDMOAD, is a rare and progresive hereditary disease of autosomal recessive inheritance which minimum ascertainment diagnostic criteria are the occurrence together of diabetes mellitus and optic atrophy before 15 years of age. Objective: To describe the clinical, biochemical and molecular profile of WS in a tertiary care hospital in Mexico. Materials and Methods: We reviewed patients records who fulfill the minimum ascertainment diagnostic criteria of WS presenting between January 1987 and May 2015 in a tertiary care hospital in Mexico. Results: Five patients fulfill the inclusion criteria (three male and two female). Diabetes mellitus was the first manifestation of the syndrome in all of them, with a mean age at diagnosis of 5.8 ± 2.71 years, while the WS diagnosis was established at a mean age of 15.8 ± 8.37 years. All the patients had optic atrophy and two of them presented with the complete DIDMOAD spectrum. We found new associations with autoimmune hepatitis and testicular cancer. Conclusions: This study shows the variability of clinical presentation of WS, as well as two new associations.

Antecedentes: El síndrome de Wolfram (SW), también conocido por el acrónimo DIDMOAD, es una enfermedad hereditaria rara y progresiva, de transmisión autosómica recesiva, cuyos criterios diagnósticos mínimos son diabetes mellitus y atrofia óptica antes de los 15 años de edad. Objetivo: Describir la presentación clínica, bioquímica y molecular del SW en un hospital de tercer nivel en México. Material y Métodos: Se revisaron los expedientes de pacientes que cumplían con criterios diagnósticos clínicos mínimos de SW atendidos entre enero de 1987 y mayo de 2015 en un hospital de tercer nivel en México. Resultados: Cinco pacientes cumplieron con los criterios de inclusión (tres hombres y dos mujeres). La diabetes mellitus fue la primera manifestación del síndrome en todos ellos, con una media de edad al diagnóstico de 5.8 ± 2.71 años, mientras que el diagnóstico del SW se estableció en promedio a los 15.8 ± 8.37 años. Todos los pacientes tenían atrofia óptica y dos presentaron el espectro DIDMOAD completo. Se describen nuevas asociaciones con hepatitis autoinmunitaria y cáncer de testículo. Conclusiones: El presente estudio muestra la variabilidad de presentación clínica del SW y dos asociaciones no descritas previamente.

Impact assessment study after 27 years of community-directed treatment with ivermectin in Galadimawa, Kaduna State, Nigeria.

PURPOSE: To assess the impact on blindness after 27 years of community-directed treatment with ivermectin (CDTI) in the Galadimawa community of Kauru Local Government in Kaduna state, Nigeria. The population of Galadimawa constituted about 12% of the total population examined during the ivermectin randomised control trial (RCT) in 1989. The RCT population of 8000 individuals was scattered over 36 villages in Kaduna state. Thus, longitudinal data are available on blindness. MATERIALS AND METHODS: After 27 years of dosing with ivermectin, the people in the community of Galadimawa were re-examined for the prevalence and causes of blindness. This was achieved by an examination of the visually disabled. The findings were compared with the situation in 1989 before the dosing commenced. RESULTS: The population of the village increased from 711 to 1419. The prevalence of blindness dropped from 4.9 to 0.96%. The most common causes of blindness were now cataract (55.2%) and optic atrophy (27.6%), whereas the most common causes in 1989 were onchocerciasis (28.3%), glaucoma (17.4%) and cataract (10.9%). People with optic atrophy were more likely to have taken fewer doses of ivermectin over the years. The blind people encountered in 2016 were on average 17 years older than those seen in 1989, which suggests that blindness, when it occurs, is delayed by almost two decades. CONCLUSION: CDTI has reduced the prevalence of blindness significantly in Galadimawa and may reflect the situation elsewhere in the Kaduna state, which is an oncho-endemic zone.

African Descent and Glaucoma Evaluation Study (ADAGES): Racial Differences in Optic Disc Hemorrhage and Beta-Zone Parapapillary Atrophy.

PURPOSE: To investigate the differences in the frequency of optic disc hemorrhage (DH) and prevalence of beta-zone parapapillary atrophy (ßPPA) between individuals of African descent (AD) and European descent (ED). DESIGN: Prospective, multicenter, observational cohort. PARTICIPANTS: A total of 1950 eyes of 1172 participants of the African Descent and Glaucoma Evaluation Study (ADAGES). METHODS: Stereoscopic disc photographs of subjects with and without glaucomatous optic neuropathy (GON) followed during the first 13 years of the ADAGES underwent masked review searching for DH and ßPPA. A total of 928 eyes (non-GON, 581; GON, 347) of 551 AD patients (non-GON, 334; GON, 217) and 1022 eyes (non-GON, 568; GON, 454) of 611 ED patients (non-GON, 334; GON, 277) were included. We compared the number of eyes with detected DH at any time during follow-up and eyes with ßPPA between the AD and ED groups. The analyses were then adjusted for clinical parameters using multivariable logistic regression. MAIN OUTCOME MEASURES: Differences in frequency of DH and prevalence of ßPPA. RESULTS: A total of 9395 stereoscopic disc photographs were reviewed. More ED eyes experience DH than AD eyes (49/1022 [4.8%] vs. 10/928 eyes [1.1%], respectively; P < 0.001), whereas ßPPA had higher prevalence in AD eyes (675 eyes [72%] vs. 659 eyes [64%]; P < 0.001). In the final multivariable model, after controlling for confounders, AD eyes were less likely to have at least 1 detected DH than ED eyes (odds ratio [OR], 0.21; 95% CI, 0.10-0.45; P < 0.001) but were more likely to have ßPPA than ED eyes (OR, 1.55; 95% CI, 1.12-2.14; P = 0.008). CONCLUSIONS: Subjects of ED are at higher risk for developing DH compared with AD subjects, whereas AD subjects have greater prevalence of ßPPA. These findings suggest that there are structural differences within the optic nerve complex between these groups. Further research is needed to determine whether racial differences in the frequency of DH and prevalence of ßPPA affect the likelihood of glaucomatous progression.

Changing patterns in paediatric optic atrophy aetiology: 1979 to 2015.

BACKGROUND: To evaluate the aetiology of paediatric optic atrophy in an Australian population. DESIGN: Retrospective review of medical records was conducted at The Children's Hospital at Westmead, Sydney, Australia. PARTICIPANTS: Two hundred twenty-seven subjects <16 years who were diagnosed with optic atrophy on fundoscopic examination between 1979 and 2015 were included in the study. METHODS: Subjects were obtained from the hospital database, which codes diagnoses for all admissions, as well as the orthoptic department database, which codes diagnoses for ophthalmology department outpatients. MAIN OUTCOME MEASURES: The predominant cause for optic atrophy was assigned to each patient. Clinical presentation was defined as the principal reason for evaluation. Demographic data included gender, affected eye and age at diagnosis. Data on medical comorbidities (cerebral palsy, developmental delay, microcephaly and seizures) and ocular comorbidities (strabismus and nystagmus) were collected. RESULTS: The mean age at initial eye review was 4.7 ± 4.4 years. There was bilateral optic atrophy in 81.5% of cases. Unilateral optic atrophy was largely due to tumours. When analysing over the three time periods, (1979-1990, 1991-2003 and 2004-2015), perinatal events (3.0%, 22.7% and 22.6%) and neurodegenerative disease (3.0%, 14.9% and 15.1%) are slowly replacing tumours (39.4%, 24.8% and 15.1%) as the top causes for paediatric optic atrophy. The incidence of other causes has remained fairly stable over time, albeit an increase in idiopathic causes. CONCLUSIONS: There has been shift in the etiological profile of optic atrophy. Whilst tumours are still an important cause of paediatric optic atrophy for an Australian population, perinatal events and neurodegenerative disease are becoming more significant.

Leading causes of certifiable visual loss in England and Wales during the year ending 31 March 2013.

PURPOSE: The last article on causes of sight impairment (SI) in England and Wales was for April 2007-March 2008. This report updates these figures for April 2012-March 2013. METHODS: In England and Wales, registration for SI is initiated by completion of a certificate of vision impairment (CVI). The main cause of visual impairment was ascertained for certificates completed April 2012-March 2013. A proportional comparison against April 2007-March 2008 was made. RESULTS: We received 24 009 CVIs of which 10 410 were for severe sight impairment (SSI) and 13 129 were for SI. These numbers were slightly higher than those observed in April 2007-March 2008 (9823 SSI; 12 607 SI). The ratio SI:SSI has remained static with 55% of all certifications being SI. The proportion of certificates without a single main cause has fallen slightly (16.6 to 14%). The proportion of certificates with a main cause of degeneration of the macula and posterior pole (mostly age-related macular degeneration (AMD)) decreased from 58.6 to 50% SSI and from 57.2 to 52.5% SI. Glaucoma remains the second most common cause (11% SSI; 7.6% SI) but hereditary retinal disorders overtook diabetes as third leading cause of SSI. CONCLUSION: AMD is still by far the leading cause of certifications for sight impairment in England and Wales (both SI and SSI). Proportionate changes have been observed since 2008, but it is important to note that a proportionate increase in one condition will impact on others.

SPG7 mutations explain a significant proportion of French Canadian spastic ataxia cases.

Hereditary cerebellar ataxias and hereditary spastic paraplegias are clinically and genetically heterogeneous and often overlapping neurological disorders. Mutations in SPG7 cause the autosomal recessive spastic paraplegia type 7 (SPG7), but recent studies indicate that they are also one of the most common causes of recessive cerebellar ataxia. In Quebec, a significant number of patients affected with cerebellar ataxia and spasticity remain without a molecular diagnosis. We performed whole-exome sequencing in three French Canadian (FC) patients affected with spastic ataxia and uncovered compound heterozygous variants in SPG7 in all three. Sanger sequencing of SPG7 exons and exon/intron boundaries was used to screen additional patients. In total, we identified recessive variants in SPG7 in 22 FC patients belonging to 12 families (38.7% of the families screened), including two novel variants. The p.(Ala510Val) variant was the most common in our cohort. Cerebellar features, including ataxia, were more pronounced than spasticity in this cohort. These results strongly suggest that variants affecting the function of SPG7 are the fourth most common form of recessive ataxia in FC patients. Thus, we propose that SPG7 mutations explain a significant proportion of FC spastic ataxia cases and that this gene should be considered in unresolved patients.