Electrophysiological findings in delayed discovery of a metallic intraocular foreign body in a child: case report.

PURPOSE: To report a case of a child with strabismus and delayed discovery of a metallic intraocular foreign body with good recovery of visual acuity and stereopsis with 36-month follow-up. METHODS: A 4-year-old girl was evaluated due to exotropia of right eye initiated 9 months before with progressive worsening. Visual acuity was 1.00 logMAR (20/200) in the right eye and 0.00 logMAR (20/20) in the left eye. Anterior segment evidenced a small paracentral corneal leukoma, posterior synechia and mild lens opacity in the temporal quadrant only in the right eye. Fundus examination in the right eye identified the presence of an intraocular foreign body, with appearance of metallic components surrounded by retinal pigmented endothelial cells atrophy. Full-field electroretinography (ERG) showed reduced amplitudes and delayed implicit times for both rods and cones in the affected eye. All tests were normal in the fellow eye. RESULTS: Pars plana vitrectomy was promptly performed in the right eye, followed by phacoemulsification with intraocular lens implantation 4 months later due to worsening of the lens opacification. The full-field ERG was repeated after the surgical procedures. The ERG showed mild worsening of all responses in the right eye. After 36 months of follow-up, visual acuity was 0.20 logMAR (20/32) with improvement of the ocular misalignment and with 60 s of arc stereopsis with ERG responses unchanged. CONCLUSION: In this young girl perforating ocular trauma with metallic material was lately diagnosed with strabismus as a sign of alert. Prompt surgical intervention and proper management were essential to provide reasonable visual function including some degree of stereopsis, even though retinal dysfunction characterized by ERG was persistent.

Natural History of Conversion of Leber's Hereditary Optic Neuropathy: A Prospective Case Series.

PURPOSE: To illustrate the natural history of Leber's hereditary optic neuropathy (LHON). DESIGN: Prospective observational case series. PARTICIPANTS: The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation. METHODS: A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged. MAIN OUTCOME MEASURES: The main outcome measures were visual acuity, HVF MD, and RNFL thickness. RESULTS: Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes. CONCLUSIONS: Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau.

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies.

Pathological mitophagy disrupts mitochondrial homeostasis in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON), a disease associated with a mitochondrial DNA mutation, is characterized by blindness due to degeneration of retinal ganglion cells (RGCs) and their axons, which form the optic nerve. We show that a sustained pathological autophagy and compartment-specific mitophagy activity affects LHON patient-derived cells and cybrids, as well as induced pluripotent-stem-cell-derived neurons. This is variably counterbalanced by compensatory mitobiogenesis. The aberrant quality control disrupts mitochondrial homeostasis as reflected by defective bioenergetics and excessive reactive oxygen species production, a stress phenotype that ultimately challenges cell viability by increasing the rate of apoptosis. We counteract this pathological mechanism by using autophagy regulators (clozapine and chloroquine) and redox modulators (idebenone), as well as genetically activating mitochondrial biogenesis (PGC1-α overexpression). This study substantially advances our understanding of LHON pathophysiology, providing an integrated paradigm for pathogenesis of mitochondrial diseases and druggable targets for therapy.

Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies.

Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex. We studied the integrity of the retinohypothalamic tract in five patients with Leber hereditary optic neuropathy, in four with dominant optic atrophy and in nine controls by testing the light-induced suppression of nocturnal melatonin secretion. This response was maintained in optic neuropathy subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case with dominant optic atrophy, compared with three age-matched controls. On these retinas, melanopsin retinal ganglion cells were characterized by immunohistochemistry and their number and distribution evaluated by a new protocol. In control retinas, we show that melanopsin retinal ganglion cells are lost with age and are more represented in the parafoveal region. In patients, we demonstrate a relative sparing of these cells compared with the massive loss of total retinal ganglion cells, even in the most affected areas of the retina. Our results demonstrate that melanopsin retinal ganglion cells resist neurodegeneration due to mitochondrial dysfunction and maintain non-image-forming functions of the eye in these visually impaired patients. We also show that in normal human retinas, these cells are more concentrated around the fovea and are lost with ageing. The current results provide a plausible explanation for the preservation of pupillary light reaction despite profound visual loss in patients with mitochondrial optic neuropathy, revealing the robustness of melanopsin retinal ganglion cells to a metabolic insult and opening the question of mechanisms that might protect these cells.

Prevalence of ocular findings regardless of visual acuity status in older adults from the Brazilian Amazon Region.

Recently, it has been recommended that population-based studies report not only frequencies of vision impairment and blindness but also any ocular abnormalities that might lead an individual to seek for eyecare services. The current study aimed to determine prevalence of ocular findings regardless of visual acuity (VA) status in older adults from the Brazilian Amazon Region. Disturbances were grouped into: Eyelids; Anterior Segment; Posterior Segment; Increased intraocular pressure; and Overall Globe. The presence of an ocular finding was considered positive when any abnormality was noted, regardless of VA. Refractive errors were not considered. A total 2384 eligible persons were enumerated and 2041 (85.6%) examined. The prevalence of ocular disturbances in either eye was 87.0% and was associated with male gender, older age, lower education, and rural residence. Overall, main findings were pterygium, cataract, and pinguecula, occurring in 58.8%, 45.4% and 17.4%, respectively. Among individuals with 20/20 VA in both eyes, the most frequent findings were pterygium, pinguecula, and glaucoma cupping, occurring in 47.4%, 31.2% and 6.5%, respectively. The high prevalence of ocular findings observed in this population reinforces that different conditions might not immediately decrease VA but can indicate risk and/or discomfort symptoms and should be considered when planning public health ophthalmic services.

Natural history of Leber's hereditary optic neuropathy: longitudinal analysis of the retinal nerve fiber layer by optical coherence tomography.

PURPOSE: To investigate by optical coherence tomography (OCT) the topographic pattern and temporal sequence of fiber loss in the peripapillary retinal nerve fiber layer (RNFL) of patients with Leber's hereditary optic neuropathy (LHON) in a longitudinal follow-up. DESIGN: Cohort study. PARTICIPANTS: Six eyes of 4 patients with molecularly defined LHON were enrolled before the subacute period of visual loss. METHODS: Subjects were studied by StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA) during a 9-month follow-up starting from the presymptomatic stage of the disease. Examinations were carried out at 4 different time points: presymptomatic stage, time of visual loss, and 3 and 9 months later. MAIN OUTCOME MEASURES: Peripapillary RNFL thickness for each quadrant of the optic nerve. Statistical comparisons were performed by ordinary analysis of variance with Dunnett's post-test. RESULTS: A significant increase of RNFL thickness was detected in the temporal and inferior quadrants between the presymptomatic stage and the disease onset (P<0.05). The 360-degree average and the superior and nasal quadrants showed a nonstatistically significant increase of thickness at this time. In the 360-degree average (P<0.01), superior (P<0.01), nasal (P<0.05), and inferior (P<0.01) quadrants, RNFL thickening showed statistically significant changes between the presymptomatic stage and the 3-month follow-up. At 3 months, a nonsignificant reduction of RNFL thickness was detected in the temporal quadrant. A significant reduction of RNFL was detected in all but the nasal quadrants between the presymptomatic stage and the 9-month Follow-up. CONCLUSIONS: The RNFL thickness increase first appeared at the temporal and inferior quadrants. Conversely, at 3 months the thickening fibers were more evident in the superior and nasal quadrants. These findings are consistent with the established preferential early involvement of the papillomacular bundle in LHON. We also demonstrated the previously unrecognized simultaneous early involvement of the inferior quadrant. The late involvement of both superior and nasal quadrants suggests a dynamic evolution of the acute stage that continues for 3 months and may represent a therapeutic window of opportunity.

Pterygium in adults from the Brazilian Amazon Region: prevalence, visual status and refractive errors.

AIMS: To determine prevalence of pterygium, its role as main cause of unilateral and bilateral visual impairment and blindness and its impact on refractive errors from adults living in a high ultraviolet exposure area in the Brazilian Amazon Region. METHODS: Cluster sampling was used in randomly selecting subjects ≥45 years of age from urban and rural areas of Parintins city. Eligible subjects were enumerated through a door-to-door household survey and invited for an eye exam including refraction. Pterygium was assessed considering location (nasal, temporal or both) and size (<3 mm or ≥3 mm reaching or not pupillary margin). RESULTS: A total of 2384 persons were enumerated and 2041 (85.6%) were examined. Prevalence of pterygium was 58.8% (95% CI 53.8% to 63.7%) and associated with male gender (OR=1.63; 95% CI 1.37 to 1.94; p=0.001), while higher education was a protective factor (OR=0.63; 95% CI 0.44 to 0.92; p=0.018). Older age and rural residence were associated with pterygium ≥3 mm reaching or not pupillary margin, while higher education was a protective factor for pterygium ≥3 mm reaching pupillary margin. Prevalence of pterygium as cause of visual impairment and blindness was 14.3% and 3.9%, respectively. Significantly higher hyperopic refractive errors were found in eyes with pterygium ≥3 mm reaching or not pupillary margin. CONCLUSIONS: Pterygium was highly prevalent and the second cause of visual impairment and blindness after provision of refractive correction. Risk factors for pterygium were male gender, advanced age, lower education and rural residency. Strategies to provide pterygium early detection and proper management should be considered by healthcare authorities in this population.

Visual impairment and blindness: an overview of prevalence and causes in Brazil.

Our purpose is to provide a summary overview of blindness and visual impairment on the context of recent Brazilian ocular epidemiologic studies. Synthesis of data from two cross-sectional population-based studies - the São Paulo Eye Study and the Refractive Error in School Children Study is presented. 3678 older adults and 2441 school children were examined between July 2004 and December 2005. Prevalence of blindness in older adults using presenting visual acuity was 1.51% decreasing to 1. 07% with refractive correction. The most common causes of blindness in older adults were retinal disorders, followed by cataract and glaucoma. In school children, the prevalence of uncorrected visual impairment was 4.82% decreasing to 0.41% with refractive correction. The most common cause of visual impairment in school children was uncorrected refractive error. Visual impairment and blindness in Brazil is an important public health problem. It is a significant problem in older Brazilians, reinforcing the need to implement prevention of blindness programs for elderly people with emphasis on those without schooling. In school-children cost-effective strategies are needed to address a readily treatable cause of vision impairment - prescription and provision of glasses.

Prevalence and Causes of Visual Impairment and Blindness in Adults Aged 45 Years and Older from Parintins: The Brazilian Amazon Region Eye Survey.

Purpose: To determine the prevalence and causes of visual impairment and blindness in adults aged 45 years and older from Parintins, Brazilian Amazon Region. Methods: A random cluster sampling method was used to identify subjects 45 years of age and older from urban and rural census sectors of Parintins city, Amazonas State, from March 2014 to May 2015. Participants underwent a detailed ocular examination, including presenting (PVA) and best corrected visual acuity (BCVA). The main cause of PVA<20/32 per eye was determined. Results: A total of 2384 subjects were enumerated and 2041 (85.6%) examined. The prevalence of presenting mild visual impairment - MiVI (<20/32 - ≥20/63) in the better-seeing eye was 17.0% [95% CI: 15.3-18.7%], and 8.5% [95% CI: 7.3-9.7%] with best correction. The prevalence of presenting moderate visual impairment - MVI (<20/63 - ≥20/200) was 18.4% [95% CI: 16.2-20.6%], and 6.9% [95% CI: 5.8-8.0%] with best correction. The prevalence of presenting bilateral VA <20/200 was 4.3% [95% CI: 3.6-5.0%], and 3.3% [95% CI: 2.5-4.0%] with best correction and increased with older age. Cataract (47.8%) and glaucoma (7.5%) were its main causes. In less severely affected eyes, uncorrected refractive errors (MVI: 42.6%; MiVI: 79.0%), cataract (MVI: 40.6%; MiVI: 13.7%) and pterygium (MVI: 7.6%; MiVI: 2.7%) were the main causes. Conclusions: Most cases of visual impairment in Parintins are either preventable or treatable, and public health initiatives should target cataract surgical services and refraction with spectacle provision.

Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber hereditary optic neuropathy (LHON).

PURPOSE: To determine the profile of neurodegeneration in Leber hereditary optic neuropathy (LHON). METHODS: We quantitated serum levels of phosphorylated neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients and 59 carriers with LHON, both molecularly characterized as harboring the G to A mutation at nucleotide 11,778 of the mitochondrial genome. The association of subject characteristics to pNF-H levels was studied with multiple regression; pNF-H data were square-root transformed to effect normality of distribution of residuals. Relationships between the square-root of pNF-H and age and sex were investigated within groups with Pearson correlation and the two-sample t-test. Linear regression was used to assess the difference between groups and to determine if the relationship of age was different between affected individuals and carriers. Results of plotting pNF-H levels by age suggested a nonlinear, quadratic association so age squared was used in the statistical analysis. ANCOVA was used to assess the influence of age and group on pNF-H levels. RESULTS: In the carrier group, there was a significant correlation of square-root pNF-H (mean=0.24 ng/ml(2)) with age (r=0.30, p=0.022) and a stronger correlation with quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml(2)) for the affected group, correlations were of similar magnitude, although they were not statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45). There was no correlation between age and pNF-H levels (mean=0.34 ng/ml(2)) in the off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There was no difference between sexes and pNF-H levels in any of the groups (affected, p=0.65; carriers, p=0.19; off-pedigree, p=0.93). CONCLUSIONS: Elevated pNF-H released into the serum of some affected LHON patients may suggest that axonal degeneration occurs at some point after loss of visual function. Increases in pNF-H levels of carriers with increasing age, not seen in off-pedigree controls, may suggest subtle subclinical optic nerve degeneration.

Teleophthalmology Support for Primary Care Diagnosis and Management.

This study was performed to evaluate a healthcare strategy based on teleophthalmology for diagnosis and management of primary healthcare users. A descriptive cross-sectional study was conducted to review the medical records of patients from January 2013 to December 2014 from primary care units in the city of São Paulo. The units referred patients, who had diabetes or high blood pressure, and were users of chloroquine compounds, for a fundus examination. The images were sent to a reading center for review, diagnosis, and patient referrals. From 9173 analyzed patients, 570 (6.2%) were excluded because of poor image quality. Of the remaining patients, 4933 (57.3%) had diabetes, 7242 (84,2%) systemic hypertension, and 113 (1.3%) used chloroquine. Of these, 989 (11.5%) patients needed ophthalmologic treatment. The most frequently prescribed treatments were cataract extraction in 692 (70%) of 989 and photocoagulation in 245 (24.8%) of 989 cases. Overall, cataract extraction was indicated in 692 (8%) of 8603 cases and photocoagulation in 245 (2.8%) of 8603 cases. When only patients with diabetes were considered, the indication for photocoagulation increased to 4.5%.The results showed that non-medical professionals could produce good-quality ocular images for screening of ocular diseases in most cases; only 6.2% of ocular images did not meet quality requirements. Most patients referred for fundus examination did not need a specific treatment, indicating that this system could be an inexpensive and reliable tool for use in developing countries.

Vision Status in Older Adults: The Brazilian Amazon Region Eye Survey.

Older adults living in remote areas with limited access to health services are at higher risk to develop visual impairment and blindness. We conducted a population-based survey to determine the vision status in subjects 45 years of age and older from urban and rural areas of Parintins city, Brazilian Amazon Region. Participants underwent ophthalmic examination, including uncorrected (UCVA), presenting (PVA) and best-corrected visual acuity (BCVA). Vision status was described as lines of visual acuity (VA) impairment and lines of VA improvement from UCVA to BCVA and from PVA to BCVA in the better-seeing eye. A total of 2384 subjects were enumerated, 2041 (85.6%) were examined, with reliable VA measurements obtained from 2025 participants. Vision status in lines of VA impairment was (mean ± standard deviation): 3.44 ± 3.53 for UCVA, 2.85 ± 3.52 for PVA and 1.50 ± 3.51 for BCVA. Female gender, older age and lower education were associated with ≥6 lines of UCVA impairment. Lines of improvement ≥3 was found in 626 (30.9%) participants and associated with female gender and rural residency. In conclusion, a third of participants could have at least three lines of VA improvement with proper refraction. Strategies to improve access to eye care and affordable glasses are needed.

Male prevalence of acquired color vision defects in asymptomatic carriers of Leber's hereditary optic neuropathy.

PURPOSE: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease resulting in loss of central vision and dyschromatopsia, caused by mitochondrial DNA point mutations. However, only a subset of the mutation carriers becomes affected, with a higher penetrance in males. This study was conducted to investigate chromatic losses in asymptomatic carriers of the LHON mutation. METHODS: Monocular chromatic discrimination was studied with the Cambridge Colour Test (CCT; Cambridge Research Systems, Ltd., Rochester, UK) along the protan, deutan, and tritan cone isolation axes in 46 LHON carriers (15 men) belonging to the same LHON maternal lineage and 74 age-matched control subjects (39 men). Inclusion criteria were absence of ophthalmic complaints and clear ocular media. A detailed neuro-ophthalmic examination was performed in all the LHON carriers. RESULTS: The differences in threshold between carriers and control subjects were significant for the three cone isolation axes at P < 0.0001. Sixty-five percent of the carriers had abnormal protan and/or deutan thresholds; some of those with higher thresholds also had elevated tritan thresholds (13%). The male thresholds were higher and more frequent than those of the women for the protan and deutan axes (ANOVA; P < 0.05), but not for tritan thresholds. In the most severe losses, the women had instances of diffuse defect whereas all the men displayed a red-green defect. CONCLUSIONS: Male LHON asymptomatic carriers had color vision losses with the red-green pattern of dyschromatopsia typical of patients affected with LHON, which includes elevation of tritan thresholds as well. This predominantly parvocellular (red-green) impairment is compatible with the histopathology of LHON, which affects mostly the papillomacular bundle. In contrast with male losses, female losses were less frequent and severe. These gender differences are relevant to understanding LHON pathophysiology, suggesting that hormonal factors may be of great importance.

The Brazilian Amazon Region Eye Survey: Design and Methods.

PURPOSE: To describe the study design, operational strategies, procedures, and baseline characteristics of the Brazilian Amazon Region Eye Survey (BARES), a population-based survey of the prevalence and causes of distance and near visual impairment and blindness in older adults residing in the city of Parintins. METHODS: Cluster sampling, based on geographically defined census sectors, was used for cross-sectional random sampling of persons 45 years and older from urban and rural areas. Subjects were enumerated through a door-to-door survey and invited for measurement of uncorrected, presenting and best-corrected visual acuity and an ocular examination. RESULTS: Of 9931 residents (5878 urban and 4053 rural), 2384 individuals (1410 urban and 974 rural) were eligible and 2041 (1180 urban and 861 rural) had a clinical examination (response rate 85.6%). The majority of participants were female (1041, 51.0%); the average age was 59.9 ± 11.1 years (60.2 ± 11.2 years for urban and 59.4 ± 11.1 years for rural); 1360 (66.6%) had primary schooling or less (58.1% in urban and 78.4% in rural) and 57.8% were resident in urban areas. The age distribution between sexes was similar (p = 0.178). Both sex and age distributions of the sample were comparable to that of the Brazilian Amazon Region population. CONCLUSIONS: The BARES cohort will provide information about the prevalence and causes of near and distance vision in this underprivileged and remote population in Brazil.

Chromatic and luminance contrast sensitivities in asymptomatic carriers from a large Brazilian pedigree of 11778 Leber hereditary optic neuropathy.

PURPOSE: To determine whether asymptomatic 11778 LHON carriers demonstrated impairments in (1) chromatic red/green (R/G) and blue/yellow (B/Y) contrast sensitivity functions (CSF) and in (2) luminance contrast sensitivity functions in the spatial CSF (SCSF) and temporal CSF (TCSF) domains. METHODS: Twenty-five carriers (8 male, 17 female; 34.1 +/- 15.1 years of age) of homoplasmic 11778 LHON from the same well-described family and 30 age-matched controls (17 male, 13 female; 29.2 +/- 7.1 years of age) were tested in one eye, randomly selected. Of the 25 eyes tested, 18 had normal fundus, 5 had swelling and microangiopathy, and 2 had temporal pallor. The R/G and B/Y CSFs were obtained after equiluminance correction with bichromatic horizontal sinusoidal gratings at 0.3, 0.7, and 2 cycles per degree (cpd); the SCSFs were obtained with achromatic gratings at 0.3, 2, 6, and 12 cpd; and the TCSFs were obtained at 2, 10, 20, and 33 Hz with sinusoidal modulation of a 2.7 degrees field with a superimposed spatial Gabor function. RESULTS: Differences between carriers and controls were statistically significant for all spatial frequencies of chromatic and luminance SCSFs, but not for the TCSFs. R/G equiluminance settings of carriers differed from those of controls (P < 0.001), requiring higher luminance in the green; B/Y equiluminance settings were not statistically different in carriers and controls. Fundus findings did not correlate with CS results. CONCLUSIONS: Luminance and chromatic spatial CS losses that affected all tested spatial frequencies, are reported in LHON asymptomatic carriers with the mtDNA 11778 mutation. No losses were found in the temporal CSF. An intriguing finding is that the blue system is substantially spared in this LHON family. These represent subclinical visual impairments in otherwise asymptomatic LHON carriers.

Uptake, Barriers and Outcomes in the Follow-up of Patients Referred for Free-of-Cost Cataract Surgery in the Sao Paulo Eye Study.

PURPOSE: To determine uptake, barriers and outcomes in the follow-up of patients referred for free-of-charge, expedited cataract surgery in the Sao Paulo Eye Study (SPES). METHODS: SPES was a population-based study of urban, low-middle income residents aged ≥50 years. Presenting visual acuity (PVA), best-corrected visual acuity, refraction, and slit-lamp examination were performed in 3677 participants. For subjects with cataract as a principal cause of best-corrected visual acuity ≤20/40, surgery was offered free of charge. Two years after the baseline study, surgery uptake, barriers to surgery, and visual outcomes were analyzed. RESULTS: Among 210 (5.71%) participants who had a cataract surgery indication at baseline, 164 (78.1%) were successfully contacted and 55 (33.5%) reported being operated on for cataract, with 51 agreeing to be re-examined. In a multiple logistic regression model, age, sex, schooling, previous cataract surgery, and PVA at baseline were not significantly associated with surgery uptake. Co-existing health conditions (20.4%), fear of surgery (12.2%) and fear of losing eyesight (11.6%) were the most frequent barriers to cataract surgery adherence. Among the 69 eyes operated on in the interval between baseline and follow-up, PVA ≥20/63 was observed in 50 (72.6%, 95% confidence interval, CI, 62.2-82.3%), PVA <20/63-20/200 in 11 (15.8%, 95% CI 8.9-22.9%) and PVA <20/200 in 8 (11.6%, 95% CI 5.3-17.9%). CONCLUSIONS: Quality of surgery is an increasing determinant of uptake rates. Although free-of-charge and expedited cataract surgery was offered, surgical outcomes might have influenced the low uptake. Aside from cataract surgery campaigns, improvement of surgeon skills, accurate biometry, treatment of ocular comorbidities, postoperative follow-up and eye-care education are needed.

Macular Microcysts in Mitochondrial Optic Neuropathies: Prevalence and Retinal Layer Thickness Measurements.

PURPOSE: To investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON). METHODS: All patients with molecularly confirmed MON, i.e. Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections. RESULTS: MM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7µm vs 122.3±9µm in MM patients (p<0.01) and 128.5±8µm vs. 122.3±9µm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mµ) compared to patients without MM [77.5±8mµ (p<0.001)] and controls [78.4±7mµ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls. CONCLUSION: The prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces.

Development of an instrument to assess vision-related quality of life in young children.

PURPOSE: Quality of life (QOL) instruments are increasingly utilized in ophthalmological research. Measuring vision-related QOL in young children is complicated by constantly evolving abilities related to normal growth and development. Our aim was to develop vision-related QOL instruments for children in different age ranges <==7 years, and to provide initial validation of these instruments. DESIGN: Cross-sectional study. SETTING: Multicenter. PATIENTS: 773 pediatric patients (age <==7 years) with a wide range of ophthalmological diagnoses. PROCEDURE: Questionnaire. A 61-item prototype instrument with a wide variety of items was applied to 403 consecutive patients. The usefulness of items was evaluated as a function of age in order to derive two age-group specific instruments and to find the age limit dividing the age groups. Thus, age-specific versions of a Children's Visual Function Questionnaire (CVFQ) were defined for ages <3 years and >/=3 years, and applied to a convenience sample of patients. OUTCOME: Subscale scores. Factor analysis helped identify underlying dimensions of the data, and corresponding subscales were defined. Validation was provided by examining the internal consistency reliability and by exploring the associations between scores and clinical characteristics. RESULTS: Subscales for General health, General vision, Competence, Personality, Family impact, and Treatment were defined, with internal consistency reliabilities ranging from 0.60 to 0.86. The association between subscales scores and age was weak, whereas strong correlations were found with the level of visual impairment and type of visual diagnosis. CONCLUSION: The CVFQ assesses the impact of visual impairment on children and their families, and is expected to become a useful tool for the pediatric vision research community.