Impact of keratoprosthesis implantation on retinal and visual pathway function assessed by electrophysiological testing.

PURPOSE: To investigate the impact of Boston Type I Keratoprosthesis (BI-Kpro) implantation on retinal and visual pathway function, respectively, assessed by full-field electroretinography (ERG) and visually evoked potentials (VEPs). METHODS: This is a prospective interventional longitudinal study, and patients with BI-Kpro implantation were assessed preoperatively and at 3 and 12 months after surgery. ERG, flash, and pattern-reversal VEPs (15' and 60' checks) along with visual acuity (VA) were performed. RESULTS: A total of 13 patients (24 to 88 years of age) were included. Mean baseline VA (logMAR) improved from 2.30 to 1.04 at 3 months and to 1.00 at 12 months. Flash VEPs were normal in 6 (46%) patients and in 10 (77%) patients at the 12-month follow-up. PVEP was non-detectable in all patients preoperatively for both check sizes. For 15' check size, 6 (46%) patients showed responses after 3 and 12 months except for 1 patient with normal responses at 12 months with the remaining non-detectable. For 60' checks, 11 (85%) patients had responses 3 months after surgery with only 9 (70%) showing responses at 12 months. Abnormal full-field ERGs were found in all patients preoperatively. Amplitude improvement was found in 10 (77%) patients from baseline to 3 months and in 8 (62%) patients from the 3- to the 12-month follow-up. CONCLUSIONS: In this small cohort of patients with BI-Kpro implantation, a remarkable improvement on visual function quantitatively assessed by electrophysiological testing was found in the majority of cases. Visual electrophysiological testing can contribute to objectively assess functional outcomes in this population.

Contribution of objectively measured grating acuity by sweep visually evoked potentials to the diagnosis of unexplained visual loss.

PURPOSE: To investigate the diagnostic contribution of grating visual acuity (GVA) measured by sweep pattern-reversal visually evoked potentials (SPRVEP) in unexplained visual loss (UVL). METHODS: This case-control study included adult patients under suspicion of UVL referred to SPRVEP and transient pattern-reversal visually evoked potentials (TPRVEP) testing. Optotype visual acuity (OVA) was measured by ETDRS 4-meter chart and GVA by SPRVEP. UVL patients were assigned into three distinctive categories, according to the presence of ocular disease, motivation, and electrophysiological evaluation, as follows: exaggerators, malingerers, and psychogenic. Healthy controls and patients with organic visual loss were also tested. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of GVA and TPRVEP parameters. RESULTS: A total of 76 patients with UVL were analyzed: 60 (79.0%) exaggerators, 11 (14.4%) malingerers, and 5 (6.6%) psychogenic. Controls were 49 subjects evaluated for TPRVEP and 28 subjects for SPRVEP. There were 13 patients with organic visual loss enrolled. Mean difference between OVA and GVA was 1.19±0.67 (median=0.84; 95% CI: 1.04 to 1.34) in UVL and 0.14 ±0.09 (median= 0.14; 95% CI: 0.08 to 0.20) in organic visual loss. The area under the ROC curve (AUC) of GVA to distinguish UVL from healthy controls was 0.998 with a cutoff of 0.09 logMAR showing specificity of 100% and sensitivity of 96.0%. CONCLUSIONS: GVA measured by SPRVEP had good diagnostic validity to discriminate patients with unexplained visual loss from healthy controls and patients with organic visual loss, demonstrating its contribution to the diagnosis of this condition.

Photopic negative response using a handheld mini-ganzfeld stimulator in healthy adults: normative values, intra- and inter-session variability.

PURPOSE: To determine normative values, intra- and inter-session variability for a range of parameters derived from the photopic negative response (PhNR) using a handheld mini-Ganzfeld stimulator in healthy normal adults. METHODS: Light-adapted flash full-field electroretinograms (ERGs) were recorded from healthy individuals with no visual complaints, visual acuity equal to or better than 0.0 logMAR (20/20 Snellen), and negative family history for visual diseases. ERGs were recorded from both eyes using a DTL® type fiber electrode after dilation of the pupils with instillation of 1 drop of tropicamide eye drops (1%). The full-field PhNR stimulus conditions were produced by a LED-based ColorBurst™ (Diagnosys LLC, Lowell, MA, USA) handheld stimulator. Red flashes of 1, 5 and 7 cd.s/m2 on a blue background of 10 cd/m2 were presented. A-wave, b-wave and PhNR amplitude (determined by both baseline to trough-BT and peak to trough-PT) and peak times were analyzed. Normal limits were determined as 5% percentile for amplitudes and 95% percentile for latencies. Intra- and inter-session variability were assessed with Wilcoxon signed-rank test, intraclass correlation coefficient (ICC) and the coefficient of variability (COV). RESULTS: Normative limits for PhNR amplitude (µV) using 1, 5 and 7 cd.s./m2 stimuli were, respectively: 20.81; 18.06 and 19.60 for BT and 69.11; 77.98; 76.51 for PT. Peak times (ms) normative limits for 1, 5 and 7 cd.s/m2 intensities were, respectively, 65.98; 78.20 and 77.96. Overall, intra-session variability assessed by coefficients of variation ranged from 1.35 to 10.28%. Inter-session variability disclosed significant intraclass correlation values for all PhNR parameters only for 1 cd.s/m2 stimuli. CONCLUSIONS: The normative values provided by this study are clinically helpful in the diagnosis of inner retinal disorders, especially those affecting retinal ganglion cells such as glaucoma and other optic neuropathies. Further studies, including a larger sample with variable age range would extend the validity of the current results.

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.

Visual function assessed by visually evoked potentials in optic pathway low-grade gliomas with and without neurofibromatosis type 1.

PURPOSE: To investigate the contribution of full-field transient pattern-reversal visually evoked potentials (PRVEP) on cross-sectional evaluations of visual function in patients with and without neurofibromatosis type 1 (NF1) affected by optic pathway low-grade gliomas (OPLGG). METHODS: Participants were children and adolescents referred for visual function evaluation and receiving treatment for OPLGG, linked (NF1-OPLGG) or not to NF1 (Non-NF1-OPLGG). An age-adjusted control group was included for comparison. Monocular full-field PRVEPs were recorded from each eye in accordance with ISCEV standards. Parameters of peak-to-peak P100 amplitude (µV) and P100 peak time (ms) were measured. Cutoff normative values obtained from controls for 15' and 60' check sizes were ≥ 9.0 µV for N75-P100 amplitude and ≤ 103.0 ms for P100 peak time. The association of age, gender, tumor resection and NF1 with P100 amplitude reduction and P100 peak time delay was explored by Firth logistic regression modeling. RESULTS: Participants were 30 patients (15 males, 60% Non-NF1) with ages from 3.6 to 19.9 years (mean ± SD = 9.2 ± 3.8 years; median = 8.4 years) and 19 controls (12 males) with ages from 3.7 to 19.9 years (mean ± SD = 10.4 ± 4.9 years; median = 9.5 years). Overall, 68% of tested eyes presented reduced P100 amplitudes for both check sizes (46% in the NF-1 and 83% in the Non-NF1) and delayed P100 for both check sizes (38% in NF1 and 89% in Non-NF1). Absence of NF1 adjusted for age, gender and tumor resection was significantly associated with marginally reduced P100 amplitude for 15' checks [odds ratio (OR): 6.26; 95% confidence interval (CI) = 0.96-40.94; p = 0.055]. CONCLUSIONS: Full-field PRVEP on cross-sectional evaluations contributed to detect visual dysfunction in two-thirds of patients with OPLGG by highlighting subclinical evidence of visual loss. Abnormalities were more frequent and more severe in OPLGG not linked to NF1 than in NF1-OPLGG; however, there was a difference in surgical management between these groups. PRVEP parameters may provide reliable evidence of visual pathway involvement in OPLGG, helping to hasten treatment before optic atrophy is detected.

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.

Gender-based normative values for pattern-reversal and flash visually evoked potentials under binocular and monocular stimulation in healthy adults.

PURPOSE: To determine gender-based normative values for pattern-reversal (PR) and flash (F) visually evoked potentials (VEP) under binocular and monocular stimulation in healthy adults. METHODS: Healthy adults (age ≥18 years) were recruited among university employees and students. Inclusion criteria were absence of abnormalities in fundoscopy, tracking ability, stereopsis and pupillary reflexes; best-corrected visual acuity ≤.00 logMAR; and refractive error (spherical equivalent) from -6.00 to +6.00. Exclusion criteria were previous intraocular surgery, systemic and/or neurological disorders. Binocular and monocular tests were performed according to International Society for Clinical Electrophysiology of Vision standards for PRVEP (reversal rate = 1.9 Hz, checkerboard stimuli 15' and 60' at 100% contrast) and FVEP (3 cd s/m2, rate = 1 Hz). VEP parameters of amplitude (µV) and peak times (ms) were measured. Inter-ocular differences, inter-peak intervals (N135-N75) and binocular summation were determined. RESULTS: Fifty-four subjects (28 females; mean age = 40.4 ± 13.7 years; median = 40.0 years) were included. Mean P100 latencies for 15' and 60' stimuli were, respectively, 94.6 ± 4.7 ms and 96.1 ± 4.2 for women. Mean values of P100 latency for men were 97.4 ± 4.9 for 15' and 97.7 ± 4.2 for 60' stimuli. Larger mean P100 for 15' checks was observed in women (12.8 ± 5.7 µV) than men (8.6 ± 2.5 µV) in PRVEP. Similar results were found for FVEP N2-P2 amplitudes (mean = 14.6 ± 4.9 for women and 9.8 ± 4.0 for men). CONCLUSIONS: Gender-based normative values for PRVEP and FVEP were determined, with women disclosing higher responses than men for smaller stimuli in the visual pathway. The use of gender-based normative values in the analysis of clinical VEP data for diagnostic and therapeutic purposes is recommendable. Additional analysis including inter-peak intervals and binocular summation ratio might improve the diagnostic power of VEP.

Ocular toxicity assessment of chronic sildenafil therapy for pulmonary arterial hypertension.

PURPOSE: The aim of this study was to investigate possible functional and structural ocular changes caused by chronic sildenafil therapy to treat pulmonary arterial hypertension (PAH). METHODS: Case-control study included patients with pulmonary arterial hypertension: chronically using sildenafil and without sildenafil treatment. A comprehensive ophthalmologic exam including ectoscopy, extrinsic ocular motility, logMAR visual acuity measurement, contrast sensitivity test, color test, anterior segment biomicroscopy, Schirmer test 1, intraocular pressure, fundus exam under pupil dilation, fundus pictures, time domain and spectral domain optical coherence tomography, ocular Doppler ultrasound were performed. Full-field electroretinography (ERG) was tested for each eye in a subgroup of sildenafil-treated patients. RESULTS: Twenty patients from each group were tested. Bilateral severe keratitis was found in seven (35 %) patients under sildenafil therapy. Lacrimal film break-up time (BUT) was significantly reduced (p = 0.006 respectively) and Doppler ultrasound showed a reduced resistance index of the central retinal artery in the group of sildenafil users (p = 0.019). No diffuse retinal functional abnormalities were found in ERG in treated patients. Visual acuity, contrast sensitivity and color discrimination were normal in both groups. No abnormalities were found in both time-domain and spectral-domain OCT for retinal parameters. CONCLUSIONS: One-third of the treated PAH group showed severe bilateral keratitis. This finding could be related to connective tissue abnormalities usually present in patients with this condition that might be exacerbated with the sildenafil usage. The resistance index of the central retinal artery was diminished in the chronic users group and it could be associated to the vasodilation caused by the medication in the choroidal vessels. An ophthalmic assessment for these patients is recommended to diagnose and treat possible ocular surface and choroidal blood flow abnormalities caused by sildenafil.

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.

Contributing factors to VEP grating acuity deficit and inter-ocular acuity difference in children with cerebral visual impairment.

PURPOSE: To investigate contributing factors to visual evoked potential (VEP) grating acuity deficit (GAD) and inter-ocular acuity difference (IAD) measured by sweep-VEPs in children with cerebral visual impairment (CVI). METHODS: VEP GAD was calculated for the better acuity eye by subtracting acuity thresholds from mean normal VEP grating acuity according to norms from our own laboratory. Deficits were categorized as mild (0.17 ≤ deficit < 0.40 log units), moderate (0.40 ≤ deficit < 0.70 log units) or severe (deficit ≥0.70 log units). Maximum acceptable IAD was 0.10 log units. RESULTS: A group of 115 children (66 males-57 %) with ages ranging from 1.2 to 166.5 months (median = 17.7) was examined. VEP GAD ranged from 0.17 to 1.28 log units (mean = 0.68 ± 0.27; median = 0.71), and it was mild in 23 (20 %) children, moderate in 32 (28 %) and severe in 60 (52 %). Severe deficit was significantly associated with older age and anti-seizure drug therapy. IAD ranged from 0 to 0.49 log units (mean = 0.06 ± 0.08; median = 0.04) and was acceptable in 96 (83 %) children. Children with strabismus and nystagmus had IAD significantly larger compared to children with orthoposition. CONCLUSION: In a large cohort of children with CVI, variable severity of VEP GAD was found, with more than half of the children with severe deficits. Older children and those under anti-seizure therapy were at higher risk for larger deficits. Strabismus and nystagmus provided larger IADs. These results should be taken into account on the clinical management of children with this leading cause of bilateral visual impairment.

Regional Disparities in Prevalence and Causes of Visual Impairment and Blindness, Cataract Surgical Coverage and Ocular Findings in Adults 50 Years and Older in Brazil: A Comparative Analysis between Two Population-Based Cross-Sectional Surveys Performed Within a 10-Year Interval.

PURPOSE: To investigate disparities in the prevalence and causes of visual impairment and blindness, cataract surgical coverage, and ocular findings in older adults from two Brazilian geo-socio-demographic areas, São Paulo and Parintins cities. METHODS: Data from two population-based studies including participants 50 years and older from the cities of São Paulo (São Paulo Eye Study - SPES, 2004) and Parintins (Brazilian Amazon Region Eye Survey - BARES, 2014) were aggregated. RESULTS: A total of 5318 participants (3677 from SPES;1641 from BARES) were included. The prevalence of severe visual impairment (SVI) and blindness were, respectively, 0.74% (0.46-1.02) and 0.77% (0.48-1.05) in SPES and 1.72% (1.09-2.35) and 3.44% (2.55-4.33) in BARES. SVI and blindness were associated with BARES study [OR = 2.27 (1.30-3.95); p = .004 - SVI] [OR:4.07 (2.51-6.60); p < .001- blindness]; and older age [OR = 10.93 (4.20-28.45); p < .001 - SPES; OR = 17.96 (8.75-36.83); p < .001 - BARES] while higher education level was a protective factor [OR = 0.21 (0.05-0.95) - SPES; p = .042; OR = 0.21 (0.05-0.91); p = .037 - BARES]. Cataract was the main cause of bilateral severe visual impairment (25.93% in SPES and 64.29% in BARES) and bilateral blindness (21.43% in SPES and 35.71% in BARES). Cataract surgical coverage was significantly lower in BARES (36.32%) compared to SPES (57.75%). CONCLUSION: The prevalence of SVI and blindness was three times higher in older adults from the Brazilian Amazon compared to those living in São Paulo city, despite a 10-year interval between the two studies. These disparities should be mitigated by initiatives to promote access to eye care services targeting underprivileged and remote Brazilian areas.

Impact of pterygium on central corneal thickness measured by optical coherence tomography in older adults.

PURPOSE: To measure the central corneal thickness (CCT) using anterior segment optical coherence tomography (AS-OCT) in older adults with and without pterygium from the Brazilian Amazon Region Eye Survey (BARES). METHODS: BARES is a population-based epidemiological cross-sectional study conducted in Parintins city. Participants were residents ≥45 years of age identified through a door-to-door interview. Eligible participants were invited for a comprehensive eye exam. Pterygium occurrence and severity were assessed by ophthalmologists through slit-lamp examination considering its location (nasal or/and temporal) and severity (lesion with extension <3 mm, ≥3 mm not reaching the pupillary margin or ≥3 mm reaching the pupillary margin). CCTs were obtained and measurements from the more severely affected eye were included. Images were analyzed offline by masked observers. RESULTS: A total of 671 subjects, 533 (79.4%) with pterygium in at least one eye and 138 (20.6%) without pterygium in either eye, were examined. The mean CCT evaluated by multiple linear regression and adjusted for demographic variables and pterygium severity was 521 ± 34 µm (median = 521; range = 304-665). Decreased CCT was significantly associated with age and pterygium severity. Individuals aged 65-74 years had CCT 7 µm thinner than those aged 45-54 years (p = 0.044), individuals aged 75 years and older had CCT 15 µm thinner than those aged 45-54 years (p = 0.001), and eyes with severe pterygium had CCT 33 µm thinner than eyes without pterygium (p < 0.001). CONCLUSIONS: The CCT analysis in this population-based sample shows that a thinner cornea is associated with pterygium severity and older age.

Trends in cataract surgical treatment within the Brazilian national public health system over a 20-year period: Implications for Universal Eye Health as a global public health goal.

Cataract is a highly prevalent, treatable, and sight threatening condition considered one of the main focuses of public health policies addressing visual impairment and blindness towards Universal Eye Health. We aimed to investigate the trends on number of cataract surgical procedures performed through the Brazilian national health system (SUS) from 2000 to 2019 while also evaluating costs associated with it. The Brazilian Public Health System Information Database (DATASUS) was used as the primary data source for procedures including extracapsular cataract extraction (ECCE) and phacoemulsification. Trends along the years were evaluated through generalized linear models. A total of 8,424,521 cataract procedures were performed from 2000 to 2019, with a significant increase along the years from 228,145 in 2000 to 663,186 in 2019 (p<0.001), a cataract surgical procedure rate change from 13.15 to 32.28 procedures per 10,000 people. It was observed a significant increase on the number of phacoemulsification (p<0.001) and a significant decrease on the number of ECCE (p<0.001). A shift on the predominant technique has occurred between 2007 and 2008 with phacoemulsification increasing its percentual representativity from 34.3% to 69.7% of all procedures, reaching 96.1% in 2019. Phacoemulsification costs per procedure increased 30.5% from from USD$119.00 to USD$155.33 (p = 0.007) and the ECCE costs per procedure increased 29.1% from USD$78.57 to USD$101.43 (p = 0.001). There is an increasing trend of procedures related to cataract treatment performed through SUS along the 20-years period and a switch on the technique predominance from ECCE to phacoemulsification was observed after 2007. The costs associated with both techniques have increased but have not followed the country's overall inflation. Data derived from DATASUS is important to understand the overall panorama of ocular health offered by the national health system and to provide information to guide healthcare leaders on management and planning of public health policies within the system.

B-scan ultrasound, visual electrophysiology and perioperative videoendoscopy for predicting functional results in keratoprosthesis candidates.

BACKGROUND/AIMS: We analysed the ability of B-scan ultrasound, ocular electrophysiology testing and videoendoscopic examination for predicting visual prognosis in Boston Type 1 keratoprosthesis (KPro-1) candidates. Indirect anatomical and electrophysiological findings and results from direct endoscopic evaluations were correlated with postoperative functional data. METHODS: In this prospective and interventional study, we included 13 individuals who had previously been indicated for Kpro-1 surgery. All subjects underwent preoperative screening, including ophthalmic evaluation, B-scan ultrasound, electrophysiological testing, and perioperative intraocular videoendoscopic evaluation (VE). B-scan ultrasound, electrophysiological testing, and VE evaluation results were categorised as favourable or unfavourable predictors of postoperative functional results according to predefined criteria. The predictability values of B-scan ultrasound, electrophysiological testing, and VE prognostication were calculated based on the visual acuity level achieved. RESULTS: All surgeries and perioperative VEs were uneventful. Preoperative best-corrected visual acuity (BCVA) ranged from light perception to counting fingers. The 1-year postoperative BCVA was better than 20/200 (satisfactory visual acuity result) in 10 eyes (76.9%) and 20/40 or better in 5 eyes (38.5%). B-scan ultrasound presented a positive predictive value (PPV) of 85.7% for satisfactory postoperative visual acuity, electroretinography showed a PPV of 66.7%, and visual evoked potential presented a PPV of 66.7%. The perioperative VE PPV of a negative finding for satisfactory visual acuity was 100%. CONCLUSIONS: Fundoscopic visualisation by intraocular VE is a minimally invasive procedure that can be used to predict functional outcomes in keratoprosthesis candidates. This technique demonstrated better prognostication in keratoprosthesis candidates than B-scan ultrasound and electrophysiological testing.

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.

Effective refractive error coverage in adults aged 50 years and older: estimates from population-based surveys in 61 countries.

BACKGROUND: In 2021, WHO Member States endorsed a global target of a 40-percentage-point increase in effective refractive error coverage (eREC; with a 6/12 visual acuity threshold) by 2030. This study models global and regional estimates of eREC as a baseline for the WHO initiative. METHODS: The Vision Loss Expert Group analysed data from 565 448 participants of 169 population-based eye surveys conducted since 2000 to calculate eREC (met need/[met need + undermet need + unmet need]). A binary logistic regression model was used to estimate eREC by Global Burden of Disease (GBD) Study super region among adults aged 50 years and older. FINDINGS: In 2021, distance eREC was 79·1% (95% CI 72·4-85·0) in the high-income super region; 62·1% (54·7-68·8) in north Africa and Middle East; 49·5% (45·0-54·0) in central Europe, eastern Europe, and central Asia; 40·0% (31·7-48·2) in southeast Asia, east Asia, and Oceania; 34·5% (29·4-40·0) in Latin America and the Caribbean; 9·0% (6·5-12·0) in south Asia; and 5·7% (3·1-9·0) in sub-Saharan Africa. eREC was higher in men and reduced with increasing age. Global distance eREC increased from 2000 to 2021 by 19·0%. Global near vision eREC for 2021 was 20·5% (95% CI 17·8-24·4). INTERPRETATION: Over the past 20 years, distance eREC has increased in each super region yet the WHO target will require substantial improvements in quantity and quality of refractive services in particular for near vision impairment. FUNDING: WHO, Sightsavers, The Fred Hollows Foundation, Fondation Thea, Brien Holden Vision Institute, Lions Clubs International Foundation.

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.

Visual function assessed by visually evoked potentials in adults with orbital and other primary intracranial tumors.

PURPOSE: The purpose of this study was to assess visual function by visually evoked potentials in adults with orbital and other primary brain tumors affecting the optic pathway. METHODS: In this retrospective case-control series, patients with orbital (intraconal and extraconal) or midline/chiasmatic tumors were included. Visually evoked potentials using pattern-reversal visually evoked potential and flash visually evoked potential stimuli were performed according to the international standards. Outcome measures were visually evoked potential parameters of amplitude (µV) and peak times (ms) measured both for the P100 component (pattern-reversal visually evoked potentials) and the N2P2 complex (flash visually evoked potential). Individual results were also compared with gender-based normative values. RESULTS: A group of 21 adult patients (17 females) and age- and sex-matched controls were evaluated. Tumor location was intraconal (6 meningiomas, 3 hemangiomas, 1 glioma), extraconal (6 meningiomas), and midline (3 pituitary adenomas, 2 hypothalamic/chiasmatic low-grade gliomas). Abnormal fundus (76%), abnormal pupillary reflexes (71%), reduced visual acuity (62%), strabismus (48%), and proptosis (38%) were present. Visually evoked potential abnormalities were found in at least one eye of all cases. Affected eyes had significantly reduced amplitudes and prolonged peak times for pattern-reversal visually evoked potentials (p < .001) and significantly reduced amplitudes for flash visually evoked potential (p < .001). In unilateral orbital tumors, abnormally prolonged pattern-reversal visually evoked potential peak times were also detected in some contralateral eyes (n = 6/16). CONCLUSION: Visually evoked potential abnormalities were found in all adult patients with orbital and other intracranial primary tumors, even in eyes with normal exam and good visual acuity. Visually evoked potential can be used as a non-invasive ancillary test to characterize and monitor visual function in subjects with these neoplastic lesions.

Grating visual acuity impairment assessed by sweep visually evoked potentials in children with optic pathway tumors unable to perform optotype acuity tests.

PURPOSE: To determine visual impairment due to optic pathway tumors in children unable to perform recognition acuity tests. METHODS: Grating visual acuity scores, in logMAR, were obtained by sweep visually evoked potentials (SVEP) in children with optic pathway tumors. The binocular grating visual acuity deficit was calculated by comparison with age-based norms and then assigned to categories of visual impairment as mild (from 0.10 to 0.39 logMAR), moderate (from 0.40 to 0.79 logMAR), or severe (≥0.80 logMAR). Interocular differences were calculated by subtraction and considered increased if >0.10 logMAR. RESULTS: The participants were 25 children (13 boys; mean ± SD age, 35.1 ± 25.9 months; median age, 32.0 months) with optic pathway tumors (24 gliomas and 1 embryonal tumor), mostly located at the hypothalamic-chiasmatic transition (n=21; 84.0%) with visual abnormalities reported by parents (n=17; 68.0%). The mean grating acuity deficit was 0.60 ± 0.36 logMAR (median, 0.56 logMAR). Visual impairment was detected in all cases and was classified as mild in 10 (40.0%), moderate in 8 (32.0%), and severe in 7 (28.0%) children, along with increased interocular differences (>0.1 logMAR) (n=16; 64.0%). The remarkable ophthalmological abnormalities were nystagmus (n=17; 68.0%), optic disc cupping and/or pallor (n=13; 52.0%), strabismus (n=12; 48.0%), and poor visual behavior (n=9; 36.0%). CONCLUSION: In children with optic pathway tumors who were unable to perform recognition acuity tests, it was possible to quantify visual impairment by sweep-visually evoked potentials and to evaluate interocular differences in acuity. The severity of age-based grating visual acuity deficit and interocular differences was in accordance with ophthalmological abnormalities and neuroimaging results. Grating visual acuity deficit is useful for characterizing visual status in children with optic pathway tumors and for supporting neuro-oncologic management.