Self-reported glaucoma prevalence and related factors, contribution to reported visual impairment, and functional burden in a cross-sectional study in Colombia.

PURPOSE: Describe the self-reported prevalence of glaucoma in Colombian older adults, emphasizing the most important risk factors and associated daily-life functional alterations. METHODS: This a secondary analysis of the Health, Wellness, and Aging survey conducted in the year 2015. Diagnosis of glaucoma was obtained from self-report. Functional variables were assessed through activities of daily living questionnaires. A descriptive analysis followed by bivariate and multivariate regression models adjusting for confounding variables was conducted. RESULTS: Self-reported prevalence of glaucoma was 5.67%, with higher rate in women, OR 1.22 (1.13-1.40) p = .003, older age OR 1.02 (1.01-1.02) p < .001, and with higher education OR 1.38 (1.28-1.50) p < .001. Glaucoma was independently associated with diabetes OR 1.37 (1.18-1.61) p < .001 and hypertension 1.26 (1.08-1.46) p = .003. It also showed statistically significant correlations with poor SRH OR 1.15 (1.02-1.32) p < .001, self-reported visual impairment 1.73 (1.50-2.01) p < .001, and impairment in money management OR 1.59 (1.16-2.08) p = .002, grocery shopping OR 1.57 (1.26-1.96) p < .001 and preparing meals OR 1.31 (1.06-1.63) p = .013 and having had falls during the last year OR 1.14 (1.01-1.31) p = 0.041. CONCLUSION: Our findings suggest the self-reported prevalence of glaucoma in older adults in Colombia to be higher than reported data. Glaucoma and visual impairment in older adults represent a public health concern, since glaucoma was associated with adverse outcomes like functional loss and risk of falling, affecting the quality of life and their participation in society.

Details and outcomes of a large cohort of MOG-IgG associated optic neuritis.

BACKGROUND: The goal of this study was to examine the temporal relationship of eye pain to visual loss and investigate whether timing of steroid treatment affects the rate and extent of visual recovery in optic neuritis (ON) from MOG-IgG associated disease (MOGAD) in a large cohort of MOGAD patients with ON. METHODS: This is a multicenter, retrospective cohort study of consecutive MOGAD patients with ON attacks seen from 2017 to 2021 fulfilling the following criteria: (1) clinical history of ON; (2) MOG-IgG seropositivity. ON attacks were evaluated for presence/duration of eye pain, nadir of vision loss, time to intravenous methylprednisolone (IVMP) treatment, time to recovery, and final visual outcomes. RESULTS: There were 107 patients with 140 attacks treated with IVMP and details on timing of treatment and outcomes. Eye pain was present in 125/140 (89%) attacks with pain onset a median of 3 days (range, 0 to 20) prior to vision loss. Among 46 ON attacks treated with IVMP within 2 days of onset of vision loss, median time to recovery was 4 days (range, 0 to 103) compared to 15 days (range, 0 to 365) in 94 ON attacks treated after 2 days (p = 0.004). Those treated within 2 days had less severe VA loss at time of treatment (median LogMAR VA 0.48, range, 0.1 to 3) compared to those treated after 2 days (median LogMAR VA 1.7, range, 0 to 3; p < 0.001), and were more likely to have a VA outcome of 20/40 or better (98% vs 83%, p = 0.01). After adjustment for the initial VA at time of treatment, the differences in final VA were no longer significantly different (p = 0.14). In addition, some patients were documented to recover without steroid treatment. CONCLUSION: This study suggests that pain precedes vision loss in the majority of ON attacks and early steroids may lead to better outcomes in MOG-IgG ON, but some patients can recover without steroid treatment. Prospective randomized clinical trials are required to confirm these findings.

OCT retinal nerve fiber layer thickness differentiates acute optic neuritis from MOG antibody-associated disease and Multiple Sclerosis: RNFL thickening in acute optic neuritis from MOGAD vs MS.

BACKGROUND: Optic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities. METHODS: This was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS. RESULTS: Sixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range [IQR]: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93-113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17-105) and 7.5 µm (IQR: 1-18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening. CONCLUSION: OCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials.

Benefit of Stimulus Size V Perimetry for Patients With a Dense Central Scotoma From Leber's Hereditary Optic Neuropathy.

Purpose: Leber's hereditary optic neuropathy (LHON) is the most common mtDNA optic neuropathy. It most frequently causes dense bilateral central scotomas that are often characterized in clinical studies by Humphrey visual field testing (HVF) using a stimulus size III. This provides numerical quantification of the visual field defect using the mean deviation. However, this size III testing strategy has limitations. We used stimulus size V to monitor these patients and evaluated intertest variability and dynamic range to determine the testing reliability and reproducibility. Methods: This was a longitudinal retrospective cohort study comparing Stimulus III and Stimulus V HVF of 62 LHON patients who had reached the plateau stage of the disease. The intertest variability and mean defect were calculated for both stimulus sizes for 38 patients. The mean defect for stimulus size V was calculated using an algorithm developed by the University of Iowa Visual Field Reading Center. Results: Stimulus size V HVFs had lower inter-test variability as measured by mean defect standard deviation (Z = 169, P < 0.01). The floor effect seen with Stimulus III HVF in LHON, was less pronounced with Stimulus V HVF. The correlation of stimulus size III and V mean defect was strong (r = 0.90, P < 0.01), and a mathematical model was constructed to calculate the Stimulus size V mean defect from the Stimulus size III results (MDstimV = 0.988 x MDStimIII + 1.35, R2 = 0.82 P < 0.01). Conclusions: Stimulus size V HVF had lower intertest variability and a better dynamic range than Stimulus size III HVF in LHON patients. This makes the stimulus V HVF a more reliable metric to follow LHON patients especially in clinical trials. The mathematical model presented can be used to generate a Stimulus V equivalent mean defect from Stimulus III HVFs. Translational Relevance: Using Stimulus V HVF in LHON patients increases its ability to detect and quantify a response to treatment, making it a useful metric for future LHON clinical trials and the clinical setting.

OCT parameters of the optic nerve head and the retina as surrogate markers of brain volume in a normal population, a pilot study.

The relationship between optical coherence tomography (OCT) measurements of the retinal structures has been described for various neurological diseases including Multiple Sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Brain volume changes, both globally and by area, are associated with some of these same diseases, yet the correlation of OCT and disease is not fully elucidated. Our study looked at normal subjects, at the correlation of OCT measurements and brain volumes, both globally and for specific regions including the pericalcarine grey matter, entorhinal grey matter, and cerebellar volume using a retrospective, cross-sectional cohort study design. Thickness of the retinal nerve fiber layer (RNFL) as measured by OCT, correlated with volume of the pericalcarine grey matter, when adjusted for age and gender. Similarly, thickness of the ganglion cell layer-inner plexiform layer complex may be associated with both entorhinal grey matter volumes and total cerebellar volumes, although our pilot study did not reach statistical significance. This suggests that both eye and brain volumes follow a similar trajectory and understanding the inter-relationship of these structures will aid in the analysis of changes seen in disease. Further studies are needed to longitudinally demonstrate these relationships.

Optical Coherence Tomography in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

Purpose: The use of optical coherence tomography (OCT) of the retina to detect inner retinal degeneration is being investigated as a potential biomarker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), and an overwhelming body of evidence indicates that discovery of disease-modifying treatments for AD should be aimed at the pre-dementia clinical stage of AD, i.e., MCI. We aimed to perform a systematic review and meta-analysis on retinal OCT in MCI. Methods: We performed a systematic review of the English literature in three databases (PubMed, Embase, and Latindex) for studies that measured retinal thickness using OCT in people with MCI and healthy controls, age 50 or older, between 1 January 2000 and 31 July 2019. Only cohort and case-control studies were reviewed, and independent extraction of quality data and established objective data was performed. We calculated the effect size for studies in the review that met the following criteria: (1) a statistically significant difference between MCI subjects and normal controls for several OCT variables, (2) use of spectral domain OCT, and (3) use of APOSTEL recommendations for OCT reporting. Weighted Hedges' g statistic was used to calculate the pooled effect size for four variables: ganglion cell layer-inner plexiform layer (GCL-IPL) complex thickness in micrometers (µm), circumpapillary retinal nerve fiber layer (pRNFL) thickness in µm, macular thickness in µm, and macular volume in µm3. For variables with high heterogeneity, a multivariate meta-regression was performed. We followed the PRISMA guidelines for systematic reviews. Results: Fifteen articles met the inclusion criteria. A total of 58.9% of MCI patients had statistically significant thinning of the pRNFL compared with normal subjects, while 61.6% of all MCI patients who had macular volume measured had a statistically significant reduction in volume compared with controls, and 50.0% of the macular GCL-IPL complexes measured demonstrated significant thinning in MCI compared with normal controls. Meta-analysis demonstrated a large effect size for decreased macular thickness in MCI subjects compared with normal controls, but there was a substantial heterogeneity for macular thickness results. The other variables did not demonstrate a significant difference and also had substantial heterogeneity. Meta-regression analysis did not reveal an explanation for the heterogeneity. Conclusions: A better understanding of the cause of retina degeneration and longitudinal, standardized studies are needed to determine if optical coherence tomography can be used as a biomarker for mild cognitive impairment due to Alzheimer's disease.

Pathophysiology of Conversion to Symptomatic Leber Hereditary Optic Neuropathy and Therapeutic Implications: a Review.

PURPOSE: Leber's hereditary optic neuropathy (LHON) is a genetic disease of the mitochondrial genome that mainly affects the retinal ganglion cells (RGC) of the inner retina resulting in central vision loss. New understandings in mitochondrial genetics are helping to elucidate the nuances of conversion and allow for new therapeutic options. RECENT FINDINGS: Appreciation of the mitochondrial fission-fusion balance has allowed for increased understanding of the cascade of events that leads to clinical conversion in LOHN. Mathematical and computational models have helped to interpret the role of ROS in conversion, both as oxidative agents and as signaling molecules for cell death. The conversion from the LHON carrier to the affected patient has been clinically characterized, but the pathophysiology is just beginning to be understood. External stressors alter the mitochondrial dynamics of RGCs, leading to ROS buildup, energy shortages, decreased biogenesis and increased mitophagy, and ultimately axon degeneration and ganglion cell death. New therapeutic alternatives targeting these newly understood pathophysiological changes in the mitochondria and directly addressing the genetic mutations involved in LHON are being developed.