Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness-a protocol for a randomised controlled trial (ASTUTE trial).

INTRODUCTION: Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care. METHODS AND ANALYSIS: The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted. ETHICS AND DISSEMINATION: The trial received Research Ethics Committee (REC) approval from South Central - Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available. TRIAL REGISTRATION: ISRCTN31474800. Registered 14 April 2020.

Topographic patterns of retinal lesions in multiple evanescent white dot syndrome.

PURPOSE: To demonstrate different topographic distributions of multiple-evanescent white dot syndrome (MEWDS) and secondary MEWDS disease and to describe possible associations. METHODS: Clinical evaluation and multimodal retinal imaging in 27 subjects with MEWDS (29 discrete episodes of MEWDS). Ophthalmic assessment included best-corrected visual acuity testing and multimodal retinal imaging with OCT, blue-light autofluorescence, fluorescein and indocyanine green angiography, fundus photography, and widefield pseudocolor and autofluorescence fundus imaging. RESULTS: The topographic distribution of MEWDS lesions was centered on or around the optic disc (n = 17, 59%), centered on the macula (n = 7, 24%), sectoral (n = 2, 7%), or was indeterminate (n = 3, 10%). The MEWDS episodes either occurred in the absence ('primary MEWDS'; n = 14, 48%) or presence of concurrent chorioretinal pathology ('secondary MEWDS'; n = 15, 52%). In patients with the latter, MEWDS lesions were often centered around a coexisting chorioretinal lesion. The majority of patients in both groups experienced resolution of their symptoms and retinal changes on multimodal imaging by 3 months. CONCLUSIONS: Distinct distributions of MEWDS lesions were identified. MEWDS may occur in tandem with other chorioretinal pathology, which may impact the topography of MEWDS lesions.

Diagnostic value of intereye difference metrics for optic neuritis in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders.

BACKGROUND: The novel optic neuritis (ON) diagnostic criteria include intereye differences (IED) of optical coherence tomography (OCT) parameters. IED has proven valuable for ON diagnosis in multiple sclerosis but has not been evaluated in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4+NMOSD). We evaluated the diagnostic accuracy of intereye absolute (IEAD) and percentage difference (IEPD) in AQP4+NMOSD after unilateral ON >6 months before OCT as compared with healthy controls (HC). METHODS: Twenty-eight AQP4+NMOSD after unilateral ON (NMOSD-ON), 62 HC and 45 AQP4+NMOSD without ON history (NMOSD-NON) were recruited by 13 centres as part of the international Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica study. Mean thickness of peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) were quantified by Spectralis spectral domain OCT. Threshold values of the ON diagnostic criteria (pRNFL: IEAD 5 µm, IEPD 5%; GCIPL: IEAD: 4 µm, IEPD: 4%) were evaluated using receiver operating characteristics and area under the curve (AUC) metrics. RESULTS: The discriminative power was high for NMOSD-ON versus HC for IEAD (pRNFL: AUC 0.95, specificity 82%, sensitivity 86%; GCIPL: AUC 0.93, specificity 98%, sensitivity 75%) and IEPD (pRNFL: AUC 0.96, specificity 87%, sensitivity 89%; GCIPL: AUC 0.94, specificity 96%, sensitivity 82%). The discriminative power was high/moderate for NMOSD-ON versus NMOSD-NON for IEAD (pRNFL: AUC 0.92, specificity 77%, sensitivity 86%; GCIP: AUC 0.87, specificity 85%, sensitivity 75%) and for IEPD (pRNFL: AUC 0.94, specificity 82%, sensitivity 89%; GCIP: AUC 0.88, specificity 82%, sensitivity 82%). CONCLUSIONS: Results support the validation of the IED metrics as OCT parameters of the novel diagnostic ON criteria in AQP4+NMOSD.

A nationwide survey of hydroxychloroquine retinopathy presenting to the hospital eye service in the United Kingdom.

BACKGROUND: The risk of developing hydroxychloroquine retinopathy is considered sufficient to justify national monitoring programmes. There are an estimated 71,144-77,170 long-term hydroxychloroquine users in the UK. However, the number of patients diagnosed with retinopathy is unknown. This study aimed to identify the number of cases and clinical characteristics of hydroxychloroquine retinopathy diagnosed annually in hospital eye services across the UK. METHODS: A nationwide, prospective case ascertainment study was undertaken using the British Ophthalmological Surveillance Unit, which sends approximately 1420 reporting cards to UK Ophthalmologists monthly. The case definition was two abnormal tests suggestive of hydroxychloroquine retinopathy. Demographic and clinical data relating to hydroxychloroquine use and retinopathy were collected from identified cases using a standardised questionnaire over a 1-year period (2018-2019). RESULTS: Sixty-six cases of hydroxychloroquine retinopathy were reported, and 46 questionnaires were received (73% response rate). Twenty-four incident cases of hydroxychloroquine retinopathy were identified (24-43 cases following adjustment). The median duration of drug therapy was 19 years (range: 4-50 years, IQR: 14.5-23 years). Fourteen patients were asymptomatic, and 9 symptomatic at diagnosis. A trend towards a lower mean deviation on visual field testing was observed in the symptomatic group (-11.55 dB versus -6.9 dB; P = 0.15). CONCLUSION: Between 1 in 1655 and 3215 (0.03-0.06%) long-term hydroxychloroquine users were diagnosed with retinopathy over the study period. We estimate that monitoring was available for 1.9-3.8% of long-term users, accounting for a lower than expected incidence. The high proportion of symptomatic retinopathy at diagnosis underlines the importance of monitoring to detect pre-symptomatic disease.

Modern Solutions for Ancient Pathogens: Direct Pathogen Sequencing for Diagnosis of Lepromatous Leprosy and Cerebral Coenurosis.

Microbes unculturable in vitro remain diagnostically challenging, dependent historically on clinical findings, histology, or targeted molecular detection. We applied whole-genome sequencing directly from tissue to diagnose infections with mycobacteria (leprosy) and parasites (coenurosis). Direct pathogen DNA sequencing provides flexible solutions to diagnosis of difficult pathogens in diverse contexts.

Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders.

BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.

Structural Abnormalities of the Central Retina in Neurofibromatosis Type 2.

INTRODUCTION: This case-control study seeks to systematically characterize the central retinal findings in a large cohort of patients with neurofibromatosis type 2 (NF2) using spectral domain optical coherence tomography (SD-OCT) as well as the examination of the potential use of this technique as a diagnostic tool in NF2. METHODS: Fifty-four patients with an NF2 diagnosis seen in a quaternary national service were age- and gender-matched to 55 controls from the normal population. Two masked assessors categorized SD-OCT images using predefined abnormalities: retinal tufts, epiretinal membrane (ERM) appearance, retinal hamartoma, and foveal contour. Specificity, sensitivity, and positive and negative predictive values were calculated for each retinal abnormality. Trends of retinal abnormalities with NF2 genetic severity groups (1. tissue mosaic; 2A. mild classic; 2B. moderate classic; and 3. severe) were investigated. RESULTS: We found retinal abnormalities in 26 patients with NF2 (48%) and 2 control patients (4%); retinal tufts were the most common abnormality therein (43%) and were not seen in controls. The specificity and sensitivity of the graded abnormalities on OCT scans in NF2 were 96% and 48%, respectively, with a positive predictive value of 93%. In our cohort, retinal tufts had a specificity of 100%, a sensitivity of 43%, and a positive predictive value of 100%. Retinal hamartomas were seen only in NF2 patients (35% sensitivity and 100% specificity). ERMs had 96% specificity and 13% sensitivity. The proportion of patients with retinal abnormalities increased statistically significantly with NF2 genetic severity; all patients within the 3. severe genetic severity had an abnormal SD-OCT. DISCUSSION/CONCLUSION: We present a systematic study of central retinal abnormalities in an NF2 population as seen on SD-OCT imaging. Our results show a high frequency of retinal abnormalities that are readily detected by SD-OCT imaging. The presence of retinal tufts may be a novel marker of NF2 with both high specificity and a positive predictive value for NF2, compared to other well-known ocular features of NF2, and may have a place in the NF2 diagnostic criteria.

The Cellular Composition of the Uveal Immune Environment.

The uveal tract consists of the iris, the ciliary body and the choroid; these three distinct tissues form a continuous layer within the eye. Uveitis refers to inflammation of any region of the uveal tract. Despite being grouped together anatomically, the iris, ciliary body and choroid are distinct functionally, and inflammatory diseases may affect only one part and not the others. Cellular structure of tissues direct their function, and understanding the cellular basis of the immune environment of a tissue in health, the "steady state" on which the perturbations of disease are superimposed, is vital to understanding the pathogenesis of those diseases. A contemporary understanding of the immune system accepts that haematopoietic and yolk sac derived leukocytes, though vital, are not the only players of importance. An array of stromal cells, connective tissue cells such as fibroblasts and endothelial cells, may also have a role in the inflammatory reaction seen in several immune-mediated diseases. In this review we summarise what is known about the cellular composition of the uveal tract and the roles these disparate cell types have to play in immune homeostasis. We also discuss some unanswered questions surrounding the constituents of the resident leukocyte population of the different uveal tissues, and we look ahead to the new understanding that modern investigative techniques such as single cell transcriptomics, multi-omic data integration and highly-multiplexed imaging techniques may bring to the study of the uvea and uveitis, as they already have to other immune mediated inflammatory diseases.

Retinal Optical Coherence Tomography in Neuromyelitis Optica.

BACKGROUND AND OBJECTIVES: To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts. METHODS: The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA). RESULTS: Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 µm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 µm, p < 0.001). GCIP layer loss (-22.7 µm) after the first ON was higher than after the next (-3.5 µm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC. DISCUSSION: Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation.

Systemic corticosteroid use in UK Uveitis practice: results from the ocular inflammation steroid toxicity risk (OSTRICH) study.

OBJECTIVES: To ascertain adherence to an international consensus target of ≤7.5 mg/day of prednisolone for maintenance systemic corticosteroid (CS) prescribing in uveitis and report the frequency of courses of high-dose systemic CS in the UK. METHODS: We conducted a national, multicentre audit of systemic CS prescribing for uveitis at 11 UK sites between November 2018 and March 2019. High-dose CS was defined as (1) maintenance >7.5 mg prednisolone for >3 consecutive months, or (2) >1 course ≥40 mg oral CS or ≥500 mg intravenous (IV) methylprednisolone in the past 12 months. Case notes of patients exceeding threshold CS doses were reviewed by an independent uveitis specialist and judged as avoidable or not, based upon a scoring matrix. RESULTS: Of 667 eligible patients, 285 (42.7%) were treated with oral or IV CS over the preceding 12 months; 96 (33.7%) of these exceeded the threshold for high-dose CS. Twenty-five percent of prescribing in patients on excess CS was judged avoidable; attributed to either prescribing long-term CS without evidence of consideration of alternative strategies, prescribing error or miscommunication. More patients received immunomodulatory therapy (IMT) in the group treated with CS above threshold than below threshold (p < 0.001) but there was no significant difference in doses of IMT. CONCLUSION: 33% of patients had been prescribed excessive corticosteroid when compared to the reference standard. An analysis of decision-making suggests there may be opportunity to reduce excess CS prescribing in 25% of these patients.

Long-term efficacy and tolerability of TNFα inhibitors in the treatment of non-infectious ocular inflammation: an 8-year prospective surveillance study.

BACKGROUND/AIM: To report the efficacy and tolerability of antitumour necrosis factor-alpha therapy (TNF inhibitors [TNFi]) in the management of non-infectious ocular inflammation, including uveitis and scleritis, in adult patients over an 8-year period. MATERIALS AND METHODS: This is a prospective cohort study of infliximab and adalimumab in the treatment of non-infectious ocular inflammatory disease. 43 of 85 adult patients on TNFi (34 infliximab, 9 adalimumab) for ≥1 year with non-infectious uveitis or scleritis were followed from 2006 to 2014. Clinical assessments, medication, adverse events and history of steroid rescues were collected at 6 monthly intervals. General quality of life (Short Form Health Survey (SF-36)) and visual quality of life (Vision-related quality of life Core Measure (VCM1)) were assessed annually. Outcome measures included rate of sustained remission, rate of relapse, systemic corticosteroid reduction, adverse events, and VCM1 and SF-36 scores. RESULTS: The median time on infliximab was 3.2 years (IQR 4.3) and on adalimumab was 2.4 years (IQR 1.8). Sustained remission was induced in 39 patients (91%) (0.5 per patient year) after a median of 1.2 years on a TNFi. 22 (51%) experienced one relapse, and 5 (12%) had two relapses. 23 (54%) had at least one adverse event; serious adverse events necessitating hospitalisation or cessation of medication occurred in four (9%) patients. 10 patients (23%) switched from the initiation of TNFi, at 1.7 years after starting, to another TNFi or another class of biologic therapy. CONCLUSION: TNFi treatment is associated with long-term drug-induced remission of ocular inflammation, visual stability and corticosteroid reduction. Adverse events were common and no new safety signals occurred. Relapse of inflammation occurs in half of the treated population.

Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO).

PURPOSE: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD. PARTICIPANTS: The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices. FINDINGS TO DATE: The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline. FUTURE PLANS: We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications.

An audit of the use of hydroxychloroquine in rheumatology clinics.

OBJECTIVE: The aim was to audit the use, indications, complications and patient information regarding HCQ treatment in rheumatology clinics in a tertiary referral centre. METHODS: During a 9-month period, we identified all patients prescribed HCQ and attending rheumatology clinics in one hospital. We established: (i) the indication for HCQ; (ii) the prevalence of HCQ overdosing based on absolute body weight (ABW); (iii) documentation of warning of risk of retinal toxicity; (iv) systemic and ocular co-morbidities; (v) ocular symptoms during treatment; and (vi) reasons for stopping HCQ. RESULTS: We identified 427 patients (104 male and 323 female). The cumulative dose of HCQ was lower in RA (median 365 g; range 6-1752 g) compared with SLE (450 g; 66-1788 g) (P = 0.105). The median duration of HCQ therapy was 4 years (range 0.1-13 years); 28% of patients with RA and 29% with SLE continued HCQ beyond 5 years. After adjusting for ABW and renal function, 10% (31/312) had been prescribed doses exceeding recommendations. Formal documentation of counselling on ocular complications was found in only one-third of patients. Three cases of HCQ retinopathy were identified (all of whom had RA). CONCLUSION: HCQ therapy is being used for >5 years in 29% of patients with rheumatic diseases, with higher than recommended doses in ∼10% of patients. We recommend more rigorous scrutiny of the use of HCQ to reduce the risk of retinopathy.

A Review of the Landscape of Targeted Immunomodulatory Therapies for Non-Infectious Uveitis.

Systemic immunomodulatory therapies are the principal means of managing non-infectious uveitis. This review aims to explore the current landscape of systemic uveitis treatments, including biologic therapies and the advent of biosimilar therapies.

IgG4-related disease presenting as posterior scleritis and vitritis, progressing to multifocal orbital involvement.

IgG4-related disease (IgG4-RD) is a rare, chronic inflammatory condition that may involve nearly every organ system. Originally identified as a cause of autoimmune pancreatitis, its characteristic histological and clinical features have been found in a wide variety of inflammatory presentations, including the eye and orbit. Here we describe an example of a case of IgG4-RD initially presenting as scleritis and vitritis, with further progression to multifocal bilateral orbital involvement. Tissue biopsy of an orbital mass was highly characteristic of IgG4-RD histology and a rapid clinical response to corticosteroids was observed. This case highlights IgG4-RD as a rare cause of intraocular inflammation that may progress to involve the orbit.

Uveitis and spondyloarthropathies.

Uveitis is a frequently occurring extra-articular manifestation of spondyloarthropathies (SpAs), ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA) and inflammatory bowel disease (IBD), occurring in both adults and children with SpA. Uveitis occurs with varying frequency according to the SpA subtype (33% in AS, 6-9% in PsA, 25% in ReA, 13% in undifferentiated SpA and 2-5% in IBD), the presence of HLA-B27 and with increasing duration of disease. The majority of cases of uveitis in SpA are attributed to acute anterior uveitis but a minority of uveitis cases occur in the posterior segment of the eye. The latter are more frequently complicated by cystoid macular oedema (CMO) and sight loss. The nature of the tissue specificity exhibited by the SpAs is poorly understood. Three current investigational approaches are discussed: high-throughput genomics to identify and confirm uveitis-specific susceptibility alleles; investigation of the role of the intestinal microbiome and its potential role in innate immune signalling in uveitis; and study of a novel IL23R-bearing cell population in several entheseal sites including the eye. The treatment for uveitis in SpAs is predominantly with topical corticosteroids for acute episodes. Among the systemic drugs used for the treatment of SpAs, infliximab, adalimumab and certolizumab are effective in reducing the frequency of uveitis but etanercept is not. Other targets in spondyloarthropathy include cytokines within the IL23/IL17 axis, of which the IL17A inhibitor secukinumab has not been shown to be effective in uveitis. Future therapeutic approaches may include small molecules such as selective and non-selective janus kinase and tyrosine kinase inhibitors.

Comparison of Visual Outcomes of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients with and without Diabetes Mellitus.

PURPOSE: Diabetic patients have a greater risk of nonarteritic anterior ischemic optic neuropathy (NAION) than nondiabetic patients. We compare visual outcomes, prevalence of bilateral/sequential ION, and predictors of visual outcomes in NAION between diabetic and nondiabetic patients. DESIGN: Case-control study. PARTICIPANTS: All 231 patients with NAION seen by the Neuro-Ophthalmology Service, Wilmer Eye Institute, between 2002 and 2011 were screened for study inclusion. METHODS: Patients presenting within 4 weeks of symptom onset (30 with diabetes mellitus, 62 control patients) were included in baseline demographic assessments of vascular risk factors. Interval and final visual outcomes (logarithm of the minimum angle of resolution [logMAR] visual acuity [VA]) were evaluated in the 81 patients in this group with clinical follow-up for ≥3 months, and population average logistic regression models were used to determine risk factors for worse visual outcomes. MAIN OUTCOME MEASURES: Visual acuity at last follow-up. RESULTS: The median follow-up duration was 38.7 weeks in diabetic patients and 52.9 weeks in nondiabetic patients. The majority (92.5%) of patients presented within 2 weeks of symptom onset. In nondiabetic patients, the most prevalent risk factor for NAION was hyperlipidemia (62.9%); for diabetic patients, NAION risk factors included hypertension (83.3%), hyperlipidemia (83.3%), and small cup-to-disc ratio (63.3%). Sequential NAION occurred in 36.8% of diabetic patients and 20.9% of nondiabetic patients. At last follow-up, 48% of diabetic and 62% of nondiabetic patients had VA better than 20/40. Similar proportions of diabetic and nondiabetic patients (8 [27%] diabetic and 14 [22.5%] nondiabetic patients) recorded a final follow-up vision of 1.0 logMAR or worse at a minimum of 3 months. Ischemic heart disease (odds ratio [OR], 7.21; P < 0.001) and greater age (OR, 1.05; P = 0.045) were associated with increased risk for final VA <20/200 in the multiple regression model (OR, 4.35; P = 0.011). CONCLUSIONS: The VA at presentation and at final follow-up in diabetic patients with NAION were not significantly different from nondiabetic controls, although diabetic patients had a higher prevalence of cardiovascular risk factors. Ischemic heart disease and greater age, but not diabetes, independently correlated with worse VA outcome.