OBJECTIVE: Anti-tumor necrosis factor (Anti-TNF) agents have proven beneficial for the treatment of chronic non-infectious uveitis, yet rare neurological complications and demyelinating disease can occur with their use. Management of uveitis and neurological disease after developing these rare complications is not well understood. We sought to identify these specific cases and their outcomes through a retrospective observational case series.
METHODS: Electronic Medical Record (EMR) chart review of 394 non-infectious uveitis patients on anti-TNF therapy focused on identifying patients seen by uveitis specialists at a single institution who were on anti-TNF therapy and had developed neurological symptoms. Cases were reviewed for subsequent management and outcomes of both their neurologic and ocular inflammatory disease.
RESULTS: Five (5) patients were included following complaints of neurological symptoms while on anti-TNF therapy. Subsequent demyelinating diagnosis, acute treatment, and long-term course were described. All five patients continue to be inactive at around three years of anti-TNF discontinuation.
CONCLUSIONS: Unidentified rare neurological symptoms and demyelinating disease associated with the use of anti-TNF agents can be detrimental to patient treatment outcomes. Emphasis is given on possible avoidance and early identification of exacerbating underlying disease through a detailed neurologic history and use of imaging when suspicion is high. Patients may have no evidence of higher neurological risk prior to starting an anti-TNF treatment. Discontinuation of an anti-TNF agent and subsequent control of disease is possible with alternative immunosuppressive treatments.

OBJECTIVE: To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients.
METHODS: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively.
RESULTS: From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8 weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk.
CONCLUSIONS: Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients.
UNASSIGNED: CRD42023394226.

OBJECTIVE: To compare the safety and efficacy of methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) in non-anterior sarcoidosis-associated uveitis.
METHODS: Retrospective study including non-anterior sarcoidosis-associated uveitis according to the revised International Workshop on Ocular Sarcoidosis criteria. The primary outcome was defined as the median time to relapse or occurrence of serious adverse events leading to treatment discontinuation.
RESULTS: 58 patients with non-anterior sarcoidosis-associated uveitis (MTX (n=33), MMF (n=16) and AZA (n=9)) were included. The time to treatment failure (ie, primary outcome) after adjustment for corticosteroids dose and the presence of vasculitis was significantly higher with MTX (median time of 34.5 months with MTX (IQR: 11.8 -not reached) vs 8.4 months (3.1-22.9) with MMF and 16.8 months (8.0-90.1) with AZA (p=0.020)). The risk of relapse at 12 months was more than twice lower in MTX as compared with MMF (p=0.046). Low visual acuity at the last visit was significantly lower with MTX (4% vs 9% in MMF vs 57% in AZA group (p=0.008)). Regarding all 75 lines of treatment (MTX (n=39), MMF (n=24) and AZA (n=12)), MTX was more effective than MMF and AZA to obtain treatment response at 3 months (OR 10.85; 95% CI 1.13 to 104.6; p=0.039). Significant corticosteroid-sparing effect at 12 months (p=0.035) was only observed under MTX. Serious adverse events were observed in 6/39 (15%), 5/24 (21%) and 2/12 (17%) with MTX, MMF and AZA, respectively.
CONCLUSIONS: In non-anterior sarcoidosis-associated uveitis, MTX seems to be more efficient compared with AZA and MMF and with an acceptable safety profile.

OBJECTIVE: Contact lens-associated keratitis (CLAK) is a common sight-threatening complication of contact lens use. Current management protocols in the UK are based on historical practice and necessitate a review for every patient within 48 hours regardless of severity, increasing the treatment burden on a resource-limited healthcare service. Our study aims to identify the different risk factors associated with CLAK, categorise CLAK using a novel grading system and recommend modifications to current management protocols based on the outcomes in the individual subgroups.
METHODS: The retrospective cohort study identified 161 eyes from 153 patients with CLAK from the electronic patient records of a tertiary eye centre between 1 July 2021 and 28 February 2022. Patients were categorised based on epithelial defect size (grade 1: <1.0 mm, grade 2: 1.0-2.0 mm, grade 3: >2.0 mm) and their risk factors, clinical features, treatments and outcomes were analysed.
RESULTS: The most significant risk factors for CLAK include extended-wear contact lens, poor hygiene and prolonged duration of wear. Grades 1 and 2 CLAKs have excellent outcomes following an empirical treatment regime with topical moxifloxacin with 96% discharged within 48 hours and 94.1% discharged in 2 weeks, respectively. Grade 3 CLAKs require prolonged average duration of treatment.
CONCLUSIONS: We recommend typical grade 1 and 2 CLAKs can be discharged with empirical fluoroquinolone treatment. Grade 3 and all CLAKs with atypical features require monitoring for resolution, further diagnostics or treatment. We provide an evidence-based approach to reduce unnecessary patient visits and optimise resource allocation in an urban setting.

OBJECTIVE: To report an epidemiological update of bacterial keratitis (BK) in a tertiary ophthalmology centre over 20 months compared with a previous study on the same timeframe from 1998 to 1999.
METHODS: 354 patients with BK documented by microbiological corneal scraping or resolutive under antibiotics treatment from January 2020 to September 2021 were analysed retrospectively.
RESULTS: One or several risk factors were found in 95.2% of patients: contact lens wear (45.2%), ocular surface disease (25.0%), systemic disease (21.8%), ocular trauma (11.9%) and ocular surgery (8.8%). The positivity rate of corneal scrapings was 82.5%, with 18.2% polybacterial. One hundred seventy-five (59.9%) bacteria were Gram-negative, and 117 (40.1%) were Gram-positive. The most common bacteria were Pseudomonas aeruginosa (32.5%), Moraxella spp (18.1%) and Staphylococcus aureus (8.2%). Final visual acuity (logarithm of the minimum angle of resolution) was associated with age (r=+0.48; p=0.0001), infiltrate size (r=+0.32; p<0.0001), ocular surface disease (r=+0.13; p=0.03), ocular trauma (r=-0.14; p=0.02) and contact lens wear (r=-0.26; p<0.0001). Gram-negative bacteria were responsible for deeper (r=+0.18; p=0.004) and more extensive infiltrates (r=+0.18; p=0.004) in younger patients (r=-0.19; p=0.003). Compared with the previous period, the positivity rate of corneal scrapings and the proportion of Gram-negative bacteria, especially Moraxella spp, increased. All P. aeruginosa and Moraxella spp were sensitive to quinolones, and all S. aureus were sensitive to both quinolones and methicillin.
CONCLUSIONS: Contact lens wear remained the leading risk factor. The bacteria distribution was reversed, with a predominance of Gram-negative bacteria and increased Moraxella spp.

OBJECTIVE: The Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including treatment exit strategies. In this article, we present the participants\' baseline characteristics after the first 3 years.
METHODS: TOFU is an observational, prospective registry and recruits patients ≥18 years of age with non-anterior non-infectious uveitis with or without a history of previous disease-modifying antirheumatic drugs (DMARDs) treatment. The data are collected in the electronic data capture software REDCap and include ophthalmological and general medical history as well as clinical findings.
RESULTS: Between 24.10.2019 and 27.12.2022, 628 patients were enrolled at 25 clinical sites in Germany and Austria. Patients with intermediate uveitis were most frequently included (n=252; 40.1%) followed by posterior uveitis (181; 28.8%), panuveitis (n=154; 24.5%) and retinal vasculitis (n=41, 6.5%). At baseline, 39.6% were treated with systemic corticosteroids, 22.3% with conventional synthetic (cs) DMARDs, 20.5% with biological (b) DMARDs and 3.6% with other systemic treatments. Average best corrected visual acuity (BCVA) was 0.69 decimal. Patients with panuveitis had the worst BCVA with 0.63 decimal. Overall, only 8 patients (1.3%) suffered from severe visual impairment.
CONCLUSIONS: Less than half of participants required DMARD treatment at baseline, with csDMARDs used more frequently than bDMARDs. The presence of severe visual impairment was low, mostly affecting patients with panuveitis. These findings are in line with comparable monocentric cross-sectional studies of tertiary uveitis centres in Germany and will allow us to generate generalisable evidence in TOFU.

OBJECTIVE: Topical agents to lower intraocular pressure (IOP) are the most common initial therapeutic measure in glaucoma prevention. This study aims to assess treatment success duration among patients initiating or intensifying topical glaucoma medication.
METHODS: Medical records (2013‒2018) for adults initiating/intensifying topical glaucoma medication were extracted from five secondary-care and tertiary-care UK ophthalmology centres. Main study outcomes were time from treatment initiation/intensification to treatment failure (<20% IOP reduction or IOP >21 mm Hg at consecutive clinic visits, or intensification of glaucoma treatment) and time from treatment change to subsequent treatment intensification.
RESULTS: Study eyes (n=6587) underwent treatment intensification 0-to-1 glaucoma drop (5358 events), 1-to-2 drops (1469 events) and 2-to-3 drops (857 events) during the observation period. Median time to treatment failure was 1.60 (95% CI 1.57 to 1.65), 1.00 (95% CI 0.94 to 1.07) and 0.92 (95% CI 0.81 to 1.02) years following escalation 0-to-1, 1-to-2 and 2-to-3 drops, respectively. Median time to treatment intensification (non-IOP-based criterion) was 4.68 (95% CI 4.50 to 5.08) years for treatment initiators, 3.83 (95% CI 3.36 to 4.08) years on escalation 1-to-2 drops and 4.35 (95% CI 3.82 to 4.88) years on escalation 2-to-3 drops. On multivariable regression, significant risk factors for both treatment failure and intensification were lower baseline visual field mean deviation, primary open-angle glaucoma and lower eyedrop count in the fellow eye; lower baseline IOP was associated with treatment failure, higher baseline IOP with treatment intensification.
CONCLUSIONS: Large-scale survival analyses provide the expected duration of treatment success from topical glaucoma medication.

OBJECTIVE: Microbial keratitis (MK) is a significant cause of blindness in sub-Saharan Africa. We investigated the feasibility of using a novel corneal impression membrane (CIM) for obtaining and processing samples by culture, PCR and whole-genome sequencing (WGS) in patients presenting with suspected MK in Malawi.
METHODS: Samples were collected from patients presenting with suspected MK using a 12 mm diameter polytetrafluoroethylene CIM disc. Samples were processed using culture and PCR for Acanthamoeba, herpes simplex virus type 1 (HSV-1) and the bacterial 16S rRNA gene. Minimum inhibitory concentrations of isolates to eight antimicrobials were measured using susceptibility strips. WGS was used to characterise Staphylococcus aureus isolates.
RESULTS: 71 eyes of 71 patients were included. The overall CIM isolation rate was 81.7% (58 positive samples from 71 participants). 69 (81.2%) of isolates were Gram-positive cocci. Coagulase-negative Staphylococcus 31.8% and Streptococcus species 14.1% were the most isolated bacteria. Seven (9.9%) participants were positive for HSV-1. Fungi and Acanthamoeba were not detected. Moxifloxacin and chloramphenicol offered the best coverage for both Gram-positive and Gram-negative isolates when susceptibility was determined using known antimicrobial first quartile concentrations and European Committee on Antimicrobial Susceptibility Testing breakpoints, respectively. WGS identified known virulence genes associated with S. aureus keratitis.
CONCLUSIONS: In a resource-poor setting, a CIM can be used to safely sample the cornea in patients presenting with suspected MK, enabling identification of causative microorganisms by culture and PCR. Although the microbiological spectrum found was limited to the dry season, these preliminary results could be used to guide empirical treatment.

OBJECTIVE: To compare the effects of repeated low-level red light (RLRL) treatment on axial length growth and refractive error changes in myopic and premyopic children.
METHODS: Subjects were assigned randomly to four subgroups: myopia-RLRL group (M-RL), myopia-control group (M-C), premyopia-RLRL group (PM-RL) and premyopia-control group (PM-C). Subjects in the RLRL group completed a 12-month treatment composed of a 3 min RLRL treatment session twice daily, with an interval of at least 4 hours, for 7 days per week. Visits were scheduled before and at 1-month, 3-month, 6-month, 9-month and 12-month follow-up after the treatment. Repeated-measures analysis of variance was used to compare the spherical equivalent refractive errors (SE) and axial length (AL) changes between the groups across the treatment period.
RESULTS: After 12 months of treatment, in the myopia group, SE and AL changes were -0.078±0.375 D and 0.033±0.123 mm for M-RL and -0.861±0.556 D and 0.415±0.171 mm for M-C; in the premyopia group, the progression of SE and AL was -0.181±0.417 D and 0.145±0.175 mm for PM-RL and -0.521±0.436 D and 0.292±0.128 mm for PM-C. PM-RL indicated a lower myopia incidence than PM-C (2.5% vs 19.4%). Additionally, the percentage of AL shortening in the M-RL was higher than that in the PM-RL before the 9-month follow-up.
CONCLUSIONS: RLRL effectively delayed myopia progression in children with myopia and reduced the incidence of myopia in premyopic children. Moreover, RLRL exhibited a stronger impact on myopic children compared with premyopic individuals.

BACKGROUND: Self-treatment with glaucoma medication (eye drops) has been associated with adherence challenges. Poor adherence results in worse outcomes in terms of visual field loss.
OBJECTIVE: To investigate patterns in medication adherence among Danish patients with glaucoma in relation to selected predictors of adherence, long-term adherence patterns, and long-term societal economic consequences of poor adherence.
METHODS: This register-based study included 30 100 glaucoma patients followed for 10 years between 2000 and 2018. Glaucoma was identified from the Danish national registers by diagnosis of Open Angle Glaucoma and/or by redeemed prescriptions of glaucoma medication. Logistic regression models were applied to estimate patient characteristics related to medical adherence. Diagnosis-related group fees were applied to estimate healthcare costs.
RESULTS: High adherence in the first year(s) of treatment was less likely among men (ORfirst year: 0.78, 95% CI: 0.75 to 0.82), younger individuals and among those with a positive Charlson Comorbidity Index (CCI) score (ORfirst year/CCI≥3: 0.71, 95% CI: 0.63 to 0.80). Adherence in the first year and in the first two years was associated with adherence in the fifth (ORfirst year: 4.55, 95% CI: 4.30 to 4.82/ORfirst two years: 6.47, 95% CI: 6.10 to 6.86) as with adherence in the 10th year with slightly lower estimates. Being medical adherent was related to higher costs related to glaucoma medication after 5 and 10 years comparing with poor adherence, whereas poor adherence was associated with a marked increase in long-term costs for hospital contacts.
CONCLUSIONS: Increasing age, female sex and low comorbidity score are correlated with better adherence to glaucoma treatment. Adherence in the first years of treatment may be a good predictor for future adherence. In the long term, patients with poor adherence are overall more expensive to society in terms of hospital contacts.