February 2022

OBJECTIVE: There are unmet needs for refractive correction in the pediatric population, especially in high-poverty communities. We reported the impact of refractive correction on vision outcomes over a 2-year follow-up in the Baltimore Reading and Eye Disease Study. DESIGN: Prospective, school-based cohort study. PARTICIPANTS: Students of second and third grades who were prescribed glasses during baseline assessment. METHODS: We conducted baseline eye exams in 12 Baltimore public schools during the fall of school year 2014-15 with follow-up visits in the spring of school year 2014-15 (first follow-up) and school year 2015-16 (second follow-up). Visual acuity (VA) was measured at distance and near with correction. Refractive status was determined based on the eye with the larger refractive error and categorized as myopia, hyperopia, and astigmatism. MAIN OUTCOME MEASURES: VA in better-seeing and worse-seeing eye at first and second follow-up, and acuity improvement from baseline. RESULTS: In the 206 students (84% African American) who completed the first follow-up, both distance (from 0.14 ± 0.20 to 0.05 ± 0.10 logMAR) and near presenting VA (from 0.08 ± 0.16 to 0.03 ± 0.06 logMAR) improved from the baseline assessment; children with more severe hyperopia showed improvement in near VA by 0.05 ± 0.16 logMAR. Children who were prescribed glasses through a school-based research study had improved vision, which was sustained into the following school year. CONCLUSIONS: Many second and third graders in Baltimore Schools needed refractive correction and benefited from provision of glasses with sustained vision improvement over the 2-year observation.

Supraspinal mechanisms of pain are increasingly understood to underlie neuropathic ocular conditions previously thought to be exclusively peripheral in nature. Isolating individual causes of centralized chronic conditions and differentiating them is critical to understanding the mechanisms underlying neuropathic eye pain and ultimately its treatment. Though few functional imaging studies have focused on the eye as an end-organ for the transduction of noxious stimuli, the brain networks related to pain processing have been extensively studied with functional neuroimaging over the past 20 years. This article will review the supraspinal mechanisms that underlie pain as they relate to the eye.

SIGNIFICANCE: Corneal haze remains a frequent post-operative finding in patients undergoing corneal cross-linking. It has been shown that autologous serum tears promote epithelial healing and reduce post-operative pain; however, the role in the prevention of corneal haze has not been reported. PURPOSE: This study aimed to compare the effect of autologous serum tears versus preservative-free artificial tears on the prevention and resolution of post-cross-linking corneal haze. METHODS: A retrospective cohort study was conducted in a sample population from one surgeon at a tertiary eye center from 2016 to 2019. Seventy-six eyes of consecutive patients who underwent cross-linking were included. Records were reviewed for corneal Scheimpflug densitometry values and maximum keratometry, epithelial healing time, and the use of either autologous serum tears or preservative-free artificial tears. Corneal densitometry values, expressed in standardized grayscale units (GSU), were recorded for the anterior 150-μm corneal stroma and in the 0.0 to 2.0 mm and 2.0 to 6.0 mm zones. RESULTS: Forty-four eyes received autologous serum tears, whereas 32 eyes received preservative-free artificial tears. The baseline GSU of the anterior stromal 0 to 2 mm annulus and the 2 to 6 mm annulus did not significantly differ between groups (P = .50 and P = .40, respectively). There was a statistically significant increase in mean GSU for both anterior 0 to 2 mm and 2 to 6 mm zones between baseline and 1 month (P < .001) and 3 months (P < .001). When comparing the two groups, no statistically significant difference was found post-operatively between the mean GSU at 1 month for the anterior 0 to 2 mm (P = .38) nor the 2 to 6 mm zone (P = .12), or for the third month (P = .60 and P = .44, respectively). CONCLUSIONS: Using Scheimpflug densitometry, we did not find a significant difference in the post-cross-linking corneal haze at 1 and 3 post-operative months between patients who use autologous serum tears and those who use preservative-free artificial tears.

BACKGROUND: There are still many research challenges and unanswered questions in relation to Epstein-Barr virus-associated uveitis. These include the presence of Epstein-Barr virus (EBV) DNA in asymptomatic patients, its pathogenicity in the uveitis eye, and the role of antiviral therapy for EBV-associated intraocular inflammation. METHODS: This was a retrospective review of prospectively collected data from the Ophthalmology Department, Rajavithi Hospital between 2015 and 2020. A qualitative assay using multiplex real-time PCR was performed to detect pathogen genes from specimens obtained from a total of 344 patients. The main outcome measure was treatment success defined by clinical improvement and absence of viral DNA confirmed by PCR. RESULTS: Of the 35 cases, 24 with complete data were enrolled in the study, including 22 with post-treatment PCR results. Sixty-seven percent were HIV-infected, and other plausible causes or coinfection with other pathogens were found in 75% of patients. Cytomegalovirus (38%) was the most common co-infecting pathogen. The most commonly employed regimen was a combination of systemic acyclovir and intravitreal ganciclovir injection (58%). Of the 22 cases who had post-treatment PCR results, absence of detection of the virus by PCR in the intraocular fluid after treatment was demonstrated in 73% of patients. CONCLUSION: Patients with EBV infection can be simultaneously co-infected with other pathogens. Systemic acyclovir and ganciclovir achieved clinical improvement in most cases, and EBV infection was cured in the majority of patients.

PURPOSE: To review the published literature to determine the efficacy and safety of homeopathic agents or vitamins in reducing ecchymosis after oculofacial surgery or laser surgery. METHODS: A literature search was conducted in the PubMed database initially in December 2019 and updated in March 2020 to identify all studies in the English language literature on the use of homeopathic agents or vitamins in oculofacial procedures, including laser surgery. The search yielded 124 citations, and 11 articles met all inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study. Eleven studies met inclusion criteria; 9 were rated level I, and 2 were rated level III. RESULTS: The agents studied in the articles identified included oral or topical Arnica montana (AM), oral Melilotus extract, topical vitamin K oxide, and topical AM combined with Rhododendron tomentosum. Metrics to describe ecchymosis varied. In 7 controlled studies, perioperative AM provided no or negligible benefit versus placebo. In 2 studies, vitamin K cream was equivalent to placebo. One study of oral Melilotus extract had less ecchymosis compared with controls in paranasal and eyelid ecchymosis at postoperative day (POD) 7, but not at PODs 1 and 4. A lone cohort study of combined topical AM and R. tomentosum lacked objective metrics and adequate controls. No serious side effects from administration of homeopathic agents or vitamins were identified. CONCLUSIONS: The current literature does not support the use of AM, vitamin K oxide, R. tomentosum, or Melilotus extract for reducing ecchymosis after oculofacial surgery or pulsed dye laser surgery.

BACKGROUND/AIMS: To determine if disorganisation of retinal inner layers (DRIL) is associated with reduced contrast sensitivity (CS) in patients with retinal vein occlusion (RVO) with a history of macular oedema (ME). METHODS: Prospective, observational cohort study. Patients with a history of ME secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) from October 2017 to July 2019 at a single institution were included. Patients underwent complete ophthalmic examination, spectral domain optical coherence tomography (SD-OCT) and CS testing using the quick contrast sensitivity function (qCSF) method. Eyes with coexisting macular disease were excluded. SD-OCT images were analysed for presence and extent of DRIL, intraretinal fluid (IRF), subretinal fluid (SRF), hyperreflective foci, epiretinal membrane (ERM), external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption, central macular thickness (CMT) and central foveal thickness (CFT). Multivariable mixed-effect linear regressions were performed for the area under the log contrast sensitivity function (AULCSF) using Stata (StataCorp). P values <0.05 were considered significant. RESULTS: 58 visits from 31 patients were included (1.9±1.2 visits per patient). 29 (50%) were for CRVO. The average age was 63.9±10.5 years. On multivariable analysis, DRIL extent (p<0.001), CMT (p=0.007), CFT (p=0.024) and moderate cataract (p=0.001) were significantly associated with worse AULCSF. CONCLUSIONS: DRIL extent is associated with reduced CS in eyes with ME secondary to RVO. DRIL is an imaging feature that has important implications for visual function.

BACKGROUND: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. METHODS: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). FINDINGS: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). INTERPRETATION: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. FUNDING: F Hoffmann-La Roche.

Diabetic optic neuropathy (DON) is a diverse complication of diabetes and its pathogenesis has not been fully elucidated. The purpose of this study was to explore dynamic cerebral activity changes in DON patients using dynamic amplitude of low-frequency fluctuation (dALFF). In total, 22 DON patients and 22 healthy controls were enrolled. The dALFF approach was used in all participants to investigate dynamic intrinsic brain activity differences between the two groups. Compared with HCs, DON patients exhibited significantly increased dALFF variability in the right middle frontal gyrus (P < 0.01). Conversely, DON patients exhibited obviously decreased dALFF variability in the right precuneus (P < 0.01). We also found that there were significant negative correlations between HADS scores and dALFF values of the right middle frontal gyrus in the DON patients (r = -0.6404, P <0.01 for anxiety and r = -0.6346, P <0.01 for depression; HADS, Hospital Anxiety and Depression Scale). Abnormal variability of dALFF was observed in specific areas of the cerebrum in DON patients, which may contribute to distinguishing patients with DON from HCs and a better understanding of DON, hyperintensities of right middle frontal gyrus may be potential diagnostic marker for DON.

PURPOSE: In Mendelian disease diagnosis, variant analysis is a repetitive, error-prone, and time consuming process. To address this, we have developed the Mendelian Analysis Toolkit (MATK), a configurable, automated variant ranking program. METHODS: MATK aggregates variant information from multiple annotation sources and uses expert-designed rules with parameterized weights to produce a ranked list of potentially causal solutions. MATK performance was measured by a comparison between MATK-aided and human-domain expert analyses of 1060 families with inherited retinal degeneration (IRD), analyzed using an IRD-specific gene panel (589 individuals) and exome sequencing (471 families). RESULTS: When comparing MATK-assisted analysis with expert curation in both the IRD-specific gene panel and exome sequencing (1060 subjects), 97.3% of potential solutions found by experts were also identified by the MATK-assisted analysis (541 solutions identified with MATK of 556 solutions found by conventional analysis). Furthermore, MATK-assisted analysis identified 114 additional potential solutions from the 504 cases unsolved by conventional analysis. CONCLUSION: MATK expedites the process of identification of likely solving variants in Mendelian traits, and reduces variability stemming from human error and researcher bias. MATK facilitates data reanalysis to keep up with the constantly improving annotation sources and next-generation sequencing processing pipelines. The software is open source and available at https://gitlab.com/matthew_maher/mendelanalysis.