A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in the PDE6B gene in the affected twins and their unaffected father. Further investigation, using genome sequencing, identified a novel ∼7.5-kb deletion (Chr 4:670,405-677,862del) encompassing the ATP5ME gene, part of the 5' UTR of MYL5, and a 378-bp (Chr 4:670,405-670,782) region from the 3' UTR of PDE6B in the affected twins and their unaffected mother. Both variants segregated with disease in the family. Analysis of the relative expression of PDE6B, in peripheral blood cells, also revealed a significantly lower level of PDE6B transcript in affected siblings compared to a normal control. PDE6B is associated with recessive rod-cone degeneration and autosomal dominant congenital stationary night blindness. Ophthalmic evaluation of these patients showed night blindness, fundus abnormalities, and peripheral vision loss, which are consistent with PDE6B-associated recessive retinal degeneration. These findings suggest that the loss of PDE6B transcript resulting from the compound heterozygous pathogenic variants is the underlying cause of recessive rod-cone degeneration in the study family.

BACKGROUND AND OBJECTIVES: Archetypal analysis (AA), a form of unsupervised machine learning, can identify quantifiable visual field (VF) patterns seen in optic neuritis (ON), known as archetypes (ATs). We hypothesized that AT weight changes over time would reflect the course of recovery and the effects of therapy in ON. We explored whether baseline AT weights would be associated with VF status at the clinical trial outcome and if ATs would indicate residual VF defects in eyes with mean deviation (MD) ≥ -2.00 at six months. METHODS: We used a published 16-AT model derived from 3892 Optic Neuritis Treatment Trial VFs (456 eyes) for all analyses. We measured AT weight changes over the six-month study period and used asymptotic regression to analyze the rate of change. We compared AT weights at six months between treatment groups. We evaluated associations between baseline AT weight thresholds and VF outcome or treatment effect. We calculated residual AT weights in eyes with MD ≥ -2.00 dB at six months. RESULTS: Over six months, AT1 (a normal VF pattern) demonstrated the greatest median weight change, increasing from 0.00% (IQR 0.00-0.00%) at baseline to 60.0% (IQR 38.3-70.8%) at six months (p < 0.001). At outcome, the intravenous methylprednisolone (IVMP) group had the highest median AT1 weight (IVMP: 63.3%, IQR 51.3-72.8%; placebo: 56.2%, IQR 35.1-71.6%; prednisone 58.3%, IQR 35.1-71.6%; p = 0.019). Eyes with AT1 weight ≥ 19% at baseline had superior median MD values (-0.91 vs. -2.07 dB, p < 0.001) and AT1 weights (70.8% vs. 57.8% p < 0.001) at six months. Only eyes with AT1 weight < 19% at baseline showed a treatment benefit for IVMP, with a higher six-month median AT1 weight compared to placebo (p = 0.015) and prednisone (p = 0.016), and a higher median MD compared to placebo (p = 0.027). At six months, 182 (80.2%) VFs with MD ≥ -2.00 had at least one abnormal AT. DISCUSSION: Changes in quantifiable, archetypal patterns of VF loss reflect recovery in ON. Machine learning analysis of the VFs in optic neuritis reveals associations with response to therapy and VF outcome, and uncovers residual deficits, not readily seen with standard evaluations.

PURPOSE: We compare the ability of resident physicians to identify retinal breaks on ultra-widefield color fundus photos using the traditional image compared to an image with a green filter overlay. METHODS: Residents were shown fundus photos of 10 eyes with either a retinal tear or hole. Participants were shown each photo twice-once with traditional color settings and once with a green filter overlay. Participants were scored on whether the break was correctly identified and timed on how long it took to identify the pathology. RESULTS: Residents were able to correctly identify more retinal breaks on fundus photos with a green filter overlay compared to photos with traditional settings (P = 0.02). Residents were also able to identify breaks on fundus photos more quickly on images with a green filter overlay compared to the traditional images (P < 0.001). CONCLUSIONS: The application of a green filter overlay may help in identifying retinal breaks.

PURPOSE: To calculate costs of treatment for diabetic macular edema (CI-DME) with bevacizumab-first (step therapy) compared to aflibercept monotherapy. DESIGN: Cost analysis of treatment arms based on a published study SUBJECTS: None METHODS: Published results from the Diabetic Retinopathy Clinical Research Network (DRCR.net) protocol AC were used to assess costs. Data incorporated in a usage and outcome model included frequency of injections, medication type, visits, and imaging. Costs were modeled based on 2022 Medicare reimbursement data for both facility (hospital-based) and non-facility settings in Miami. Outcomes were similar in Protocol AC so were not differentially studied. Results were extrapolated so as to estimate lifetime (17 years for the age of the cohort). RESULTS: Over the 2 years reported in protocol AC, the cost required to treat in the facility (nonfacility setting) was $42,000 ($32,000) in the aflibercept monotherapy group and $29,000 ($22,000) in the bevacizumab-first group. Extrapolated modeled lifetime costs were $158,000 ($136,000) and $125,000 ($103,000), respectively. The total cost with bevacizumab-first was 33% lower at year 2 and 21% lower at year 17 compared with aflibercept monotherapy. Savings per year for the 2 year results were $6,500 ($5000) in the facility (non-facility) setting. For the extrapolated 17 year model annual savings were $1900 ($1900) in the facility (non-facility) setting. The professional fees accounted for a minority of overall costs; in contrast, medication costs accounted for 82% of the total costs for the aflibercept monotherapy and 73% in the bevacizumab-first group at 2 years. Our model predicted an additional 15% lifetime cumulative savings if patients still not meeting threshold criteria after switching to aflibercept were placed back on bevacizumab, and a similar degree of improvement if those on not meeting threshold criteria on aflibercept monotherapy were switched to bevacizumab. MAIN OUTCOME MEASURES: Cost of treatment options. CONCLUSION: Medication is the dominant driver of the total expenses associated with the treatment of diabetic macular edema. While cost savings are realized with bevacizumab-first step therapy, the magnitude was not as much as might be intuited, probably due to the high (70%) incidence of patients switching to aflibercept within Protocol AC.

Purpose: To report visual function and quality of life (VF/QOL) using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the ocular surface disease index (OSDI) in patients in the chronic phase of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods: The NEI-VFQ-25 questionnaire was administered to 15 patients who received protocol-based care in the form of topical medications with or without amniotic membrane transplantation (AMT) for acute SJS/TEN. The scores obtained were compared with scores from a healthy population. The associations between the NEI-VFQ-25 and dry eye symptoms as measured by OSDI questionnaire were also studied. Results: Patients were surveyed at a mean of 4.47 ± 2.22 years after acute SJS/TEN. Eleven patients received AMT in the acute phase. The median best corrected visual acuity at the time of administration of the questionnaire was 20/20. The mean composite NEI-VFQ-25 score was 86.48 ± 12. Patients who received protocol-based treatment in the acute phase of SJS/TEN had comparable NEI-VFQ-25 scores with healthy subjects on all subscales except ocular pain (p = 0.027) and mental health (p = 0.014), which were significantly reduced. The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = -0.75, p = 0.001). Conclusion: A protocol-based management strategy composed of early ophthalmic evaluation, grading based on severity, the use of topical corticosteroids and AMT in the acute phase of SJS/TEN in patients with ocular complications helped preserve the VF/QOL. This study highlights the impact of appropriate management of the ocular complications in the acute phase of SJS/TEN.

OBJECTIVE: To quantify changes in ductions following nasal transposition of the split lateral rectus muscle (NTSLR) for treating third nerve palsy. DESIGN: Retrospective cohort study. PARTICIPANTS: A single eye from each patient with third nerve palsy treated with NTSLR with ocular motility measurements. METHODS: Observation of changes in pre- and postoperative ductions. Outcome measures including patient demographic and surgical factors associated with the ability to adduct beyond the midline after NTSLR were evaluated using multivariable logistic regression. RESULTS: A total of 116 patients met the inclusion criteria for this study. The NTSLR significantly decreased abduction (median of 0 limitation [interquartile range (IQR), 0-0] prior to surgery to -4 [IQR, -4 to -3] after NTSLR; p < 0.001), with a corresponding improvement in adduction (median, -5 [IQR, -5 to -4] prior to surgery to -4 [IQR, -4 to -3] after NTSLR; p < 0.001). There was no change in median supraduction or infraduction after NRSLR (p > 0.05). The ability to adduct beyond the midline after NTSLR was demonstrated in 42% of patients. Although not statistically significant, a trend toward a postoperative ability to adduct beyond the midline was seen in patients who had concurrent superior oblique muscle tenotomy (odds ratio [OR] = 5.08; 95% CI, 0.91-40.9) or who were designated with partial rather than complete third nerve palsy (OR = 2.29; 95% CI, 0.82-6.70). CONCLUSIONS: NTSLR improves the horizontal midline positioning of eyes with third nerve palsy. Most eyes lose the ability to abduct, but some regain a modest ability to adduct while vertical ductions remain unchanged.

Contact lenses are a safe and effective method for correction of refractive error and worn by an estimated 45 million Americans. Because of the widespread availability and commercial popularity of contact lenses, it is not well appreciated by the public that contact lenses are U.S. Food and Drug Administration (FDA)-regulated medical devices. Contact lenses are marketed in numerous hard and soft materials that have been improved over decades, worn in daily or extended wear, and replaced in range of schedules from daily to yearly or longer. Lens materials and wear and care regimens have impact on the risks of contact lens-related corneal inflammatory events and microbial keratitis. This article reviews contact lens safety, with specific focus on the correction of refractive error in healthy eyes.

Background: Retinal vascular abnormality is an important part of ocular systemic sclerosis (SSc), and long-term use of chloroquine can lead to retinal toxicity. This study was conducted to evaluate retinal microvascular changes using optical coherence tomography angiography (OCTA) in patients with SSc and SSc patients on long-term chloroquine treatment. Methods: Fifteen SSc patients without chloroquine (30 eyes), 15 SSc patients taking long-term chloroquine (30 eyes) and 15 healthy controls (30 eyes) were recruited to this cross-sectional study. OCTA was used to examine the superficial and deep retinal capillary plexus in the macular retina of each eye. The densities of microvessels (MIR), macrovessels (MAR) and total microvessels (TMI) in the superficial and deep retina of the three groups were calculated and compared. We used the hemisphere segmentation method [superior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)] and Early Treatment Diabetic Retinopathy Study (ETDRS) method [right (R), superior (S), left (L), and inferior (I)] to analyze changes in retinal microvascular density. Results: The superficial and deep retinal MIR density in SSc patients decreased (P<0.05) compared with the healthy control group. This significant difference was found in both superficial and deep layers in S, L, SR, SL and IL regions (P<0.05), and additionally in the R and I regions in the superficial layer (P<0.05). Similarly, compared with SSc patients who did not take chloroquine, the superficial and deep retinal MIR density of SSc patients on long-term chloroquine also decreased (P<0.05). This significant difference was found in both superficial and deep layers in R, I and IL regions (P<0.05), and additionally in the IR region in the superficial layer (P<0.05). Conclusions: The OCTA results suggest that retinal MIR density is decreased in SSc patients, and that long-term use of chloroquine will aggravate this damage, resulting in a further decrease in retinal MIR density.

IMPORTANCE: Literature and anecdotal evidence suggest a relationship between male sex and retinopathy of prematurity (ROP). It is not known whether a difference, if present, is sex-related pathophysiologic predisposition or sex difference in meeting ROP screening criteria. OBJECTIVE: To evaluate the association of sex with the development of treatment-warranted ROP. DATA SOURCES: PubMed, Embase, and Web of Science databases were searched from 2000 to 2022. The search strategy used keywords including retinopathy of prematurity or ROP or retrolental fibroplasia and treatment or anti-VEGF or bevacizumab or ranibizumab or aflibercept or conbercept or laser or cryotherapy and gender or sex or male or female and medical subject headings terms. STUDY SELECTION: All studies reporting on treatment with anti-vascular endothelial growth factor, laser photocoagulation, and/or cryotherapy for ROP were identified. Studies reporting sex distribution in the treatment group were included in the meta-analysis. Exclusion criteria included case reports, case series of fewer than 10 treated patients, systematic reviews, conference abstracts, letters to the editor, animal studies, and non-English records. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened and extracted the data following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The proportions of treated male and female infants were combined using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Numbers and percentages of male and female infants treated for ROP. RESULTS: Of 11 368 identified studies, 316 met inclusion criteria, yielding a total of 31 026 treated patients. A higher percentage of male infants were treated for ROP (55% [95% CI, 0.54%-0.55%]), with low heterogeneity between studies (I2 = 34%; P < .001). Thirty-eight studies reported sex distribution in the screened population (170 053 patients; 92 612 [53%] male vs 77 441 [47%] female). There was no significant difference in the odds of receiving treatment between screened male and female infants (pooled odds ratio, 1.04 [95% CI, 0.91-1.18]; P = .67). CONCLUSIONS AND RELEVANCE: More male infants are treated for ROP than female infants. This could be due to a known relative pathophysiological fragility of preterm male infants in addition to a difference in ROP screening rates, with more male infants meeting the criteria than female infants. These findings have implications for future studies and may prompt more careful clinical monitoring of male neonates.