The Association of Sickle-Cell Disorders With Diabetic Retinopathy: A Large Database Study.

Purpose: To evaluate the association of sickle-cell disease (SCD) and sickle-cell trait (SCT) disease with diabetic retinopathy (DR) in patients with diabetes mellitus (DM). Design: Population-based, retrospective cohort study utilizing data from the TriNetX Research Network, including 119 million patients across 80 health care organizations worldwide. Participants: Diabetes mellitus patients (type 1 [T1DM] or 2 [T2DM]), with or without SCD and SCT, were included. Three cohorts were analyzed, including (1) DM patients without SCD, SCT, or sickle-cell/hemoglobin-C; (2) DM with SCD; and (3) DM with SCT. Methods: All patients with DM were categorized into 3 cohorts based on the presence of SCD and SCT. Each cohort underwent 1:1 propensity score matching for demographics, blood glucose levels, hemoglobin A1C, and other relevant comorbidities. Main Outcome Measures: Risk of DR in DM patients with and without SCD or SCT. Results: There was no significant difference in the risk of any T1DR between those with and without SCD. However, for those with SCT, there was a notable twofold increased risk for T1-proliferative DR (PDR) (relative risk [RR]: 2.03; 95% confidence interval [CI]: 1.33-3.01). In contrast, there was an elevated risk for any T2DR in patients with SCD (RR: 1.50; 95% CI: 1.19-1.88), particularly due to higher PDR risks in T2DM patients (RR: 1.83; 95% CI: 1.29-2.60). The risk of mild to moderate T2DM non-PDR was also found to be higher in patients with SCT. Conclusions: The risk of any DR was increased in T2DM patients with SCD or SCT, with increased risks for PDR in patients with SCT and T1DM. This indicates there may be a potential role of sickle-cell disorders in diabetic eye disease progression. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Using Large Language Models to Generate Educational Materials on Childhood Glaucoma.

PURPOSE: To evaluate the quality, readability, and accuracy of large language model (LLM) generated patient education materials (PEMs) on childhood glaucoma, and their ability to improve existing online information's readability. DESIGN: Cross-sectional comparative study. METHODS: We evaluated responses of ChatGPT-3.5, ChatGPT-4, and Bard to three separate prompts requesting they write PEMs on "childhood glaucoma." Prompt A required PEMs be "easily understandable by the average American." Prompt B required PEMs be written "at a 6th-grade level using Simple Measure of Gobbledygook (SMOG) readability formula." We then compared responses' quality (DISCERN questionnaire, Patient Education Materials Assessment Tool (PEMAT)), readability (SMOG, Flesch-Kincaid Grading Level (FKGL)), and accuracy (Likert Misinformation scale). To assess the improvement of readability for existing online information, Prompt C requested LLM rewrite 20 resources from a Google search of keyword "childhood glaucoma" to the American Medical Association-recommended "6th-grade level." Rewrites were compared on key metrics such as readability, complex words (≥3 syllables), and sentence count. RESULTS: All 3 LLM generated PEMs that were of high quality, understandability, and accuracy (DISCERN≥4, ≥70% PEMAT understandability, Misinformation score=1). Prompt B responses were more readable than Prompt A responses for all 3 LLM (p≤0.001). ChatGPT-4 generated the most readable PEMs compared to ChatGPT-3.5 and Bard (p≤0.001). Although Prompt C responses showed consistent reduction of mean SMOG and FKGL scores, only ChatGPT-4 achieved the specified 6th-grade reading level (4.8 ± 0.8 and 3.7 ± 1.9, respectively). CONCLUSION: LLMs can serve as strong supplementary tools in generating high quality, accurate, and novel PEMs, and improving the readability of existing PEMs on childhood glaucoma.

Trends in Medicare Submitted Charges to Allowed Payment Ratios for Ophthalmology Services.

Purpose: Many physicians charge more than the Medicare insurance program pays. Current charge-to-payment ratios in ophthalmology and trends over the years are unknown. In this work, we examined physician charge-to-payment ratios in ophthalmology across procedures and consultations. Methods: We utilized data from 100% final-action physician/supplier Part B Medicare fee-for-service (FFS) population from 2015 to 2020. We retrieved data on ophthalmic procedures and consultations, both facility-based and non-facility-based, conducted by ≥ 50 ophthalmologists. We analyzed median charge-to-payment ratios, which were calculated as submitted charges divided by the Medicare-allowed payments, between ophthalmic procedures and consultations to assess for trends over the study period. Results: We find that the median charge-to-payment ratio for all current procedural terminology (CPT) codes in 2020 was 2.23 (Interquartile range (IQR): 1.54-3.27) as compared to 2.00 (IQR: 1.39-2.92) in 2015, an overall 2.76% average annual growth rate from 2015-2020. For ophthalmic procedures, the median charge-to-payment ratio in 2020 was 3.03 (IQR: 2.13-4.41) compared to 2.79 (IQR: 1.96-3.97) in 2015, corresponding to a 2.01% AAGR from 2015-2020. For consultations, those rates were 2.06 (IQR: 1.48-2.96), 1.85 (IQR: 1.33-2.59), and 2.71%, respectively. Conclusion: We found that the submitted charge-to-Medicare payment ratios among ophthalmic procedures and consultations have steadily increased since 2015. However, there was a relatively low rate of excess charges for ophthalmology services compared to other surgical-based specialties with minimal variation among providers.

Effect of Oral Prednisone on the Prevention and Management of Proliferative Vitreoretinopathy After Open-Globe Injury.

Purpose: To determine the impact of oral prednisone on the final visual acuity (VA) and prevention of proliferative vitreoretinopathy (PVR) in patients having pars plana vitrectomy (PPV) for globe injuries. Methods: A retrospective chart review was performed of all globe injuries with an initial repair and subsequent PPV between 2009 and 2018. Data included the initial VA, zones of injury, initial closure date, time to secondary intervention (PPV), oral prednisone (1 mg/kg/day) use, the final VA, and enucleation rate. Multivariable regression models were used to assess the impact of oral prednisone use on anatomic and functional outcomes. Results: The mean (±SD) patient age was 46.25 ±18.56 years (range, 13-92); 131 (83.9%) were men. Oral prednisone intake was recorded in 81 patients (52.3%). The prednisone group had significantly more zone 3 involvement (P = .001), worse initial VA (2.28 vs 1.92 logMAR; P = .003), and a greater mean number of surgeries (P = .020) than the no-steroids (control) group but an equivalent final logMAR VA (1.57 vs 1.52; P = .881). The prednisone group had significant VA improvement (P = .025); however, oral prednisone use did not predict the development of PVR (29.23% vs 12.90%; odds ratio [OR], 2.81; 95% CI, 0.89-8.85) or retinal detachment (27.27% vs 29.58%; OR, 0.59; 95% CI, 0.23-1.56). Conclusions: Despite a worse initial clinical presentation, patients who received oral prednisone had significant visual improvement compared with the control group. However, oral prednisone (1 mg/kg/day) use at the time of injury did not decrease the PVR rate.

The impact of the COVID-19 pandemic on ocular trauma in American infants and toddlers.

PURPOSE: To assess the impact of the COVID-19 pandemic on infant and toddler ocular trauma in the United States. METHODS: This retrospective analysis of ocular injury data for children ≤3 years of age focused on epidemiologic trends in pediatric ocular injuries in the United States caused by consumer products from 2017 to 2021 and compared differences between pre-pandemic (2017-2019) and pandemic (2020-2021) time periods. Data were collected from the US Consumer Product Safety Commission National Electronic Injury Surveillance System, which includes emergency department visits caused by consumer product-related injuries from a nationally representative sample of hospitals. RESULTS: The national-level estimate of ocular injuries in infants and toddlers was 51,250 (95% CI, 30471-72030). Most injuries occurred at home. We found a significant decline in the proportion of projectile ocular injuries from 0.89% (95% CI, 0.35-2.25) to 0.12% (95% CI, 0.03-0.45) (P = 0.037). The proportion of patients diagnosed with chemical-burn-related injuries increased significantly, from 23.34% (95% CI, 19.73-27.38) in the pre-pandemic period to 31.63% (95% CI, 26.98-36.69) in the pandemic period (P = 0.048), with 71.75% (95% CI, 65.25-77.46) due to cleaning products. After adjusting for confounding variables, the odds of sustaining a chemical-burn-related injury in the post-pandemic period were 1.51 times higher than in the pre-pandemic period (95% CI, 1.10-2.08). CONCLUSIONS: The proportion of children diagnosed with chemical-burn-related injuries increased significantly in the post-pandemic period, with a large portion due to cleaning products.

Risk of abducens nerve palsy following COVID-19 vaccination.

PURPOSE: To investigate the prevalence and risk of new-onset abducens nerve palsy and acute-onset diplopia following mRNA COVID-19 vaccination. METHODS: In this retrospective, population-based study, patient data from the COVID-19 Research Network of TriNetX was searched via the TriNetX Analytics platform for patients who received specific vaccinations based on Common Procedural Technology codes. We recorded instances of newly diagnosed abducens nerve palsy and diplopia within 21 days following each vaccination event. RESULTS: Of the 3,545,224 patients (mean age at vaccination, 46.2 ± 21.3 years) who received the mRNA COVID-19 vaccine, 12 (<0.0001%) patients had a new diagnosis of abducens nerve palsy and 453 (0.013%) had acute-onset diplopia within 21 days of first dose of COVID-19 vaccination. After propensity score matching, the relative risk for new abducens nerve palsy diagnosis after the first dose of COVID-19 vaccination was not significantly different from that after influenza (RR, 0.77), Tdap (RR, 1.0), or the second dose of the COVID-19 vaccinations (RR, 1.00). Furthermore, there was a lower risk of abducens nerve palsy diagnosis after the first dose of the COVID-19 vaccination compared with the risk after COVID-19 infection (RR, 0.15). CONCLUSIONS: The risk of a new abducens nerve palsy diagnosis following the first dose of the COVID-19 vaccine is lower than the risk associated with COVID-19 infection itself. There is no evidence to suggest a causal relationship between COVID-19 vaccination and the development of abducens nerve palsy.

Association of Primary Open-Angle Glaucoma with Diabetic Retinopathy among Patients with Type 1 and Type 2 Diabetes: A Large Global Database Study.

PURPOSE: To assess the correlation between primary open-angle glaucoma (POAG) and the risk of developing diabetic retinopathy (DR) in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). DESIGN: A retrospective cohort study leveraging the global patient database of TriNetX Research Network. PARTICIPANTS: The study included 44 359 patients with diabetes mellitus (DM) with POAG and 4 393 300 patients with DM without any glaucoma ≥ 18 years of age. Propensity score matching harmonized the cohorts to 39 680 patients each, covering diagnoses from January 1, 2005, to January 1, 2023. METHODS: We analyzed data using specific International Classification of Diseases, 10th Revision (ICD-10) codes for DM and glaucoma. We matched the cohorts using propensity score matching, adjusting for age, sex, race/ethnicity, blood markers, relevant medical history, and ophthalmic service use. MAIN OUTCOME MEASURES: The primary outcome was the first-time occurrence of DR, including nonproliferative DR (NPDR) and proliferative DR (PDR), in patients with DM with and without glaucoma at 1-, 5-, and 10-year intervals from their individual index dates. RESULTS: At 10 years, patients with T1DM with POAG exhibited a heightened risk for any DR (adjusted risk ratios [RRs], 4.12; 95% confidence interval [CI], 3.05-5.57, P < 0.0001) and PDR (RR, 7.02; 95% CI, 3.62-13.61, P < 0.0001). Patients with T2DM and POAG also faced an increased 10-year risk for any DR (RR, 2.47; 95% CI, 2.28-2.68, P < 0.0001) and PDR (RR, 3.82; 95% CI, 3.09-4.70, P < 0.0001). The combined association of POAG on DR risk in those with T1DM and T2DM at 10 years was found to be significantly higher among patients with POAG (5.45%) compared with those without glaucoma (2.12%) (adjusted hazard ratio [aHR], 2.33; 95% CI, 2.14-2.53). The cumulative incidence of DR was significantly higher in the POAG group compared with nonglaucoma counterparts after a decade (log-rank P < 0.001). CONCLUSIONS: Our findings underscore a substantial association between POAG and DR development in both T1DM and T2DM patients, emphasizing the need for vigilant screening and comprehensive management in glaucomatous patients with DM to mitigate the risk of DR. Future research should delve into elucidating the causal mechanisms driving these observed associations. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intraoperative complications and visual outcomes of cataract surgery in neovascular age-related macular degeneration.

PURPOSE: To compare the rate of intraoperative complications and visual outcomes in patients with neovascular age-related macular degeneration (NvAMD) and control eyes without NvAMD undergoing phacoemulsification. SETTING: Multicenter study. DESIGN: Retrospective, nonrandomized comparative study. METHODS: Eyes were classified based on the presence or absence of an NvAMD diagnosis. The main outcomes were (1) the rate of intraoperative complications, (2) the logMAR visual acuity (VA) at 4 to 12 weeks postoperatively in both groups, and (3) the reinjection rate of intravitreal antivascular endothelial growth factor after phacoemulsification. RESULTS: Preoperative VA was worse in the NvAMD group (0.9 ± 0.5) compared with the reference group (0.6 ± 0.5). We observed no difference in the rate of posterior capsule rupture (PCR) (2.90% vs 2.77%; P = .889), dropped lens fragments (0.46% vs 0.29%; P = .618), or zonular dialysis (0.46% vs 0.58%, P = .749) between the 2 groups. Receiving ≥10 intravitreal injections before cataract surgery predicted the likelihood of PCR with an odds ratio of 2.86 (P = .027). Proportions of eyes achieving a visual gain of ≥0.3 logMAR (∼3 Snellen lines equivalent) was lower in NvAMD eyes (39.2% vs 63.7%; P < .0001). We observed 203 eyes (73%) in the active treatment group and 139 eyes (36%) in the inactive treatment group received >1 intravitreal injection after phacoemulsification (P < .0001). CONCLUSIONS: The risk for PCR was higher for eyes receiving ≥10 intravitreal injections before phacoemulsification. Only 39% of eyes with NvAMD had visual improvement by ≥3 Snellen lines.

Quality, Reliability, Technical Quality, and Readability of Google Online Information on Childhood Glaucoma.

PURPOSE: To evaluate the quality, reliability, technical quality, and readability of online information related to childhood glaucoma. METHODS: In this cross-sectional study, no human subjects were studied. Analysis was done for online websites on childhood glaucoma. The terms "childhood glaucoma," "pediatric glaucoma," "congenital glaucoma," "buphthalmos," and "big eyes" were entered into the Google search engine and the first 100 search results were assessed for quality, reliability, technical quality, and readability. Peer-reviewed articles, patient forum posts, dictionary definitions, and websites that appeared as targeted ads, were not in English, or were not focused on humans were excluded. Each website was evaluated for (1) quality and reliability using the DISCERN, HONcode, and JAMA criteria; (2) technical quality assessing 11 technical aspects; and (3) readability using six separate criteria (Flesch-Kincaid Reading Ease Score and Grade Level, Gunning Fog Index score, the Simple Measure of Gobbledygook Index, Coleman-Liau Index, and Automated Readability Index). RESULTS: The median scores for the DISCERN, HONcode, and JAMA criteria were 2.6 (range = 1 to 4.75; 1 = worst, 5 = best), 10 (range = 0 to 16; 0 = worst, 16 = best), and 2 (range = 0 to 4; 0 = worst, 4 = best), respectively. The median technical quality score was 0.7. Readability was poor among most websites, with a median Flesch-Kincaid grade Grade Level Score of 9.3. The median Gunning Fog Index score was 9.8. There was a statistically significantly higher JAMA score and Gunning Fog Index score among the private websites compared to the institutional websites. However, institutional websites had higher technical quality. CONCLUSIONS: Online information on childhood glaucoma had poor to moderate quality and reliability. The technical quality is good; however, most websites' readability was above the recommended 5th to 6th grade reading level. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

Ophthalmology Faculty Diversity Trends in the US.

Importance: Enhancing the diversity of ophthalmologists can potentially contribute to diminishing disparities in eye care. Objectives: To investigate longitudinal trends in the representation of individuals underrepresented in medicine (URiM) and women among ophthalmology faculty compared with other specialties and to assess disparities between ophthalmology faculty demographic characteristics and the US population. Design, Setting, and Participants: In this cross-sectional study, a comprehensive analysis of Association of American Medical Colleges Faculty Roster data between 2000 and 2021 was conducted, using data from the US Medical School Faculty report on 56 438 ophthalmology faculty members. Main Outcomes and Measures: The data set was used to differentiate ophthalmology faculty members by gender, rank, and designation as a URiM individual. Outcome measures included changes in URiM and non-URiM faculty proportions, faculty rank, gender, department chair positions, and the US population between 2000 and 2021. Results: A total of 56 438 ophthalmology faculty members (37 511 men [66.5%]) were included in the study. The number of ophthalmology faculty increased from 1820 in 2000 to 3151 in 2021. Across all years, URiM female faculty represented 3.1% of ophthalmologists (1733 of 56 438), while URiM men accounted for 3.5% (1983 of 56 438). Overall, non-URiM men constituted 63.0% of ophthalmologists (35 528 of 56 438), and non-URiM women accounted for 30.5% (17 194 of 56 438). The proportion of URiM male faculty remained stable from 2000 to 2021 (63 of 1820 [3.5%] vs 104 of 3151 [3.3%]), with a small increase in URiM women faculty at junior faculty positions (2000, 40 of 1820 [2.2%]; 2021, 129 of 3151 [4.1%]; difference, 1.9% [95% CI, 0.9%-2.9%]). Proportions of non-URiM men decreased from 71.2% (1295 of 1820) in 2000 to 55.3% (1743 of 3151) in 2021 (difference, 15.8% [95% CI, 13.1%-18.6%]) and proportions of non-URiM women increased from 23.2% (422 of 1820) in 2000 to 37.3% (1175 of 3151) in 2021 (difference, 14.1% [95% CI, 11.5%-16.7%]). In terms of faculty rank, there were increases in representation of women from 2000 to 2021 at assistant professor (from 11.2% [203 of 1819] to 19.7% [622 of 3165]; difference, 8.5% [95% CI, 6.5%-10.5%]), associate professor (from 4.6% [83 of 1819] to 8.6% [271 of 3165]; difference, 4.0% [95% CI, 2.6%-5.4%]), and professor levels (from 2.8% [51 of 1819] to 7.1% [223 of 3165]; difference, 4.3% [95% CI, 3.9%-6.1%]). URiM representation remained stable at most ranks. Compared with other specialties, ophthalmology had among the lowest percentage change in URiM faculty. The expansion of ophthalmology's URiM faculty representation was less than one-third that of the diverse US population. Conclusion and Relevance: These findings highlight substantial growth in ophthalmology faculty and an increase in women's representation across several faculty ranks. However, URiM representation has remained largely unchanged, despite an increase at the associate professor level. This finding emphasizes the need for continued efforts to enhance diversity in academic ophthalmology.

Forecasting Retirement in Pediatric Ophthalmology.

This cross-sectional study uses a forecasting model to assess the potential loss of pediatric ophthalmology care in the US due to potential ophthalmologist retirement.

Association of Neighborhood Environment with the Outcomes of Childhood Glaucoma.

PURPOSE: To determine the association between different neighborhood environment factors and the outcomes of childhood glaucoma. DESIGN: A retrospective cohort. PARTICIPANTS: Childhood glaucoma patients ≤ 18 years of age at the time of diagnosis. METHODS: A retrospective chart review of childhood glaucoma patients who presented to Boston Children's Hospital between 2014 and 2019. Data collected included etiology, intraocular pressure (IOP), management, and visual outcomes. Child Opportunity Index (COI) was used as a metric of neighborhood quality. MAIN OUTCOMES MEASURES: The association of visual acuity (VA) and IOP with COI scores using linear mixed-effect models, adjusting for individual demographics. RESULTS: A total of 221 eyes (149 patients) were included. Of these, 54.36% were male and 56.4% were non-Hispanic Whites. The median age at the time of presentation was 5 months for primary glaucoma and 5 years for secondary glaucoma. The median age at the last follow-up was 6 and 13 years for primary and secondary glaucoma, respectively. A chi-square test revealed that the COI, health and environment, social and economic, and education indexes between primary and secondary glaucoma patients were comparable. For primary glaucoma, the overall COI and a higher education index were associated with a lower final IOP (P < 0.05), and higher education index was associated with a lower number of glaucoma medications at the last follow-up (P < 0.05). For secondary glaucoma, higher overall COI, health and environment, social and economic, and education indices were associated with better final VA (lower logarithms of the minimum angle of resolution VA) (P < 0.001). CONCLUSIONS: Neighborhood environment quality is a potentially important variable for predicting outcomes in childhood glaucoma. Lower COI scores were associated with worse outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impact of axial length on visual outcomes and complications in phacoemulsification surgery: a multicenter database study.

PURPOSE: To analyze the impact of axial length (AL) on the visual outcome and rate of perioperative complications in phacoemulsification surgery. DESIGN: Retrospective clinical database study. METHODS: Cataract surgery data of 217,556 eyes was extracted from the electronic medical records of 8 ophthalmic centers in the United Kingdom from July 2003 to March 2015. A total of 88,774 eyes without ocular co-pathologies were grouped eyes according to AL (mm): short AL (< 22), average AL (22-26; reference group), and long AL (> 26). MAIN OUTCOMES AND MEASURES: We analyzed visual acuity (VA) outcomes at 4 weeks, 4-12 weeks, and 12-24 weeks postoperatively, as well as the incidence of posterior capsular rupture (PCR), torn iris (TI), cystoid macular edema (CME), and retinal detachment (RD). RESULTS: Mean pre-operative VA (logMAR) was the worst in eyes with long AL compared to average and short AL eyes (VA 0.59 vs. 0.58 and 0.56; p < 0.001). However, post-operative VA at 4-12 weeks was slightly better in the long AL group (0.14 in short and average AL; 0.12 in long AL, p < 0.001). We observed an increased odds of TI in the short AL group (OR 2.09, 95% CI 1.60-2.75). There was increased risk of RD in long AL eyes (p < 0.001). However, PCR and CME rates were not different. CONCLUSION: In the absence of any coexisting ocular pathology, AL alone did not have an impact on VA improvement or the risk of encountering PCR or CME. The risk of TI was greater in the short AL group, and the risk of RD was higher in the long AL group.

Ahmed and Baerveldt Glaucoma Drainage Devices in Childhood Glaucoma: A Meta-Analysis.

PRCIS: The effectiveness of Ahmed glaucoma valve (AGV) and Baerveldt glaucoma implant (BGI) was comparable in the management of childhood glaucoma over the long term despite initial better success rate with BGI. There were higher tube block and retraction rates in the BGI group and higher tube exposure rates in the AGV group. PURPOSE: To evaluate the outcomes and safety of AGV and BGI in childhood glaucoma. MATERIALS AND METHODS: We performed a systematic literature review of publications from 1990 to 2022 in PubMed, EMBASE, ClinicalTrials.gov, Ovid MEDLINE, Cochrane CENTRAL, and google scholar for studies evaluating AGV and BGI in childhood glaucoma. Primary outcome measures were intraocular pressure (IOP) reduction and glaucoma medication reduction. The secondary outcome measures were the success rates and incidence of postoperative complications. We conducted a meta-analysis using a random effects model. RESULTS: Thirty-two studies met the inclusion criteria. A total of 1480 eyes were included. The mean IOP reduction was 15.08 mm Hg ( P < 0.00001) for AGV and 14.62 ( P < 0.00001) for the BGI group. The mean difference between pre and postoperative glaucoma medications was 1 ( P < 0.00001) fewer medications in the AGV group and 0.95 ( P < 0.0001) fewer medications in the BGI group. There was a lower success rate in the AGV versus BGI groups at 2 years [63% vs 83%, respectively ( P < 0.0001) and 3 years (43% vs 79%, respectively ( P < 0.0001)]; however, the success was higher for AGV at 5 years (63% vs 56% in the BGI group, P < 0.001). The incidence of postoperative complications was comparable in the AGV and BGI groups, with rates of 28% and 27%, respectively. CONCLUSIONS: The IOP and glaucoma medication reduction, success rates, and incidence of postoperative complications were comparable in Ahmed and Baerveldt groups. Most literature comes from retrospective low-quality studies on refractory childhood glaucoma. Further larger cohort studies are needed.

Corneal Adverse Events Associated with SARS-CoV-2/COVID-19 Vaccination: A Systematic Review.

Vaccines against coronavirus disease 2019 (COVID-19) have played an important global role in reducing morbidity and mortality from COVID-19 infection. While the benefits of vaccination greatly outweigh the risks, adverse events do occur. Non-ocular adverse effects of the vaccines have been well-documented, but descriptions of ophthalmic effects remain limited. This systematic review aims to provide an overview of reported cases of corneal adverse events after receiving vaccination against COVID-19 and to compile existing clinical data to bring attention to these phenomena. Our review discusses corneal graft rejection, including proposed mechanisms, herpetic keratitis, and other reported corneal complications. Ophthalmologists and primary care physicians should be aware of such possible associations.

Temporal Alterations of Sphingolipids in Optic Nerves After Indirect Traumatic Optic Neuropathy.

Purpose: To identify optic nerve (ON) lipid alterations associated with sonication-induced traumatic optic neuropathy (TON). Design: Experimental study. Subjects: A mouse model of indirect TON was generated using sound energy concentrated focally at the entrance of the optic canal using a laboratory sonifier with a microtip probe. Methods: Analyses of datasets generated from high-performance liquid chromatography-electrospray tandem mass spectrometry of ONs dissected from the head of the ON to the optic chiasm at 1 day, 7 days, and 14 days postsonication compared with that in nonsonicated controls. Main Outcome Measures: Lipid abundance alterations in postsonicated ONs were evaluated using 1-way analysis of variance (false discovery rate-adjusted significant P value < 0.01), lipid-related gene sets, biochemical properties, and receiver operating characteristic to identify lipids associated with optic neuropathy. Results: There were 28 lipid species with significantly different abundances across the control and postsonication groups. The 2 most significantly upregulated lipids included a sphingomyelin (SM) species, SM(d40:7), and a hexosylceramide (CerG1) species, CerG1(d18:1/24:2). Hexosylceramide (d18:1/24:2) was noted to have a stepwise increasing trend from day 1 to day 14 after sonication-induced optic neuropathy. Investigation of biophysical properties showed notable enrichment of lipids with high and above-average transition temperatures at day 14 after sonication. Lipid-related gene set analysis revealed enrichment in sphingolipid and glycosphingolipid metabolic processes. The best classifier to differentiate day 14 postsonication from controls, based on area under the receiver operating characteristic curve, was CerG1(d18:1/24:2) (area under the receiver operating characteristic curve: 1). Conclusions: Temporal alterations in sphingolipid metabolism and biochemical properties were observed in the ON of mice after sonication-induced optic neuropathy, with notable elevations in sphingomyelin and hexosylceramide species. Hexosylceramide (d18:1/24:2) may be associated with damage after indirect trauma, indicating that lipid membrane abnormalities may be a mediator of pathology due to trauma.

Mitochondrial Triglyceride Dysregulation in Optic Nerves Following Indirect Traumatic Optic Neuropathy.

The purpose of this work is to identify mitochondrial optic nerve (ON) lipid alterations associated with sonication-induced traumatic optic neuropathy (TON). Briefly, a mouse model of indirect TON was generated using sound energy concentrated focally at the entrance of the optic canal using a laboratory sonifier (Branson Digital Sonifier 450, Danbury, CT, USA) with a microtip probe. We performed an analysis of a previously generated dataset from high-performance liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). We analyzed lipids from isolated mitochondria from the ON at 1 day, 7 days, and 14 days post-sonication compared to non-sonicated controls. Lipid abundance alterations in post-sonicated ON mitochondria were evaluated with 1-way ANOVA (FDR-adjusted significant p-value < 0.01), debiased sparse partial correlation (DSPC) network modeling, and partial least squares-discriminant analysis (PLS-DA). We find temporal alterations in triglyceride metabolism are observed in ON mitochondria of mice following sonication-induced optic neuropathy with notable depletions of TG(18:1/18:2/18:2), TG(18:1/18:1/18:1), and TG(16:0/16:0/18:1). Depletion of mitochondrial triglycerides may mediate ON damage in indirect traumatic optic neuropathy through loss energy substrates for neuronal metabolism.