Topical insulin in neurotrophic keratopathy after diabetic vitrectomy.

To assess the efficacy and safety of topical insulin (TI) for treating neurotrophic keratopathy (NK) within one-month post-diabetic vitrectomy (DV) compared to conventional non-invasive measures, we conducted this retrospective case-control study including all eyes that developed acute NK (stages 2 and 3) following DV between October 2020 and June 2023. The control group included NK cases managed with preservative-free lubricant eye drops and prophylactic topical antibiotics. In contrast, the study group included NK cases treated with TI [1 unit per drop] four times daily, in addition to the previously mentioned treatment. The primary outcome measure was time to epithelial healing. Secondary outcome measures included any adverse effect of TI or the need for amniotic membrane transplantation (AMT). During the study period, 19 patients with a mean age of 49.3 ± 8.6 years received TI versus 18 controls with a mean age of 52.5 ± 10.7 years. Corneal epithelial healing was significantly faster in the TI-treated group compared to controls, with a mean difference of 12.16 days (95% CI 6.1-18.3, P = 0.001). Survival analysis indicated that the insulin-treated group had 0% and 20% of NK stages 2 and 3, respectively, that failed to achieve corneal epithelial healing, compared to 20% and 66.7% for the control group (P < 0.001). In the control group, two eyes required AMT due to progressive thinning. Additionally, three patients in the control group, progressing to stage 3 NK, were switched to TI, achieving healing after a mean of 14 days. No adverse effects were reported in the TI-treated group. Our study suggests that TI can effectively and safely promote the healing of NK after DV.

Quality, Reliability, Readability, and Accountability of Online Information on Leukocoria.

PURPOSE: To evaluate the quality, reliability, and readability of online patient educational materials on leukocoria. METHODS: In this cross-sectional study, the Google search engine was searched for the terms "leukocoria" and "white pupil." The first 50 search outcomes were evaluated for each search term based on predefined inclusion criteria, excluding duplicates, peer-reviewed papers, forum posts, paywalled content, and multimedia links. Sources were categorized as "institutional" or "private." Three independent raters assessed each website for quality and reliability using DISCERN, Health on the Net Code of Conduct (HONcode), and JAMA criteria. Readability was evaluated using seven formulas: Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG) Index, Automated Readability Index (ARI), Linsear Write (LW), Gunning Fog Index (GFI), and Coleman-Liau Index (CLI). RESULTS: A total of 51 websites were included. Quality, assessed by the DISCERN tool, showed a median score of 4, denoting moderate to high quality, with no significant differences between institutional and private sites or search terms. HONcode scores indicated variable reliability and trustworthiness (median: 10, range: 3 to 16), with institutional sites excelling in financial disclosure and ad differentiation. Additionally, institutional and private sites performed well in reliability and accountability, as measured by the JAMA Benchmark criteria (median: 3; range: 1 to 4). Readability, averaging an 11.3 ± 3.7 grade level, did not differ significantly between site types or search terms, consistently falling short of the recommended sixth-grade level for patient educational materials. CONCLUSIONS: The patient educational materials on leukocoria demonstrated moderate to high quality, commendable reliability, and accountability. However, the readability scores were above the recommended level for the layperson. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

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 the readability of online information. DESIGN: Cross-sectional comparative study. METHODS: We evaluated responses of ChatGPT-3.5, ChatGPT-4, and Bard to 3 separate prompts requesting that they write PEMs on "childhood glaucoma." Prompt A required PEMs be "easily understandable by the average American." Prompt B required that 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 Grade Level [FKGL]), and accuracy (Likert Misinformation scale). To assess the improvement of readability for existing online information, Prompt C requested that 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 LLMs 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 ≤ .001). ChatGPT-4 generated the most readable PEMs compared to ChatGPT-3.5 and Bard (P ≤ .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). CONCLUSIONS: LLMs can serve as strong supplemental tools in generating high-quality, accurate, and novel PEMs, and improving the readability of existing PEMs on childhood glaucoma.

Quality, Reliability, and Readability of Online Information on Idiopathic Intracranial Hypertension.

BACKGROUND: To evaluate the quality & reliability, technical quality, and readability of patient-targeted online information on idiopathic intracranial hypertension. METHODS: In this cross-sectional study, we searched Google and Bing search engines for the terms "idiopathic intracranial hypertension" and "pseudotumor cerebri." We evaluated the first 50 search outcomes for each search term. Peer-reviewed articles, targeted advertisements, book chapters, videos, personal blogs, websites intended for healthcare professionals, and non-English websites were excluded. Websites were classified as institutional or private. Two independent reviewers assessed each website for 1) quality and reliability using DISCERN, Health on the Net Code of Conduct (HONcode), and JAMA criteria and 2) technical quality based on 11 criteria. Readability was evaluated using 6 measures (Flesch-Kincaid Reading Ease score and grade level, Gunning Fog, Simple Measure of Gobbledygook (Smog) index, Coleman-Liau index, and automated readability index). RESULTS: Sixty-three websites (37 institutional) were included. The mean scores for the DISCERN, HONcode, and JAMA criteria were 3.6 ± 1 (1-4.8; 1: worse, 5: best), 10.3 ± 2.8 (2-16; 0: worse, 16: best), and 2 ± 1.3 (0-4; 0: worse, 4: best), respectively. The mean technical quality score was 0.8 ± 0.1 (0.5-1). The mean Flesch-Kincaid grade level score was 8.9 ± 1.8 (3.3-13.3). For Flesch-Kincaid grade level, 47 (74.6%) websites scored a grade level of 10 or less. For Gunning Fog Score, 35 websites (55.6%) scored from 7.3 to 10.8. For the Smog Index, 46 (73%) websites scored 5.7-8. The mean Coleman Liau Index was 16 ± 2.1 (9.6-22.2). For the automated readability index, 30 (50.7%) websites scored less than the eighth grade. No statistically significant difference was present between institutional and private websites except for JAMA, which scored higher in private websites (2.4 vs 1.7, P = 0.03). CONCLUSIONS: Our findings suggest that online information on idiopathic intracranial hypertension/pseudotumor cerebri for patients generally demonstrates moderate to good quality and reliability. Although most websites maintain credible technical quality, the readability exceeds recommended levels for the average American reader. This may impede understanding, emphasizing the need for future improvements.

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.

Debulking corneal biopsy with tectonic amniotic membrane transplantation in refractory clinically presumed fungal keratitis.

The treatment of fungal keratitis (FK) is challenging due to the subacute indolent course, and initial misdiagnosis. In this retrospective case series, we highlight both the diagnostic and therapeutic roles of corneal biopsy together with amniotic membrane transplantation (AMT) in patients with refractory clinically presumed FK. Debulking biopsy and tectonic AMT were performed during the initial presentation. Biopsy specimens were sent for KOH smears and cultures. After KOH smears confirmed the presence of fungal elements, topical voriconazole 1% was prescribed for the first 72 h then tailored according to the clinical response and the culture results. The outcome measures were complete resolution of infection and restoration of corneal integrity. Cases associated with culture proven bacterial keratitis were excluded. Twelve cases were included in the study. KOH smears confirmed the presence of fungal growth in all specimens. Cultures grew Aspergillus in 6/12 cases, sensitive to voriconazole (5/6) and amphotericin (3/6); Fusarium (4/12), sensitive to both voriconazole and amphotericin; and no growth in 2/12 cases. Amphotericin 0.15% eye drops were added to the 7 cases with proven sensitivity and to the remaining 2 culture negative cases. Gradual resolution of infection was seen in all cases after 35.6 ± 7.8 days. In FK, a debulking biopsy simultaneously with AMT help decrease the microbial load, suppress the inflammatory process, support the corneal integrity, confirm the presence of fungal pathogen.

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. 2024;61(3):198-203.].

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.

Corneal stem cells niche and homeostasis impacts in regenerative medicine; concise review.

The limbal stem cells niche (LSCN) is an optimal microenvironment that provides the limbal epithelial stem cells (LESCs) and strictly regulates their proliferation and differentiation. Disturbing the LSCN homeostasis can lead to limbal stem cell dysfunction (LSCD) and subsequent ocular surface aberrations, such as corneal stromal inflammation, persistent epithelial defects, corneal neovascularisation, lymphangiogenesis, corneal opacification, and conjunctivalization. As ocular surface disorders are considered the second main cause of blindness, it becomes crucial to explore different therapeutic strategies for restoring the functions of the LSCN. A major limitation of corneal transplantation is the current shortage of donor tissue to meet the requirements worldwide. In this context, it becomes mandatory to find an alternative regenerative medicine, such as using cultured limbal epithelial/stromal stem cells, inducing the production of corneal like cells by using other sources of stem cells, and using tissue engineering methods aiming to produce the three-dimensional (3D) printed cornea. Limbal epithelial stem cells have been considered the magic potion for eye treatment. Epithelial and stromal stem cells in the limbal niche hold the responsibility of replenishing the corneal epithelium. These stem cells are being used for transplantation to maintain corneal epithelial integrity and ultimately sustain optimal vision. In this review, we summarised the characteristics of the LSCN and their current and future roles in restoring corneal homeostasis in eyes with LSCD.

Current and Emerging Therapies for Limbal Stem Cell Deficiency.

The corneal epithelium serves to protect the underlying cornea from the external environment and is essential for corneal transparency and optimal visual function. Regeneration of this epithelium is dependent on a population of stem cells residing in the basal layer of the limbus, the junction between the cornea and the sclera. The limbus provides the limbal epithelial stem cells (LESCs) with an optimal microenvironment, the limbal niche, which strictly regulates their proliferation and differentiation. Disturbances to the LESCs and/or their niche can lead to the pathologic condition known as limbal stem cell deficiency (LSCD) whereby the corneal epithelium is not generated effectively. This has deleterious effects on the corneal and visual function, due to impaired healing and secondary corneal opacification. In this concise review, we summarize the characteristics of LESCs and their niche, and present the current and future perspectives in the management of LSCD with an emphasis on restoring the function of the limbal niche.

Acute Uveitis following COVID-19 Vaccination.

PURPOSE: To describe a case of juvenile idiopathic arthritis (JIA)-associated anterior uveitis after receiving the Sinopharm COVID-19 vaccine. METHODS: A retrospective case report. RESULTS: An 18-year-old girl, with a history of antinuclear antibody positive oligoarticular JIA, presented with bilateral anterior uveitis 5 days after the second dose of the Sinopharm COVID-19 vaccine. Ocular examination revealed anterior uveitis with reduced visual acuity in both eyes. Anterior segment optical coherence tomography showed hyperreflective dots in the anterior chamber (AC) and fine endothelial granularities representing the circulating cells in the AC. Uveitis in both eyes resolved gradually after topical steroid treatment without recurrence. CONCLUSION: This report demonstrates a potential causal association of COVID-19 vaccine with anterior uveitis.

Phlyctenular Keratoconjunctivitis in a Patient With COVID-19 Infection.

ABSTRACT: The coronavirus disease 2019 global pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several ophthalmic manifestations have been reported to be associated with SARS-CoV-2 infection, including conjunctivitis, acute sixth nerve palsy, and multiple cranial neuropathies. We present a unique case of unilateral phlyctenular keratoconjunctivitis in a 5-year-old boy in the setting of SARS-CoV-2 infection.

Mobility improvement of patients with peripheral visual field losses using novel see-through digital spectacles.

PURPOSE: To evaluate see-through Augmented Reality Digital spectacles (AR DSpecs) for improving the mobility of patients with peripheral visual field (VF) losses when tested on a walking track. DESIGN: Prospective Case Series. PARTICIPANTS: 21 patients with peripheral VF defects in both eyes, with the physical ability to walk without assistance. METHODS: We developed the AR DSpecs as a wearable VF aid with an augmented reality platform. Image remapping algorithms produced personalized visual augmentation in real time based on the measured binocular VF with the AR DSpecs calibration mode. We tested the device on a walking track to determine if patients could more accurately identify peripheral objects. MAIN OUTCOME MEASURES: We analyzed walking track scores (number of recognized/avoided objects) and eye tracking data (six gaze parameters) to measure changes in the kinematic and eye scanning behaviors while walking, and assessed a possible placebo effect by deactivating the AR DSpecs remapping algorithms in random trials. RESULTS: Performance, judged by the object detection scores, improved with the AR DSpecs (P<0.001, Wilcoxon rank sum test) with an average improvement rate of 18.81%. Two gaze parameters improved with the activated algorithm (P<0.01, paired t-test), indicating a more directed gaze on the central path with less eye scanning. Determination of the binocular integrated VF with the DSpecs correlated with the integrated standard automated perimetry (R = 0.86, P<0.001), mean sensitivity difference 0.8 ± 2.25 dB (Bland-Altman). CONCLUSIONS: AR DSpecs may improve walking maneuverability of patients with peripheral VF defects by enhancing detection of objects in a testing environment.

Role of Matrix Metalloproteinase 9 in Ocular Surface Disorders.

OBJECTIVES: (1) To explore the role and significance of Matrix Metalloproteinase 9 (MMP-9), a proteolytic enzyme, in various ocular surface diseases of inflammatory, infectious, and traumatic etiology (2), to further elucidate the molecular mechanisms responsible for its overexpression in ocular surface disease states, and (3) to discuss possible targets of therapeutic intervention. METHODS: A literature review was conducted of primary sources from 1995 onward using search results populated from the US National Library of Medicine search database. RESULTS: MMP-9 overexpression has been found in in vitro and in vivo models of dry eye disease (DED), corneal ulceration, microbial keratitis, corneal neovascularization, ultraviolet light-induced radiation, and a host of additional surface pathologies. MMP-9 is involved in an intricate signal transduction cascade that includes induction by many proinflammatory molecules including interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-a), nuclear factor kappa light chain enhancer of activated B cells (NF-kB), platelet-activating factor, activator protein 1 (AP-1), and transforming growth factor beta (TGF-B). MMP-9 expression is blunted by a diverse array of molecular factors, such as tissue inhibitors of metalloproteinases, cyclosporine A (CyA), PES_103, epigalloccatechin-3-gallate (EGCG), N-acetylcysteine (NaC), ascorbate, tetracyclines, and corticosteroids. Inhibition of MMP-9 frequently led to improvement of ocular surface disease. CONCLUSIONS: Novel insights into the mechanistic action of MMP-9 provide potential for new therapeutic modulations of ocular surface diseases mediated by its overexpression.

In-vivo Three-dimensional Characteristics of Bowman's Layer and Endothelium/Descemet's Complex Using Corneal Microlayer Tomography in Healthy Subjects.

Purpose: To characterize the three-dimensional (3D) thickness profile and age-related changes of Bowman's layer (BL), and endothelium/Descemet's membrane (En/DM) complex among healthy individuals using Corneal Microlayer Tomography (CML-T), and to describe its repeatability and accuracy.Methods: Sixty-six eyes of 41 healthy volunteers; 27 eyes (< 40 years old), and 39 eyes (>40 years old) were imaged using HD-OCT. Automatic and manual segmentation of the corneal layers was performed, and 3D thickness maps were generated, using custom-built CML-T software. A regional analysis of mean thickness parameters between the 2 age groups was performed. A regression analysis was used to assess the correlation between age, and thickness maps. Intraclass Correlation Coefficients (ICC), Coefficients of Variation (COV), and Bland-Altman plots were used to assess the reliability of the repeated measurements in 198 locations.Results: CML-T successfully mapped the BL and En/DM in all included eyes. Thickness maps showed a significant increase in corneal thickness (CT), BL thickness (BMT), and En/DM complex thickness (DMT) toward the periphery with a mean difference 28 µm (p < .001), 1.1 µm (p < .001), and 1.4 µm (p < .001), respectively. There was a strong correlation between age and central DMT (r = 0.61; p < .001), while there was no correlation between age and both CT, and BMT. ICC values ranged from 0.9 (BMT) to 0.997 (DMT), and from 0.808 (BMT) to 0.979 (CT) for intraoperator repeatability of manual measurements, and the accuracy of auto matic measurements, respectively. COV values were lower than 7.5% in all cases.Conclusion: CML-T is a novel tool that can generate 3D-thickness maps of both BL and En/DM. CT, BMT, and DMT increase toward the periphery in healthy corneas. DMT increases with aging, while BMT does not. We also report excellent repeatability, accuracy and good agreement between automatic and manual measurements.