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.

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.

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.

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.

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 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.

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.

Peripheral Ulcerative Keratitis: A Review.

Peripheral ulcerative keratitis (PUK) is a rare but serious ocular condition that is an important clinical entity due to its ophthalmological and systemic implications. It is characterized by progressive peripheral corneal stromal thinning with an associated epithelial defect and can be associated with an underlying local or systemic pro-inflammatory condition, or present in an idiopathic form (Mooren ulcer). Associated conditions include autoimmune diseases, systemic and ocular infections, dermatologic diseases, and ocular surgery. Cell-mediated and auto-antibody-mediated immune responses have been implicated in the pathogenesis of PUK, destroying peripheral corneal tissue via matrix metalloproteinases. Clinically, patients with PUK present with painful vision loss, a peripheral corneal ulcer, and often adjacent scleritis, episcleritis, iritis, or conjunctivitis. Diagnostic evaluation should be focused on identifying the underlying etiology and ruling out conditions that may mimic PUK, including marginal keratitis and Terrien marginal degeneration. Treatment should be focused on reducing local disease burden with topical lubrication, while simultaneously addressing the underlying cause with antimicrobials or anti-inflammatory when appropriate. Existing and emerging biologic immunomodulatory therapies have proven useful in PUK due to autoimmune conditions. Surgical treatment is generally reserved for cases of severe thinning or corneal perforation.

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.

Electron microscopic comparison of the donor cut edges using femtosecond laser-assisted keratoplasty versus conventional keratoplasty.

PURPOSE: To describe and compare the histological changes in the cut edges of the remaining donor corneal rim using femtosecond laser-assisted keratoplasty (FAK) versus conventional penetrating keratoplasty (PK) via light and transmission electron microscopic examination. METHODS: This was a prospective observational study of 10 eyes; 5 FAK (top-hat technique) and 5 conventional PK. Main outcomes were histological findings at the cut edge of the donor corneal rim (at 3, 6, 9, and 12 o'clock). RESULTS: Cellular and ultra-cellular changes in the form of stromal edema, disorganized collagen fibers, and nuclear changes were more prominent in the FAK eyes as compared to the conventional PK ones. CONCLUSION: FAK induces more collateral damage in the cut edge of corneal donor graft at cellular and ultra-cellular levels, compared to conventional trephination. Further studies are required to investigate the clinical ramifications of this observation.

Comparison of Autonomous AS-OCT Deep Learning Algorithm and Clinical Dry Eye Tests in Diagnosis of Dry Eye Disease.

OBJECTIVE: To evaluate a deep learning-based method to autonomously detect dry eye disease (DED) in anterior segment optical coherence tomography (AS-OCT) images compared to common clinical dry eye tests. METHODS: In this study, 27,180 AS-OCT images were prospectively collected from 151 eyes of 91 patients. Images were used to train and test the deep learning model. Masked cornea specialist ophthalmologist diagnoses were used as the gold standard. Clinical dry eye tests were performed on patients in the DED group to compare the results of the model. The dry eye tests performed were tear break-up time (TBUT), Schirmer's test, corneal staining, conjunctival staining, and Ocular Surface Disease Index (OSDI). RESULTS: Our deep learning model achieved an accuracy of 84.62%, sensitivity of 86.36%, and specificity of 82.35% in the diagnosis of DED. The positive likelihood ratio was 4.89, and the negative likelihood ratio was 0.17. The mean DED probability score was 0.81 ± 0.23 in the DED group and 0.20 ± 0.27 in the healthy group (P < 0.01). The deep learning model accuracy in the diagnosis of DED was significantly better than that of corneal staining, conjunctival staining, and Schirmer's test (P < 0.05). There was no significant difference between the deep learning diagnostic accuracy and that of the OSDI and TBUT. CONCLUSION: Based on preliminary results, reliable autonomous diagnosis of DED with our deep learning model was achieved, when compared with standard dry eye clinical tests that correlated significantly more or similarly to diagnoses made by cornea specialist ophthalmologists.

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.

Prediction of corneal graft rejection using central endothelium/Descemet's membrane complex thickness in high-risk corneal transplants.

To determine whether measurements of Endothelium/Descemet complex thickness (En/DMT) are of predictive value for corneal graft rejection after high-risk corneal transplantation, we conducted this prospective, single-center, observational case series including sixty eyes (60 patients) at high risk for corneal graft rejection (GR) because of previous immunologic graft failure or having at least two quadrants of stromal vascularization. Patients underwent corneal transplant. At 1st, 3rd, 6th, 9th, and 12th postoperative month, HD-OCT imaging of the cornea was performed, and the corneal status was determined clinically at each visit by a masked cornea specialist. Custom-built segmentation tomography algorithm was used to measure the central En/DMT. Relationships between baseline factors and En/DMT were explored. Time dependent covariate Cox survival regression was used to assess the effect of post-operative En/DMT changes during follow up. A longitudinal repeated measures model was used to assess the relationship between En/DMT and graft status. Outcome measures included graft rejection, central Endothelium/Descemet's complex thickness, and central corneal thickness (CCT). In patients with GR (35%), the central En/DMT increased significantly 5.3 months (95% CI: 2, 11) prior to the clinical diagnosis of GR, while it remained stable in patients without GR. During the 1-year follow up, the rejected grafts have higher mean pre-rejection En/DMTs (p = 0.01), compared to CCTs (p = 0.7). For En/DMT ≥ 18 µm cut-off (at any pre-rejection visit), the Cox proportional hazard ratio was 6.89 (95% CI: 2.03, 23.4; p = 0.002), and it increased to 9.91 (95% CI: 3.32, 29.6; p < 0.001) with a ≥ 19 µm cut-off. In high-risk corneal transplants, the increase in En/DMT allowed predicting rejection prior to the clinical diagnosis.

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.