Automated In Vivo Phenotypic Screening Platform for Identifying Factors that Affect Cell Regeneration Kinetics.

Various strategies for replacing retinal neurons lost in degenerative diseases are under investigation, including stimulating the endogenous regenerative capacity of Müller Glia (MG) as injury-inducible retinal stem cells. Inherently regenerative species, such as zebrafish, have provided key insights into mechanisms regulating MG dedifferentiation to a stem-like state and the proliferation of MG and MG-derived progenitor cells (MGPCs). Interestingly, promoting MG/MGPC proliferation is not sufficient for regeneration, yet mechanistic studies are often focused on this measure. To fully account for the regenerative process, and facilitate screens for factors regulating cell regeneration, an assay for quantifying cell replacement is required. Accordingly, we adapted an automated reporter-assisted phenotypic screening platform to quantify the pace of cellular regeneration kinetics following selective cell ablation in larval zebrafish. Here, we detail a method for using this approach to identify chemicals and genes that control the rate of retinal cell regeneration following selective retinal cell ablation.

Subconjunctival Administration of an Adeno-Associated Virus Expressing Stanniocalcin-1 Provides Sustained Intraocular Pressure Reduction in Mice.

Purpose: To investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained (IOP) lowering agent with a reduced ocular surface side effect profile. Design: In vivo preclinical investigation in mice. Subjects: C57BL/6J, DBA/2J, prostaglandin F (FP) receptor knockout mice. Methods: Normotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 µL; 6 × 109 viral genomes [VGs]) in 1 eye and the same volume and concentration of ssAAV2-green fluorescent protein (GFP) or the same volume of phosphate-buffered saline in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 × 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 × 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Prostaglandin F receptor knockout mice were injected subconjunctivally with 6 × 109 VGs of ssAAV2-STC-1-FLAG or phosphate-buffered saline. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. Intraocular pressure was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1-FLAG and other treatments including daily topical latanoprost. Main Outcome Measures: Intraocular pressure assessment. Results: Subconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 3 postinjection (17.4%; 17.1 ± 0.8 vs. 14.1 ± 0.8 mmHg, P < 0.001). After the IOP-lowering effect had waned, a second injection restored the ocular hypotensive effect. Subconjunctivally delivered ssAAV2-STC-1-FLAG lowered IOP in DBA/2J mice (16.9%; 17.8 ± 2.0 vs. 14.8 ± 0.9 mmHg, P < 0.001) and steroid-mediated ocular hypertensive mice (20.0%; 19.0 ± 0.6 vs. 15.2 ± 0.7 mmHg, P < 0.001) over the experimental period. This construct also reduced IOP to a similar extent in wild-type (15.9%) and FP receptor knockout (15.7%) mice compared with the fellow eye. A related construct also lowered IOP without the FLAG tag in a similar manner. Reduction in conjunctival TNFα was seen when comparing subconjunctivally delivered ssAAV2-STC-1-FLAG to daily topical latanoprost. Conclusions: Subconjunctival delivery of the STC-1 transgene with a vector system may represent a novel treatment strategy for sustained IOP reduction and improved ocular tolerability that also avoids the daily dosing requirements of currently available medications. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Predicting Choroidal Nevus Transformation to Melanoma Using Machine Learning.

Purpose: To develop and validate machine learning (ML) models to predict choroidal nevus transformation to melanoma based on multimodal imaging at initial presentation. Design: Retrospective multicenter study. Participants: Patients diagnosed with choroidal nevus on the Ocular Oncology Service at Wills Eye Hospital (2007-2017) or Mayo Clinic Rochester (2015-2023). Methods: Multimodal imaging was obtained, including fundus photography, fundus autofluorescence, spectral domain OCT, and B-scan ultrasonography. Machine learning models were created (XGBoost, LGBM, Random Forest, Extra Tree) and optimized for area under receiver operating characteristic curve (AUROC). The Wills Eye Hospital cohort was used for training and testing (80% training-20% testing) with fivefold cross validation. The Mayo Clinic cohort provided external validation. Model performance was characterized by AUROC and area under precision-recall curve (AUPRC). Models were interrogated using SHapley Additive exPlanations (SHAP) to identify the features most predictive of conversion from nevus to melanoma. Differences in AUROC and AUPRC between models were tested using 10 000 bootstrap samples with replacement and results. Main Outcome Measures: Area under receiver operating curve and AUPRC for each ML model. Results: There were 2870 nevi included in the study, with conversion to melanoma confirmed in 128 cases. Simple AI Nevus Transformation System (SAINTS; XGBoost) was the top-performing model in the test cohort [pooled AUROC 0.864 (95% confidence interval (CI): 0.864-0.865), pooled AUPRC 0.244 (95% CI: 0.243-0.246)] and in the external validation cohort [pooled AUROC 0.931 (95% CI: 0.930-0.931), pooled AUPRC 0.533 (95% CI: 0.531-0.535)]. Other models also had good discriminative performance: LGBM (test set pooled AUROC 0.831, validation set pooled AUROC 0.815), Random Forest (test set pooled AUROC 0.812, validation set pooled AUROC 0.866), and Extra Tree (test set pooled AUROC 0.826, validation set pooled AUROC 0.915). A model including only nevi with at least 5 years of follow-up demonstrated the best performance in AUPRC (test: pooled 0.592 (95% CI: 0.590-0.594); validation: pooled 0.656 [95% CI: 0.655-0.657]). The top 5 features in SAINTS by SHAP values were: tumor thickness, largest tumor basal diameter, tumor shape, distance to optic nerve, and subretinal fluid extent. Conclusions: We demonstrate accuracy and generalizability of a ML model for predicting choroidal nevus transformation to melanoma based on multimodal imaging. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Protein profile of purified plasma- and aqueous humor-derived extracellular vesicles from patients with ocular toxoplasmosis

ABSTRACT Purpose: To characterize the extracellular vesicle protein cargo in the aqueous humor and plasma of patients with ocular toxoplasmosis. Methods: Aqueous humor and plasma were collected from six patients with active ocular toxoplasmosis and six patients with cataract. Extracellular vesicles were isolated, and western blotting and mass spectrometry were performed for protein analysis. Results: All plasma samples from patients with ocular toxoplasmosis and cataract were positive for the tetraspanins CD63 and TSG101. However, the aqueous humor from patients with ocular toxoplasmosis was positive only for CD63. Sixty-seven new unreported proteins were identified in the aqueous humor and plasma of patients with the ocular toxoplasmosis and cataract. Of the 67 proteins, 10 and 7 were found only in the cataract and ocular toxoplasmosis groups, respectively. In general, these proteins were involved in immune system activation and retina homeostasis and were related to infections and retina-associated diseases. Conclusion: The distinct protein signatures between ocular toxoplasmosis and cataract may be helpful in the differential diagnosis of ocular toxoplasmosis. However, more studies are needed to better understand the role of these proteins in the pathogenesis of ocular toxoplasmosis.

Varenicline Solution Nasal Spray 0.03 Mg for the Treatment of Dry Eye Disease Following Photorefractive Keratectomy.

Purpose: To evaluate the use of varenicline solution nasal spray 0.03 mg (VNS) as a treatment option for the signs and symptoms of dry eye disease following photorefractive keratectomy (PRK). Patients and methods: Subjects electing to undergo PRK were randomized to VNS (study group) or vehicle (control group) twice daily and started treatment with VNS 28 days prior to surgery with continued use of the treatment for 84 days after PRK. After starting treatment, subjects were seen on the day of the procedure and postoperatively at days 2, 3, 4, 7, 28 and 84. The primary outcome measure was the mean change in NEI-VFQ-25, a dry eye item questionnaire, from baseline to day 84. The second primary outcome measure was the rate of corneal epithelial healing following PRK. Secondary outcome measures included eye dryness score (EDS), tear break up time and visual outcomes. The use of rescue therapy was also evaluated. Results: Twenty-one subjects were enrolled in the study group, and twenty subjects were enrolled in the control group. Results from the NEI-VFQ-25 questionnaire revealed positive results in both groups and the between-group difference was not statistically significant (P > 0.05). There was a trend towards faster re-epithelialization in patients treated with VNS vs placebo, where 100% epithelial closure was observed by Day 3 in the VNS group versus Day 4 in the control group; however, the between-group difference was not statistically significant (P > 0.05). Three subjects had rescue therapy in the control group while a single subject was rescued in the study group. A higher rate of eyes achieved vision of 20/16 or better in the study group (82.5%) versus the control group (72.5%) at 3 months. Conclusion: VNS is a favorable dry eye treatment option for patients following PRK, particularly in patients hoping to avoid additional topical medications or punctal occlusion. The higher percentage of eyes with UCDVA of 20/16 or better in the treatment group may suggest optimization of epithelial recovery after PRK.

Alleviation of Allergic Rhinoconjunctivitis Symptoms in Participants Treated with a 0.005% Tacrolimus Eye-Drop Solution.

Purpose: This randomized, placebo-controlled, crossover, double-blind trial aimed to evaluate the efficacy and safety of Tacrosolv, a novel 0.005% tacrolimus eye-drop solution, in adults with grass pollen-induced allergic conjunctivitis. Methods: A total of 64 adult participants were randomized to receive 2.5 µg or 5 µg tacrolimus/eye/day or placebo treatment for 8 days, with grass pollen exposure on day 1 and day 8. After a 2-week washout period, placebo participants crossed over to Tacrosolv treatment and vice versa, with repeated treatment and exposure. During exposure, participants recorded ocular, nasal, and respiratory allergy symptoms every 15 minutes. The primary endpoint was the mean total ocular symptom score (TOSS) on day 8. Objective ocular safety parameters were assessed before, during, and after exposure. Adverse events were recorded throughout the study. Results: On day 8, high-dose Tacrosolv reduced the TOSS compared to placebo towards the end of exposure (p<0.05 at time points 3 hours, 45 minutes and 4 hours). A 26% reduction in baseline adjusted TOSS from day 1 to day 8 was observed in participants treated with high-dose Tacrosolv, whereas placebo-treated participants showed no difference in TOSS between day 1 and day 8. Nasal symptoms were reduced on both day 1 and day 8 in participants treated with high-dose Tacrosolv (p<0.05). No safety concerns were raised. All adverse events were resolved within the study period. Conclusion: High-dose Tacrosolv is safe and effective for alleviating symptoms of allergic rhinoconjunctivitis. Trial Registration: NCT04532710; EudraCT No. 2019-002847-62.

Behcet's disease-related panuveitis following COVID-19 vaccination: A case report.

BACKGROUND: Behcet's disease (BD) is an inflammatory disorder known for various symptoms, including oral and genital ulcers and ocular inflammation. Panuveitis, a severe eye condition, is rare as the first sign of BD. CASE SUMMARY: We present an unusual case of a 30-year-old man who developed panuveitis after receiving the mRNA-based coronavirus disease 2019 (COVID-19) vaccine (Moderna). Laboratory tests ruled out infections, but he had a positive HLA-B51 result and a history of genital ulcer and oral ulcers, leading to a BD diagnosis. Treatment with corticosteroids improved his condition. Interestingly, he had another episode of panuveitis after the second mRNA vaccine dose, which also responded to corticosteroids. CONCLUSION: This case highlights the rare onset of BD following mRNA COVID-19 vaccination, suggesting a potential link between these vaccines and BD's eye symptoms, emphasizing the importance of quick treatment in similar cases.

Lipid-based nanoparticles: innovations in ocular drug delivery.

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.

Dry eye disease and spondyloarthritis: expanding the spectrum of systemic inflammatory disorders associated with ocular surface disease. Data from the international AIDA Network Spondyloarthritis Registry.

Objective: Dry eye disease (DED) is a condition associated with a myriad of systemic disorders. According to recent preliminary data, axial spondylarthritis (axial-SpA) could represent a new entity associated with DED. Therefore, this study aimed to assess DED in patients with axial SpA by performing quantitative and qualitative specific tests to investigate the potential association between DED and ocular surface damage in patients with axial-SpA and to identify potential variables associated with DED. Methods: A total of 71 patients with axial-SpA who fulfilled the Assessment of SpondyloArthritis International Society (ASAS) classification criteria and 19 healthy controls were enrolled in this study. Both the patients and the controls underwent a complete ocular assessment aimed at evaluating the tear film and ocular surface, which included the Schirmer test, tear break-up time (TBUT), fluorescein staining, and lissamine green staining. The Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients. Results: DED symptoms were reported in 46 (64.8%) patients and three (15.8%) healthy controls (p = 0.0004). The odds ratio for receiving a diagnosis of axial-SpA based on the presence of dry-eye-related symptoms was 9.2 (95% C.I. 2.72-42.52, p = 0.001). The Schirmer test values of < 6 mm/5 min were observed in 31 (43.7%) patients with axial-SpA and two (10.5%) healthy controls (p = 0.013); a TBUT of <5 s was observed in 34 (47.9%) patients with axial-SpA and six (31.6%) healthy controls. The median OSDI score was found to be 22.9 (IQR = 29.35) among the patients with axial-SpA and 0.0 (IQR = 4.69) among the healthy controls (p = 0.009). The fluorescein and lissamine green staining of the ocular surface indicated a significantly higher Oxford Grading Scale in the patients with axial-SpA than in the healthy controls. Conclusion: Patients with axial-SpA often complain of eye dryness, which may be quantified with the self-administered OSDI questionnaire and objectively assessed through the tests commonly used for the diagnosis of DED. Patients suspected of having axial-SpA should routinely be asked about dry eye symptoms and evaluated for potential corneal and conjunctival damage.

High prevalence of xerophthalmia linked to socio-demographic and nutritional factors among vitamin A-deficient rural primary schoolchildren in Malaysia.

Vitamin A deficiency (VAD) remains a major health issue in developing nations, contributing to preventable childhood blindness. However, there is lack of recent data on xerophthalmia, especially among school-aged children in Malaysia. We hypothesized that xerophthalmia persists among rural schoolchildren in Malaysia and potentially associated with socio-demographic status and malnutrition. We conducted a cross-sectional study on 596 schoolchildren (8-12 years) from ten rural primary schools located in five states across Malaysia. Children meeting the criteria for xerophthalmia assessment included those diagnosed with vitamin A deficiency (VAD) (plasma retinol < 0.70 µmol/L) and marginal VAD (plasma retinol 0.70 to < 1.05 µmol/L). The overall prevalence of xerophthalmia was 48.8%, with the most common ocular sign being conjunctival xerosis (38.9%). The occurrence of xerophthalmia was negatively associated with retinol-binding protein 4 (RPB4) (P=0.003), alpha-carotene (P=0.04), hemoglobin (P=0.004), weight (P=0.02), body mass index (BMI) (P=0.04) and WAZ (weight-for-age z-score) (P=0.04) status. Based on multivariate logistic regression analysis, a higher risk of xerophthalmia was observed in boys (Adjusted odd ratio [AOR]: 1.7, 95% confidence interval [CI]: 1.2-2.5) and Orang Asli (OA, indigenous) schoolchildren (AOR: 2.0, 95% CI: 1.3-3.0), while schoolchildren with overweight/obesity status (AOR: 0.5, 95% CI: 0.3-0.8) were associated with a reduced risk of xerophthalmia. The present study unveils a high prevalence of xerophthalmia among vitamin A-deficient primary schoolchildren in rural areas of Malaysia, especially among the indigenous community. The identified socio-demographic and nutritional factors associated to xerophthalmia would facilitate the implementation of more targeted interventions in addressing these issues.

The effect of intra- and inter-fractional motion on target coverage and margins in proton therapy for uveal melanoma.

INTRODUCTION: This study aims to assess the effective lateral margin requirements for target coverage in ocular proton therapy (OPT), considering the unique challenges posed by eye motion and hypofractionation. It specifically addresses the previously unaccounted-for uncertainty contribution of intra-fractional motion, in conjunction with setup uncertainties, on dosimetric determination of lateral margin requirements. Method: The methodology integrates dose calculations from the in-house developed treatment planning system OCULARIS with measured intra-fractional motion, patient models from EyePlan and Monte Carlo (MC) sampling of setup uncertainties. The study is conducted on 16 uveal melanoma patients previously treated in the OPTIS2 treatment room at the Paul Scherrer Institute (PSI). Results: The retrospective simulation analysis highlights a significant impact of non-systematic factors on lateral margin requirements in OPT. Simulations indicate that reducing the 2.5 mm clinical lateral margin, represented by a 2.1 mm margin in this work, would have resulted in inadequate target coverage for two patients, revealing a greater impact of non-systematic factors on lateral margin requirements. Conclusions: This work characterizes intra-fractional motion in 16 OPT patients and identifies limitations of clinical margin selection protocols for OPT applications. A novel framework was introduced to assess margin sufficiency for target coverage. The findings suggest that prior research underestimated non-systematic factors and overestimated systematic contributions to lateral margin components. This re-evaluation highlights the critical need to prioritize the management of non-systematic uncertainty contributions in OPT.

Cysteinyl Leukotriene Receptor Antagonism by Montelukast to Treat Visual Deficits.

Montelukast, a Food and Drug Administration-approved drug for asthma and allergic rhinitis modulates leukotriene (LT) receptors and serves as a critical anti-inflammatory agent. Recent research suggests that the LT signaling pathway targeted by montelukast has broader implications for diseases such as fibrosis, cardiovascular diseases, cancer, cerebrovascular disease, and immune defense. This expanded understanding highlights montelukast's potential for repurposing in conditions involving aberrant stress mechanisms, including ocular diseases marked by inflammation, oxidative stress, ER stress, and apoptosis, among several others. This review delves into montelukast's therapeutic mechanisms across various diseases, draws parallels to ocular conditions, and examines clinical trials and associated adverse effects to underscore the unmet need for cysteinyl LT receptor antagonism by montelukast as an effective therapy for visual deficits.

Inflammation in Dry Eye Disease-Pathogenesis, Preclinical Animal Models, and Treatments.

Dry eye disease (DED) is a rapidly growing ocular surface disease with a significant socioeconomic impact that affects the patients' visual function and, thus, their quality of life. It is distinguished by a loss of tear film homeostasis, leading to tear film instability, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities, with all of these playing etiological roles in the propagation of the vicious DED circle. While current treatments primarily focus on reducing tear film instability and hyperosmolarity, increasingly more attention is being placed on tackling the underlying inflammation that propagates and potentiates these factors. As such, preclinical models are crucial to further elucidate the DED pathophysiology and develop novel therapeutic strategies. This review outlines the role of inflammation in DED, highlighting related signs and diagnostic tools before focusing on relevant preclinical animal models and potential therapeutic strategies to tackle DED-associated inflammation.

Helicobacter pylori and Its Treatment Impact on Immune-Mediated Ocular Diseases.

PURPOSE: Helicobacter pylori (HP), which colonizes exclusively in the gastrointestinal tract, has been reported to dysregulate the immune response and gives rise to several extra-gastrointestinal autoimmune disorders. However, the relationship between HP and immune-mediated ocular diseases remains ambiguous. This study aims to clarify the association between immune-mediated ocular diseases and HP infection, as well as the impact of HP treatment on the incidence of immune-mediated ocular diseases. METHODS: This is a retrospective population-based study using National Health Insurance Research Database in Taiwan. Patients with newly diagnosed peptic ulcer disease or HP infection between 2009 and 2015 were identified as HP group and compared to the non-HP group with one-to-one exact matching. Moreover, the incident risk of immune-mediated ocular diseases and its two subgroups (ocular surface and orbital inflammation group, intraocular inflammation group) were compared in HP patients with or without treatment. RESULTS: A total of 1,030,119 subjects in the non-HP group and 1,030,119 patients in the HP group were enrolled. The incidence rate of immune-mediated ocular diseases was significantly higher in the HP group (95% confidence interval (CI): 2.534-2.547). The incident rate ratio was significantly higher in HP with treatment than without treatment (HR: 1.654, 95% CI: 1.641-1.668). The Cox proportional hazards regression model demonstrated a significantly increased HR of immune-mediated ocular diseases in HP treated group (HR: 2.265, 95% CI: 2.024-2.534) and less increased HR in HP non-treated group (HR: 1.427, 95% CI: 1.273-1.598) when comparing to non-HP group. Subgroup analysis demonstrated a significantly higher incidence rate of ocular surface and orbital inflammation as well as intraocular inflammation in the HP group. CONCLUSION: This study illustrated a higher incidence of immune-mediated ocular diseases in HP infection, and a heightened risk following HP eradication.

Authors Reply to Letter to the Editor - In Response to: Comment on Bocanegra-Oyola et al.'s "Clinical Characteristics of Ocular Mucous Membrane Pemphigoid: A Systematic Review and Meta-Analysis".

In response to Dr. Kasperkiewicz's commentary on our meta-analysis conducted by Bocanegra-Oyola et al., we fully agree with refining diagnostic processes for ocular pemphigoid, particularly in differentiating it from pseudopemphigoid. We concur that relying solely on clinical findings may result in misdiagnoses. Confirming the diagnosis via biopsy can be challenging, requiring multiple biopsies in some patients, and should always be supported by a multidisciplinary clinical assessment involving ophthalmologists and dermatologists.

Elevated Anti-Cyclic Citrullinated Peptide Levels Associated with Filamentary Keratitis.

PURPOSE: To assess two cases of filamentary keratitis with elevated serum levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies without known rheumatoid arthritis (RA). METHODS: A retrospective chart review was conducted on cases with filamentary keratitis and elevated anti-CCP antibodies between January 2021 and January 2023. Patient demographics, clinical characteristics, and serological test results were reviewed. RESULTS: The first patient, a 77-year-old man, presented with foreign body sensation and eye redness. He reported mild dry mouth but no joint pain or known autoimmune disease, though he had a family history of RA. Schirmer test scores were 7 and 12 mm in the right and left eyes, with an ocular staining score (OSS) of 12 in each eye. His serum anti-CCP antibody level was >2,777 U. Over 3 years of follow-up, he showed no signs of RA development. The second patient, an 84-year-old man, presented with severe burning and light sensitivity but no dry mouth or joint pain. Schirmer test scores were 2 and 3 mm in the right and left eyes, with OSS of 9 and 5, respectively. His serum anti-CCP level was 1330 U. He developed inflammatory arthritis and was diagnosed with RA 16 months after initial presentation. CONCLUSION: This report suggests that filamentary keratitis with elevated serum anti-CCP antibody levels may indicate early RA. These findings underscore the importance of anti-CCP testing in filamentary keratitis patients, even without typical RA symptoms. Further research is needed to explore the link between anti-CCP antibodies and ocular surface diseases in RA.

Evaluation of tear film function by Oculus Keratograph 5M and IDRA ocular surface analyser.

PURPOSE: The aim of this study was to evaluate the function of tear film with Oculus Keratograph 5M (Oculus K5M) and IDRA ocular surface analyser (IDRA), analyse their consistency and explore the potential of IDRA in the diagnosis of dry eye disease (DED). METHODS: This cross-sectional study enrolled 36 participants (DED group, 14 eyes; non-DED group, 22 eyes). The parameters of tear film function, including the first noninvasive breakup time (fNIBUT), average NIBUT (aNIBUT), tear meniscus height (TMH), lipid layer thickness (LLT), lipid layer colour (LLC), lipid layer uniformity (LLU), morphology of meibomian glands (MGs) and MG loss, were obtained with Oculus K5M and IDRA. The consistency of parameter measurements between the two devices was evaluated. RESULTS: All the parameters except LLT, which can be measured only by IDRA, were not significantly different between the two instruments in DED eyes. However, IDRA reported lower values of fNIBUT, aNIBUT and TMH as well as higher MG loss scores in non-DED eyes than Oculus K5M did (p < 0.001, < 0.001, = 0.002, and = 0.002, respectively). Further regression analysis revealed that aNIBUT and LLT measured by IDRA were the optimal parameters for diagnosing DED (OR = 0.567 and 0.845, p = 0.057 and 0.043, respectively), and their combination had the strongest diagnostic potential (AUC = 0.841, sensitivity = 85.7%, and specificity = 77.3%). CONCLUSION: As a user-friendly noninvasive device, the tear film function parameters measured by IDRA were highly consistent with those measured by Oculus K5M in DED patients. The combination of aNIBUT and LLT measured by IDRA had the best diagnostic accuracy for DED.

Comparison of the Diagnosis and Management of Demodex Blepharitis Between Eye Care Practitioners in India and Australasia - A Survey-Based Comparison.

Aim: The primary aim of this study was to compare how eyecare professionals in disparate regions of the world diagnose and manage Demodex blepharitis. A secondary aim was to explore interprofessional differences in diagnostic and management practices. Methods: Ophthalmologists and optometrists from India and Australia/New Zealand, were invited to complete an online survey on Demodex blepharitis. Clinical practice patterns relating to patients with Demodex blepharitis, with details of how they investigate and manage Demodex blepharitis in clinical practice, were collected along with clinician demographics and general perceptions on eyelid health. Mann-Whitney U, and Fisher's exact tests were used for statistical analysis. Results: A total of 261 eyecare professionals completed the survey, comprising 207 from India (84% optometrists) and 54 from Australia and New Zealand (91% optometrists). Almost 70% of practitioners across the 3 countries recognized Demodex blepharitis as a cause of ocular discomfort, yet only 45% reported attempting to identify Demodex in their patients. There were significant differences noted in clinical practice between those in Australasia and India. Perceived prevalence of Demodex blepharitis also differed (60% in Australasia vs 27% in India; p<0.01), as well as, the choice of slit lamp magnification used to detect the mites (25x in Australasia vs 16x in India; p = 0.02), preferred treatment option to manage Demodex blepharitis (tea tree oil in Australasia vs Standard lid hygiene in India; p = 0.01), treatment duration (from 3-4 weeks to over 12 weeks in Australasia vs 3-4 weeks in India; p = 0.02) and treatment application frequency (once daily in Australasia vs twice daily in India; p = 0.01). Conclusions: This study highlights differences in clinical evaluation and treatment practices between eyecare professionals in India and Australasia. Overall, practitioners in Australia and New Zealand were more evidence-based in their investigation and management. However, in both regions, interprofessional differences in perceived optimal treatment duration and frequency were reported.

Clinical Manifestations and Outcomes of Ocular Graft Versus Host Disease following Allogeneic Stem Cell Transplantation.

Purpose: To evaluate clinical presentation of chronic ocular graft-versus-host disease (GVHD), laterality of presentation, and longitudinal changes in patients undergoing allogeneic stem cell transplantation. Methods: This is a retrospective longitudinal analysis of 60 eyes from 30 patients who had undergone hematopoietic stem cell transplantation. Demographic characteristics, clinical history, comorbidities, and other organ involvements were taken into account for analysis. We also undertook complete evaluation of the eyes, including cornea and anterior segment, posterior segment, Schirmer test, tear break-up time, ocular surface disease index, and intraocular pressure. Results: The mean age of the patients was 34.3 ± 11 years. The mean time for the diagnosis of ocular GVHD was 232.8 days (95% CI: 153.6, 311.9). The common findings at the first visit were bilateral blepharitis (n = 5, 17%), meibomitis (n = 4, 13%), and conjunctival congestion (n = 3, 10%). While bilateral cataract was present in one (3%) patient at the first visit, at 18 months, five (17%) patients had bilateral cataract and one (3%) patient had unilateral cataract. Grade 1 (n = 17), grade 2 (n = 9), and grade 3 (n = 4) superficial punctate epithelial erosions (SPEEs) were also observed at the first visit. However, SPEEs were seen in only 11 eyes at 18 months; all of these cases were grade 1 SPEEs. Long-term findings included cataract, telangiectasia, blepharospasm, conjunctival congestion, grade 1 SPEEs, corneal filaments, and tear film debris. Conclusion: Although the initial presentations were SPEEs, meibomitis, blepharitis, and conjunctival congestion, these inflammatory conditions were reduced over time with proper management. However, there was an increase in the proportion of patients with cataract. It is important to regularly monitor these patients in order to identify and manage the initial as well as the late ocular manifestations of chronic GVHD.

Investigating Optic Nerve Sheath Diameter in Prone Position Spinal Surgery Patients: A Pilot Study.

Purpose: This study aimed to evaluate the effect of intraoperative positioning and ocular immobility on the amount of cerebrospinal fluid around the optic nerve in patients undergoing prone spinal surgery by measuring the optic nerve sheath diameter (ONSD) using ultrasound. Methods: Consecutive participants (n = 15 patients, 30 eyes) were scanned preoperatively, intraoperatively approximately 20 minutes before the end of the surgery, and postoperatively in the post-anesthesia care unit at least 10 min after the completion of the surgery at one academic hospital. Results: On average, patients who underwent prone spinal surgery had a 21% increase in ONSD intraoperatively, with a positive time-dependent relationship with the overall length of surgery (P < 0.001). ONSDs postoperatively returned to baseline and were not significantly different from preoperative measurements. Conclusion: Our findings suggest pooling and inadequate clearance of perioptic cerebrospinal fluid during prone spinal surgery that improves following termination of the procedure and return of the patient to an upright position.