Ocular Effects Research Articles

Physically Crosslinked Polymeric Network for Controlled and Mucoadhesive Release of Miconazole for Topical Ocular Delivery

Background: Eudragit L100, filled with miconazole and gelatinous polymeric eye drops, is designed to sustain the drug release and increase ocular effect. Methods: The solvent diffusion technique was used to obtain the polymeric solution. The formulations developed were fully characterized and examined. Results: The optimized drug had a particle size of 71.15 2.3 nm, a zeta potential of approx. 2.57 to 0.76 mV, a polydispersity index of approx. 0.184 and a capture efficiency of 0.10% of 58.049. The prepared efforts showed a fungicidal effect on Candidiasis albicans cultures. Conclusion: The polymeric solution containing the drug-filled with miconazole (MZ) showed an abrupt release in the first hours, followed by the pattern of sustained drug release. A higher cumulative corneal permeability was observed from MZ-containing polymeric solution, which prolonged MZ release in goat eyes. Mucoadhesive liners containing miconazole-loaded Eudragit L100 polymeric solution provide a promising approach to the ocular administration of miconazole (a fungicide) for the treatment of ocular infections requiring long-term drug administration.

COMBINATION OF DEXAMETHASONE IMPLANT AND ANTI-VEGF IN THE MANAGEMENT OF DIABETIC MACULAR EDEMA: A SYSTEMATIC REVIEW

Background: Anti Vascular Endothelial Growth Factor (anti-VEGF) and dexamethasone implant (DEX) are suggested as the first and second-line therapy for Diabetic Macular Edema (DME). However, persistent DME were found after six months of routine anti-VEGF injection. Intravitreal steroids have the advantage to control the inflammatory component of DME. Combining intravitreal anti-VEGF and DEX may reduce macular edema more effectively and more quickly theoretically. Hence, we aim to review the efficacy of adding DEX to anti-VEGF in treating DME. Methods: Literatures were obtained using comprehensive searching on PubMed and Proquest using the keywords “Dexamethasone implant”, “anti-VEGF therapy”, and “Diabetic Macular Edema” including their synonyms between 2018 to 2023. Non-English studies, animal studies, review articles, case studies, and editorial letters were excluded. This result was presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Results: A total of 3 studies with 265 eyes were included. All of the studies had Central Foveal Thickness (CFT) and Best Corrected Visual Acuity (BCVA) as the main outcomes. Improved CFT was seen in all of the studies (all p<0.05) with ∆CFT (200,40 μm in 6 months and 413 μm in 12 months). Most studies showed improved visual acuity after 8 months of injections which were shown by ∆BCVA (8,84 letters in 6 months and 21,6 letters in 12 months) and increased intraocular pressure as an adverse effect of steroids. Conclusion: Combination of DEX and anti-VEGF showed improvement in CFT and BCVA. Further studies are required due to the controversial intravitreal steroids’ ocular adverse effect.

Beneficial Effects of Micronutrient Supplementation in Restoring the Altered Microbiota and Gut-Retina Axis in Patients with Neovascular Age-Related Macular Degeneration-A Randomized Clinical Trial.

Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)-known for their anti-inflammatory properties-on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography-mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations-such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing-this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut-retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.

Spinacia Oleracea: Exploring the Therapeutic Potential in Persian Medicine and Modern Pharmacology.

Spinach is a widely cultivated dark leafy vegetable highly regarded for its medicinal properties in traditional Persian medicine. It is rich in vitamins, minerals, flavonoids, carotenoids, and other bioactive compounds, and this review aims to explore the historical applications of spinach in Persian medicine and juxtapose them with current scientific evidence. Despite its historical significance, there remains a need to comprehensively evaluate and integrate traditional knowledge with modern research on the therapeutic benefits of spinach. To achieve this, a comprehensive search was conducted in Persian medicine references and scientific databases to gather information on the traditional uses, chemical composition, and pharmacological effects of spinach. Studies that met the inclusion criteria were meticulously categorized, and relevant data were analyzed to draw insightful comparisons. Persian medicine describes spinach as a nutrient-rich, laxative, and fast-digesting agent with therapeutic effects on inflammation, lung diseases, back pain, sore throats, jaundice, urinary disorders, joint pain, eye inflammation, insomnia, dementia, and more. Modern studies have substantially corroborated these traditional uses, revealing that spinach possesses antioxidant, anti-inflammatory, anti-cancer, blood sugar-lowering, lipid-lowering, anti-obesity, neurological, ocular, and musculoskeletal effects. Spinach exhibits a wide range of beneficial effects on various health conditions. Its widespread availability, low cost, and exceptional nutritional richness position it as a promising candidate for further investigation. Future studies should explore the clinical effectiveness of spinach in various diseases, while taking into consideration the principles emphasized in Persian medicine to guide research and inform therapeutic strategies.

Ocular effects of synthetic cannabinoids: a case-control study.

To evaluate the ocular effects of "Bonzai", a synthetic cannabinoid (SC), in seropositive and seronegative users. Sixty eyes of 60 consecutive male patients with a history of "Bonzai" use and 30 eyes of 30 age-matched male healthy controls were enrolled in this case-control study. Patients with past "Bonzai" use were grouped as seropositive (n:30) and seronegative (n:30) according to urine toxicology tests. All groups were compared for blood pressures, intraocular pressure, foveal and parafoveal retinal thicknesses, subfoveal and parafoveal choroidal thicknesses, measurements of the peripapillary retinal nerve fibre layer (RNFL), and macular ganglion cell complex (GCC), subfoveal total choroidal, luminal and stromal areas, and choroidal vascularity index (CVI). No differences were noted in blood pressures between the groups (p > 0.05). The mean intraocular pressure was significantly lower in the seropositive group than in the other groups (p < 0.001). Foveal and retinal thicknesses, RNFL, and GCC measurements did not differ between the groups (p > 0.05). Subfoveal and parafoveal choroidal thicknesses and areas were lower in the seropositive group than in the other groups (p < 0.001, for all). CVI increased in both groups with "Bonzai" use compared to the control group (p < 0.001, for all). This study indicates that intraocular pressure may decrease, and choroidal changes may be observed in SC users. Further clinical studies with a larger sample size, especially using purified SC for therapeutic purposes, are needed to confirm the present findings, and further histopathologic studies are required to clarify the changes in the choroid despite SC seronegativity. NCT06235346.

Ocular and Systemic Effects of Intravitreal Dexamethasone Sustained Release Implant in Refractory Diabetic Macular Edema

Abstract Purpose Intravitreal therapies with anti-VEGF medications are regarded as effective treatment option. The biodegradable intravitreal implant, Ozurdex (Allergan, Irvine, CA, USA) depends on slow-release dexamethasone. The present study aimed to assess the safety of intravitreal Ozurdex in patients with refractory DME. Methods This prospective study included patient with resistant DME who received intravitreal Ozurdex. baseline clinical evaluation, change in best corrected visual acuity BCVA and central retinal thickness CRT were analysed, intra ocular pressure, HbA1c, adverse effects were recorded. Results The reported CRT measurements showed significant decrease in the first 3 months post injection. The reported BCV showing significant improvement from the baseline values, there was significant increase in IOP in the first month only which was controlled with medical treatment, with no influence on HbA1c. Conclusions for patients with refractory macular oedema, Ozudex implant showed improvement in visual acuity and decreased macular thickness and there was no influence on metabolic control, side effects such as increase of intraocular pressure may require medical treatment.

Immune-mediated meibomian gland dysfunction and dry eye disease related to trastuzumab emtansine chemotherapy in HER2 breast cancer: A case report

One of the most commonly administered drugs for human epidermal growth factor receptor 2 (HER2) breast cancer is trastuzumab emtansine (TDM-1). Unfortunately, this drug causes ocular surface disease as an adverse effect. This case report describes the diagnosis and management of meibomian gland dysfunction (MGD) and dry eye related to TDM-1 in HER2 a breast cancer patient. Our patient was a 43-year-old female diagnosed with HER2 breast cancer with metastasis to the peritoneum and liver. After a cycle of TDM-1 chemotherapy, she complained of recurrent hordeolum, ocular discomfort, and blurry vision. We initially prescribed topical and oral medications and gradually combined them with hordeolum incision and drainage, in-office meibomian gland expression, and intense pulse light therapy to improve symptoms. Ocular adverse effects due to anticancer agents are not preventable. Ophthalmologists must be aware of them and instigate needed therapy to ensure patients’ compliance with cancer treatment and improve quality of life.

Comparison of Different Cycloplegic Refraction Regimens for Children

In the process of a pediatric eye exam, cycloplegic refraction is a crucial step. Since no single cycloplegic drug is ideal, a combination regimen is employed. This study compares the ocular (refractive power and pupil diameter) and systemic (blood pressure and heart rate) effects of administering a combination of 1% cyclopentolate and 2.5% phenylephrine, with or without 1% tropicamide, to children with refractive errors. This study aimed to discover a more feasible regimen for children. This was a single-blind study, a randomized clinical trial conducted from November–December 2020 in children with mild to moderate refractive errors. Group A received 1% cyclopentolate, 2.5% phenylephrine, and 1% tropicamide (SFT), whereas group B received 1% cyclopentolate and 2.5% phenylephrine (SF). The outcomes were measured using an auto refractometer and IOL Master® 700. Before and 60 minutes after medication was administered, blood pressure and heart rate were measured. There were 54 participants (108 eyes) with an average age of 12.85± 2.84 years. Although the SFT group's refractive power and pupil width were greater than those of the SF group, the differences were not statistically significant (p=0.271 and p=0.088). Heart rate (p=0.521) and blood pressure (systolic p=0.201; diastolic p=0.950) did not significantly differ between the two groups. Despite mydriasis manifested more rapidly in the SFT group, there was no discernible difference in the cycloplegic effects between those groups. SF might be a more feasible regimen for cycloplegic refraction in children with refractive errors.

Short pulse grid and subthreshold micropulse laser (the sandwich grid) plus intravitreal ranibizumab for the treatment of diabetic macular edema

ObjectiveTo investigate the effects of two laser treatment procedures combined, short pulse grid laser (SP) and subthreshold micropulse laser (MP) (the sandwich grid [SWG] technique), plus intravitreal ranibizumab (IVR) on central subfield thickness (CSFT), best-corrected visual acuity (BCVA) and macular sensitivity in patients with diabetic macular edema (DME).MethodsForty-five eyes (of 33 patients) with center-involving DME were treated with the SWG laser technique plus IVR and followed for 12 months. Laser treatment was performed at baseline: SP laser spots were placed in a grid pattern in the macular area (500 µm from the fovea) according to the extension of DME; subsequently, MP laser was delivered up to the edge of the fovea. MP laser re-treatment sessions could be performed every 3 months if DME was present and CSFT was ≥ 300 μm on SD-OCT. IVR injection was performed at baseline and repeated monthly if CSFT > 300µm. Preoperatively and monthly, ophthalmological examination was performed including measurements of BCVA, CSFT, and macular sensitivity.ResultsOne-year follow-up data is available for 37 eyes of 27 patients. Mean ± SE CSFT (µm) was 509.36 ± 25.14 and 325.76 ± 15.34 at baseline and 12 months, respectively. A significant reduction in mean CSFT was observed at all study visits compared to baseline (p < 0.001). Mean ± SE BCVA (logMAR) was 0.62 ± 0.04 and 0.45 ± 0.04 at baseline and 12 months, respectively. A significant improvement in mean BCVA was observed at all study visits compared to baseline (p < 0.001). Mean ± SE macular sensitivity (dB) was 17.85 ± 0.80 and improved to 19.05 ± 0.59 after one year of follow-up (p = 0.006). The mean number of IVR injections was 8.29 ± 0.63. The mean number of MP laser procedures including the initial SWG laser session was 3.67 ± 0.22. No ocular or systemic adverse effects were observed.ConclusionThe SWG laser technique plus IVR was associated with significant improvement in macular edema, BCVA, and macular sensitivity in patients with center-involving DME.Clinical Trial Number (CAAE)22969019.4.0000.5440.

Preliminary antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery in primary open-angle glaucoma.

To investigate the antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery (MIGS). Human trabecular meshwork (TM) cells were treated with different concentrations of adrenaline (0%, 0.0005%, 0.01%), and we measured the effects on contractility, cell viability and the expression of key cell cycle and fibrosis genes. Adrenaline 0.05% was also injected intracamerally in five primary open-angle glaucoma patients undergoing iStent inject or MINIject surgery combined with phacoemulsification. All patients were assessed for ocular and systemic adverse reactions, including the effects on intraoperative pupil size, preoperative and postoperative visual acuity, intraocular pressure, and anterior segment OCT results. Adrenaline significantly reduced the contractility of TM cells in a dose-dependent manner (87.8%, 80.6%, 7.9% matrix contraction with adrenaline 0%, 0.0005%, 0.01%, respectively). Adrenaline did not exhibit any significant cytotoxicity even at high concentrations (P > 0.05). Adrenaline 0.01% significantly downregulated the expression of key cell cycle genes in the G2 and M phases, and also decreased the expression of MRTFB and ACTA2 genes (P < 0.05). Intracameral injections of adrenaline 0.05% in the five MIGS patients did not result in any ocular or systemic adverse effects. We recommend intracameral injections of adrenaline 0.05% as a cheap and safe drug to be used before MIGS insertion. Adrenaline decreases the risk of bleeding from the trabecular meshwork and also exhibits antifibrotic effects by arresting the cell cycle, thereby increasing the postoperative success rates in MIGS. What is known Fibrosis is the main cause of surgical failure in minimally invasive glaucoma surgery (MIGS). Mitomycin-C and 5-fluorouracil are too toxic to be used inside the eye. What is new Adrenaline reduced the contractility of trabecular meshwork cells and inhibited the expression of key cell cycle genes and fibrosis genes, without significant cytotoxicity. Intracameral injection of adrenaline 0.05% did not result in any ocular or systemic adverse reactions in MIGS patients.

Ocular and Periocular Tattoo Adverse Effects: A Review.

Ocular and periocular tattoos, involving ink application to the eyeball or surrounding skin, have gained popularity as forms of self-expression. However, this trend raises significant concerns about potential complications that can adversely affect ocular health and esthetics. Awareness of these risks is crucial for both patients and practitioners. A comprehensive literature review was conducted, focusing on studies discussing complications related to ocular and periocular tattooing. Relevant studies were identified through the MEDLINE, PubMed, and Ovid databases. The reviewed papers were evaluated based on study design, including blinding, sample size, control use, randomization, and objective endpoints, and classified according to the Oxford Center for Evidence-Based Medicine evidence hierarchy. The review identified a wide range of complications, including immediate issues like bleeding, infections (conjunctivitis, endophthalmitis), and allergic reactions. Delayed reactions included granuloma formation, often requiring further treatment. The most serious risk identified was potential visual impairment due to improper technique or ink placement. With the growing trend in ocular and periocular tattooing, there is an urgent need for increased awareness of associated risks. It is crucial to ensure that only qualified professionals perform these procedures, emphasizing the importance of understanding ocular anatomy. Developing strict regulatory guidelines and prioritizing research on the long-term effects of these tattoos are essential for patient safety. A collaborative approach among healthcare providers, regulatory bodies, and educational institutions is needed to mitigate risks and promote best practices in cosmetic tattooing.

MERTK Inhibitor Associated Retinal Toxicity in a Human.

The MER proto-oncogene tyrosine kinase (MERTK) helps maintain the homeostasis of the retinal pigmented epithelium (RPE). Additionally, MERTK regulates the innate immune system. As such inhibition of MERTK has gained recent interest as a target for cancer therapeutics. Herein, we present on MERTK inhibitor associated retinal toxicity in a human. A 43-year-old male with past medical history of esophageal adenocarcinoma was enrolled in a trial studying the MERTK inhibitor PF-07265807. As part of the study protocol, the patient was seen every two to three weeks for dilated fundus exams and ancillary testing. Data on the patient's relevant past medical history, ophthalmic exam findings, and imaging performed at baseline and subsequent ophthalmology visits was obtained via retrospective chart review. At the patient's baseline visit, his dilated exam and testing were normal. Seven months after starting the MERTK inhibitor the patient developed subtle but reproducible signs of retinal toxicity with disruption of the extrafoveal ellipsoid zone on optical coherence tomography and extrafoveal hyper-autofluorescence on short wavelength fundus autofluorescence. The patient's vision remained stable throughout the study; however, the medication was stopped due to the unknown ocular effects as well as progression of the patient's cancer. Patients taking MERTK inhibitors should be monitored by an ophthalmologist while on the drug. If toxicity develops, discussion of whether to continue the medication should take place between the patient, ophthalmologist, and oncologist, with consideration of the risks of vision loss versus benefits of taking the medication from a cancer perspective.

Bio-spectroscopic investigation linking changes of retinal structure with short-term administration of Amiodarone and revealing the ameliorative effect of vitamin E supplementation

Long term use of Amiodarone (AMIO) is associated with the development of ocular adverse effects. This study investigates the short term effects, and the ameliorative consequence of vitamin E on retinal changes that were associated with administration of AMIO. This is accomplished by investigating both retinal structural and conformational characteristics using Fourier transform infrared spectroscopy (FTIR) and Fundus examination. Three groups of healthy rabbits of both sexes were used; the first group served as control. The second group was orally treated with AMIO (160 mg /kg body weight) in a daily basis for two weeks. The last group orally received AMIO as the second group for two weeks then, oral administration of vitamin E (100 mg/kg body weight) for another two weeks as well. FTIR results revealed significant structural and conformational changes in retinal tissue constituents that include lipids and proteins due to AMIO administration. AMIO treatment was associated with fluctuated changes (increased/decreased) in the band position and bandwidth of NH, OH, and CH bonds. This was concomitant with changes in the percentage of retinal protein constituents in particularly α-helix and Turns. AMIO facilitates the formation of intra-molecular hydrogen bonding and turned retinal lipids to be more disordered structure. In conclusion, the obtained FTIR data together with principal component analysis provide evidence that administration of vitamin E following the treatment with AMIO can ameliorate these retinal changes and, these biophysical changes are too early to be detected by Fundus examination.

Aerosolization ocular surface microorganisms accumulation effect during non-contact tonometer measurements

PurposeThis study aimed to verify that aerosolization ocular surface microorganisms (AOSMs) accumulated during non-contact tonometry (NCT) measurements.MethodsA total of 508 participants (740 eyes) were enrolled in the study. In Experiment 1, before NCT was performed on each eye, the air was disinfected, and environment air control samples were collected via Air ideal® 3P (Bio Merieux). During NCT measurements, microbial aerosol samples were collected once from each eye. In Experiment 2, we collected initial blank control samples and then repeated Experiment 1. Finally, in Experiment 3, after the background microbial aerosol investigation, we cumulatively sampled AOSMs from each 10 participants then culture once, without any interventions to interrupt the accumulation. The collected samples were incubated and identified using matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS).ResultsPathogenic Aerococcus viridans and other microorganisms from human eyes can spread and accumulate in the air during NCT measurements. The species and quantity of AOSMs produced by NCT measurements can demonstrate an accumulation effect.ConclusionAOSMs generated during NCT measurements are highly likely to spread and accumulate in the air, thereby may increase the risk of exposure to and transmission of bio-aerosols.

Celebration to Consequence: Case Report of Late Onset Ocular Effects of Firework Injuries

Firework-related injuries, particularly ocular trauma, pose a significant public health concern during cultural celebrations. We explore the case of a 20-year-old male who sustained firework-induced ocular trauma at the age of seven, subsequently developing traumatic cataract and glaucomatous optic atrophy. The patient presented with decreased vision and pain in the left eye (LE), 13 years post-injury. He underwent cataract surgery nine years after the incident, with subsequent development of glaucomatous optic atrophy. Examination revealed visual acuity impairment, exotropia, and pupil abnormalities in the LE, along with scleral thinning and corneal opacity. Posterior segment evaluation showed optic nerve cupping and hemorrhages. Gonioscopy indicated angle recession and synechiae in the LE. Optical coherence tomography revealed retinal nerve fiber layer defects. Elevated intraocular pressure in the LE was successfully managed with anti-glaucoma medication. Firework-related ocular trauma can lead to long-term complications, including traumatic cataract and glaucomatous optic atrophy. Timely cataract surgery and vigilant follow-up are essential for early detection and management of secondary glaucoma. Regulatory measures to mitigate firework-related injuries are imperative to prevent such incidents and preserve visual health.

Linezolid Optic Neuropathy

Various systemic antimicrobials have been known to cause ocular adverse effects. Linezolid has been shown to be effective in treating multidrug-resistant tuberculosis. Though, long-term treatment is discontinued by the related side effects, such as ocular and peripheral neuropathy. In a developing country like India, where there is increasing burden of multidrug-resistant tuberculosis, ophthalmologists and physicians should be aware of linezolid induced optic neuropathy so that monitoring of visual functions in patients on long-term linezolid treatment can be done to avoid serious neurological consequences.

Ocular Adverse Effects of Over-the-Counter Cosmetics and Personal Care Products Reported to the Food and Drug Administration.

Personal care and cosmetic products can cause periocular and ocular adverse effects (AEs), for example, ocular surface disease, trauma, and hypersensitivity. The publicly available Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) database includes AE reports by consumers, healthcare practitioners, and manufacturers. The purpose of this study was to characterize ophthalmic AE associated with cosmetics and personal care products reported by the FDA CAERS database. AE related to the eye or ocular adnexa from cosmetics submitted by consumers, healthcare practitioners, and manufacturers from January 2004 to June 2022 were identified after filtering using the Medical Dictionary for Regulatory Activities coding system. Demographic information, case outcome, and categories of product and AE were included. Chi-square analysis, with statistical significance at a = 0.05, was performed to ascertain variation in ocular, periocular, and general outcomes by product category. Reports of ophthalmic AEs related to cosmetics per year increased from 2006 to 2018, reaching a maximum of 161 reports in 2018, then decreased from 2018 to 2021. In total, 959 and 1382 unique periocular and ocular AEs were reported. There were 1711 total incidences of reported periocular AEs and 2485 ocular AEs. The most reported periocular AEs were inflammation (770/1711) and hypersensitivity (331/1711). The most reported ocular effects were discomfort (946/2485) and inflammation (709/2485). Ocular, periocular, and general outcomes significantly varied by product category. Consumers, healthcare practitioners, and manufacturers should be made aware of potential ophthalmic AE and outcomes associated with cosmetics and personal care products.

Ocular Adverse Effects of TNF-α Inhibitors in the FDA Adverse Event Reporting System (FAERS)

Autoimmune inflammatory diseases affect 7.6-9.4% of the global population, predominantly women. TNF-α inhibitors (TNFI) have revolutionized rheumatic disease treatment but are associated with serious ocular adverse events (AEs). We analyzed FAERS data for adalimumab, etanercept, and infliximab (1998-2024), documenting patient demographics and the top 10 ocular AEs for each TNFI. Of the 45,445 reported ocular AEs, 66.6% were in females and 50.3% were in adults aged 18-64. The most common AEs included visual impairment (7,093), cataract (5,730), and blurred vision (5,586). There were 2,271 reports of blindness. The distribution of AEs was similar across adult age groups but rare in pediatric patients and those over 85. A review by da Silva et al corroborates our findings, identifying uveitis, optic neuropathy, and retinal toxicity among others. FAERS data showed 1,927 uveitis cases linked to adalimumab, 1,054 to etanercept, and 1,076 to infliximab. These AEs may result from TNF-α binding in ocular tissues, paradoxically causing and treating uveitis. Our study highlights the severity of ocular AEs with TNFI use, suggesting a need for vigilance in monitoring patients, especially given the potential for irreversible blindness. The limitations include voluntary reporting and underreporting in FAERS, underscoring the need for further research to better understand these risks.

Accuracy and Completeness of Large Language Models About Antibody-Drug Conjugates and Associated Ocular Adverse Effects.

The purpose of this study was to assess the accuracy and completeness of 3 large language models (LLMs) to generate information about antibody-drug conjugate (ADC)-associated ocular toxicities. There were 22 questions about ADCs, tisotumab vedotin, and mirvetuximab soravtansine that were developed and input into ChatGPT 4.0, Bard, and LLaMa. Answers were rated by 4 ocular toxicity experts using standardized 6-point Likert scales on accuracy and completeness. ANOVA tests were conducted for comparison between the 3 subgroups, followed by pairwise t-tests. Interrater variability was assessed with Fleiss kappa tests. The mean accuracy score was 4.62 (SD 0.89) for ChatGPT, 4.77 (SD 0.90) for Bard, and 4.41 (SD 1.09) for LLaMA. Both ChatGPT (P = 0.03) and Bard (P = 0.003) scored significantly better for accuracy when compared with LLaMA. The mean completeness score was 4.43 (SD 0.91) for ChatGPT, 4.57 (SD 0.93) for Bard, and 4.42 (SD 0.99) for LLaMA. There were no significant differences in completeness scores between groups. Fleiss kappa assessment for interrater variability was good (0.74) for accuracy and fair (0.31) for completeness. All 3 LLMs had relatively high accuracy and completeness ratings, showing LLMs are able to provide sufficient answers for niche topics of ophthalmology. Our results indicate that ChatGPT and Bard may be slightly better at providing more accurate answers than LLaMA. As further research and treatment plans are developed for ADC-associated ocular toxicities, these LLMs should be reassessed to see if they provide complete and accurate answers that remain in line with current medical knowledge.

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

PurposeTo 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 intraocular pressure (IOP) lowering agent with a reduced ocular surface side effect profile. DesignIn vivo pre-clinical investigation in mice SubjectsC57BL/6J, DBA/2J, FP receptor knockout mice MethodsNormotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 μL; 6 x 109 viral genomes [VGs]) in one eye and the same volume and concentration of ssAAV2-GFP or the same volume of PBS in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 x 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 x 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. FP receptor knockout mice were injected subconjunctivally with 6 x 109 VGs of ssAAV2-STC-1-FLAG or PBS. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. IOP 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 and other treatments including daily topical latanoprost. Main outcome measuresIOP assessment ResultsSubconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 2 post injection (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 (19.4%; 18.7 ±0.9 vs 15.1 ± 0.5 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 to 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. ConclusionsSubconjunctival 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.