Reitinger JC, Reed DM, Peres C
… +6 more, Fan S, Gulati V, Kazemi A, Sit AJ, Moroi SE, Toris CB
J Ocul Pharmacol Ther
· 2025 Jun · PMID 40229142
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To identify reasons for variable intraocular pressure (IOP) responses to latanoprost and timolol in healthy volunteers and to generate the control group as part of Eye Dynamics and Engineering Network. In this multicent...To identify reasons for variable intraocular pressure (IOP) responses to latanoprost and timolol in healthy volunteers and to generate the control group as part of Eye Dynamics and Engineering Network. In this multicenter, randomized, crossover study (NCT01677507), both eyes of 106 healthy subjects (212 eyes) were treated with latanoprost or timolol for 7 days, with a 6-week washout between treatments. Ocular biometrics, tonometry, and aqueous humor dynamics (AHD) were assessed at baseline and day 8 of each treatment. Subjects were divided into responders and nonresponders using cutoffs of >15% or >10% IOP reduction. Treatment effects and correlations were analyzed with paired t-tests. More subjects responded to latanoprost (54%) than timolol (27%) at >15% cutoff ( < 0.01). Responders had higher mean baseline IOP than nonresponders for both drugs at both cutoffs ( < 0.01). Among timolol nonresponders ( = 56), 39% responded to latanoprost in both eyes, 20% in one eye, and 41% in neither. Among latanoprost nonresponders ( = 31), 13% responded to timolol in both eyes, 13% in one eye, and 74% in neither. Latanoprost increased uveoscleral outflow, while timolol reduced aqueous flow and outflow facility. Low baseline uveoscleral outflow was associated with latanoprost response. Higher baseline IOP predicted better responses to both drugs. Higher baseline uveoscleral outflow predicted nonresponse to latanoprost. No AHD differences were linked to the timolol response. Timolol nonresponders were often responsive to latanoprost, but not vice versa.
In 2023, Xdemvy® (0.25% lotilaner ophthalmic solution) was approved by the U.S. FDA for treating Demodex blepharitis in humans. This article reviews lotilaner's history, physicochemical properties, pharmacokinetics, phar...In 2023, Xdemvy® (0.25% lotilaner ophthalmic solution) was approved by the U.S. FDA for treating Demodex blepharitis in humans. This article reviews lotilaner's history, physicochemical properties, pharmacokinetics, pharmacology, clinical outcomes, and other indications for which it is being evaluated clinically. Furthermore, the article discusses Demodex blepharitis, alternative treatments used in the clinic to ameliorate its symptoms, and other drugs in development. Prior to its approval in humans, lotilaner found extensive application in treating parasitic infections in cats and dogs. Lotilaner was previously approved in 2017 as an oral veterinary medicine (Credelio®) for canines to treat demodicosis, other mite infections, and tick infections. Lotilaner belongs to the isoxazoline class of drugs and is a potent arthropod-selective gamma-aminobutyric acid-gated chloride ion channel inhibitor. Like several other drugs in the isoxazoline class, lotilaner has a long plasma half-life and high plasma protein binding of about 99.9%. When used as indicated, lotilaner treats infested Demodex blepharitis in 42 days, with its antiparasitic action starting within 24 h. Furthermore, lotilaner is also being evaluated for its efficacy in other conditions such as Lyme disease and dry eye disease. Other products evaluated for treating Demodex blepharitis include ivermectin eye ointment, ivermectin-metronidazole gel, permethrin cream, terpinen-4-ol wipes, and hypochlorous acid spray. Along with these, azithromycin eye drop, azithromycin/loteprednol eye drop, and other treatments are being evaluated for treating blepharitis. Other drugs from the isoxazoline drug class including afoxolaner, sarolaner, and fluralaner, could also be potentially explored for human use.
Corticosteroid use as an anti-inflammatory agent in infective conjunctivitis has been met with concerns about prolonged infection. This systematic review aims to evaluate the safety and efficacy of corticosteroids as a t...Corticosteroid use as an anti-inflammatory agent in infective conjunctivitis has been met with concerns about prolonged infection. This systematic review aims to evaluate the safety and efficacy of corticosteroids as a treatment for infective conjunctivitis. A comprehensive search was conducted on PubMed, Cochrane, Scopus, ScienceDirect, Embase, and ProQuest for clinical trials of topical corticosteroids with or without combination with other medications in bacterial or viral conjunctivitis up to November 2023. The studies were screened, and data on safety and efficacy were extracted. The quality of studies was assessed using the Jadad Scale. Meta-analysis was performed using the random-effects model, with heterogeneity assessed with the statistic. We found ten clinical trials that met the inclusion criteria. Overall meta-analysis revealed significant clinical resolution in dexamethasone-containing therapy compared to non-corticosteroid treatment (OR 1.51; 95% CI 1.19-1.92), with several studies reporting significantly reduced clinical symptoms severity. Two of the six studies assessing viral and bacterial eradication reported significantly improved viral clearance rates. Meta-analysis indicated no difference in ocular adverse effects compared to nonsteroid therapy (OR 1.33; 95% CI 0.82-2.16). In conclusion, corticosteroid use in infective conjunctivitis is relatively safe and may help improve clinical resolution and reduce symptom severity, especially when combined with antibiotics and antiseptics.
To describe the clinical effects of a novel, combined ocular lubricant for treating patients with dry eye disease. A noncomparative, retrospective cohort of 67 eyes (67 patients) with a confirmed diagnosis of dry eye di...To describe the clinical effects of a novel, combined ocular lubricant for treating patients with dry eye disease. A noncomparative, retrospective cohort of 67 eyes (67 patients) with a confirmed diagnosis of dry eye disease using the ocular surface disease index (>12), tear osmolarity, and ocular surface parameters (noninvasive break-up time, meniscus height, and meibography) evaluated using the Cornea550 were included. All patients were treated with a combination of 0.5% carboxymethylcellulose, glycerin 0.9%, and trehalose 3% with a dosing regimen of one drop four times a day for 1 month with a final evaluation of the same parameters. We included 67 eyes (80.6% females) with a mean age of 48.3 ± 16.2 years (standard deviation [SD]). In total, 37% of the subjects had comorbidities such as hypothyroidism (9%), ocular rosacea (4%), Sjogren's syndrome (4%), and arterial hypertension (4%). Of these, 34% were taking systemic medications and 56.7% had previous ocular surgery. The mean ocular surface disease index score before treatment was 57.6 ± 17.2 (SD) and 22.2 ± 12.9 points (SD) after treatment ( < 0.05). Other parameters such as noninvasive break-up time, meniscus height, and meibography improved without a statistically significant difference. Cristal Tears Plus is a novel, combined, and multipurpose treatment for dry eye disease.
J Ocul Pharmacol Ther
· 2025 Jun · PMID 39960822
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Ocular trauma leads to loss of corneal clarity resulting in vision deficits. Autophagy plays a critical role in the extracellular matrix, tissue repair, and homeostasis but its precise mechanistic role in regulating corn...Ocular trauma leads to loss of corneal clarity resulting in vision deficits. Autophagy plays a critical role in the extracellular matrix, tissue repair, and homeostasis but its precise mechanistic role in regulating corneal function remains unknown. The present study investigated the modulation of autophagy-related genes ( and ) in healthy and injured canine corneal stromal fibroblasts (CSFs). Primary CSFs were generated from healthy donor canine corneas and grown in minimum essential medium. Following incubation, cultures were exposed to nitrogen mustard (NM) and subjected to an autophagy activator, rapamycin (R), or vehicle treatment. Phase-contrast microscopy, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and immunofluorescence staining were used to study the role of autophagy genes in canine corneal wound healing . Phase-contrast microscopy showed that NM exposure led to morphological changes with stress fibers in CSFs, which was noticeably decreased by rapamycin treatment. Treatment of CSFs with rapamycin alone showed fibroblast hypertrophy while vehicle-treated population of CSFs exhibited typical spindle morphology. The qRT-PCR showed increased expression of and mRNA when treated with NM, NM+R, and R in comparison to vehicle-treated CSFs. expression was upregulated in the NM and NM+R treatment groups but was reduced in the R-treated group. Immunofluorescence showed similar results of the protein levels. This study suggests that autophagy is an essential component in corneal healing post-injury. Further, results suggest that targeting autophagy may offer an attractive treatment option to reestablish corneal clarity following ocular insult.
Cyclosporine A (CsA) is a primary treatment for dry eye disease (DED). Ophthalmic solutions containing CsA are available in concentrations of 0.05%, 0.09%, and 0.1%. While 0.1% CsA solutions have been used to treat DED,...Cyclosporine A (CsA) is a primary treatment for dry eye disease (DED). Ophthalmic solutions containing CsA are available in concentrations of 0.05%, 0.09%, and 0.1%. While 0.1% CsA solutions have been used to treat DED, their safety and effectiveness remains somewhat uncertain. Therefore, we conducted a meta-analysis to evaluate their safety and efficacy. We searched PubMed, Cochrane Database, Embase, and Web of Science for randomized controlled trials (RCTs) that compared 0.1% CsA solutions with their vehicle. Statistical analysis was performed using Review Manager 5.4.1. We included six RCTs (2,170 patients) with follow-up periods ranging from 4 weeks to 6 months. A total of 1,119 patients (51.56%) with DED were treated with 0.1% CsA. The mean age of patients was 57.9 ± 4.8 years, with 79.7% being female. The total corneal fluorescein staining (tCFS) at last follow-up [mean differences (MD) -0.49; 95% confidence interval (CI) (-0.73, -0.24); < 0.0001], at 4 weeks [MD -0.64; 95% CI (-1.07, -0.22); 0.003], and central corneal fluorescein staining (cCFS) [MD -0.19; 95% CI (-0.35, -0.03); 0.02] scores were lower in patients treated with 0.1% CsA compared with vehicle. The Lissamine Green conjunctival staining (LGCS) [MD -0.51; 95% CI (-0.78, -0.24); 0.0002] and ocular surface disease index (OSDI) scores [MD -3.04; 95% CI (-5.84, -0.23); 0.03] were lower in the 0.1% CsA group compared with vehicle. Adverse events associated with 0.1% CsA solution in the treatment of DED varied across studies, but were generally mild to moderate. Notably, similar events were also significantly present in the vehicle group, supporting the safety profile of this treatment. Ophthalmic 0.1% CsA seems safe for treating DED, and significantly reduced tCFS, cCFS, LGCS, and OSDI scores compared with vehicle solutions.
To test the effects of dedicator of cytokinesis protein 1 (DOCK1) with its binding partner engulfment and cell motility protein 1 (ELMO1)-Rac1 axis on the vitreous-induced biological functions of retinal pigment epitheli...To test the effects of dedicator of cytokinesis protein 1 (DOCK1) with its binding partner engulfment and cell motility protein 1 (ELMO1)-Rac1 axis on the vitreous-induced biological functions of retinal pigment epithelial (RPE) cells. Rac1 activity in RPE cells after vitreous stimulation was detected via a pull-down assay. The related protein expression levels were examined via western blot analysis. DOCK1 and ELMO1 knockdown cells were generated via CRISPR-Cas9 technology. Cytoskeletal reorganization was detected by immunofluorescent localization of F-actin. Cell proliferation, migration, invasion, and contraction ability were measured via the CCK8 assay, wound healing assay, transwell invasion assay, and collagen contraction assay. Rac1 activity was significantly elevated in ARPE-19 cells stimulated with vitreous fluid for 30 min to 3 h. Depletion of either DOCK1 or ELMO1 with CRISPR/Cas9 attenuated vitreous-stimulated Rac1 activity, thus reversing the vitreous-induced cytoskeletal rearrangements. The functional cell biology results revealed that deficiencies of DOCK1 and ELMO1 significantly impeded the migration, invasion, and contraction abilities of vitreous-stimulated human RPE cells. This study demonstrated that the DOCK1/ELMO1-Rac1 axis plays an essential role in the pathogenesis of proliferative vitreoretinopathy (PVR), thus suggesting that interruption of this axis has potential for PVR therapy.
Glaucoma is a chronic, progressive disease of visual loss and blindness that is often managed pharmacologically. The objective of this study was to evaluate glaucoma drug prescribing trends by ophthalmologists in the Uni...Glaucoma is a chronic, progressive disease of visual loss and blindness that is often managed pharmacologically. The objective of this study was to evaluate glaucoma drug prescribing trends by ophthalmologists in the United States from 2018 to 2022. Data on ophthalmologist prescribers were abstracted from Medicare Part D Prescriber Public Use Files to identify the total number of claims for each drug. Drugs were classified by type (generic or brand-name) and by drug class (carbonic anhydrase inhibitors, alpha-2 agonists, beta-blockers, prostaglandin analogs, rho kinase inhibitors, parasympathomimetic drugs, and mixed-mechanism drugs). The types of drugs prescribed were compared longitudinally. Forty glaucoma drugs were prescribed under Medicare Part D from July 1st, 2018, to June 30th, 2022. A dip in total claims and claims by drug class was observed from 2018-2019 to 2019-2020. This was followed by increases to the greater number of claims in 2021-2022. Prostaglandin analogues were the most frequently prescribed class, and the most commonly prescribed drugs were latanoprost, timolol, and the dorzolamide/timolol combination. The majority of claims consisted of generics, and this value increased longitudinally as well. The most rapidly growing class prescribed by physicians was rho kinase inhibitors. Longitudinal differences in Medicare Part D glaucoma drug claims may reflect changing practice patterns and preferences among providers. An increasing number of claims annually, with the exception of the COVID-19 pandemic onset, reflects the growing prevalence of glaucoma. The utilization of new glaucoma agents, such as rho kinase inhibitors, is rapidly increasing as a new therapeutic option.
To investigate the effectiveness of re-esterified triglyceride form of omega 3 (rTG-omega 3) on patients with meibomian gland dysfunction (MGD) after cataract surgery. This multicenter, randomized, investigator-blinded,...To investigate the effectiveness of re-esterified triglyceride form of omega 3 (rTG-omega 3) on patients with meibomian gland dysfunction (MGD) after cataract surgery. This multicenter, randomized, investigator-blinded, clinical study was conducted between June 2021 and March 2023 and enrolled 107 patients with MGD who had undergone cataract surgery within 3 months at seven sites across South Korea. Patients were randomly assigned to rTG-omega 3 group or a control group. We compared (1) tear film break-up time (TBUT) (s), (2) corneal fluorescein staining score [National Eye Institute/Industry (NEI) scale], (3) conjunctival fluorescein staining score (NEI scale), (4) strip meniscometry (SM) tube score (mm), (5) MGD stage, (6) MG quality, (7) MG expressibility, (8) Standard Patient Evaluation of Eye Dryness (SPEED) score, and (9) Ocular Surface Disease Index (OSDI) scores at baseline and 6 and 12 weeks. TBUT, corneal fluorescein staining score, and SM tube score were significantly improved in the rTG-omega 3 group compared with control group ( = 0.005, = 0.003, and = 0.0049, respectively). Subjective questionnaire responses were also improved significantly (SPEED score, = 0.022; OSDI score, = 0.0011). MGD parameters were not significantly different. However, during subanalysis, significant improvements in MG quality and expressibility were observed in the MGD stage 4 group with rTG-omega 3 supplementation ( = 0.0177 and 0.0205, respectively). rTG-omega 3 supplementation facilitated improvements in both objective and subjective parameters. In particular, MG quality and expressibility were significantly improved in the severe MGD group.
Age-related macular degeneration (AMD) poses a significant threat to visual health among the elderly, necessitating urgent preventive measures as the global population ages. Extensive research has implicated oxidative st...Age-related macular degeneration (AMD) poses a significant threat to visual health among the elderly, necessitating urgent preventive measures as the global population ages. Extensive research has implicated oxidative stress (OS)-induced retinal damage as a primary contributor to AMD pathogenesis, prompting investigations into potential therapeutic interventions. Among the various nutrients studied for their potential in AMD risk reduction, antioxidants have shown promise, with initial findings from the Age-Related Eye Disease Study suggesting a correlation between antioxidant supplementation and decreased AMD progression. This article explores the scientific foundation supporting the therapeutic efficacy of tocotrienol-rich fraction (TRF) as a viable candidate for slowing AMD progression, based on interventional studies. AMD is characterized by OS, inflammation, dysregulated lipid metabolism, and angiogenesis, all of which TRF purportedly addresses through its potent anti-inflammatory, lipid-lowering, antiangiogenic, and antioxidant properties. The review underscores TRF's promising attributes, aiming to deepen understanding of AMD pathogenesis and advocate for TRF-based pharmacological interventions to enhance therapeutic outcomes. Given the pressing need for effective AMD treatments, TRF represents a promising avenue for intervention, offering hope for improved vision outcomes and enhanced quality of life for individuals affected by this debilitating condition.
Keratoconus is a progressive corneal ectasia characterized by irregular astigmatism, leading to corneal scarring and decreased vision. Corneal cross-linking (CXL) is the standard treatment to halt disease progression, bu...Keratoconus is a progressive corneal ectasia characterized by irregular astigmatism, leading to corneal scarring and decreased vision. Corneal cross-linking (CXL) is the standard treatment to halt disease progression, but its effectiveness in transepithelial (epithelium-on, epi-on) approaches is limited by the low permeability of the corneal epithelium to riboflavin (Rb). This study aimed to enhance transepithelial Rb penetration in bovine corneas using Rb-modified tannic acid-coated superparamagnetic iron oxide nanoparticles (Rb-TA-SPIONs) under an external magnetic field. SPIONs were synthesized via co-precipitation, modified with TA and Rb, and characterized by physicochemical techniques. The average size of the Rb-TA-SPIONs was 46 ± 5.3 nm, with a saturation magnetization of 55.9 emu/g. experiments involved the application of 0.1% Rb to bovine corneas, and penetration was evaluated under epi-on conditions with iontophoresis (1-5 mA, 5 min). In addition, a 0.1% Rb-containing nanocarrier solution was tested under magnetic fields of 1-300 Gauss. Results showed increased Rb penetration with rising electric current density and Rb-TA-SPION penetration with stronger magnetic fields, compared with epi-on control groups. Specifically, Rb penetration increased from 0.036% ( ≤ 0.01) at 1 mA to 0.059% ( ≤ 0.001) at 5 mA in the iontophoresis group and from 0.035% ( ≤ 0.001) at 1 G to 0.054% ( ≤ 0.001) at 300 G in the magnetic group. These findings indicate that magnetic nanoparticle-assisted Rb delivery, guided by an external magnetic field, could improve potential CXL efficacy by enhancing Rb penetration and corneal permeability.
Posterior segment ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion, are leading causes of vision impairment and blindness worldwide. Effective management of thes...Posterior segment ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion, are leading causes of vision impairment and blindness worldwide. Effective management of these conditions remains a formidable challenge due to the unique anatomical and physiological barriers of the eye, including the blood-retinal barrier and rapid drug clearance mechanisms. To address these hurdles, nanostructured drug delivery systems are proposed to overcome ocular barriers, target the retina, and enhance permeation while ensuring controlled release. Traditional therapeutic approaches, such as intravitreal injections, pose significant drawbacks, including patient discomfort, poor compliance, and potential complications. Therefore, understanding the physiology and clearance mechanism of eye could aid in the design of novel formulations that could be noninvasive and deliver drugs to reach the target site is pivotal for effective treatment strategies. This review focuses on recent advances in formulation strategies for posterior segment ocular drug delivery, highlighting their potential to overcome these limitations. Furthermore, the potential of nanocarrier systems such as gel, niosomes, hydrogels, dendrimers, liposomes, nanoparticles, and nanoemulsions for drug delivery more effectively and selectively is explored, and supplemented with illustrative examples, figures, and tables. This review aims to provide insights into the current state of posterior segment drug delivery, emphasizing the need for interdisciplinary approaches to develop patient-centric, minimally invasive, and effective therapeutic solutions.
Povidone-iodine (PI) is the standard antiseptic for intravitreal injections (IVIs), while chlorhexidine (CHX) is a potential alternative. The efficacy of PI versus CHX in preventing endophthalmitis remains debated, with...Povidone-iodine (PI) is the standard antiseptic for intravitreal injections (IVIs), while chlorhexidine (CHX) is a potential alternative. The efficacy of PI versus CHX in preventing endophthalmitis remains debated, with studies showing mixed results. To compare the effectiveness of using PI compared with CHX in IVI procedures regarding endophthalmitis rates, culture-positive endophthalmitis rates, and changes in visual acuity. A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched the PubMed, EMBASE, Cochrane, and Web of Science databases for studies using PI compared with CHX in the IVI procedure. Statistical analysis was done using R software. Four studies encompassing 453,340 eyes were included. The pooled results showed no statistical differences in endophthalmitis rates [odds ratio (OR): 1.26; 95% confidence interval (CI): 0.53-3.00]. In those who received the CHX group, there was no decrease in the rates of culture-positive endophthalmitis (OR: 2.04; 95% CI: 0.76-5.47), and the pooled results revealed no statistical differences in the mean change in visual acuity between the CHX and PI groups at final follow-up [mean difference: -0.02; 95% CI: -0.40 to 0.36]. Significant heterogeneity was identified in the post-procedure endophthalmitis rate and culture-positive endophthalmitis rate. Despite finding a trend toward higher rates of endophthalmitis with CHX, there are no statistical differences in using PI compared with CHX. However, our results are limited due to high heterogeneity. PI remains the gold standard, and a widespread shift to CHX cannot be justified based on the findings of this analysis.
Cyclosporin A (CsA) is a drug used to prevent immune rejection in corneal transplantation. Most grafts performed today are endothelial grafts which are complicated with poor penetration of CsA into the endothelium due to...Cyclosporin A (CsA) is a drug used to prevent immune rejection in corneal transplantation. Most grafts performed today are endothelial grafts which are complicated with poor penetration of CsA into the endothelium due to its hydrophobicity. To improve CsA penetration into the corneal a new ocular formulation of CsA 2% with Miglyol was developed and is commercially available. The purpose of this pharmacokinetic study was to determine the concentrations of CsA in all layers of the cornea, in particular in the endothelium after topical administration of CsA 2%-Miglyol in rabbits. Sixteen rabbits were divided in 4 groups according to the time from the last instillation of CsA 2%-Miglyol to corneal sampling. Rabbit eyes received one drop of CsA twice a day for 5 days. Corneal tissue and plasma samples were collected at 2, 6, 12, and 24 h. CsA concentrations were measured using liquid chromatography-tandem mass spectrometry method. Maximum concentrations (Cmax) of CsA were obtained in corneal tissues within 2 h after the last instillation of CsA 2%-Miglyol, except in the endothelium (12 h). Cmax were 59.75 ± 12.09 ng/mg, 15.66 ± 4.31 ng/mg, 5.17 ± 0.88 ng/mg, and 2.65 ± 0.47 ng/mg for the epithelium, endothelium, anterior stroma and posterior stroma. CsA concentrations remained high over a 24-h in all corneal layers. The topical application of CsA 2%-Miglyol allowed a high concentration of CsA in the corneal endothelium. The good penetration of CsA into the endothelium suggests that this formulation can be effective to prevent endothelial graft rejection.
Vitamin E is renowned for its potent antioxidant properties, crucial for shielding cells against oxidative stress and damage. Deficiency in this vitamin can lead to various health issues, including neurodegenerative dise...Vitamin E is renowned for its potent antioxidant properties, crucial for shielding cells against oxidative stress and damage. Deficiency in this vitamin can lead to various health issues, including neurodegenerative diseases, due to its pivotal role in preserving cell membrane integrity and combating cellular oxidative damage. While its importance for overall health, including neurodegeneration, is acknowledged, the specific correlation between vitamin E deficiency and distinct ocular neurodegenerative disorders need to be further explored. This review delves into the molecular mechanisms of vitamin E in ocular neurodegenerative disorders; diabetic retinopathy, age-related macular degeneration, glaucoma, and cataracts, and emphasising the therapeutic implications drawn from existing evidence. Relationship between vitamin E and ocular neurodegenerative disorders is widely researched on, with its primary protective mechanisms attributed to its antioxidant and anti-inflammatory properties. However, studies on the supplementation of vitamin E among human subjects present mixed results, suggesting its complexities and variability depending on factors such as the specific disorder, disease stage, genetic differences, and form of vitamin E utilized. In conclusion, while vitamin E holds promise in mitigating ocular neurodegeneration through its antioxidant and anti-inflammatory properties, its supplementation's efficacy remains nuanced and context dependent. More research works are essential to elucidate its precise role and therapeutic potential in combating various ocular neurodegenerative disorders.