Outcomes of Post-Cataract Surgery Endophthalmitis Managed Without Microbial Cultures.

PURPOSE: To evaluate outcomes of eyes with post-cataract surgery endophthalmitis that were managed without microbial cultures. DESIGN: This retrospective, single-center comparative cohort study identified all cases of endophthalmitis after cataract surgery presenting between February 1, 2014, and November 1, 2022. SUBJECTS: All eyes presenting with presumed endophthalmitis requiring in-office treatment with intravitreal antibiotics and either a vitreous or aqueous tap were included. METHODS: Endophthalmitis cases were divided into the "culture group" if the vitreous or aqueous specimens were sent for microbiologic sampling or into the "no culture group" if an aqueous or vitreous tap was performed but not sent for microbiologic sampling. MAIN OUTCOME MEASURES: Best corrected visual acuity (VA) 12 months following endophthalmitis presentation, incidence of retinal detachment, and need for subsequent procedures. RESULTS: Of the 232 endophthalmitis cases identified, 196 (85%) were in the "culture group" and 36 (15%) were in the "no culture group". At endophthalmitis presentation, eyes in the "culture group" had a mean (SD) logMAR VA [Snellen Equivalent] of 2.14 (0.8) [20/2760] and mean (SD) logMAR VA in the "no culture group" was 1.93 (0.8) [20/1702] (p=0.185). At 12-month follow up, mean (SD) logMAR VA for the "culture group" was 0.80 (1.0) [20/126] and 0.41 (0.5) [20/50] in the "no culture group" (adjusted difference = 0.41, 95% CI = -0.043 - 0.857, p=0.076). Twenty of 196 (10%) eyes in the "culture group" developed secondary retinal detachments within 12 months of presentation compared to 0 in the "no culture group" (p=0.045). CONCLUSIONS: Eyes with endophthalmitis following cataract surgery managed without microbiologic cultures have similar visual outcomes to eyes managed with microbiologic cultures and may be less likely to develop secondary retinal detachments. This may be an acceptable strategy to manage endophthalmitis after cataract surgery when prompt access to a microbiologic facility is unavailable.

Retinal Tear and Retinal Detachment Following Cataract Surgery in Eyes with a Previous History of Treated Phakic Retinal Tears.

OBJECTIVE: To investigate the incidence and outcomes of retinal tear (RT) and retinal detachment (RD) after cataract extraction in patients with a history of previous phakic RT. DESIGN: Retrospective case series. SUBJECTS: Phakic eyes with RT that were successfully treated with laser photocoagulation or cryotherapy and subsequently underwent cataract surgery. METHOD: A retrospective review of phakic eyes treated for RTs between April 1, 2012 and May 31, 2023 was performed. Exclusions included prior vitreoretinal surgery before cataract removal and follow-up of less than 6 months post-cataract surgery. MAIN OUTCOME MEASURES: The incidence of RTs and RDs after cataract surgery, along with visual and anatomic outcomes. RESULTS: Of 12,109 phakic eyes treated for RTs, 1039 (8.6%) eyes underwent cataract surgery. After exclusions, 713 eyes of 660 patients were studied. The mean (standard deviation, SD) follow-up period post-cataract surgery was 34.8 (24.6) months with a median of 239 and 246 days to a new RT or RD development. The overall incidence for diagnosis of post-cataract surgery RT and RD was 7.3% (52/713) (2.9% and 4.3%, respectively), with a one-year incidence of 5.6% (2.2% and 3.4%, respectively). Multivariable regression analysis identified a higher risk of RT/RD among younger individuals (odds ratio [OR] 1.034; 95% confidence interval [CI] 1.004-1.065, P=0.028), males (OR 2.058; 95% CI 1.110-3.816, P=0.022), and those with shorter interval between laser treatment and cataract surgery (OR 1.001; 95% CI 1.001-1.001, P=0.011). Single surgery anatomic success for the RD repair was achieved in 25 eyes (80.6%) at 3 months, with a 100% final reattachment rate. The median final logMAR visual acuity was 0.10 (20/25) for RT, showing no significant change from post-cataract surgery, and 0.18 (20/30) for RD, a significant worsening from after cataract surgery. CONCLUSION: One year post-cataract surgery, the rate of diagnosed RT and RD in patients with previously treated RTs was relatively high, occurring in nearly 1 in 18 eyes. Higher risk was noted among younger individuals, males, and patients with a shorter interval between initial treatment for RT and cataract surgery. RD repair achieved good anatomical results, but vision declined.

SUPRACHOROIDAL TRIAMCINOLONE ACETONIDE FOR REFRACTORY POSTOPERATIVE CYSTOID MACULAR EDEMA.

PURPOSE: To investigate outcomes of suprachoroidal triamcinolone acetonide (XIPERE, Bausch + Lomb) for the treatment of refractory postoperative cystoid macular edema. METHODS: Medical records of patients receiving suprachoroidal triamcinolone acetonide for postoperative cystoid macular edema were reviewed. Primary outcomes were visual acuity and central foveal thickness. RESULTS: A total of 32 eyes from 32 patients with a median (interquartile range) follow-up duration of 6 (2-7) months and 1 (1-2) suprachoroidal triamcinolone acetonide injection were included; 19 (59.4%) had a history of vitrectomy. The median (interquartile range) central foveal thickness decreased from 492 (379-629) µm to 267 (187-388) µm at 1 month (P < 0.001), 362 (218-521) µm at 3 months (P = 0.005), and 339 (206-514) µm at the final visit (P < 0.001). The median logarithm of the minimal angle of resolution visual acuity improved from 0.65 (0.48-0.97, 20/89) at baseline to 0.54 (0.35-0.88, 20/69) (P = 0.058) at 1 month, 0.54 (0.33-0.84, 20/69) at 3 months (P = 0.121), and 0.60 (0.33-0.88, 20/80) at the final visit (P = 0.021). Vitrectomized eyes had similar findings. Six eyes (18.8%) developed elevated intraocular pressure (>24 mmHg) (range: 25-49 mmHg) with a median intraocular pressure elevation of 13.5 mmHg compared with baseline, and all had prior glaucoma or ocular hypertension. CONCLUSION: Suprachoroidal triamcinolone acetonide reduced macular edema and improved vision in refractory postoperative cystoid macular edema, including vitrectomized eyes. Intraocular pressure should be monitored, especially in those with a history of glaucoma or ocular hypertension.

A multi-center analysis of visual outcomes following open globe injury.

The purpose of this study was to examine how demographics, etiology, and clinical examination findings are related to visual outcomes in subjects with open globe injury (OGI) across a large and generalizable sample. A retrospective cohort analysis was performed using data collected from the electronic medical records of four tertiary university centers for subjects with OGI presenting from 2018 to 2021. Demographic information, injury mechanisms, clinical exam findings, visual acuity (VA) at presentation and most recent follow-up were recorded. In subjects with bilateral OGIs, only right eyes were included. A modified ocular trauma score (OTS) using presenting VA, the presence of perforating injury, OGI, and afferent pupillary defect was calculated. The risk of subjects' demographic characteristics, ocular trauma etiology, clinical findings and modified OTS on the presence of monocular blindness at follow-up were assessed using univariable and multivariable regression models. 1426 eyes were identified. The mean age was 48.3 years (SD: ± 22.4 years) and the majority of subjects were men (N = 1069, 75.0%). Univariable analysis demonstrated that subjects of Black race were 66% (OR: 1.66 [1.25-2.20]; P < 0.001) more likely to have monocular blindness relative to White race at follow-up. OTS Class 1 was the strongest predictor of blindness (OR: 38.35 [21.33-68.93]; P < 0.001). Based on multivariable analysis, lower OTS category (OTS Class 1 OR: 23.88 [16.44-45.85]; P < 0.001) moderately predicted visual outcomes (R2 = 0.275, P < 0.001). OGI has many risks of poor visual outcome across patient groups that vary by demographic category, mechanism of injury, and clinical presentation. Our findings validate that a modified OTS remains a strong predictor of visual prognosis following OGI in a large and generalizable sample.

Screen failures in clinical trials in retina.

PURPOSE: Disparities in clinical trials are a major problem due to significant underrepresentation of certain gender, racial and ethnic groups. Several factors including stringent eligibility criteria and recruitment strategies hinder our understanding of retinal disease. Thus, we aimed to study the various reasons of screen failures and specific patient and study characteristics among screen failures. DESIGN: This is a cross-sectional retrospective study METHODS: Screening data of 87 trials from 6 centers were analyzed. Study characteristics (disease studied, phase of trial, route of drug administration) and patient demographics (age, gender, race, ethnicity, and employment status) were compared among different causes of screen failures. Screen failures were broadly classified into six categories: exclusion due to vision-based criteria, exclusion due to imaging findings, exclusion due to other factors, patient-related criteria, physician related criteria and miscellaneous. Descriptive statistics, Pearson Chi-square test and ANOVA were used for statistical analysis. MAIN OUTCOME MEASURES: Determine the prevalence of various reasons for screen failures in multiple trials and its trend among different study and patient characteristics. RESULTS: Among 87 trials and 962 patients, 465(48.2%) patients were successfully randomized and 497(51.8%) patients were classified as screen failures. The trials were conducted for various retinal diseases. Mean age was 76.50 ±10.45 years and 59.4% were females. Predominantly whites(93.4%) and unemployed/retired patients(66.6%) were screened. Of the 497 screen failures, most were due to patients not meeting inclusion criteria of imaging findings (n=221[44.5%]) followed by inclusion of vision-based criteria (n=73 [14.7%]), exclusion due to other factors (n=75[15.1%]), patient-related (n=34[6.8%]), physician-related (n=28[5.6%]) and miscellaneous reasons (n= 39[17.8%]). Reason for screen failure was not available for 27(5.4%) patients. A higher proportion of patients screened for surgical trials (15%) declined to participate in the study compared to non-invasive trials involving topical drugs and photobiomodulation (0%).(p=0.02) CONCLUSION: Patients not meeting the imaging and vision-cased criteria were the most common reasons for screen failures. Whites and unemployed patients predominantly participated in clinical trials. Patients are more inclined to continue participation in non-invasive clinical trials compared to surgical trials. Better recruitment strategies and careful consideration of study criteria can aid in decreasing the rate of screen failures.

Conversion to faricimab after prior anti-vascular endothelial growth factor therapy for persistent diabetic macular oedema.

BACKGROUND: To assess the anatomical and functional outcomes in eyes with persistent diabetic macular oedema (pDME) on chronic anti-vascular endothelial growth factor therapy switched to intravitreal faricimab. METHODS: Patients with pDME on chronic anti-vascular endothelial growth factor therapy that were switched to faricimab and received at least three injections at our institution between April 2022 and May 2023 were included in this study. Patients were excluded if they had complete response to previous treatment but were switched to extend treatment intervals if they had steroid or laser treatment for DME within 6 months prior to switch. Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT) and Snellen visual acuity (VA) were obtained before and after three intravitreal faricimab injections. Generalised estimating equations were used to analyse the change in CFT and VA. RESULT: During the study period, 69 eyes of 53 patients met inclusion criteria. The mean age was 68.6±9.0 years. The mean number of injections prior to switch was 18.1±16.0. Pre-switch mean logarithm of the minimal angle of resolution VA was 0.40±0.30 (Snellen equivalent 20/50) and 0.38±0.27 (Snellen equivalent 20/48) after three faricimab injections (p=0.397). Mean CFT improved from 380±155 microns to 323±147 microns (p<0.001). No ophthalmic or systemic adverse events occurred during the study period. CONCLUSIONS: Intravitreal faricimab can improve anatomic outcomes while maintaining visual acuity in eyes with pDME previously treated with anti-VEGF therapy.

ChatGPT enters the room: what it means for patient counseling, physician education, academics, and disease management.

PURPOSE OF REVIEW: This review seeks to provide a summary of the most recent research findings regarding the utilization of ChatGPT, an artificial intelligence (AI)-powered chatbot, in the field of ophthalmology in addition to exploring the limitations and ethical considerations associated with its application. RECENT FINDINGS: ChatGPT has gained widespread recognition and demonstrated potential in enhancing patient and physician education, boosting research productivity, and streamlining administrative tasks. In various studies examining its utility in ophthalmology, ChatGPT has exhibited fair to good accuracy, with its most recent iteration showcasing superior performance in providing ophthalmic recommendations across various ophthalmic disorders such as corneal diseases, orbital disorders, vitreoretinal diseases, uveitis, neuro-ophthalmology, and glaucoma. This proves beneficial for patients in accessing information and aids physicians in triaging as well as formulating differential diagnoses. Despite such benefits, ChatGPT has limitations that require acknowledgment including the potential risk of offering inaccurate or harmful information, dependence on outdated data, the necessity for a high level of education for data comprehension, and concerns regarding patient privacy and ethical considerations within the research domain. SUMMARY: ChatGPT is a promising new tool that could contribute to ophthalmic healthcare education and research, potentially reducing work burdens. However, its current limitations necessitate a complementary role with human expert oversight.

Clinical Outcomes of Faricimab in Patients with Previously Treated Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the anatomic and functional outcomes in eyes with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF therapy in response to intravitreal faricimab. DESIGN: Retrospective, interventional, consecutive case series. SUBJECTS: Patients with previously treated nAMD who received ≥ 4 consecutive injections of faricimab were included. The study period was from March through November 2022. METHODS: Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT), maximum fibrovascular pigment epithelial detachment (fvPED) height, and Snellen visual acuity (VA) were obtained. Generalized estimating equations were used to analyze the change in CFT, maximum fvPED height, and logarithm of the minimum angle of resolution VA. MAIN OUTCOME MEASURES: Change in CFT, maximum fvPED height, and Snellen VA before faricimab and after ≥ 4 faricimab intravitreal injections. RESULTS: During the study period, 218 eyes of 191 patients met inclusion criteria. Mean age was 79.9 (range, 70.6-89.2) years. The mean number of intravitreal anti-VEGF injections received before faricimab was 34.2 (range, 6.4-62). The following results were found after ≥ 4 faricimab injections. Mean logarithm of the minimum angle of resolution VA before switching to faricimab was 0.58 (Snellen VA ∼20/76; range, 20/22-20/264) and was 0.55 (Snellen VA ∼20/71; range, 20/21-20/235; P = 0.20) after switching. Mean maximum fvPED height was 195.0 (range, 50.2-339.8) µm before switching to faricimab and improved to 165.0 (range, 33.6-296.4; P < 0.001) µm after switching. Mean CFT was 354.8 (range, 184.7-524.9) µm before switching to faricimab and improved to 306.6 (range, 144.4-468.8; P < 0.001) after switching. The proportion of eyes with intraretinal fluid was 36.7% (80/218 eyes) before switching, and decreased to 24.8% (54/218 eyes, P < 0.001) after switching. The proportion of eyes with subretinal fluid was 53.2% (116/218 eyes) before switching and decreased to 26.6% (58/218 eyes, P < 0.001) after switching. CONCLUSIONS: Intravitreal faricimab may improve anatomic outcomes in patients with previously treated nAMD, while maintaining VA in the short-term. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Incidence and Outcomes of Recurrent Retinal Detachment after Cataract Surgery in Eyes with Prior Retinal Detachment Repair.

OBJECTIVE: To investigate the incidence and outcomes of recurrent retinal detachment (RD) after cataract extraction (CE). DESIGN: Retrospective case series. SUBJECTS: Phakic eyes with RD that were successfully repaired with pneumatic retinopexy (PR), scleral buckle (SB), pars plana vitrectomy (PPV), or combined PPV/SB and subsequently underwent cataract surgery. METHODS: A retrospective review of phakic eyes that underwent successful RD repair followed by subsequent cataract surgery between April 2012 and January 2023 was performed. Patients with multiple RD surgeries before CE and those with silicone oil tamponade before cataract surgery were excluded. Eyes that redetached were matched 1:2 with eyes that did not redetach after cataract surgery. MAIN OUTCOME MEASURES: Incidence of redetachment after cataract surgery as well as visual and anatomic outcomes at 6 months after first redetachment and at the final visit. RESULTS: Of 4833 phakic eyes at the time of initial RD, 1893 patients (39.2%) underwent cataract surgery. After applying exclusion criteria, 763 patients were included. The mean (standard deviation) duration of follow-up was 48.4 (29.1) months. The overall incidence of retinal redetachment after cataract surgery was 2.5% (19/763 eyes). The rate of redetachment based on the type of initial RD repair was 9.1% (1/11), 5.3% (2/38), 2.8% (9/317), and 1.8% (7/397) for PR, SB, PPV, and combined PPV/SB, respectively (P = 0.24). The median (interquartile range [IQR]; range) duration between the cataract surgery and first redetachment was 301 (104-1222; 8-2760) days. Single surgery anatomic success for the RD repair after cataract surgery was achieved in 17 eyes (89.5%) at 3 months and 14 eyes (73.7%) at 6 months and at the final visit. Final anatomic success rate for reattachment was 100% (19/19). The median (IQR) logarithm of the minimal angle of resolution visual acuity (VA) at the final visit was 1.00 (0.18-2.00, Snellen equivalent, 20/200) with significant worsening compared with vision after cataract surgery (0.18 [0.10-0.48], 20/30) (P = 0.001). CONCLUSION: Recurrent RD was not uncommon in patients with a prior history of RD repair after CE. Reoperation resulted in relatively favorable anatomic success but there were declines in VA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.

Intrastromal versus subconjunctival injection of mesenchymal stem/stromal cells for promoting corneal repair.

PURPOSE: Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model. METHODS: Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and immunostaining. RESULTS: hBM-MSC injection successfully healed epithelial defects regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced corneal opacity and neovascularization and improved ASOCT parameters compared to subconjunctival injection or no treatment (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by in vivo (up to 2 weeks) and in vitro assessments (up to 4 weeks). CONCLUSIONS: Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.

Cellular senescence implication in mustard keratopathy.

Mustard agents are vesicants that were used in warfare multiple times. They are potent alkylating agents that activate cellular pathways of apoptosis, increase oxidative stress, and induce inflammation. Eyes are particularly susceptible to mustard exposure with a wide range of ocular surface damage. Three main categories of mustard-related eye injuries are acute, chronic, and delayed-onset manifestations. Mustard keratopathy (MK) is a known complication characterized by corneal opacification, ulceration, thinning, and neovascularization that can lead to severe vision loss and discomfort. Recently, a few reports demonstrated the role of senescence induction as a new pathological mechanism in mustard-related injuries that could affect wound healing. We ran the first murine model of delayed-onset MK and nitrogen mustard-induced senescence, evaluating the pathological signs of senescence in the cornea using beta-galactosidase staining. Our results suggest that nitrogen mustard exposure causes senescence in the corneal cells, which could be the underlying mechanism for chronic and late-onset ocular surface damage. We also found a significant correlation between the percentage of positive beta-galactosidase staining and the degree of fibrosis in the cornea. This provides valuable insight into the possible role of anti-senescence drugs in the near future for accelerating corneal healing and restricting fibrosis in patients with mustard keratopathy.

Appropriateness and Readability of ChatGPT-4-Generated Responses for Surgical Treatment of Retinal Diseases.

OBJECTIVE: To evaluate the appropriateness and readability of the medical knowledge provided by ChatGPT-4, an artificial intelligence-powered conversational search engine, regarding common vitreoretinal surgeries for retinal detachments (RDs), macular holes (MHs), and epiretinal membranes (ERMs). DESIGN: Retrospective cross-sectional study. SUBJECTS: This study did not involve any human participants. METHODS: We created lists of common questions about the definition, prevalence, visual impact, diagnostic methods, surgical and nonsurgical treatment options, postoperative information, surgery-related complications, and visual prognosis of RD, MH, and ERM, and asked each question 3 times on the online ChatGPT-4 platform. The data for this cross-sectional study were recorded on April 25, 2023. Two independent retina specialists graded the appropriateness of the responses. Readability was assessed using Readable, an online readability tool. MAIN OUTCOME MEASURES: The "appropriateness" and "readability" of the answers generated by ChatGPT-4 bot. RESULTS: Responses were consistently appropriate in 84.6% (33/39), 92% (23/25), and 91.7% (22/24) of the questions related to RD, MH, and ERM, respectively. Answers were inappropriate at least once in 5.1% (2/39), 8% (2/25), and 8.3% (2/24) of the respective questions. The average Flesch Kincaid Grade Level and Flesch Reading Ease Score were 14.1 ± 2.6 and 32.3 ± 10.8 for RD, 14 ± 1.3 and 34.4 ± 7.7 for MH, and 14.8 ± 1.3 and 28.1 ± 7.5 for ERM. These scores indicate that the answers are difficult or very difficult to read for the average lay person and college graduation would be required to understand the material. CONCLUSIONS: Most of the answers provided by ChatGPT-4 were consistently appropriate. However, ChatGPT and other natural language models in their current form are not a source of factual information. Improving the credibility and readability of responses, especially in specialized fields, such as medicine, is a critical focus of research. Patients, physicians, and laypersons should be advised of the limitations of these tools for eye- and health-related counseling. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

VITRECTOMY FOR VITREOUS HEMORRHAGE ASSOCIATED WITH RETINAL VEIN OCCLUSION: Visual Outcomes, Prognostic Factors, and Sequelae.

PURPOSE: To report the outcomes of pars plana vitrectomy for vitreous hemorrhage (VH) associated with retinal vein occlusion and to identify prognostic indicators. METHODS: Interventional, retrospective consecutive case series between 2015 and 2021. RESULTS: The study included 138 eyes of 138 patients (64 female and 74 male); 81 patients had branch retinal vein occlusion and 57 had central retinal vein occlusion. The mean age was 69.8 years. The mean duration between the diagnosis of VH and surgery was 79.6 ± 115.3 (range, 1-572) days. The mean follow-up was 27.2 months. The logarithm of the minimum angle of resolution visual acuity significantly improved from 1.95 ± 0.72 (Snellen equivalent, 20/1782) to 0.99 ± 0.87 (20/195) at 6 months and to 1.06 ± 0.96 (20/230) at the final visit (both P < 0.001). The visual acuity at 6 months improved by three or more lines in 103 eyes (75%). Postoperative complications during follow-up included recurrent VH in 16 eyes (12%) (of which 8 eyes underwent reoperations), rhegmatogenous retinal detachment in six eyes (4%), and new neovascular glaucoma in three eyes (2%). Worse final visual acuity was significantly associated with older age ( P = 0.007), concurrent neovascular glaucoma ( P < 0.001), central retinal vein occlusion ( P < 0.001), worse preoperative visual acuity ( P < 0.001), postoperative new neovascular glaucoma ( P = 0.021), and postoperative retinal detachment ( P < 0.001). The duration of VH was not associated with visual outcomes ( P = 0.684). Preoperative antivascular endothelial growth factor injections and tamponade did not prevent postoperative recurrent VH. CONCLUSION: Pars plana vitrectomy is effective for VH associated with retinal vein occlusion, regardless of the duration of hemorrhage. However, pre-existing risk factors and postoperative sequelae may limit visual recovery.

Extracellular-Vesicle-Based Therapeutics in Neuro-Ophthalmic Disorders.

Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown promise in promoting nerve regeneration in ocular diseases. In particular, EVs derived from MSCs have been demonstrated to promote axonal regeneration and functional recovery in various animal models of optic nerve injury and glaucoma. EVs contain various neurotrophic factors and cytokines that can enhance neuronal survival and regeneration, promote angiogenesis, and modulate inflammation in the retina and optic nerve. Additionally, in experimental models, the application of EVs as a delivery platform for therapeutic molecules has revealed great promise in the treatment of ocular disorders. However, the clinical translation of EV-based therapies faces several challenges, and further preclinical and clinical studies are needed to fully explore the therapeutic potential of EVs in ocular disorders and to address the challenges for their successful clinical translation. In this review, we will provide an overview of different types of EVs and their cargo, as well as the techniques used for their isolation and characterization. We will then review the preclinical and clinical studies that have explored the role of EVs in the treatment of ocular disorders, highlighting their therapeutic potential and the challenges that need to be addressed for their clinical translation. Finally, we will discuss the future directions of EV-based therapeutics in ocular disorders. Overall, this review aims to provide a comprehensive overview of the current state of the art of EV-based therapeutics in ophthalmic disorders, with a focus on their potential for nerve regeneration in ocular diseases.

Mustard Gas-Induced Ocular Surface Disorders: An Update on the Pathogenesis, Clinical Manifestations, and Management.

PURPOSE: Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries. METHODS: Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye." RESULTS: Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging. CONCLUSIONS: MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease.

Applications of mesenchymal stem cells in ocular surface diseases: sources and routes of delivery.

INTRODUCTION: Mesenchymal stem cells (MSCs) are novel, promising agents for treating ocular surface disorders. MSCs can be isolated from several tissues and delivered by local or systemic routes. They produce several trophic factors and cytokines, which affect immunomodulatory, transdifferentiating, angiogenic, and pro-survival pathways in their local microenvironment via paracrine secretion. Moreover, they exert their therapeutic effect through a contact-dependent manner. AREAS COVERED: In this review, we discuss the characteristics, sources, delivery methods, and applications of MSCs in ocular surface disorders. We also explore the potential application of MSCs to inhibit senescence at the ocular surface. EXPERT OPINION: Therapeutic application of MSCs in ocular surface disorders are currently under investigation. One major research area is corneal epitheliopathies, including chemical or thermal burns, limbal stem cell deficiency, neurotrophic keratopathy, and infectious keratitis. MSCs can promote corneal epithelial repair and prevent visually devastating sequelae of non-healing wounds. However, the optimal dosages and delivery routes have yet to be determined and further clinical trials are needed to address these fundamental questions.