Ocular Surface Research Articles

Toxicity of nuclear-localized GFP in reporter mice

Various techniques using fluorescent reporter probes have been developed, such as GFP transgenic mouse lines that are used to detect spatial–temporal expression levels of genes. Although GFP expression is largely considered non-toxic, recent reports have indicated that under certain conditions GFP can display cellular toxicity. We hereby report the nuclear toxicity of H2B-GFP using a K14 specific Tet-on reporter mouse system. Using this system, GFP accumulates in the nucleus of all K14 expressing cells, such as the ocular surface epithelia and ocular adnexa. Expression of high levels of nuclear GFP during embryonic stages led to an eye open-at-birth (EOB) phenotype and abnormal ocular adnexa development and during adult and aging stages showed notable toxicity to ocular tissues. Other tissues, such as skin, also presented multiple defects associated with H2B-GFP expression. This toxicity was found to be concentration dependent, with homozygous mice presenting extremely high toxicity, while heterozygous mice presented limited toxicity. Upon induction, the accumulation of H2B-GFP in the nucleus of homozygous mice led to apoptosis within 2 weeks. This study therefore shows that although the use of nuclear GFP reporter mice is a valuable tool, at high levels, nuclear GFP can be toxic, leading to cell death and affecting tissue function.

A Selective Melatonin 2 Receptor Agonist, IIK7, Relieves Blue Light-Induced Corneal Damage by Modulating the Process of Autophagy and Apoptosis

This study aims to investigate the effect of the selective MT2 receptor agonist, IIK7, on corneal autophagy and apoptosis, aiming to reduce corneal epithelial damage and inflammation from blue light exposure in mice. Eight-week-old C57BL/6 mice were divided into BL-exposed (BL) and BL-exposed with IIK7 treatment (BL + IIK7 group). Mice underwent blue light exposure (410 nm, 100 J) twice daily with assessments at baseline and on days 3, 7, and 14. Corneal samples were analyzed for MT2 receptor expression, autophagy markers (LC3-II and p62), and apoptosis indicators (BAX expression and TUNEL assay). Then, mice were assigned to normal control, BL, and BL + IIK7. Ocular surface parameters, including corneal fluorescein staining scores, tear volume, and tear film break-up time, were evaluated on days 7 and 14. On day 14, reactive oxygen species (ROS) levels and CD4+ IFN-γ+ T cells percentages were measured. The BL group exhibited higher LC3-II and p62 expression, while the BL + IIK7 group showed reduced expression (p < 0.05). The TUNEL assay showed reduced apoptosis in the BL + IIK7 group compared to the BL group. ROS levels were lower in the BL + IIK7 group. The BL + IIK7 group showed improved ocular surface parameters, including decreased corneal fluorescein staining and increased tear volume. The percentages of CD4+ IFN-γ+ T cells indicated reduced inflammatory responses in the BL + IIK7 group. The MT2 receptor agonist IIK7 regulates corneal autophagy and apoptosis, reducing corneal epithelial damage and inflammation from blue light exposure.

Comparative evaluation of autologous tissue-engineered ocular and oral mucosal tissue grafts- a prospective randomized controlled trial

BackgroundBilateral ocular surface disease resulting from Stevens Johnson Syndrome (SJS) and chemical injuries are visually debilitating and difficult to treat. Ocular surface reconstruction by various means has been reported with variable results. This study addresses an unmet need for a prospective clinical trial comparing the outcomes of transplanting autologous oral and conjunctival epithelial cell constructs on human amniotic membrane by ex vivo tissue engineering.MethodsA prospective, randomized controlled clinical trial was prospectively applied for registration, with the clinical trial registry of India (CTRI), with the approval of the Institute Ethics Committee number IEC/NP-99/11.04.2014 and CTRI No. REF/2018/10/021791, the study also registered with the WHO-recognized trial registry, International Standard Randomised Controlled Trial Number (ISRCTN) registration reference number 45780. The study was conducted to compare clinical outcomes of two different tissue-engineered cell grafts, Cultivated Oral Mucosal Epithelial Transplantation (COMET) and Conjunctival Cultivated Epithelial Transplantation (CCET) for ocular surface reconstruction in patients with bilateral ocular surface disease due to Stevens-Johnson Syndrome or chemical injuries. Fifty patients were enrolled and randomized to either the COMET or CCET group. A uniform pre-op and post-op protocol using standard medications was followed for all patients Parameters assessed at baseline, day 1, 1 week, 2 weeks, 1 month, 2 months, 3 months and 6 months postoperatively included patient comfort, best corrected visual acuity (BCVA), ocular surface status and corneal clarity. The efficacy was measured in terms of improvement of vision, reduction in vascularization, symblepharon and corneal clarity.ResultsIn the study, 50 patients (50 eyes; mean ages of 29 ± 15.86 years and 26.36 ± 10.85 years, respectively; range, 12–65 years) were enrolled, with 25 patients each in the COMET and CCET groups. Out of them, 36% were female and 64% were male; the causes were Steven Johnson syndrome (48), and chemical injury (2). Mean pre-operative BCVA was log MAR 1.73 ± 0.57 for COMET and 1.99 ± 0.33 for the CCET group. Pre-operatively all 50 enrolled patients had opaque corneas pre-operatively, symblepharon that extended to the cornea categorised as grade 3 and corneal vascularization that went beyond the pupil’s boundary into the central zone encluaching on the visual axis. The minimal follow-up time was six months. Following surgery postoperatively, the BCVA considerably improved in the COMET group by 1.51 ± 0.58 compared to the CCET group by 1.91 ± 0.33 at 3 months. BCVA at 6 months was 1.73 ± 0.56 in the COMET group and 1.99 ± 0.31 in the CCET group, which is not statistically significant and comparable to the BCVA before surgery. The corneal clarity was significantly improved in COMET group 25 eye (100%) at 2 month, 3month and 19 eye (76%), 6eye (24%) at 6 months when compared to CCET group 15 eye improved (60%), 9 eyes (36%) not improved and one eye with opaque cornea (4%) at 2 months. 22 eye (88%) had not improved, 2 eye (8%) opaque cornea and 1 eye (4%) improved at 3 months. At 6 months 21 eye (84%) were not improved, 4 eye (16%) eye became opaqued at 6 months. Compared to preoperative conditions, both groups had improved corneal clarity significantly (p > 0.005). Of the 50 patients with grade 3 symblepharon extended to the cornea, were completely resolved 19 (76%) in COMET group when compared to CCET group 22 eye (88%) not improved. Similarly, 19 eye (76%) had a improvement in corneal vascularization when compared to the CCET group not improved 25 eye (100%) at 6months. No adverse event was observed in any of either group during the follow up periods.ConclusionBoth cell types are effective to restore the ocular surface integrity in bilateral ocular surface disease. Whereas COMET is safe and efficacious in terms of improvement of clinical parameters including, BCVA, corneal clarity, reduction in vascularization and preventing the recurrence of symblepharon postoperatively 3months and 6 months. In addition, the CCET group maintained the stability of the ocular surface and had improvement in corneal clarity and a decrease in vascularization at 3 months compared to their pre-operative characteristics.

Targeting Nrf2 signaling in dry eye.

Dry eye, the most common ocular surface disease, can cause ocular surface tissue damage and discomfort symptoms and seriously affect people's quality of life. The etiology of dry eye is diverse, and its pathogenesis is complex. The oxidative stress reaction is considered to be among the important factors in the pathogenesis of dry eye. Therefore, activating the antioxidant system has a potential therapeutic effect on dry eye. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is considered the most important antioxidant pathway in the body. The activation of the Nrf2 signaling pathway and its interaction with other pathways are important mechanisms to prevent the occurrence and development of dry eye. This review describes the structure and function of Nrf2, summarizes the changes in the oxidative stress response in dry eye, focuses on the potential mechanism of the Nrf2 signaling pathway in the treatment of dry eye, and, finally, summarizes the drugs that activate the Nrf2 signaling pathway in the treatment of dry eye.

Conjunctival and Corneal Endothelium Profile in a Sample of Healthy Electronic Cigarette Smokers

Objective: Though e-cigarette is thought of as a healthy alternative way of smoking, the unknown nicotine concentration level and chemical compounds from the aerosol mist and flavourings are potentially harmful and may exert irritation or damage to the ocular surface. Thus, a cross-sectional study was conducted to identify the conjunctival and corneal endothelium profile among healthy e-cigarette smokers, and the relationship between smoking behaviour with the conjunctival and corneal endothelium profile. Material and Methods: Seventeen healthy e-cigarette smokers and 17 non-smokers were recruited for this study where their palpebral redness, bulbar redness, limbal redness, conjunctival roughness, central corneal thickness, endothelial cell density, and coefficient of variation of endothelium cell area were assessed using slit lamp biomicroscope and specular microscope. Results: There was a non-significant, higher mean rank observed in the total palpebral redness, total bulbar redness, total limbal redness, total conjunctival roughness, central corneal thickness, endothelial cell density, and coefficient of variation of the endothelium cell area in e-cigarette smokers compared to non-smokers (p-value>0.05). Only smoking frequency and total palpebral redness showed a statistically significant, positive, and fair correlation (r=0.349, p-value=0.043), while no other smoking behaviour showed a significant correlation (p-value<0.05). Conclusion: The use of e-cigarettes showed no significant impact on the conjunctival and corneal profile among the users, but further research with comprehensive evaluation is required in a larger sample size of more established e-cigarette smoking profiles.

Microvascular alterations of the ocular surface and retina in connective tissue disease-related interstitial lung disease.

To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease (CTD-ILD) and healthy controls (HCs) by optical coherence tomography angiography (OCTA) and to investigate the changes in microvascular density in abnormal eyes. For a retrospective case-control study, a total of 16 patients (32 eyes) diagnosed with CTD-ILD were selected as the ILD group. The 16 healthy volunteers with 32 eyes, matched in terms of age and sex with the patients, were recruited as control group. The macular retina's superficial retinal layer (SRL) and deep retinal layer (DRL) were examined and scanned using OCTA in each individual eye. The densities of retinal microvascular (MIR), macrovascular (MAR), and total microvascular (TMI) were calculated and compared. Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods: central annuli segmentation method (C1-C6), hemispheric segmentation method [uperior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and Early Treatment Diabetic Retinopathy Study (ETDRS) methods [superior (S), inferior (I), left (L), and right (R)]. The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis. The OCTA data demonstrated a statistically significant difference (P<0.05) in macular retinal microvessel density between the two groups. Specifically, in the SRL and DRL analyses, the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group (P<0.05). Furthermore, using the hemispheric segmentation method, the ILD group showed notable reductions in SL, SR, and IL in the superficial retina (P<0.05), as well as marked decreases in SL and IR in the deep retina (P<0.05). Similarly, when employing the ETDRS method, the ILD group displayed substantial drops in superficial retinal S and I (P<0.05), along with notable reductions in deep retinal L, I, and R (P<0.05). In the central annuli segmentation method, the ILD group exhibited a significant decrease in the superficial retinal C2-4 region (P<0.05), whereas the deep retina showed a notable reduction in the C3-5 region (P<0.05). Additionally, there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR. Furthermore, there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI (P<0.001). Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group. Conversely, their fundus retinal microvascular density is significantly lower. Furthermore, CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group. The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases, thereby enhancing disease management.

Bioengineered Human Limbal Stem Cell–Derived Epithelial Sheets for Ocular Surface Reconstruction

Bioengineered Human Limbal Stem Cell–Derived Epithelial Sheets for Ocular Surface Reconstruction

A limbal stem cell deficiency murine model with residual limbal stem cells.

Bilateral limbal stem cell deficiency (LSCD) is a significant cause of corneal blindness and is more difficult to treat, as compared with unilateral LSCD because no source of autologous limbal stem cells (LSCs) remains in these patients. Thus, bilateral patients could be candidates for treatment with allogeneic LSC transplants that require long-term systemic immunosuppression therapy. Thus, if possible, for the correct candidates, using autologous LSCs could be a preferred treatment. Recent in vivo laser confocal microscopic examination of the ocular surface in situ , combined with impression cytology, has indicated that some patients diagnosed with a complete bilateral LSCD possess residual LSCs. However, it remains unknown whether these residual LSCs still have stem cell potential due to the lack of animal models that mimic this pathology. The goal of the current study is to make a complete LSCD model that possesses evidence of residual LSCs. We induced complete LSCD in mice using two methods: (1) removed the corneal epithelium and the epithelial basement membrane using a rotating burr, and (2) removed the corneal epithelium using 20% ethanol but retained an intact epithelial basement membrane. A complete LSCD was defined by a lack of CK12-positive corneal epithelial cells and the presence of infiltrating CK19-positive conjunctival epithelial cells. Corneas were examined for wound closure, corneal opacity, LSC exhaustion, and inflammation. We observed that complete LSCD mice without an intact epithelial basement membrane resulted in few residual LSCs. By contrast, complete LSCD mice that retained the epithelial basement membrane were accompanied by a reduced inflammatory response plus a significant number of residual LSCs. This model will allow future studies to determine the function of residual LSCs in complete LSCD.

Axis "microbiota – gut – eye": a review

Every organ in the human body has its own microbiota, and the eye, a complex multi-component organ, is no exception. Due to the limitations of traditional methods, detailed study of the ocular microbiome began only in 2010 as part of the Eye Microbiome Project, when advances in research methods made it possible to obtain detailed data, although there had been debate previously about whether microorganisms were even able to attach to the ocular surface due to the layers of the tear film, which have antibacterial properties. The cornea, conjunctiva, lacrimal glands and tear film, meibomian glands and microbiome form the microenvironment of the ocular surface, interacting together and resisting irritants, allergens and pathogens. Homeostasis of the ocular microbiota is critical for maintaining the health of the visual organ. Most microorganisms are found on the cornea and conjunctiva, and modern research methods, including 16S rRNA sequencing, have allowed us to establish the "core" of the ocular surface microbiota, identifying the most common types: Staphylococcus, Corynebacterium, Propionibacterium, and Streptococcus, although the exact composition of the “core” remains debatable. Many factors can influence the composition of the microbiome, including age, contact lens wear, ophthalmic medications, and antibiotics. Like the microbiome of many other organs, the ocular surface microbiome is influenced by the gut microbiome: this relationship has been called the "microbiota – gut – eye" axis. Within the "gut – eye" axis, healthy gut microbiota produce short-chain fatty acids, indoles, polyamines, and other substances that have a beneficial effect on the immune system and retinal health. The state of dysbiosis leads to disruption of homeostasis, and the increasing inflammatory reaction can contribute to damage to the optic nerve and progression of eye disease. Some ophthalmologic diseases, such as diabetic retinopathy, age-related macular degradation, choroidal neovascularization, uveitis, primary open-angle glaucoma, Sjogren's syndrome, dry eye syndrome are associated with dysbiosis of the intestinal microbial composition. Correction of intestinal dysbiosis using various methods can lead to a decrease in the risk of eye diseases, although additional research is needed to discover new methods for treating ophthalmologic pathologies along the "microbiota – gut – eye" axis.

Outcomes of sclerokeratoplasty in severe ocular surface disease

Sclerocorneal grafts are procedures considered in cases with extensive corneal and scleral tissue destruction. The study aims to describe sclerokeratoplasty outcomes in severely diseased eyes. We performed a retrospective review of clinical records. Demographic characteristics, medical history, surgical indications, aetiology of perforation, visual outcomes, complications associated with the surgical procedure, and ocular integrity at the end of the follow-up were obtained. Wilcoxon-signed rank tests and Mann-Whitney tests were used to compare complications between groups and outcomes at final follow-up. Survival analysis was performed to analyse vision preservation and global integrity and presented in Kaplan-Meier curves. 40 eyes from 40 patients with a mean age of 48.83 ± 18.85 years and a mean follow-up of 21.13 ± 33.92 months were included in the study. Median corrected visual acuity before and after the procedure remained at 2.8 logMAR. Twenty-seven eyes presented complications. The most common complications were a persistent epithelial defect in 11, hypertension in 10, and perforation in 8 eyes. More than half of the eyes (67.5%) presented with either one or more of all complications after corneoscleral graft. No significant differences were found regarding age, gender, or DM history. Concerning perforation, a significant difference was found between infectious and non-infectious only in the presentation of ocular hypertension (p = 0.048). Vision was preserved in 72.5% of the eyes, with a median survival probability of 4.12 years. Preservation of the ocular integrity was achieved in 85% of the eyes, with a median survival probability of 12 years. Sclerokeratoplasty despite being challenging and technically demanding followed by defiant complications, in some situations such as infectious keratitis and autoimmune diseases, is likely a procedure that salvages the eye and preserves vision.

Serial intravitreal injections in age-related macular degeneration patients from the dry eye disease perspective: a cross-sectional study

BackgroundTo evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD).MethodsPatients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI.ResultsForty-two nAMD patients with a mean age of 63.3 ± 19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6–22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p = 0.872), avgNITBUT (6.2 vs. 7.2, p = 0.968), Shirmer-1 results (7 vs. 7, p = 0.854), corneal staining (0.3 vs. 0.2, p = 0.341), lower and upper MG loss rate (29.3 vs. 28.4, p = 0.162, and 27.1 vs. 26.9, p = 0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p = 0.042, and r:0.365, p = 0.047).ConclusionThe results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements.

Technique of Excision of Double Head Pterygium with Conjunctival Autograft from both Eyes

Background: Pterygium is not just a degenerative disease, but may be a proliferative disorder of the ocular surface. Objective: The aim of this study was to describe a technique of conjunctival autograft from both eyes for primary double head pterygium and evaluate its post operative result. Methodology: This retrospective study was conducted in the department of Ophthalmology at Monno Medical College, Manikganj, Bangladesh from July 2022 to December 2022 for duration of six months. After fulfill the selection criteria underwent conjunctival autograft from both eyes. Primary outcome measure was recurrence rate, graft retraction, Tenon's granuloma, dellen formation. Results: The highest patients belong to 35 to 45 years age group is about 18(60.0%) in this study. The number of male patients was 10 and that of female patient 20. There was no recurrence in this study. However, there were postoperative oedema (6.66%), sub-conjunctival haemorrhage (63.33%), graft retraction (20.0%), dellen (0.0%), Tenon’s granuloma (10.0%). Conclusion: In conclusion conjunctival autograft from both eyes appears to be successful technique with 0 recurrence rate in treating double head pterygium. Journal of Monno Medical College June, 2024;10 (1):03-06

Association between pets and dry eye symptoms: A Chinese national-based study

BackgroundPet-derived allergens are another source of indoor air pollution which could affect human health. However, the association between pet ownership and the risk of dry eye symptoms (DES) remains to be elucidated. MethodsWe conducted a nationwide cross-sectional survey among Chinese residents aged over 12 years from June 20, 2022 to August 31, 2022. The Ocular Surface Disease Index-6 (OSDI-6) questionnaire was utilized to evaluate the presence of DES. Multivariable logistic regression models were used to analyze the associations between pet ownership and DES. Subgroup analyses were conducted based on sex, age, residence and affective disorders, and sensitivity analysis by excluding participants with major ocular diseases. The interactions between pet ownership and other risk factors on DES were explored in the additive scale by calculating the synergy index (SI). ResultsA total of 21,916 subjects replied to the questionnaire. The prevalence of DES was 43.6 % (95 % confidence interval (CI), 43.0 %–44.3 %). Pet ownership was significantly associated with increased risk of DES (Odds ratio (OR): 1.13, 95%CI: 1.05–1.21), especially among the elderly (OR: 1.28, 95%CI: 1.09–1.51) and urban residents (OR: 1.13, 95%CI: 1.04–1.24). The individual effect of allergic rhinitis on DES was 2.59 (95%CI: 1.27–5.53), while the joint effect of pets and allergic rhinitis was 5.26 (95%CI: 1.20–36.74), suggesting a synergistic interaction with a SI of 2.48 (95%CI: 0.25–24.39). Furthermore, the interaction analysis also indicated a synergistic interaction between pet ownership and low health literacy with a SI of 1.12 (95%CI: 0.66–1.87). ConclusionPet ownership was identified as a risk factor for DES. The synergistic interaction of pet ownership and allergic rhinitis suggests shared mechanisms between DES and allergic conditions.

Multiomics integration unravels genotype‐microbiome interactions shaping the conjunctival transcriptome

AbstractGene expression is a molecular phenotype shaped by the interplay between genotype and environment. The microbiome represents a critical environmental exposure for the host. However, the genotype‐microbiome interactions (GMIs) shaping the host transcriptome remain largely unexplored. Here, we integrated conjunctival multiomics data from 120 pairs of twins to investigate GMIs. We identified 272,972 expression quantitative trait loci associated with 5946 genes and 241,073 genotype‐controlled correlations between gene expression and microbial abundance. We developed a modeling approach, MicroGenix, that screens for GMIs from host genome, transcriptome, and microbiome data and identifies GMIs associated with the disease through gene‐based association tests. We applied MicroGenix to the conjunctival data set and found that incorporating GMIs into gene expression prediction models significantly increased prediction accuracy. The genes with increased accuracy were overrepresented by those encoding cell adhesion molecules. We further used MicroGenix to predict the transcriptome from conjunctival metagenomes and identified GMIs associated with ocular surface disease. Our work provides a resource for studying host‐microbiome interactions at the conjunctiva and a computational approach to investigate GMIs using multiomics data.

Managing Ocular Surface Disease in Glaucoma Treatment: A Systematic Review.

Ocular surface disease (OSD) is a frequent disabling challenge among patients with glaucoma who use benzalkonium chloride (BAK)-containing topical glaucoma medications for prolonged periods. In this comprehensive review, we evaluated the prevalence of OSD and its management, focusing on both current and future alternatives. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used to assess a) the impact of active ingredients and preservatives on the ocular surface and b) the efficacy of preservative-free (PF) alternatives and adjunctive therapies. BAK-containing glaucoma medications were found to significantly contribute to OSD by increasing corneal staining, reducing tear film stability, and elevating ocular surface disease index (OSDI) scores. Transitioning to PF formulations or those with less cytotoxic preservatives, such as Polyquad® and SofZia®, demonstrated a marked improvement in OSD symptoms. In particular, the use of adjunct cyclosporine A, through its anti-inflammatory and enhanced tear film stability actions, was shown to be very beneficial to the ocular surface. Therefore, the most effective management of OSD is multi-factorial, consisting of switching to PF or less cytotoxic medications, adjunct use of cyclosporine A, and early incorporation of glaucoma surgical treatments such as laser trabeculoplasty, trabeculectomy, glaucoma drainage devices, or minimally invasive glaucoma surgery (MIGS).

Impact of Neurostimulation, Immunomodulation, Topical Medication Application, and Surgical Reconstruction on Corneal Nerve Function and Regeneration.

The corneal epithelium, supplied by thousands of nerve endings, plays a substantial role in absorbing and distributing nutrients along the ocular surface. Many studies have explored the influence of various modalities in regulating tear production to manage corneal disorders and dry eye disease. These findings have highlighted the advantages of enhancing corneal nerve function and regeneration through neurostimulation, neural signaling, immunomodulation, topical medication application, and surgical reconstruction. The purpose of this narrative review article was to provide an overview of the current state of knowledge on this topic based on a PubMed database literature search for relevant animal and human studies investigating the modification of the trigeminal pathway to restore corneal nerve function and improve overall ocular health. Further investigation into this area of research is important to help guide new therapeutic targets for the prevention and development of treatments of corneal degeneration.

Treatment of Ocular Surface Disease in Ocular Cicatricial Pemphigoid

ABSTRACT Purpose While substantial research has focused on systemic immunomodulatory therapy for ocular cicatricial pemphigoid (OCP), limited data exist on managing associated ocular surface disease (OSD). This study evaluates treatments for OCP-related OSD at our institution. Methods We conducted a retrospective analysis of patients diagnosed with cicatrizing conjunctivitis at the University of Colorado Hospital from January 1, 2013, to October 31, 2023. Patients with cicatrizing conjunctivitis due to non-OCP conditions were excluded, and disease severity was classified using the Foster Staging System. Results Our review included 30 patients with OCP, all with at least six months of follow-up. The mean age of symptom onset (n = 19) was 62.2 years (SD = 16.4), while the mean age at diagnosis (n = 28) was 65.1 years (SD = 12.7). The most common OSD treatments at the last visit were preservative-free artificial tears (87%), topical corticosteroids (43%), autologous serum eye drops (40%), topical antibiotics (30%), and topical immunomodulators (23%). All patients used at least one treatment, with 83.3% on prescription therapies. Patients averaged 3.33 (SD: 1.4) treatments, with 1.7 (SD: 1.2) being prescriptions. Topical immunomodulators had the highest discontinuation rate at 73.1% (n = 19/26). Autologous serum eye drops and topical corticosteroids were the least discontinued treatments. Number of total treatments, prescriptions, and procedures sharply increased at stage three OCP. Conclusions The number of treatments and procedures increased with OCP severity, indicating that advanced OCP often necessitated more intensive OSD management.

Dasatinib and erianin co-loaded ion-responsive in-situ hydrogel for effective treatment of corneal neovascularization

Corneal neovasularization (CNV) is one of the leading causes for visual impairment. Dasatinib is a multi-target tyrosine kinase inhibitor, which can inhibit both platelet derived growth factor receptor and Src family kinases. Erianin exhibits excellent anti-inflammatory and anti-angiogenic effects. In this study, dasatinib and erianin were found to synergically inhibit the proliferation, migration and tube formation of Ea.hy926 cells, the three most important cellular processes of CNV. Next, dasatinib and erianin were co-encapsulated in nanostructured lipid carriers (dasa-eri-NLC), which increased the solubility of dasatinib by about 1790 times, increased the solubility of erianin by about 3 times. To improve its retention time on the ocular surface, dasa-eri-NLC was mixed with gellan gum (dasa-eri-NLC-gel), which achieved a sol-gel transformation when got in contact with tears. The dasa-eri-NLC-gel exhibited good rheological properties with shear thinning properties, extended the ocular residence time by more than 6 times, sustained the drug release, improved the corneal permeability of drug and exhibited good biocompatibility. Finally, the in vivo anti-CNV effect was evaluated in an alkaline burned mouse model of CNV, in which, the dasa-eri-NLC-gel significantly impeded the development and pathological changes of CNV, inhibited the expression of TNF-α, VEGF-A, HIF-1α, Src, pSrc in the cornea. In summary, dasa-eri-NLC-gel safely and efficiently delivered dasatinib and erianin to the cornea and exhibited significantly anti-CNV effect via inhibiting various angiogenesis related cytokines or factors. Dasa-eri-NLC-gel showed a great promise for the treatment of CNV and our study laid a solid foundation for future clinical transformation.

Acquired Ankyloblepharon Correction Using Ocular Surface and Tarsal Mucous Membrane Grafting in Cicatrizing Ocular Surface Diseases

Purpose: To report the long-term surgical outcomes of acquired ankyloblepharon correction using mucous membrane graft. Methods: Five eyes of 4 patients (median age, 19 years) with acquired ankyloblepharon were managed using eyelid splitting and mucous membrane graft anchored to the recti muscles on the bulbar surface in the respective quadrant and onto the bare tarsal surface. Outcome measures include a change in the palpebral fissure width, ability to fit scleral contact lenses, visual acuity, and cosmesis. Results: The underlying etiologies of ankyloblepharon were chronic Stevens-Johnson syndrome (n = 3), and chemical injury (n = 2). All 5 eyes had conjunctival shortening, and 3 had severe dry eyes (median Schirmer 4.5 mm). Four eyes had limbal stem cell deficiency. The median horizontal palpebral fissure width improved to 22 mm from 8 mm. This single-staged surgical technique allowed for fornix formation and prosthetic replacement of the ocular surface ecosystem lens fitting in all 5 eyes. Median logMAR visual acuity improved from 2.1 to 0.7 following ankyloblepharon release, prosthetic replacement of the ocular surface ecosystem lens fitting in 4 eyes, and keratoprosthesis in 1 eye. Repeat mucous membrane graft for recurrent symblepharon in 1 quadrant was required in 2 eyes where complete 360 degrees bulbar and tarsal conjunctiva loss were present preoperatively. At the median follow-up period of 27 months, all patients reported better cosmesis and had no symblepharon recurrence following repeat surgery in 2 eyes and single surgery in 3 eyes. The donor site healed well without any complications. No mitomycin C or symblepharon ring was used. Conclusion: Ocular surface and adnexal reconstruction using bulbar and tarsal mucous membrane grafts help visually rehabilitate patients with acquired ankyloblepharon secondary to cicatrizing ocular surface disorders.

Efficacy of Amniotic Membrane Grafting for the Treatment of Chemical and Thermal Ocular Surface Injuries: A Report by the American Academy of Ophthalmology

To evaluate the published literature on the efficacy of amniotic membrane grafting (AMG) in the management of acute chemical and thermal ocular surface burns with respect to the rate of corneal re-epithelialization and improvement of visual acuity or corneal clarity. Literature searches were conducted in the PubMed database in May 2023 and updated in January 2024 and were limited to the English language without date restrictions. The searches yielded 474 citations; 58 were reviewed in full text, and 9 met the inclusion criteria. Four studies were rated level II, and 5 studies were rated level III. This assessment focuses on 3 level II articles that provided consistent primary and secondary outcomes but demonstrated suboptimal study design with respect to power calculations and lacked a priori sample-size calculations. Amniotic membrane grafting significantly improved corneal re-epithelialization compared with medical therapy alone in eyes with moderate-grade burns. For severely burned eyes, AMG demonstrated no advantage over medical therapy. Additionally, AMG demonstrated no significant advantage over medical therapy for improved visual acuity or corneal clarity for moderate or severe ocular surface burns. The best available level II evidence suggests that AMG in the setting of acute ocular surface burns has efficacy in hastening re-epithelialization in moderate burns. As an adjuvant to medical therapy, it did not demonstrate a benefit in improving re-epithelialization in severe burns or visual acuity or corneal clarity in either moderate or severe burns. Proprietary or commercial disclosure may be found after the references.