Epithelial Defects Research Articles

A Comprehensive Review on Acanthamoeba Keratitis: An Overview of Epidemiology, Risk Factors, and Therapeutic Strategies.

Acanthamoeba keratitis (AK) is a rare but severe corneal infection caused by the free-living amoeba, Acanthamoeba, which is ubiquitously present in the environment. This condition predominantly affects contact lens wearers but can also occur in non-lens users, particularly those exposed to contaminated water or with compromised immune systems. AK is characterized by progressive corneal inflammation, epithelial defects, and ulceration, which can lead to significant visual impairment or blindness if not promptly diagnosed and treated. This review aims to provide a comprehensive overview of AK by synthesizing current knowledge on its epidemiology, risk factors, pathophysiology, clinical manifestations, diagnostic approaches, and therapeutic strategies. The review also highlights preventive measures and public health strategies to reduce the incidence of this debilitating condition. A detailed examination of existing literature was conducted, focusing on the global incidence of AK, demographic trends, and various risk factors such as contact lens use, environmental exposures, and immunity status. The review also delves into the pathophysiology of Acanthamoeba infection, the host immune response, and the challenges in distinguishing AK from other forms of infectious keratitis. Therapeutic strategies, including medical and surgical interventions, are analyzed, along with emerging treatments. The global incidence of AK has increased, particularly among contact lens users, due to poor hygiene practices and environmental exposures. Early diagnosis remains challenging, often leading to delayed treatment and poorer outcomes. Biguanides and diamidines are the mainstays of medical therapy, with surgical options considered in advanced cases. Emerging therapies, such as photodynamic therapy and antimicrobial peptides, show promise in enhancing treatment outcomes.AK poses a significant threat to ocular health due to its potential for severe visual impairment and the complexities associated with its diagnosis and treatment. Early recognition, appropriate management, and public health initiatives focused on prevention are crucial for improving patient outcomes. Ongoing research and a collaborative approach among healthcare providers are essential to advancing the understanding and management of AK.

Classification of Hydroxychloroquine Retinopathy: A Literature Review and Proposal for Revision.

Establishing universal standards for the nomenclature and classification of hydroxychloroquine retinopathy is essential. This review summarizes the classifications used for categorizing the patterns of hydroxychloroquine retinopathy and grading its severity in the literature, highlighting the limitations of these classifications based on recent findings. To overcome these limitations, I propose categorizing hydroxychloroquine retinopathy into four categories based on optical coherence tomography (OCT) findings: parafoveal (parafoveal damage only), pericentral (pericentral damage only), combined parafoveal and pericentral (both parafoveal and pericentral damage), and posterior polar (widespread damage over parafoveal, pericentral, and more peripheral areas), with or without foveal involvement. Alternatively, eyes can be categorized simply into parafoveal and pericentral retinopathy based on the most dominant area of damage, rather than the topographic distribution of overall retinal damage. Furthermore, I suggest a five-stage modified version of the current three-stage grading system of disease severity based on fundus autofluorescence (FAF) as follows: 0, no hyperautofluorescence (normal); 1, localized parafoveal or pericentral hyperautofluorescence on FAF; 2, hyperautofluorescence extending greater than 180° around the fovea; 3, combined retinal pigment epithelium (RPE) defects (hypoautofluorescence on FAF) without foveal involvement; and 4, fovea-involving hypoautofluorescence. These classification systems can better address the topographic characteristics of hydroxychloroquine retinopathy using disease patterns and assess the risk of vision-threatening retinopathy by stage, particularly with foveal involvement.

Treatment outcome of spontaneous chronic corneal epithelial defects in brachycephalic dogs comparing Boxers and non-Boxers: A retrospective multicenter study of 420 dogs.

To compare characteristics and treatment outcomes of spontaneous chronic corneal epithelial defects (SCCEDs) in brachycephalic non-Boxers and Boxers. We hypothesized that brachycephalic non-Boxers develop SCCEDs at a younger age and develop complications more frequently than Boxers. Retrospective review of medical records of brachycephalic dogs treated for SCCEDs between January 2018 and December 2022 in multiple ophthalmology referral centers in the UK. Data recorded included breed, age, time of onset, treatment prior to referral, treatment at referral, time to heal, need for further procedures, and complications. A total of 464 SCCEDs in 420 dogs were included composed of 173 Boxers with 200 SCCEDs and 247 brachycephalic non-Boxer dogs with 264 SCCEDs. Boxers were significantly older (median 8.2, range 4.5-12.7 years) than brachycephalic non-Boxers (median 7.2, range 1.6-15.9 years) (p < .001). The first treatment (cotton-tipped applicator [CTA] debridement, diamond burr debridement, superficial keratectomy, grid keratotomy, punctate keratotomy, or combinations of these) selected was significantly different between groups (p < .001). Healing, excluding cases addressed by CTA debridement, following the first procedure was significantly more successful in Boxers (p = .049). Excluding cases addressed by CTA debridement, 9.6% of SCCEDs in Boxers (20/200) and 13.4% (32/239) of non-Boxers required more than one procedure. In the non-Boxer group, 9.5% (25/264) developed complications, contrasting with 4% (8/200) in the Boxer group. Non-Boxers were more likely to develop complications after the first treatment (p = .006). Non-Boxer brachycephalic dogs develop SCCEDs younger than Boxers. This study suggests SCCEDs in brachycephalic non-Boxers may be less likely to heal following one mechanical treatment and are more likely to develop complications.

Dysregulated Airway Host Defense in Hyper IgE Syndrome due to STAT3 Mutations.

Hyper IgE syndrome (STAT3-HIES), also known as Job's syndrome, is a rare immunodeficiency disease typically caused by dominant-negative STAT3 mutations. STAT3-HIES syndrome is characterized by chronic pulmonary infection and inflammation, suggesting impairment of pulmonary innate host defense. To identify airway epithelial host defense defects consequent to STAT3 mutations that, in addition to reported mutant STAT3 immunologic abnormalities, produce pulmonary infection. STAT3-HIES sputum was evaluated for biochemical/biophysical properties. STAT3-HIES excised lungs were harvested for histology; bronchial brush samples were collected for RNA sequencing and in vitro culture. A STAT3-HIES-specific mutation (R382W), expressed by lentiviruses, and a STAT3 knockout, generated by CRISPR/Cas9, were maintained in normal human bronchial epithelia under basal or inflammatory (IL1β) conditions. Effects of STAT3 deficiency on transcriptomics, and epithelial ion channel, secretory, antimicrobial, and ciliary functions were assessed. Mucus concentrations and viscoelasticity were increased in STAT3-HIES sputum. STAT3-HIES excised lungs exhibited mucus obstruction and elevated IL1β expression. STAT3 deficiency impaired CFTR-dependent fluid and mucin secretion, inhibited expression of antimicrobial peptides, cytokines, and chemokines, and acidified airway surface liquid at baseline and post-IL1β exposure in vitro. Notably, mutant STAT3 suppressed IL1R1 expression. STAT3 mutations also inhibited ciliogenesis in vivo and impaired mucociliary transport in vitro, a process mediated via HES6 suppression. Administration of a γ-secretase inhibitor increased HES6 expression and improved ciliogenesis in STAT3 R382W mutant cells. STAT3 dysfunction leads to multi-component defects in airway epithelial innate defense, which, in conjunction with STAT3-HIES immune deficiency, contributes to chronic pulmonary infection.

Outcome of posterior lamellar replacement with oral mucous membrane graft in lid margin sequalae of Steven Johnson syndrome

: to address common lid margin sequalae presented in steven Johnson syndrome and to assess the outcome of posterior lamellar replacement with oral mucous membrane graft. : This single center longitudinal study was conducted in Ispahani Islamia Eye Institute and Hospital. 56 diagnosed cases of Steven Johnson syndrome with lid margin sequalae during the period of July 2020 to June 2023 were included in the study. Patients with ocular cicatrizing pemphigoid and chemical burn were excluded from the study. Demographic profile, presenting lid margin sequalae, outcome of surgery and complication after intervention and its management were properly evaluated and recorded. : A total of 98 eyelids (upper and lower) in 56 patients were evaluated. The Mean age was 38.33 ± 15.22 years (range 6 – 70 years). 21 patients were male and 35 were female (male: female=1:1.66). 14 patients had unilateral defect and 42 patients have bilateral defect. Most common lid margin sequalae was lid margin keratinization (85.71%), distichiasis (62.5%), trichiasis (21.42%) and entropion (8.92%). All lid margin defect were successfully corrected by posterior lamellar replacement with oral mucous membrane graft. During 6 months post-operative follow up, significant symptomatic relief from epiphora, foreign body sensation, pain and photophobia were achieved in all patients. There was remarkable reduction of conjunctival inflammation (88.63%) and persistent corneal epithelial defect (71.42%). Mean visual acuity was significantly improved. Common complications of the surgery were misdirected lashes (7.14%), dislodgement of graft (2.04%%), and recurrent entropion (2.04%). All complication was successfully managed through appropriate second procedure.Posterior lamellar resection with an oral mucous membrane graft for modifying lid margin defects in Steven-Johnson syndrome shows promising results.

The clinical outcomes of minor salivary gland transplantation for severe dry eye disease secondary to chronic Stevens-Johnson syndrome

PurposeTo study the outcomes of minor salivary gland transplantation for severe dry eye disease secondary to chronic Steven Johnson Syndrome. MethodsIt was an ambispective, interventional case series conducted at Rajendra Prasad Centre for Ophthalmic Sciences, Delhi, India from 2022 to 2023 evaluating the outcomes of minor salivary gland transplantation with anchorage of the minor salivary glands to superior rectus muscle in twenty cases of severe dry eye disease secondary to chronic Steven-Johnson Syndrome. The pre-operative clinical parameters were compared to those at post-operative 1 year follow-up. ResultsAt 1 year follow-up, there was an improvement in mean Schirmer-1 value (p = 0.0004), hyperemia score (p = 0.0004), keratinization score (p = 0.04), corneal epithelial defect score (p = 0.0004), corneal opacification score (p = 0.001), corneal neovascularization score (p = 0.001), palisades of Vogt score (p = 0.007), corneal keratinization score (p = 0.04) and corneal conjunctivalization score (p = 0.08). ConclusionThe minor salivary gland transplantation is a viable management option for cases with severe dry eye disease secondary to chronic Steven Johnson Syndrome with clinical improvement in corneal and conjunctival parameters of the ocular surface.

Complications After Pediatric Penetrating Keratoplasty: An IRIS Registry Study.

To describe the frequency of postoperative complications in children undergoing penetrating keratoplasty (PK). This retrospective cohort study included pediatric patients (aged 0-18 years) in the Intelligent Research in Sight (IRIS) Registry who underwent primary PK between January 2013 and December 2020. Patients were identified using Current Procedure Terminology codes. Postoperative complications were identified using International Classification of Diseases Revision 9 and 10 codes and categorized as complications affecting the anterior segment (epithelial defect, infectious keratitis, neurotrophic keratitis, and glaucoma) or posterior segment (vitreous hemorrhage, retinal detachment, choroid detachment, choroidal hemorrhage, endophthalmitis, epiretinal membrane, and proliferative vitreoretinopathy). Of the 544 pediatric patients undergoing PK, 259 (47.6%) experienced postoperative complications. Anterior segment complications (n = 222, 40.8%) were more common than posterior segment complications (n = 96, 17.6%). The most common anterior complication was infectious keratitis (n = 163, 30.0%) with a median onset time of 275 days (IQR 50-560 days) after surgery. Vitreous hemorrhage (n = 52, 9.6%) and retinal detachment (n = 48, 8.8%) were the most common posterior segment complications. Infectious keratitis was the most common postoperative complication in children undergoing PK. More complications occurred in the anterior segment (70%) of the eye as compared with the posterior segment (30%). These findings demonstrate the challenges associated with pediatric PK and may help guide postoperative monitoring and management.

Infectious crystalline keratopathy-clinical-microbiological profile and outcome of management.

To describe the clinical features, management, and long-term outcome of Infectious crystalline keratopathy(ICK). The medical records of clinically diagnosed and microbiologically proven cases of ICK were reviewed from January 2011 to December 2022. Clinical characteristics include the presence of whitish needle-like projections with branching, limited to anterior-mid stroma. Keratoplasty being the most common risk factor, graft-related microbial keratitis during the same period was also studied. The demography, clinical profile, microbiology, treatment, and outcome were analyzed, and compared with secondary graft infiltrate(GI). Medical records of 24 cases with ICK were reviewed. The mean age was 49.3 ± 20.1years, with 15(62.5%) males. Prior keratoplasty was done in 18 (75%) cases, with a mean graft size of 10.1 ± 1.5mm, and mean interval between the last graft and presentation was 9.7 ± 6.2 (3-90) months. In comparison to GI (n = 24), ICK patients (n = 18,75%) were less symptomatic, presented late (7.3 ± 6.5days vs 16.3 ± 19.4, p = 0.003), using frequent topical steroids (> 3 times/day, p = 0.006), smaller infiltrate size < 4mm (p = 0.008), central (p = 0.02), less associated with epithelial defect (p = 0.0001), hypopyon (p = of 0.0002), corneal perforation (p = 0.0006), and surgical management (p = 0.03). On microbiology, 22 (91.6%) ICK cases were culture positive, 14 (63.6%) gram-positive, 3 (13.6%) gram-negative, 2 (9%) mixed bacteria, and 3 (13.6%) fungus, comparable with GI. ICK affects poor ocular surfaces usually following keratoplasty with larger graft size, the use of steroids being the most common association, and it responds to medical management as compared to GI.

Age-related epithelial defects limit thymic function and regeneration

The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals.

Metabolic dysfunction mediated by HIF-1α contributes to epithelial differentiation defects in eosinophilic esophagitis

Investigating the contributory role that epithelial cell metabolism plays in allergic inflammation is a key factor to understanding what influences dysfunction and the pathogenesis of the allergic disease eosinophilic esophagitis (EoE). We previously highlighted the absence of hypoxia signaling through HIF-1α in EoE contributes to esophageal epithelial dysfunction. However, metabolic regulation by HIF-1α has not been explored in esophageal allergy. Herein, we sought to define the role of HIF-1α-mediated metabolic dysfunction in esophageal epithelial differentiation processes and barrier function in EoE. In RNA-sequencing derived from EoE patient biopsies, we observed the expression pattern of key genes involved in mitochondrial metabolism/oxidative phosphorylation (OXPHOS) and glycolysis. Bioenergetics analysis using Seahorse was performed on EPC2-hTERT cells to decipher the metabolic processes involved in epithelial differentiation processes. In addition, air-liquid interface cultures were employed to delineate metabolic dependency mechanisms required for epithelial differentiation. Transcriptomic analysis identified an increase in genes associated with OXPHOS in patients with EoE. Epithelial origin of this signature was confirmed by complex V immunofluorescence of patient biopsies. Bioenergetic analysis in vitro revealed that differentiated epithelium was less reliant on OXPHOS compared with undifferentiated epithelium. Increased OXPHOS potential and reduced glycolytic capacity was mirrored in HIF1A-knockdown EPC2-hTERT cells which portray a significant absence of terminal markers of epithelial differentiation, including involucrin. Pharmacological glucose transport inhibition phenocopied this, while rescue of the HIF-1α-deficient phenotype using the pan-prolyl hydroxylase inhibitor DMOG resulted in restored expression of epithelial differentiation markers. An OXPHOS-dominated metabolic pattern in EoE patients, brought about largely by the absence of HIF-1α-mediated glycolysis, is linked with the deficit in esophageal epithelial differentiation.

Effects and Safety of 5% Lifitegrast Ophthalmic Solution in Patients With Dry Eye Disease Associated With Ocular Graft-Versus-Host Disease.

Introduction Graft-versus-host disease (GVHD) is a common sequela of hematopoietic stem cell transplant (HSCT). While HSCT is often curative for certain hematologic malignancies, acute and chronic GVHD remains an important cause of morbidity and mortality in post-transplant patients. Ocular involvement is one manifestation of chronic GVHD that can present similarly to chronic dry eye with tear film abnormalities, aqueous deficiency, and corneal epithelial defects through melting and perforation. Current management includes frequent use of artificial tears and oral or topical glucocorticoids as tolerated. There is a need for long-term, steroid-sparing therapeutics in the management of ocular GVHD (oGVHD). Lifitegrast is approved for the treatment of chronic dry eye and may have therapeutic potential in the treatment of oGVHD. The aim of this study was to investigate the efficacy and safety of topical lifitegrast in the management of oGVHD. Methodology A prospective randomized clinical trial (NCT04792580) was performed on 32 enrolled patients with diagnosed oGVHD. Subjects underwent a two-week washout period consisting of preservative-free artificial tears dosed twice a day, after which they were randomized to the treatment arm (5% lifitegrast ophthalmic solution) or placebo arm (vehicle solution) for four weeks. Endpoints included Symptom Assessment iN Dry Eye (SANDE) score, unanesthetized Schirmer score, Ocular Surface Disease Index questionnaire score, fluorescein staining, tear film breakup time, meibum quantity, and turbidity. Safety endpoints included intraocular pressure, visual acuity, and rate of treatment-related adverse effects. Statistical analysis was done with a t-test or Wilcoxon rank-sum test. Results The primary and secondary efficacy endpoints were met, with statistically significant reductions in mean SANDEand unanesthetized Schirmer score observed at four weeks post-randomization. No serious adverse events related to the use of either lifitegrast or vehicle were observed, and no worsening of visual acuity or intraocular pressure occurred in the intention-to-treat analysis. However, further inference was limited due to insufficient statistical power owing to significant washout and a 50% dropout rate from the all-enrolled analysis set. The most common causes of study dropout were worsening of unrelated medical conditions (not GVHD) and improvement of SANDE score or Schirmer score outside of the inclusion criteria range during the washout period. Conclusions Lifitegrast may be a useful steroid-sparing agent in the long-term management of oGVHD. This study provides further support for the clinical evidence of lifitegrast in the management of dry eye signs and symptoms, although further sufficiently powered clinical trials are warranted to better understand its efficacy in the oGVHD population. Personalized treatment options targeting distinct manifestations of oGVHD in the cornea, tear film, lid margin, and conjunctiva are needed in the effective management of this multifaceted and complex disease.

The effect of platelet-rich plasma and sodium alginate hydrogel on corneal wound healing after corneal alkali burns in rats with computer-assisted anterior segment optical coherence tomography image analysis

Our objective was to determine the effect of a semi-synthetic sodium alginate hydrogel and its combination with platelet-rich plasma (PRP) on histopathological, biochemical, clinical, and anterior segment optical coherence tomography (AS-OCT) data. Alkali chemical burn of the cornea was induced. Injured rats were randomly divided into five equal groups and topically treated with phosphate-buffered saline (sham), platelet-rich plasma (PRP), 0.5% sodium citrate, a semi-synthetic sodium alginate hydrogel, or a combination of PRP and hydrogel (combined group) three times daily. The degree of corneal opacity (CO), corneal epithelial staining (CES), percentage of corneal epithelial defects (CEDP), degree of ciliary hyperemia (CH), neovascularization size (NVS), and extent of neovascularization (NVE) were evaluated. AS-OCT was performed at nine days, and then rats were sacrificed. Histological examination and enzyme-linked immunosorbent assays were performed to detect the concentrations of IL-1β and MMP-9 in the cornea. There were no significant differences between the groups regarding CEDP, CO, CES, CH, NVS, or NVE on the first day after corneal alkali burn injury (p > 0,05). At the last examination, CO was significantly lower in the PRP group than in the sham group (p = 0,044), while the CO concentrations were similar in terms of NVS (p > 0,05). Similarly, in terms of tissue MMP-9 levels, there were no significant differences between groups (p > 0,05). However, there was a significant difference in tissue IL-1β levels between the groups (p < 0,001). In the PRP and combined groups, the level of IL-1β was significantly lower than that in the sham group (p = 0,043 and p = 0,036, respectively). There was a significant difference in epithelial necrosis between the PRP, and it was the lowest in the combined group (p = 0,003). Epithelial thickness was highest in the combined group (p = 0,002). CEDP was significantly different at the last visit between the groups (p = 0.042). The fastest epithelial closing rate was observed for the combined group (p = 0,026). There was a significant negative correlation between tissue MMP-9 levels and corneal solidity and between tissue MMP-9 levels and the corneal area according to the AS-OCT measurements (p = 0,012 and p = 0,027, respectively). When used alone, topical hydrogel application did not significantly enhance the healing of corneal wounds. However, when combined with PRP, it leads to an increased rate of epithelial closure and neovascularization. This combination did not exacerbate inflammation or corneal opacity compared to PRP alone. The anticoagulant citrate solution in the PRP tube did not prove effective. The synergistic use of PRP and hydrogel could enhance epithelial thickness and reduce epithelial necrosis. The use of new parameters for corneal wound healing assessment was facilitated through AS-OCT image processing.

Prevalence of Certain Corneal Conditions and their Demographic Risk Factors; Tehran Geriatric Eye Study.

Corneal abnormalities are one of the important reasons for visual impairment. There is little evidence of the prevalence of different types of corneal abnormalities. The aim of this study was to assess the prevalence of various corneal abnormalities and identify the key risk factors associated with these abnormalities in an elderly population residing in Tehran. The Tehran Geriatric Eye Study (TGES) was conducted as a cross-sectional study, utilizing a population-based approach and employing stratified cluster random sampling. The study focused on individuals aged 60 years and above residing in Tehran. An ophthalmologist performed a slit lamp examination to evaluate the eyelid, cornea, and crystalline lens. The prevalence of posterior embryotoxon (PE), punctate epithelial defect (PED), pigment on endothelium (POE), corneal dystrophy (CDys), corneal vascularization (CV), and corneal degeneration (CDeg) were estimated to be 0.08% (95% confidence interval [CI]: 0.02 to 0.40), 8.77% (95% CI: 6.64 to 11.51), 0.57% (95% CI: 0.33 to 0.98), 0.53% (95% CI: 0.33 to 0.82), 0.95% (95% CI: 0.60 to 1.52), and 44.87% (95% CI: 41.80 to 47.98), respectively. Overall, approximately 49.08% of the participants exhibited some form of corneal abnormality in at least one eye. The multiple logistic regression model revealed that increasing age was significantly associated with PED, CV, and CD. Furthermore, illiterate participants had a significantly higher prevalence of PE. The findings of this study indicate that approximately half of the elderly population aged 60 years and above in Tehran have at least one corneal abnormality, with corneal degeneration being the most prevalent. Age was identified as the primary determinant of corneal abnormalities.

Clinical Characteristics of Ocular Mucous Membrane Pemphigoid: A Systematic Review and Meta-Analysis

ABSTRACT Purpose To synthesize the evidence and generate a combined weighted measure on the frequency of ocular manifestations of mucous membrane pemphigoid (OMMP). Methods Systematic literature review and meta-analysis, searching PubMed, Embase, VHL, and Google Scholar. Articles reporting patients with mucous membrane pemphigoid and ocular involvement were included. At least, two reviewers independently and in parallel participated in all the following phases; preliminary screening, full-text review, risk of bias assessment by validated tools, and data extraction. Qualitative analysis and meta-analysis were conducted. This study was previously registered in PROSPERO (CRD42023451844). Results Thirty-five studies met the inclusion criteria, comprising 1,439 patients and 1,040 eyes summarized in qualitative analysis. Twenty-eight studies were included in the meta-analysis. Ages included ranged from 60.4 to 75 years. Women were reported with more frequency. The mean time for diagnosis was 55.1 months, usually with bilateral ocular disease in 90% (95% CI 78%; 96%). Trichiasis and entropion were the most frequent manifestations in up to 92%, followed by symblepharon and punctate keratitis. Ankyloblepharon, persistent epithelial defects, and visual impairment were less frequent complications. Direct immunofluorescence positivity in conjunctival biopsies was 54% (95% CI 43%; 64%). Extraocular involvement was highly frequent, being oral and skin involvement the most frequently reported. Conclusions Our systematic review and meta-analysis evidenced that patients around 60 years of age are the most affected population with a female preponderance, usually with bilateral ocular involvement. Trichiasis and entropion were the most frequent findings; although visual impairment and persistent epithelial defects were less reported, they should not be overlooked in suspected OMMP.

Comparative study on corneal epithelium healing: effects of crosslinked hyaluronic acid and amniotic membrane extract eye drops in rats.

Corneal ulcers are common lesions in both human and veterinary medicine. However, only a few studies have evaluated the efficacy of cross-linked hyaluronic acid (X-HA) eye drops on corneal wound healing. To our knowledge, this is the first study to demonstrate and compare the efficacy of amniotic membrane extract eye drops (AMEED) and X-HA for corneal wound healing in rats. A total of 15 male Wistar rats (30 eyes) were used in this study. Then, 10 eyes were treated with X-HA, AMEED, or 0.9% saline. After general and topical anesthesia, a superficial corneal ulcer was created using a corneal trephine. The defect was further polished with a diamond burr. Three groups of 10 eyes each were treated with either one drop of 0.75% X-HA or AMEED or 0.9% saline (control), administered every 12 h for a duration of 72 h. The median epithelial defect area (MEDA), expressed as a percentage of the total corneal surface, was measured at 0, 12, 24, 36, 48, and 72 h. Re-epithelization time scores were also evaluated. The Kruskal-Wallis test was used to compare median times for re-epithelization and histopathologic scores between groups, while the Friedman test (for paired data) was employed to compare results from the serial analysis of MEDA and vascularization scores between groups. MEDA was not significantly different between X-HA and AMEED. However, MEDA was significantly smaller in the X-HA group compared to the control group at 36 h (2.73 interquartile range (IQR) 5.52% x 9.95 IQR 9.10%, P=0.024) and 48 h (0.00 IQR 0.26% x 6.30 IQR 8.54%, P=0.030). The overall time for re-epithelization was significantly lower in the X-HA group (3.00 IQR 3.00) compared to the AMEED (6.5 IQR 3.00) and control (7.00 IQR 1.00) groups (P=0.035). Vascularization, hydropic degeneration, and epithelial-stromal separation were significantly less observed in samples in the X-HA-treated compared to samples in the AMEED- and saline-treated groups. Significantly more corneal epithelium cells were labeled for caspase3 in samples from the AMEED- and saline-treated groups compared to those from the X-HA-treated group. Topical X-HA has been shown to accelerate corneal epithelial healing. AMEED did not decrease corneal re-epithelialization time. X-HA may also potentially be used as an adjunct therapy for treating corneal ulcers in clinical situations.

Effects of Ripasudil Hydrochloride on Epithelial Repair in a Mouse Cornea

Purpose Effect of topical administration of a Rho kinase inhibitor, ripasudil, on epithelial wound healing in a mouse cornea was investigated. Effects of treatment of cultured human corneal epithelial cell (HCEC) line and organ-cultured corneal epithelium with ripasudil on expression of p-ERK was also examined. Methods Epithelial defects with a diameter of 2.0 mm were prepared in the central corneas of C57BL/6 mice with or without 1-week travoprost pre-treatment, to which ripasudil or PBS as a control was instilled every 6 h immediately after preparation. The mice eyes were cultured with or without travoprost for 24-hrs. The expression levels of p-ERK in epithelium of mice eyes were compared by immunostaining after further 24-hrs culture with or without ripasudil for 24-hrs. HCEC were cultured with or without ripasudil and processed for examination for proliferation activity and protein expression of p-ERK by either immunostaining or Western blotting. The cells were also treated with or without travoprost for 24-hrs, and were further cultured with or without ripasudil. Expression levels of p-ERK were examined by Western blotting. Results Ripasudil treatment suppressed post-debridement epithelial healing in association with reduced proliferation activity in peripheral (limbal) epithelium in cornea with or without pre-treatment with travoprost. Ripasudil treatment accelerated p-ERK expression. Ripasudil supplementation upregulated proliferation with increased p-ERK in HCEC. Conclusion Ripasudil treatment promotes wound healing of the mouse corneal epithelium by enhancing cell proliferation on peripheral (limbal) epithelium.

Retrospective analysis on the outcomes of contact lens-associated keratitis in a tertiary centre: an evidence-based management protocol to optimise resource allocation

Background/aimsContact lens-associated keratitis (CLAK) is a common sight-threatening complication of contact lens use. Current management protocols in the UK are based on historical practice and necessitate a review for every...

Toxicity and efficacy of type I interferons on the ocular surface: in vitro, animal, and clinical studies

PurposeTo investigate the toxicity of type I interferons (IFNs) on the ocular surface and assess their efficacy in ocular surface tumors. MethodsWe examined the effects of IFN-α2a, IFN-α2b and IFN-β on corneal epithelial cells and stromal fibroblasts in vitro as well as the impact of IFN-α2a on the ocular surface in mice. Additionally, we analyzed the therapeutic and adverse effects of topically administered IFN-α2a and IFN-α2b in patients with ocular surface tumors. Risk factors contributing to side effects were explored. ResultsIFN-α2a, IFN-α2b or IFN-β reduced cell viability and induced pro-inflammatory cytokines in corneal epithelial cells and stromal fibroblasts. Furthermore, IFNs enhanced the expression of major histocompatibility complex class II and CD40 in corneal epithelial cells. In mice, subconjunctival IFN-α2a injection did not induce corneal epithelial defects or opacity, nor did it reduce aqueous tears or conjunctival goblet cells. In patients, topical IFN-α2a or IFN-α2b administration decreased tumor size and prevented recurrence; however, it was associated with mild side effects, including corneal epitheliopathy and conjunctival hyperemia. These complications were associated with longer IFN use, the presence of underlying ocular surface disease and concurrent use of mitomycin C or anti-glaucoma eye drops. ConclusionAlthough type I IFNs cause direct toxicity on corneal cells, they do not induce significant side effects on the healthy ocular surface. Considering its therapeutic and preventive effects, topical type I IFN is safe and effective for treating ocular surface tumors. The potential for ocular side effects should be considered in eyes with identified risk factors.

Indications and Outcomes of Emergency Keratoplasty in a Major New Zealand Eye Tertiary Referral Center, 2000 to 2021.

To report the indications and outcomes of emergency keratoplasty over a 21-year period in Greenlane Clinical Centre, the major tertiary eye referral center in Auckland, New Zealand (Aotearoa). A retrospective review of medical records of all emergency keratoplasties performed in Greenlane Clinical Centre from January 2000 to September 2021 was conducted. Demographic, preoperative, intraoperative, and 1-year postoperative data were collected. Emergency keratoplasty was performed in 102 eyes of 97 patients (54 men), comprising 5.6% of transplants performed (N = 1830) in this period. The mean age was 53 years (range = 4-95 years, SD = 20). Patients of Māori ethnicity were overrepresented (31%). Corneal perforation was present in 90% of eyes, and microbial keratitis was the most common indication. Bacteria were the most commonly isolated organisms (38%). The mean preoperative and 12-month postoperative best potential corrected distance visual acuity was 1.6 and 1.2 (logMAR), respectively. All cases of therapeutic keratoplasty achieved initial therapeutic success, with no eyes lost or requiring repeat emergency keratoplasty. Complications included nonhealing epithelial defects (19%), cataract (19%), glaucoma (15%), allograft rejection (13%), and corneal melting (5%). Fifteen cases (15%) had documented graft failure at 12 months. Multivariate analysis revealed that younger age was the only statistically significant factor associated with failure at 12 months. Emergency keratoplasty was the indication for 5.6% of keratoplasties performed. Our results compare favorably with those in the literature, possibly because of early intervention and lower incidence of fungal keratitis. The reported overrepresentation of Māori has important implications for health access and delivery in New Zealand.

The use of rh-NGF in the management of neurotrophic keratopathy.

Neurotrophic keratitis or keratopathy (NK) is a degenerative corneal disease induced by impairment of the trigeminal nerve function. This condition may lead to persistent epithelial defects, corneal ulceration, and perforation. The diagnosis of NK requires a careful investigation of any ocular and systemic condition associated with the disease and ocular surface and corneal sensitivity examinations. In the past, several medical and surgical procedures were used to treat this condition with different clinical effectiveness. Cenegermin is a recombinant human nerve growth factor (rh-NGF) that supports corneal reinnervation. Different clinical trials have demonstrated the safety and efficacy of topical cenegermin in patients with moderate to severe neurotrophic keratitis. In this review, we report the literature on clinical results regarding the treatment of NK with cenegermin since its approval by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in 2017 and 2018, respectively.