Artificial intelligence in retinal screening using OCT images: A review of the last decade (2013-2023).

BACKGROUND AND OBJECTIVES: Optical coherence tomography (OCT) has ushered in a transformative era in the domain of ophthalmology, offering non-invasive imaging with high resolution for ocular disease detection. OCT, which is frequently used in diagnosing fundamental ocular pathologies, such as glaucoma and age-related macular degeneration (AMD), plays an important role in the widespread adoption of this technology. Apart from glaucoma and AMD, we will also investigate pertinent pathologies, such as epiretinal membrane (ERM), macular hole (MH), macular dystrophy (MD), vitreomacular traction (VMT), diabetic maculopathy (DMP), cystoid macular edema (CME), central serous chorioretinopathy (CSC), diabetic macular edema (DME), diabetic retinopathy (DR), drusen, glaucomatous optic neuropathy (GON), neovascular AMD (nAMD), myopia macular degeneration (MMD) and choroidal neovascularization (CNV) diseases. This comprehensive review examines the role that OCT-derived images play in detecting, characterizing, and monitoring eye diseases. METHOD: The 2020 PRISMA guideline was used to structure a systematic review of research on various eye conditions using machine learning (ML) or deep learning (DL) techniques. A thorough search across IEEE, PubMed, Web of Science, and Scopus databases yielded 1787 publications, of which 1136 remained after removing duplicates. Subsequent exclusion of conference papers, review papers, and non-open-access articles reduced the selection to 511 articles. Further scrutiny led to the exclusion of 435 more articles due to lower-quality indexing or irrelevance, resulting in 76 journal articles for the review. RESULTS: During our investigation, we found that a major challenge for ML-based decision support is the abundance of features and the determination of their significance. In contrast, DL-based decision support is characterized by a plug-and-play nature rather than relying on a trial-and-error approach. Furthermore, we observed that pre-trained networks are practical and especially useful when working on complex images such as OCT. Consequently, pre-trained deep networks were frequently utilized for classification tasks. Currently, medical decision support aims to reduce the workload of ophthalmologists and retina specialists during routine tasks. In the future, it might be possible to create continuous learning systems that can predict ocular pathologies by identifying subtle changes in OCT images.

Latent mutations in the ancestries of alleles under selection.

We consider a single genetic locus with two alleles A1 and A2 in a large haploid population. The locus is subject to selection and two-way, or recurrent, mutation. Assuming the allele frequencies follow a Wright-Fisher diffusion and have reached stationarity, we describe the asymptotic behaviors of the conditional gene genealogy and the latent mutations of a sample with known allele counts, when the count n1 of allele A1 is fixed, and when either or both the sample size n and the selection strength |α| tend to infinity. Our study extends previous work under neutrality to the case of non-neutral rare alleles, asserting that when selection is not too strong relative to the sample size, even if it is strongly positive or strongly negative in the usual sense (α→-∞ or α→+∞), the number of latent mutations of the n1 copies of allele A1 follows the same distribution as the number of alleles in the Ewens sampling formula. On the other hand, very strong positive selection relative to the sample size leads to neutral gene genealogies with a single ancient latent mutation. We also demonstrate robustness of our asymptotic results against changing population sizes, when one of |α| or n is large.

Blood-Derived Eye Drops for the Treatment of Corneal Neuropathic Pain.

Blood-derived preparations, including autologous or allogenic serum, umbilical cord serum/plasma, and platelet-rich plasma eye drops, contain various growth factors, cytokines, and immunoglobulins that resemble natural tears. These components play important roles in corneal cell migration, proliferation, and wound healing. Blood-derived eye drops have demonstrated clinical effectiveness across a spectrum of ocular surface conditions, encompassing dry eye disease, Sjögren's syndrome, graft-versus-host disease, and neuropathic corneal pain (NCP). Currently, management of NCP remains challenging. The emergence of blood-derived eye drops represents a promising therapeutic approach. In this review, we discuss the benefits and limitations of different blood-derived eye drops, their mechanisms of action, and treatment efficacy in patients with NCP. Several studies have demonstrated the clinical efficacy of autologous serum eye drops in relieving pain and pain-like symptoms, such as allodynia and photoallodynia. Corneal nerve parameters were also significantly improved, as evidenced by increased nerve fiber density, length, nerve reflectivity, and tortuosity, as well as a decreased occurrence of beading and neuromas after the treatment. The extent of nerve regeneration correlated with improvement in patient-reported photoallodynia. Cord plasma eye drops also show potential for symptom alleviation and corneal nerve regeneration. Future directions for clinical practice and research involve standardizing preparation protocols, establishing treatment guidelines, elucidating underlying mechanisms, conducting long-term clinical trials, and implementing cost-effective measures such as scaling up manufacturing. With ongoing advancements, blood-derived eye drops hold promise as a valuable therapeutic option for patients suffering from NCP.

Neuropathic Corneal Pain: Tear Proteomic and Neuromediator Profiles, Imaging Features, and Clinical Manifestations.

PURPOSE: To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, and clinical manifestations in neuropathic corneal pain (NCP) patients. DESIGN: Cross-sectional study. METHODS: A total of 20 NCP patients and 20 age-matched controls were recruited. All subjects were evaluated by corneal sensitivity, Schirmer test, tear break-up time, and corneal and ocular surface staining, Ocular Surface Disease Index and Ocular Pain Assessment Survey questionnaires were administered, as well as IVCM examinations for corneal nerves, microneruomas, and epithelial and dendritic cells. Tears were collected for neuromediator and proteomic analysis using enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. RESULTS: Burning and sensitivity to light were the 2 most common symptoms in NCP. A total of 188 significantly dysregulated proteins, such as elevated metallothionein-2, creatine kinases B-type, vesicle-associated membrane protein 2, neurofilament light polypeptide, and myelin basic protein, were identified in the NCP patients. The top 10 dysregulated biological pathways in NCP include neurotoxicity, axonal signaling, wound healing, neutrophil degradation, apoptosis, thrombin signaling mitochondrial dysfunction, and RHOGDI and P70S6K signaling pathways. Compared to controls, the NCP cohort presented with significantly decreased corneal sensitivity (P < .001), decreased corneal nerve fiber length (P = .003), corneal nerve fiber density (P = .006), and nerve fiber fractal dimension (P = .033), as well as increased corneal nerve fiber width (P = .002), increased length, total area and perimeter of microneuromas (P < .001, P < .001, P = .019), smaller corneal epithelial size (P = .017), and higher nerve growth factor level in tears (P = .006). CONCLUSIONS: These clinical manifestations, imaging features, and molecular characterizations would contribute to the diagnostics and potential therapeutic targets for NCP.

Effectiveness of simulation models and digital alternatives in training ophthalmoscopy: A systematic review.

PURPOSE: Traditional direct ophthalmoscopy (TDO) is the oldest method of fundus examination; however, it has fallen out of use due to its technical difficulty and limitations to clinical utility, amidst the advent of potentially better options. A spectrum of new technologies may help in addressing the shortcomings of TDO: simulation mannequins with non-tracked TDO, simulation models with tracked TDO, and smartphone ophthalmoscopy (SFO). METHODOLOGY: A systematic search of PubMed, Embase, and Cochrane databases for all studies evaluating usage of simulation mannequins/models and SFO in ophthalmology education was performed, from inception till April 2023 with no language restriction. We ensured that we included all possible relevant articles by performing backward reference searching of included articles and published review articles. RESULTS: We reviewed studies on non-tracked TDO (n = 5), tracked TDO (n = 3) and SFO (n = 12). Non-tracked TDO and SFO were superior in training competency relative to control (TDO on real eyes). Intriguingly, tracked TDO was non superior to controls. SFO appears to enhance the learning effectiveness of ophthalmoscopy, due to real-time projection of the retina view, permitting instantaneous and targeted feedback. Learners reported improved ergonomics, including a wider field of view and more comfortable viewing distance. Retention of images and recordings permitted the audit of learning and paves the way for storage of such images in patients' electronic medical record and rapid dissemination for specialist referral. CONCLUSIONS: Smartphone ophthalmoscopy (SFO) permits integration of both the practice and learning of ophthalmoscopy, and the auditing of both. These advantages over traditional methods (with simulation or otherwise) may lead to a paradigm shift in undergraduate ophthalmology education. However, the nascency of SFO necessitates preservation of traditional techniques to tide through this period of transition.

A Systematic Review of Tear Vascular Endothelial Growth Factor and External Eye Diseases.

We aim to summarize the current evidence of Vascular endothelial growth factors (VEGF)s in external eye diseases and determine whether serum and plasma VEGF levels are associated with tear and ocular surface tissues. A systematic search of PUBMED and EMBASE was conducted using PRISMA guidelines between October 2022 and November 2023, with no restriction on language or publication date. Search terms included relevant MESH terms. These studies were evaluated for quality, and an assessment of the risk of bias was also carried out. Extracted data were then visually represented through relevant tables or figures. The initial literature search yielded 777 studies from PUBMED, 944 studies from EMBASE, and 10 studies from manual searches. Fourteen eligible studies were identified from 289 articles published from 2000 to 2023 in the English language or with English translations, including rabbit models, murine models, and human-derived samples. Most studies were retrospective in nature and case-control studies. Various common external eye diseases, such as dry eye disease (DED) and allergic eye disease were investigated. Despite limitations and small sample sizes, researchers have found elevated tissue levels of the VEGF in the vascularized cornea, especially in animal models, but there is no evidence of clear changes in the tear concentrations of VEGF in DED and allergic eye disease. Tear VEGF is associated with corneal vascularization. Anti-VEGF therapies may have the potential to manage such conditions.

Bursts of coalescence within population pedigrees whenever big families occur.

We consider a simple diploid population-genetic model with potentially high variability of offspring numbers among individuals. Specifically, against a backdrop of Wright-Fisher reproduction and no selection, there is an additional probability that a big family occurs, meaning that a pair of individuals has a number of offspring on the order of the population size. We study how the pedigree of the population generated under this model affects the ancestral genetic process of a sample of size two at a single autosomal locus without recombination. Our population model is of the type for which multiple-merger coalescent processes have been described. We prove that the conditional distribution of the pairwise coalescence time given the random pedigree converges to a limit law as the population size tends to infinity. This limit law may or may not be the usual exponential distribution of the Kingman coalescent, depending on the frequency of big families. But because it includes the number and times of big families, it differs from the usual multiple-merger coalescent models. The usual multiple-merger coalescent models are seen as describing the ancestral process marginal to, or averaging over, the pedigree. In the limiting ancestral process conditional on the pedigree, the intervals between big families can be modeled using the Kingman coalescent but each big family causes a discrete jump in the probability of coalescence. Analogous results should hold for larger samples and other population models. We illustrate these results with simulations and additional analysis, highlighting their implications for inference and understanding of multilocus data.

The Conjunctival Microbiome and Dry Eye: What We Know and Controversies.

ABSTRACT: Dry eye disease is a common multifactorial condition that may be idiopathic or associated with autoimmune conditions, such as Sjogren syndrome. Commensal microorganisms modify immune responses, so it is relevant to understand how they modify such immune-mediated diseases. Microbiota in the gut regulate inflammation in the eye, and conversely, severe inflammation of the ocular surface results in alteration of gut microbiome. The conjunctiva microbiome can be analyzed using 16S or shotgun metagenomics. The amount of microbial DNA in ocular surface mucosa relative to human DNA is limited compared with the case of the intestinal microbiome. There are challenges in defining, harvesting, processing, and analyzing the microbiome in the ocular surface mucosa. Recent studies have shown that the conjunctiva microbiome depends on age, presence of local and systemic inflammation, and environmental factors. Microbiome-based therapy, such as the use of oral probiotics to manage dry eye disease, has initial promising results. Further longitudinal studies are required to investigate the alteration of the conjunctival microbiome after local therapy and surgery.

Two-Photon and Multiphoton Microscopy in Anterior Segment Diseases of the Eye.

Two-photon excitation microscopy (TPM) and multiphoton fluorescence microscopy (MPM) are advanced forms of intravital high-resolution functional microscopy techniques that allow for the imaging of dynamic molecular processes and resolve features of the biological tissues of interest. Due to the cornea's optical properties and the uniquely accessible position of the globe, it is possible to image cells and tissues longitudinally to investigate ocular surface physiology and disease. MPM can also be used for the in vitro investigation of biological processes and drug kinetics in ocular tissues. In corneal immunology, performed via the use of TPM, cells thought to be intraepithelial dendritic cells are found to resemble tissue-resident memory T cells, and reporter mice with labeled plasmacytoid dendritic cells are imaged to understand the protective antiviral defenses of the eye. In mice with limbal progenitor cells labeled by reporters, the kinetics and localization of corneal epithelial replenishment are evaluated to advance stem cell biology. In studies of the conjunctiva and sclera, the use of such imaging together with second harmonic generation allows for the delineation of matrix wound healing, especially following glaucoma surgery. In conclusion, these imaging models play a pivotal role in the progress of ocular surface science and translational research.

Neuropathic Corneal Pain after Coronavirus Disease 2019 (COVID-19) Infection.

INTRODUCTION: This is a case report of a patient with neuropathic corneal pain after coronavirus disease 2019 (COVID-19) infection. METHODS: A previously healthy 27-year-old female presented with bilateral eye pain accompanied by increased light sensitivity 5 months after COVID-19 infection. She was diagnosed with neuropathic corneal pain based on clear corneas without fluorescein staining, alongside the presence of microneuromas, dendritic cells, and activated stromal keratocytes identified bilaterally on in vivo confocal microscopy. RESULTS: The patient's tear nerve growth factor, substance P, and calcitonin gene-related peptide levels were 5.9 pg/mL, 2978.7 pg/mL, and 1.1 ng/mL, respectively, for the right eye and 23.1 pg/mL, 4798.7 pg/mL, and 1.2 ng/mL, respectively, for the left eye, suggesting corneal neuroinflammatory status. After 6 weeks of topical 0.1% flurometholone treatment, decreased microneuroma size, less extensive dendritic cells, and reduced tear nerve growth factor and substance P levels were observed. The scores on the Ocular Pain Assessment Survey showed an improvement in burning sensation and light sensitivity, decreasing from 80% and 70% to 50% for both. CONCLUSIONS: Neuropathic corneal pain is a potential post-COVID-19 complication that warrants ophthalmologists' and neurologists' attention.

Salivary Gland Transplantation as a Promising Approach for Tear Film Restoration in Severe Dry Eye Disease.

With increased awareness of dry eye disease (DED), a multitude of therapeutic options have become available. Nevertheless, the treatment of severe DED remains difficult. In a patient whose DED is related to the loss of lacrimal function without severe destruction of the salivary glands, autologous transplantation of the latter as functioning exocrine tissue to rebuild a stable tear film is an attractive idea. All three major and minor salivary glands have been used for such transplantation. Due to the complications associated with and unfavorable prognosis of parotid duct and sublingual gland transplantation, surgeons now prefer to use the submandibular gland (SMG) for such procedures. The transplantation of the SMG not only has a high survival rate, but also improves dry eye symptoms and signs for more than 20 years post-surgery. The regulation of the secretion of the transplanted SMG is critical because the denervated SMG changes its mechanism of secretion. Innovative procedures have been developed to stimulate secretion in order to prevent the obstruction of the Wharton's duct and to decrease secretion when postoperative "epiphora" occurs. Among the minor salivary glands, the transplantation of the labial salivary glands is the most successful in the long-term. The measurement of the flow rates of minor salivary glands and donor-site selection are critical steps before surgery.

The Association of Dry Eye Disease with Functional Visual Acuity and Quality of Life.

BACKGROUND: Dry eye disease (DED) is a common chronic condition with increasing prevalence. Standard discriminative visual acuity is not reflective of real-world visual function, as patients can achieve normal acuities by blinking. METHODS: Participants recruited from a tertiary referral eye centre were divided into two groups-Severe DED (with significant, central staining) and Mild DED (absence of such staining). Functional Visual Acuity (FVA) in both groups was assessed using the DryeyeKT mobile application and Impact of Vision Impairment (IVI) questionnaire to assess quality of life (QOL). RESULTS: Among the 78 participants (74.4% women), 30 (38.5%) had Severe DED and 48 (61.5%) Mild DED. In women, Severe DED produced a significantly worse FVA of 0.53 ± 0.20 vs. 0.73 ± 0.30 in the Mild DED group (p = 0.006). FVA decreased with increasing age, showing a significant inverse correlation (r = -0.55). A poorer FVA ≤ 0.6 was seen in older patients (68.2 years ± 7.68) vs. an FVA > 0.6 in younger patients (58.9 years ± 10.7), p < 0.001. When adjusting for age, FVA was still 0.107 lower in the Severe DED group, p = 0.003. There was significant difficulty in performing specific daily activities in the Severe DED group, after adjusting for age, gender and FVA. CONCLUSIONS: FVA is reduced in severe DED and older people. Severe DED significantly impacts certain aspects of QOL. However, no significant relationship was found between FVA and QOL. FVA is not the only reason for the compromise of health-related QOL in severe dry eye.

Allogeneic Umbilical Cord Plasma Eyedrops for the Treatment of Recalcitrant Dry Eye Disease Patients.

BACKGROUND: Dry eye disease is a significant disease in Singapore. While there have been studies using allogenic cord serum for the treatment of dry eye disease, treatment of dry eyes with allogenic umbilical cord plasma drops has yet to be started in Singapore. PURPOSE: To evaluate the effectiveness of umbilical cord plasma eyedrops for the treatment of recalcitrant dry eyes in a local Singaporean context. METHODS: This is an observational, longitudinal, interventional study for dry eye patients who did not show clear improvement after standard therapy. Patients were recruited from 2020 to 2023 from the dry eye clinic of the Singapore National Eye Center. Umbilical cord plasma was delivered frozen to patients and stored in home freezers. All participants underwent a standardized clinical evaluation for dry eye, and data were collected. RESULTS: There were 40 participants (7 males and 33 females). The duration of follow-up was 5.52 ± 1.57 months. Kerato-epitheliopathy staining score, TBUT (tear breakup time), and SPEED (Standard Patient Evaluation of Eye Dryness Questionnaire) scores significantly improved after treatment. No statistically significant improvement was found in terms of visual acuity, according to Schirmer's score. CONCLUSION: Cord plasma eye drops significantly improved kerato-epitheliopathy staining scores in recalcitrant dry eye patients. Allogeneic plasma is a promising form of treatment for recalcitrant dry eye.

Patch formation driven by stochastic effects of interaction between viruses and defective interfering particles.

Defective interfering particles (DIPs) are virus-like particles that occur naturally during virus infections. These particles are defective, lacking essential genetic materials for replication, but they can interact with the wild-type virus and potentially be used as therapeutic agents. However, the effect of DIPs on infection spread is still unclear due to complicated stochastic effects and nonlinear spatial dynamics. In this work, we develop a model with a new hybrid method to study the spatial-temporal dynamics of viruses and DIPs co-infections within hosts. We present two different scenarios of virus production and compare the results from deterministic and stochastic models to demonstrate how the stochastic effect is involved in the spatial dynamics of virus transmission. We compare the spread features of the virus in simulations and experiments, including the formation and the speed of virus spread and the emergence of stochastic patchy patterns of virus distribution. Our simulations simultaneously capture observed spatial spread features in the experimental data, including the spread rate of the virus and its patchiness. The results demonstrate that DIPs can slow down the growth of virus particles and make the spread of the virus more patchy.

Quantum molecular resonance electrotherapy (Rexon-Eye) for recalcitrant dry eye in an Asian population.

Objectives: To assess the safety, efficacy, patients' satisfaction and acceptability of Rexon-Eye electrotherapy in treating Asian severe dry eye disease (DED) patients. Methods: Prospective parallel-arm pilot study recruiting 40 DED Chinese patients with >moderate recalcitrant DED (Contact Lens Research Unit [CCLRU] > grade 2). Subjects were randomized into 2 groups, undergoing four weekly treatment sessions each: group 1 received full treatment power; group 2 received control treatment (power 1 treatment). Non-invasive tear break-up time (NIBUT), cornea fluorescein staining graded via CCLRU and Schirmer's I test were compared pre- and 2 months post-treatment. The SPEED and QUEST questionnaires that evaluated subjective symptoms and treatment satisfaction, respectively, at baseline and 2 weeks post-treatment were carried out. Tear cytokine levels in both groups were examined at 2 weeks post-treatment. Results: The amount of improvement in post-treatment corneal staining in the inferior corneal zone was significant in Group 1 (p = 0.038) but not in Group 2 (p = 0.832). Group 1 eyes with worse baseline staining (total score >9.8) had a significantly greater reduction of corneal staining than those with better baseline staining (-11.7 ± 1.98 vs. -4.6 ± 2.89, p < 0.001). There were no other significant differences in NIBUT, Schirmer's 1 and cornea fluorescein staining grading within or between the groups.: Group 1 (n = 24) had improved subjective dryness scores compared to Group 2 (n = 16) (SPEED score: 6.38 + 4.16 vs. 10.0 + 6.36, p = 0.04). No significant differences were seen in 11 tear cytokine levels at 2 weeks post-treatment between the 2 groups. Conclusion: In Asian DED patients treated with Rexon-Eye, inferior cornea staining showed significant improvement compared to placebo, and eyes with greater cornea staining at baseline achieved a greater improvement in staining. There were no other significant improvements in NIBUT and Schirmer's 1. Rexon-Eye also improved subjective DED scores in 41.7% of eyes without any adverse effects.

Molecular Basis of Transglutaminase-2 and Muscarinic Cholinergic Receptors in Experimental Myopia: A Target for Myopia Treatment.

Myopia, a prevalent refractive error disorder worldwide, is characterized by the elongation of the eye, leading to visual abnormalities. Understanding the genetic factors involved in myopia is crucial for developing therapeutic and preventive measures. Unfortunately, only a limited number of genes with well-defined functionality have been associated with myopia. In this study, we found that the homozygous TGM2-deleted gene in mice protected against the development of myopia by slowing down the elongation of the eye. The effectiveness of gene knockdown was confirmed by achieving a 60 percent reduction in TGM-2 transcript levels through the use of TGM-2-specific small interfering RNA (siRNA) in human scleral fibroblasts (SFs). Furthermore, treating normal mouse SFs with various transglutaminase inhibitors led to the down-regulation of TGM-2 expression, with the most significant reduction observed with specific TGM-2 inhibitors. Additionally, the study found that the pharmacological blockade of muscarinic receptors also slowed the progression of myopia in mice, and this effect was accompanied by a decrease in TGM-2 enzyme expression. Specifically, mice with homozygous mAChR5, mAChR1, and/or mAChR4 and knockout mice exhibited higher levels of TGM-2 mRNA compared to mice with homozygous mAChR2 and three knockout mice (fold changes of 5.8, 2.9, 2.4, -2.2, and -4.7, respectively; p < 0.05). These findings strongly suggest that both TGM-2 and muscarinic receptors play central roles in the development of myopia, and blocking these factors could potentially be useful in interfering with the progression of this condition. In conclusion, targeting TGM-2 may have a beneficial effect regarding myopia, and this may also be at least partially be the mechanism of anti-muscarinic drugs in myopia. Further studies should investigate the interaction between TGM-2 and muscarinic receptors, as well as the changes in other extracellular matrix genes associated with growth during the development of myopia.

Impact of Exposomes on Ocular Surface Diseases.

Ocular surface diseases (OSDs) are significant causes of ocular morbidity, and are often associated with chronic inflammation, redness, irritation, discomfort, and pain. In severe OSDs, loss of vision can result from ocular surface failure, characterised by limbal stem cell deficiencies, corneal vascularisation, corneal opacification, and surface keratinisation. External and internal exposomes are measures of environmental factors that individuals are exposed to, and have been increasingly studied for their impact on ocular surface diseases. External exposomes consist of external environmental factors such as dust, pollution, and stress; internal exposomes consist of the surface microbiome, gut microflora, and oxidative stress. Concerning internal exposomes, alterations in the commensal ocular surface microbiome of patients with OSDs are increasingly reported due to advancements in metagenomics using next-generation sequencing. Changes in the microbiome may be a consequence of the underlying disease processes or may have a role in the pathogenesis of OSDs. Understanding the changes in the ocular surface microbiome and the impact of various other exposomes may also help to establish the causative factors underlying ocular surface inflammation and scarring, the hallmarks of OSDs. This review provides a summary of the current evidence on exposomes in various OSDs.

Conjunctival infiltrates and cytokines in an experimental immune-mediated blepharoconjunctivitis rat model.

Purpose: To characterize the histopathological and immunological findings of a rat model of allergic blepharoconjunctivitis (BC) and demonstrate its potential utility for the assessment of BC therapies. Methods: Sprague-Dawley (SD) rats were immunized with ovalbumin (OVA) and topically challenged with OVA (BC group) or PBS (control group), while a corticosteroid group was pre-treated with triamcinolone acetate 24 h before the challenge. Morphological features were evaluated and tissues were harvested for histological, flow cytometry and cytokine analysis. Results: The BC group rats developed eyelid excoriations, redness, and conjunctival edema 24 h after the OVA challenge, while corticosteroid pre-treated and PBS-challenged rats were unaffected. The BC features were reduced despite repeated challenges for 5 days. Massive immune cell infiltration was observed in conjunctivae of BC rats, while no significant infiltration was seen in the other groups. Populations of T cells, mono-macrophages, neutrophils, and NK cells made up more than 77% of CD45+7AAD- cells in the conjunctival tissues. T cell proportions were increased at 96 h compared to 24 h post-challenge, while macrophages decreased during the same time period. Eosinophils and intraepithelial neutrophils were detected in the BC rats, but not in the PBS and corticosteroid groups. BC eyes had significantly higher levels of IFN-γ and IL-2, while IL-4 and IL-6 levels were similar to controls. Conclusion: A robust BC response was detected in this rat model which was suppressed by corticosteroid pre-treatment. Immune cell composition and cytokine profiles changed over time.

New developments in the management of persistent corneal epithelial defects.

A persistent epithelial defect (PED) is a corneal epithelial defect that failed to heal after 2weeks. It is a condition that carries much morbidity, and our understanding of PED remains poor, with current treatment methods often having unsatisfactory outcomes. With PEDs becoming more prevalent, more efforts are required to establish reliable treatment modalities. Our reviews describe the causes of PEDs and the different approaches developed to manage them, as well as their associated limitations. Emphasis is placed on understanding various advances in the development of new treatment modalities. We have also described a case of a woman with a background of graft-versus-host disease on long-term topical corticosteroids who developed complicated PED involving both eyes. The current approach to managing PEDs generally involves exclusion of an active infection, followed by treatment modalities that aim to encourage corneal epithelial healing. Success rates, however, remain far from desirable, as treatment remains challenging due to multiple underlying etiologies. In summary, advances in the development of new therapies may be able to facilitate progress in the understanding and treatment of PED.