Neuropeptide alpha-Melanocyte stimulating hormone preserves corneal endothelial morphology in a murine model of Fuchs dystrophy.

Fuchs endothelial corneal dystrophy is a heterogenous disease with multifactorial etiology, and genetic, epigenetic, and exogenous factors contributing to its pathogenesis. DNA damage plays a significant role, with ultraviolet-A (UV-A) emerging as a key contributing factor. We investigate the potential application of neuropeptide α-melanocyte stimulating hormone (α-MSH) in mitigating oxidative stress induced endothelial damage. First, we examined the effects of α-MSH on a cultured human corneal endothelial cell line (HCEnC-21T) exposed to hydrogen peroxide (H2O2) induced oxidative DNA damage. We performed immunofluorescence and flow cytometry to assess DNA damage and cell death in the cultured cells. Additionally, we used an established mouse model that utilizes ultraviolet light to induce corneal endothelial cell damage resulting in decreased CEnC number, increased cell size variability, and decreased percentage of hexagonal cells. This endothelial decompensation leads to an increase in corneal thickness. Following UV-A exposure, the mice were systemically treated with α-MSH, either immediately after exposure (early treatment) or beginning two weeks post-exposure (delayed treatment). To evaluate treatment efficacy, we analyzed CEnC density and morphology using in vivo confocal microscopy, and central corneal thickness using anterior segment optical coherence tomography. Our findings demonstrated that α-MSH treatment effectively protects HCEnC-21T from free-radical induced oxidative DNA damage and subsequent cell death. In vivo, α-MSH treatment, mitigated the loss of CEnC density, deterioration of cell morphology and suppression of the resultant corneal swelling. These results underline the potential application of α-MSH as a therapeutic agent for mitigating corneal endothelial damage.

Potential applications of mesenchymal stem cells in ocular surface immune-mediated disorders.

We explore the interaction between corneal immunity and mesenchymal stem/stromal cells (MSCs) and their potential in treating corneal and ocular surface disorders. We outline the cornea's immune privilege mechanisms and the immunomodulatory substances involved. In this realm, MSCs are characterized by their immunomodulatory properties and regenerative potential, making them promising for therapeutic application. Therefore, we focus on the role of MSCs in immune-mediated corneal diseases such as dry eye disease, corneal transplantation rejection, limbal stem cell deficiency, and ocular graft-versus-host disease. Preclinical and clinical studies demonstrate MSCs' efficacy in promoting corneal healing and reducing inflammation in these conditions. Overall, we emphasize the potential of MSCs as innovative therapies in ophthalmology, offering promising solutions for managing various ocular surface pathologies.

Thyroid Eye Disease: Advancements in Orbital and Ocular Pathology Management.

Thyroid Eye Disease (TED) is a debilitating autoimmune condition often associated with thyroid dysfunction, leading to significant ocular and orbital morbidity. This review explores recent advancements in the management of TED, focusing on both medical and surgical innovations. The introduction of Teprotumumab, the first FDA-approved drug specifically for TED, marks a pivotal development in medical therapy. Teprotumumab targets the insulin-like growth factor-1 receptor (IGF-1R), effectively reducing inflammation and tissue remodeling. Clinical trials demonstrate its efficacy in reducing proptosis and improving quality of life, making it a cornerstone in the treatment of active, moderate-to-severe TED. Surgical management remains critical for patients with chronic TED or those unresponsive to medical therapy. Advancements in orbital decompression surgery, including image-guided and minimally invasive techniques, offer improved outcomes and reduced complications. Innovations in eyelid and strabismus surgery enhance functional and cosmetic results, further improving patient satisfaction. The management of TED necessitates a multidisciplinary approach involving endocrinologists, ophthalmologists, oculoplastic surgeons, radiologists, and other specialists. This collaborative strategy ensures comprehensive care, addressing the diverse aspects of TED from thyroid dysfunction to ocular health and psychological well-being. Future directions in TED treatment include emerging pharmacological therapies targeting different aspects of the disease's pathophysiology and advanced surgical techniques aimed at enhancing precision and safety. This review underscores the importance of a personalized, multidisciplinary approach in managing TED, highlighting current advancements, and exploring potential future innovations to improve patient outcomes and quality of life.

IL-6 induces Treg dysfunction in desiccating stress-induced dry eye disease.

Regulatory T cells (Tregs) play a critical role in maintaining immune homeostasis, and their dysfunction is implicated in the pathogenesis of various autoimmune disorders, including dry eye disease (DED). Treg dysfunction in DED allows T-helper cell 17 (Th17) mediated chronic inflammation at the ocular surface. In this study, the factors causing Treg dysfunction in DED were investigated. We observed reduced expression of Treg functional markers - FoxP3, CD25, and CTLA-4 in the cells isolated from DED mice (DED Tregs). Additionally, DED Tregs showed increased expression levels of receptors for pro-inflammatory cytokine receptors, namely IL-6R, IL-17RA, and IL-23R. An increased expression level of pro-inflammatory cytokine receptors was observed on exposing Tregs isolated from naïve mice (NTregs) to IL-6 or IL-17, but not IL-23, with a concomitant downregulation of FoxP3, CD25, and CTLA-4 in these cells. Furthermore, among these cytokines, IL-6 induced the most pronounced loss of Treg mediated suppression of Th17 proliferation and IL-10 secretion. In vitro and in vivo blockade of IL-6 effectively restored function in DED Tregs, leading to enhanced suppressive function against proliferating Th17 cells and ameliorating disease severity. In conclusion, this study provides insights into mechanisms of Treg dysregulation in DED, specifically delineating the effect of Th17-associated cytokines, with IL-6 emerging as the critical factor inducing Treg dysfunctionality. These findings highlight the potential for developing novel therapeutic interventions for DED through restoration of immunosuppressive function of Tregs.

Whole-eye transplantation: Current challenges and future perspectives.

Whole-eye transplantation emerges as a frontier in ophthalmology, promising a transformative approach to irreversible blindness. Despite advancements, formidable challenges persist. Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival. Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive, prompting the exploration of neurotrophic support and immunomodulatory interventions. Immunological tolerance, paramount for graft acceptance, confronts the distinctive immunogenicity of ocular tissues, driving research into targeted immunosuppression strategies. Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks. Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities. Biomaterials, stem cell therapies, and precision immunomodulation represent promising avenues in this pursuit. Ultimately, the aim of this review is to critically assess the current landscape of whole-eye transplantation, elucidating the challenges and advancements while delineating future directions for research and clinical practice. Through concerted efforts, whole-eye transplantation stands to revolutionize ophthalmic care, offering hope for restored vision and enhanced quality of life for those afflicted with blindness.

Immunopathological mechanisms and clinical manifestations of ocular graft-versus-host disease following hematopoietic stem cell transplantation.

Graft-versus-host disease is among the most common clinical complications following allogeneic hematopoietic stem cell transplantation. It causes inflammation-mediated destruction and dysfunction of various organ systems including ocular tissues in 60-90% of the patients and is termed ocular GVHD (oGVHD). In oGVHD, donor-derived T-cells recognize host antigens as foreign, resulting in immune dysregulation, inflammation and fibrosis of lacrimal glands, meibomian glands, cornea, and conjunctiva. The clinical presentation in oGVHD patients range from mild dry eye symptoms to catastrophic inflammation mediated pathological changes which can cause corneal perforation and blindness. In this review article, we provide detailed insights into the impact of mucosal barrier disruption, the afferent and efferent phases of immunological response involving activation of antigen presenting cells and T cells, respectively. We evaluate the evidence outlining the effector phase of the disease leading to cellular destruction and eventually fibrosis in patients with oGVHD. Finally, we discuss the well-established criteria for the diagnosis of oGVHD.

Local administration of myeloid-derived suppressor cells prevents progression of immune-mediated dry eye disease.

Myeloid derived suppressor cells (MDSCs) are a heterogenous population of immature hematopoietic precursors with known immunoregulatory functions. The immunosuppressive role of MDSCs has been highlighted in several inflammatory ophthalmic disorders; however, their therapeutic application in suppressing the immune-mediated changes in dry eye disease (DED) has not been studied. We observed significant reduction in antigen presenting cell (APC) frequencies and their maturation in the presence of MDSCs. Moreover, co-culturing MDSCs with T helper 17 cells (Th17) resulted in reduced Th17 frequencies and their IL-17 expression. On the contrary, MDSCs maintained regulatory T cell frequencies and enhanced their function in-vitro. Furthermore, we delineated the role of interleukin-10 (IL-10) secreted by MDSCs in their immunoregulatory functions. We confirmed these results by flow cytometry analysis and observed that treatment with MDSCs in DED mice effectively suppressed the maturation of APCs, pathogenic Th17 response, and maintained Treg function and significantly ameliorated the disease. The results in this study highlight the potential therapeutic application of MDSCs in treating refractory DED.

COVID-19 pathogenesis.

The pathogenesis of COVID-19 involves a complex interplay between host factors and the SARS-CoV-2 virus, leading to a multitude of clinical manifestations beyond the respiratory system. This chapter provides an overview of the risk factors, genetic predisposition, and multisystem manifestations of COVID-19, shedding light on the underlying mechanisms that contribute to extrapulmonary manifestations. The chapter discusses the direct invasion of SARS-CoV-2 into various organs as well as the indirect mechanisms such as dysregulation of the renin-angiotensin-aldosterone system (RAAS), immune response dysfunctions within the innate and adaptive immune systems, endothelial damage, and immunothrombosis. Furthermore, the multisystem manifestations of COVID-19 across different organ systems, including the cardiovascular, renal, gastrointestinal, hepatobiliary, nervous, endocrine and metabolic, ophthalmic, ear-nose-throat, reproductive, hematopoietic, and immune systems are discussed in detail. Each system exhibits unique manifestations that contribute to the complexity of the disease.

Management of multi-surface ocular burns caused by molten iron.

Ocular thermal burns are medical emergencies that require immediate intervention before the standard management protocol, which involves obtaining a detailed history and performing an ophthalmic examination. In this case report, we report the clinical manifestations of ocular burns caused by molten iron and the steps taken for good clinical outcomes. The patient presented with an inferior epithelial defect and limbal and lower lid ischemia at four hours post-injury. Over the course of treatment, due to non-resolving epithelial defect and increased superior lid notching, amniotic membrane transplantation (AMT) and lid repair by pentagon wedge excision were performed. Following AMT, the corneal surface completely healed with residual opacity and neovascularization. Additionally, limbal ischemia was significantly reduced with the restoration of normal lid anatomy. Corneal burns initiate a cascade of inflammatory reactions disrupting the balance between pro- and anti-angiogenic factors, leading to corneal neovascularization. The eyelid damage can lead to necrosis of tissues with eschar formation and eventually quantitative tissue loss. Therefore, timely intervention is the key to the successful management of ocular burns.

Reliability of Ahmed glaucoma valve surgical videos for educational purposes.

PURPOSE: The use of video-based social media platforms is increasing among trainee residents, fellows, and practicing ophthalmologists. In this study, we objectively evaluate the quality of Ahmed glaucoma valve (AGV) implantation videos on open access, video-based internet platforms. DESIGN: Internet-based cross-sectional study. PARTICIPANTS: Not applicable. METHODS: In this cross-sectional study, 23 websites publishing medical surgery training video content were queried using the keyword "Ahmed glaucoma valve implantation". MAIN OUTCOME MEASURES: The descriptive statistics of video parameters were noted, and the videos were assessed using established scoring systems-Sandvik, Health on the Net Foundation Code of Conduct (HON code), mDISCERN, and Global Quality Score (GQS) scores. Video Quality Score (VQS) was determined based on the 14 steps per the AGV implantation rubric. RESULTS: One hundred and nineteen videos were evaluated, and 35 were excluded. The total quality of all 84 videos according to their Sandvik, HON Code, GQS, DISCERN, and VQS scores was 11.79 ± 1.70 (excellent quality), 6.86 ± 0.75 (excellent quality), 3.97 ± 0.93 (good quality), 3.26 ± 0.66 (fair quality) and 11.45 ± 2.67 (good quality), respectively. No significant correlation was found between the descriptive parameters and video quality score. However, no significant correlation was found between the descriptive parameters and video quality score. CONCLUSIONS: The objective analysis showed that the video quality ranged from good to excellent. AGV implantation videos were sparse on exclusive ophthalmology surgical video portals. Therefore, more peer-reviewed videos following standardized rubric are needed on open-access surgical video platforms.

Ocular complications of plasma cell dyscrasias.

Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal antibody. These disorders are associated with various systemic findings, including ophthalmological disorders. A search of PubMed, EMBASE, Scopus and Cochrane databases was performed in March 2021 to examine evidence pertaining to ocular complications in patients diagnosed with plasma cell dyscrasias. This review outlines the ocular complications associated with smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, plasmacytomas, multiple myeloma, Waldenström's macroglobulinemia, systemic amyloidosis, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome, and cryoglobulinemia. Although, the pathological mechanisms are not completely elucidated yet, wide-ranging ocular presentations have been identified over the years, evolving both the anterior and posterior segments of the eye. Moreover, the presenting symptoms also help in early diagnosis in asymptomatic patients. Therefore, it is imperative for the treating ophthalmologist and oncologist to maintain a high clinical suspicion for identifying the ophthalmological signs and diagnosing the underlying disease, preventing its progression through efficacious treatment strategies.

Conventional type I migratory CD103+ dendritic cells are required for corneal allograft survival.

Corneal transplant rejection primarily occurs because of the T helper 1 (Th1) effector cell-mediated immune response of the host towards allogeneic tissue. The evidence suggests that type 1 migratory conventional CD103+ dendritic cells (CD103+DC1) acquire an immunosuppressive phenotype in the tumor environment; however, the involvement of CD103+DC1 in allograft survival continues to be an elusive question of great clinical significance in tissue transplantation. In this study, we assess the role of CD103+DC1 in suppressing Th1 alloreactivity against transplanted corneal allografts. The immunosuppressive function of CD103+DC1 has been extensively studied in non-transplantation settings. We found that host CD103+DC1 infiltrates the corneal graft and migrates to the draining lymph nodes to suppress alloreactive CD4+ Th1 cells via the programmed death-ligand 1 axis. The systemic depletion of CD103+ DC1 in allograft recipients leads to amplified Th1 activation, impaired Treg function, and increased rate of allograft rejection. Although allograft recipient Rag1 null mice reconstituted with naïve CD4+CD25- T cells efficiently generated peripheral Treg cells (pTreg), the CD103+DC1-depleted mice failed to generate pTreg. Furthermore, adoptive transfer of pTreg failed to rescue allografts in CD103+DC1-depleted recipients from rejection. These data demonstrate the critical role of CD103+DC1 in regulating host alloimmune responses.

Imaging-based Assessment of Choriocapillaris: A Comprehensive Review.

PURPOSE: Over the past two decades, advancements in imaging modalities have significantly evolved the diagnosis and management of retinal diseases. Through these novel platforms, we have developed a deeper understanding of the anatomy of the choroidal vasculature and the choriocapillaris. The recently developed tools such as optical coherence tomography (OCT) and OCT angiography (OCTA) have helped elucidate the pathological mechanisms of several posterior segment diseases. In this review, we have explained the anatomy of the choriocapillaris and its close relationship to the outer retina and retinal pigment epithelium. METHODS: A comprehensive search of medical literature was performed through the Medline/PubMed database using search terms: choriocapillaris, choroid, quantification, biomarkers, diabetic retinopathy, age-related macular degeneration, choroidal blood flow, mean blur rate, flow deficit, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, indocyanine green angiography, OCTA, Doppler imaging, uveitis, choroiditis, white dot syndrome, tubercular serpiginous-like choroiditis, choroidal granuloma, pachychoroid, toxoplasmosis, central serous chorioretinopathy, multifocal choroiditis, choroidal neovascularization, choroidal thickness, choroidal vascularity index, choroidal vascular density, and choroidal blood supply. The search terms were used either independently or combined with choriocapillaris/choroid. RESULTS: The imaging techniques which are used to qualitatively and quantitatively analyze choriocapillaris are described. The pathological alterations in the choriocapillaris in an array of conditions such as diabetes mellitus, age-related macular degeneration, pachychoroid spectrum of diseases, and inflammatory disorders have been comprehensively reviewed. The future directions in the study of choriocapillaris have also been discussed. CONCLUSION: The development of imaging tools such as OCT and OCTA has dramatically improved the assessment of choriocapillaris in health and disease. The choriocapillaris can be delineated from the stromal choroid using the OCT and quantified by manual or automated methods. However, these techniques have inherent limitations due to the lack of an anatomical distinction between the choriocapillaris and the stromal choroid, which can be overcome with the use of predefined segmentation slabs on OCT and OCTA. These segmentation slabs help in standardizing the choriocapillaris imaging and obtain repeatable measurements in various conditions such as diabetic retinopathy, age-related macular degeneration, pachychoroid spectrum, and ocular inflammations. Additionally, Doppler imaging has also been effectively used to evaluate the choroidal blood flow and quantifying the choriocapillaris and establishing its role in the pathogenesis of various retinochoroidal diseases. As tremendous technological advancements such as wide-field and ultra-wide field imaging take place, there will be a significant improvement in the ease and accuracy of quantifying the choriocapillaris.

Atezolizumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis and Takotsubo cardiomyopathy.

Atezolizumab is a humanised monoclonal IgG1 antibody that is used in treating many solid malignancies. Endocrinopathies are known but a rare adverse event of these immunotherapeutic drugs. Autoimmune diabetes induced by atezolizumab has been rarely reported in the literature. We report the case of a woman in her eighth decade with no known history of diabetes who developed new-onset autoimmune diabetes and Takotsubo cardiomyopathy due to the adverse effects of atezolizumab therapy for hepatocellular carcinoma. We also review the characteristics and outcomes of cases previously reported in the literature.

Prevalence of neurotrophic keratopathy in patients with chronic ocular graft-versus-host disease.

PURPOSE: To determine the prevalence, clinical characteristics, and risk factors associated with neurotrophic keratopathy (NK) in patients with chronic ocular graft-versus-host disease (oGVHD). DESIGN: Retrospective cohort study. METHODS: We performed a chart review of patients diagnosed with chronic oGVHD between January 2015 and December 2018 at a single academic institution and recorded demographic data, systemic and ocular comorbidities, history of hematologic malignancy, transplant characteristics, oGVHD severity scores, and adnexal and ocular examination findings. We determined the prevalence of NK and clinical characteristics associated with NK in these patients. A multivariate logistic regression analysis was performed to determine the risk factors associated with NK in these patients. MAIN OUTCOME MEASURE: Prevalence of NK in chronic oGVHD. RESULTS: We identified 213 patients diagnosed with chronic oGVHD following hematopoietic stem cell or bone marrow transplantation from our electronic patient database, and the prevalence of NK was 14%. The mean age of oGVHD patients with NK was 62.6 ± 12.9 years; 48% were women, 19 had unilateral NK, and ten had bilateral NK. In the cohort, 56%, 20%, and 24% eyes of the patients had grades 1, 2, and 3 of NK, respectively. The mean time to diagnose NK after transplantation was 52.9 ± 45.4 months. oGVHD patients diagnosed with NK had a significantly higher NIH oGVHD severity score (p = 0.04) and a lower corneal sensation score (p = 0.0001) than those without NK. Our analyses showed a significantly higher CFS score (p = 0.01) and a trend toward lower Schirmer test scores (p = 0.16) and tear break-up times (p = 0.08) in oGVHD patients with NK. Additionally, we observed a significantly higher prevalence of persistent epithelial defect (p = 0.0001), corneal ulceration (p = 0.0001), and corneal perforation (p = 0.005) in oGVHD patients diagnosed with NK. A logistic regression analysis to determine factors associated with NK showed that a higher NIH oGVHD score (odds ratio [OR] = 2.03, p = 0.026) and history of cataract surgery (odds ratio [OR] = 5.03, p = 0.001) are significant risk factors for NK in oGVHD patients. CONCLUSIONS: The prevalence of NK in chronic oGVHD patients was 14% during the study period. Our analysis shows that oGVHD patients with a higher NIH oGVHD severity score and previous history of cataract surgery are at a higher risk of developing NK and may develop severe sequelae such as persistent epithelial defect or corneal ulceration.

Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial.

PURPOSE: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation. DESIGN: Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil. PARTICIPANTS: Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft. METHODS: Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks. MAIN OUTCOME MEASURE: The 52-week endothelial immune rejection rate. RESULTS: Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis. CONCLUSIONS: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.

Eye-tunes: role of music in ophthalmology and vision sciences.

Although the healing effect of music has been recognized since time immemorial, there has been a renewed interest in its use in modern medicine. This can be attributed to the increasing focus on holistic healing and on the subjective and objective aspects of well-being. In ophthalmology, this has ranged from using music for patients undergoing diagnostic procedures and surgery, as well as for doctors and the operation theatre staff during surgical procedures. Music has proven to be a potent nonpharmacological sedative and anxiolytic, allaying both the pain and stress of surgery. This review aims to explore the available evidence about the role of music as an adjunct for diagnostic and surgical procedures in current ophthalmic practices.

Metastatic squamous cell carcinoma of the colon: a conundrum in colorectal malignancies.

Small-cell carcinoma of the colon is an extremely rare tumour, with poorly understood pathogenesis and unestablished treatment guidelines. The first case was documented in 1919, and only about 100 cases of this condition have been reported to this date. In this case report, we present a case of sigmoid squamous cell carcinoma that eventually led to bowel perforation and was diagnosed on histopathology after emergent surgical intervention. Additionally, we also review the incidence, epidemiology, pathogenesis, immunohistological markers, neogenomics and therapeutic strategies for the same.

Application of Artificial Intelligence in the Diagnosis and Management of Corneal Diseases.

Diagnosis and treatment planning in ophthalmology heavily depend on clinical examination and advanced imaging modalities, which can be time-consuming and carry the risk of human error. Artificial intelligence (AI) and deep learning (DL) are being used in different fields of ophthalmology and in particular, when running diagnostics and predicting outcomes of anterior segment surgeries. This review will evaluate the recent developments in AI for diagnostics, surgical interventions, and prognosis of corneal diseases. It also provides a brief overview of the newer AI dependent modalities in corneal diseases.

Prevalence and Risk Factors Associated With Corneal Perforation in Chronic Ocular Graft-Versus-Host-Disease.

PURPOSE: To determine the prevalence and risk factors associated with corneal perforation in patients with chronic ocular graft-versus-host disease (oGVHD). METHODS: We reviewed the case records of 405 patients diagnosed with chronic oGVHD over 8 years at a single academic center and assessed the prevalence of corneal perforation in the cohort. We reviewed patient demographics, indication for and type of hematopoietic stem cell transplantation (HSCT), time elapsed between HSCT and perforation, and clinical characteristics including oGVHD severity scores, ocular comorbidities, and topical medications at the time of perforation. Data were analyzed to determine the characteristics of patients with corneal perforation and establish the risk factors. RESULTS: Of the 405 patients with chronic oGVHD, 15 (3.7%) developed a corneal perforation. The mean age of patients at the time of perforation was 64 ± 11 years and 10 (67%) were men. The median time to corneal perforation was 3.3 years post-HSCT. Although perforation occurred unilaterally in all cases, 44% had epithelial defects and 38% had stromal abnormalities in the contralateral eye. Of the patients with corneal perforation, 9 (60%) had a National Institute of Health oGVHD severity score of 2 and 6 (40%) had a score of 3. Patients with chronic oGVHD on antiglaucoma drops had a significantly higher risk of corneal perforation (P < 0.001). CONCLUSIONS: Corneal perforation is a rare but vision-threatening complication of chronic oGVHD. Our study emphasizes the need for frequent and long-term follow-up of patients with oGVHD regardless of the severity of disease. In particular, patients with chronic oGVHD on topical antiglaucoma medications should be monitored closely due to a higher risk for corneal perforation.