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Severe ocular allergic diseases, such as atopic keratoconjunctivitis and vernal keratoconjunctivitis, cause severe allergic inflammation in the conjunctiva and corneal epithelial damage, resulting in visual disturbances. The involvement of damage (danger)-associated molecular patterns (DAMPs/alarmins) in the pathogenesis of these diseases has been recognized. Alarmins released from damaged corneal epithelial cells or eosinophils play a critical role in the induction of corneal lesions, vicious loop of corneal injury, and exacerbation of conjunctival allergic inflammation. Alarmins in the conjunctiva also play an essential role in the development of both allergic inflammation, based on the acquired immune system, and type 2 inflammation by innate immune responses in the ocular surface. Therefore, alarmins may be a potentially important therapeutic target in severe refractory ocular allergic diseases.

Sex hormones are molecules produced by the gonads and to a small extent by the adrenal gland, which not only determine the primary and secondary sexual characteristics of an individual, differentiating man from woman, but also participate in the functioning of the various systems of the body. The evidence that many eye diseases differ in terms of prevalence between men and women has allowed us, in recent years, to carry out several studies that have investigated the association between sex hormones and the pathophysiology of eye tissues. Specific receptors for sex hormones have been found on the lacrimal and meibomian glands, conjunctiva, cornea, lens, retina, and choroid. This work summarizes the current knowledge on the role that sex hormones play in the pathogenesis of the most common ocular disorders and indicates our clinical experience in these situations. The aim is to stimulate an interdisciplinary approach between endocrinology, neurology, molecular biology, and ophthalmology to improve the management of these diseases and to lay the foundations for new therapeutic strategies.

Ocular infection with Toxoplasma gondii causes toxoplasmosis in mice. However, following ocular infection with tachyzoites, the cause of the accompanying progressive changes in hippocampal-dependent tasks, and their relationship with the morphology and number of microglia, is less well understood. Here, in 6-month-old, female BALB/c mice, 5 μl of a suspension containing 48.5 × 10 6 tachyzoites/ml was introduced into the conjunctival sac; control received an equal volume of saline. Before and after instillation, all mice were subject to an olfactory discrimination (OD) test, using predator (cat) feces, and to an open-field (OF) task. After the behavioral tests, the animals were culled at either 22 or 44 days post-instillation (dpi), and the brains and retinas were dissected and processed for immunohistochemistry. The total number of Iba-1-immunolabeled microglia in the molecular layer of the dentate gyrus was estimated, and three-dimensional reconstructions of the cells were evaluated. Immobility was increased in the infected group at 12, 22, and 43 dpi, but the greatest immobility was observed at 22 dpi and was associated with reduced line crossing in the OF and distance traveled. In the OD test, infected animals spent more time in the compartment with feline fecal material at 14 and at 43 dpi. No OD changes were observed in the control group. The number of microglia was increased at 22 dpi but returned to control levels by 44 dpi. These changes were associated with the differentiation of T. gondii tachyzoites into bradyzoite-enclosed cysts within the brain and retina. Thus, infection of mice with T. gondii alters exploratory behavior, gives rise to a loss in predator's odor avoidance from 2 weeks after infection, increased microglia number, and altered their morphology in the molecular layer of the dentate gyrus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Soares, Leão, Freitas, Alves, Tavares, Costa, Menezes, Oliveira, Guerreiro, Assis, Araújo, Franco, Anaissi, Carmo, Morais, Demachki, Diniz, Nunes, Anthony, Diniz and Diniz.)

Background: Ligneous conjunctivitis is a rare form of chronic pseudomembranous conjunctivitis which usually starts during infancy. We report on an unsual case of recurrent ligneous conjunctivitis after cataract surgery in a 67-year-old male patient., Methods: The equipment used for the slit-lamp images was a Haag Streit slit lamp BX900 Sn 00,406 with 16 × magnifications. The used batch number of the camera was sn00406 and the software was from the company CCS Pawlowski Merge Eye. There were no filters used. The images were saved with a resolution of 300 DPI. Neither downstream nor averaging was used to enhance the resolution of the image in the case presentation section or the figure legend. The equipment used for the cross-sectional histologic images was a Zeiss Axioskop 40 microscope with an objective lens Zeiss A-Plan × 20/0.45 (Zoom 6.3 × TV 2/3″″C). The used camera was AxioCam MRc5 and the software was ZEN 3.2. The cross-sectional histologic images were saved with a resolution of 2584 × 1936 Pixels. Neither downstream nor averaging was used to enhance the resolution of the image in the case presentation section or the figure legend., Case Presentation: This is a rare case report of ligneous conjunctivitis in a 67-year-old male patient who presented a recurrent conjunctival granuloma after five excisions following cataract surgery in his left eye. We performed a tumor excision with free conjunctival autograft. The histology showed a fibrin crust including macrophages, granulocytes, lymphocytes, and reactively altered squamous cell nests. These findings were consistent with a ″pseudomembrane in conjunctivitis lignosa″. We administered a topical combination of plasminactivator, heparin, cortisone and cyclosporine., Conclusion: This treatment with the combination of plasminactivator, heparin, cortisone and cyclosporine has proven to be effective in preventing the recurrence of ligneous conjunctivitis., (© 2022. The Author(s).)

Superior limbic keratoconjunctivitis (SLK) is characterized by chronic inflammation of the superior limbus and superior bulbar and tarsal conjunctivae. Patients also often have fine punctate staining of the limbus and adjacent area, superior limbic proliferation seen as thickening of the limbal epithelium and surrounding conjunctiva, and occasionally filaments at the superior limbus and upper cornea. SLK frequently presents with ocular irritation, foreign body sensation, and photophobia. SLK can be associated with other ocular and non-ocular conditions, such as thyroid disease. Although the pathogenesis of SLK is still unknown, it is thought to be related to mechanical injury, tear film instability, or an autoimmune/inflammatory etiology. Many patients with SLK can be asymptomatic or have symptoms that resolve or remit spontaneously. For symptomatic SLK, patients are managed medically with treatments such as lubricants, topical anti-inflammatory or immunomodulatory medications, punctal occlusion, and bandage contact lenses. Patients with symptoms refractory to medical management may need surgical interventions. We detail the current literature on the epidemiology, clinical manifestations, associated conditions, histopathology, pathogenesis, and treatment of SLK., (Copyright © 2021. Published by Elsevier Inc.)

Objective: The aim of this retrospective study was to review the clinical data and outcomes of patients that suffered ectopic cilium (EC)., Animals Studied: One hundred and twelve dogs from multiple private practices in France, with a clinical diagnosis of EC were included in the study., Results: The mean age of affected dogs was 2.3 years. There were 64 females and 48 males. The most represented breeds were the Shi Tzu, the French Bulldog, the English Bulldog and the Chihuahua. Eleven dogs were affected bilaterally. The upper eyelid was implicated in 93.5% of the cases, with the median portion being the most affected. No statistical difference was observed between the right and the left eye. EC were associated with distichiasis in 50% of the cases. Pigmentation of the conjunctiva at the point of exit of the EC was present in 58% of the cases. EC were short in 75% and long in 25% of the cases. Corneal complications were statistically associated with short EC. The corneal lesions associated with EC were keratitis (94%), corneal granuloma (0.8%), corneal fibrosis (2.7%), corneal degeneration (0.8%), superficial corneal ulcer (68.7%), deep corneal ulcer (8%) and perforating corneal ulcer (0.8%). The surgeries which consisted of the removal of the hair follicle was successful in 88.4% of the cases., Conclusion: EC is a rare condition which can be treated successfully by the removal of the hair follicles. It must be suspected in cases of corneal lesions unresponsive to medical treatment., (© 2021 American College of Veterinary Ophthalmologists.)

Purpose: To evaluate the effect of direct cell injury of cryotherapy on eyelid sebaceous gland carcinoma cells by an ex vivo cryotherapy experiment., Methods: It was a prospective interventional case series. Six patients with biopsy-proven nodular sebaceous gland carcinoma were included. After excision of the mass, a thin slice of the mass resembling the thickness of the conjunctiva was shaved off and was oriented over the broad end of a tissue forceps. Cryotherapy was applied to both its anterior and posterior aspects by the triple freeze-thaw technique. The mass was then labeled and sent separately for histopathological evaluation by fixation and staining., Results: A total of six patients with a mean age of 58.2 ± 15.5 years were included. There were four females and two males. The mean duration of the lesion was 21.6 ± 17.51 months. All patients had involvement of the upper eyelid. The patients were clinically staged as T2b (n=2), T1a (n=2), T2c (n=1), and T3a (n=1) respectively. There was no regional lymphadenopathy or metastasis in any of the cases. The experimental cryo-tissue containing the cryo-treated lesion revealed the presence of viable tumor cells (>50%) in all six specimens., Conclusion: The direct cell injury caused by cryotherapy may not be sufficient to kill all the residual sebaceous gland carcinoma cells on the tumor bed., Competing Interests: None

Purpose: The aim of this study was to evaluate the prevalence of histopathologically confirmed ocular surface squamous neoplasia (OSSN) in clinically diagnosed pterygium samples at a tertiary center in Northern California, over a 10-year period (2009-2019)., Methods: A retrospective chart review of patients older than 18 years with clinically diagnosed benign pterygium requiring excision was conducted. Clinically suspected pterygia were excised using standard techniques and routinely submitted to the University of California Davis for pathologic evaluation. Demographic, clinical, surgical, and pathological information were recorded and analyzed. The prevalence rate of OSSN was calculated., Results: A total of 348 consecutive specimens were evaluated. The mean (±SD) age of the patients was 58 ± 12 years, with a near equal sex representation. A total of 57 (16%) pterygia were recurrent at initial presentation. Histopathologic results demonstrated a single case of OSSN. This patient did not have a documented history of carcinoma in other organs or any history of herpes virus, human papilloma virus, or human immunodeficiency virus infection., Conclusions: The prevalence of histopathological OSSN in clinically suspected pterygia within our sample was approximately 0.3%. Because of shared clinical characteristics of pterygia and OSSN, a high index of suspicion and judicious use of anterior segment optical coherence tomography enable for effective preoperative diagnosis of OSSN. However, in the absence of clinical expertise or high-resolution optical coherence tomography, routine tissue pathologic examination may be warranted., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The impact of particulate matter (PM) on ocular surface health has attracted increased attention in recent years. Previous studies have reported that differences in the chemical composition of PM can affect the toxicological response. However, available information on the toxic effects of chemical components of PM on the ocular surface is insufficient. In this paper, we aimed to investigate the toxicity effects of chemical components of PM on the ocular surface, focusing on the effects of four different types of nanoparticles (NPs) in human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs), which include titanium dioxide (TiO 2 ), carbon black (CB), zinc dioxide (ZnO), and silicon dioxide (SiO 2 ). We found that the in vitro cytotoxic effects of CB, ZnO, and SiO 2 NPs are dependent on particle properties and cell type as well as the exposure concentration and time. Here, the order of increasing toxicity was SiO 2 → CB → ZnO, while TiO 2 demonstrated no toxicity. Moreover, toxic effects appearing more severe in HCECs than HCjECs. Reactive oxygen species (ROS)-mediated oxidative stress plays a key role in the toxicity of these three NPs in HCECs and HCjECs, leading to apoptosis and mitochondrial damage, which are also important contributors to aging. Sirtuin1 (SIRT1) as an NAD+-dependent protein deacetylase that seems to play a potential protective role in this process. These findings implied that ROS and/or SIRT1 may become a potential target of clinical treatment of PM- or NP-related ocular surface diseases., (© 2022. The Author(s).)

Purpose: The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI)., Methods: Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications., Results: Included were 15 patients (10 women and 5 men; 36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient., Conclusions: RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated., Competing Interests: D. S. Chu serves as a speaker for Abbvie and Novartis and as a consultant for Aldeyra Therapeutics Dompé, Mallinckrodt and Santen Pharmaceuticals. S. D. Anesi serves as a consultant for Mallinckrodt and Santen Pharmaceuticals, Allakos, Eyepoint, and Takeda and as a speaker for AbbVie, Mallinckrodt, and Eyepoint. A. J. W. Huang serves as a speaker for Mallinckrodt. C. S. Foster serves as a consultant for Aldeyra Therapeutics, Allakos, Bausch & Lomb Surgical, Eyegate Pharma, Genentech, Novartis, and pSivida and as a speaker for Alcon and Allergan and Mallinckrodt pharmaceuticals. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pterygium is a kind of common conjunctival degeneration. The pathogenesis of pterygium is complex, and various biomarkers provide new targets for treatment and prognosis. Currently, the most common treatment for pterygium is surgical excision, but it is invasive risk and has a high recurrence rate. Since the development of sequencing, gene chip technology, and proteomics technologies has been rapid, research on the internal mechanism of disease has been facilitated. This review focuses on recent advances in the discovery of biomarkers from the fields of genetics, proteomics, and epigenetics and their likely functional mechanisms and clinical applications in pterygium., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Ocular surface squamous neoplasia (OSSN) comprises neoplasm arising from the ocular surface, which includes conjunctiva, cornea, and limbus and ranges from mild dysplasia to invasive squamous cell carcinoma., Purpose: The aim of this work was to study the spectrum of OSSN based on histopathological analysis. Materials and., Methods: This was a retrospective cross-sectional study comprising 776 histopathologically diagnosed cases of OSSN from January 2004 to December 2014., Results: The mean age of presentation of OSSN was 45 years (median, 45 years; 2 to 87 years) with male preponderance (74%). The most common age group of presentation was 41-60 years (n = 299; 39%). The most common type of OSSN was invasive squamous cell carcinoma seen in 50% (n = 383) eyes followed by severe dysplasia/carcinoma in situ in 31% (n = 250) eyes. Tumor infiltration at base was seen in 16% (n = 124), positive margins in 32% (n = 248), scleral infiltration in 14% (n = 109), intraocular extension in 3% (n = 23), and orbital extension in 4% (n = 26) eyes. OSSN was associated with actinic keratosis in 21% (n = 165) cases., Conclusion: Based on histopathology, invasive squamous cell carcinoma is the most common form of OSSN in the Asian Indian population., Competing Interests: None

Sebaceous adenoma of the conjunctiva is a very rare lesion of uncertain origin. It is usually associated with Muir-Torre syndrome in which neoplasms are also found in other parts of the body. We present the case of a 71-year-old man without a previous or family history of neoplasia, who presented with severe inflammation and an infection in his right eye associated with a tumor of the conjunctiva near the caruncle. The lesion was excised and histopathology revealed a sebaceous adenoma. Microsatellite instability was not observed immunohistochemically. He remains alive and well., (Copyright © 2019 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: To evaluate whether allergic conjunctivitis (AC) could be induced by Acanthamoeba excretory-secretory protein (ESP) and analyze the therapeutic effect of resolvin (Rv) D1 and antiallergic agents., Methods: Human conjunctival epithelial cells (HCVCs) were treated with 10 µg/well of ESP, and Th2 cytokines were measured using real-time PCR. C57BL/6 mice were treated with 10 µg/5 µL of ESP after sensitization, and conjunctivas isolated from the mice were stained with hematoxylin and eosin (H&E) for the analysis of eosinophils and periodic acid-Schiff (PAS) for the analysis of goblet cells. Cytokine levels in the eye-draining lymph nodes (dLNs) and spleens were measured using the enzyme-linked immunosorbent assay (ELISA). Then, the treatment effects of RvD1 and the antiallergic agents (olopatadine, bepotastine, and alcaftadine) on the HCVCs, mouse conjunctivas, dLNs, and spleens were assessed., Results: Th2 cytokines were increased in the ESP-treated conjunctival cells. Mouse conjunctivas treated with ESP showed significant infiltration of eosinophils and goblet cells, and the dLN and spleen exhibited increased IL-4, IL-5 and IL-13 levels. All findings were significantly decreased upon treatment with RvD1 and the antiallergic agents., Conclusions: Acanthamoeba could be used to establish an animal model of AC, which could be effectively treated with RvD1 or topical antiallergic agents.

Purpose: To investigate whether transvascular indocyanine green (ICG) dye leakage is associated with conjunctival malignancy., Methods: This is a prospective interventional study. Patients presenting with circumscribed conjunctival melanocytic disorders (CMDs) were included and examined using color photography, anterior segment optical coherence tomography to measure lesion size, and fluorescein and ICG angiography to measure vascular pattern and leakage. Time to vascular leakage was measured by 2 independent observers. Lesions were characterized as benign or malignant based on histopathological features., Results: Thirty patients with CMD were included: 22 lesions were benign (conjunctival nevus, n = 20; conjunctival melanocytic intraepithelial neoplasia without atypia, n = 2) and 8 were malignant (in situ conjunctival melanoma n = 2; invasive conjunctival melanoma, n = 6). Malignant lesions had larger mean maximal diameters (11.0 ± 4.5 vs. 4.2 ± 2.5 mm, P = 0.003) and more frequently showed intrinsic tumor vasculature (8 of 8 vs. 10 of 22, P = 0.007). The mean time to ICG leakage was 350.9 ± 165.9 seconds in benign and 59.6 ± 22.1 seconds (P = 0.002) in malignant lesions and was inversely correlated with lesion size and thickness., Conclusions: Time to angiographic ICG dye leakage is significantly shorter in malignant versus benign CMD., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the efficacy of topical application of 3% diquafosol sodium (DQS) and tocopherol (TCP) acetate mixtures in a mouse model of experimental dry eye (EDE)., Methods: After exposure to desiccating stress for 5 days, eye drops consisting of 3% DQS alone, 0.01% TCP alone, or 3% DQS and 0.005% or 0.01% TCP mixture were applied for the treatment of EDE. Tear volume, tear film break-up time (TBUT), corneal fluorescein staining scores (CFSS), and tear film lipid layer grades (TFLLG) were measured at 0, 5 and 10 days after treatment. The 2',7'-dichlorodihydrofluorescein diacetate assay (DCFDA) for reactive oxygen species (ROS) production, enzyme-linked immunosorbent assay (ELISA) for malondialdehyde (MDA), and flow cytometry for CD4 + interferon (IFN)-γ+ T cells were evaluated on the ocular surface at 10 days after treatment. In addition, levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and chemokine CC motif ligand 4 (CCL4) in the conjunctiva were measured using a multiplex immunobead assay, and conjunctival goblet cells were counted by periodic acid-Schiff staining at 10 days after treatment., Results: Both the TCP mixture groups indicated a significant improvement in TBUT, ROS production, and MDA concentrations compared to those in the DQS alone group. Furthermore, the 0.01% TCP mixture group also showed higher tear film lipid layer grades and conjunctival goblet cell density and lower corneal fluorescein staining scores, number of CD4 + IFN-γ+ T cells, and levels of TNF-α, IL-1β, and CCL4 than the DQS alone group ( P  < 0.05)., Conclusions: Application of eye drops containing the mixture of DQS and TCP could stabilize the tear film lipid layer, improve TBUT and corneal epithelial damages, decrease ROS production, inflammatory molecules, and T cells, and increase conjunctival goblet cell density on the ocular surface. Topical DQS and TCP mixtures may have a greater therapeutic effect on clinical signs, oxidative damage, and inflammation of dry eye than DQS eye drops.

Purpose: to assess the effect of topical administration of the Neurokin-1 receptor (NK1R) antagonist Fosaprepitant in a pre-clinical model of ocular Graft-versus-Host disease (GVHD)., Methods: BALB/c mice were pre-conditioned by myeloablative total body irradiation and subjected to allogeneic bone marrow transplantation and mature T cell infusion (BM + T). BM-transplanted mice (BM) were used as controls. Ocular GVHD was specifically assessed by quantifying corneal epithelial damage, tear secretion, blepharitis and phimosis, 3 times/week for 28 days post-transplantation. A group of BM + T mice received Fosaprepitant 10 mg/mL, 6 times/day, topically, from day 7-29 after transplantation. After sacrifice, the expression of NK1R, CD45, CD3, and CXCL10 was quantified in the cornea, conjunctiva, and lacrimal gland by immunohistochemistry., Results: BM + T mice developed corneal epithelial damage (day 0-29, p < 0.001), blepharitis (day 0-29, p < 0.001), and phimosis (day 0-29, p < 0.01), and experienced decreased tear secretion (day 21, p < 0.01) compared to controls. NK1R was found upregulated in corneal epithelium (p < 0.01) and lacrimal gland (p < 0.01) of BM + T mice. Fosaprepitant administration significantly reduced corneal epithelial damage (p < 0.05), CD45 + (p < 0.05) and CD3 + (p < 0.01) immune cell infiltration in the cornea and conjunctiva (p < 0.001 and p < 0.001, respectively). In addition, Fosaprepitant reduced the expression of CXCL10 in the cornea (p < 0.05) and in the lacrimal gland (p < 0.05)., Conclusions: Our results suggest that NK1R represents a novel druggable pathway for the therapy of ocular GVHD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To explore clinical features and outcomes of ocular surface squamous neoplasia (OSSN) treated with primary interferon (IFN)-α2b, based on patient cigarette smoking status., Methods: Retrospective nonrandomized, interventional cohort study on 212 consecutive tumors in 194 patients, all of whom were treated with topical and/or injection IFNα2b., Results: There were 88 tumors in 76 patients with current or past smoking history (smokers) and 124 tumors in 118 nonsmoking patients (nonsmokers). A comparison (smokers vs. nonsmokers) revealed smokers with more frequent bilateral disease (16% vs. 3%, P = 0.003), more frequent involvement of inferior forniceal (34% vs. 21%, P = 0.03) and inferior tarsal conjunctiva (38% vs. 24%, P = 0.04), greater mean number of clock hour involvement (4.1 vs. 3.5 clock hours, P = 0.04), and greater dome growth pattern (30% vs. 15%, P = 0.01). There was no difference regarding method of IFNα2b administration as topical (61% vs. 71%, P = 0.14), injection (10% vs. 6%, P = 0.32), or combination topical/injection (28% vs. 23%, P = 0.33). A comparison revealed smokers with more frequent recurrence after initial response (23% vs. 13%, P = 0.04). There was no difference regarding initial tumor response or time to response, treatment side effects, or systemic outcomes., Conclusions: Regarding ocular surface squamous neoplasia, smokers more often display bilateral, dome-shaped tumors with inferior forniceal or tarsal involvement, and greater extent than nonsmokers. After treatment with topical and/or injection IFNα2b, control is equivalent, but smokers show greater recurrence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Significance: Dry eye is one of the leading causes for individuals to seek eye care, whereas the pathogenesis is poorly understood. One mechanism in which dry eye inflammation may ensue is by the release of damage-associated molecular patterns (DAMPs) by damaged cells to stimulate the production of cytokines and matrix metalloproteinases. Examining DAMP levels on the ocular surface during dry eye disease (DED) will increase our understanding of their potential involvement in the pathogenesis of DED., Purpose: This study aimed to quantitate DAMPs, high-mobility group box 1 (HMGB1), and heat shock proteins on the ocular surface of normal and dry eye subjects and to examine the impact of low-humidity environment (LHE) on DAMPs and inflammation in dry eye subjects., Methods: Basal tears (10 to 20 μL) and conjunctival impression cytology samples were analyzed for HMGB1, HSP-27, HSP-60, HSP-70, and HSP-90α by ELISA or Luminex assays in normal (n = 15) and DED (n = 15) subjects. In addition, a subset of DED subjects were exposed to LHE for 2 hours. The level of DAMPs in the tear film was evaluated by ELISA or Luminex assay. Interleukin 6, interleukin 8, or metalloproteinase (MMP) 9 mRNA were quantitated by real-time polymerase chain reaction from conjunctival impression cytology samples., Results: Compared with age-matched normal subjects, HMGB1 was significantly elevated in the tear film of DED subjects (P = .03), whereas there was no significant difference in heat shock proteins. Conjunctival impression cytology samples revealed no significant difference in intracellular DAMP levels between both groups. After exposure to an LHE, there was an increase in corneal staining (P = .005), HSP-60 levels in the tear film (P = .01), and MMP-9 mRNA in the conjunctiva (P = .001)., Conclusions: Dry eye subjects had higher levels of HMGB1 in their tear film. Exposure to an LHE worsened corneal staining, increased conjunctival MMP-9 mRNA expression, and increased tear film HSP-60 levels. Larger studies are needed to understand the involvement of DAMPs in stimulating dry eye inflammation., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Purpose: The aim was to evaluate the effectiveness of bacterial cellulose membrane (BCM) in preventing fibrosis in trabeculectomy and the biocompatibility of BCM with conjunctiva and sclera., Materials and Methods: Twenty-one eyes of 21 adult rabbits underwent fornix-based trabeculectomy. Standard surgery was done to control group (CG, n=7). Mitomycin-C (MMC) (0.3 mg/mL, 3 min) was applied to MMC group only (MMCG, n=7). BCM (~100 µm thick, 10×10 mm, single layer) was covered on the sclerotomy area before conjunctiva was closed in BCM group (BCMG, n=7). Intraocular pressures (IOP) were measured before, and 7, 14, 28, and 45 days after surgery (IOP-POD7, POD14, POD28, POD45). The IOP decrease were expressed as DIOP%-POD7, DIOP%-POD14, DIOP%-POD28, and DIOP%-POD45. The rabbits were sacrificed on the 45th day. Conjunctival vessel number, degrees of fibrosis, total inflammation, foreign body reaction, inflammatory cell types (B cells, T cells, plasma cells), macrophages, bleb spaces and the expression of α-smooth muscle actin were studied using histopathology and immunohistochemistry techniques. The groups were compared using nonparametric tests., Results: There was no statistically significant difference between the groups regarding baseline IOP and DIOP%-POD7 (P>0.05). While DIOP%-POD14, 28 and 45 were similar between BCMG and MMCG, they were significantly lower in CG (P<0.05). The lowest conjunctival vessel number was detected in the MMCG but the difference was not significant. There was no difference between BCMG and CG with regard to the numbers of B cells, T cells, and macrophages, however, these cells were significantly lower in MMCG (P<0.05). Five cases had mild and 2 cases had moderate foreign body reaction in the BCMG. There was mild to moderate inflammation in all BCM cases. While fibrosis and α-smooth muscle actin staining were higher in the CG (P<0.001), they were minimal in the BCM and MMCGs., Conclusions: BCM showed good biocompatibility and provided better control of IOP with minimal fibrosis at the trabeculectomy site compared with the control group., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Autoimmune epithelitis and chronic inflammation are one of the characteristic features of the immune pathogenesis of Sjögren's syndrome (SS)-related dry eye disease. Autoimmune epithelitis can cause the dysfunction of the excretion of tear fluid and mucin from the lacrimal glands and conjunctival epithelia and meibum from the meibomian glands. The lacrimal gland and conjunctival epithelia express major histocompatibility complex class II or human leukocyte antigen-DR and costimulatory molecules, acting as nonprofessional antigen-presenting cells for T cell and B cell activation in SS. Ocular surface epithelium dysfunction can lead to dry eye disease in SS. Considering the mechanisms underlying SS-related dry eye disease, this review highlights autoimmune epithelitis of the ocular surface, chronic inflammation, and several other molecules in the tear film, cornea, conjunctiva, lacrimal glands, and meibomian glands that represent potential targets in the treatment of SS-related dry eye disease.

Purpose: This study aimed to analyze the association of tear matrix metalloproteinase 9 (MMP-9) immunoassay with the severity of dry eye (DE) signs and symptoms through qualitative, semiquantitative, and quantitative evaluations of immunoassay band., Materials and Methods: This cross-sectional study enrolled 320 eyes of 320 patients. The clinical signs of DE were assessed using the Ocular Surface Disorder Index (OSDI) score, visual analogue scale (VAS), tear breakup time (tBUT), tear volume evaluation by tear meniscometry, and staining scores of the cornea and conjunctiva by the Oxford grading scheme. The tear MMP-9 immunoassay results were interpreted using qualitative (positive or negative), semi-quantitative (reagent band density on a four-point scale: 0 = negative; 1 = weakly positive; 2 = moderately positive; 3 = strongly positive), and quantitative (ratio of reagent band density to control band density) indicators., Results: Positive MMP-9 immunoassay results were significantly related to shorter tBUT, tBUT ≤3 seconds, higher corneal staining score, corneal staining score ≥2, and conjunctival staining score ≥2. The semi-quantitative results of the MMP-9 immunoassay were positively correlated with higher corneal staining score (r = 0.122, p = 0.029) and negatively correlated with tBUT (r = -0.125, p = 0.025). However, in the quantitative analysis, none of the DE signs or symptoms were correlated to the band density of the MMP-9 immunoassay., Conclusions: The positive MMP-9 immunoassay results were related to the severity of ocular signs of DE. However, using quantitative measures of the MMP-9 immunoassay to assess the clinical severity of DE requires further investigation., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The present study was designed to investigate the role of myofibroblast transdifferentiation and the conjunctival renin-angiotensin system (RAS) in the pathogenesis of graft-versus-host disease (GVHD)-associated conjunctival fibrosis., Methods: A mouse model of major histocompatibility-matched allogeneic transplantation was used to induce GVHD, with male B10.D2 mice as donors and female BALB/c mice as recipients. Male BALB/c to female BALB/c syngeneic transplantation was used as control. Y chromosome staining in the spleen cells obtained from female recipient mice was used to confirm engraftment. The phenol red thread test and fluorescein staining were used to quantify tears and corneal keratopathy. Eyes were harvested at 4 and 8 weeks after the transplant for alpha-smooth muscle actin (α-SMA), angiotensinogen, and angiotensin-converting enzyme (ACE) immunostaining. Conjunctiva was harvested for gene expression quantification of α-SMA, angiotensinogen, and ACE., Results: More than 80% of the spleen cells in the recipient mice were chromosome Y positive, thus conforming successful engraftment. A significant decrease in tear secretion and a marked increase in corneal keratopathy score after allogeneic transplantation indicated the onset of ocular GVHD in these mice. A significant increase in α-SMA gene expression and the presence of a large number of α-SMA-positive cells was noted in the bulbar orbital conjunctiva of mice after allogeneic transplantation. Allogenic transplantation also caused a significant increase in the gene expression and protein expression of angiotensinogen and ACE in the subconjunctival eyelid area., Conclusions: Results of the present study demonstrate that GVHD-associated conjunctival fibrosis is accompanied by myofibroblast formation and activation of the local conjunctival RAS.

Purpose: Certain systemic conditions are reported to be risk factors for dry eye disease (DED), but their associations with DED severity are not well studied. We evaluated whether systemic conditions reported to be DED risk factors are associated with severity of DED signs and symptoms., Design: Secondary analysis of data from the Dry Eye Assessment and Management Study, a large-scale multicenter randomized clinical trial of patients with moderate to severe DED., Participants: Five hundred thirty-five adult patients with moderate to severe DED from 27 United States centers., Methods: Patients reported their medical history at baseline. They underwent ocular surface examinations and symptom evaluation using standardized protocols at baseline, 6 months, and 12 months. We analyzed the associations of systemic conditions (a systemic disease or smoking history) reported as potential DED risk factors with the severity of DED signs and symptoms using generalized linear regression models adjusted by age, gender, race, and visit., Main Outcome Measures: Dry eye disease symptoms assessed using the Ocular Surface Disease Index (OSDI), 6 DED signs (tear film break-up time, anesthetized Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, tear osmolarity, and meibomian gland dysfunction), and a composite signs severity score from 0 to 1 (1 = most severe)., Results: The mean age was 58 years; 81% were women. More severe DED signs were associated significantly with Sjögren syndrome (mean composite signs severity score 0.52 with disease vs. 0.43 without disease; P < 0.001), facial rosacea (0.47 vs. 0.43; P = 0.002), rheumatoid arthritis (0.47 vs. 0.42; P = 0.002), peripheral artery disease (0.50 vs. 0.43; P < 0.001), and daily smoking history (0.45 vs. 0.43; P = 0.047). Thyroid dysfunction, osteoarthritis, diabetes, irritable bowel syndrome, hypercholesterolemia, hypertension, and hypertriglyceridemia were not associated significantly with DED signs. No conditions were associated significantly with OSDI., Conclusions: In this large, well-characterized cohort of patients with DED assessed under standardized procedures, patients with certain systemic diseases and smoking history showed more severe DED signs compared with patients without the conditions. The profile of significant DED signs varied by systemic condition, reflecting different DED causes. Understanding the systemic conditions and underlying causes that predispose some patients to severe DED can improve management., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The rehabilitation of visual acuity with severe conjunctival fibrosis depends on ocular reconstruction with suitable conjunctival substitutes. In this study, we have developed poly(lactic acid) (PLA) electrospun nanofibrous membranes (EFMs) surface coated by cellulose nanofibrils (CNF) and/or silk peptide (SP). The CNF coating improved the hydrophilicity and the SP coating proliferated conjunctival epithelial cells (CjECs). To prevent post-operative infections, the composite scaffolds were loaded with levofloxacin (LF), constantly exerting efficient bactericidal effects. In in vivo evaluations, the PLA EFMs presented excellent therapeutic effects by promoting structural and functional restoration of conjunctiva after transplant. Even with reduced topical administration of antibiotics, the coloboma treated with LF loaded scaffolds presented no infections. It could be deduced that the potent bacterial inhibition feature could save troubles for patients by minimizing the application of antibiotics post-surgery. Hence, the developed PLA EFMs loaded with LF could be promising conjunctival substitutes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: To evaluate the ocular symptoms and findings of children diagnosed with Crimean-Congo hemorrhagic fever (CCHF)., Methods: In this prospective study, children diagnosed with CCHF who underwent a complete ophthalmologic examination during the hospitalization period were included., Results: Twenty-four children with a mean age of 12.4 ± 3.6 years were included study. The most common ocular finding was conjunctival hyperemia and was observed in 50% of patients. Nine (37.4%) children had abnormalities in fundus examination. Two (8.3%) of them had dilated retinal veins, and 7 (29.1%) had tortuous retinal vessels. No significant difference was found between mild to moderate and severe disease groups in terms of ocular symptoms and ophthalmologic examination findings (P > 0.05, for all)., Conclusions: The increased retinal vessel tortuosity was detected as a fundus examination finding in children with CCHF. Both ophthalmologists and pediatricians should be aware of the various ocular manifestations of CCHF for rapid diagnosis and management., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The human conjunctival epithelial cells (HCEC) line the inner sides of the eyelids and the anterior part of the sclera. They include goblet cells that secret mucus into the tear film that protects the ocular surface. The conjunctival epithelium is subjected to mechano-physical stimuli due to eyelid movement during blinking, during wiping and rubbing the eyes, and when exposed to wind and air currents. We cultured primary HCEC under air-liquid interface (ALI) conditions in custom-designed wells that can be disassembled for installation of the in vitro model in a flow chamber. We exposed the HCEC after ALI culture of 8-10 days to steady and oscillatory airflows. The in vitro model of HCEC was exposed to steady wall shear stresses (sWSS) of 0.5 and 1.0 dyne/cm 2 for lengths of 30 and 60 min and to oscillatory wall shear stresses (oWSS) of 0.5 and 0.77 dyne/cm 2 amplitudes for a length of 10 min. Cytoskeletal alterations and MUC5AC mucin secretion in response to WSS were investigated using immunohistochemically fluorescent staining and enzyme-linked lectin assay (ELLA), respectively. The results revealed that both exposure times and sWSS values increased the polymerization of F-actin filaments while mucin secretion decreased. However, after a recovery of 24 h in the incubator we observed a decrease of F-actin fibers and mucin secretion only for exposure of 30 min. The length of exposure was more influential on cytoskeletal alterations than the level of sWSS. The very small effect of sWSS on mucin secretion is most likely related to the much smaller amount of goblet cell than in other mucus-secreting tissue. The results for both oWSS amplitudes revealed similar trends regarding F-actin and mucin secretion. Immediately post-exposure we observed an increase in polymerization of F-actin filaments while mucin secretion decreased. However, after 24-h recovery we observed that both F-actin and mucin secretion returned to the same values as for unexposed cultures. The results of this study suggest that WSS should be considered while exploring the physiological characteristics of HCEC., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: HIV infection is associated with a variety of ocular surface diseases. Understanding the difference of the ocular microbiota between HIV-infected and healthy individuals as well as the influence of antiretroviral therapy will help to investigate the pathogenesis of these conditions., Methods: A cross-sectional study was conducted on subjects including HIV-negative individuals, untreated HIV-infected individuals, and HIV-infected individuals with antiretroviral therapy. Conjunctival microbiota was assessed by bacterial 16S rRNA sequencing of the samples obtained from the conjunctival swab., Results: The microbial richness in ocular surface was similar in HIV-negative, untreated HIV-positive, and highly active antiretroviral therapy (HAART) subjects. The bacterial compositions were similar in the two HIV infection groups but were significantly different from the HIV-negative group. HAART changed the beta diversity of bacterial community as determined by Shannon index. CD4+ T cell count had no significant influence on the diversity of ocular microbiota in HIV-infected individuals., Conclusions: The data revealed the compositional and structural difference in conjunctival microbial community in subjects with and without HIV infection, indicating that HIV infection or its treatment, may contribute to ocular surface dysbiosis.

Antiproliferative therapies are crucially important for improving the success rate of the glaucoma filtration surgeries. In this study, we investigated the potential efficacy of Forkhead Domain Inhibitory-6 (FDI-6) in inhibiting post-trabeculectomy subconjunctival fibrosis. In vitro, the effect of FDI-6 (10 μM) on fibrotic response and its underlying mechanism were investigated in rabbit tenon's fibroblasts (RTFs) treated with or without transforming growth factor-β1 (TGF-β1, 20 ng/mL). In vivo, FDI-6 (40 μM) was injected subconjunctivally to a rabbit trabeculectomy model. Intraocular pressure (IOP) changes were monitored within the 14-day period post-surgery. Bleb morphology and subepithelial fibrosis at the operating area were evaluated with slit lamp and confocal microscopic examinations and with histologic examinations. The results showed that, in cell culture studies, FDI-6 suppressed the proliferation, migration, collagen gel contraction and the expression levels of fibronectin (FN) and α-smooth muscle actin (α-SMA) in RTFs with TGF-β treatment by down-regulating the TGF-β1/Smad2/3 signaling pathway. In animal studies, the IOPs of the FDI-6-treated group were significantly lower than those of the saline-treated group after trabeculectomy. The FDI-6-treated eyes showed a better bleb appearance with fewer blood vessels compared to the saline-treated eyes. The analysis of confocal microscopy in vivo and histopathology revealed that subconjunctival fibrosis after trabeculectomy was significantly attenuated in the FDI-6-treated group compared to the controls. In conclusion, our studies indicate that FDI-6 exerts an inhibitory effect on subconjunctival fibrosis caused by trabeculectomy, holding potentials as a new antiproliferative agent used in anti-glaucoma filtration surgeries in the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Elevated intraocular pressure (IOP) is a significant risk factor for vision loss due to glaucoma, which is a major cause of blindness worldwide. Glaucoma filtration surgery (GFS) is an important method to reduce IOP by guidance of aqueous humor into a newly built filtration bleb in the conjunctiva; management of the wound healing mechanism is essential for the success of GFS. Here, we investigated the roles of interleukin (IL)-6 family members during the wound healing process after GFS. At the surgical site, the expression levels of genes encoding IL-6, oncostatin M (OSM), their receptors, and collagen I were elevated at 3 h after GFS, whereas the levels of genes encoding transforming growth factor (TGF)-β, α-smooth muscle actin (SMA), type IV collagen, and fibronectin were elevated at 3 days after GFS. IL-6 trans-signaling and OSM signaling suppressed TGF-β-induced expression of α-SMA and collagen IV, as well as activation of the non-canonical TGF-β pathway, suggesting that IL-6 and OSM may aid in controlling the phase transition from inflammation to proliferation and remodeling. The suppressive effects of OSM were accompanied by STAT3 activation, such that STAT1 function was complementary to STAT3. Taken together, these observations indicated that IL-6 family members constitute early response genes after GFS, which can suppress TGF-β-induced expression of late response genes at the surgical site after GFS., (Copyright © 2021. Published by Elsevier Ltd.)

Recurrence is the most common problem following pterygium surgery. Whether bevacizumab can prevent pterygium recurrence is controversial. To address this point, we carried out a meta-analysis of randomized controlled trials evaluating the efficacy and safety of bevacizumab in the treatment of pterygium. We searched the PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature, China National Knowledge Infrastructure, and Wan fang databases up to September 20, 2020 for relevant articles. We used the Cochrane assessment tool to evaluate the methodologic quality of the included studies, and calculated the relative risk (RR) and 95% confidence interval (CI) of the reported recurrence and complication rates. A total of 17 studies including 1124 patients with 1144 eyes were included in the meta-analysis. The combined results showed that bevacizumab significantly reduced the recurrence rate of pterygium after surgery (RR = 0.652, 95% CI: 0.504-0.845, Z = 3.24, P = 0.001) and was not significantly associated with the occurrence of postoperative complications compared to control treatments (RR = 0.832, 95% CI: 0.604-1.145, Z = 1.13, P = 0.259). A subgroup analysis showed that the rate of pterygium recurrence was significantly lower with bevacizumab than in the control group at a dose of 2.5 mg (RR = 0.47, 95% CI: 0.24-0.91) administered by subconjunctival injection (RR = 0.54, 95% CI: 0.39-0.75) after a follow-up time of ≤ 6 months (RR = 0.63, 95% CI: 0.45-0.88). Thus, bevacizumab can reduce the risk of pterygium recurrence after surgery, and does not differ from placebo or other drug treatments in terms of the risk of complications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

The glycocalyx is the main component of the transcellular barrier located at the interface between the ocular surface epithelia and the external environment. This barrier extends up to 500 nm from the plasma membrane and projects into the tear fluid bathing the surface of the eye. Under homeostatic conditions, defense molecules in the glycocalyx, such as transmembrane mucins, resist infection. However, many pathogenic microorganisms have evolved to exploit components of the glycocalyx in order to gain access to epithelial cells and consequently exert deleterious effects. This manuscript reviews the implications of the ocular surface epithelial glycocalyx to bacterial, viral, fungal and parasitic infection. Moreover, it presents some ongoing controversies surrounding the functional relevance of the epithelial glycocalyx to ocular infectious disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Argüeso, Woodward and AbuSamra.)

Purpose : To demonstrate the reliability of conjunctival biopsy analyzed by direct immunofluorescence (DIF) and supplemented with avidin-biotin complex immunoperoxidase (ABC) in diagnosing oMMP, and report therapy response in biopsy-positive patients, particularly when previously biopsy-negative elsewhere. Methods : Retrospective outcomes review of 136 consecutive patients after conjunctival biopsy for suspected oMMP. Results : Among 136 patients, 66% were diagnosed with oMMP by DIF and 13% via supplemental ABC immunoperoxidase. Sensitivity increased from 79.6% with DIF to 95.6% with supplemental ABC. Among 57 biopsy-positive patients, 77% were in remission at 1-year follow-up and 88% after 2 years. Of 34 previous biopsy-negative but now biopsy-positive patients with a 2-year follow-up, 91% achieved remission, including all 16 diagnosed via DIF and ABC. Conclusion : Conjunctival biopsy analyzed by histopathology and DIF supplemented by ABC has high reliability for diagnosing oMMP and is a useful tool to use before starting long-term immunomodulatory therapy in a patient with suspected oMMP.

Purpose: Toll-like receptor 3 (TLR3), as a damage-associated molecular pattern sensor, can detect self-RNA released from necrotic cells induced by ultraviolet B (UVB) radiation exposure. Pterygium formation is believed to be a tumorigenesis-like process induced by UVB exposure. In this study, we aimed to investigate the expression pattern of TLR3 in pterygium specimens and cultured pterygial epithelial cells (PECs)., Methods: Human pterygium and ipsilateral pterygium-free conjunctiva from the same patients were used in this study. The expression of TLR3 and nuclear factor-kappa B (NF-κB) was investigated in these specimens. PECs were exposed to UVB radiation to determine the effect of UVB on the expression of TLR3 and the activation of NF-κB., Results: The immunofluorescence study showed stronger TLR3 expression in superficial epithelial cells in the pterygial epithelium in comparison with the normal conjunctival epithelium. The expression of TLR3 decreased in intensity from the superficial epithelium toward the basal cell layer, implying a correlation between UVB exposure and TLR3 expression. Differential TLR3 expression patterns in pterygial and conjunctival tissues were also found in quantitative PCR analyses. PECs after UVB irradiation had higher protein levels of TLR3 and phospho-NF-κB than those of the PECs without irradiation. Immunofluorescence studies showed that UVB irradiation induced the nuclear translocation of NF-κB in the PECs. In PECs with the targeted TLR3 gene silencing, the expression of phospho-NF-κB was not induced by UVB irradiation., Conclusions: Our results indicate that UVB exposure, TLR3 expression, and NF-κB activation may be a critical sequence that leads to the formation of pterygium.

Purpose: We aimed to evaluate activation of conjunctiva-associated lymphoid tissue (CALT) in patients with keratitis using in vivo confocal microscopy (IVCM) and conjunctival impression cytology (CIC)., Methods: In addition to anterior segment photography and corneal fluorescein staining, IVCM revealed the palpebral conjunctiva in all subjects, and CIC and immunofluorescence staining were performed., Results: Diffuse lymphoid tissue cell density in the eyes of patients with keratitis was significantly greater compared with healthy volunteers (P < 0.001). Similar trends were found in perifollicular lymphocyte density (P < 0.001), follicular density (P = 0.029), follicular center reflection intensity (P = 0.011), and follicular area (P < 0.001). Immunofluorescence staining showed that the proportions of CD4+ (61.7% ± 8.0% vs. 17.3% ± 10.2%, respectively, P < 0.001) and CD8+ (46.9% ± 10.0% vs. 19.6% ± 11.5%, respectively, P < 0.001) cells in patients with keratitis was greater compared with healthy volunteers. Interestingly, we also observed changes in the contralateral eye in subjects with keratitis., Conclusions: Our research suggests that CALT, as an ocular immune structure, is activated and plays an important role in the pathogenesis of keratitis. This has been overlooked previously. CALT is also active in the contralateral eye of subjects with keratitis.

Purpose: To report a case of solitary plasmacytoma of the conjunctiva with corneal encroachment and to review the literature of all published cases., Methods: A 70-year-old man presented with 1-month history of pain and watering in the right eye, 7 months after undergoing cataract surgery in the same eye., Results: The mass was surgically excised. Pathology and immunohistochemistry were consistent with plasmacytoma. Staging studies found no evidence of systemic disease., Conclusions: To our knowledge, this is the first case of plasmacytoma in the literature to involve the cornea. This case was not associated with systemic disease. Surgical excision and brachytherapy remain options for cases without corneal involvement., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To report the unexpected finding of ocular surface neoplasia (OSSN) on conjunctival tissue removed during pterygium surgery and subjected to histopathology analysis., Methods: This is an observational, descriptive retrospective study in which all the samples removed during surgery between 1997 and 2020 with a clinical diagnosis of pterygium were sent for histopathology analysis in which an unexpected OSSN was found., Results: There were 461 cases with a preoperative diagnosis of pterygium, with a mean age of 30.14 ± 10.6 years. In this group, there was an unexpected finding of OSSN in 69 cases (14.96%) of the surgical samples, with a mean age of 46 ± 8.2 years (31.86 ± 12.13)., Conclusions: The unexpected coincidence of pterygium and OSSN is frequent, although varies depending on the geographical location. We recommend performing a histopathology analysis on every pterygium removed., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Diabetes mellitus (DM) induces damage to the ocular surface, which leads to vision decline. In the current study, we investigated whether N-acetylcysteine (NAC) plays a protective role in diabetes-induced ocular surface damage. The diabetic mice model was treated with 0.3% NAC topically. Corneal epithelial integrity, tear volume and corneal sensitivity were examined by sodium fluorescein staining, phenol red cotton thread and esthesiometer respectively. The level of reactive oxygen species (ROS) was measured with 2',7-dichlorofluorescein diacetate. The expression of NLRP3, IL-1β and caspase-1 were evaluated by RT-PCR, western blot and immunostaining. The level of SOD1 was assessed by RT-PCR. We found that the expression of NLRP3, IL-1β and caspase-1 were elevated in diabetic cornea and conjunctiva. Treatment with NAC improved corneal epithelial integrity, increased tear production and corneal sensitivity in diabetic mice. Moreover, NAC markedly attenuated ROS accumulation and decreased NLRP3, IL-1β and caspase-1 levels in diabetic cornea and conjunctiva. These results suggest that NAC improves ocular surface damage in STZ-induced diabetic mice, which may be related to the inhibition of the ROS/NLRP3/Caspase-1/IL-1β signaling pathway., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose/aim: Dry eye (DE) disease is a multifactorial disease in which uncontrolled inflammation can lead to corneal epithelium lesions and symptoms of discomfort. The aim of the present study was to evaluate the efficacy of two cyclosporine emulsions in a mouse model of DE with corneal epithelium lesions., Materials and Methods: Six- to 9-week-old female C57BL/6 N mice were housed in a controlled-environment room to induce DE. Following DE development, mice were instilled with: QD 0.1%CsA cationic emulsion (CaEm), BID 0.05%CsA anionic emulsion (AEm), or left untreated. Aqueous tear production and corneal epithelium lesions were assessed throughout the experiment. At the end of the treatment period, left eyes were sampled, fixed, and stained for histology, while the cornea, conjunctiva, and lacrimal gland of right eyes were sampled for transcriptomic analysis., Results: Corneal lesion scores were reduced by 10.4%, 18.4%, and 10.9% at day 6, 10, and 14, respectively, with CaEm (QD), and by 2.6%, 3.0%, and 5.5% at day 6, 10, and 14, respectively, with AEm (BID). Histology demonstrated that 7 out of 10 DE mice presented moderate to severe ocular lesions, while only 2 and 5 out of 10 mice presented slight to moderate ocular lesions when treated with the CaEm (QD) and AEm (BID), respectively. The transcriptomic profile analysis suggests that a different set of inflammatory genes are modulated in the cornea, conjunctiva, and lacrimal gland upon DE development. In addition, the two emulsions distinctively modulate the gene expression profile., Conclusions: This study demonstrates that both emulsions were effective at reducing corneal lesions, with the CaEm (QD) being slightly better than the AEm (BID). Interestingly, this study suggests that ocular tissues may not respond similarly to a dry environment and that a different set of genes is modulated by the two formulations in the ocular tissues.

Sulfur mustard (SM; bis (2-chloroethyl) sulfide) is a potent vesicant which causes irritation of the conjunctiva and damage to the cornea. In the present studies, we characterized the ocular effects of SM in New Zealand white rabbits. Within one day of exposure to SM, edema and hazing of the cornea were observed, followed by neovascularization which persisted for at least 28 days. This was associated with upper and lower eyelid edema and conjunctival inflammation. The conjunctiva is composed of a proliferating epithelium largely consisting of stratified columnar epithelial cells overlying a well-defined dermis. Superficial layers of the conjunctival epithelium were found to express keratin 1, a marker of differentiating squamous epithelium, while in cells overlying the basement membrane expressed keratin 17, a marker of stratified squamous epithelium. SM exposure upregulated keratin 17 expression. Mucin 5 ac producing goblet cells were interspersed within the conjunctiva. These cells generated both acidic and neutral mucins. Increased numbers of goblet cells producing neutral mucins were evident after SM exposure; upregulation of expression of membrane-associated mucin 1 and mucin 4 in the superficial layers of the conjunctival epithelium were also noted. These data demonstrate that ocular exposure of rabbits to SM causes significant damage not only to the cornea, but to the eyelid and conjunctiva, suggesting multiple targets within the eye that should be assessed when evaluating the efficacy of potential countermeasures., (Copyright © 2021 Elsevier Inc. All rights reserved.)