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BACKGROUND: Infectious conjunctivitis is common in Nepal. MATERIALS AND METHODS: This prospective study recruited 60 patients with presumed acute infectious conjunctivitis from the B.P. Koirala Lions Center for Ophthalmic Studies in Kathmandu, Nepal. Swabs from the conjunctiva and anterior nares were processed for metagenomic RNA deep sequencing (RNA-seq). RESULTS: Pathogens were identified in 55% of cases. RNA viruses were the most common pathogen class identified. Severe acute respiratory syndrome coronavirus 2 was the most common RNA virus identified. CONCLUSIONS: Acute infectious conjunctivitis varies by location. Contrary to expectations, RNA viruses predominated. Repeat surveillance may be useful and RNA-seq allows for detection of the unexpected pathogen including RNA viruses.

BACKGROUND: Promotion of facial cleanliness is recommended for the elimination of blinding trachoma, largely because of observational studies that have found an association between various measures of facial uncleanliness and trachoma. However, when a field grader assesses both facial cleanliness and trachoma, associations may be biased. Assessment of photographs of the face and conjunctiva by masked graders may provide a less biased estimate of the relationship between facial cleanliness and trachoma. METHODS: Face photographs, conjunctival photographs, and conjunctival swabs were obtained on a random sample of 0-9-year-old children from each of 40 communities in Amhara region, Ethiopia. Face photographs were assessed for the presence of seven measures of an unclean face (i.e., wet nasal discharge, dry nasal discharge, wet ocular discharge, dry ocular discharge, food, dust/dirt, and flies) by three independent masked photo-graders. Conjunctival photographs were similarly graded in a masked fashion for signs of clinically active trachoma. Conjunctival swabs were processed for Chlamydia trachomatis DNA. RESULTS: Of 2073 children with complete data, 808 (39%) had evidence of clinically active trachoma, 150 (7%) had evidence of ocular chlamydia infection, and 2524 (91%) had at least one measure of an unclean face. Dry ocular discharge had the strongest association with clinically active trachoma (age- and sex-adjusted prevalence ratio [PR] 1.4, 95% CI 1.2-1.6) and ocular chlamydia infection (PR 1.9, 95%CI 1.3-2.9), although significant associations were observed between each of the measures of facial uncleanliness and trachoma. CONCLUSIONS: Masked assessment of face and conjunctival photographs confirmed prior observational studies that have noted associations between various measures of facial uncleanliness and trachoma. The causal relationship between facial uncleanliness and trachoma is unclear since many features used to measure facial cleanliness (e.g., ocular discharge, nasal discharge, and flies) could be consequences of antecedent ocular chlamydia infection. TRIAL REGISTRATION: NCT02754583, clinicaltrials.gov.

Purpose of reviewThis study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody-drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs).Recent findingsADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced ocular surface AEs are well reported, the reporting of corneal pseudomicrocysts is limited, complicating the development of therapies to prevent or treat ADC-related ocular surface toxicity.SummaryThree of 11 FDA-approved ADCs have been implicated with corneal pseudomicrocysts, with incidence ranging from 41 to 100% of patients. Of the six ADCs that reported ocular surface AEs, only three had ocular substudies to investigate the benefit of preventive therapies including topical steroids, vasoconstrictors, and preservative-free lubricants. Current preventive therapies demonstrate limited efficacy at mitigating pseudomicrocysts and other ocular surface AEs.

PURPOSE: To evaluate VEGF-C-induced lymphoproliferation in conjunction with 5-fluorouracil (5-FU) antimetabolite treatment in a rabbit glaucoma filtration surgery (GFS) model. METHODS: Thirty-two rabbits underwent GFS and were assigned to four groups (n = 8 each) defined by subconjunctival drug treatment: (a) VEGF-C combined with 5-FU, (b) 5-FU, (c) VEGF-C, (d) and control. Bleb survival, bleb measurements, and IOP were evaluated over 30 days. At the end, histology and anterior segment OCT were performed on some eyes. mRNA was isolated from the remaining eyes for RT-PCR evaluation of vessel-specific markers (lymphatics, podoplanin and LYVE-1; and blood vessels, CD31). RESULTS: Qualitatively and quantitatively, VEGF-C combined with 5-FU resulted in blebs which were posteriorly longer and wider than the other conditions: vs. 5-FU (P = 0.043 for longer, P = 0.046 for wider), vs. VEGF-C (P

PurposeDiabetes mellitus causes diabetic keratopathy (DK). This and other ocular surface disorders are underdiagnosed and problematic for affected patients as well as recipients of diabetic donor corneas. Thus, it is important to find noninvasive means to facilitate determination of the potentially vision-threatening DK. It has been reported that diabetic corneas uptake significantly less oxygen (O2) than healthy controls. However, an integral assessment of the ocular surface is missing.MethodsUsing an optic-fiber O2 micro-sensor (optrode) we demonstrated recently that the healthy ocular surface displays a unique spatiotemporal map of O2 consumption. We hypothesize that diabetes impairs the spatiotemporal profile of O2 uptake at the ocular surface.ResultsUsing streptozotocin (STZ)-induced diabetic mice, we found diminished O2 uptake and loss of the unique pattern across the ocular surface. A diabetic cornea consumes significantly less O2 at the bulbar conjunctiva and limbus, but not the central and peripheral cornea, compared to controls. Further, we show that, contrary to the healthy cornea, the diabetic cornea does not increase the O2 consumption at the limbus in the evening as the normal control.ConclusionsAltogether, our measurements reveal a previously unknown impairment in O2 uptake at the diabetic cornea, making it a potential tool to diagnose ocular surface abnormalities and suggesting a new etiology mechanism.

BACKGROUND: Transthyretin amyloidosis (ATTR) is a significant cause of cardiomyopathy and other morbidities in the elderly and Black Americans. ATTR can be treated with new disease-modifying therapies, but large shortfalls exist in its diagnosis. The objective of this study was to test whether TTR amyloid can be detected and imaged in the conjunctiva using a novel small-molecule fluorescent ocular tracer, with the implication that ATTR might be diagnosable by a simple eye examination. METHODS: Three approaches were used in this study. First, AMDX-9101 was incubated with in vitro aggregated TTR protein, and changes in its excitation and emission spectra were quantified. Second, a cadaver eye from a patient with familial amyloid polyneuropathy type II TTR mutation and a vitrectomy sample from an hATTR patient were incubated with AMDX-9101 and counterstained with Congo Red and antibodies to TTR to determine whether AMDX-9101 labels disease-related TTR amyloid deposits in human conjunctiva and eye. Last, imaging of in vitro aggregated TTR amyloid labeled with AMDX-9101 was tested in a porcine ex vivo model, using a widely available clinical ophthalmic imaging device. RESULTS: AMDX-9101 hyper-fluoresced in the presence of TTR amyloid in vitro, labeled TTR amyloid deposits in postmortem human conjunctiva and other ocular tissues and could be detected under the conjunctiva of a porcine eye using commercially available ophthalmic imaging equipment. CONCLUSIONS: AMDX-9101 enabled detection of TTR amyloid in the conjunctiva, and the fluorescent binding signal can be visualized using commercially available ophthalmic imaging equipment. TRANSLATIONAL RELEVANCE: AMDX-9101 detection of TTR amyloid may provide a potential new and noninvasive test for ATTR that could lead to earlier ATTR diagnosis, as well as facilitate development of new therapeutics.

Background: Due to its location, the ocular surface is exposed to environmental microbes. Innate immune cells including macrophages are first line defense against infections. In vitro exposure to high glucose as well as diabetes-associated hyperglycemia has been shown to affect innate immune cell function and population. The present study was designed to examine the effect of diabetes-associated hyperglycemia on the lacrimal gland, conjunctiva and cornea macrophage population, phenotypic changes and cytokines/chemokines. Methods: Mouse model of Streptozotocin-induced diabetes was used to induce hyperglycemia. Immunostaining for CD11b and F4/80 was performed to stain macrophages in whole mount cornea, conjunctiva and 50 µm lacrimal gland sections. Flowcytometry was performed on single cell suspension to identify macrophage phenotypes and activation using CD11b, F4/80, CD80, CD206 and MHCII staining. Real time PCR was performed to quantify gene expression for macrophage-associated cytokines (IL-1β, TNF-α, IFN-γ) and chemokine (CCL2). Results: Our data demonstrates the diabetes-associated hyperglycemia caused a rapid onset and significant decrease in macrophage population in lacrimal gland, conjunctiva and cornea. The onset of this noted decrease was as early as 7 days after hyperglycemia in lacrimal gland and conjunctiva followed by a notable increase towards recovery only in conjunctiva but not in the lacrimal gland. The cornea tissue showed a steady decline up to the tested time point of 28 days. Further, hyperglycemia did not cause any notable changes in macrophage phenotypes, their activation status or the expression of IL-1β, TNF-α, IFN-γ, CCL2 except in the cornea where an increase in the cytokine levels was noted after 7 days of hyperglycemia Conclusion: Our data shows that diabetes-associated hyperglycemia can cause a significant decrease in microphage population with changing their plasticity or activation status in lacrimal gland, conjunctiva and cornea but the kinetics of decrease and recovery show differential pattern specific for each tissue. [ABSTRACT FROM AUTHOR]

In vivo confocal microscopy (IVCM) is a non-invasive imaging technique used to visualize the layers of the cornea and conjunctiva in real time. In patients with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC), this technology can be useful in diagnosing and monitoring the disease, as well as evaluating the efficacy of treatments. IVCM can reveal subclinical abnormalities in the corneal and conjunctival epithelium such as inflammatory cell infiltrates and tissue damage, which can provide insight into the pathogenesis of AKC. In AKC, IVCM reveals changes around the conjunctival papillae, inflammatory cells around punctate defects in the corneal epithelium, changes in subbasal nerve morphology, and deteriorations in the goblet cells in the meibomian gland are observed. In VKC, alterations can be observed in the diameter, brightness and nucleus/cytoplasm ratio of the superficial epithelial cells in the cornea. The use of IVCM in AKC and VKC can therefore aid in the early detection and management of the disease, as well as contribute to a better understanding of its underlying mechanisms. Keywords:Atopic keratoconjunctivitis, vernal keratoconjunctivitis, in vivo confocal microscopy, cornea, conjunctiva, meibomian glands: [ABSTRACT FROM AUTHOR]

Conjunctival chemosis usually undergoes spontaneous resolution; sometimes, it requires treatment. We present the case of a 43 years-old female patient who developed bilateral conjunctival chemosis following upper and lower blepharoplasty. Two months after the operation, patient underwent bilateral snip conjunctivoplasty with methylene blue demarcation of the chemotic conjunctiva. [ABSTRACT FROM AUTHOR]

The understanding of the role played by extracellular vesicles (EVs) in different tissues has improved significantly in the last years, but remains limited concerning the conjunctiva, a complex eye tissue whose role is pivotal for corneal protection. Here, we conducted a comparative study to isolate and characterize EVs from human conjunctival epithelial (IM-HConEpiC) and human conjunctival mesenchymal stromal cell (Conj-MSCs) secretomes using different isolation methods: differential ultracentrifugation (UC), and a combination of ultrafiltration (UF) with precipitation or size exclusion chromatography (SEC). EVs were characterized by total protein content, size, morphology, and expression of protein markers. EV functional effect was tested in an in vitro oxidative stress model. We successfully recovered EVs with the three methods, although significantly higher yields were obtained with UF-precipitation. Dynamic light scattering analysis confirmed the presence of nano-sized particles, being UC-isolated EVs larger than those isolated by UF-precipitation and UF-SEC. Atomic Force Microscopy showed EVs with a slightly ellipsoidal morphology. EVs enriched with UF-precipitation method were further analyzed, confirming the expression of Alix, CD63, TSG101, and Syntenin-1 by Western blotting and showing that Conj-MSC-derived EVs significantly reduced oxidative stress on IM-HConEpiC. Therefore, we conclude that UF-precipitation is the most efficient method for conjunctival EV enrichment. [ABSTRACT FROM AUTHOR]

Background: Managing recurrent pterygium combined with symblepharon presents significant challenges in ophthalmology. Clinicians aim to reconstruct the ocular surface, alleviate eye movement restrictions, and minimize recurrence risks. Objective: Evaluation of efficacy and safety of continuous blanket sutures (CBS) for fixation of large autologous conjunctival grafts in patients with severe recurrent pterygium with symblepharon. Methods: Retrospective, observational case series. Thirty-nine patients (40 eyes) were included, all with severe recurrent pterygium with symblepharon. During surgery, CBS was employed to affix large autologous conjunctival grafts to the exposed sclera, aiming to restore the ocular surface to smoothness as much as possible. All patients were followed up for more than one year. Main outcome measures include the rate of recurrence, improvement of eye movement, and intraoperative and postoperative complications. Results: Nearly all patients exhibited a smooth ocular surface and largely restored physiological structures during the follow-up period. There were no graft loss or contraction cases until the last follow-up, with only three eyes experiencing a pterygium recurrence (recurrence rate 7.5%, 3/40). Preoperative eye movement limitations improved significantly from 2.10 ± 0.71 (range 1–3) to 0.33 ± 0.53 (range 0–2; p < 0.001) post-surgery. Other postoperative complications included varying degrees of corneal scarring and a single instance of conjunctival granulomatous hyperplasia (1 eye, 2.5%). Conclusion: When addressing severe recurrent pterygium with Symblepharon, using CBS to secure large autologous conjunctival grafts during surgery can achieve favorable postoperative outcomes. This surgical method is safe and feasible and effectively rebuilds a smooth ocular surface, improves the appearance of the ocular surface, and reduces the recurrence rate of pterygium after excision. [ABSTRACT FROM AUTHOR]

Background: To present a case of conjunctival growth on the amniotic membrane and subsequent pathology revealing conjunctival squamous metaplasia in a patient with Stevens-Johnson syndrome. Case presentation: A 21-year-old female presented with painful, blurred vision in both eyes for two weeks. She was diagnosed with Stevens-Johnson syndrome 5 weeks before. Due to bilateral corneal epithelial defects, ProKera®, an amniotic membrane corneal bandage with a polycarbonate ring, was placed in both eyes. However, three weeks later, a slit-lamp examination revealed vascularized tissue growth from the palpebral conjunctiva to the amniotic membrane, along with symblepharon formation in the left eye. The patient underwent conjunctival biopsy, amniotic membrane removal, and symblepharon release. Pathology report showed the growth of squamous epithelium on the acellular amniotic membrane. Immunohistochemistry further supported the diagnosis, revealing squamous markers through p40 staining and highlighting the presence of the amniotic membrane using trichrome stain. Three months later, the patient's visual acuity had improved to 20/25 and no symblepharon was noted. Conclusions: This is the first case of conjunctival squamous metaplasia on amniotic membrane associated with Stevens-Johnson syndrome. Our case indicates that, despite the anti-inflammatory properties of amniotic membrane, conjunctival squamous metaplasia may arise after amniotic membrane grafting due to intense inflammation in Stevens-Johnson syndrome. Clinicians should conduct regular monitoring before amniotic membrane dissolution to preclude the development of conjunctival squamous metaplasia on the membrane and potential invasion into the cornea. [ABSTRACT FROM AUTHOR]

In vivo confocal microscopy (IVCM) is a non-invasive imaging technique used to visualize the layers of the cornea and conjunctiva in real time. In patients with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC), this technology can be useful in diagnosing and monitoring the disease, as well as evaluating the efficacy of treatments. IVCM can reveal subclinical abnormalities in the corneal and conjunctival epithelium such as inflammatory cell infiltrates and tissue damage, which can provide insight into the pathogenesis of AKC. In AKC, IVCM reveals changes around the conjunctival papillae, inflammatory cells around punctate defects in the corneal epithelium, changes in subbasal nerve morphology, and deteriorations in the goblet cells in the meibomian gland are observed. In VKC, alterations can be observed in the diameter, brightness and nucleus/cytoplasm ratio of the superficial epithelial cells in the cornea. The use of IVCM in AKC and VKC can therefore aid in the early detection and management of the disease, as well as contribute to a better understanding of its underlying mechanisms.

Abstract The understanding of the role played by extracellular vesicles (EVs) in different tissues has improved significantly in the last years, but remains limited concerning the conjunctiva, a complex eye tissue whose role is pivotal for corneal protection. Here, we conducted a comparative study to isolate and characterize EVs from human conjunctival epithelial (IM-HConEpiC) and human conjunctival mesenchymal stromal cell (Conj-MSCs) secretomes using different isolation methods: differential ultracentrifugation (UC), and a combination of ultrafiltration (UF) with precipitation or size exclusion chromatography (SEC). EVs were characterized by total protein content, size, morphology, and expression of protein markers. EV functional effect was tested in an in vitro oxidative stress model. We successfully recovered EVs with the three methods, although significantly higher yields were obtained with UF-precipitation. Dynamic light scattering analysis confirmed the presence of nano-sized particles, being UC-isolated EVs larger than those isolated by UF-precipitation and UF-SEC. Atomic Force Microscopy showed EVs with a slightly ellipsoidal morphology. EVs enriched with UF-precipitation method were further analyzed, confirming the expression of Alix, CD63, TSG101, and Syntenin-1 by Western blotting and showing that Conj-MSC-derived EVs significantly reduced oxidative stress on IM-HConEpiC. Therefore, we conclude that UF-precipitation is the most efficient method for conjunctival EV enrichment.

Abstract Over the past few decades, the expanded applications of in-vivo confocal microscopy (IVCM) have greatly enhanced the knowledge of a variety of conjunctival diseases. IVCM allows non-invasively detailed observation of tarsal, palpebral and bulbar conjunctiva, from the superficial to the substantia propria at the cellular level. IVCM has been shown as a powerful tool for the assessment of morphological changes in both physiological and pathological conditions. High-resolution images of different cellular phenotypes, together with quantifiable results, open new insights into understanding the mechanisms of conjunctival diseases, as well as provide valuable and longitudinal information for the diagnosis and therapeutic evaluation. This review aims to provide an overview of the current knowledge on the applications of IVCM on conjunctival disorders, including aging changes, dry eye-related morphological changes, glaucoma and glaucoma surgery-related morphological changes, conjunctival neoplasm, pterygium, allergic conjunctivitis, trachomatous scarring, and the conjunctiva-associated lymphoid tissue (CALT) changes. In this review, we highlight the key findings of previous studies and discusses the current limitations and challenges of IVCM in assessing the structural characteristics of the conjunctiva. Furthermore, we consider possible future directions for unlocking the full potential of IVCM applications. The insights presented here will contribute to a more comprehensive understanding of the applications of IVCM in conjunctival diseases.

Abstract Introduction Cutaneous malignant melanomas rarely occur in the eye, usually in the eyelids or the conjunctiva. Conjunctival malignant melanomas are even rarer. Most melanomas are dark in color as they are pigmented. However, amelanotic conjunctival malignant melanomas, a scarce variant of the cancer, can be challenging to diagnose accurately. Case presentation We present two cases of white Caucasian Swedish-born women who were diagnosed with unilateral amelanotic malignant melanoma in the conjunctiva of the eye. In the first case, the patient was an 81-year-old woman who was suffering from redness and foreign body sensation in the left eye. The initial diagnosis was blepharitis. Three biopsies were taken, which showed malignant melanoma in the eyelid and the conjunctiva. Unfortunately, the eye and the rest of the orbit could not be saved, and the patient had to undergo an orbital exenteration. In the second case, the patient was a 50-year-old woman, and the tumor was localized in the temporal conjunctiva of the left eye. The initial diagnosis was pinguecula, but at the time of surgery, the physician suspected conjunctival intraepithelial neoplasia. The tumor was not completely removed, so adjuvant brachytherapy and local chemotherapy were used. The eye was preserved. No neck and/or lung metastasis was detected in either case at the time of diagnosis. Conclusions Conjunctival amelanotic malignant melanomas should be suspected when tumors are present in the eye and/or the eyelids. By suspecting amelanotic malignant melanoma, the delay in treatment can be shortened. Treating them as soon as possible is essential to minimize the risk of metastasis.

Background: Conjunctivochalasis (CCh) is characterized by loose, redundant conjunctival folds that result in tear film instability. For cases that are refractory to conventional therapies, surgical treatment may be used to address the underlying pathophysiology. AIMS: The aim of this study was to assess the clinical outcome of fornix reservoir restoration surgery with cryopreserved amniotic membrane (AM) in patients with symptomatic CCh. Setting and Design: This was an observational, retrospective, single-site study. MATERIALS AND METHODS: Retrospective review of eyes with CCh that underwent fornix deepening reconstruction with conjunctival recession and AM transplantation with at least 3 months of follow-up. Outcome measures, which were assessed at 2 ± 1 weeks postoperatively and at the last follow-up visit, included CCh severity, symptoms, tear break-up time (TBUT), corneal and conjunctival fluorescein staining, subconjunctival hemorrhage, and delayed tear clearance. Statistical Analysis Used: Wilcoxon signed–rank test and Fisher’s exact test were used for statistical analysis. Results: Ten eyes (76.9%) presented with Grade 3 CCh, and 3 eyes (23.1%) presented with Grade 2 CCh along with ocular irritation (100%), epiphora (84.6%), dryness (76.9%), ocular pain (38.5%), and photophobia (23.1%). Following surgical intervention, CCh severity significantly improved to Grade 0 in all eyes. This was accompanied by a significant improvement in corneal staining, symptoms, and resolution of conjunctival staining/subconjunctival hemorrhage. Conclusion: Surgical treatment using the reservoir restoration procedure addresses the pathophysiology of CCh as demonstrated by improved symptoms, TBUT, and corneal and conjunctival staining.

John D Rodriguez,1,2 Samantha Kerti,3 Adam Hamm,3 George W Ousler,1 Ethan Bensinger,1,2 Sadie Burnham,1,2 Mark B Abelson1,2,4,5 1Ora, Inc, Andover, MA, USA; 2Andover Eye Institute, Andover, MA, USA; 3Statistics and Data Corporation, Tempe, AZ, USA; 4Ophthalmology, Harvard Medical School, Cambridge, MA, USA; 5Mass Eye and Ear, Boston, MA, USACorrespondence: John D Rodriguez, Email jrodriguez@oraclinical.comPurpose: The absence of a standardized diagnostic method for clinical signs of Dry Eye Disease (DED) complicates clinical trials for future treatments. This paper evaluated Lissamine Green (LG) conjunctival staining as a valid, stable and modifiable endpoint for both clinical practice and clinical trials.Methods: Screening and pre-randomization data from two identically designed clinical trials for DED resulted in a pooled dataset of 494 subjects. Inclusion was based on reported symptoms, lissamine green (LG) conjunctival staining, Fluorescein (Fl) corneal and conjunctival staining, and Schirmer’s Test (ST). Outcome measures were assessed based on the modifiability of LG staining to exposure to a Controlled Adverse Environment (CAE®), correlation of LG to Fl staining, relative variation of LG staining scores and Schirmer test scores, and the correlation of LG staining with symptom scores.Results: The modifiability of LG conjunctival staining to environmental exposure was demonstrated, with nasal LG and FL staining displaying the most similar percent change. Nasal LG conjunctival staining scores for subjects with ST scores of less than 8mm were significantly higher than for subjects with ST greater than 8mm. LG staining scores were more consistent (25% change from baseline threshold) than ST scores. Finally, statistically significant correlations were found between LG staining and a number of symptom scores.Conclusion: This evaluation demonstrates the superiority of the utilization of a clinical endpoint focused on ocular surface damage. The reproducibility and modifiability of LG conjunctival staining to controlled adverse environment, coupled with its significant correlation with symptoms, positions it as an exemplary clinical sign endpoint for clinical management and in clinical trials. Our findings advocate for the adoption of LG conjunctival staining as a primary endpoint in both clinical research and drug development, offering a more effective means of identifying and addressing ocular surface damage in the realm of DED.Keywords: dry eye, conjunctiva, stain, lissamine green clinical trials, controlled adverse environment, disease models, drug screening, dry eye disease, efficacy endpoints

Introduction: Conjunctival melanoma (CM) is a rare but potentially lethal ocular malignancy that arises from melanocytes in the conjunctiva. Its clinical presentation can mimic other more common conjunctival lesions, such as squamous cell carcinoma (SCC), leading to diagnostic challenges. Case Presentation: We present a case of CM initially misdiagnosed as conjunctival SCC due to overlapping clinical features. Conclusion: CM presenting as nonpigmented, conjunctival tumor is a diagnostic challenge. Clinicians should maintain a high index of suspicion for conjunctival melanocytic or amelanotic lesions, particularly those with atypical features. [ABSTRACT FROM AUTHOR]

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

Background: This study aims to determine the incidence of conjunctival chemosis during phacoemulsification and to explore the possible mechanism and treatments. Methods: Patients with or without chemosis during phacoemulsification by the same operator within two years were included. The initial site of chemosis, the chemosis originated time, and the degree of chemosis at the end of the surgery were recorded. The differences in phacoemulsification energy/time and irrigation volume were compared between two groups. Meanwhile, the distance between the clear corneal incision (CCI) and the end of the Bowman's layer, surgically induced astigmatism (SIA), intraocular pressure and central corneal thickness were also compared between the two groups. Results: The incidence of intraoperative chemosis was 9.17% (66/720). The distance between CCI and the end of the Bowman's layer in the chemosis group was significantly longer than that in the non-chemosis group postoperatively (P < 0.0001). The initial sites of chemosis were located on both sides of the external opening of the CCI. The average time from the phacoemulsification probe introducing into the anterior chamber to the originating of chemosis was 30.23 ± 49.23s. Conclusion: Intraoperative chemosis is related to the distance from CCI to the end of Bowmen's layer. The residual conjunctiva around the incision wraps the phacoemulsification probe sleeve to form a passage, the leakage fluid enters the subconjunctiva through this passage, forming chemosis. Conjunctival incision on both sides of CCI can effectively prevent the development of chemosis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness and safety of a method for repairing an eroded Ahmed glaucoma valve (AGV) tube using two short scleral tunnels made in tandem with a 22G needle instead of covering the eroded tube with another scleral graft. Methods: From May 12, 2015, to July 27, 2019, we retrospectively reviewed eight patients at Ningbo Aier Eye Hospital who developed AGV tube erosion secondary to necrosis of their overlying conjunctiva and scleral grafts. This defect was repaired in all the patients using the double short tandem scleral tunnel technique, which involved the creation of double short tandem scleral tunnels made by a 22G needle. Two parallel-to-limbus scleral incisions were made 3 mm and 6 mm from the limbus first, then a curved 22G needle was inserted between the two scleral cuts to make one scleral tunnel, the other scleral tunnel was completed during the first surgery, inserted the tube into the two tunnels. The mean length of time between the AGV placement and the first erosion was 12.25 ± 6.36 months (3–24 months). The mean age of the patients was 65.50 ± 11.70 years (49–78 years). Results: The surgical outcome was assessed in terms of the tectonic integrity of the conjunctiva over the follow-up period (12 months). There was no AGV tube erosion, scleral thinning, or ocular infection after a mean of 41.25 ± 26.54 months of follow-up in all eight patients. Conclusion: AGV tube erosion following shunt surgery can be successfully managed using the improved double short tandem scleral tunnel technique. [ABSTRACT FROM AUTHOR]

Trabeculectomy is a primary surgical procedure used to reduce intraocular pressure (IOP) in patients with glaucoma. Despite its effectiveness, it can lead to significant complications, including hypotony, choroidal effusion, blebitis, and bleb leaks. Bleb leaks require prompt medical or surgical intervention to prevent severe complications such as blebitis and bleb-associated endophthalmitis. In recent years, the indications for collagen cross-linking (CCL) have expanded beyond corneal ectatic diseases to include various ocular conditions such as keratitis and leaking blebs. Here, we present the case of a 70-year-old male patient with a leaking avascular cystic bleb. Following treatment with a combination of conjunctival CCL, topical gentamicin, a dorzolamide/timolol combination, and a therapeutic contact lens, the patient experienced cessation of bleb leakage and an increase in IOP. [ABSTRACT FROM AUTHOR]

Purpose: Ocular graft-versus-host disease (oGVHD) affects more than half of the patients following allogeneic hematopoietic stem cell transplantation (HSCT). The disease onset and the pathogenesis of oGVHD are not well understood. We hope to identify the triggers and explore the clinical signs and symptoms of oGVHD development at the early stages. Methods: The records of post-HSCT patients seen consecutively in a 1-year span in a single provider's clinic were reviewed. The history, symptoms, and clinical findings of the patients with erosive tarsal conjunctival lesions (ETCLs) were analyzed. Results: Out of the 228 patients screened, 19 had clinically witnessed ETCL in at least one eye during the period. Twelve (63%) patients had a never-before-described nodular erosion on the subtarsal conjunctiva; seven (37%) had previously described pseudomembranous erosions. The ocular symptom onset was within 1 month after immunosuppression (IS) taper, vaccination, or donor lymphocyte infusion (DLI) in 16 of the 19 patients. While 16 (84%) patients reported painless mucous discharge, only 9 (47%) reported dryness as the initial symptom. Within 6 months, only 4 (21%) had discharge but 15 (82%) patients endorsed dryness. Subepithelial conjunctival fibrosis followed ETCL immediately in situ. Corneal punctate staining increased with time, while aqueous tear production decreased. Conclusions: The ETCL described is likely one of the earliest detectable findings of oGVHD and triggered by certain immunogenic events. The ocular symptoms of wet mucous discharge should be considered a warning sign for oGVHD onset, particularly when it occurs shortly after prominently immunogenic events. [ABSTRACT FROM AUTHOR]

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient's tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD. [ABSTRACT FROM AUTHOR]

Background: Pseudoexfoliation syndrome (PEX) is a common age-related ocular condition characterized by the accumulation of a fibrillar, pseudoexfoliative material on the anterior segment of the eye. This study aims to investigate the histopathological characteristics of pseudoexfoliative material within different ocular structures, including the eyelid, conjunctiva, and anterior lens capsule. Methods: A total of 32 anterior lens capsules, 3 eyelid fragments, and 12 conjunctival specimens were obtained from patients clinically diagnosed with PEX during ocular surgeries at the Onioptic Hospital of Ophthalmology. The tissue specimens were subsequently processed using the classical histological technique of paraffin embedding. This process enabled the production of serial sections with a thickness of 4 microns, facilitating the microscopic examination of fine details. The sections were stained with the hematoxylin-eosin (HE) method for the observation of microscopic structures. Results: This study's findings reveal that PEX material, characterized by its fibrillar and amorphous components, is consistently present across multiple ocular structures, including the anterior lens capsule, eyelid, and conjunctiva. When stained with H&E, the PEX material typically appears as amorphous, eosinophilic deposits. Under higher magnification, these deposits exhibit a fibrillar structure, often appearing as irregular, granular, or filamentous aggregates. Conclusions: The deposit of fibrillar material in the eyelid and conjunctiva, though less commonly emphasized compared to other structures, is a significant finding that sheds light on the systemic nature of the syndrome. The consistent identification of fibrillar eosinophilic deposits across these structures highlights the systemic distribution of PEX material, reinforcing the notion that PEX syndrome is not confined to the anterior segment of the eye. [ABSTRACT FROM AUTHOR]

Pterygium is a common ocular disorder that can result in eye irritation and loss of corneal transparency. Surgical treatment is the main intervention for pterygium removal, with various techniques aimed at minimizing recurrence rates. This review compares the effectiveness of surgical techniques for pterygium treatment in terms of recurrence rates, including the bare sclera technique and conjunctival autograft using biological glue, sutures, and autologous blood. Articles were reviewed from the PubMed, SciELO, and LILACS databases, using the keywords: pterygium surgery, conjunctival autograft with glue or fibrin glue or biological glue or sutures or autologous blood, bare sclera, recurrence. The bare sclera technique showed a recurrence rate of 11%, while the conjunctival autograft technique using biological glue, sutures, and autologous blood demonstrated average recurrence rates of 3.75%, 6.5%, and 6.96%, respectively. The conjunctival autograft technique with biological glue presented the lowest recurrence rates, followed by conjunctival autograft with sutures, autologous blood, and bare sclera. Some studies found no significant difference between the recurrence rates of the suture and biological glue techniques, highlighting the need for further research. [ABSTRACT FROM AUTHOR]

Introduction: Cutaneous malignant melanomas rarely occur in the eye, usually in the eyelids or the conjunctiva. Conjunctival malignant melanomas are even rarer. Most melanomas are dark in color as they are pigmented. However, amelanotic conjunctival malignant melanomas, a scarce variant of the cancer, can be challenging to diagnose accurately. Case presentation: We present two cases of white Caucasian Swedish-born women who were diagnosed with unilateral amelanotic malignant melanoma in the conjunctiva of the eye. In the first case, the patient was an 81-year-old woman who was suffering from redness and foreign body sensation in the left eye. The initial diagnosis was blepharitis. Three biopsies were taken, which showed malignant melanoma in the eyelid and the conjunctiva. Unfortunately, the eye and the rest of the orbit could not be saved, and the patient had to undergo an orbital exenteration. In the second case, the patient was a 50-year-old woman, and the tumor was localized in the temporal conjunctiva of the left eye. The initial diagnosis was pinguecula, but at the time of surgery, the physician suspected conjunctival intraepithelial neoplasia. The tumor was not completely removed, so adjuvant brachytherapy and local chemotherapy were used. The eye was preserved. No neck and/or lung metastasis was detected in either case at the time of diagnosis. Conclusions: Conjunctival amelanotic malignant melanomas should be suspected when tumors are present in the eye and/or the eyelids. By suspecting amelanotic malignant melanoma, the delay in treatment can be shortened. Treating them as soon as possible is essential to minimize the risk of metastasis. [ABSTRACT FROM AUTHOR]

Purpose: To compare the safety and effectiveness of standalone Kahook Dual Blade (KDB) excisional goniotomy to standalone ab-interno Xen gel stent implantation in eyes with moderate-to-severe open-angle glaucoma (OAG). Methods: A single-center, retrospective study including eyes with moderate-to-severe OAG undergoing standalone KDB goniotomy or Xen gel stent implantation was conducted. Intraocular pressure (IOP), the number of antiglaucoma medications taken daily, and best-corrected visual acuity (BCVA) were recorded at baseline and for up to 36-months. Primary outcomes assessed included changes from baseline in IOP and the number of antiglaucoma medications taken. Intergroup comparisons were conducted using independent-samples Student's t-tests. The incidence of intraoperative and postoperative adverse events and the need for glaucoma surgical re-interventions were also recorded. Results: Eyes receiving standalone KDB (n=26) or Xen gel stent (n=45) surgery were analyzed. The baseline mean IOP and number of antiglaucoma medications in both groups were as follows: KDB: 23.2 ± 6.0 mmHg, 2.2 ± 1.4 medications; Xen: 22.7 ± 8.8 mmHg, 3.0 ± 1.0 medications. At 36 months, IOP was reduced to 16.6 ± 5.4 mmHg in KDB eyes (n=23, − 23.5%; p=0.0004) and 15.3 ± 5.6 mmHg in Xen gel stent eyes (n=15, − 22.1%; p=0.006), while number of antiglaucoma medications was reduced to 1.1 ± 0.7 (− 30.8%; p=0.0005) and 2.2 ± 1.4 (− 25.6%; p=0.01), respectively. Three eyes (11.5%) in the KDB group and 19 eyes (42.2%) in the Xen gel stent group required additional surgery before month 36 due to refractory high IOP. Conclusion: Both KDB goniotomy and Xen gel stent implantation significantly lowered the IOP and antiglaucoma medication burden in patients with moderate-to-severe OAG. While the Xen gel stent is frequently used to treat moderate-to-severe OAG patients with uncontrolled IOP, standalone KDB goniotomy may be equally effective as a long-term intervention, reducing the need for subsequent glaucoma surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Dry eye disease includes a large variety of different ocular surface diseases. What all have in common is the resulting lubrication deficiency. Although the pathophysiology is multicausal, the common nominator is the threat of normal ocular surface balance and homeostasis. In homeostasis, the close link and interconnection of cellular basic mechanisms is essential for the functionality of the ocular surface. Any challenge threatening homeostasis implies cell stress. The ability of the ocular surfaces (conjunctiva and cornea) to cope and adapt to the resulting stress load decides over the ability to regain homeostasis or to drift to an altered stage of balance, recently identified as allostasis. This review outlines the importance of cellular stress as a key hub of the vicious circle and the importance of the integrated stress response system. Basic considerations for cellular recovery and the potential re-establishment of homeostasis are discussed. Disturbance or insufficiency of the tear film challenges the regulatory systems of the ocular surfaces. The reaction of the surfaces includes temporary mechanisms engaged in the preservation of homeostasis. However, strong or persisting challenges can lead to the potential exhaustion of the coping capacity. This again activates the vicious circle with chronic inflammation and autocatalytic deterioration. Hence, the factors challenging the homeostasis should be addressed in time. Amongst them are a varying osmolarity, constant presence of small lesions at the epithelium, acidification, attrition with mechanical irritation, and onset of pain and discomfort. Each of them and, especially when occurring simultaneously, impose stress on the coping mechanisms and lead to a stress response. Many stressors can culminate, leading to an exhaustion of the coping capacity, outrunning normal resilience. Reaching the limits of stress tolerance leads to the manifestation of a lubrication deficiency as the disease we refer to as dry eye disease (DED). To postpone its manifestation, the avoidance or amelioration of stress factors is one key option. In DED, this is the target of lubrication therapy, substituting the missing tear film or its components. The latter options include the management of secondary sequelae such as the inflammation and activation of reparative cascades. Preventive measures include the enhancement in resilience, recovery velocity, and recovery potential. The capacity to handle the external load factors is the key issue. The aim is to guard homeostasis and to prevent intercellular stress responses from being launched, triggering and invigorating the vicious circle. Considering the dilemma of the surface to have to cope with increased time of exposure to stress, with simultaneously decreasing time for cellular recovery, it illustrates the importance of the vicious circle as a hub for ocular surface stress. The resulting imbalance triggers a continuous deterioration of the ocular surface condition. After an initial phase of the reaction and adaption of the ocular surface to the surrounding challenges, the normal coping capacity will be exhausted. This is the time when the integrated stress response (ISR), a protector for cellular survival, will inevitably be activated, and cellular changes such as altered translation and ribosome pausing are initiated. Once activated, this will slow down any recovery, in a phase where apoptosis is imminent. Premature senescence of cells may also occur. The process of prematurization due to permanent stress exposures contributes to the risk for constant deterioration. The illustrated flow of events in the development of DED outlines that the ability to cope, and to recover, has limited resources in the cells at the ocular surface. The reduction in and amelioration of stress hence should be one of the key targets of therapy and begin early. Here, lubrication optimization as well as causal treatment such as the correction of anatomical anomalies (leading to anatomical dry eye) should be a prime intent of any therapy. The features of cellular stress as a key hub for the vicious circle will be outlined and discussed. [ABSTRACT FROM AUTHOR]

Background: Sudden volcanic eruptions can lead to volcanic ash entering the eyes, causing severe discomfort and complicating evacuation efforts. The specific effects of volcanic ash on ocular tissues, especially when wearing soft contact lenses (SCLs), are not well documented, prompting this experimental investigation. Methods: White rabbits with normal eyes were randomly divided into three groups: (1) a bare eye group: bare eye + volcanic ash exposure + eye washing, (2) an SCL group: SCL-wearing eye + volcanic ash exposure + eye washing, and (3) a control group: eye washing only. In groups 1 and 2, volcanic ash was applied to one eye under topical anesthesia, followed by immediate saline rinsing. Slit-lamp microscopy and histopathological analysis were conducted after euthanasia. Results: Slit-lamp and histopathological examinations revealed more significant corneal and conjunctival erosion in the bare eye group compared to the SCL group, which showed limited damage. The control group displayed no ocular damage. Conclusions: Guidelines from the "Volcanic Ash Health Effects: A Guide for the Public" by the National Research Institute for Earth Science and Disaster Resilience recommend removing SCLs during ashfall. Our findings suggest that the damage to the corneal and conjunctival epithelium is less severe in SCL-wearing eyes than in bare eyes, recommending that SCL wearers prioritize evacuation over lens removal during sudden ashfall. [ABSTRACT FROM AUTHOR]

Background: High Intensity Macro and Micro Focused Ultrasound (HIFU) is a safe and effective method for the treatment of skin laxity. However, the application of high-intensity focused ultrasound energy on eyelids has been associated with potential ocular complications including traumatic cataract, iridocyclitis, and conjunctival hemorrhage, among others. Case presentation: A 40-year-old female developed blurred vision in her left eye after receiving HIFU treatment on binocular eyelids, and her left far vision was 20/66. The examination revealed left eye iris depigmentation and conjunctival hemorrhage. Both eyes exhibited multiple white streaking or tadpole-shaped opacities in the lenses. Conclusion: Excessive ultrasonic energy generated by HIFU can cause protein denaturation, leading to conditions such as traumatic cataract, visual impairment, injuries to the iris and conjunctiva when applied to the eyes. We recommend that individuals undergoing cosmetic treatment in the periorbital region should be highly aware of the possible ocular side effects. [ABSTRACT FROM AUTHOR]

Anemia is a common problem that affects a significant part of the world's population, especially in impoverished countries. This work aims to improve the accessibility of remote diagnostic tools for underserved populations. Our proposal involves implementing algorithms to estimate hemoglobin levels using images of the eyelid conjunctiva and a calibration label captured with a mid-range cell phone. We propose three algorithms: one for calibration label segmentation, another for palpebral conjunctiva segmentation, and the last one for estimating hemoglobin levels based on the segmented images from the previous algorithms. Experiments were performed using a data set of children's eyelid images and calibration stickers. An L1 norm error of 0.72 g/dL was achieved using the SLIC-GAT model to estimate the hemoglobin level. In conclusion, the integration of these segmentation and regression methods improved the estimation accuracy compared to current approaches, considering that the source of the images was a mid-range commercial camera. The proposed method has the potential for mass screening in low-income rural populations as it is non-invasive, and its simplicity makes it feasible for community health workers with basic training to perform the test. Therefore, this tool could contribute significantly to efforts aimed at combating childhood anemia. [ABSTRACT FROM AUTHOR]

Pterygium is often associated with chronic ultraviolet (UV) radiation exposure and characterized by the overgrowth of conjunctiva and extracellular matrix (ECM) remodeling. Notably, several studies in the skin have demonstrated that chronic UV radiation can upregulate Granzyme B (GrB) expression and increase ECM degradation. The aim of this study was to compare GrB expression between pterygium and healthy controls and to further link this GrB expression to mast cells. Post-mortem pterygium tissues and conjunctival tissues from age-matched controls were used to assess GrB expression via immunofluorescence and microscopy. We found a significantly higher density of GrB+ cells from pterygium specimens compared to healthy controls. Furthermore, many of the GrB+ cells in pterygium specimens co-expressed tryptase, a mast cell marker. These findings suggest a role for conjunctival mast cell-secreted GrB in the pathogenesis of pterygium and highlight GrB as a possible therapeutic target in delaying or halting pterygium progression. [ABSTRACT FROM AUTHOR]

Cystinosis is a rare autosomal recessive lysosomal storage disease associated with high mortality and morbidity rates. The most distinctive ocular manifestations of cystinosis are photophobia, tearing, and blurred vision. Herein, we assessed the ocular involvement of four patients from two families diagnosed with infantile nephropathic cystinosis using optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM). Anterior segment OCT demonstrated multiple hyperreflective punctate deposits, and IVCM revealed needle-shaped bright crystal deposits in the corneal stroma in all patients. Three patients also had crystal deposits in the epithelium, where epithelial cell disruption was observed. Crystal deposits around the subepithelial nerve plexus were noted in some sections. In one patient, round and needle-shaped bright deposits along with inflammatory cells were observed in the limbal region of the conjunctiva. Infrared fundus images of two female siblings revealed hyperreflective crystal-like deposits around the optic disc, macula, and peripheral retina, and enhanced depth imaging OCT showed accumulation of crystals in all layers of the retina. [ABSTRACT FROM AUTHOR]

Purpose: To determine the thickness of the conjunctiva, episclera and sclera in healthy individuals using anterior segment optical coherence tomography (AS‐OCT). Methods: We prospectively included 107 healthy individuals of different age groups (18–39 years, 40–54 years, 55–69 years and ≥70 years). For each eye, AS‐OCT scans of four quadrants (temporal, nasal, superior and inferior) were acquired. The thickness of the conjunctiva, episclera and sclera was measured for each scan. In addition, the axial length of both eyes was measured, and general characteristics, including smoking, allergies and contact lens use, were collected. Results: The mean conjunctival thickness was significantly different between the nasal and superior quadrants (87 ± 30 μm vs. 77 ± 16 μm; p < 0.001), as well as the superior and inferior quadrants (77 ± 16 μm vs. 86 ± 19 μm; p = 0.001). The mean episcleral thickness was larger in the superior (174 ± 54 μm) and inferior (141 ± 43 μm) quadrants, compared to the nasal (83 ± 38 μm) and temporal quadrants (90 ± 44 μm). The mean scleral thickness of the inferior quadrant was the largest (596 ± 64 μm), followed by the nasal (567 ± 76 μm), temporal (516 ± 67 μm) and superior (467 ± 52 μm) quadrants (all p < 0.001). The averaged scleral thickness increased 0.96 μm per age year (0.41–1.47 μm, p < 0.001). Conclusions: This study provides an assessment of the thickness of scleral and adjacent superficial layers in healthy individuals determined on AS‐OCT, which could enable future research into the use of AS‐OCT in diseases affecting the anterior eye wall. [ABSTRACT FROM AUTHOR]

Dexamethasone (DEX) is used to treat ocular surface diseases. However, regulating DEX duration in tears while preventing its absorption into the anterior chamber is critical for balancing its therapy effects and the side effects. In this study, a novel magnetic nanoparticle (MNP)-micelle (MC) co-delivery system (MMDS) was developed. The MC moiety in the MMDS served as the carrier for DEX and the MNP part endowed the MMDS with magnetic-responsive properties. To extend its residency, the MMDS was magnetically attracted by an external magnet after instilling, which acted as a precorneal drug-depot enabling a sustainable release of DEX in tears. With combination of magnet treatment, the topical instillation of MMDS@DEX significantly prolonged the DEX-retention in tears and increased the DEX-concentration in the cornea and conjunctiva, as well as concurrently reduced the DEX-level in the aqueous humor, when compared with the commercial DEX eye drop treatment. The combination of MMDS@DEX and magnet treatment exerted significantly better therapeutic effects against DED with smaller side effects than conventional treatments including DEX suspension, commercial DEX eye drops, as well as the MMDS@DEX treatment alone. The present work provided a new method for the effective delivery of DEX to ocular surface tissues while reducing its side effects, which will be beneficial to the treatments of a wide range of ocular surface diseases. This article reports a novel dexamethasone (DEX)-micelle and magnetic nanoparticle (MNP) co-delivery system (MMDS@DEX) as a precorneal DEX-depot for effectively DEX-delivery towards eye-surface tissues to balance its therapy effects and side effects. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the expression levels of ACE2 in ocular glands and to investigate the effect of S protein on them. Male C57BL/6J mice were used for the experiments. The expression levels of ACE2 are highest in the Meibomian glands, followed by the conjunctiva, the cornea, and the lacrimal glands. Co-immunoprecipitation assays confirmed direct binding between ACE2 and S protein in ocular surface epithelia and Meibomian glands. CD45+ cell infiltration was found in the S protein treatment group, which was accompanied by upregulation of inflammation-related cytokines. There was also prominent cell apoptosis in the S protein treatment group. In conclusion, not only the cornea and the conjunctiva, but also the Meibomian glands express ACE2, and S protein could induce ocular surface epithelial cell and Meibomian gland cell inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The aim of this study was to report the nearly ubiquitous prevalence of melanocytic hyperplasia in benign pterygia/pingueculae and establish that the entity is insufficiently recognized. METHODS: This is a retrospective immunohistochemical pathology case series of 30 consecutive pterygia/pingueculae samples selected from an ophthalmic pathology database at a single institution. Histopathologic and immunohistochemistry analyses with anti-SOX-10 and anti-MART-1 antibodies were used for identifying melanocytes. The number of squamous cells intervening between melanocytes was determined. RESULTS: The frequency of dendritic melanocytes was found to meet the criteria for dendritic melanocytic hyperplasia in 29 of 30 pterygia/pingueculae samples using specific antibodies. Melanocytes were found in several patterns: diffuse (28%), multifocal (28%), and focal (44%). In each case, the melanocytes were distributed as single melanocytes at the base; clusters of melanocytes were seen in 17% of samples. There were an average of about two intervening epithelial cells between melanocytes at the base. CONCLUSION: When diagnosed with immunohistochemistry, dendritic melanocytic hyperplasia is nearly ubiquitous in pterygia and pingueculae. Melanocytic hyperplasia may have a distribution that includes nests and single melanocytes above the basal layer, which can be confused with forms of primary acquired melanosis. It is important for pathologists to recognize these lesions as a distinct benign clinicopathologic entity.

Purpose: Insulin has been postulated as a novel and effective treatment for re-epithelialization of the ocular surface and different pathologies have been suggested as possible indications. Observations: A 69-year-old diabetic male was referred for a left non-healing conjunctival epithelial defect over the superotemporal scleral patch used in the placement of the Ahmed ClearPath. In the left eye, he was on latanoprost/timolol once daily, prednisolone 1 % once daily and tobramycin/dexamethasone ointment at night. Best-corrected visual acuity was 20/20 in the right eye and 20/25 in the left eye. Slit lamp examination of the left eye showed patches of avascular scleral tissue nasally and superiorly, conjunctival and Tenon defect over a thin avascular scleral patch graft. The patient was started on Humulin insulin 1UI/mL 6 times a day and the defect healed after 3 months of treatment. Conclusions and importance: Insulin eye drops may be used in the treatment of chronic conjunctival epithelial defects following implantation of glaucoma drainage devices.

BackgroundDue to its location, the ocular surface is exposed to environmental microbes. Innate immune cells including macrophages are first line defense against infections. In vitro exposure to high glucose as well as diabetes-associated hyperglycemia has been shown to affect innate immune cell function and population. The present study was designed to examine the effect of diabetes-associated hyperglycemia on the lacrimal gland, conjunctiva and cornea macrophage population, phenotypic changes and cytokines/chemokines.MethodsMouse model of Streptozotocin-induced diabetes was used to induce hyperglycemia. Immunostaining for CD11b and F4/80 was performed to stain macrophages in whole mount cornea, conjunctiva and 50 µm lacrimal gland sections. Flowcytometry was performed on single cell suspension to identify macrophage phenotypes and activation using CD11b, F4/80, CD80, CD206 and MHCII staining. Real time PCR was performed to quantify gene expression for macrophage-associated cytokines (IL-1β, TNF-α, IFN-γ) and chemokine (CCL2).ResultsOur data demonstrates the diabetes-associated hyperglycemia caused a rapid onset and significant decrease in macrophage population in lacrimal gland, conjunctiva and cornea. The onset of this noted decrease was as early as 7 days after hyperglycemia in lacrimal gland and conjunctiva followed by a notable increase towards recovery only in conjunctiva but not in the lacrimal gland. The cornea tissue showed a steady decline up to the tested time point of 28 days. Further, hyperglycemia did not cause any notable changes in macrophage phenotypes, their activation status or the expression of IL-1β, TNF-α, IFN-γ, CCL2 except in the cornea where an increase in the cytokine levels was noted after 7 days of hyperglycemiaConclusionOur data shows that diabetes-associated hyperglycemia can cause a significant decrease in microphage population with changing their plasticity or activation status in lacrimal gland, conjunctiva and cornea but the kinetics of decrease and recovery show differential pattern specific for each tissue.

Purpose: To report a rare case of a conjunctival blue nevus in a child. Observations: A 10-year-old girl underwent an excisional biopsy for an atypical growing melanocytic conjunctival lesion. The diagnosis of a conjunctival blue nevus was confirmed on histopathology. We describe the histopathology and the anterior segment optical coherence tomography features of a blue nevus in a 10-year-old child along with a review of literature. Conclusion and importance: Conjunctival blue nevus is rare and has rarely been reported in a child. Multimodal imaging may help document lesion progression. This condition should remain in the differential for a growing, pigmented conjunctival lesion.

We report the case of a 21-year-old Cameroonian woman residing in France for one year, who presented to our department with left eye discomfort and itching. Examination revealed a mobile translucent cord beneath the nasal-inferior conjunctiva, prompting suspicion of loaiasis. Anesthesia was administered for extraction, revealing a 31 mm male Loa loa. A positive microfilarial load, albeit low, confirmed the diagnosis and the diagnostic workup excluded other locations. Treatment with diethylcarbamazine was well-tolerated. This case highlights the importance of considering loaiasis in non-endemic regions and underscores the need for interdisciplinary collaboration in its diagnosis and management. [ABSTRACT FROM AUTHOR]

Abstract Purpose To report the results of using autologous Tenon patch grafts for managing giant full-thickness macular holes (FTMHs) when other alternatives are not applicable. Methods The same surgical technique was performed in all three cases. Briefly, a small fragment of Tenon’s tissue was collected. The graft was introduced through a 23G trocar and released over the macular hole under a bubble of PFCL. The patch is delicately pushed towards the edges of the hole to slide underneath. The PFCL bubble is then actively aspirated next to the optic disc. Tamponade with gas or silicone oil is subsequently injected, with care taken to minimize fluid turbulence during the procedure. Results The outcomes of autologous Tenon patch grafts in three giant FTMHs are reported. In the first case, silicone oil tamponade was injected, in the second, C2F6 gas was injected. And in the third case, that of a woman with advanced glaucoma, no tamponade was left in the eye. No adverse effects were observed during or after the procedures. Closure of the macular hole and functional improvement were documented during the follow-up period in all three cases. Conclusion With a follow-up of up to 6 months, the Tenon patch graft appeared to be a promising technique for managing complex cases of FTMH. Additional studies to investigate long-term outcomes and determine the most appropriate indications are warranted.

Abstract Objective To examine the clinical characteristics, diagnosis and treatment, and prognosis of ocular amyloidosis in a Chinese population. Methods A retrospective case series study was conducted. The clinical data of 37 patients with ocular amyloidosis were collected and the clinical characteristics, diagnosis and treatment, and prognosis were summarized and analyzed. Results The 37 patients included 12 males and 25 females ranging in age from 22 to 75 years, with median age of 49 years. The clinical signs and symptoms included a conjunctival mass in 37 patients (100%), periorbital discomfort or pain in 29 patients (61.9%), ptosis in 18 patients (23.8%), exophthalmos or eyeball displacement in 3 patients (14.3%), restricted eye movement in 2 patients (9.52%), vision loss in 1 patient (4.76%), and diplopia in 1 patient (4.76%). A total of 29 patients had only conjunctival involvement and 8 patients had concomitant orbital and conjunctival involvement. The main treatment for patients with conjunctival involvement was surgical resection. Thirty-one patients had stable disease, 4 patients progressed or relapsed, and 2 patients were lost to follow-up. Conclusion Ocular amyloidosis most commonly presents as an eyelid or conjunctival mass or diffuse thickening and can also present as an orbital mass. Diagnosis is mainly dependent on histopathological examination. Surgery is the main treatment and is done to confirm the diagnosis to guide further treatment, preserve function, and prevent complications that threaten visual acuity. Close postoperative follow-up is necessary.

A clinical case of ocular surface xerosis in a patient with previously undiagnosed skin ichthyosis is presented. Clinical manifestations of change occurring in the eyes of the patient disease are outlined, and a complex of therapeutic measures to maintain the eye surface in ichthyosis is proposed.

ObjectivesThis study aimed to define the antimicrobial peptide (AMP) expression pattern of the equine ocular surface and amniotic membrane using a targeted qPCR approach and 3'Tag-sequencing. It will serve as a reference for future studies of ocular surface innate immunity and amniotic membrane therapies.ProceduresA targeted qPCR approach was used to investigate the presence of orthologs for three of the most highly expressed beta-defensins (DEFB1, DEFB4B, and DEFB103A) of the human ocular surface and amniotic membrane in equine corneal epithelium, conjunctiva, and amniotic membrane. 3'Tag-sequencing was performed on RNA from one sample of corneal epithelium, conjunctiva, and amniotic membrane to further characterize their AMP expression.ResultsEquine corneal epithelium, conjunctiva, and amniotic membrane expressed DEFB1, DEFB4B, and DEFB103A. DEFB103A was expressed at the highest amounts in corneal epithelium, while DEFB4B was most highly expressed in conjunctiva and amniotic membrane. 3'Tag-sequencing from all three tissues confirmed these findings and identified expression of five additional beta-defensins, 11 alpha-defensins and two cathelicidins, with the alpha-defensins showing higher normalized read counts than the beta-defensins.ConclusionsThis study identified AMP expression in the equine cornea and conjunctiva, suggesting that they play a key role in the protection of the equine eye, similar to the human ocular surface. We also determined that equine amniotic membrane expresses a substantial number of AMPs suggesting it could potentiate an antimicrobial effect as a corneal graft material. Future studies will focus on defining the antimicrobial activity of these AMPs and determining their role in microbial keratitis.

OBJECTIVES: The aim of this study was to retrospectively evaluate the signalment, treatment, surgical technique and outcomes for feline symblepharon. METHODS: A retrospective medical record review and standardized grading of clinical descriptions and photographs was undertaken. RESULTS: Forty kittens (54 eyes) aged 3-46 weeks had symblepharon of five types in various combinations: eyelid deformation (24 kittens; 32 eyes); ankyloblepharon (four kittens; four eyes); conjunctiva-to-conjunctiva (11 kittens; 12 eyes); third eyelid-to-conjunctiva (24 kittens; 29 eyes); and corneoconjunctival adhesions (14 kittens; 16 eyes). At initial presentation, 23 (43%) eyes were affected by one type of symblepharon, 25 (46%) eyes by two types and six (11%) eyes by three types; 11 (20%) corneas were ulcerated. Twenty-four (44%) eyes of 18 (45%) kittens were managed medically. Surgery was performed under general anesthesia/sedation (30 occasions) or topical anesthesia (21 occasions) on 30 (56%) eyes of 22 kittens; 12 eyes (40%) underwent multiple surgeries. Four techniques were commonly employed: separation of conjunctival-to-conjunctival adhesions ± eyelid margins (14 eyes); resection of third eyelid adhesions ± temporary tacking of the third eyelid (modified Arlts pterygium technique; 18 eyes); en bloc resection of the third eyelid (two eyes); and separation of corneoconjunctival adhesions (14 eyes). Median duration of follow-up was 55 days (range 1-1051). Median symblepharon grade in kittens treated surgically improved for all types except corneoconjunctival symblepharon. Median symblepharon grade in kittens receiving medical management remained the same or improved. Corneoconjunctival symblepharon opacity decreased for eyes treated surgically but increased for eyes treated medically. Three eyes were enucleated due to complications of corneoconjunctival symblepharon. At final presentation, symblepharon persisted in 46 (85%) eyes; however, menace response was evident in 13/16 eyes and dazzle reflex in 23/23 eyes. CONCLUSIONS AND RELEVANCE: Symblepharon is a heterogeneous group of conditions with diverse anatomic involvement, clinical appearance and impact, optimal treatment and prognosis for vision.

Objective: To examine the clinical characteristics, diagnosis and treatment, and prognosis of ocular amyloidosis in a Chinese population. Methods: A retrospective case series study was conducted. The clinical data of 37 patients with ocular amyloidosis were collected and the clinical characteristics, diagnosis and treatment, and prognosis were summarized and analyzed. Results: The 37 patients included 12 males and 25 females ranging in age from 22 to 75 years, with median age of 49 years. The clinical signs and symptoms included a conjunctival mass in 37 patients (100%), periorbital discomfort or pain in 29 patients (61.9%), ptosis in 18 patients (23.8%), exophthalmos or eyeball displacement in 3 patients (14.3%), restricted eye movement in 2 patients (9.52%), vision loss in 1 patient (4.76%), and diplopia in 1 patient (4.76%). A total of 29 patients had only conjunctival involvement and 8 patients had concomitant orbital and conjunctival involvement. The main treatment for patients with conjunctival involvement was surgical resection. Thirty-one patients had stable disease, 4 patients progressed or relapsed, and 2 patients were lost to follow-up. Conclusion: Ocular amyloidosis most commonly presents as an eyelid or conjunctival mass or diffuse thickening and can also present as an orbital mass. Diagnosis is mainly dependent on histopathological examination. Surgery is the main treatment and is done to confirm the diagnosis to guide further treatment, preserve function, and prevent complications that threaten visual acuity. Close postoperative follow-up is necessary. Keypoints: • Ocular amyloidosis most commonly presents as an eyelid or conjunctival mass or diffuse thickening and can also present as an orbital mass. • Diagnosis is mainly dependent on histopathological examination. Surgery is the main treatment and is done to confirm the diagnosis to guide further treatment, preserve function, and prevent complications that threaten visual acuity. [ABSTRACT FROM AUTHOR]

Although the eye can be subjected to therapeutic manipulation, some of its structures are highly inaccessible. Thus, conventional therapeutic administration pathways, such as topical or systemic routes, usually show significant limitations in the form of low ocular penetration or the appearance of side effects linked to physiology, among others. The critical feature of many xenobiotics is the drug gradient from the concentrated tear reservoir to the relatively barren corneal and conjunctival epithelia, which forces a passive route of absorption. The same is true in the opposite direction, towards the ocular surface (OS). With the premise that tears can be regarded as equivalent to or a substitute for plasma, researchers may determine drug concentrations in the OS fluid. Within this framework, a survey of scholarly sources on the topic was conducted. It provided an overview of current knowledge, allowing the identification of relevant theories, methods, and gaps in the existing research that can be employed in subsequent research. OS fluid (tears particularly) has enormous potential as a source of biological material for external drug screening and as a biomarker of various systemic diseases. Given the numerous alternate matrices, knowledge of their properties is very important in selecting the most appropriate specimens in toxicological analyses. [ABSTRACT FROM AUTHOR]