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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.

Long-acting injectable formulations of dexamethasone with minimal invasiveness are highly desired to manage chronic ocular inflammatory conditions. Here, we applied microcrystals (MCs) of a hydrophobic acetone-based ketal-linked prodrug of dexamethasone (SKD) to treat postoperative ocular inflammation. We compared the efficacy and safety of SKD MCs through subconjunctival (SC) injection with that of Maxidex (a topical suspension of dexamethasone MCs) through SC injection and eye drops in the phacoemulsification combined with intraocular lens implantation (Phaco-IOL) rabbit model. In Phaco-IOL rabbit eyes, a single SC injection of SKD MCs (0.4 mg dexamethasone equiv.) showed anti-inflammatory effects comparable to Maxidex eye drops and completely alleviated the inflammation within 28 days, while an SC injection of Maxidex at the same dose only provided anti-inflammatory effects for 7 days. The study on the dose-dependent anti-inflammatory effects of SKD MCs showed no significant difference in anti-inflammatory effects for the high dosage (0.8 mg dexamethasone equiv.) and the low dosage (0.4 mg dexamethasone equiv.) in 28 days. Nevertheless, systematic drug distribution of SKD MCs and Maxidex in normal rabbits after SC injection demonstrates that the drug concentration in conjunctiva was higher for the high dosage and that a considerable amount of prodrug and dexamethasone could still be detected in the cornea and iris-ciliary body at least 84 days for SKD MCs at high dosage. Furthermore, no persistent elevated intraocular pressure and abnormality in retinal structure and thickness were observed, confirming the excellent safety of long-acting SKD MCs post-SC injection. Our findings provide valuable insights into using prodrug-based MCs for treating ocular postoperative inflammation, and the detailed drug distribution analysis would promote the clinical translation of these MCs in ocular diseases. [Display omitted] • SC injection of SKD MCs effectively controls ocular inflammation in Phaco-IOL rabbits. • SC injection of Maxidex only shows ocular anti-inflammatory effects for a week. • SKD MCs can sustain the in vivo release of Dex more than 84 days after SC injection. • SKD MCs are safe for ocular applications after SC injection. [ABSTRACT FROM AUTHOR]

Summary: Background: The conjunctiva of the eye is a mucosal surface that is colonised by various bacteria. Following surgery, trauma or other underlying conditions the normal flora may cause eye infection such as conjunctival and corneal infections, or endophthalmitis. Objectives: This study aimed to investigate the bacterial population and antibiotic resistance of the conjunctiva in healthy horses. Study design: Random sampling of ocular samples from 20 horses during the winter (2019). Methods: Swab samples were collected from the eyes of 20 healthy horses of different breeds, ages and sexes in Tehran province, Iran. The swabs were cultured on blood agar and MacConkey agar and incubated at 37°C for 24–48 h. The isolated bacteria were characterised using cellular morphology, gram‐staining and biochemical tests. Sensitivity and resistance to 10 different antibiotics were measured using an antibiogram test. Results: Results showed that the bacterial population consisted of various species, with Bacillus cereus being the most frequent. There were no significant differences in the frequency of isolated bacteria between sexes and age groups. There were no significant differences in the sensitivity of the bacterial flora of the eyes to colistin, ceftiofur, florfenicol, amoxicillin and ampicillin between either different age groups or different sexes of the horses (p > 0.05). However, sensitivity to enrofloxacin and ciprofloxacin was significantly correlated with the age groups of the horses (p > 0.05). A significant difference in sensitivity to trimethoprim‐sulfamethoxazole between various sexes of horses was observed. Main limitations: The nonuniformity of the follow‐up examination, reliance on owners or caregivers of the horse for follow‐up information and lack of adequate financial resources to study more horses. Conclusions: The study suggests that the frequency of individual bacteria comprising the bacterial flora in horses' eyes is influenced by housing and management conditions rather than age and sex. [ABSTRACT FROM AUTHOR]

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]

Purpose: To study cellular and neural changes around the donor and recipient areas after pterygium excision combined with autologous conjunctival transplantation using corneal confocal microscopy, we evaluated the postoperative impact of this surgical procedure. Methods: Patients with primary pterygium located on the nasal side who visited the Department of Ophthalmology of Wuxi Second People's Hospital between April and August 2023 were enrolled. Age-matched healthy eyes were included as the control group. IVCM was performed in the affected eyes, 6 months after pterygium excision. The images of the central conjunctival cells in the recipient and donor areas, the cells of each layer of the cornea around the recipient and donor area (around 2 mm from the nasal and upper corneal margins), and the structures of the corneal margins were recorded in the affected eyes and statistically compared with the corresponding areas in the control eyes. Results: Seventeen eyes of 14 patients with primary pterygium located on the nasal side (mean 64 ± 8.74 years old), and 17 eyes of nine patients as age-matched normal controls were included. Compared with those of normal eyes, the density of corneal pterygoid epithelium around the recipient area (5104 ± 599 cells/mm2 vs. 5700 ± 515 cells/mm2, P < 0.01) and the central conjunctival epithelial cells in the recipient areas (3984 ± 453 cells/mm2 vs. 4834 ± 244 cells/mm2, P < 0.01) were significantly lower 6 months postoperatively. However, the superficial stromal, deep stromal, and endothelial cell densities around the recipient area exhibited no significant differences (P > 0.05). Highly illuminated basal cells were visible at the nasal corneal margin, with an irregular intersection of fibrous tissue with corneal epithelial cells. More dendritic Langerhans cell infiltration was seen in the junctional area. Compared with those in the normal eyes, the densities of the corneal pterygoid epithelium (4896 ± 428 cells/mm2 vs. 5557 ± 367 cells/mm2, P < 0.01), deep stromal cells (337 ± 65 cells/mm2 vs. 419 ± 39 cells/mm2, P < 0.01), endothelial cells (2305 ± 170 cells/mm2 vs. 2547 ± 212 cells/mm2, P < 0.01) around the donor area and the central conjunctival epithelial cells (3700 ± 446 cells/mm2 vs. 4282 ± 272 cells/mm2, P < 0.01) in the donor area were significantly lower 6 months postoperatively. However, no significant differences were observed in superficial stromal cell density (P > 0.05). A slight wavy interfacial intersection was visible on the superior corneal margin, with some of the highlighted basal cells visible. Conclusions: Pterygium excision combined with autologous conjunctival transplantation with corneal stem cells can better promote the repair of most corneal cells around the recipient area and fence-like structures of the corneal rim 6 months postoperatively, but there may be some damage to the corneal conjunctival structures around the donor area. [ABSTRACT FROM AUTHOR]

In vivo confocal microscopy (IVCM) is a unique imaging technique that permits noninvasive evaluation of the ocular surface on the cellular level. High-resolution images of all layers of the cornea are obtained in real-time with IVCM, and the acquired images are often comparable to ex vivo histochemical analysis of corneal biopsy specimens. The basic morphological features of the healthy living cornea as viewed by IVCM are reported in many domestic animal species, and the number of published descriptions of ocular surface pathologies in companion animals is progressively expanding. There is great potential for IVCM to improve the detection, characterization, and management of diverse ocular surface diseases in companion animals. This review summarizes several established and emerging clinical applications of IVCM in companion animal ocular surface disease, including infectious keratitis, corneal foreign bodies, corneal dystrophies and degenerations, ocular surface masses, corneal endotheliitis, pigmentary keratitis, and evaluation of corneal nerves. [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]

Purpose: To determine the association between the severity of trachomatous conjunctival scarring (TS) of the upper eyelid conjunctiva and trachomatous trichiasis (TT) severity in TT surgical patients. Methods: A cross-sectional study was conducted amongst adults with TT who were referred to surgical camps in Bahi District, Tanzania, for TT surgery. Participants underwent ocular examination. The presence and severity of TS was evaluated in photographs of the everted upper eyelid. TT severity was assessed at the time of the ocular exam based on the number of lashes touching the globe and/or evidence and extent of epilation. Ordinal logistic models were used to examine the association between the severity of TS and TT severity. Results: A total of 627 eyes of 388 participants were included. Mean age was 65 years (ranging from 21–98), 81% were females, and 62% had bilateral TT. 93% of eyes with any TT had at least moderate TS; 62% of eyes had severe TS. An increase in TS severity was associated with an increase in the severity of TT. Using as a reference eyes with none to mild TS, in eyes with moderate TS the odds of increased severity of TT was 1.30 (95% CI 0.67–2.51), in eyes with severe TS the odds was 4.20 (95% CI 2.23–7.92). Conclusion: In cases of trachomatous trichiasis presenting for surgery, the severity of TT was significantly associated with the severity of TS with almost all cases of TT having moderate or severe scarring. [ABSTRACT FROM AUTHOR]

Background Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV and solid organ transplant recipients, 2 immunosuppressed populations, may help identify novel etiologic relationships with infectious agents. Methods We used 2 linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified according to site and histology codes. Standardized incidence ratios were used to compare risk in people with HIV and solid organ transplant recipients with the general population. For selected cancer entities, incidence rate ratios were calculated for indicators of immunosuppression within each population. Results We identified 38 047 cancer cases in solid organ transplant recipients and 53 592 in people with HIV, yielding overall standardized incidence ratios of 1.66 (95% confidence interval [CI] = 1.65 to 1.68) and 1.49 (95% CI = 1.47 to 1.50), respectively. A total of 43 cancer entities met selection criteria, including conjunctival squamous cell carcinoma (people with HIV standardized incidence ratio = 7.1, 95% CI = 5.5 to 9.2; solid organ transplant recipients standardized incidence ratio = 9.4, 95% CI = 6.8 to 12.6). Sebaceous adenocarcinoma was elevated in solid organ transplant recipients (standardized incidence ratio = 16.2, 95% CI = 14.0 to 18.6) and, among solid organ transplant recipients, associated with greater risk in lung and heart transplant recipients compared with recipients of other organs (incidence rate ratio = 2.3, 95% CI = 1.7 to 3.2). Salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma showed elevated risk in solid organ transplant recipients (standardized incidence ratio = 3.9,  4.7, and  3.2, respectively) but not in people with HIV. However, risks for these cancers were elevated following an AIDS diagnosis among people with HIV (incidence rate ratio = 2.4, 4.3, and  2.0, respectively). Conclusions Elevated standardized incidence ratios among solid organ transplant recipients and people with HIV, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival squamous cell carcinoma, sebaceous adenocarcinoma, salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: Current practice for diagnostic biopsy of lacrimal gland lesions entails an orbitotomy procedure via an upper eyelid crease or lateral canthotomy skin incision. We describe a novel surgical technique to address these lesions via the lateral conjunctival fornix. Methods: Retrospective case series of all patients who underwent a lateral fornix orbitotomy procedure for incisional or excisional diagnostic biopsy of lacrimal gland lesions. The procedure involves a conjunctival incision in the lateral fornix remote from the openings of the lacrimal ductules, and an intraperiosteal surgical corridor to access the lacrimal gland. Results: The study cohort included 16 patients (3 male, 13 female) with a mean age of 48.3 years (range, 24.0–78,9 years). The sampled lesions involved the orbital lobe in 14 patients, the palpebral lobe in 1 patient, and the entire gland in 1 patient. A histopathological diagnosis was obtained in all cases. Postoperatively, new moderate adduction deficit developed in one patient (6.3%) that recovered after adhesiolysis of the conjunctival scar. 3 patients (18.8%) experienced transient mild limitation of adduction or abduction. There was no new or worse ptosis or dry eye disease related to the surgery. The mean length of postoperative follow-up was 1.3 years (median 1.0 years, range, 0.6–4.7 years). Conclusion: The lateral fornix orbitotomy approach was successful in obtaining biopsy specimens of histopathological diagnostic value. It provides transconjunctival access to the lacrimal gland without damage to the excretory lacrimal ductules or displacement of the eyelid support system. Key messages: What is known • Traditional techniques to biopsy lacrimal gland lesions entail transcutaneous orbitotomy procedures via an upper eyelid crease or lateral canthus incision. • Transconjunctival approaches via the superolateral fornix are discouraged for the risk of damage to the excretory lacrimal ductules. What is new • The lateral fornix orbitotomy provides intraperiosteal extraconal access to the lateral orbit. • Lesions of the orbital or palpebral lobe of the lacrimal gland can be safely and effectively biopsied via a lateral fornix conjunctival incision. [ABSTRACT FROM AUTHOR]

Objective: To determine the associations between lid and conjunctival injuries (LACI), non‐fatal strangulation (NFS) and domestic family violence (DFV) in non‐sexual assault. Methods: The present study involves an analysis of LACI in a clinical audit of 85 sequential non‐sexual assault presentations. Results: LACI was present in 26.9% of non‐sexual assault cases, and 47.4% of LACI patients also experienced NFS. LACI was sustained in the context of DFV in 62.9% of cases. Females made up 69.2% of LACI patients, with those between 14 and 29 years most at risk. Children were present in 12.8% of cases, 78.2% of perpetrators were male and 44.9% of patients had previously been assaulted by the same perpetrator. Conclusions: LACI is frequently associated with NFS and/or DFV. Since NFS increases future homicide attempts and events more than sixfold, LACI is an important signal about a patient's homicide risk, expanding the dimensions of the care needed. Those experiencing LACI during an assault also need to be referred for comprehensive eye examination as soon as possible. With consent, systematic forensic photography of LACI enables its assessment and documentation, which assists the legal process. These conclusions should drive legislative consideration and reform, plus expanded education for clinicians and police. [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]

Background: The ocular microbiome of the human eye has been analyzed using both the conventional approach of cultivating bacteria on growth media and by next generation sequencing (amplicon and metagenomic sequencing) to ascertain the gross microbial diversity of cultivable and uncultivable bacteria. Research design and methods: Both the methods demonstrated that the ocular surface microbiome is influenced by gender, age, ethnicity, microhabitat of the eye, and ocular diseases. The ocular surface microbiome of individuals with ocular diseases like keratitis, conjunctivitis, blepharitis, scleritis, orbital cellulitis, endophthalmitis, uveitis, etc., is described with relevance to pathogenesis of the disease. Results: The ocular microbiome of healthy individuals and individuals with above ocular diseases is highlighted. For instance, the conjunctivae of patients with bacterial keratitis had a predominance of pathogenic bacteria (Pseudomonas spp. Staphylococcus spp. Streptococcus spp. Acinetobacter spp. etc.) compared to the healthy controls and this predominance of pathogens in the diseased state of the eye may be causing or exacerbating ocular surface inflammation in keratitis. Based on the attributes of the bacteria (commensal, probiotic, proinflammatory, pathogenic and anti-inflammatory status) the manifestation of ocular diseases is discussed. Conclusions: Thus, it is likely that ocular surface microbiomes are associated with other ocular diseases. [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]

Purpose: To study the positivity rate of conjunctival realtime polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design: Systematic review and diagnostic accuracy meta-analysis. Methods: MEDLINE and EMBASE were queried using medical subject headings terms. Diagnostic accuracy meta-analyses and forest plots were obtained using the RevMan software. Results: After deduplication, appraisal of abstract titles and full-text analysis of 1441 articles, 42 articles with 3351 COVID-19 patients were included in this review. Of these, 412 conjunctival swabs/Schirmer paper strips tested positive for SARS-CoV-2 by RT-PCR. The pooled sensitivity of the RT-PCR tests across the 24 studies with laboratory-confirmed COVID-19 patients was 10.3%. Conclusions: Only 1 in 10 RT-PCR tests performed on conjunctival swabs were positive for SARS-CoV-2. Although this suggests that SARS-CoV-2 is likely present and detectable in the conjunctiva, this detection method has low diagnostic potential. [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]

Background: People living with HIV are disproportionately represented among people with severe mpox. Mild and self‐limiting conjunctival involvement has been well‐documented, and severe ocular complications, including keratitis, corneal scarring, and the associated loss of vision, are increasingly recognized. Tecovirimat is the first‐line antiviral therapy for severe mpox, but data around the efficacy of systemic antiviral agents for mpox are limited, particularly in cases of ocular mpox. Case Report: Here, we describe a case of sight‐threatening necrotic blepharokeratoconjunctivitis in a person with advanced HIV, requiring an extended course of tecovirimat due to persistent mpox viral shedding for nearly 5 months. [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: Pterygium is atriangular fibroelastic degeneration of the conjunctiva and subconjunctival tissue. Methods: quasi experimental study, comprising 52 patients aged from 35 to 60 during perid from April 2021 to April 2022 who underwent pterygium excision and autologus conjunctival graft. A total of 52 participants were enrolled and followed before and after 1 and 3 months after surgery by pentacam Scheimpflug camera . Results: there were significant changs in keratometric astigmatism at 1 month and 3 months compared with preoperative mean keratometric astigmatism, and there were statistically significant reduction in mean refractive astigmatism at 1 month and3 months postoperatively compared with preoperative mean refractive astigmatism. Also, a significant increase of spherical power of the cornea, there were statistically significant increase in average K1 at 1 month 3 months postoperatively compared with preoperative average K, There were statistically significant increase in average K 2 after 1 month,3 months, postoperatively compared with preoperative average K2, The mean BCVA was 0.31(0.13 SD) equivalent Decimal value preoperatively and improved significantly at 1 month postoperatively 0.48 (0.13 SD) equivalent Decimal value, P <0.001) and 3 months postoperatively 0.60( 0.13 SD), P <0.001) when compared with preoperative values. Conclusions: pterygium excision was associated with significant improvement in astigmatism. [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]

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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]

Pterygium is a wing-shaped fibrovascular growth extending from the conjunctiva onto the cornea. This review aims to provide a comprehensive overview of pterygium, including its etiology, clinical presentation, diagnosis, treatment options, and prognosis. A literature search was conducted using PubMed and Google Scholar databases. Findings suggest that pterygium is primarily associated with UV exposure and occurs more frequently in tropical and subtropical regions. Diagnosis is primarily clinical, with treatment options ranging from conservative management to surgical intervention. While generally benign, pterygium can cause visual disturbances and has a significant recurrence rate post-surgery. [ABSTRACT FROM AUTHOR]