JAK1, SKI, ZBTB16 as potential biomarkers mediate the inflammatory response in keratoconjunctivitis sicca.

Keratoconjunctivitis sicca (KCS) is an ocular condition characterized by insufficient tear production and inflammatory irritation, with Sjögren's syndrome (SS) being a major causative factor. This study aimed to extract patient transcriptomic data from the GEO database to identify signature genes associated with the diagnosis and treatment of KCS and the expression of three key genes were experimentally verified. We performed a difference analysis on the SS patient dataset and performed a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the resulting genes. Additionally, a Weighted Gene Co-expression Network Analysis (WGCNA) was constructed. Machine learning techniques were employed to analyze the most strongly correlated gene modules with SS traits. These findings were further validated using KCS immune-correlation microarrays as a validation set. The correlation of the three identified genes with 22 immune cells was assessed through immune infiltration analysis. Subsequently, a rat model of desiccated keratoconjunctivitis was established, and the modeling situation and expression of characteristic genes were analyzed at the morphological, tissue, and molecular levels. Bioinformatic prediction revealed that the expression of JAK1, SKI, ZBTB16 not only differed in the machine learning validation set, but also correlated with some immune cells in the immune infiltration analysis. The results of animal experiments showed that the transcription and expression levels of these three genes were significantly different in rat KCS tissues and normal tissues, and there were also differences in the expression of JAK1 and SKI in rat peripheral blood, as well as significant up-regulation of the expression of related inflammatory factors in KCS tissues. Through bioinformatics prediction and animal experimental validation, this study identified three differentially expressed genes in SS mediated KCS patients, which provide new potential biological targets for the diagnosis and treatment of KCS.

Clinical manifestations of chronic pancreatitis in English cocker spaniels.

BACKGROUND: Chronic pancreatitis (CP) is common in English cocker spaniels (ECS). It is histologically similar to IgG4-related disease (IgG4-RD) in humans and is characterized by duct destruction, interlobular fibrosis, and dense periductular and perivenous lymphocytic aggregates. However, the clinical manifestations of CP in ECS have not been previously described. OBJECTIVES: Characterize the clinical manifestations of CP in a group of ECS, including similarities and differences to IgG4-RD in humans. ANIMALS: One-hundred four ECS with CP and 44 client owned control ECS without CP (both healthy and diseased controls). METHODS: Affected dogs were divided into 2 groups according to the methods used to diagnose CP. Case records were searched for signalment, clinical, and clinicopathological findings, and evidence of keratoconjunctivitis sicca (KCS), proteinuria, other immune-mediated diseases, and anal sacculitis. RESULTS: Involvement of other organs was common. Affected ECS presented with a high frequency of KCS (n = 49), proteinuria (n = 47), anal gland disease (n = 36), atopy (n = 21), and other immune-mediated diseases (n = 16). Those with parti-color hair coats, particularly blue roan, had a strong association with CP, suggesting a link between coat color and autoimmune conditions in this breed. CONCLUSIONS AND CLINICAL IMPORTANCE: English cocker spaniels with CP show clinical similarities to humans with IgG4-RD and common involvement of other organs. Clinicians should evaluate affected Cocker Spaniels for proteinuria, keratoconjunctivitis sicca, and other potential immune-mediated diseases.

A CXCR3-Activating Peptide Increases Tear Break Up Time and Corrects Corneal haze in a Rabbit Model of Environmental Dry Eye.

Purpose: Environmentally-triggered dry eye disease (DED) or keratoconjunctivitis sicca (KCS), which constitutes the majority of DED cases, currently is palliatively treated with aqueous replacement solutions that do not target the dysfunction of the mucin and lipid components of tears. We tested whether a peptide that increased goblet cell numbers in a model of scleral chemical injury would also improve tear quality in environmental DED. Methods: Environmental DED was established by exposing New Zealand white rabbits (8 per group, female) to 20% humidity with rapid air replacement and b.i.d. atropine sulfate eyedrops for 3 weeks prior to test article administration; this continued for the subsequent 3 weeks of testing. Animals were dosed by (A) saline, (B) b.i.d. eyedrop of peptide in saline, (C) b.i.d. eyedrop of peptide in coacervate, or (D) weekly subconjunctival injection of peptide. In vitro, human conjunctival epithelial cells (HCjE) were exposed to TNFα in the presence or absence of peptide to determine inflammatory responsiveness. Results: The environmental DED was established with both Schirmer and TBUT being reduced at the start of test article; these levels were maintained as low through the testing period. All three treatment regimens increased TBUT approximately 3x to levels greater than prior to desiccation (P < 0.01), with little effect on Schirmer. Corneal haze was present in all eyes after induction, and completely reversed in 36 of 48 eyes across the treatments (P < 0.05). Co-treatment of HCjE with peptide reduced the production of TNFα in response to an inflammatory stimulus. Conclusions: The treatment of environmental DED/KCS with a peptide that activates CXCR3 improved tear quality and reversed corneal pathology by promoting tear stability and likely dampening the corneal inflammation, while not affecting aqueous volume of the tears.

Schirmer tear test-1 with open or closed eyelids: An evaluation in brachycephalic and nonbrachycephalic dogs.

PURPOSE: Assess aqueous tear production when measured with the dogs' eyelids open or closed. METHODS: Thirty healthy dogs (15 Shih Tzus, 15 Labrador retrievers) were recruited. With the order of testing randomized for each dog, two sessions (separated by 30 min) of STT-1 testing were performed with the dogs' eyelids closed or open. Schirmer strip wetness (every 10 s for 60 s) and number of time(s) the strip dislodged during testing were recorded in each eye. Preferred STT-1 method was surveyed via a global Listserv of the veterinary ophthalmology community. RESULTS: STT-1 values were significantly higher in closed versus open eyes in Shih Tzus (18.6 ± 2.7 mm/min vs. 16.3 ± 2.5 mm/min; p = .002) and Labrador retrievers (21.6 ± 2.9 mm/min vs. 17.8 ± 3.2 mm/min, p < .001), findings that were also significant at times <60 s for either breed (p ≤ .004). Schirmer strips dislodged from six dogs with open eyelids and no dogs with closed eyelids. Maximal STT-1 difference with closed versus open eyelids was 13 mm/min in Labrador retrievers and 7 mm/min in Shih Tzus. Survey results from 275 veterinarians showed STT-1 performed with "closed eyelids" (38.5%), "open eyelids" (26.9%), or "never paid attention, sometimes closed, sometimes open" (34.6%). CONCLUSIONS: Eyelids status (closed or open) during STT-1 testing had a significant impact on aqueous tear secretion in brachycephalic and nonbrachycephalic dogs, highlighting the importance of consistency when repeating STT-1 in a canine patient. STT-1 differences are likely due to sustained reflex tearing throughout the test duration when the dogs' eyelids are closed.

Acute calcareous corneal degeneration in a patient with chronic graft-versus-host disease.

Objective: To describe acute calcareous corneal degeneration as a complication of chronic graft-versus-host disease. Materials and methods: Clinical case and review of the literature. Results: We presented a case of bilateral acute calcareous corneal degeneration in a patient with chronic graft-versus-host disease. Conclusions: Chronic graft-versus-host disease (cGVHD) occurs in 50-70% of bone marrow transplantation patients, the most frequent ocular complication being keratoconjunctivitis sicca (KCS). Calcareous corneal degeneration is a type of calcium deposition that can be secondary to chronic ocular inflammation or dry eye, but there are few cases reported of acute calcareous corneal degeneration and recurrent perforation in cGVHD. Abbreviations: GVHD = Chronic graft-versus-host disease, aGVHD = Acute graft-versus-host disease, cGVHD = Chronic graft-versus-host disease, KCS = Keratoconjunctivitis sicca, PKP = Penetrating keratoplasty, AMT = Amniotic membrane transplantation, PRGF = Plasma rich in growth factors, OD = Right eye, OS = Left eye.

Immunologic basis for development of keratoconjunctivitis sicca in systemic autoimmune diseases: Role of innate immune sensors.

The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign danger signals (including desiccating stress) on the ocular surface with an initial non-specific innate inflammatory response. If unchecked, this can lead to activation of dendritic cells that present antigen and prime T and B cells resulting in an adaptive immune reaction. These reactions generally resolve, but dysfunctional, hyper-responsive immune cells found in systemic autoimmune diseases that are recruited to the ocular surface can amplify inflammatory stress responses in the ocular surface and glandular tissues and result in autoimmune reactions that disrupt tear stability and lead to chronic dry eye disease. We here propose that unique features of the ocular surface immune system and the impact of systemic immune dysregulation in autoimmune diseases, can predispose to development of dry eye disease, and exacerbate severity of existing dry eye.

Sjögren's syndrome.

Sjögren's syndrome (SS) is characterised as keratoconjunctivitis sicca (dry eyes), xerostomia (dry mouth) commonly associated with salivary gland enlargement, and is referred to as Primary Sjögren's syndrome. It is known as Secondary Sjögren's syndrome when it occurs in patients, with connective tissue disease, such as rheumatoid arthritis, systemic lupus erythematosus, polyarthritis nodosa, polymyositis, and systemic sclerosis. SS has also been associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation, human immunodeficiency syndrome (AIDS), hepatitis C infection (HCV), chronic biliary cirrhosis, neoplastic and myeloplastic syndromes, fibromyalgia, and chronic fatigue syndrome.

Autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution: a clinical comparative study / Colírio de soro autólogo diluído com metilcelulose 0,5% e solução salina 0,9%: um estudo clínico comparativo

ABSTRACT Purpose: This clinical study compared autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution. The subjective criteria for symptom improvement and the objective clinical criteria for response to therapy were evaluated. Methods: This longitudinal prospective study enrolled 23 patients (42 eyes) with persistent epithelial defects or severe dry eye disease refractory to conventional therapy who had been using autologous serum 20% prepared with methylcellulose for > 6 months and started on autologous serum diluted in 0.9% saline solution. The control and intervention groups consisted of the same patients under alternate treatments. The subjective criteria for symptom relief were evaluated using the Salisbury Eye Evaluation Questionnaire. The objective clinical criteria were evaluated through a slit-lamp examination of the ocular surface, tear breakup time, corneal fluorescein staining, Schirmer's test, rose Bengal test, and tear meniscus height. These criteria were evaluated before the diluent was changed and after 30, 90, and 180 days. Results: In total, 42 eyes were analyzed before and after 6 months using autologous serum diluted with 0.9% saline. No significant differences were found in the subjective criteria, tear breakup time, tear meniscus, corneal fluorescein staining, or rose Bengal test. Schirmer's test scores significantly worsened at 30 and 90 days (p=0.008). No complications or adverse effects were observed. Conclusions: This study reinforces the use of autologous serum 20% as a successful treatment for severe dry eye disease resistant to conventional therapy. Autologous serum in 0.9% saline was not inferior to the methylcellulose formulation and is much more cost-effective.

RESUMO Objetivo: Este estudo comparou o colírio de soro au tólogo manipulado com metilcelulose a 0,5% com solução salina 0,9%. Critérios subjetivos de melhora dos sintomas e critérios clínicos objetivos para resposta à terapia foram avaliados. Métodos: Este estudo prospectivo longitudinal envolveu 23 pacientes (42 olhos) com defeitos epiteliais persistentes ou doença de olho seco grave refratária à terapia convencional que usavam colírio de soro autólogo 20% preparado com metilcelulose por mais de 6 meses e iniciaram soro autólogo diluído em solução salina 0,9%. Os grupos controle e intervenção consistiam dos mesmos pacientes sob tratamentos alternados. Os critérios subjetivos para o alívio dos sintomas foram avaliados usando o Salisbury Eye Evaluation Questionnaire. Os critérios objetivos foram avaliados por meio de exame em lâmpada de fenda incluindo: tempo de ruptura da lágrima, coloração da córnea com fluoresceína, teste de Schirmer, coloração com rosa bengala e altura do menisco lacrimal. Esses critérios foram avaliados antes da troca do diluente e após 30, 90 e 180 dias. Resultados: Um total de 42 olhos foram analisados antes e após 6 meses usando soro autólogo diluído com solução salina 0,9%. Nenhuma diferença significativa foi encontrada nos critérios subjetivos, tempo de ruptura da lágrima, menisco lacrimal, coloração com fluoresceína ou rosa bengala. Os resultados dos testes de Schirmer pioraram significativamente em 30 e 90 dias (p=0,008). Não foram observadas complicações ou efeitos adversos. Conclusões: Este estudo reforça o uso do colírio de soro autólogo 20% como um tratamento de sucesso para a doença do olho seco grave resistente à terapia convencional. O soro autólogo diluído em solução salina a 0,9% não foi inferior à formulação de metilcelulose.

Real-world treatment patterns of OTX-101 ophthalmic solution, cyclosporine ophthalmic emulsion, and lifitegrast ophthalmic solution in patients with dry eye disease: a retrospective analysis.

BACKGROUND: Dry eye disease (DED) is a disorder characterized by loss of tear film homeostasis that causes ocular surface inflammation and damage. The incidence of DED increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA®; OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis®; CsA), and lifitegrast ophthalmic solution 5% (Xiidra®; LFT) are anti-inflammatory agents indicated for DED. This analysis compared treatment patterns in patients with DED receiving OTX-101, CsA, or LFT. METHODS: This real-world, retrospective, longitudinal cohort study utilized Symphony Health Integrated Dataverse claims from July 2019 to June 2021. The dataset included all patients with OTX-101 claims and patients with CsA or LFT claims randomly selected 2:1 to OTX-101. Patients were sorted into 3 cohorts based on index treatment. Index date was that of first treatment claim, and follow-up period was from index date to end of clinical activity or data availability. Time to treatment discontinuation (TTD), probability of discontinuation, and treatment persistence were assessed for OTX-101 vs. CsA, then OTX-101 vs. LFT. Subgroup analysis was performed based on age and prior DED treatment. Kaplan-Meier analysis and log-rank test were used to examine TTD. A logistic model evaluated association between index treatment and discontinuation. Unadjusted and adjusted odds ratios, 95% confidence intervals, and P-values were reported, with statistically significant associations based on P-values < 0.05. RESULTS: Overall, 7102 patients (OTX-101 n = 1846; CsA n = 2248; LFT n = 3008) were eligible. Median TTD was 354 days for patients receiving OTX-101 vs. 241 days for CsA and 269 days for LFT. Log-rank test indicated TTD was significantly longer for patients on OTX-101 vs. CsA (P = 0.033). Patients on CsA were 35% more likely to discontinue treatment than patients on OTX-101; OTX-101 and LFT groups had similar discontinuation rates. After 360 days, 49.8% of patients receiving OTX-101 remained on treatment vs. 39.4% of patients on CsA (P = 0.036) and 44.0% of patients on LFT (P = 0.854). CONCLUSIONS: Patients receiving OTX-101 remained on treatment significantly longer and were significantly less likely to discontinue treatment than patients on CsA. Older patients remained on OTX-101 significantly longer than CsA. These findings highlight treatment pattern differences in patients with DED receiving these anti-inflammatory agents.

Inflammatory bowel disease and the associated risk of dry eye and ocular surface injury: a nationwide matched cohort study.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with lacrimal gland dysfunction and ocular inflammation. The objective of this research was to elucidate the temporal relationships between IBD, dry eye disease (DED), and corneal surface damage. METHODS: In a matched nationwide cohort study, we evaluated the risk of DED and corneal surface damage associated with IBD. Multivariable Cox proportional hazards regression analyses were implemented to estimate the risk of ocular complications. RESULTS: A total of 54,293 matched pairs were included for analyses. The median follow-up time was 8.3 years (interquartile range: 5.5 - 10.5). The period incidence of DED was 8.18 and 5.42 per 1000 person-years in the IBD and non-IBD groups, respectively. After adjusting for confounders, statistically significant associations were found between IBD and DED [adjusted hazard ratio (aHR): 1.43, 95% confidence interval (CI): 1.35 - 1.51, p < 0.0001], Sjögren's syndrome-related (aHR: 1.67, 95% CI:1.46 - 1.90, p < 0.0001) and non-Sjögren's syndrome-related subtypes (aHR: 1.38, 95% CI: 1.30 - 1.46, p < 0.0001). Furthermore, increased risks of corneal surface damage (aHR: 1.13, 95% CI: 1.03 - 1.24, p = 0.0094) among the patients with IBD were observed when compared with the controls. Other independent factors associated with corneal surface damage were age (aHR: 1.003), sex (male vs. female, aHR: 0.85), and monthly insurance premium (501-800 vs. 0-500 U.S. dollars, aHR: 1.45; ≥ 801 vs. 0-500 U.S. dollars, aHR: 1.32). CONCLUSIONS: Our results suggested that IBD was an independent risk factor for DED and ocular surface damage. Clinical strategies are needed to prevent visual impairment or losses in these susceptible patients.

Optimal acupuncture protocol improving symptoms of typical dry eye syndrome: meta-analysis and systematic review.

Previous meta-analyses have shown a superiority of acupuncture over artificial tear for treating typical dry eye syndrome (DES). However, given that the acupuncture protocols were quite diverse in the randomized controlled trials (RCTs) included in the meta-analyses, it is necessary to establish the acupuncture guidelines. Thus, the optimal acupuncture protocol involved in improvements of tear-film breakup time (BUT) or Schirmer tear test (STT) was examined by meta-analyses for RCTs in patients with typical DES. Eight databases until Jun 2018 were searched for 21 RCTs (n = 1542 eyes) comparing effectiveness of acupuncture versus artificial tear control. Indirect comparison of Bucher analysis was used to find specific acupoints (SAPs) improving BUT or STT by comparing the outcomes between subgroups of the RCTs including and excluding certain SAPs. Meta-analysis was examined for the outcomes in subgroups of the RCTs based on the number of SAPs, and network meta-analysis was for multiple pairwise comparisons across the protocols using the SAPs to yield relative effects. The Bucher analyses identified nine SAPs with positive effects on BUT or STT, and the positive relations of two SAPs involved in improvements of both BUT and STT suggested potential combinations of three ('KI3-LI4-SP6' or 'KI3-GB14-ST2') or four SAPs ('KI3-BL1-EX-HN7-SP6'). Subgroup meta-analyses showed the SAP-depending improvements of BUT or STT in the subgroups including more than three SAPs, compared with the artificial tear control. Meta-regression and network meta-analyses revealed significant correlations between the number of SAPs and the improvements of BUT and STT, and demonstrated that acupuncture using four SAPs for 21-30 days, particularly at two-three times per week, can be optimal for improving the symptoms of typical DES. These results provide useful information for guiding acupuncture in clinical trials for DES.

Dry eye in Parkinson's disease: a narrative review.

In Parkinson's disease (PD) patients, a wide range of ocular and visual disorders are present. Tear film instability, inflammation and dysfunction of the ocular surface, and the presence of symptoms of visual disturbance characterize dry eye, a multifactorial disease of the ocular surface. Based on a literature search, we discuss the frequency, pathogenesis, and influence on the quality of life of patients with dry eye in Parkinson's disease. Furthermore, we review the available means of diagnosis and management of dry eye. An improvement in awareness and recognition of dry eye is needed to provide suitable, personalized therapeutic options for PD patients, aiming to improve their quality of life, independence, and safety.

Autoimmune Inflammatory Eye Disease: Demystifying Clinical Presentations for the Internist.

PURPOSE OF REVIEW: Provide a framework for recognizing key symptoms and clinical findings in patients with autoimmune inflammatory eye disease. RECENT FINDINGS: The most common manifestations of autoimmune inflammatory eye disease are episcleritis, scleritis, uveitis (anterior, intermediate, posterior, and panuveitis), and keratoconjunctivitis sicca. Etiologies can be idiopathic or in association with a systemic autoimmune condition. Referral of patients who may have scleritis is critical for patients presenting with red eyes. Referral of patients who may have uveitis is critical for patients presenting often with floaters and vision complaints. Attention should also be directed to aspects of the history that might suggest a diagnosis of a systemic autoimmune condition, immunosuppression, drug-induced uveitis, or the possibility of a masquerade condition. Infectious etiologies should be ruled out in all cases. Patients with autoimmune inflammatory eye disease may present with ocular or systemic symptoms alone, or in combination. Collaboration with ophthalmologists and other relevant specialists is vital to optimal long-term medical care.

Comparison of strip meniscometry and Schirmer tear test results and tear film breakup time between healthy dogs and dogs with dry eye disease / Comparação entre o teste de meniscometria em tira, o teste lacrimal de Schirmer e o tempo de ruptura do filme lacrimal em cães normais e com olho seco

ABSTRACT Purpose: To compare strip meniscometry and Schirmer tear test 1 results and tear film breakup time between dogs with normal eyes and dogs diagnosed with keratoconjunctivitis sicca. Methods: One-hundred fifty-six eyes of 78 dogs, 88 normal eyes, and 68 eyes diagnosed with keratoconjunctivitis sicca were included in the study. The tests were performed in the following sequence: Schirmer tear test 1 was used to allocate the dogs to the normal or keratoconjunctivitis sicca group, followed by the strip meniscometry test and tear film breakup time measurement. Results: The results (mean ± standard deviation) of the tests in the normal group were as follows: Schirmer tear test 1, 22.75 ± 3.88 mm/min; strip meniscometry test, 10.01 ± 2.35 mm/5 sec; and tear film breakup time, 25.82 ± 5.47 sec. In the keratoconjunctivitis sicca group, the results were as follows: Schirmer tear test 1, 6.10 ± 4.44 mm/min; strip meniscometry test, 3.03 ± 2.62 mm/5 sec; and tear film breakup time, 10.78 ± 4.23 sec. The Spearman correlation coefficient in the keratoconjunctivitis sicca group was very high, with a significant difference between the strip meniscometry test and Schirmer tear test 1 (r=0.848, p<0.001), and moderate and significant between the strip meniscometry test and tear film breakup time (r=0.773, p<0.001). The cutoff for the strip meniscometry test for keratoconjunctivitis sicca was 7.0 mm/5 sec. Keratoconjunctivitis sicca was suspected when the values were <10 mm/5 sec. Conclusions: This study provided strip meniscometry test values from dogs with normal eyes and eyes with keratoconjunctivitis sicca, with high sensitivity and specificity compared with those of the Schirmer tear test 1. In the future, the strip meniscometry test may be another important quantitative test and could complement the gold standard Schirmer tear test for the diagnosis of keratoconjunctivitis sicca in dogs, an excellent animal model for the study of the disease.

RESUMO Objetivo: Comparar o teste de meniscometria em tira com o teste lacrimal de Schirmer 1 e o tempo de ruptura do filme lacrimal, em cães com olhos normais e cães com diagnóstico de ceratoconjuntivite seca. Métodos: Cento e cinquenta e seis olhos de 78 cães, 88 olhos normais e 68 olhos com diagnóstico de ceratoconjuntivite seca. Os testes foram realizados na seguinte sequência: o teste lacrimal de Schirmer 1 foi utilizado para alocar os cães no grupo normal ou no grupo ceratoconjuntivite seca, seguido pelo teste de meniscometria em tira e tempo de ruptura do filme lacrimal. Resultados: As médias e desvios-padrão para os olhos normais foram: teste lacrimal de Schirmer 1 = 22,75 ± 3,88 mm / min; teste de meniscometria em tira = 10,01 ± 2,35 mm / 5 seg; tempo de ruptura do filme lacrimal = 25,82 ± 5,47 seg; e para os olhos do grupo ceratoconjuntivite seca foram: teste lacrimal de Schirmer 1 = 6,10 ± 4,44 mm / min; teste de meniscometria em tira = 3,03 ± 2,62 mm / 5 seg; tempo de ruptura do filme lacrimal = 10,78 ± 4,23 seg. O teste de correlação de Spearman no grupo ceratoconjuntivite seca foi muito alto, com diferença significativa entre teste de meniscometria em tira e teste lacrimal de Schirmer 1 (r=0,848, p<0,001), moderada e significativa entre teste de meniscometria em tira e tempo de ruptura do filme lacrimal (r=0,773, p<0,001). O cut-off para teste de meniscometria em tira para ceratoconjuntivite seca foi identificado em 7,0 mm / 5 seg, valores abaixo de 10 mm / 5 seg podem ser considerados suspeitos para KCS. Conclusões: Este estudo forneceu valores de teste de meniscometria em tira em olhos normais e com ceratoconjuntivite seca em cães, revelando alta sensibilidade e especificidade em comparação com o teste lacrimal de Schirmer 1. No futuro, o teste de meniscometria em tira pode ser outro teste quantitativo importante e pode complementar o teste lacrimal de Schirmer padrão ouro para o diagnóstico de ceratoconjuntivite seca em cães, um excelente modelo animal para o estudo de ceratoconjuntivite seca.

Chloroquine and Hydroxychloroquine in the Treatment of Dry Eye Disease.

The role of chloroquine (CQ) and hydroxychloroquine (HCQ) in the management of dry eye disease is still unclear. This systematic review and meta-analysis investigates the efficacy and feasibility of CQ and HCQ in patients with dry eye disease. In February 2023, PubMed, Embase, Google Scholar, and Web of Science were accessed. Data from 462 patients (mean age 54.4 ± 2.8 years) were collected. Compared to baseline, the tear breakup time (p < 0.0001) and Schirmer I test (p < 0.0001) were significantly increased, and the Ocular Surface Disease Index (OSDI, p < 0.0001) and corneal staining (p < 0.0001) were significantly decreased at the last follow-up in the CQ/HCQ group. At the last follow-up, the OSDI was significantly lower in the CQ/HCQ group compared to the control group (p < 0.0001). Corneal staining was significantly greater in the control group compared to the CQ/HCQ group (p < 0.0001). The Schirmer I test showed no significant difference between the groups (p = 0.2). Altogether, CQ and HCQ improved the symptoms and signs of dry eye disease.

The impact of dry eye disease on corneal nerve parameters: A systematic review and meta-analysis.

PURPOSE: Dry eye disease (DED) is a growing global health problem with a significant impact on the quality of life of patients. While neurosensory abnormalities have been recognised as a contributor to DED pathophysiology, the potential role of in vivo corneal confocal microscopy in detecting nerve loss or damage remains unclear. This systematic review with meta-analysis (PROSPERO registered CRD42022381861) investigated whether DED has an impact on sub-basal corneal nerve parameters. METHODS: PubMed, Embase and Web of Science Core Collection databases were searched from inception to 9 December 2022. Studies using laser scanning confocal microscopy to compare corneal nerve parameters of DED with healthy eyes were included. Study selection process and data extraction were performed by two independent members of the review team. RESULTS: Twenty-two studies with 916 participants with DED and 491 healthy controls were included, with 21 of these studies included in subsequent meta-analyses. There was a decrease in total corneal nerve length (-3.85 mm/mm2 ; 95% CI -5.16, -2.55), corneal main nerve trunk density (-4.81 number/mm2 ; 95% CI -7.94, -1.68) and corneal nerve branch density (-15.52 number/mm2 ; 95% CI -27.20, -3.84) in DED eyes compared with healthy eyes, with subgroup analysis demonstrating that these differences were more evident in studies using NeuronJ software, a semi-automated procedure. While this review found evidence of loss of corneal nerve parameters in eyes with DED compared with healthy controls, particularly with the use of a semi-automated image analysis method, it is evident that there is substantial heterogeneity between studies in terms of corneal nerve imaging methodology. CONCLUSIONS: Standardisation is required in terms of terminology and analysis, with more research needed to potentially improve the clinical applicability and practicality of corneal nerve imaging. Further investigation is also required to confirm the diagnostic accuracy of this imaging modality and its potential for monitoring DED treatment efficacy.

Honey-Related Treatment Strategies in Dry Eye Disease.

This systematic review and meta-analysis investigated whether honey-related treatment strategies improve the signs and symptoms of patients with dry eye disease (DED). In March 2023, the following databases were accessed for clinical trials investigating the efficacy of honey-related treatment strategies in DED: PubMed, Web of Science, Google Scholar, and EMBASE. The following data were extracted at baseline and at the last follow-up: Ocular Surface Disease Index, tear breakup time, Schirmer I test, and corneal staining. Data from 323 patients were retrieved (53.3% female, mean age 40.6 ± 18.1 years). The mean follow-up was 7.0 ± 4.2 weeks. All the endpoints of interest significantly improved from baseline to the last follow-up: tear breakup time (p = 0.01), Ocular Surface Disease Index (p < 0.0001), Schirmer I test (p = 0.0001), and corneal staining (p < 0.0001). No difference was found in tear breakup time (p = 0.3), Ocular Surface Disease Index (p = 0.4), Schirmer I test (p = 0.3), and corneal staining (p = 0.3) between the honey-related treatment strategies and the control groups. According to our main results, honey-related treatment strategies are effective and feasible to improve symptoms and signs of DED.

The Association between Autoimmune Thyroid Disease and Ocular Surface Damage: A Retrospective Population-Based Cohort Study.

Autoimmune thyroid diseases (ATDs) are potentially connected to lacrimal gland dysfunction and ocular surface disruption. This study aimed to evaluate the relationships between ATD, dry eye disease (DED), and corneal surface damage. In a matched nationwide cohort study, we used Taiwan's National Health Insurance research database to compare the incidences of DED and corneal surface damage between subjects with and without ATD. Multivariable Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the ophthalmological outcomes. A total of 50,251 matched pairs with 748,961 person-years of follow-up were included for analysis. The incidence of DED was 16.37 and 8.36 per 1000 person-years in the ATD and non-ATD groups, respectively. ATDs were significantly associated with increased DED (aHR: 1.81, 95% CI: 1.73-1.89, p < 0.0001). This association was generally consistent across the subgroups of age, sex, different comorbidity levels, and use of systemic corticosteroids or not. Furthermore, patients with ATD had a higher risk of corneal surface damage compared with non-ATD subjects (aHR: 1.31, 95% CI: 1.19-1.44, p < 0.0001), including recurrent corneal erosions (aHR: 2.00, 95% CI: 1.66-2.41, p < 0.0001) and corneal scars (aHR: 1.26, 95% CI: 1.01-1.59, p = 0.0432). Other independent factors for corneal surface damage were age, sex, diabetes mellitus, Charlson Comorbidity Index scores, and use of systemic corticosteroids. Our results suggested that ATDs were associated with higher risks of DED and corneal surface damage. Considering the high prevalence of ATD, prophylactic and therapeutic strategies should be further developed to prevent irreversible vision loss in this susceptible population.

Association of serum 25-hydroxyvitamin D concentrations with Schirmer tear test 1 and tear film breakup time in dogs.

BACKGROUND: The association between vitamin D and canine keratoconjunctivitis sicca (KCS) has not been investigated in dogs. OBJECTIVES: To investigate the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with Schirmer tear test 1 (STT-1) and tear film breakup time (TFBUT) in dogs. METHODS: Sixty-one clinically healthy, client-owned dogs were enrolled. STT-1 and TFBUT were measured in 122 (61dogs) and 82 (41 dogs out of total 61 dogs) eyes, respectively. Serum 25(OH)D concentrations were evaluated by quantitative chemiluminescent immunoassay. The dogs were classified into 6 groups according to the evaluations (STT-1: group 1, normal [≥ 15 mm/min] in both eyes; group 2, normal in one eye and abnormal [< 15 mm/min] in the fellow eye; group 3, abnormal in both eyes; TFBUT: group 4, normal [≥ 20 sec] in both eyes; group 5, normal in one eye and abnormal [< 20 sec] in the fellow eye; group 6, abnormal in both eyes). RESULTS: STT-1 was positively correlated with TFBUT (p < 0.001). Among the STT-1 groups, the mean serum 25(OH)D concentration in group 1 was significantly higher than in groups 2 and 3 with positive correlation (p < 0.001). However, there were no significant differences among the TFBUT groups 4, 5, and 6. CONCLUSIONS: In dogs, it was found that serum 25(OH)D concentrations had a greater effect on quantitative KCS than qualitative KCS. Therefore, it is considered that measurement of serum 25(OH)D concentration could be included in the diagnostic tests in canine quantitative KCS patients.

Ocular disease as the presenting sign of rheumatoid arthritis - An observational case series.

Rheumatoid arthritis (RA) is an inflammatory auto-immune multi-system disorder affecting the synovial joints. Ocular manifestations occur in a significant proportion of patients with RA. Although there are literature studies available indicating that ocular involvement can be the presenting sign in RA, reports available are sparse. Our case series is a report of seven patients presenting with ocular manifestations of RA. It highlights the fact that familiarity with the characteristic features of RA among ophthalmologists and physicians helps in making a timely diagnosis, assessing the disease activity, and understanding how a diagnosis of systemic disease made on ocular manifestations can alter the course of the disease in terms of reducing morbidity and prolonging life expectancy.