Monica Alves

Dry Eye Disease Treatment: A Systematic Review of Published Trials and a Critical Appraisal of Therapeutic Strategies

Dry eye disease (DED) treatment is an area of increasing complexity, with the emergence of several new treatment agents in recent years. Evaluation of the efficacy of these agents is limited by heterogeneity in outcomes definition and the small number of comparative studies. We provide a systematic review of clinical trials (CTs) related to DED treatment and a critical appraisal of CT public databases. CT reports obtained from eight databases were reviewed, as well as public free-access electronic databases for CT registration. Data evaluation was based on endpoints such as symptoms, Schirmer test, ocular surface staining scores, recruitment of patients, type and efficacy of the drug, and the design and site of performance of the study. Forty-nine CTs were evaluated involving 5,189 patients receiving DED treatment. Heterogeneity in study design prevented meta-analysis from yielding meaningful results, and a descriptive analysis of these studies was conducted. The most frequent categories of drugs for DED in these studies were artificial tears, followed by anti-inflammatory drugs and secretagogues. Although 116 studies have been completed, according to the registration database for clinical trials, only 17 of them (15.5%) were published. Out of 185 registered CTs related to DED, 72% were performed in the USA. The pharmaceutical industry sponsored 78% of them. The identification of effective DED treatment strategies is hindered by the lack of an accepted set of definitive criteria for evaluating disease severity.

Comparison of Diagnostic Tests in Distinct Well-Defined Conditions Related to Dry Eye Disease

Purpose This study compares signs, symptoms and predictive tools used to diagnose dry eye disease (DED) and ocular surface disorders in six systemic well-defined and non-overlapping diseases. It is well known that these tests are problematic because of a lack of agreement between them in identifying these conditions. Accordingly, we provide here a comparative clinical profile analysis of these different diseases. Methods A spontaneous and continuous sample of patients with Sjögrens syndrome (SS) (n = 27), graft-versus-host-disease (GVHD) (n = 28), Graves orbitopathy (n = 28), facial palsy (n = 8), diabetes mellitus without proliferative retinopathy (n = 14) and glaucoma who chronically received topical drugs preserved with benzalkonium chloride (n = 20) were enrolled. Evaluation consisted of a comprehensive protocol encompassing: (1) structured questionnaire - Ocular Surface Disease Index (OSDI); (2) tear osmolarity (TearLab Osmolarity System - Ocusense); (3) tear film break-up time (TBUT); (4) fluorescein and lissamine green staining; (5) Schirmer test and (6) severity grading. Results One hundred and twenty five patients (aged 48.8 years-old±14.1, male:female ratio = 0.4) were enrolled in the study, along with 24 age and gender matched controls. Higher scores on DED tests were obtained in Sjögren Syndrome (P<0.05), except for tear film osmolarity that was higher in diabetics (P<0.001) and fluorescein staining, that was higher in facial palsy (P<0.001). TFBUT and OSDI correlated better with other tests. The best combination of diagnostic tests for DED was OSDI, TBUT and Schirmer test (sensitivity 100%, specificity 95% and accuracy 99.3%). Conclusions DED diagnostic test results present a broad range of variability among different conditions. Vital stainings and TBUT correlated best with one another whereas the best test combination to detect DED was: OSDI/TBUT/Schirmer.

Is dry eye an environmental disease

Previous studies have revealed that eye contact with either air pollutants or adverse indoor and/or outdoor environmental conditions can affect tear film composition and ocular surface components. These effects are mediated by selective binding of the environmental agents to ocular surface membrane receptors, leading to activation of pro inflammatory signaling pathways. The aim of the current review was to examine the published evidence associated with environmental factors and ocular surface disease and dry eye. Specifically, the reader will appreciate why it is possible to refer to them as mediators of Environmental Dry Eye Disease (EDED), a singular clinical entity inside DED context, directly caused by pollutants and/ or adverse climatic conditions. The indicators and clinical findings are described along with EDE differential diagnosis in its acute and the chronic phases. Based on strong existing evidence of clinical reports and epidemiological observations regarding DED and environmental factors we conclude that there is a straight cause-and-effect relationship between ambient stresses and DED. International standards and web-based tools are described for monitoring worldwide environmental conditions referring localities and populations susceptible to EDED. This information is beneficial to health providers to pinpoint the individuals and predisposed groups afflicted with DED. Such insights may not only improve the understanding and treatment of DED but also help to identify the contributing factors and lower the frequency and progression of EDED.

Dry eye disease caused by viral infection: review

Dry eye disease and ocular surface disorders may be caused or worsened by viral agents. There are several known and suspected virus associated to ocular surface diseases. The possible pathogenic mechanisms for virus-related dry eye disease are presented herein. This review serves to reinforce the importance of ophthalmologists as one of the healthcare professional able to diagnose a potentially large number of infected patients with high prevalent viral agents.

Insulin replacement restores the vesicular secretory apparatus in the diabetic rat lacrimal gland

PURPOSE In the lacrimal gland (LG) acinar cells, signaling regulates the release of secretory vesicles through specific Rab and SNARE exocytotic proteins. In diabetes mellitus (DM), the LGs are dysfunctional. The aim of this work was to determine if secretory apparatus changes were associated with any effects on the secretory vesicles (SV) in diabetic rats as well as the expression levels of constituent Rab and members of the SNARE family, and if insulin supplementation reversed those changes. METHODS DM was induced in male Wistar rats with an intravenous dose of streptozotocin (60 mg/kg). One of the two diabetic groups was then treated every other day with insulin (1 IU). A third control group was injected with vehicle. After 10 weeks, Western blotting and RT-PCR were used to compared the Rab and SNARE secretory factor levels in the LGs. Transmission electron microscopy evaluated acinar cell SV density and integrity. RESULTS In the diabetes mellitus group, there were fewer and enlarged SV. The Rab 27b, Rab 3d, and syntaxin-1 protein expression declined in the rats with diabetes mellitus. Insulin treatment restored the SV density and the Rab 27b and syntaxin expression to their control protein levels, whereas the Vamp 2 mRNA expression increased above the control levels. CONCLUSIONS Diabetes mellitus LG changes were associated with the declines in protein expression levels that were involved in supporting exocytosis and vesicular formation. They were partially reversed by insulin replacement therapy. These findings may help to improve therapeutic management of dry eye in diabetes mellitus.

Buphthalmos development in adult: case report

To report a case of extensive globe enlargement due to secondary glaucoma in a young adult suffering from ocular surface disorders related to hypohidrotic ectodermal dysplasia. To the best of our knowledge, this is the first report of buphthalmos in the adulthood.