Systematic review of ocular surface treatments in the setting of thyroid eye disease.

Introduction: Approximately 85% of patients with thyroid eye disease experience ocular surface symptoms. Although corneal exposure plays a role in inducing inflammatory changes to the ocular surface, multiple studies reveal more complexity to the abnormal tear film composition and parameters in thyroid eye disease patients including those who do not have proptosis or increased corneal exposure. Currently, a majority of cases of thyroid associated dry eye symptoms are given treatments intended for ocular surface disease arising from different etiologies. Methods: Medline via Ovid, Cochrane CENTRAL, PubMed, and Google Scholar were systematically searched for articles evaluating the efficacy of treatments for dry eye symptoms in patients with thyroid eye disease. Articles were from all geographic regions and dates ranged from inception until October 2023. Results: Seven papers ultimately met inclusion criteria and were included in this review. These papers revealed that multiple topical and non-topical treatment modalities address dry eye symptoms in thyroid eye disease and improve subjective and objective ocular surface parameters. However, due to the few studies that exist and due to disparities in sample size and study design, no overwhelming best practices were identified that could influence clinical practice. Conclusion: This systematic review identifies the current treatments that exist and highlights the clear unmet need for a large population suffering with dry eye symptoms. Ideally, further well-designed investigations into this area would target topical, non-invasive modalities to develop first line options for thyroid eye disease patients.

Scanning Electron Microscopy (SEM) Evaluation of the Ultrastructural Effects on Conjunctival Epithelial Cells of a New Multiple-Action Artificial Tear Containing Cross-Linked Hyaluronic Acid, Cationic Liposomes and Trehalose.

The authors performed an ex vivo and in vivo evaluation of the ultrastructural effects on the conjunctival epithelial cells of a new multiple-action tear substitute containing cross-linked hyaluronic acid, lipids and trehalose (Trimix®), using scanning electron microscopy (SEM) with conjunctival impression cytology. The ex vivo study highlights the persistence and distribution of the product at 5 and 60 min on a monolayer of conjunctival epithelial cells and an increase in microvilli density at the 60 min evaluation. In vivo examination was conducted on three subjects with different grades of ocular surface inflammation, treated with one drop of the product twice daily for thirty days. At the baseline (T0) and twelve hours after the last administration of the tear drop (T30), impression cytology of the upper bulbar conjunctiva for SEM evaluation of conjunctival epithelial cells was carried out. Slit lamp examination (SLE), corneal and conjunctival Fluotest, tear film break-up time (TBUT), and ocular surface disease index (OSDI) questionnaires were also performed to correlate the ultrastructural results with the clinical findings. After 30 days of treatment, a significant improvement in all clinical and symptomatic parameters and in the condition of the ocular surface was detected, with microvillar regeneration and strengthening in all the patients, and a complete restoration in 2/3 of them. The persistence and distribution of the product on the epithelial cells was also noted 12 h after the last administration. The results, therefore, suggest a marked epitheliotropic effect along with a high residence time of the tear substitute.

A Systematic Review on the Association Between Tear Film Metrics and Higher Order Aberrations in Dry Eye Disease and Treatment.

We systematically reviewed published research on dry eye disease and its association with higher order aberrations (HOAs). The purpose of this review was to first determine if an association between tear film metrics and HOAs exists and second to determine if the treatment of dry eyes can improve tear film metrics and HOAs together. A search was conducted in Entrez PubMed on 25 April 2021 using the keywords "higher order aberrations" and "dry eye". The initial search yielded 61 articles. After publications were restricted to only original articles measuring HOA outcomes in patients with dry eye, the final yield was 27 relevant articles. Of these 27 papers, 12 directly looked at associations and correlations between dry eyes and HOA parameters. The remaining 15 studies looked at dry eye interventions and HOA outcomes and parameters. There is clear evidence demonstrating that dry eyes and HOAs have an association, and that the tear film is one of the most important factors in this relationship. There is also a direct correlation between tear film metrics and HOAs. Improvements in HOAs with dry eye interventions provide further evidence to support the intricate relationship between the two. Despite the clear association between HOAs and dry eye disease, further research is still required in the realm of clinical application as dry eye interventions vary depending on many factors, including patient severity and eye drop viscosity.

Hyaluronic acid in the treatment of dry eye disease.

Dry eye disease (DED) is a highly prevalent and debilitating condition affecting several hundred million people worldwide. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan commonly used in the treatment of DED. This review aims to critically evaluate the literature on the safety and efficacy of artificial tears containing HA used in DED treatment. Literature searches were conducted in PubMed, including MEDLINE, and in Embase via Ovid with the search term: "(hyaluronic acid OR hyaluronan OR hyaluronate) AND (dry eye OR sicca)". A total of 53 clinical trials are included in this review, including eight placebo-controlled trials. Hyaluronic acid concentrations ranged from 0.1% to 0.4%. Studies lasted up to 3 months. A broad spectrum of DED types and severities was represented in the reviewed literature. No major complications or adverse events were reported. Artificial tears containing 0.1% to 0.4% HA were effective at improving both signs and symptoms of DED. Two major gaps in the literature have been identified: 1. no study investigated the ideal drop frequency for HA-containing eyedrops, and 2. insufficient evidence was presented to recommend any specific HA formulation over another. Future investigations assessing the optimal drop frequency for different concentrations and molecular weights of HA, different drop formulations, including tonicity, and accounting for DED severity and aetiology are essential for an evidence-based, individualized approach to DED treatment.

Interpersonal Communication in Eye Care: An Analysis of Potential Impacts on Cataract Surgery Candidates' Expectations and Behaviors.

Purpose: To identify cataract surgery candidates' knowledge, beliefs, desires and emotions as they relate to cataract surgery generally as well as to their behavioral intent to adhere to a doctor-recommended pre-surgical ocular surface prep routine designed to improve refractive outcomes and prevent surgical complications. Methods: This national, noninterventional, cross-sectional, mixed methods survey included 278 US adults ages 65 and older with no history of cataract surgery in either eye. Results: Only 20% of participants said they want to have cataract surgery, and even fewer (8%) said they wish they could have cataract surgery right away. Fear was the predominant emotion in one out of every three respondents and was correlated with intention to delay having cataract surgery for as long as possible (r = 0.44). Fewer than 2% of participants said their doctors recommended home-health strategies to combat the risks of ocular surface disease preoperatively. However, most say they would use a pre-surgical prep kit if their doctor gave them one (87%), asked them to buy one (83%), or directed them to obtain one online (71%). Conclusion: These findings negate the popular assumption that patients are in a hurry to have their cataract surgery right away and, therefore, may resist physician recommendations to address ocular surface disease pre-operatively.

Dry Eye Treatment with Topical Cyclosporine 0.1% in Chondroitin Sulfate Ophthalmic Emulsion.

PURPOSE: To evaluate the efficacy of topical cyclosporine 0.1% in chondroitin sulfate emulsion for the treatment of dry eye. METHODS: This retrospective multicenter study included 100 eyes of 50 dry eye patients aged ≥18 years, with preoperative ocular surface disease index (OSDI) score >12 or corneal staining grade >1 (in either eye) who underwent dry eye treatment with topical cyclosporine 0.1% in chondroitin sulfate emulsion (Klarity-C, ImprimisRx) for 3 months. Postoperative evaluation included comparison of the changes in OSDI score and corneal staining grade after 3 months of treatment from baseline. RESULTS: From baseline to 3 months, a statistically significant improvement in mean OSDI scores (38.19 vs 24.18, p <0.001) as well as mean corneal staining grade (3.62 vs 2.20, p <0.001) was observed. The proportion of subjects with severe dry eye decreased from 62% to 20% and more than one-third (34%) of patients were in the normal OSDI range. The percentage of eyes with corneal staining grade of 2 or 3 decreased from 21% (baseline) to 8% at 3 months; 50% of the eyes had corneal staining grade of 0. The treatment was found to be safe with no adverse events observed in the study. CONCLUSION: Dry eye treatment with twice daily cyclosporine 0.1% in chondroitin sulfate emulsion was found to be safe and effective in reducing signs and symptoms of dry eye.

A Comprehensive Review of the Clinical Trials Conducted for Dry Eye Disease and the Impact of the Vehicle Comparators in These Trials.

Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by loss of homeostasis of the tear film and accompanied by symptoms such as ocular discomfort and visual disturbance. DED is one of the most common reasons for seeking medical care in the United States and across the world. Despite this, there are a limited number of pharmacologic therapies for the treatment of DED in the United States and Europe. This review examines the different pivotal trials for DED medications and the impact the vehicle in each trial.In recent clinical trials, the vehicle of the active formulation of the medication is often used as the active comparator. A literature review of published dry eye clinical trials was performed to identify the pivotal clinical trials of DED medications and to compare treatment effect and further understand the impact of the vehicle on clinical trial outcomes.The pivotal clinical trials for the currently approved treatments for dry eye have widely varying study designs. The variations include differences in inclusion criteria, outcome measures and efficacy endpoints, and whether or not the use of concomitant artificial tears is allowed. These differences make it difficult for accurate comparisons to be made between DED medications. Each trial demonstrated that the vehicle alone has some beneficial effect on signs and symptoms of dry eye disease.This review discusses the varying trial designs and vehicles used in the pivotal studies for the four approved dry eye medications in the United States and Europe, as well as novel vehicles under development and clinical trial recommendations.

SIDRE: Symptomatic Improvement of Dry Eye Study.

PURPOSE: The aim of this study was to evaluate the effectiveness of lifitegrast 5% ophthalmic solution in reducing the symptoms of eye dryness using Ocular Surface Disease Index (OSDI) questionnaire. METHODS: A single-center study was undertaken to evaluate the clinical outcomes. Fourteen subjects (12 female and 2 male) with symptoms of dry eye and a positive history of recent use of artificial tears were included in the study. OSDI questionnaire scores on the severity of symptoms, visual functionality, and quality of life related to the condition were recorded pre- and post-therapy. Subsequently, score data were analyzed for statistical significance. RESULTS: The mean age of the 14 subjects was 44.86 (standard deviation [SD] ±3.08) years, with a range of 23-62 years. Mean duration of the evaluation was 28.79 days with a range of 25-34 days. Baseline OSDI mean score was 49.40 (SD ±1.28), and post-therapy mean score was 42.26 (SD ±0.99). Data analysis revealed that the scores were statistically significantly improved post-lifitegrast therapy in comparison to baseline (p=0.00041). CONCLUSION: Lifitegrast 5% ophthalmic solution may be a beneficial therapeutic option in the management of symptoms associated with dry eye disease.

Sex hormones and the dry eye.

The greater prevalence of dry eye in women compared to men suggests that sex hormones may have a role in this condition. This review aims to present evidence for how sex hormones may affect the ocular structures involved in the production, regulation and maintenance of the normal tear film. It is hypothesised that hormone changes alter the homeostasis of the ocular surface and contribute to dry eye. Androgens impact on the structure and function of the meibomian and lacrimal glands and therefore androgen deficiency is, at least in part, associated with the aetiology of dry eye. In contrast, reports of the effects of oestrogen and progesterone on these ocular structures and on the conjunctiva are contradictory and the mechanisms of action of these female-specific sex hormones in the eye are not well understood. The uncertainty of the effects of oestrogen and progesterone on dry eye symptoms is reflected in the controversial relationship between hormone replacement therapy and the signs and symptoms of dry eye. Current understanding of sex hormone influences on the immune system suggests that oestrogen may modulate a cascade of inflammatory events, which underlie dry eye.