Elsevier

The Ocular Surface

Volume 11, Issue 3, July 2013, Pages 181-192
The Ocular Surface

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

https://doi.org/10.1016/j.jtos.2013.02.002Get rights and content

Abstract

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.

Introduction

Dry eye disease (DED)1 affects a substantial segment of the world population with increasing frequency.2, 3, 4 DED treatment strategies have been recently modified to include anti-inflammatory agents, hormones, secretagogues, free fatty acids, and antioxidants.5, 6, 7, 8 As a result, a number of different therapeutic options are commercially available, and many other approaches have been patented, indicating that the number of options will increase in the near future.9 Yet, eye care professionals continue to have difficulties managing moderate-to-severe DED.10

The evaluation of the relative efficacy of DED therapeutics is challenging for several reasons, including the limited number of comparative efficacy trials, the absence of a universally accepted set of criteria to define therapeutic outcome, and the fact that some of the published studies dealt specifically with Sjogren syndrome.5, 11, 12, 13 Transparency of clinical trial (CT) results was improved in recent years by their obligatory registration in public databases.14 The analysis of these databases offers a new opportunity to follow ongoing clinical development programs for the treatment of DED and allows us to anticipate how the therapeutic armamentarium might be in the future.

To obtain a more meaningful assessment of current DED treatment strategies, we performed a systematic review of published DED CTs, as well as an analysis of CT registry databases.

Section snippets

Published Reports

Published studies involving treatment of DED contained in MedLine (PubMed) (http://www.ncbi.nlm.nih.gov/sites/entrez), EMBASE (http://www.embase.com/), BIOSIS (http://thomsonreuters.com/products_services/science), Cinahal (http://www.ebscohost.com/cinahl/), SIGLE (http://opensigle.inist.fr/), ZETOC (http://zetoc.mimas.ac.uk/), Current Controlled Trials (http://www.controlled-trials.com/mrct/) and LILACS (http://bases.bireme.br/cgi-bin) were searched with the key words “dry eye” (Medical Subject

Systematic Review of Literature on Dry Eye Treatment

In total, 106 studies were identified in the literature search, of which 49 fulfilled the inclusion criteria (Table 2).19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 Among the 57 excluded studies were experimental studies, case reports, cases series, and reviews (Figure 1).

Forty-nine CTs that examined the effectiveness of DED treatment in 5,189

Discussion

Using electronic databases, we reviewed studies comparing commercially available DED therapeutic strategies and novel candidates for treating DED. The identification of effective treatment strategies is hindered by the lack of an accepted set of consensual criteria to evaluate disease severity and treatment efficacy. Despite this limitation, several CTs addressing DED are ongoing worldwide.

One reason for the absence of evidence-based information on DED therapeutics is that most treatments are

Acknowledgment

The authors acknowledge the NIH Fellows Editorial Board for reviewing the manuscript.

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  • Cited by (0)

    This study was supported by grants from the following Brazilian governmental institutions: Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FAEPA).

    The authors have no financial or proprietary interest in any concept or product discussed in this article.

    Single-copy reprint requests to Monica Alves, MD, PhD (address below).

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