ORIGINAL ARTICLE SKIN AND EYE DISEASES Clinical trials in allergic conjunctivits: a systematic review F. Mantelli 1 , A. Lambiase 1 , S. Bonini 2 & S. Bonini 1 1 Department of Ophthalmology, Campus Bio-Medico University of Rome, Rome; 2 Department of Internal Medicine, Second University of Naples, Naples, Italy To cite this article: Mantelli F, Lambiase A, Bonini S, Bonini S. Clinical trials in allergic conjunctivits: a systematic review. Allergy 2011; 66: 919–924. Allergic diseases have dramatically increased in the last decades (1). Among them, ocular allergy represents one of the most common clinical conditions encountered in clinical practice. Moreover, in the last years, an increase in its world- wide prevalence has been observed because of an increased use of contact lenses, an increased exposure to environmental factors such as smoke and pollution, and an increase in asso- ciated atopic disorders (2–4). In a recent survey in Italy from tertiary referral centers, ocular allergy accounts for 25% of all the ocular surface diseases (5). In fact, the term of ocular allergy includes distinct clinical conditions, such as Seasonal or Perennial Allergic Conjuncti- vitis (SAC and PAC), Vernal Keratoconjunctivitis (VKC), and atopic keratoconjunctivitis (AKC) (6, 7). Another form of allergic conjunctivitis, named Giant Papillary Conjunctivi- tis (GPC), is usually observed in contact lens wearers (8). The presence of conjunctival papillae or follicles, the type of conjunctival secretion, the involvement of the cornea, and the prevalence of specific symptoms, such as itching, redness, burning, photophobia, tearing, or dryness, may help in the differential diagnosis between these different forms of ocular allergy (9). While SAC and PAC generally represent a mild-to-moderate disease, in AKC and VKC, inflammation frequently involves the cornea, resulting in more severe symptoms and possibly permanent visual damage (10–12). In spite of the clinical, immunologic, prognostic, and ther- apeutic differences of these clinical entities, they may all share a common allergen sensitization, similar symptoms, but a variable response to topical antiallergic, anti-inflammatory, or immunosuppressive agents (13). The efficacy of topical antiallergic compounds has been extensively studied in the last 45 years as their number increased after the launch of the first antiallergic eye drops, Cromolyn, in the 1980s (14–16). In the present systematic review, we evaluated the clinical trials in allergic conjunctivitis published from 1965 to 2008, as well as the most recent clinical trials (registered on http:// www.clinicaltrials.gov) that have started in the last 5 years and are either currently recruiting patients or have recently been completed. These studies were evaluated following the Keywords allergic conjunctivitis; clinical outcomes; ocular allergy; PICO question. Correspondence Professor Stefano Bonini, Department of Ophthalmology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy. Tel.: (+39) 06-225419185 Fax: (+39) 06-22541456 E-mail: s.bonini@unicampus.it Accepted for publication 6 December 2010 DOI:10.1111/j.1398-9995.2010.02536.x Edited by: Thomas Bieber Abstract Background: Ocular allergy represents one of the most common conditions encoun- tered by allergists and ophthalmologists. However, there is wide variability of study designs in clinical trials of allergic conjunctivitis, which results in conflicting evidence on their optimal management. We conducted a systematic review of clinical trials to critically evaluate their quality and to highlight biases to be avoided in future clinical research in ocular allergy. Methods: Clinical trials in allergic conjunctivitis performed since 1965 were retrieved, and data on patients, interventions, comparison of interventions, and out- comes were extracted. Four authors independently assessed articles for inclusion in the systematic review and assessed trials’ quality using the Jadad scale. Results: Three hundred and sixty-two trials were included in the study. Only a minority of trials fulfilled all the criteria of proper clinical trial design. In most of the studies, there was a very limited use of objective (quantifiable) parameters for both patients’ selection and evaluation of drug efficacy and safety. Several outcomes of primary importance, such as disease relapses and recurrence rate, were omitted in clinical trials of allergic conjunctivitis. Conclusions: Evidence coming out of clinical trials in ocular allergy is limited, and this affects the strength of recommendations to health care providers and policy makers for optimal management. Standardized diagnostic criteria for patient selec- tion and quantifiable primary outcomes are recommended to improve the design of future clinical trials in allergic conjunctivitis. Allergy Allergy 66 (2011) 919–924 ª 2011 John Wiley & Sons A/S 919