Cochrane Review: Sublingual immunotherapy for treating allergic conjunctivitis
Authors: Calderon Moises A , Penagos Martin , Sheikh Aziz , Canonica Giorgio W , Durham Stephen 
Published: May 2012

AbstractBackgroundAllergic ocular symptoms, although frequently trivialised, are common and represent an important comorbidity of allergic rhinitis. Sublingual Immunotherapy (SLIT) is an effective and well‐tolerated treatment for allergic rhinitis, but its effects on symptoms of ocular allergy have not been well established.ObjectivesTo evaluate the efficacy of SLIT compared with placebo for reductions in ocular symptoms, topical ocular medication requirements and conjunctival immediate allergen sensitivity.Search methodsWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 1), MEDLINE (January 1950 to January 2011), EMBASE (January 1980 to January 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2011), Web of Science (January 1970 to January 2011), Biosis Previews, (January 1979 to January 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled‐trials.com) (January 2011), ClinicalTrials.gov (www.clinicaltrials.gov) (January 2011), the Australian New Zealand Clinical Trials Registry (ANZCTR) (www.actr.org.au) (July 2010), SCOPUS (November 2008) and the UK Clinical Trials Gateway (January 2010). There were no language or date restrictions in the search for trials. All electronic databases except for SCOPUS, the UK Clinical Trials Gateway and ANZCTR were last searched on 19 January 2011.Selection criteriaRandomised controlled trials (RCTs), double‐masked and placebo controlled, which evaluated the efficacy of SLIT in patients with symptoms of allergic rhinoconjunctivitis (ARC) or allergic conjunctivitis (AC).Data collection and analysisThe primary outcome was the total ocular symptom scores. Secondary endpoints included individual ocular symptom scores (such as itchy eyes, red eyes, watery eyes, swollen eyes), ocular medication scores (eye drops) and conjunctival immediate allergen sensitivity (CIAS). Data were analysed and reported as standardised mean differences (SMDs) using Review Manager software.Main resultsForty‐two trials (n = 3958 total participants; n= 2011 SLIT and n = 1947 placebo) had available data to evaluate the efficacy of SLIT on AC and were included in the meta‐analyses. Heterogeneity among studies (I2 statistic) was around 50% or below for all endpoints. Sublingual immunotherapy induced a significant reduction in both total ocular symptom scores (SMD ‐0.41; 95% confidence interval (CI) ‐0.53 to ‐0.28; P < 0.00001; I2 = 59%) and individual ocular symptom scores for red eyes (SMD ‐0.33; 95% CI ‐0.45 to ‐0.22; P < 0.00001; I2 = 27%), itchy eyes (SMD ‐0.31; 95% CI ‐0.42 to ‐0.20; P < 0.00001; I2 = 46%) and watery eyes (SMD ‐0.23; 95% CI ‐0.34 to ‐0.11; P < 0.0001; I2 = 42%) compared to placebo. Those participants having active treatment showed an increase in the threshold dose for the conjunctival allergen provocation test (SMD 0.35; 95% CI 0.00 to 0.69; P = 0.05; I2 = 43%). No significant reduction was observed in ocular eye drops use (SMD ‐0.10; 95% CI ‐0.22 to 0.03; P = 0.13; I2 = 34%).Authors' conclusionsOverall, SLIT is moderately effective in reducing total and individual ocular symptom scores in participants with ARC and AC. There were however some concerns about the overall quality of the evidence‐base, this relating to inadequate descriptions of allocation concealment in some studies, statistical heterogeneity and the possibility of publication bias. There is a need for further large rigorously designed studies that study long‐term effectiveness after discontinuation of treatment and establish the cost‐effectiveness of SLIT.Plain Language SummarySublingual immunotherapy (tablets, spray or drops under the tongue) to treat inflammation of the conjunctiva due to allergyConjunctivitis means inflammation of the conjunctiva. The conjunctiva is the thin 'skin' that covers the white part of the eyes and the inside of the eyelids. Allergic conjunctivitis is the inflammation of the conjunctiva due to allergy. The most common cause is an allergy to pollen during the hay fever season. Symptoms include red eyes, itching, increased tearing and swelling of the conjunctiva and eyelids. If allergic conjunctivitis is combined with nasal allergy, the condition is termed allergic rhinoconjunctivitis. When medications do not provide enough relief another option is immunotherapy, which builds immunity to the allergen causing the reaction. Immunotherapy can be given under the tongue, nasally or by injection. This review included 42 trials with a total of 3958 participants with allergic conjunctivitis; 2011 who had sublingual immunotherapy and 1947 who had placebo. This review found that sublingual immunotherapy (that is, administered under the tongue) can reduce symptoms of allergic conjunctivitis.