What is the aim of this review?
We conducted this Cochrane review to find out whether autologous serum eye drops work as treatment for dry eye. Cochrane researchers searched for all relevant studies seeking an answer to this question and found five studies.
What are the key messages of this review?
Eye drops containing autologous serum might be better at improving dry eye symptoms than artificial tear drops in the short term (two weeks). We found very little information as to whether autologous serum eye drops work long term or for clinical measures of dry eye.
What was studied in this review?
Dry eye is a common disorder of the tear film, which is a layer of tears covering the surface of the eye. Dry eye affects many adults older than 40 years of age. People with dry eye may feel discomfort in one or both eyes and have sensitivity to light. There are clinical tests that are used by healthcare professionals to measure the amount of tears the eye produces and how fast tears leave the eye. Sometimes these clinical measures do not match the symptoms; a person can have severe dry eye and normal clinical test results, or mild dry eye and abnormal clinical test results.
One common treatment for dry eye is artificial tears, which provide lubrication to the surface of the eye. However, artificial tears lack the biological nutrients found in natural tears that are critical to maintenance of the tear film. Eye drops made by separating liquid and cellular components of the patient’s blood, known as autologous serum eye drops, have been shown to possess many of the same biological nutrients found in natural tears. Because of this fact, autologous serum eye drops are believed to be a better tear substitute and have been proposed as treatment for dry eye.
What are the main results of the review?
We found five studies in people with dry eye from Australia, Chile, Japan, and Turkey. These studies compared autologous serum eye drops versus traditional artificial tears or saline solution for treatment of dry eye. We could not combine results of the five studies in analysis owing to differences in what each study evaluated. In one study, people who received autologous serum eye drops showed better improvement in symptoms after two weeks than those who received artificial tears. However, results after longer treatment (four weeks or more) and for other outcomes had problems that prevent us from saying whether autologous serum is truly better than artifical tears or saline. The authors of this review conclude that autologous serum versus artificial tears might provide benefit for treatment of dry eye in the short term. However, the overall benefit seems unclear at this time, and much more research is needed in this area.
How up-to-date is the review?
Cochrane review authors searched for studies that had been published up to July 5, 2016.
Overall, investigators reported inconsistency in possible benefits of AS for improving participant-reported symptoms and other objective clinical measures. There might be some benefit in symptoms with AS compared with artificial tears in the short-term, but we found no evidence of an effect after two weeks of treatment. Well-planned, large, high-quality RCTs are warranted to examine participants with dry eye of different severities by using standardized questionnaires to measure participant-reported outcomes, as well as objective clinical tests and objective biomarkers to assess the benefit of AS therapy for dry eye.
Theoretically, autologous serum eye drops (AS) offer a potential advantage over traditional therapies on the assumption that AS not only serve as a lacrimal substitute to provide lubrication but contain other biochemical components that allow them to mimic natural tears more closely. Application of AS has gained popularity as second-line therapy for patients with dry eye. Published studies on this subject indicate that autologous serum could be an effective treatment for dry eye.
We conducted this review to evaluate the efficacy and safety of AS given alone or in combination with artificial tears as compared with artificial tears alone, saline, placebo, or no treatment for adults with dry eye.
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We also searched the Science Citation Index Expanded database (December 2016) and reference lists of included studies. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 July 2016.
We included randomized controlled trials (RCTs) that compared AS versus artificial tears for treatment of adults with dry eye.
Two review authors independently screened all titles and abstracts and assessed full-text reports of potentially eligible trials. Two review authors extracted data and assessed risk of bias and characteristics of included trials. We contacted investigators to ask for missing data. For both primary and secondary outcomes, we reported mean differences with corresponding 95% confidence intervals (CIs) for continuous outcomes. We did not perform meta-analysis owing to differences in outcome assessments across trials.
We identified five eligible RCTs (92 participants) that compared AS versus artificial tears or saline in individuals with dry eye of various origins (Sjögren's syndrome-related dry eye, non-Sjögren's syndrome dry eye, and postoperative dry eye induced by laser-assisted in situ keratomileusis (LASIK)). We assessed the certainty of evidence as low or very low because of lack of reporting of quantitative data for most outcomes and unclear or high risk of bias among trials. We judged most risk of bias domains to have unclear risk in two trials owing to insufficient reporting of trial characteristics, and we considered one trial to have high risk of bias for most domains. We judged the remaining two trials to have low risk of bias; however, these trials used a cross-over design and did not report data in a way that could be used to compare outcomes between treatment groups appropriately. Incomplete outcome reporting and heterogeneity among outcomes and follow-up periods prevented inclusion of these trials in a summary meta-analysis.
Three trials compared AS with artificial tears; however, only one trial reported quantitative data for analysis. Low-certainty evidence from one trial suggested that AS might provide some improvement in participant-reported symptoms compared with artificial tears after two weeks of treatment; the mean difference in mean change in symptom score measured on a visual analogue scale (range 0 to 100, with higher scores representing worse symptoms) was -12.0 (95% confidence interval (CI) -20.16 to -3.84; 20 participants). This same trial found mixed results with respect to ocular surface outcomes; the mean difference in mean change in scores between AS and artificial tears was -0.9 (95% CI -1.47 to -0.33; 20 participants; low-certainty evidence) for fluorescein staining and -2.2 (95% CI -2.73 to -1.67; 20 participants; low-certainty evidence) for Rose Bengal staining. Both staining scales range from 0 to 9, with higher scores indicating worse results. The mean change in tear film break-up time was 2.00 seconds longer (95% CI 0.99 to 3.01; 20 participants; low-certainty evidence) in the AS group than in the artificial tears group. Investigators reported no clinically meaningful differences in Schirmer’s test scores between groups (mean difference -0.40 mm, 95% CI -2.91 to 2.11; 20 participants; low-certainty evidence). None of these three trials reported tear hyperosmolarity and adverse events.
Two trials compared AS versus saline; however, only one trial reported quantitative data for analysis of only one outcome (Rose Bengal staining). Trial investigators of the two studies reported no differences in symptom scores, fluorescein staining scores, tear film break-up times, or Schirmer's test scores between groups at two to four weeks' follow-up. Very low-certainty evidence from one trial suggested that AS might provide some improvement in Rose Bengal staining scores compared with saline after four weeks of treatment; the mean difference in Rose Bengal staining score (range from 0 to 9, with higher scores showing worse results) was -0.60 (95% CI -1.11 to -0.09; 35 participants). Neither trial reported tear hyperosmolarity outcomes. One trial reported adverse events; two of 12 participants had signs of conjunctivitis with negative culture that did resolve.