March 2014




Review of autologous serum for dry eye finds more research needed

by Vanessa Caceres EyeWorld Contributing Writer

Severe dry eye

Slit lamp photo of a patient with severe dry eye. Fluorescein staining of the cornea demonstrates significant punctate epithelial erosions inferiorly. Pre-corneal tear film is almost non-existent.

Source: Esen K. Akpek, MD

Inconsistent research made definitive conclusions difficult

In the quest to treat patients with severe dry eye, some ophthalmologists use autologous serum drops. Just how effective are the drops in treating dry eye? A review article published last year in the Cochrane Database of Systematic Reviews took a closer look at this topic.1 Ultimately, they concluded that more research needs to be done.

An extensive review

The study investigators, led by Qing Pan, MD, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, and Department of Ophthalmology, Zhejiang Provincial People's Hospital, Hangzhou, China, noted in the review that autologous serum eye drops can provide lubrication and important biochemical components that mimic natural tears for dry eye patients. They also noted that serum eye drops are becoming a more popular second-line therapy to treat dry eye. For these reasons, they wanted to evaluate the efficacy and safety of serum eye drops compared with artificial tears as analyzed in previous randomized controlled trials.

Two of the review authors screened titles and abstracts and extracted relevant data. They found a total of 402 titles and abstracts but whittled that down to 360 after eliminating duplicate reports. They then identified 30 reports from 29 studies that might be relevant for the review. Despite the initially large number of potential titles and abstracts, they were only able to find four studies relevant to their exacting research criteria, specifically randomized clinical trialsthree full-text reports from three trials and one full-text report and conference abstract that presented results from another trial.

A total of 72 participants with dry eye due to various etiologies (e.g., Sjogren's syndrome, non- Sjogren's syndrome, and post-LASIK) were included in the four trials. The number of participants per trial ranged from 12 to 27, and the age range was 30 to 60 years old in three trials and 50 to 75 years old in a fourth trial.

Participants in all four trials were instructed to use 20% autologous serum four, five, or six times a day. Participants in the four trials received similar instructions regarding serum drop storage. Each trial used a different method to evaluate participants' symptom improvement, and each trial had a different follow-up time.

The findings

The four trials analyzed by Dr. Pan and co-investigators had varying results. One trial with 12 participants showed no improvement in participant-reported symptoms when comparing 20% serum drops and artificial tears at one month. In two of the trials with a total of 32 participants, the serum drops showed some improvement in participant-reported symptoms compared with artificial tears after two weeks of use. A fourth trial had positive results and a mean difference in tear break-up time of two seconds after two weeks. The use of serum drops did not show any improvements related to aqueous tear production based on Schirmer test results, tear quality based on fluorescein staining or rose bengal staining, and ocular surface condition based on impression cytology compared with artificial tears. However, as the investigators pointed out, these measurements were not done consistently among all four trials. Some trials used these measurements and some did not.

None of the trials evaluated tear osmolarity, corneal topography, fluorescein clearance, or conjunctival biopsy. The studies also did not report quality of life or economic analyses.

Three trials did not provide any information on adverse events. One trial reported two participants using serum drops with signs of conjunctivitis with negative culture, but the cases resolved with treatment.

The investigators concluded that the trials included in their review showed inconsistency in any benefits that serum drops might provide. "Twenty percent [serum drops] might provide some benefit in improving participant-reported symptoms in the short term (two weeks), but improvement was not observed through longer periods of follow-up," the investigators wrote. The investigators concluded that larger-scale randomized controlled trials are needed to make any definitive conclusions about the effects of autologous serum eye drops for dry eye. They went on to specify how such a trial should be designed, pointing out the need for stratification by age and dry eye severity, a comparison of serum drops to artificial tears or other treatments, and the evaluation of additional concentrations of serum drops. "Any future studies should utilize standardized and validated scoring systems of dry eye clinical severity and symptom questionnaires," they wrote. "Objective biomarkers such as tear osmolarity, tear cytokines, and HLA-DR expression by ocular surface cells should be applied as outcomes in conjunction with participant symptoms." Future trials should include both short-term (two to four weeks) and long-term (six to 12 months) outcomes, they added.

From a practical perspective

Other dry eye researchers agree with the investigators' conclusion that there's a need for large-scale trials involving serum drops for dry eye.

"It's time for a big study, but this isn't an area companies are excited about funding unless there's a product involved," said Stephen C. Pflugfelder, MD, professor of ophthalmology, Baylor College of Medicine, Houston.

Because dry eye improvement involves the reporting of subjective patient-reported symptoms, it makes efficacy reporting that much more difficult, Dr. Pflugfelder said. Dr. Pflugfelder uses serum in severe dry eye cases where patients do not respond to other common therapies, including cyclosporine ophthalmic emulsion (Restasis, Allergan, Irvine, Calif.). He also will use plasma instead of serum drops.

Penny A. Asbell, MD, professor of ophthalmology, and director of the cornea and refractive services, Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, will use serum drops with appropriate patients but added it can be a "pain in the neck" to create the drops due to sterile technique, the process a lab must go through to create the drops, the potential risk for infections because the drops do not have preservatives, and the special care patients must take to store the drops. She thinks trials such as the ones identified in the Cochrane review are also difficult because they include patients who have tried just about all other dry eye treatments, with no effect.

"We need a bigger trial, but with people who are not at the end of their rope," she said. Some research may be on the horizon, however. Dr. Pan said that after the Cochrane review was published, a group of Australian researchers emailed her about their plans for a larger-scale trial with serum drops. Plus, Dr. Asbell said she is involved with clinical research from R-Tech Ueno (Tokyo) that will enroll patients for a phase 1/2 clinical trial of genetically recombinant human serum albumin solution (RU-101) for severe dry eye in the United States. Albumin is the main protein in blood and in serum eye drops, Dr. Asbell said.


1. Pan Q, Angelina A, Zambrano A, Marrone M, Stark WJ, Heflin T, Tang L, Akpek EK. Autologous serum eye drops for dry eye. Cochrane Database of Systematic Reviews. 2013; 8. Art. No.: CD009327. DOI: 10.1002/14651858. CD009327.pub2.

Editors' note: Dr. Asbell has financial interests with R-Tech Ueno. Drs. Pan and Pflugfelder have no financial interests related to this article.

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