A Meta-Analysis of the Efficacy of Hyaluronic Acid Eye Drops for the Treatment of Dry Eye Syndrome

Abstract

Hyaluronic acid (HA) is commonly used for treating dry eye syndrome (DES). This meta-analysis was performed to compare the efficacies of HA- and non-HA-based eye drops, including saline and conventional artificial tears (ATs), for the treatment of dry eye disease. Eight databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials, DBpia, KoreaMed, KMBASE, RISS, KISS) were searched for studies comparing the efficacies of HA- and non-HA-based ATs in patients with DES published up to September 2020. Two independent reviewers assessed the quality and extracted the relevant data. The mean differences of Schirmer's (SH) test scores, tear breakup times (TBUT), corneal fluorescein staining scores (Oxford scale, 0-4), and ocular surface disease indexes were calculated. The standard mean difference and 95% confidence interval were calculated using a random effect model. Nineteen studies, including 2078 cases, were included. HA eye drops significantly improved tear production compared with non-HA-based eye drops (standard mean difference (SMD) 0.18; 95% confidence interval (CI) 0.03, 0.33). In a subgroup analysis, the SH test scores and TBUT values after using HA significantly increased compared to those measured after using saline (SMD 0.27; 95% CI 0.05, 0.49 and SMD 0.28; 95% CI 0.03, 0.52, respectively). Based on these results, HA eye drops may be superior to non-HA eye drops including normal saline and ATs. Further research is needed to assess the efficacies stratified by age, treatment duration, the severity of dry eye, and optimal dosages.

Keywords: dry eye; hyaluronic acid; meta-analysis.

Figure 1

Study selection process.

Figure 2

Comparison of the changes on SH test scores (mm/5 min) in HA and non-HA groups using the fixed effect model. The non-HA group was classified into (A) saline and (B) ATs depending on whether lubricant was included. Subgroup analysis was performed between HA and (A) saline and between HA and (B) ATs. SH test: Schirmer’s test; HA: Hyaluronic acid; ATs: Artificial tears; SMD: Standardized Mean Difference; CI: Confidence interval.

Figure 3

Comparison of the changes on TBUT values (seconds) in HA and non-HA groups using the fixed effect model. The non-HA group was classified into (A) saline and (B) ATs depending on whether lubricant was included. Subgroup analysis was performed between HA and (A) saline and between HA and (B) ATs. TBUT: Tear break-up time; HA: Hyaluronic acid; ATs: Artificial tears; SMD: Standardized Mean Difference; CI: Confidence interval.

Figure 4

Comparison of the changes on corneal fluorescein staining score (Oxford scale, 0–4) in (HA) and ATs using the fixed effect model. The corneal fluorescein staining score was only extracted from ATs. HA: Hyaluronic acid; ATs: Artificial tears: SMD: Standardized Mean Difference; CI: Confidence interval.

Figure 5

Comparison of the changes on OSDI value in HA and non-HA groups using the fixed effect model. The non-HA group was classified into (A) saline and (B) ATs depending on whether lubricant was included. Subgroup analysis was performed between HA and (A) saline and between HA and (B) ATs. OSDI: Ocular surface disease index; HA: Hyaluronic acid; ATs: Artificial tears; SMD: Standardized Mean Difference; CI: Confidence interval.