Efficacy And Safety Of Dual Polymer Hyaluronic Acid/Hydroxypropyl Guar Artificial Tears In Rheumatoid Arthritis–Associated Dry Eye Disease: A 12 Week Prospective Interventional Study

To evaluate the adjunctive efficacy and safety of dual‑polymer hyaluronic acid (HA)/hydroxypropyl‑guar (HPG) artificial tears in rheumatoid arthritis–associated dry eye disease (RA‑DED) among patients who remained symptomatic despite a stable 0.1% fluorometholone regimen. The primary objective was the Month‑1 change in symptoms by the Ocular Surface Disease Index (OSDI). Secondary objectives assessed non‑invasive tear break‑up time (NITBUT), corneal fluorescein staining (CFS; NEI scale), Schirmer’s test (without anesthesia), and tear meniscus height (TMH) over 12 weeks, with prospectively defined safety evaluations.

Single‑centre, prospective, open‑label, interventional study conducted at Chang Gung Memorial Hospital, Keelung, Taiwan; approved by the Chang Gung Medical Foundation IRB (No. 202301617B0A3) and registered on ClinicalTrials.gov (NCT06209879). Study flow: 2‑week screening, 2‑week wash‑out, baseline (Day 0), and 12‑week treatment with monthly visits (Days 28/56/84).

Adults with stable RA (ACR/EULAR 2010) and DED (TFOS DEWS II) symptomatic on a steroid‑based regimen entered a 2‑week wash‑out, then received 0.15% HA with HPG artificial tears (1–2 drops QID, both eyes) plus 0.1% fluorometholone (TID; ≥5‑min interval) for 12 weeks; no other topical therapies were allowed. Efficacy: OSDI (primary at Day 28), NITBUT by LipiView® II, CFS (NEI scale), Schirmer’s (no anesthesia), TMH; safety included slit‑lamp biomicroscopy, visual acuity, and adverse events. Statistics: Shapiro-Wilk, paired t‑/Wilcoxon tests with Bonferroni as needed, and linear mixed models (time + baseline fixed; subject random). Of 39 screened, 37 enrolled; 36 completed (per‑protocol).

OSDI improved from 26.5 ± 10.78 to 22.1 ± 11.20 at Day 28 (mean change −4.4 ± 10.28; 95% CI −7.89 to −0.94; p=0.014); reductions persisted through Day 84 (Day 56: −4.0 ± 14.66; p=0.111; Day 84: −3.3 ± 10.80; p=0.078). CFS decreased significantly on Day 56 (−0.8 ± 2.15; p=0.034) and on Day 84 (−1.3 ± 2.25; p=0.001). NITBUT showed small, non‑significant increases (largest on Day 84), while Schirmer’s test and TMH showed no significant change. No adverse events occurred; slit‑lamp and visual acuity remained clinically stable throughout.

Adjunctive dual‑polymer HPG/HA artificial tears added to a stable corticosteroid regimen were well tolerated and produced clinically meaningful improvements in symptoms (OSDI) by one month and progressive reductions in corneal staining by three months in RA‑DED. While tear stability and aqueous metrics did not change significantly, the symptomatic and epithelial benefits support this regimen as a useful option for RA‑DED management. Larger controlled trials are warranted.