Topical fluorometholone treatment for ocular dryness in patients with Sjögren syndrome: a randomized clinical trial in China

Abstract

The purpose of the study was to evaluate the efficacy of an ophthalmic solution containing 0.1% fluorometholone (FML) and 0.1% sodium hyaluronate (HA) for the treatment of ocular dryness in Sjögren syndrome (SS) patients.Forty SS patients were randomly assigned to the FML or cyclosporin A (CsA) treatment groups. The FML group was treated with 0.1% FML and 0.1% HA, and the CsA group was treated with 0.5% CsA and 0.1% HA. Primary outcomes were corneal fluorescein staining (CFS), the Ocular Surface Disease Index (OSDI) score, conjunctival goblet cell density, and the severity of conjunctival congestion. Patients were also evaluated based on tear film breakup time (TFBUT) and the Schirmer test. After 8 weeks of treatment, the mean CFS scores were significantly lower in both the groups, compared with the baseline values, and the CFS score of the FML group at week 2 was significantly lower than that of the CsA group (P = 0.042). The OSDI scores improved significantly in both the groups throughout the study, and the OSDI score in the FML group at week 4 was significantly lower than that of the CsA group (P = 0.042). After 8 weeks of therapy, the conjunctival goblet cell density was significantly higher in both the groups (P < 0.001 for both) compared with the baseline values. Conjunctival congestion was reduced in both the groups throughout the study, and the severity in the FML group was significantly less at week 4 compared with that in the CsA group (P = 0.035). The TFBUT in the FML group at week 8 was significantly longer than in the CsA group (P = 0.04). Treatment using topical 0.1% FML provided faster improvement in the symptoms of ocular dryness in SS patients compared with topical 0.5% CsA.

FIGURE 1

Study design. During the 2-week run-in period, the patients were instructed to abstain from the use of any topical ophthalmic medication. During the 8-week treatment period, both the groups were treated with an ophthalmic solution containing 0.1% HA 4 times per day. In addition, the CsA group was treated with an ophthalmic solution containing 0.5% CsA twice a day, and the FML group was treated with an ophthalmic solution containing 0.1% FML 4 times per day. Both the eyes of each patient were treated at all of the time points. CsA = cyclosporine, FML = fluorometholone, HA = sodium hyaluronate.

FIGURE 2

Fluorescein staining score. Fluorescein staining was graded in each quarter of the corneal zone based on the following 4-point scale: 0 (no staining), 1 (<50% staining), 2 (≥50% staining), and 3 (100% staining).

FIGURE 3

Changes of fluorescein staining. ⁺Significantly different from the baseline value (FML group: P < 0.001 at weeks 2, 4, and 8; CsA group: P = 0.136 at week 2, P < 0.001 at week 4, and P < 0.001 at week 8). ^∗Significant intergroup difference (P = 0.042 at week 2). CsA = cyclosporine, FML = fluorometholone, W = week.

FIGURE 4

The mean OSDI during 8 weeks follow-up. ⁺Significantly different from the baseline value (FML group: P < 0.001 at weeks 2, 4, and 8; CsA group: P = 0.007 at week 2, P < 0.001 at weeks 4 and 8). ^∗Significant intergroup difference (P = 0.042 at week 4). CsA = cyclosporine, FML = fluorometholone, OSDI = Ocular Surface Disease Index, W = week.

FIGURE 5

Number of conjunctival goblet cells in the CsA and FML patients at baseline and after 8 weeks of treatment. (A) Conjunctival goblet cells were stained with periodic acid-Schiff (PAS) stain. The arrow indicates a PAS-positive cell (bar = 100 μm). a: Conjunctival goblet cells in the FML group before treatment. b: Conjunctival goblet cells after 8 weeks of FML treatment. c: Conjunctival goblet cells in the CsA group before treatment. d: Conjunctival goblet cells after 8 weeks of CsA treatment. (B) Density of PAS-positive conjunctival goblet cells. ⁺Significantly different from the baseline value (FML group: P < 0.001 at weeks 4 and 8; CsA group: P < 0.001 at weeks 4 and 8). No significant intergroup difference was observed at any time point (P = 0.653 at week 4; P = 0.934 at week 8). CsA = cyclosporine, FML = fluorometholone, W = week.

FIGURE 6

Tear film breakup time (TFBUT). ⁺Significantly different from the baseline value (FML group: P = 0.005 at week 2, P < 0.001 at weeks 4 and 8; CsA group: P = 0.01 at week 2, P = 0.034 at week 4, and P = 0.001 at week 8). ^∗Significant intergroup difference (P = 0.040 at week 8). CsA = cyclosporine, FML = fluorometholone, W = week.

FIGURE 7

Intraocular pressure (IOP). The intraocular pressure had increased by 0.4 mm Hg in the FML group and decreased by 1.15 mm Hg in the CsA group at week 8 (P = 0.389). CsA = cyclosporine, FML = fluorometholone, W = week.