Longer Systemic Sclerosis Duration May Raise Risk for Dry Eye Disease

Systemic sclerosis (SSc) has the potential to prompt fibrotic shifts within the lacrimal gland, and reduce conjunctival goblet cells that release mucin — 2 key clinical aspects of dry eye disease (DED). A study published in Clinical Ophthalmology is the first to assess specific possible predictive variables for SSc-related DED, using the Tear Film and Ocular Surface Society’s Dry Eye Workshop (DEWS) II diagnostic criteria

In the prospective analysis, investigators assessed 84 patients (57 women, 27 men); 59 with the diffuse subtype and 25 with limited SSc who visited a university hospital scleroderma clinic in Thailand. The research excluded individuals whose advanced SSc prevented biomicroscopy, and those with additional connective tissue conditions such as Sjögren syndrome. DED was defined with the DEWS II method as a score 13 or higher on the Ocular Surface Disease Index (OSDI) plus 1 positive objective test; in this study, Schirmer I, tear film break-up time (TBUT), or ocular surface staining. 

The average age of participants was 55.58±10.63 years, and 72.6% displayed best corrected visual acuity (BCVA) of 45 ETDRS letters or better  Of the total sample, 44 patients were diagnosed with DED, an overall prevalence of 52.38%. Of those diagnosed with DED in the limited SSc group, 72.0% were women vs 66.1% in the diffuse SSc group. Patients with diffuse subtype exhibited significantly higher skin tightness and total skin score than in the limited SSc group, but in multivariate analysis did not show a large difference in DED occurrence (P =.205).

In a univariate model, factors associated with DED proved to be older age (P =.004), and SSc duration (P =.019). However, in multivariate analysis, while age was still considerably associated (P =.023); disease duration (P =.085), along with age at diagnosis (P =.055), and skin tightness (P =.06) approached statistical significance. The study also shows, as previous research has, strong evidence of a female predilection for DED in patients with SSc.

“Dry eye symptoms do not correlate well with dry eye evaluation tests; therefore, DED should be evaluated in all SSc patients, particularly those with older age and longer disease duration, so that early treatment can prevent the risk of serious complications,” according to the study authors.

Previous studies estimate DED occurrence in SSc at between 37% to 79%, but have employed different benchmarks for diagnosing the disorder. This percentage range agrees with the current paper — a rate of 52.38% according to DEWS II criteria, compared with 70.2% using only TBUT. Further, prior research has found conflicting results for whether aqueous deficiency or tear evaporation leads to SSc-related DED. The present study demonstrated 61.4% of those with DED exhibited a mix of the 2 etiologies. 

“DED is a consequence of SSc. Fibrotic changes in the lacrimal gland lead to a decreased production of aqueous tears. In addition, reducing the number of goblet cells in the conjunctival epithelium causes a decrease in tear film mucin layer secretion. Consequently, excessive evaporation of tears from the eye surface causes DED,” the study shows.

Because there was not a significant association between diffuse or limited SSc subtypes for DED onset, and greater correlations emerged in time elements such as longer SSc duration, the investigators speculate that as the disease advances, microvascular and other changes worsen, along with a progression of DED.

Limitations of this analysis include a small group of participants with no DED, exclusion of advanced patients who could not complete a full eye examination, and lack of follow-up data due to a cross-sectional design. A strength is being the first to evaluate specific factors that may contribute to dry eye disease in patients with scleroderma.