Ocular surface disease index in Graves' orbitopathy: a cross-sectional study

Abstract

Introduction: Graves' Orbitopathy (GO) is an autoimmune disorder characterized by inflammation of orbital tissues, leading to various ocular manifestations, including ocular surface disease. This cross-sectional study aimed to assess the presence of ocular surface disease using the Ocular Surface Disease Index (OSDI) in patients with Graves' disease (GD) and moderate-to-severe active GO compared to those with GD and mild non-active GO. Additionally, we aimed to investigate the correlation between ocular surface disease and the eye features of GO.

Methods: Consecutive GD patients with GO referred to the Ophthalmology and Endocrinology Units of the University Hospital of Pisa between June 2022 and February 2023 were enrolled. OSDI scores were obtained from 79 GD patients, categorized into moderate-to-severe active GO and mild non-active GO groups.

Results: OSDI scores were significantly higher in patients with moderate-to-severe active GO compared to those with mild non-active GO (P=0.0006). A cutoff value of 33 for positive tests revealed a higher frequency of pathological OSDI in moderate-to-severe active GO patients compared to mild non-active GO patients (P=0.0221; OR 3.673, CI 1.277-9.531). Within the moderate-to-severe active GO group, a significant positive correlation was found between OSDI and Clinical Activity Score (CAS) (R= 0.3867, 95% CI from 0.1403 to 0.5880; P=0.0030). Using a cutoff value of 55 (the 75th percentile of the study population), patients with CAS ≥ 3 had a significantly higher proportion of pathological OSDI compared to those with CAS <3 (P=0.0039; OR 4.075, CI 1.619-10.39). Proptosis values ≥ 22 mm and the presence of lagophthalmos were identified as significant risk factors for ocular surface disease development (P=0.0406 and P=0.0493, respectively).

Discussion: Our study highlights a significantly higher prevalence of ocular surface disease, as measured by OSDI, in patients with moderate-to-severe active GO compared to those with mild non-active disease. The degree of GO activity positively correlates with ocular surface involvement, and proptosis and lagophthalmos increase the risk of its occurrence. These findings emphasise the importance of assessing and managing ocular surface health in GO patients. Early identification and appropriate treatment of ocular surface disease need to be pursued to improve patient management.

Keywords: Graves’ disease; Graves’ orbitopathy; dry eye disease; ocular surface disease; ocular surface disease index; thyroid autoimmunity.

Figure 1

Multivariate effects of clinical and demographic key variables on Ocular Surface Disease Index (OSDI) in the cohort study population. The independent effects of age, CAS, proptosis, eyelid aperture, GD duration, GO duration and diplopia on the Ocular Surface Disease Index (OSDI) scores in the cohort. The analysis controls for potential confounders and reveals the unique contribution of each variable to the observed outcomes. P value significance: P <0.05, *. CAS, clinical activity score; GD, Graves’ Disease; GO, Graves’ Orbitopathy.

Figure 2

Patients with moderate-to-severe active Graves Orbitopathy (GO) experience worsened Ocular Surface Disease Index (OSDI) compared with mild non-active GO patients. (A) Comparison of the OSDI between patients with moderate-to-severe active GO and patients with mild non-active GO. The statistical significance was assessed by Mann-Whitney test. P value significance: P <0.001, ***. (B) Comparison of the frequency of pathological OSDI (>33) between patients with moderate-to-severe active GO and patients with mild non active GO. Statistical analysis was performed using Fisher exact test yielding both P value and odds ratio (OR).

Figure 3

Ocular Surface Disease Index (OSDI) positively correlates with the Clinical Activity Score (CAS) in patients with moderate-to-severe active Graves Orbitopathy (GO). (A) Correlation between CAS (Log10 values) and OSDI within the group of moderate-to-severe active GO patients. The correlation coefficient (R) and its significance (P value) were obtained by linear regression analysis. (B) Comparison of the frequency of pathological OSDI between patients with CAS ≥3 and patients with CAS <3. A cutoff of 55, which was equal to the 75^th percentile of the study population, was used to increase specificity. P value and odds ratio (OR) were obtained by Fisher exact test.

Figure 4

Proptosis and lagophthalmos are potential risk factors for the occurrence of ocular surface disease in patients with Graves’ Orbitopathy. (A) Comparison of the Ocular Surface Disease Index (OSDI) between patients with proptosis ≥22 and patients with proptosis <22. The statistical significance was assessed by Mann-Whitney test. P value significance: P <0.05, *. (B) Comparison of the OSDI between patients with and without lagophthalmos. The statistical significance was assessed by Mann-Whitney test. P value significance: P <0.05, *.