Graves’ ophthalmopathy (GO) is an autoimmune inflammatory condition frequently associated with hyperthyroidism (1). The etiology of GO is not yet fully understood. The prevailing hypothesis suggests that antigens shared between the thyroid and the orbit trigger the remodeling of extraocular muscles and orbital connective tissue through an inflammatory response (2). The clinical activity score (CAS) is the most widely used metric for assessing disease activity in patients with GO, however, it has the disadvantage of relying on subjective entirely. In addition, it is clearly a kind of bias when only using CAS scores for Asian patients (3). Consequently, there is a pressing need for an objective indicator to assess disease progression.

Mean platelet volume (MPV) measures the average size of platelets in the blood and has been linked to various diseases, including GO. Thyroid diseases, particularly hyperthyroidism and hypothyroidism, influence various hematological parameters, and changes in MPV can reflect these perturbations in thyroid function (4, 5). Patients with GO, an autoimmune condition often associated with graves’ disease, may also experience alterations in platelet dynamics due to the inflammatory nature of the disease. Previous studies have indicated that MPV correlates negatively with thyroid hormone levels, particularly free T3 and T4, suggesting that lower thyroid hormone levels may be associated with increased MPV. Increased MPV has been reported in conditions characterized by systemic inflammation, and thyroid diseases often involve inflammatory pathways that could further complicate the relationship between MPV and the prevalence of ophthalmopathy (6).

The initial quantitative study of orbital CT scans examined the common diameter and cross-sectional area of the extraocular muscle (7). The use of CT revealed that the disease severity in patients with GO is positively correlated with extraocular muscle volume and activity (8). MRI can assess active GO by comparing the signal intensity ratio of the extraocular muscles to that of normal tissue (9). However, CT has been increasingly utilized for the clinical diagnosis of GO patients due to its ease of examination and lower costs. Recently, some researchers have identified the SII as a potential parameter for evaluating disease activity and severity in GO. To our knowledge, there is a relative scarcity of clinical studies validating the inflammatory condition through orbital imaging examinations. Our study represents a pioneering effort in assessing the inflammatory condition through the measurement of extraocular muscles using CT assistance.

Complete blood counts between the GO group and the control group showed differences. The mean NC was 3.77 ± 1.72 in the GO group and 3.14 ± 0.88 in the control group (p=0.024). The mean LC was 0.40 ± 0.16 in the GO group and 0.34 ± 0.09 in the control group (p<0.05). The mean PDW was 13.45 ± 2.71 in the GO group and 12.05 ± 1.66 in the control group (p<0.01). The mean MPV was 9.79 ± 1.21 in the GO group and 10.39 ± 0.86 in the control group (p=0.005). Other serum indices showed no significant differences (Table 1).

The correlation analysis showed that there was not obvious correlation between thickness of EOM with thyroid function and some blood counts (p>0.05). Worth notably, thickness of EOM was positively correlated with the age (r=0.573, p<0.01), NC (r=0.363, p<0.01), MC (r=0.647, p<0.001) and MPV (r=0.310, p<0.05) (Figure 2).

Linear regression analysis revealed that MPV (r=1.356, p<0.05) and age (r=0.181, p<0.01) exhibited positive correlation with the thickness of extraocular muscles (Table 2). CAS showed no significant relationship with any blood parameters, while NOSPEC demonstrated positive correlation with NC, LC, NLR, and MLR (Table 3). There existed positive correlation between MPV and muscle thickness after excluding various influencing factors such as age, FT4, CAS, and NOSPEC through partial correlation analysis (r=0.494, p=0.001) (Figure 3).

The present study is dedicated to examining alterations in complete blood counts and objective parameters of extraocular muscles via CT examination. By integrating these metrics, the research aims to utilize objective measurements of EOM to reflect systemic inflammatory condition. Complete blood counts have been extensively employed in clinical research across various conditions, including cardiovascular disease, cancer, and pregnancy, and have been established as risk factors for these diseases (10, 11). However, studies examining these associations in Graves’ disease remain relatively scarce. Previous research has indicated that higher values of the monocyte to high-density lipoprotein ratio (MHR), NLR and PLR are positively correlated with disease activity in GO (12). The balance of these parameters is disrupted in the presence of thyroid disease. Our findings reveal elevated levels of NC, LC, and PDW, alongside reduced MPV in patients with GO. Significant differences in MPV, NLR, PLR, and SII were observed between GO and healthy groups. Contrary to our findings, other studies have reported that MPV is higher in patients with abnormal thyroid function (13, 14). Changes in blood cell counts may reflect alterations in overall inflammatory status. MPV serves as an indicator of platelet activation (15). Literature consistently demonstrates that MPV is a valuable marker in assessing the progression and prognosis of various pathological conditions (16). MPV tends to elevate in certain diseases, such as inflammation, tumors, cardiovascular diseases, and tuberculosis, as well as rheumatoid arthritis (17, 18). However, some researchers argue that decreased MPV may indicate increased disease activity in patients with active ulcerative colitis (19). The reduction in MPV may be attributed to inflammatory conditions leading to excessive platelet consumption, consequently resulting in decreased platelet volume (20).

Our final results indicated that the MPV decreased in patients with GO. We speculate that this may be related to the following factors: the function of the thyroid is affected, leading to changes in hormone levels that enhance the phagocytosis of the reticuloendothelial system, thereby shortening platelet lifespan and resulting in a decrease in MPV.

Previous studies have demonstrated that extraocular muscle thickening is more pronounced in older patients, which aligns with our findings (21). Imaging examinations revealed that medial rectus (MV) enlargement was the most common manifestation, with some patients exhibiting increases in both MV and other extraocular muscles such as fat volume (FV) (22). This phenomenon may be related to the pathogenesis of GO, suggesting that increased orbital MV is an early manifestation of GO, while increased FV occurs at a later stage (23). Notably, increased MV is associated with more severe GO. Our research identified a positive correlation between muscle thickness, MPV, and age. Furthermore, after controlling for confounding variables such as age, CAS, NOSPEC, thyroid function, and other factors, MPV still demonstrated a strong positive correlation with the thickness of EOM. It has been suggested that MPV varies according to the intensity of inflammation: during low-grade inflammation, larger platelets (PLTs) are released from the bone marrow; conversely, in high-grade inflammation, the consumption of large PLTs exceeds their release, resulting in a decrease in MPV (24). The activity of inflammation can be reflected in the shape of the extraocular muscles, with initial stages of the disease characterized by muscle thickening (9, 25). In our study, MPV can, to some extent, reflect the state of inflammation. Given the relationship between MPV and EOM, we propose that EOM parameters may serve as novel biomarkers for assessing systemic inflammation. Further research is warranted to uncover additional clinical correlations between MPV and GO. Our study was limited by a relatively small sample size, which may have constrained our ability to detect relationships between certain variables. Additionally, the sample may not fully represent all populations affected by GO, potentially limiting the generalizability of our findings. Our study provides new insights into assessing disease severity through the overall inflammatory condition in GO, offering a more objective measure than the CAS. Future studies should explore the deeper connections between MPV and other hematological measures and GO activity. Furthermore, long-term follow-up studies will enhance our understanding of disease progression and improve treatment decision-making. In conclusion, a positive correlation exists between MPV and EOM thickness after excluding confounding factors such as age, TF4, CAS, and NPSPEC. Therefore, we conclude that extraocular muscle thickness may potentially serve as a biomarker for inflammatory conditions in GO.