DED is an extremely frequent ophthalmological condition that significantly impacts vision and patients’ quality of life [32]. There is a frequent association between DED and several ARDs, like pSS, SLE, and RA. Compared with dry eye patients without systemic autoimmune disease, cell injury and apoptosis on the ocular surface is more severe and treatment is trickier for dry eye patients with systemic autoimmune disease [33]. Due to the abnormal immune systems, patients with ARDs appear to have pathological autoantibodies in their bodies, which will bind to autoantigens and cause abnormal immune responses [34]. This immunological disorder can impact a variety of organs or systems, the eye can become a target organ due to its unique anatomic structure and immune privilege. Abnormal immune stimulation could influence ocular surface balance, resulting in inflammation and changes in the quantity and quality of tears, ultimately leading to the occurrence of DED [33, 35, 36].
Autoimmune-related DED is not a new topic, but there have been few studies on the comparison of dry eye pathogenesis in different ARDs. This study aims to investigate and compare the differences in ocular surface involvement and systemic conditions in ordinary 79 patients with ARDs, who visited the department of rheumatology and immunology due to rheumatic diseases, instead of visiting the department of ophthalmology due to eye symptoms, including RA, SLE, and pSS patients.
SLE is characterized by autoantibody production and immune complex deposition in the blood vessels throughout the whole body that leads to target tissue injury [37]. In our study, among all ARDs patients, SLE patients are the youngest with the shortest disease duration, most of them with low disease activity, mild ocular surface symptoms, and signs. Our study found that the prevalence of DED in SLE is not high (7.6%), and all of the types were EDE, as a previous meta-analysis showed the overall prevalence of DED in SLE patients was only 10–21% [38]. Because meibomian glands are vascular-rich tissues [39] that may become the target tissue of SLE autoimmunity, causing meibomian gland dysfunction, which is the most common cause of EDE. Eyelid abnormalities may be a major cause of SLE-associated DED. Our study also found the severity of goblet cell loss and pathological ocular surface squamous metaplasia in SLE was consistent with pSS, these phenomena can even appear before the occurrence of signs and symptoms of dry eye. Our study found most pro-inflammatory cytokines, such as IL-1β, IL-6, and IL-8 were lowest in SLE patients among all ARDs patients, indicating ocular surface inflammation was relatively mild in SLE patients compared with RA and pSS patients, but still significantly worse than normal [40]. Therefore, although the incidence of DED in SLE patients is the lowest, the pathological squamous metaplasia and inflammation of the ocular surface should not be underestimated, and it can be predicted that DED will appear in the later stage. The eye needs to be closely followed up and observed, and timely pharmacological intervention for dry eyes if necessary.
In our study, among all ARDs patients, RA and pSS patients older with longer disease duration, moderate and high disease activity. About half of them have obvious symptoms and signs of DED. Most ocular surface pro-inflammatory cytokines are relatively high compared with SLE. Excessive pro-inflammatory cytokines in tears could lead to corneal damage [41], this also explains that the number of FL-positive patients in RA and pSS is greater than the number of FL-positive in SLE patients. The incidence of DED is relatively high (38.5% in RA and 45% in pSS) and MDE is the main type of dry eye. The ocular surface pathological squamous metaplasia was relatively mild in RA compared with pSS and SLE, but still more serious than normal according to our previous research. pSS is a chronic inflammatory autoimmune disease that is characterized by lymphocytic infiltration of the exocrine glands resulting in dry mouth and dry eyes [14]. Therefore, the high incidence of DED in pSS patients is natural and well-known. However, as same as previous research [42], DED is fairly common even in RA patients without SS in our study, with obvious dry eye symptoms and signs, and pathological squamous metaplasia on the ocular surface occurred. Therefore, a detailed ocular surface assessment of RA patients and timely dry eye treatment are very important to these patients, which contribute to the delayed progression of DED. Moreover, it should be emphasized that only in RA patients, the degree of ocular surface squamous metaplasia increases with disease duration.
In our study, dry eye was the most prominent manifestation of ocular surface involvement in all ARDs patients, none of them had other significant ocular surface disorders such as corneal epithelial defects, corneal opacity, and symblepharon. Our study also found that dry eye severity in all patients with ARDs was independent of disease activity, the deterioration of systemic condition does not necessarily result in subsequent aggravation of DED. Conversely, dry eye cannot be excluded, even in patients only experiencing the mild form of the disease. Due to the special structure of the blood-ocular barrier [43], topical pharmacotherapy is more important than systemic immunosuppressant therapy in ARDs-related dry eye, such as artificial tears, autologous serum eye drops, corticosteroid eye drops, even immunosuppressant eye drops [44].
In conclusion, to think of ARDs as merely a disease of rheumatic diseases is misleading, ocular complications especially dry eye always should be taken into consideration, which can easily be overlooked in the early stages and seriously affect the quality of life of patients in the late stages. In addition to pSS, dry eye and ocular surface squamous metaplasia were also prevalent in SLE and RA that were without SS. Therefore, all ARDs patients should be encouraged to have regular ophthalmological examinations and supplemental topical drug therapy.