The Prevalence of Dry Eye Syndrome in Systemic Lupus Erythematosus Patients in Saudi Arabia

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic multi-systemic autoimmune connective tissue disorder that is known to have variable manifestations with a remitting/relapsing course depending on the affected system. SLE can affect all the major organs in the human body including the heart, brain, and kidneys. Although the eye is not a primary target of autoimmune insult in SLE patients, one third of patients can present with significant ocular manifestations as it can affect any part of the ocular system. Furthermore, ocular involvement could be the first presenting symptom of SLE and may mirror the systemic disease activity. The worldwide prevalence of SLE varies, however, based on a study conducted in 2002 in central Saudi Arabia, the prevalence of SLE was estimated to be 19.28 per 100,000. Study Aim: To identify the prevalence of dry eye syndrome in Systemic Lupus Erythematosus diagnosed patients in Riyadh. Methods: A cross sectional study that involved a total of 135 patients from Rheumatology outpatient clinic setting at King Khalid University Hospital in Riyadh, Kingdom of Saudi Arabia. Data was collected via McMonnies questionnaire, which is used as a screening tool for dry eye syndrome. Data analysis included descriptive statistics computed for continuous variables, including means, standard deviation (SD), minimum and maximum values, as well as 95% confidence interval (CI). Percentages and 95% CI were used for categorical variables. Results: Out of 135 SLE patients, females were 87.4% ± 2.9 (95%CI: 80.6–92.1.3), while males were 12.6% ± 2.9 (95%CI: 7.9–19.4), Among the 118 female patients, 56% (n=66) lied between the age of 25-45 years. Most common symptom in 45.9% (95%CI: 37.6–54.5) of our patients was Dryness of Eyes. The predominant age group of our cohort was that of 25–45 years (57%) Among our cohort, 50.4% (95%CI: 41.9–58.8) patients suffered from Dry eye syndrome, with 12.6% males and 87.4% females. Conclusion: A high prevalence of dry eye syndrome was found in our study with a percentage of 50.4%, also a female predominance was found in patients having dry eye syndrome.


Introduction
Systemic Lupus Erythematosus (SLE) is a chronic multi-systemic autoimmune connective tissue disorder and is known to have variable manifestations with a remitting/relapsing course. Dry eye syndrome is the most common ocular manifestation of SLE and is reported to be 36% in a study by wangkaew and colleagues (Wangkawe et al., 2006) and 28% in another study (Gilboe, Kvien, Uhlig, & Husby, 2001). However, it was also shown to be under-diagnosed according to multiple studies. SLE is known to affect all major organs in the human body including the heart, brain, and kidneys. (http://emedicine.medscape.com/article/332244-overview?src=refgatesrc1#a5) Despite the absence of the exact clear etiology behind SLE, it is thought to be multifactorial. Diverse genetic, environmental, immune-regulatory, and infectious factors contribute to one's susceptibility to the disease (Boonsopon, Maghsoudlou, & Foster, 2015;Silpa-archa, Lee, & Foster, 2015). The worldwide prevalence of SLE varies, however, based on a study conducted in 2002 in central Saudi Arabia, the prevalence of SLE was estimated to be 19.28 per 100,000 (Al-Arfaj et al., 2002). 90% of SLE affects women commonly at childbearing age, the female to male ratio is 11:1 during these years. (http://emedicine.medscape.com/article/332244-overview?src=refgatesrc1#a5) The presence of four of the 11 criteria listed by the American College of Rheumatology classification makes the diagnosis of SLE, serially or simultaneously. The revised criteria include malar rash, discoid rash, skin photosensitivity, oral ulcers, non-erosive arthritis, serositis, renal involvement, neurological disorder, hematologic disorder, immunologic disorder, and positive antinuclear antibodies. The presence of 4 of these 11 criteria confirms the diagnosis of SLE and yields a sensitivity of 85% and a specificity of 95% for SLE (Hochberg, 1997). However, the clinical manifestations may vary significantly from one patient to another, ranging from indolent to fulminant. (http://emedicine.medscape.com/article/332244-overview?src=refgatesrc1#a5) One third of patients can present with significant ocular manifestations as it can affect any part of the ocular system including the anterior segment, posterior segments, lacrimal system, optic nerve, and blood supply leading to sight-threating sequalae (Al-Arfaj et al., 2002;M. Cojocaru, I. Cogocaru, Silosi, & Varbie, 2011;Sivaraj, Durrani, Denniston, Murray, & Gordon, 2007;Palejwala, Walia, & Yeh, 2012;Shougy & Tabbara, 2016). Although, the eye is not a primary target of autoimmune insult in SLE patients, ocular involvement could be the first presenting symptom of SLE and may mirror the systemic disease activity. In addition to the effect of SLE on the eyes, medications used in the treatment of SLE can have adverse side effects on the eyes. Hence, emphasizing the significant role of ophthalmologists and regular follow up at the clinic for early recognition of ocular involvement and drug induced toxicity as well (Boonsopon et al., 2015;Al-Arfaj et al., 2002;M. Cojocaru et al., 2011;Sivaraj et al., 2011). SLE can result in a wide spectrum of ocular diseases owing to the deposition of immune complexes in numerous locations such as in blood vessels of the conjunctiva, retina, choroid, sclera, ciliary body, and in the peripheral nerves of the cornea, conjunctiva, and the ciliary body. As a result, patients can present with a wide variety of clinical presentations depending on the involved anatomical location. Keratoconjuctivitis Sicca and retinal involvement are the two most common manifestations. Other common manifestations of SLE include cataract which may either be due to inflammation or steroid use, scleritis and lupus retinopathy (Al-Arfaj et al., 2002;M. Cojocaru et al., 2011;Sivaraj et al., 2011). Depositions of immune complexes in the lacrimal glands may result in secondary Sjogren's syndrome, which results in "Keratoconjuctivitis Sicca" which is a term used for dry eyes due to reduced tear production (Sivaraj et al., 2011). Sjogren's syndrome is a chronic autoimmune disease that can be diagnosed by the presence of the triad: 1. Dry eye syndrome 2. Dry mouth and a 3. Connective tissue diseases such as SLE and RA. It can affect both lacrimal and salivary glands resulting in destruction of the exocrine function leading to dryness of the eyes and mouth. Dry eye syndrome symptoms include tearing, red eye, photophobia, blurry vision, burning sensation and foreign body sensation. Dry eye syndrome can be attributed to three causes: either a reduction in the production of tears, an increase in the evaporation of tears or abnormal production of tear film components. Irrespective of the underlying trigger, severe and serious complications may arise due to dryness of the cornea, such as infectious or sterile corneal ulcers, persistent epithelial defects, descemetocele, and corneal perforation in severe cases, therefore, early recognition of the condition is vital to prevent such consequences by providing the appropriate management in a timely manner (Palejwala et al., 2012;Shougy & Tabbara, 2016;Phadatare, Momin, Nighojkar, Askarkar, & Singh, 2015). Furthermore, SLE patients are prone to have peripheral neuropathy resulting in compromised sensation preventing early presentation to the Ophthalmology clinic, hence, highlighting the importance of early screening and regular follow-up at the Ophthalmology clinic in SLE patients to prevent sight-threating sequalae (Sivaraj et al., 2011)

Methodology
This is a cross-sectional study that was carried out at the Rheumatology outpatient clinic in King Khalid University Hospital, which is one of the main tertiary hospitals in Riyadh, the capital of Saudi Arabia. The study population involved a total of 135 patients with established diagnosis of SLE according to the ACR criteria during the period of three consecutive months. Data was gathered using the McMonnies questionnaire, which is a validated screening tool for dry eye syndrome that was made by Prof. Charles McMonnies, approval was obtained for the use of his questionnaire in this study. The questionnaire consists of 12 questions and each answer is encoded with a score according to McMonnies scoring system. A total score of 14.5 is the cut-off point for diagnosing the patient with dry eye syndrome; thus, the total score will be calculated for each patient to diagnose dry eye syndrome. The sensitivity and specificity of the questionnaire reaches up to 98% and 97%, respectively. An Arabic version of the McMonnies screening questionnaire was used following the validation of its translation. The questionnaire was translated into Arabic by a bilingual familiar with medical terms, followed by back translation by a bilingual familiar with medical terms and blind to the original English version. Patients with other ocular conditions leading to dry eye syndrome were excluded from this study, such as 7 th nerve palsy and eyelid malposition. Patients with positive history of ocular surgeries were also eliminated. Data analysis included descriptive statistics computed for gjhs.ccsenet.org Global Journal of Health Science Vol. 15, No. 7;2023 continuous variables, including means, standard deviation (SD), minimum and maximum values, as well as 95% confidence interval (CI). Percentages and 95% CI were used for categorical variables. Between-groups comparisons were performed student's t-test. Software STATA 13 (Stata Corp., TX, USA) was used in our analysis. A statistical significance threshold of P-value = 0.05 was adopted. No attempt at data imputation was made.
Statistically significant correlations for dry eye syndrome are tabulated in Table 6. gjhs.ccsenet.org Global Journal of Health Science Vol. 15, No. 7;2023  To the best of our knowledge, there are no studies that estimate the prevalence of dry eye syndrome in SLE patients, especially in the Kingdom of Saudi Arabia. However, dry eye syndrome was reported to be one of the common ocular manifestations of SLE and is frequently associated with secondary Sjogren's syndrome. (Hochberg, 1997) Correspondingly, our cohort study revealed a total of 50.4% (95%CI: 41.9-58.8) patients suffered from dry eye syndrome, of which 87.4% were found to be females, with 12.6% males. Furthermore, according to our analysis, the severity of the dry eye syndrome worsened with longer duration of diagnosis, as 63.4% of patients suffering from dry eye syndrome were diagnosed for more than 20 years. Other significant correlations were age, gender, arthritis, dryness of nose mouth, throat, and chest. Our study showed female predominance as it included a total of 118 females and 17 males, which is possibly due to the predominance of SLE in females (M. Cojocaru et al., 2011). A total of 64 females, were diagnosed with dry eye syndrome with the majority being in the age group of 25-45 years, followed by the age group of >45 years, however, only few patients were younger than 25 years old. While a total of only 4 males had dry eye syndrome 2 of them were over the age of 45 years, 1 was between 25-45 years of age and 1 in the age group of <25 years. Drops were prescribed to 50.4% of the participants, while 57% of patients with dry eye syndrome were prescribed drops and 11% of non-dry eye syndrome patients. Ultimately, our study reports a high percentage of dry eye syndrome in SLE patients, hence, stressing the importance of early screening, diagnosing and management to avoid sight-threating complications.

Conclusion
High prevalence of dry eye syndrome was found in our study with a percentage of 50.4%. A female-preponderance was found, which could be due to the predominance of females in SLE patients. Therefore, we recommend early referral of SLE patients to Ophthalmology clinic for screening of SLE related ocular manifestations including and not limited to dry eye syndrome to avoid further sight threating complications. Additionally, we encourage raising awareness towards ocular manifestations in SLE patients among physicians and the patients.

Funding Statement
This research was not financially supported by any institute.