Objective: To determine the association of dryness of eyes with rheumatoid arthritis severity.
Method: The cross-sectional, observational study was conducted at the Jinnah Medical College Hospital, Karachi, from December 2020 to May 2021, and comprised adult patients of either gender with rheumatoid arthritis who were diagnosed on the basis of clinical and serological investigations. Data was collected using a structured pre-tested questionnaire. Ocular Surface Disease Index questionnaires with Tear Film Breakup Time were used to assess the severity of dry eyes. Disease Activity Score-28 with erythrocyte sedimentation rate was used to assess the severity of rheumatoid arthritis. Association between the two was explored. Data was analysed using SPSS 22.
Results: Of the 61 patients, 52(85.2%) were females and 9(14.8%) were males. The overall mean age was 41.7±12.8 years, with 4(6.6%) aged <20 years, 26(42.6%) aged 21-40 years, 28(45.9%) aged 41-60 years and 3(4.9%) aged >60years. Further, 46(75.4%) subjects had sero-positive rheumatoid arthritis, 25(41%) had high severity, 30(49.2%) had severe Occular Surface Density Index score and 36(59%) had decreased Tear Film Breakup Time. Logistic Regression analysis showed there were 5.45 times higher odds of having severe disease among the people with Occular Surface Density Index score >33 (p=0.003). In patients with positive Tear Film Breakup Time, there were 6.25 higher odds of having increased disease activity score (p=0.001).
Conclusion: Disease activity scores of rheumatoid arthritis were found to have strong association with dryness of eyes, high Ocular Surface Disease Index score and increased erythrocyte sedimentation rate.
Keywords: Rheumatoid arthritis, Tear film breakup time, Disease activity score-28, Dry eye, Ocular surface disease index. (JPMA 73: 275; 2023)
Submission completion date: 2-01-2022 - Acceptance date: 07-09-2022
The ocular surface needs a tear film covering the whole surface of the eye in order to maintain its health and protective function. Dry eye is a multifactorial disease in which tears and ocular surface are accompanied with the characteristic symptoms of discomfort, visual disturbance and tear film instability as well as increased permeability of tear film and ocular surface inflammation.1,2
Among the patients with dry eye syndrome, some patients are complicated with systemic immune diseases. The prevalence of dry eyes in primary Sjogren’s syndrome (SS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) are the highest in systemic immune diseases. These autoimmune diseases are caused by infiltration of lymphocytes and plasma cells in salivary and lacrimal glands which play a major role in glandular destruction that causes dry eyes. The dry eye symptoms and signs of such patients are often more serious, the treatment effect is poorer, and the prognosis is not ideal.3,4
When compared to the incidence of dry eye in the general population, which ranges 5-17%, the incidence among RA individuals is substantially greater (19-31%).1 Recent studies show that the pathogenesis of dry eye is similar to the other extra-articular complications of RA which includes mucosal autoimmune disease.5 It is speculated that the degree of dry eye may also change with the systemic conditions, due to the influence of systemic immune response. The current study was planned to determine the association of dry eye withe RA severity.
Patients and Methods
The cross-sectional, observational study was conducted at the Jinnah Medical College Hospital, Karachi, from December 2020 to May 2021. After approval from the institutional ethics review committee, the sample was raised using non-probability, consecutive sampling technique.
Those included were adult patients of either gender diagnosed RA on the basis of serological and clinical investigations who were negative for anti-Ro and anti-La antibodies. Those excluded were patients with comorbidities, including thyroid disease, vitamin A deficiency and diabetes mellitus (DM). Patients who had a history of alcohol abuse and smoking, those with a history of skin allergies and taking treatment for dry skin, patients taking the antidepressants, antihistamine, beta blockers, and accutane and other retinoids for the preceding 6 months were also excluded. Besides, patients currently taking ocular topical treatment, or had previous ocular surgical treatment or were on treatment in the preceding six months, and patients with history of ocular trauma or using contact lens in the preceding 6 months were excluded as well.
After taking informed consent from the subjects, data was collected using a pre-designed proforma. The calculation of Disease Activity Score-28 with erythrocyte sedimentation rate (DAS-28-ESR) score was done and on the same day the patient was assessed for Tear Film Breakup Time (TBUT) after which the Ocular Surface Disease Index (OSDI) score was worked out.6-9
Data was analysed using SPSS 22. Quantitative data was presented as mean and standard deviation. Qualitative data was presented as frequencies and percentages. Data was further assessed using t-test and Chi-square test, while logistic regression analysis was also run. P<0.05 was considered statistically significant.
Of the 158 patients assessed, 61(38.6%) were included; 52(85.2%) females and 9(14.8%) males (Figure 1). The overall mean age was 41.7±12.8 years, with 4(6.6%) aged <20 years, 26(42.6%) aged 21-40 years, 28(45.9%) aged 41-60 years and 3(4.9%) aged >60 years. Demographic and clinical data was noted in detail (Table 1). In terms of ESR values, majority had ESR >20 (Figure 2). TBUT time (Figure 3) and OSDI score (Figure 4) were also noted.
Further, 46(75.4%) subjects had sero-positive RA, 25(41%) had high severity, 30(49.2%) had severe OSDI score and 36(59%) had decreased TBUT (Table 2).
Factors associated serological status of RA included dry eyes (Table 3).
There were 5.45 times higher odds of having severe disease among RA patients with OSDI score >33 (p=0.003). In patients with positive TBUT, there were 6.25 higher odds of having increased disease activity score (p=0.001) (Table 4).
In terms of ESR values, majority had ESR >20 (Figure 2). TBUT time (Figure 3) and OSDI score (Figure 4) were also noted.
Studies in the past have shown some controversies regarding the association of dryness of eye with RA severity.10
In the current study, 36 of 61 RA patients had dry eye, which was assessed with TBUT, which showed significant correlation with RA severity (DAS-28), and there was 6.7 times higher odds for high OSDI score to have increased DAS-28 score. Also, there was 5.5 times higher odds of increased ESR leading to increased DAS-28 score.
Contrarily, a study concluded that there was no correlation between dry eye with DAS-28 scores.11 However, the other study found positive correlation between duration of disease and dryness of eyes, while the current study found no such association. A study concluded that there was negative correlation for Schirmer test scores, duration of disease, relationship of DAS-28 score and ocular manifestation of RA.12 Fujita et al. concluded that dryness of eyes can be seen in patients with or without Sjogren syndrome, but the relationship between disease severity and dryness of eye was not significant.13 Another study said there was no significant association of eye dryness with RA severity.14
However, some studies reported some relationship between eye dryness and DAS-28 parameters.15,16 These studies hypothesised that the positive results were due to a non-standard drug regime. In the current study as well, most patients were diagnosed late which delayed their treatment.
Dryness of eyes has been a major concern for rheumatologists while treating RA patients with multiple comorbidities. Eyes should always be examined especially in the patients with DAS-28 score of >5, starting with the screening of symptoms by using OSDI score and along with the confirmatory test TBUT (10s). Dry eye questionnaires and OSDI scores can also be used to screen and confirm the disease respectively.4,17
The current study has certain limitations, sample size was not calculated in this study and only those patients were enrolled in the study who fulfilled the inclusion criteria and visited during specified time of study. Due to limited resources, TBUT was used to confirm eye dryness when assessment with other modalities, like Schirmer test, Lissamine Green test and tear osmolarity test, would have given more specific results.
DAS-28 score of RA had a strong association with eye dryness, high OSDI score and raised ESR. RA patients should be screened for eye dryness.
Disclaimer: The text was presented as a Poster at the 24th Pakistan Society of Rheumatology Conference held at Bhurban, Murree, on Oct 1-2, 2021.
Conflict of Interest: None.
Source of Funding: None.
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