Grant: CIHR Fellowship

Rheumatoid arthritis (RA) and lupus are forms of inflammatory arthritis that affect at least 1 of every 100 Canadians, mainly females. Immune dysfunction leads to organ and joint damage, disability, work loss, pain, fatigue and early mortality. Hydroxychloroquine (HCQ), an anti-malarial drug, is also a long-term treatment for lupus and RA that improves survival. Though effective, low cost, and generally safe, one serious adverse effect of HCQ is irreversible retinopathy (damage to the back of the eye) that can lead to vision loss and blindness. Retinopathy was thought to be rare (<2% of long-term HCQ users), but in a recent study using more sensitive screening tests, many more were affected (7.5%). As a result, guidelines now call for HCQ users to have these new, more sensitive eye tests every year, to diagnose it earlier. But much is unknown about the risk of retinopathy, risk factors, and impact of earlier diagnosis on patients' vision, survival and quality-of-life. For example, detecting more cases of mild retinopathy (which may not progress) could simply increase patients' anxiety. To fill these gaps, we will use electronic healthcare data (without names or identifying information) to follow ~3,000 people with lupus and RA who have used HCQ for at least 5 years. We will use new statistical methods to estimate of the risk of retinopathy (overall, and with HCQ different doses), and risk factors, which may include female sex, increased age, kidney disease, and using higher doses of HCQ. We will also study its progression over time - we expect severe cases of retinopathy will progress to vision loss, but milder cases will not. Finally, we will also see what happens when patients stop HCQ, or reduce the dose. While that may help prevent vision loss, risk of death may increase alongside. Our findings will help clinicians and patients make more informed treatment decisions to reduce their chances of vision loss, while optimising their survival and quality-of-life