Introduction
SLE is an autoimmune disease of unknown aetiology, characterised by bouts of immune-mediated inflammation and tissue injury. Hydroxychloroquine (HCQ) is the main drug used to treat lupus; HCQ has been shown to reduce flares1 2 and confer a protective effect on survival.2 3 Additionally, HCQ use is associated with reduced frequency and severity of organ damage.2 4 Recent data show that HCQ reduces SLE flares by 57% and disease activity by 32%.5–7 HCQ is classified as a disease-modifying antirheumatic drug due to its ability to alter ‘antigen-processing’ by antigen-presenting cells. This is thought to decrease SLE activity at a molecular level and has direct anti-inflammatory effects.
HCQ is generally a well-tolerated drug. That said, HCQ use is linked to a number of adverse effects, which may be broadly classified by severity. While more common, gastrointestinal distress, aquagenic pruritus and other dermatological complaints rarely necessitate discontinuation of treatment. On the other hand, retinal, neuromuscular and cardiac effects usually dictate withdrawal and are occasionally irreversible.8
Retinal toxicity and blindness are the most concerning side effects of HCQ. HCQ toxicity is dependent on daily dose, duration of use and total consumption.9 The exact pathophysiology of retinal toxicity attributed to HCQ is speculated but remains unclear. Binding of the agent to melanin in the retinal pigment epithelium (RPE) may concentrate the drug in this region, but it has also been suggested that toxicity originates in the photoreceptor layer with secondary RPE damage. In either case, impairment of lysosomal function and autophagy contributes to RPE degeneration and photoreceptor loss.10
The American Academy of Ophthalmology (AAO) has provided formal recommendations on screening for chloroquine (CQ) and HCQ retinopathy, the most recent iteration of which was released in 2016.9 These guidelines provide a framework for ophthalmologists and rheumatologists by reviewing patient risk factors, predictors of toxicity, dosage recommendations, preferred screening methodology and management following diagnosis. These guidelines recommend a weight-based dosing (≤5 mg/kg real weight), but also state that although the risk of HCQ toxicity ‘is smaller with low doses, it is not clear that there is any truly ‘safe’ dosage for long durations of use’. In making these guidelines, the risk assessments were based on outcomes of characteristic visual field pattern defects combined with retinal findings on optical coherence tomography (OCT).11 It is unclear whether rheumatologists are familiar and compliant with the 2016 AAO guidelines and the risk factors associated with blindness, including duration of use, medical history of renal or macular disease, and tamoxifen use.
Previous studies have estimated the frequency of HCQ retinal toxicity between 1.0% and 7.5%.9 Additionally, the proportion of patients with retinal toxicity is under 1% for the first 5 years, increases to 2% after 10 years, and increases to about 20% after 20 years of exposure. For patients taking ≥5 mg/kg dose, the risk of retinal toxicity is two to three times higher for the same time frame increments.9 Additionally, higher HCQ blood levels are associated with increased risk of HCQ retinopathy.12
While HCQ-related blindness is uncommon, the potential for these harmful side effects raises concern among patients, rheumatologists and ophthalmologists. Whether retinal toxicity measured by OCT has the same ominous prognosis as decreased visual fields resulting in long-term damage and possible blindness remains to be determined.11 There are limited data on the actual risk and prevalence of HCQ-induced blindness in patients with SLE.
This study was initiated to investigate the frequency of HCQ retinal toxicity and blindness in the experience of self-reported lupus experts, and to assess the knowledge of and adherence to the 2016 AAO guidelines.