Hydroxychloroquine (HCQ) toxicity causes 'bull's eye maculopathy'. The Marmor 2016 guidelines recommend baseline and annual screening with SD-OCT and visual field testing. The proposed mechanism of HCQ retinal toxicity involves:
- A HCQ accumulation in melanin-containing RPE cells alters lysosomal pH, impairing phagocytosis of photoreceptor outer segments ✓
- B HCQ directly photolyzes retinal chromophores when exposed to UV light, generating toxic free radicals
- C HCQ inhibits the visual cycle enzyme RPE65, preventing 11-cis retinal regeneration
- D HCQ blocks potassium channels in Muller cells, causing retinal edema and cone cell decompensation
Explanation
HCQ is a lysosomotropic agent: it is a weak base that accumulates in acidic compartments such as lysosomes. In RPE cells (which have high melanin content, as melanin binds HCQ avidly), lysosomal alkalinization impairs acid hydrolase activity and the autophagy-lysosomal pathway required for normal phagocytosis and degradation of photoreceptor outer segment discs. This leads to accumulation of undegraded outer segment material, oxidative stress, and photoreceptor and RPE cell death. The parafoveal cone photoreceptors (particularly in Asian patients, where a pericentral pattern predominates rather than the classic parafoveal bull's-eye of Western patients) are earliest and most severely affected. SD-OCT shows parafoveal photoreceptor IS/OS layer thinning before visual symptoms or VF changes.
Reference: Khurana Comprehensive Ophthalmology, 7th ed.
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Written and medically reviewed by the StethoPrep medical team.