Hydroxychloroquine Retinopathy

This powerpoint reviews hydroxychloroquine retinopathy including the clinical findings and the updated American Academy of Ophthalmology screening guidelines (revised in 2016). It includes images depicting the typical paracentral visual field loss, spectral domain optical coherence tomography findings and fundus autofluorescence findings.

Hydroxychloroquine Retinopathy Zoë R. Williams, M.D. David A. DiLoreto Jr., M.D., Ph.D. Flaum Eye Institute University of Rochester School of Medicine and Dentistry Hydroxychloroquine Retinopathy • Photoreceptor loss  outer nuclear layer degeneration  disruption of RPE • Classic description: bilateral bull’s-eye maculopathy due to ring of parafoveal RPE depigmentation (late finding) • Retinopathy irreversible • Goal of screening is detection before RPE damage • If hydroxychloroquine is discontinued prior to RPE damage, progression limited to 1 year then stabilizes de Sisternes L, Hu J, Rubin DL, Marmor MF. Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: inner versus outer retina, parafovea versus peripheral fovea. Invest Ophthalmol Vis Sci 2015;56:3415–26. Clinical Findings • Visual field defects usually occur 5 degrees from center, except in Asian patients where may be ≥10 degrees from center • SD-OCT shows parafoveal thinning of photoreceptor and outer nuclear layer  "flattening" of foveal depression and "flying saucer sign" where outer nuclear layer in foveal center is unaffected • FAF in early maculopathy shows a ring of hyperfluorescence (accumulation of lipofuscin) in early stage and a ring of hypofluoresence (loss of photoreceptor and retinal pigment epithelial layer) in later stages • mf-ERG shows amplitude reduction • Fundus exam shows irregularity in macular pigmentation in early phase, ring of pigment dropout in advanced stage, and peripheral bone spicule formation, vascular attenuation, and optic disc pallor in end-stage Stokkermans TJ, Falkowitz DM, Trichonas G. Chloroquine and Hydroxychloroquine Toxicity. 2023 Aug 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Visual Field Testing HVF 10-2 shows bilateral paracentral visual field defects within 5⸰ Fundus Autofluorescence Fundus autofluorescence shows ring of hyperfluorescence (due to accumulation of lipofuscin) bilaterally in early stage Spectral Domain Macular OCT Spectral domain macular optical coherence tomography shows parafoveal thinning of photoreceptor and outer nuclear layer. The outer nuclear layer in foveal center is unaffected American Academy of Ophthalmology Screening Recommendations for Hydroxychloroquine Retinopathy • Maximum daily dose ≤5 mg/kg real weight correlates better with risk than ideal weight • Risk of toxicity at recommended doses up to 5 years is < 1% and up to 10 years is < 2% but increases to approximately 20% after 20 years • High dose and long duration of use are most significant risk factors. Other major risk factors are renal disease or concurrent use of tamoxifen • Baseline fundus examination performed to rule out pre-existing maculopathy. Annual screening after 5 years for patients on standard doses and without major risk factors. Marmor MF et al. American Academy of Ophthalmology Statement. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology 2016;123:1386-1394. American Academy of Ophthalmology Screening Recommendations for Hydroxychloroquine Retinopathy Annual screening after 5 years • Annual automated visual fields and spectral domain optical coherence tomography (SD OCT) • 10-2 except for Asian patients where 24-2 or 30-2 VF protocol recommended to assess for retinopathy outside central 20⸰ of VF • Evaluate beyond central macula in Asian patients (classic “bull’s-eye” distribution infrequent, show early damage in more peripheral pattern) Additional testing: • Multifocal electroretinogram (mfERG) and fundus autofluorescence (FAF) to corroborate visual field/ SD OCT changes Marmor MF et al. American Academy of Ophthalmology Statement. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology 2016;123:1386-1394. Stokkermans TJ, Falkowitz DM, Trichonas G. Chloroquine and Hydroxychloroquine Toxicity. 2023 Aug 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. References • Marmor MF et al. American Academy of Ophthalmology Statement. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology 2016;123:1386-1394. • de Sisternes L, Hu J, Rubin DL, Marmor MF. Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: inner versus outer retina, parafovea versus peripheral fovea. Invest Ophthalmol Vis Sci 2015;56:3415–26. • Marmor MF. Comparison of screening procedures in hydroxychloroquine toxicity. Arch Ophthalmol 2012;130:461–9. • Stokkermans TJ, Falkowitz DM, Trichonas G. Chloroquine and Hydroxychloroquine Toxicity. 2023 Aug 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-.