VA 20/70 ph 20/40 OD, 20/60 ph 20/40 OS. IOP 22 OD, 20 OS. Pupils round reactive, no RAPD. Extraocular movement intact bilaterally. VFFTC.
Slit lamp examination normal
Dilated fundus exam showed RPE mottling temporal to the fovea in both eyes and chorioretinal scar inferonasal to the left optic nerve
Age-related macular degeneration
HVF 10-2 in 2017 demonstrated nasal superior > inferior arcuate parafoveal depressions consistent with the pattern of the parafoveal EZ/IZ disruption seen on OCT which was worse temporally and inferiorly
Hydroxychloroquine affects the pH of intracellular vacuoles, modifying the function of lysosomes and antigen processing in antigen-presenting cells.
Hydroxychloroquine furthermore affects DNA/RNA synthesis in photoreceptors. Membranous cytoplasmic bodies also form in retinal ganglion cells, leading to cell death. RPE cells can bind the drug in an inactive form on melanin granules but once the binding capacity is exceeded, cell damage occurs.
Immediate cessation of hydroxychloroquine when definitive toxicity is detected
Progression of maculopathy may progress for 1-3 years depending on the severity of maculopathy at the time of drug cessation
No effective treatment to reverse hydroxychloroquine toxicity
The maximum recommended dose for hydroxychloroquine is 5mg/kg of actual body weight. This is a revised recommendation from the AAO in 2016, based on the work of Marmor and Melles in analyzing data from a large Northern California patient population.
Risk factors for toxicity include:
Dose > 5mg/kg actual body weight
Longer duration of use
Concurrent tamoxifen use
Presence of other retinal or macular disease
Minimum screening is at baseline (within one year of starting drug) and then annually starting at five years of use, sooner if any risk factors are present
Screening consists of:
HVF 10-2 (white stim) for all patients (add HVF 24-2 for Asian patients)
Consider: fundus autofluorescence, multifocal ERG
Prognosis and Future Directions
The Ophthalmology and Rheumatology services at LAC+USC are collaborating to improve the screening process for patients taking hydroxychloroquine to eliminate the incidence of new toxicity in the LA County DHS patient population.
Hallberg A, Naeser P, Andersson A. Effects of long-term chloroquine exposure on the phospholipid metabolism in retina and pigment epithelium of the mouse. Acta Ophthalmol (Copenh). 1990;68:125-130.
Leung LS, Neal JW, Wakelee HA, et al. Rapid onset of retinal toxicity from ghigh-dose hydroxychloroquine given for cancer therapy. Am J Ophthalmol 2015; 160:799-805.
Lyons JS, Severns ML. Using multifocal ERG ring ratios to detect and follow plaquenil retinal toxicity: a review: review of mfERG ring ratios in plaquenil toxicity
Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol 2014;132:1453-60.
Marmor MF, Kellner U, Lai TY, et al. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 revision). American Academy of Ophthalmology
Perlman E, Friday R, Greenberg P, et al. Dosechecker: Solving the hydroxychloroquine dosing dilemma with a smart phone app. 2017 ACR/ARHP Annual Meeting. Abstract number 2635. Sep 18, 2017.
Rosenthal AR, Kolb H, Bergsma D, Huxsoll D, Hopkins JL. Chloroquine retinopathy in the rhesus monkey. Invest Ophthalmol Vis Sci. 1978;17:1158-1175.
Wolfe F, Marmor MF. Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2010;62:775-784.