RPE damage may predict hydroxychloroquine retinopathy progression

This retrospective study found that severe hydroxychloroquine retinopathy usually progresses for at least 3 years after the drug is stopped, and this progression is most strongly linked to RPE damage.  

The authors reviewed the charts of 11 patients with hydroxychloroquine retinopathy followed for up to 40 months after drug cessation using SD-OCT as well as functional tests. They stratified the patients into three categories based on the degree of hydroxychloroquine retinopathy: early (patchy parafoveal damage shown on field or objective testing), moderate (a 50% to 100% parafoveal ring of optical coherence tomography thinning but intact retinal pigment epithelium [RPE]), and severe (visible bull’s-eye RPE damage). 

Early and moderate cases showed minimal anatomic change in after cessation of hydroxycholoquine. However, in severe cases in which the RPE was affected, there was progressive foveal thinning and loss of the ellipsoid zone for at least 3 years after drug cessation. Visual acuity and visual fields showed no consistent change. Fundus autofluorescence showed little or no change except in severe cases in which the bull’s-eye damage expanded progressively.

It is important to recognize hydroxychlorquine retinopathy early, before RPE damage, using multimodal testing with OCT, visual fields, fundus autofluorescence and multifocal ERG in an effort to decrease the risk of continued progression after drug cessation.

They write that the mechanism of progressive hydroxychloroquine retinopathy after the drug is discontinued is unclear due to the complex pharmacodynamics of the drug. Hydroxychloroquine binds strongly to melanin, which could be either a reservoir for damage or a protective mechanism. Clearance of hydroxychloroquine from the body takes many months after it is discontinued, and a very low concentration may be detectable in blood a year later.

But it is unclear whether the small amount bound to RPE melanin is high enough to maintain a local retinal concentration that would cause continued neural damage for many years. It seems more likely that photoreceptor cells become metabolically compromised after long exposure, and the greater the insult, the greater the likelihood that these cells will eventually decompensate and die.

The authors conclude that the critical predictor for severe progression appears to be the presence of RPE damage, and the critical predictor for retaining visual acuity appears to be integrity of foveal outer segment structures (including the ellipsoid zone). As recommended by the American Academy of Ophthalmology, annual screening should use both 10-2 fields and SD-OCT and look for early changes before there is any visible bull’s-eye.