New Technique May Help Detect Hydroxychloroquine-induced Eye Problems

By Lorraine L. Janeczko

March 23, 2019

NEW YORK (Reuters Health) - Swept-source optical coherence tomography angiography (SS-OCTA) may detect eye abnormalities in patients taking hydroxychloroquine (HCQ) longer than five years to treat systemic lupus erythematosus (SLE), a pilot study conducted in Spain suggests.

"SS-OCTA could provide more valuable data to detect early HCQ retinopathy when compared with the actually existent screening tools," researchers write in the British Journal of Ophthalmology, online March 6.

Dr. Raimondo Forte and colleagues from the Institut Catala de Retina in Barcelona evaluated 20 eyes in 10 patients with SLE who were under HCQ treatment for at least five years and compared them with 36 eyes in 18 healthy control patients who were not treated with HCQ. The HCQ treatment duration averaged 10 years and ranged from five to 15 years, and the cumulative dose/body weight was 15.86 g/kg.

The SLE patients did not show disease activity according to the Systemic Lupus Erythematosus Disease Activity Measure, and none had developed ocular manifestations of SLE since being first diagnosed with the disease. None of the eyes revealed signs of retinopathy.

Patients in both groups underwent SS-OCTA to evaluate the retinal superficial capillary plexus, middle capillary plexus and deep capillary plexus (DCP) and the choriocapillaris (CC).

Patients treated with HCQ showed reduced vessel density in the central subfield, in the nasal and temporal subfields of the deep capillary plexus. Compared with controls, the patients taking HCQ also had significantly enlarged foveal avascular zones in the three retinal capillary plexuses, reduced foveal choroidal thickness, and a higher frequency of choriocapillary flow voids.

"In conclusion, in patients with SLE, without ophthalmoscopically evident microangiopathy and treated with HCQ for more than 5 years, we found choroidal thinning and vascular abnormalities at SS-OCTA in the three retinal capillary plexuses and CC," the researchers conclude, with no abnormalities present at multifocal electroretinography, OCT, automated visual field or fundus autofluorescence.

Dr. Paul S. Bernstein, a professor of ophthalmology and visual sciences at the Moran Eye Center of the University of Utah School of Medicine in Salt Lake City, told Reuters Health by email, "All patients on HCQ longer than 5 years should be monitored for retinal toxicity because some will develop irreversible visual loss; however, the changes are subtle and detecting the earliest signs of toxicity can be very difficult."

"If SS-OCTA can indeed detect HCQ toxicity earlier than current screening tests, it could be added to our current armamentarium of screening tests for HCQ toxicity," added Dr. Bernstein, who was not involved in the study. "However, it should be noted that none of the patients had detectable toxicity. And it is not clear how the test will be useful to distinguish the rare individuals destined to get toxicity who need to be taken off of an otherwise useful drug."

Dr. James P. Dunn, director of the Uveitis Unit of Wills Eye Hospital in Philadelphia said by email, "The strength of the study is its prospective, masked comparison format of SS-OCTA with the current 'standard of care' testing for HCQ toxicity from the American Academy of Ophthalmology (spectral domain optical coherence tomography (SD-OCT), multifocal electroretinography (mfERG), Humphrey 102 automated visual field testing, and fundus autofluorescence)."

But Dr. Dunn, who also was not involved in the study, cautioned that this was a pilot study of patients who varied widely in duration as well as daily and cumulative HCQ dosing; the study was underpowered to detect significant differences between the two groups; it did not include patients with other potential causes of abnormal OCTA results, such as macular degeneration or patients with diseases other than lupus; and other exclusion criteria were very broad.

The authors and Drs. Bernstein and Dunn recommend further related research in larger groups of patients.

Dr. Forte did not respond to requests for comment.


Br J Ophthalmol 2019.