LONDON – Retinopathy in patients taking long-term hydroxychloroquine for rheumatic conditions requires assessment by those experienced with specialized ophthalmic imaging, according to study findings presented at the European Congress of Rheumatology.

Nonspecific abnormalities, which often are unrelated to hydroxychloroquine (HCQ), can be seen with many of the tests recommended by current ophthalmology guidelines. These changes need “careful interpretation by retina specialists,” the study’s investigators wrote in a poster presentation.

HCQ is used widely for the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis, and many other inflammatory or autoimmune conditions, but it can cause irreversible eye damage and is often associated with prolonged (greater than 5 years) use. Specifically, it can cause a type of end-stage retinopathy called bull’s-eye maculopathy, which is where the fovea becomes hyperpigmented, much like the bull’s-eye on a dartboard. This can lead to substantial vision loss (blind spots) if not caught early.

Although it is reasonably rare to develop end-stage retinopathy, there is currently no treatment for HCQ-induced retinopathy. Stopping the drug may not necessarily stop the retinal damage, and drug withdrawal may not be an option in many patients given the lack of alternative options to treat the symptoms of SLE, study author and ophthalmologist Syed Mahmood Ali Shah, MBBS, MD, said in an interview.

Dr. Shah and his associates at Johns Hopkins University in Baltimore reported on applying the 2011 American Academy of Ophthalmology (AAO) guidelines on screening for HCQ retinopathy (Ophthalmology. 2011;118:415-22) to an academic practice. They also estimated the prevalence of HCQ retinopathy among 135 consecutively treated patients with SLE using recommended tests. The mean duration of HCQ use was 12.5 years.

The 2011 AAO guidelines – which in March 2016 were updated (Ophthalmology 2016 Jun;123:1386-94) – recommended the use of three “ancillary” tests in addition to the usual clinical ophthalmic examination and assessment of visual fields: optical coherence tomography (OCT), fundus autofluorescence (FAF), and multifocal electroretinography (mfERG). Dr. Shah and his colleagues used these three tests together with eye-tracking microperimetry (MP) as a substitute for Humphrey Visual Fields (HVF), which is a common visual field test used in the United States.

Early HCQ-induced eye damage as seen on microperimetry.

One difference between the 2011 guidelines and 2016 revision is that “the baseline exam can now be performed relying [only] on the fundus exam, with additional imaging required only for abnormal patients,” Dr. Shah said. “Overall, the guidelines have not changed on how often and how much you follow up,” he added. “The change is that there is no need to do these tests at baseline unless changes of the fundus are present.” However, OCT has become more widely used in many offices and has been recognized as the most useful objective test and shall be performed if there are any abnormal findings of the fundus.

A total of 266 eyes were examined using these imaging methods and interpreted by experienced retina specialists. Overall, HCQ-related abnormalities were noted in 14 (5%) eyes using OCT, 18 (7%) using FAF, 27 (10%) eyes using mfERG, and 20 (7%) using MP.

MP had the lowest discrepancy between the overall number of eyes with abnormalities (72 [27%] of 266) detected and the number of eyes with abnormalities related to HCQ (20 [28%] of 72), followed by OCT (21% and 25%, respectively), FAF (19% and 35%) and mfERG (37% and 28%). Only four patients (3%) showed changes in all four tests suggestive of HCQ retinopathy.

Late HCQ-induced eye damage as seen on microperimetry of the same eye of the same patient.

In the absence of baseline data from the AAO recommended ancillary tests before the use of HCQ, “it may be difficult to interpret changes seen on these tests since most of the screenings are done by regular ophthalmologists who lack the equipment and experience with specialized testing such as mfERG, FAF, and OCT,” Dr. Shah and his coauthors noted. “We found a substantial number of cases with abnormalities unrelated to HCQ.”

Giving some practical advice, Dr. Shah noted that “before a patient starts treatment with HCQ, they should undergo a baseline ophthalmic assessment. Then if the patient complains of any vision changes, even if they have been taking the drug for less than 5 years, they should be reassessed.”

While repeat follow-up is, of course, necessary, he intimated that it is necessary to find a balance of risk and cost in regard to the frequency of screening for drug-related damage. “The American Academy of Ophthalmology currently recommends that a baseline fundus exam be performed shortly after starting HCQ. Ancillary OCT and visual fields shall only be performed if the fundus is abnormal at this baseline exam. However, since most retina specialists get OCT and visual field testing anyway it is wise to look at these as well,” he suggested. After 5 years of using the drug, they must be seen more regularly, and this is the point when ophthalmologists can decide if this should be every 6 months or annually, with the latter recommended by the AAO guidelines for patients with no additional risk factors.

The study was supported by noncommercial grants. Dr. Shah had no conflicts of interest to disclose.

HCQ eye toxicity needs experience to assess