Advanced quantitative imaging offers potential to improve screening

February 1, 2010

New non-invasive imaging modalities are showing promise for enabling earlier detection of hydroxychloroquine retinopathy compared with current recommended screening techniques.

In a poster presented at the Retina Congress, Kimberly Stepien, MD, assistant professor of ophthalmology at the institute, and colleagues reported on findings from imaging performed with spectral-domain optical coherence tomography (SD-OCT) and adaptive optics (AO) in two patients with evidence of hydroxychloroquine retinopathy based on clinical examination.

Detecting toxicity

"Discontinuing hydroxychloroquine at the earliest sign of retinal toxicity is important for preserving vision," she said. "Although retinopathy can continue to progress after hydroxychloroquine is stopped, there [are] multifocal ERG data suggesting that early toxicity can be reversible with prompt cessation of the drug.

"Therefore, the sooner hydroxychloroquine toxicity is detected, the sooner treatment can be stopped to [try to] preserve vision," she said. "Our experience with SD-OCT and AO imaging is limited, and further research is needed.

"However, these techniques are showing exciting potential for identifying hydroxychloroquine retinopathy at a 'pre-clinical' state and simultaneously offer a number of additional advantages compared [with] current screening methods that make them attractive monitoring tools," she added.

Currently, the American Academy of Ophthalmology Preferred Practice Patterns for screening for hydroxychloroquine retinopathy recommend an annual comprehensive eye exam and testing with either perimetry (10-2 Humphrey Visual Field Analyzer, Carl Zeiss Meditec) or an Amsler grid. Use of additional imaging is left to the discretion of the provider.

"Extensive retinal damage has to occur before retinopathy can be detected by these testing methods, and fundoscopic changes tend to be a late finding," Dr. Stepien said. "Furthermore, Amsler grid testing can be very subjective, and [visual field] testing has a learning curve, with many tests being inconclusive.

"Other modalities, including multifocal ERGs, have shown promise," she said. "However, this test is expensive, requires special instrumentation as well as special training for administration and interpretation, and is not usually available in the clinic, so that a second appointment is required."

Value of SD-OCT and AO imaging

SD-OCT and AO imaging are non-invasive tests that provide objective, quantitative findings, she said. SD-OCT can be acquired rapidly and is fairly readily available as a clinical tool. AO imaging may be more sensitive than SD-OCT because it allows for direct visualization of individual photoreceptor cells in vivo, she said.

"Although only a limited number of AO instruments are being used as research units worldwide, work toward the development of a clinical system is occurring," Dr. Stepien said. "It is possible that these systems will become commercially available for use in the clinical setting in the future."

For the purposes of this study, the AO imaging was performed with a research system developed at the institution in The Joe Carroll Lab. Two platforms were used for SD-OCT imaging (Spectralis, Heidelberg Engineering; Bioptigen, Bioptigen).

"We have both units at our institution," Dr. Stepien said. "[Because] each has its own set of advantages and disadvantages, we were interested in comparing the findings obtained with the different machines."

In areas documented as affected by hydroxychloroquine retinopathy based on conventional assessments, SD-OCT imaging revealed loss of the photoreceptor inner segment/outer segment (IS/OS) junction, thinning of the outer nuclear layer, and a downward displacement of the inner retina.

The researchers currently are collecting more cases. Ideally they would like to follow a larger population of hydroxychloroquine-treated patients over time to see whether the early changes noted on SD-OCT and AO imaging evolve to true hydroxychloroquine retinopathy and to see if the findings from these tools can improve understanding of the pathogenesis of hydroxychloroquine retinopathy.

"So far, the SD-OCT and AO images have shown that the outer retina is most affected by hydroxychloroquine toxicity, and the AO data suggest that cone photoreceptors are likely more affected than rods," Dr. Stepien concluded. "As we collect more cases, we hope to gain further insights."