Redefining the Spectrum of Pentosan Polysulfate Retinopathy: Multimodal Imaging Findings from a Cross-Sectional Screening Study

Abstract

Purpose : There is growing evidence of a direct association between Pentosan polysulfate (PPS) (the only FDA approved oral medication for the treatment of interstitial cystitis) therapy and the development of macular changes. Using multimodal retinal imaging, we describe an expanded spectrum of findings among PPS users.

Methods : Thirty-nine participants who were current or recent users of PPS underwent a brief eye exam answered a comprehensive medical and ophthalmic questionnaire, including dosage and duration of PPS exposure. Multimodal imaging including color fundus photography, fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) was obtained. Images were evaluated by expert graders at the Wisconsin Reading Center. Abnormalities were categorized as definitive toxicity (DT) if seen on both FAF and SD-OCT and questionable toxicity (QT) if seen on either FAF or SD-OCT.

Results : The mean PPS daily dose of the study cohort was 282mg (88-400mg), while the mean cumulative dose was 915g (19-3650g) over a mean period of 8.8 years (2 months-25 years). DT was identified in 24 (31%) of eyes and QT in 8 (10%) of eyes. A total of 16 (41%) participants had at least one eye graded as DT, while bilateral DT was seen in 8 (20.5%) participants. Retinal pigment epithelium (RPE) abnormalities (thickening and/or thinning) were present in all DT eyes. RPE atrophy was seen in 7 (18.0%) eyes, predominantly outside the central subfield. SD-OCT features include the presence of a flying-saucer sign and consistent interdigitation zone abnormalities ranging from thickening to disruption. FAF abnormalities were seen in 22 (91.6%) eyes, and in 18 (75%) eyes these were found outside the central subfield and extending beyond the arcades. Predominant hypoautofluorescence was present in 13 (54.1 %) eyes, compared to 3 (12%) eyes with predominant hyperautofluorescence and 5 (20.8%) eyes with a predominant mixed appearance.

Conclusions : A PPS retinopathy prevalence of 41% is higher than previously reported and suggests a wider phenotypic spectrum of structural abnormalities among PPS users. The RPE and outer retina are the most common areas of macular changes, with a constellation of findings often seen outside the macula. The subtle and atypical findings in this cohort should prompt clinicians to consider lowering the threshold for diagnosing PPS retinopathy.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.