Expanded clinical spectrum of pentosan polysulfate sodium-associated pigmentary maculopathy

Abstract

Purpose : We recently described a novel maculopathy in 6 patients at 1 institution reporting chronic intake of pentosan polysulfate sodium (PPS), one of two FDA-approved therapies for interstitial cystitis (IC). While causality has yet to be proven, these findings were suggestive of a newly described, vision-threatening medication toxicity. We performed a retrospective review of patient records across 4 institutions to further characterize this condition. We hypothesized that the maculopathy would consistently manifest in patients with chronic PPS exposure, and predominantly affect the retinal pigment epithelium (RPE).

Methods : Medical and imaging records of patients with confirmed PPS-associated maculopathy at the Emory Eye Center (n=16), Casey Eye Institute (n=6), Kellogg Eye Center (n=8) and Northern California Retina Vitreous Associates (n=3) were reviewed for demographics, visual symptoms, history of IC and PPS intake, and exam findings. Color fundus photography, optical coherence tomography (OCT) and fundus autofluorescence (AF) images were evaluated to assess the phenotypic spectrum.

Results : 32 female and 1 male patients were evaluated. Mean age and IC symptom duration were 58.8 years (SD: ±10.9) and 19.3 (SD: ±10.7) years, respectively. Mean duration of PPS intake and daily dose per kg body weight were 13.8 years (SD: ±5.6) and 5.18 mg/kg (SD: ±1.36), respectively. The three leading symptoms included metamorphopsia, blurred vision, and prolonged dark adaptation. Average logMAR visual acuity was 0.14 (SD: ±0.26) and 0.17 (SD: ±0.28) in right and left eyes, respectively. Pathology manifested bilaterally in the posterior pole. Fundus photography most often (Figure 1A) revealed hyperpigmented macular spots and/or RPE atrophy, often with interspersed pale yellow flecks. AF (Figure 1B) classically revealed a well circumscribed pattern of mottled hyper- and hypoautofluorescent spots involving the fovea, spreading outward in a confluent pattern. OCT (Figure 1C) showed foci of RPE nodularity associated with hyperreflectance on near infrared reflectance imaging. Cystoid macular edema was present in 5 patients.

Conclusions : PPS-associated maculopathy manifests in male and female patients reporting chronic PPS intake. Imaging reveals RPE injury centered on the posterior pole. We recommend drug cessation in affected patients. Ongoing work will further explore causality, pathogenesis and screening guidelines.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.