Phenotypic Spectrum of Pentosan Polysulfate Sodium–Associated Maculopathy: A Multicenter Study

Joshua D. Levinson, MD  |  October 1, 2019

September 2019

Adam M. Hanif, MD; Stephen T. Armenti, MD, PhD; Stanford C. Taylor, MD, et al. Phenotypic Spectrum of Pentosan Polysulfate Sodium–Associated Maculopathy A Multicenter Study. JAMA Ophthalmol. Sept 2019.

Pentosan polysulfate sodium (brand name: Elmiron) is used to treat interstitial cystitis (IC), a chronic pain syndrome of the bladder. In 2018, Pearce et al. described a novel pigmentary maculopathy in 6 patients taking long-term PPS.  A retrospective study was performed by Hanif and colleagues compiling cases from 4 institutions to further characterize clinical findings in PPS-associated maculopathy.

Expert reviewers assessed retinal imaging available for patients exposed to PPS. Thirty-five patients with PPS-associated maculopathy were identified. Interstitial cystitis most commonly occurs in females, and 97% of included patients were female. The median age was 60 years. Median length of time taking PPS was 15 years (range 3-22). The median daily dose was 300mg.

The most common referring diagnoses were pattern dystrophy and macular degeneration. Symptoms included blurred vision, metamorphopsia and decreased dark adaptation. Central visual acuity was preserved (median Snellen equivalent 20/25) in most patients, although 6 patients had center-involving atrophy (median Snellen equivalent 20/70).

All cases of PPS-maculopathy were bilateral. The most common fundus finding was paracentral hyperpigmented spots (53%). Pathologic findings were more notable on fundus autofluorescence imaging (FAF) with densely packed hyperautofluorescent and hypoautofluorescent spots being most typical. In 56% of cases, there was a well-circumscribed region of disease in the posterior pole. The phenotypical appearance resembles pattern dystrophy. The authors noted one unique FAF finding is that in eyes with involvement of the peripapillary retina, there was often a peripapillary hypoautofluorescent halo which is distinct from the perippapillary sparing often seen in ABCA-4 related retinopathies.

Optical coherence tomography (OCT) revealed focal elevation or thickening of the retinal pigment epithelium with ellipsoid-zone changes. Cystoid macular edema was present in 9 eyes of 6 patients. Longitudinal data over 3 years was present for 8 patients; hyperpigmented parafoveal spots were noted to spread within the macula over time with an expanding area of FAF-involvement.

PPS-associated maculopathy is a newly discovered retinal drug toxicity. It is important for clinicians to be aware of this association so that signs of toxicity can be recognized. FAF findings are typically more striking than funduscopic appearance, and multimodal imaging may aid in diagnosis. In most cases, patients were symptomatic despite preserved central acuity. Further study is necessary to determine the incidence of disease and establish screening guidelines.

FAF images from a 73 year old female patient with suspected PPS-maculopathy. This patient was seen at the Retina Group of Washington and was not included in the published study. Note the well- circumscribed prominent speckled hyper- and hypoautofluorescent changes in the posterior pole. There is a peripapillary hypoautofluorescent halo which the study authors noted to be distinct from peripapillary sparing typically seen in pattern dystrophy.

Joshua D. Levinson, MD

The Retina Group of Washington
Fairfax, VA

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