Age-Related Macular Degeneration Masquerade: A Review of Pentosan Polysulfate Maculopathy and Implications for Clinical Practice

Abstract

Pentosan polysulfate (PPS) sodium (Elmiron) is the only Food and Drug Administration (FDA)-approved oral medication to treat interstitial cystitis, also known as bladder pain syndrome. A symptomatic pigmentary maculopathy associated with PPS was reported in 2018. Since then, recognition of this unique drug toxicity has increased rapidly. This potentially sight-threatening side effect prompted the FDA in June 2020 to update the label for PPS to warn about "retinal pigmentary changes." A challenging feature of pentosan maculopathy is its ability to mimic many other retinal conditions, including inherited retinal dystrophies such as pattern dystrophy, mitochondrially inherited diabetes and deafness, and Stargardt disease, and age-related macular degeneration. In this review, we discuss the history of PPS maculopathy and its implications for thousands of at-risk interstitial cystitis patients. We use published literature and an illustrative case from our institution to highlight the importance of diagnosing PPS maculopathy. We also compare PPS maculopathy to age-related macular degeneration, explain why differentiating between the 2 is clinically important, and highlight avenues for further research. Finally, we highlight the paucity of data on patients of color and why this lack of understanding may impact patient care.

Figure 1.

A and B, At presentation, color photos show macular hyperpigmented spots, yellow-orange deposits and patchy RPE atrophy OU and retinal hemorrhage OS. C and D, late frame of the fluorescein angiogram shows blockage from the hemorrhage OS with surrounding leakage. OS indicates left eye; OU, both eyes; RPE, retinal pigment epithelium.

Figure 2.

OCT stack with a horizontal cut through the foveal center at each time point showing evolution of both eyes. A and B, At initial visit, this 47-year-old woman had drusen and SDDs OU, and subretinal fluid with subretinal hyperreflective material OS consistent with CNV OS. C and D, 2 months after initial presentation, scattered RPE elevations and SDDs OU with regressed CNV OS. E and F, 2 years after initial presentation, there was new subretinal fluid OD, RPE/EZ irregularities, diffuse RPE elevations, EZ band irregularities OU. G and H, 8 years after presentation, diffuse RPE/EZ band irregularities. CNV indicates choroidal neovascularization; EZ indicates ellipsoid zone; OCT, optical coherence tomography; OD, right eye; OS, left eye; OU, both eyes; RPE, retinal pigment epithelium; SDD, subretinal drusenoid deposits.

Figure 3.

A, Color fundus photo of right eye. B–D, early, mid, and late frames, respectively, of fluorescein angiogram showing mild-late leakage near the fovea.

Figure 4.

A and B, Color photographs from June 17, 2021, patient aged 55, showing yellowish deposits and macular pigment deposition. C and D, Fundus autofluorescence shows a densely packed array of macular hypo- and hyperautofluorescent spots involving the retina nasal to the optic disc OS > OD as well as a hypoautofluorescent peripapillary halo. OD indicates right eye; OS, left eye.