New Insights Into Pentosan Polysulfate Maculopathy

Abstract

BACKGROUND AND OBJECTIVE: To provide new insights into toxic maculopathy secondary to pentosan polysulfate (PPS) utilizing multimodal testing. PATIENTS AND METHODS: Retrospective case-series of four patients from two academic centers evaluated with multimodal imaging, electrophysiology, dark adaptometry (DA), and genetic testing. RESULTS: Median age was 58 years, exposure to PPS was 18.5 years, and cumulative dose of was 2,025 grams. Seven of eight eyes had visual acuity of 20/40 or better. Optical coherence tomography (OCT) angiography demonstrated increased choriocapillaris flow voids (54.25%) in cases compared to controls (13.2%). Two subjects had abnormal foveal avascular zone configurations. Two subjects demonstrated collapse of the retinal pigment epithelium nodular excrescences and progressive retinal thinning over 4 to 5 years on OCT. Electrophysiology was normal (3/3 patients), but DA was delayed (2/2 patients). CONCLUSIONS: The authors describe novel findings of PPS maculopathy, including flow voids in the choriocapillaris. Progressive retinal thinning may suggest a secondary retinal effect. These findings may improve understanding of the pathophysiology. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:13–22.]

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

“…Hanif and coworkers proposed 2 other possibilities based on the similarity of the structure of the composite glycosaminoglycans to PPS itself: direct toxicity to RPE that would inhibit processing of photoreceptor outer segments or disruption of the interphotoreceptor matrix that mediates the photoreceptor-RPE relationship, especially because the insoluble components of the interphotoreceptor matrix are comprised of chondroitin sulfate proteoglycans 33,39 . Findings of choriocapillaris dropout may implicate a vascular cause as is the case in early and late AMD 40–42 …”

“…33,39 Findings of choriocapillaris dropout may implicate a vascular cause as is the case in early and late AMD. [40][41][42] Complications and Progression PPS maculopathy can also cause vision loss through progression of RPE atrophy, cystoid macular edema (CME), and/or choroidal neovascularization (CNV). 6,24,25,33 In the study by Hanif and coworkers, 33 39% of eyes had AF-and OCT-validated evidence of parafoveal RPE atrophy that coalesced and involved the fovea with increasing severity.…”

Pigmentary Maculopathy in Interstitial Cystitis/Bladder Pain Syndrome Treated with Oral Pentosan Polysulfate: A Review

“…To note, the maculopathy group had a higher mean cumulative dose of PPS and longer duration of PPS use (1,600±849 g versus 864±852 g; p<0.0001; and 13.6 years versus 7.48 years; p<0.0001, respectively). 48 Further indications on prevalence can be derived from the study by Ludwig et al, 11 as described above. The percentage of patients who received PPS and were later diagnosed with maculopathy is estimated to be 2.4%.…”

“…Publication of this small, retrospective case series triggered further articles discussing a possible link between PPS and pigmentary maculopathy. [6][7][8][9][10][11][12][13] These articles prompted an ongoing discussion in the media, and concern amongst patients with IC/BPS. As a result of the published findings, the summary of product characteristics 14 of PPS was updated in 2019 15 by the EMA and in 2020 16 by the FDA to include a pigmentary maculopathy warning with long-term use (>5 years), with recommendations for regular ophthalmological examinations.…”

Update on Retinal Drug Toxicities

“…Another study reported that OCTA showed choriocapillaris flow voids. The authors hypothesize that the drug toxicity primarily damages the choriocapillaris, which then leads to observed RPE changes and atrophy [ 25 ].…”