Pigmentary Maculopathy in Patients with Interstitial Cystitis: Association with Pentosan Polysulfate and Other Therapies

Abstract

Purpose

To examine the association between the development of pigmentary maculopathy and exposure to pentosan polysulfate sodium (PPS) and other therapies in patients with interstitial cystitis (IC).

Design

Single-center retrospective study.

Subjects

Patients diagnosed with IC who had ≥2 eye examinations at Wake Forest School of Medicine between January 2011 and August 2021.

Methods

Two masked retina specialists evaluated available multimodal imaging for pigmentary maculopathy using the established criteria, with any disagreements adjudicated by a third reviewer. Cases were categorized by severity and analyzed for associations with medication exposure.

Main Outcome Measures

Association between the development of pigmentary maculopathy with PPS exposure duration and cumulative dose, and concurrent IC medication use.

Results

A total of 336 patients with IC (176 with PPS exposure, 160 without) were included. Patients with PPS exposure had increased odds of exposure to hydroxyzine (odds ratio [OR]: 4.76, P < 0.0001), amitriptyline (OR: 2.62, P < 0.0002), phenazopyridine or pyridium (OR: 1.68, P = 0.036), narcotics (OR: 2.68, P < 0.0001), oxybutynin (OR: 1.93, P = 0.041), cystoscopy with hydrodistention (OR: 4.001, P < 0.0001), bladder instillation (OR: 6.83, P < 0.0001), and vaginal valium (OR: 9.515, P = 0.033). Of the 122 patients with retinal imaging (71 with PPS exposure, 51 without), 8 patients (16 eyes) were graded to have pigmentary maculopathy and all 8 patients had PPS exposure. The median duration of PPS exposure in patients with moderate/severe maculopathy was 121 months (interquartile range [IQR] 117, 121) with a median cumulative dose of 929 200 mg (IQR 799 200; 1 109 100), which were significantly higher than patients with mild or no maculopathy (median duration 35 months [IQR 10, 63], P = 0.002 and median dose 166 800 mg [IQR 44 600; 569 100], P = 0.004). Higher proportions of patients with pigmentary maculopathy than those without had concurrent exposure to PPS and amitriptyline/nortriptyline (75% vs. 34.9%, P = 0.015) or PPS and cyclosporine (37.5% vs. 1.6%, P = 0.003).

Conclusions

Pentosan polysulfate sodium exposure, and not IC itself, was associated with the development of pigmentary maculopathy. Longer duration and higher cumulative dose were associated with worse maculopathy. Patients on PPS were more likely to be on multiple other therapies for IC. Concurrent exposure to PPS and amitriptyline/nortriptyline or cyclosporine may increase the risk of developing maculopathy but these results should be validated by larger prospective studies.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.