Pentosan Polysulfate Sodium-Associated Pigmentary Retinopathy: Risk Factors and Fundus Findings

Abstract

Purpose To evaluate the risk factors and fundus findings of patients with potential PPS-associated retinopathy. Patients and Methods A retrospective chart review was performed of patients exposed to PPS who had a dilated fundus examination at a large retina-only practice from 2018–21. Multimodal images were evaluated by masked reviewers. Results A total of 148 patients were included, of whom 33 (22%) had PPS-associated retinopathy, and 115 (78%) did not. The mean age was 60.3 years old, and the mean follow-up was 11.8 months. The PPS-associated retinopathy group had higher mean cumulative doses of PPS (1600g±849 vs 864g±852, P < 0.0001, Mann–Whitney test) and longer duration of PPS use (13.6 years vs 7.48, P < 0.0001). There was no statistically significant difference based on a history of kidney or liver disease or the dosage per day for the weight, body mass index, body surface area, or lean body weight. Of the patients with PPS-associated retinopathy whose genetic results were available, 15 of 16 (93%) were heterozygous for variants of uncertain significance. Conclusion A longer duration of PPS use and higher cumulative dosage of PPS were associated with an increased risk of developing PPS-associated pigmentary retinopathy. The role of genetic mutations in patients exposed to PPS is still to be determined.

Retinal Toxicity Induced by Chemical Agents

“…Common symptoms include blurred vision, difficulty reading, metamorphopsia, paracentral scotomas, and prolonged dark adaptation. Signs comprise parafoveal pigmented deposits at the level of the RPE, vitelliform deposits, and patchy paracentral RPE atrophy similar in appearance to pattern dystrophy [ 87 , 88 , 89 ]. Since PPS is an inhibitor of heparanase, used chronically, a study investigated the consequence of the absence of this enzyme in knockout mice (KO) [ 90 ].…”

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

“…In an earlier interim evaluation of this study after the inclusion of 50 patients, Wang et al 9 reported a prevalence of pigmentary maculopathy associated with PPS of 20% (10 out of 50). According to the data provided, only two of these 10 (4%) patients had pigmentary maculopathy, according to the definition given by Pearce et al, 5 Hanif et al, 41 and Christiansen et al 42 A recent retrospective chart review performed by Leung et al 48 at a large retina-only practice showed that 33 (22%) of 148 patients with PPS exposure had signs of maculopathy. As none of these eyes fulfilled all the diagnostic criteria stipulated by Pearce et al, 5 Hanif et al, 41 and Christiansen et al, 42 no further conclusions can be drawn.…”

“…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%.…”

Pentosan polysulfate maculopathy: Keep an eye out for this masquerader

“…7 Subsequent studies independently conducted at numerous centers have reported a significant dose-response relationship between PPS exposure and presence of maculopathy. [8][9][10][11][12][13] A study from 2020 demonstrated prevalence rates of 13%, 30%, and 42% among patients with 500-999 grams (g), 1000-1499 g, and >1500 g of cumulative PPS exposure, respectively. 8 In another study from earlier this year, researchers found prevalence rates of 46% and 83% among patients with cumulative PPS exposures of 1500-2000 g and ≥2000 g. 11 Studies of large administrative claims databases have yielded mixed findings.…”