2018 report linked long-term use of pentosan polysulfate sodium (PPS) to a vision-threatening macular disease. 1 Subsequent larger studies have corroborated this finding, demonstrating a strong drug-disease association. [2][3][4] Affected patients typically report difficulty with reading and problems with dark adaptation. Retinal imaging demonstrates characteristic changes within the retinal pigment epithelium (RPE) and at the RPE-photoreceptor interface, with some patients exhibiting fovea-involving RPE atrophy. 3,5 Because PPS has been widely prescribed since its approval by the US Food and Drug Administration in 1996, thousands of patients are at risk. 4 Although affected patients are typically advised to discontinue PPS therapy, little is known about the evolution of this newly described retinopathy after drug cessation. The present study is a retrospective evaluation of outcomes after drug cessation in a group of affected individuals across 2 institutions. MethodsThis retrospective study was approved by each participating institution's institutional review board and was conducted at Emory University. Data collection was performed systemati-IMPORTANCE Recent studies have linked a vision-threatening maculopathy with long-term use of pentosan polysulfate sodium (PPS).OBJECTIVE To evaluate the disease course in PPS-associated maculopathy after drug cessation.

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Individuals with pentosan polysulfate sodium (PPS) maculopathy commonly report symptoms of prolonged dark adaptation and difficulty reading. We hypothesize that PPS maculopathy causes degradation of visual function not fully captured with visual acuity testing. METHODS. Subjects with PPS maculopathy underwent multimodal evaluation of retinal structure and function. Structural changes were graded as moderate or advanced. Patientreported visual function was assessed with the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ-39) and Low Luminance Questionnaire (LLQ). Objective functional evaluations included Early Treatment of Diabetic Retinopathy Study (ETDRS) bestcorrected visual acuity (BCVA), Pelli-Robson contrast sensitivity, mesopic microperimetry, and dark adaptometry. Functional testing results were correlated with structural disease category. RESULTS. Thirteen patients (26 eyes), median age 62 years (range, 37-76), completed the study. Median ETDRS letter score was 82 (Snellen equivalent 20/25). Median NEI-VFQ-39 and LLQ composite scores were 65 (range, 33-88) and 41 (range, 20-92), respectively. Median contrast sensitivity was 1.65 (range, 0.15-1.95), and median mesopic microperimetry average thresholds and percent reduced thresholds were 26 decibels (range, 0.4-28.6) and 21.6% (range, 0-100%), respectively. Median rod intercept time was 14.1 minutes (range, 4.4-20.0). Eyes with advanced disease based on retinal structure had significantly worse retinal function for several testing modalities. CONCLUSIONS. PPS maculopathy causes considerable visual function degradation that is not fully captured with BCVA testing. There was good correlation between other measures of visual function and disease severity. These findings deepen our concern regarding this patient safety issue.

Recent studies have implicated long-term pentosan polysulfate use with vision loss from a newly described macular condition. Affected patients report difficulty with reading and adjusting to dim lighting, and they occasionally develop severe visual disability. Macular changes resemble those seen in age-related macular degeneration, potentially leading to misdiagnosis. The objectives of this Current Commentary are to summarize studies evaluating the association between pentosan polysulfate use and macular disease, to educate pentosan polysulfate prescribers about the clinical manifestations of this condition, and to provide recommendations for screening at-risk patients.