Urology Rx Linked to Maculopathy

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Researchers at Emory University report a unique maculopathy associat­ed with chronic exposure to pentosan polysulfate sodium (PPS), a drug approved by the FDA in 1996 to treat discomfort associated with interstitial cystitis (IC).¹

Previously unreported. The pre­viously unreported maculopathy is thought to primarily affect the retinal pigment epithelium (RPE). It may be mistaken for other well-known macular disorders such as pattern dystrophy or age-related macular degeneration (AMD).

“Hundreds, if not thousands, of patients diagnosed with pattern dystrophy and AMD since the drug’s approval may actually have a prevent­able drug-associated maculopathy,” said senior author Nieraj Jain, MD, at Emory Eye Center in Atlanta.

EVIDENCE. These images, taken over a two-year period in one patient, demonstrate the progressive nature of the patchy RPE atrophy noted in more severe cases of PPS-associated maculopathy.

Detective work. After seeing a string of patients with similar pigmentary macular changes and a past history of IC, the researchers culled their clinic’s electronic medical records for PPS. Within the prior two years, six patients had previously been identified by the authors for an un­known pigmen­tary maculopathy. “That makes it one of the more common condi­tions that we saw in our clinic of hereditary retinal diseases,” Dr. Jain said. (Since study publication in November 2018, the number of affected patients has grown to 15.)

Findings of note. The new entity mimics hereditary pattern dystrophies, yet none of the patients had a family history of hereditary retinal degener­ation, and none showed a pathogenic genetic mutation. Findings on fundus autofluorescence imaging were quite prominent, yet the fundus exam re­vealed only subtle paracentral hyper­pigmentation at the level of the RPE, with surrounding pale yellow deposits.

Median exposure to PPS was 186 months; most patients reported trouble reading and experienced prolonged dark adaptation despite generally well-preserved visual acuity.

Clinical implications. “PPS-asso­ciated maculopathy has a permanent spot on our differential diagnosis for atypical pigmentary maculopathies,” said lead author William Pearce, MD, at the Georgia Eye Institute in Savan­nah. “It is important that clinicians are aware of this association when evalu­ating patients with macular dystrophy or degeneration, as it could easily be overlooked due to the subtle findings.”

Looking ahead. Dr. Jain stressed that causality must be confirmed. Neverthe­less, he advises his affected patients to stop taking PPS. Should a cause and ef­fect be determined, was there anything about the drug-approval process that could have prevented this? “Probably not, given that these patients were on the drug for years before manifesting visual symptoms,” said Dr. Jain. “On the other hand, as pharmaceuticals become increasingly complex, we should rec­ognize the vital role that clinicians play in the postmarket surveillance of novel therapies.”

—Miriam Karmel

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1 Pearce WA et al. Ophthalmology. 2018;125(11):1793-1802.

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Relevant financial disclosures—Drs. Jain and Pearce: None.

For full disclosures and the disclosure key, see below.

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