Choriocapillaris Flow Deficits May Predict Pentosan Polysulfate Sodium Toxicity

Pentosan polysulfate sodium (PPS) use may result in a choriocapillaris flow deficit (CC FD) prior to the presentation of macular toxicity, according to research published in the American Journal of Ophthalmology.

Researchers enrolled 15 patients treated with PPS (mean age, 58.9±10.4 years; 100% women) and 15 age-matched controls (mean age, 59.8±11 years; 40% women) in a retrospective, clinical cohort analysis to compare CC FD between individuals treated with a high dose of PPS (cumulative dose, 1974±666 g; 17.6±6.8 treatment years) and healthy controls. Patients underwent optical coherence tomography angiography (OCTA), fundus autofluorescence (FAF), and visual acuity assessment. Patients treated with PPS were screened with multimodal imaging to rule out PPS maculopathy. 

All participants had a visual acuity of 20/25 or better and normal OCTA, FAF, multicolor, near-infrared reflectance (NIR) and ultra-widefield fundus color and autofluorescence images.

Compared with age-matched controls, individuals who received PPS exhibited choriocapillaris flow impairment before showing toxicity on OCT, FAF, and near infrared reflectance. Overall, CC FD% was 32.7±3.6% in patients treated with PPS compared with 28.6±4.3% in control individuals (P =.023). This finding suggests that the choriocapillaris could be the first structure to show signs of ocular toxicity, according to the report.  

“Earlier detection of PPS macular toxicity is essential given the recent reports of progressive maculopathy, even with discontinuation of the drug,” according to the researchers. “En face OCTA analysis of CC-FD% has proven to be an innovative tool to assess the choroid in [age-related macular degeneration] and may even predict the development of geographic atrophy.”

Study limitations include a small sample size, retroscopic nature, and failure to sex-match the study and control groups.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Levin MF, Santina A, Corradetti G, et al. Pentosan polysulfate sodium-associated maculopathy: early detection using OCT angiography and choriocapillaris flow deficit analysis. Am J Ophthalmol. Published online July 24, 2022. doi:10.1016/j.ajo.2022.07.015