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Ophthalmic Drug Delivery Systems

Ophthalmic Drug Delivery Systems

Ophthalmic drug delivery faces major limitations due to poor absorption across the corneal membrane. This process is primarily driven by diffusion and is influenced by two main factors: the physicochemical properties of the drug and tear drainage. Most ophthalmic drugs, such as pilocarpine, epinephrine, atropine, and local anesthetics, are weak bases. They are typically formulated at an acidic pH to enhance chemical stability. However, this leads to high ionization, reducing their ability to...

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Pentosan Polysulfate Maculopathy Following Subcutaneous Injections for Arthritis.

Adrian T Fung^1,2,3,4, David Sarraf^5,6, Jose M Carrillo^7,8

¹Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

JAMA Ophthalmology

|December 11, 2025

Summary

This summary is machine-generated.

Pentosan polysulfate sodium (PPS) can cause retinal toxic effects even with subcutaneous administration, potentially at lower doses than oral use. Early recognition and caution are advised due to possible maculopathy progression.

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Area of Science:

Ophthalmology
Pharmacology
Toxicology

Background:

Pentosan polysulfate sodium (PPS) is associated with retinal toxic effects, primarily reported after oral administration.
The potential for retinal toxicity following subcutaneous PPS administration remains less understood.

Purpose of the Study:

To investigate and characterize the exposure, clinical presentation, and multimodal imaging findings of toxic maculopathy resulting from subcutaneous PPS administration for arthritis treatment.

Main Methods:

A multi-institutional, retrospective case series involving 3 patients with pentosan polysulfate maculopathy (PPM) after subcutaneous PPS for arthritis.
Analysis included drug dosage, visual acuity, and multimodal retinal imaging features.

Main Results:

Three patients developed PPS toxic maculopathy after subcutaneous administration for arthritis, with low cumulative doses (45.5–96 g over 7–10 years).
Multimodal imaging revealed features consistent with PPS retinal toxic effects in all cases.

Conclusions:

Subcutaneous PPS administration can lead to retinal toxic effects and maculopathy, potentially at lower doses than oral administration due to higher bioavailability.
Early detection using multimodal imaging is crucial to minimize exposure and prevent misdiagnosis. Caution is recommended due to potential maculopathy progression even after drug cessation.