Impact of Systemic Medications on Retinal Function

Impact of Systemic

Medications on Retinal Function by Khor Hui-Min

Systemic medications can cause a ripple effect of unwanted retinal toxicity.

Ocular side effects of systemic drugs include abnormal and/ or blurred vision, poor focusing ability, dry or irritated eyes, color perception changes and altered pupil size. The reaction, and its severity, depends on the amount of drug administered, the nature of the drug and the route of administration, as well as pathophysiologic variables, age and gender, drug interactions in multiple drug therapy, and allergies to drugs.

The retinal pigment epithelium (RPE) is a likely target for systemically administered compounds, since the underlying choroid is highly vascularized. The specialized pigment epithelium has numerous functions that all maintain the integrity and function of photoreceptors. Consequently, said the experts, toxic effects on the pigment epithelium will eventually affect the neural retina. During a symposium on the “Impact of Systemic Medications on Retinal Function” at the 13th Asia-Pacific Vitreo-retina Society Congress (APVRS 2019) held last November in Shanghai, China, various esteemed researchers presented their latest findings and techniques.

Dr. Elliott Sohn, associate professor and director of surgical and medical retina fellowships at the University of Iowa, U.S., spoke on the disruption of the pigment epithelium from drugs like thioridazine (an antipsychotic drug), dideoxyinosine (an HIV treatment) and deferoxamine (a commonly used ironchelating agent to treat transfusionrelated hemosiderosis).

On the retinal toxicity of systemic and topical medications, delegates heard that thioridazine, a piperidine antipsychotic drug that previously was widely used to treat schizophrenia and psychosis, can cause acute toxicity in high doses, producing symptoms such as blurred vision, dyschromatopsia (reddish or brownish discoloration of vision) and nyctalopia. On the other hand, retinal changes (including retinal depigmentation) have been reported in patients receiving dideoxyinosine; related systemic toxicities of deferoxamine include sight-threatening ocular toxicity involving the RPE.

Dr. William F. Mieler from the University of Illinois, U.S., discussed chloroquine and hydroxychloroquine. Chloroquine is used for the prevention and treatment of malaria and amoebiasis; while hydroxychloroquine, a less toxic metabolite of chloroquine, is used as treatment for rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and

Sjogren’s syndrome. Both can cause retinopathy, but the effects are seen in hydroxychloroquine much less frequently, and without crossing the blood-retinal barrier. High dose and long duration of treatment are the greatest risk factors for toxicity, and the primary screening tools are automated perimetry and SD-OCT. Toxicity is not reversible, thus prevention is the key.

Dr. Mieler also talked about pentosan polysulfate sodium (PPS), a semisynthetic polysulfated xylan used in the prevention and treatment of thrombi, as a novel therapy in the treatment and management of mucopolysaccharidoses, as well as treatment of interstitial cystitis or nephritis.

“The potential side effects of using PPS are visual impairment, as well as macular pigment mottling and excrescences on Bruch’s membrane. The long-term effects are not yet fully known, although progressive atrophy has been documented,” said Dr. Mieler.

Further, Dr. Mieler also presented on chemotherapeutics, mitogen-activated protein kinases (MEK) and checkpoint inhibitors. For checkpoint inhibitors, side effects typically occur within a few weeks to a few months after initiating treatment and can usually be managed with topical or systemic corticosteroids.

Dr. Shibo Tang, vice president of the Aier Eye Hospital Group, China, discussed cystoid macular edema (CME), which affects the central retina or macula. Although painless, this condition leads to the formation of multiple cyst-like (cystoid) areas of fluid in the macula and causes retinal swelling (edema).

Dr. Joo Yong Lee from the Asan Medical Center, University of Ulsan College of Medicine in Seoul, Korea, spoke on vascular occlusion caused by quinine sulfate, cisplatin/BCNU (carmustine), interferon, oral contraceptives, ergot alkaloids, gemcitabine and antibiotics (vancomycin, aminoglycosine). He also spoke on retinal adverse events caused by anti-cancer agents.

“Retinal specialists should always consider the possibility that retinal problems are associated with systemic medications. Since there is no consensus on routine ophthalmologic monitoring after systemic medication, prompt consultation with a retinal specialist can lead to early detection, proper diagnosis and appropriate treatment,” explained Dr. Lee.

Prof. Dr. Young Hee Yoon, also from the Asan Medical Center, discussed crystalline deposition: “In addition to morphological changes of tamoxifen retinopathy on SD-OCT, its vascular changes on OCT, such as telangiectatic vascular change at the deep capillary plexus and right-angled vessels, are similar to those observed in the early stages of MacTel2.”

“These findings suggest that the target Müller cell dysfunction could be a potential therapeutic strategy in the management of tamoxifen retinopathy,” said Prof. Dr. Yoon.

In conclusion, Dr. Mieler advised delegates that there are thousands of therapeutic medications available on the market, but relatively few cause retinal complications. “Therefore it is important to recognize the usual patterns of toxicity, and be alert for possible new associations in the future,” he said.

Editor’s Note:

The 13 th Asia-Pacific Vitreo-retina Society Congress (APVRS 2019) was held in Shanghai, China, on

November 22-24, 2019. Media MICE Pte Ltd, PIE magazine’s parent company was the Official Media Partner at APVRS 2019. Reporting for this story also took place at APVRS 2019.