January-February 2020

IN FOCUS

What your patient is taking and its effect on the eye
Drugs patients are taking and their impact on the retina, optic nerve


by Ellen Stodola Editorial Co-Director




A 56-year-old female with lupus had been taking
hydroxychloroquine for more than 30 years without retinal surveillance. Spectral domain optical coherence tomography revealed bilateral parafoveal atrophy of the ellipsoid zone and outer retina. Note sparing of the central fovea, which allowed the patient to maintain 20/20 visual acuity.
Source: Christina Weng, MD




Fundus autofluorescence illustrates the “bullseye” parafoveal ring of hyper-autofluorescence thought to represent photoreceptor damage preceding significant retinal pigment epithelium degeneration.
Source: Christina Weng, MD

Some patients take a variety of medications, and it’s important for ophthalmologists to know what medications patients are on and how they might affect the eye. Christina Weng, MD, Pravin Dugel, MD, and Robert Noecker, MD, highlighted some of the medications that may affect the retina and optic nerve, what to look for, and how to handle these patients.

Hydroxychloroquine

One of the most common of these medications is hydroxychloroquine, Dr. Weng said. This is primarily used to treat autoimmune diseases, like rheumatoid arthritis and lupus, but it can have a negative effect on the outer retina, particularly the photoreceptor ellipsoid zone, as well as the retina pigment epithelium (RPE). The RPE is a common place where a lot of these toxicities occur, she said.
Hydroxychloroquine-induced retinal toxicity typically manifests in a slow, progressive manner, Dr. Weng said, adding that this drug probably has the most data on associated toxicity. “We try to follow formal screening guidelines, though most patients don’t have toxicity during the initial period using this medication,” she added. It’s thought that less than 1% of patients have toxicity at 5 years, but if you look after 20 years, up to 20% will have some degree of toxicity, which is why screening is so important.
Hydroxychloroquine causes irreversible toxicity in the macula and retina, Dr. Noecker said, so the ophthalmologist’s job is to establish a baseline and monitor the patients moving forward. The incidence of toxicity is low, he said, but it does correspond to the dose that patients take and how many years they’ve been taking it. “There’s no magic cutoff,” he said. “But the longer they’re taking it and the higher the dose, the higher the risk.” Dr. Noecker said it’s a good idea to watch these patients every 6 months or so, taking photos for comparison.
He said to look for characteristic changes in the macula. Frequently, the earliest changes are the functional findings, like visual field or electrophysiology, but it can be subtle, he said.
“We usually recommend before patients start the drug that the rheumatologist send them to us for a baseline examination, and we’ll dilate the eyes and take a look to see if there’s any changes in the eye,” Dr. Weng said. At this point, she said it’s particularly important to look for macular degeneration.
In addition to visual fields, spectral-domain OCT is important as well. That’s where you’ll first see the atrophy of the ellipsoid zone, often before there are any visible findings on fundus examination and hopefully before the RPE is involved, she said. When it is involved, the prognosis gets more grim. OCT is wonderful for detecting this, according to Dr. Weng. She also recommends fundus autofluorescence or a multifocal ERG, if available, which can help draw out subtle abnormalities in patients with early disease.
There have been reports that even after discontinuing the medication, patients can continue to have progression for some time, Dr. Weng said. Thus, even after patients stop the medication, they need to keep following up. Patients may notice a central or paracentral scotoma, Dr. Weng added, and on OCT you’re looking for parafoveal outer retinal changes. Most patients don’t recognize anything in the earlier stages, so physicians will most likely see the changes on these tests before patients start complaining of symptoms.
If a patient starts to exhibit signs of toxicity, Dr. Weng recommends working with the patient’s rheumatologist to seek an acceptable alternative medication to avoid further potential long-term effects.
Dr. Dugel agreed that hydroxychloroquine is the most common drug ophthalmologists need to screen for. It turns up as a classic bullseye pattern of RPE loss, Dr. Dugel said, but by the time you see it, it’s quite late and there’s some evidence that it stays behind in the RPE cells even after stopping the medication.
“We know now with the OCT that there are subtle changes to look for early on in the ellipsoid zone to allow us to identify before seeing the bullseye pattern,” he said. “What we’ll see is the ellipsoid loss that has a kind of parafoveal distribution.” The classic appearance may change a bit because toxicity may be more parafoveal in Caucasians but more peripheral in Asians. The point is that it’s important to screen patients on a regular basis with OCT and catch potential toxicity earlier, Dr. Dugel said.

Ethambutol

Another drug with the potential for ocular toxicity is ethambutol, which is used for tuberculosis treatment. It causes what is sometimes mistaken for a retinal problem, Dr. Dugel said, but it really damages the optic nerve. It’s usually bilateral and symmetric and can cause photophobia, poor dark adaptation, and color changes. For patients on this drug, Dr. Dugel suggested regular assessment. Changes may be noticed in vision, visual field, and color vision, and it may also be helpful to look at the OCT.
This can lead to a pretty severe optic neuropathy, Dr. Weng said. While there are no formal screening guidelines, patients will generally have toxicity appear 4–12 months after starting the medication. As such, many physicians bring patients in monthly during the first year.
There have been reports of toxic effects being reversible, if detected early enough, Dr. Weng said, so time is of the essence in these cases. She added that this drug isn’t often used long term.

Pentosan

Pentosan is another potentially toxic drug, used to treat bladder issues such as interstitial cystitis. It was only recently learned that pentosan can cause pigmentary maculopathy, Dr. Weng said, which can cause damage to the outer retina and RPE.
This was found incidentally by an ophthalmologist, Nieraj Jain, MD, who noticed that there was something that looked similar to macular degeneration and identified this drug as the common thread. This is a maculopathy that is located in the central macula, which is unfortunate, Dr. Weng said, because that’s the area most responsible for central and sharp vision.
This toxicity can closely mimic macular degeneration or geographic atrophy, she said, so many of these patients potentially had a previous diagnosis of macular degeneration when it could have actually represented pentosan pigmentary maculopathy.
No current screening guidelines exist, Dr. Weng said, and the full extent of damage or abnormality it can cause is unknown. She added that it’s important to work with urology colleagues as physicians learn more about this condition.
Dr. Dugel said that changes may look like dry macular degeneration and patients may be misdiagnosed. Patients with this type of maculopathy are often younger (40s and 50s), so if the patient is on pentosan, they should be looked at.

Other drugs

Dr. Dugel mentioned the possible toxicity of drugs used for cancer, specifically several used to treat breast cancer.
Additionally, he mentioned MEK inhibitors and immune checkpoint inhibitors. MEK inhibitors can disrupt the outer blood retinal barrier and cause fluid to accumulate in the subretinal space, he said. If you stop the medication, the fluid usually resolves.
However, a lot of cancer drugs are being used in patients with advanced disease, so it may not be possible to stop them, he added.
Meanwhile, immune checkpoint inhibitors target the tumor by increasing T-cell function. The T-cells attack the tumors but can also trigger uveitis. Additionally, Dr. Dugel said these can cause VKH-like conditions, which can cause multiple subretinal fluid accumulations and RPE detachments.
Dr. Noecker mentioned drugs that alter blood flow as potentially problematic.
For example, anti-impotence drugs can change the circulation and may cause a drop in circulation around the eye. In those cases, you worry about dropping the blood supply too much to the optic nerve or parts of the retina. This could potentially cause vein occlusion in the retina. There are often symptomatic changes in the vision, which may be transient, Dr. Noecker said.
Additionally, blood pressure medications may be something to look out for, Dr. Noecker said, as these may impact the optic nerve and good circulation of the retina. In glaucoma, physicians are worried about drugs that drop diastolic pressure too low, he said.

At a glance

• It’s important to pay attention to the medications your patients are taking; some are toxic to the retina or optic nerve and may have irreversible effects.
• Hydroxychloroquine is a common medication but may not show toxic effects until after many years of use. It’s important to monitor these patients and co-manage with the prescribing doctor.
• Some of the toxic effects and signs of drugs like ethambutol and pentosan can mimic other retinal issues, so it’s important to keep a close eye on medications that patients are taking.

About the doctors

Christina Weng, MD

Baylor College of Medicine
Houston, Texas

Pravin Dugel, MD
Retinal Consultants of Arizona
Phoenix, Arizona

Robert Noecker, MD
Ophthalmic Consultants
of Connecticut
Fairfield, Connecticut

Relevant disclosures

Dugel: None
Noecker: None
Weng: None

Contact

Dugel: pdugel@gmail.com
Noecker: noeckerrj@gmail.com
Weng: Christina.Weng@bcm.edu

Drugs patients are taking and their impact on the retina, optic nerve Drugs patients are taking and their impact on the retina, optic nerve
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2020-01-13T13:54:48Z
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