Hydroxychloroquine, sold under the brand name Plaquenil, is a medication prescribed for certain autoimmune conditions. It is a disease-modifying antirheumatic drug (DMARD) that decreases the underlying inflammation caused by the immune system attacking its own tissues. This action reduces pain and swelling associated with arthritis and can prevent long-term joint damage.
Originally developed to treat malaria, hydroxychloroquine was later found effective for systemic lupus erythematosus and rheumatoid arthritis. While its precise mechanism is not fully understood, it is believed to interfere with the immune system’s communication pathways to control disease activity. Patients may notice improvement in one to two months, with full benefits taking up to six months to appear.
The Connection to Retinal Toxicity
Long-term use of hydroxychloroquine can lead to a condition called hydroxychloroquine retinopathy, which involves damage to the retina. The retina is the layer of tissue at the back of the eye that is sensitive to light. This toxicity is concentrated in the macula, the central part of the retina responsible for sharp, detailed vision used for reading and recognizing faces.
The damage is related to the drug’s interaction with cells in the retina. Hydroxychloroquine has a high affinity for melanin, a pigment in the retinal pigment epithelium (RPE), which nourishes the retina. The drug binds to this melanin and accumulates in RPE cells over time, and this buildup is thought to be toxic, leading to the breakdown of both RPE and photoreceptor cells.
As toxicity progresses, it can result in bull’s-eye maculopathy. This term describes a ring of damaged tissue surrounding a relatively spared central macula. This pattern is a classic sign of advanced retinal damage.
Identifying High-Risk Patients
Several factors can increase a patient’s likelihood of developing hydroxychloroquine retinopathy, making close monitoring important for certain individuals. These factors include:
- The daily dose of the medication, with risk being lower when the dose is kept at or below 5 milligrams per kilogram (mg/kg) of real body weight.
- The duration of treatment, as the risk is low within the first five to seven years but rises substantially with cumulative exposure.
- Impaired kidney function, as the kidneys are responsible for clearing the drug from the body and reduced function can lead to accumulation.
- The presence of a pre-existing retinal or macular disease, which makes an individual more vulnerable to the drug’s effects.
- Concurrent use of the drug tamoxifen, which carries its own risk of retinal toxicity that can be amplified when taken with hydroxychloroquine.
Screening and Monitoring Protocols
To ensure safe use, specific screening protocols are recommended to detect retinal toxicity at its earliest stages. The American Academy of Ophthalmology guidelines begin with a baseline eye examination within the first year of starting the medication. This initial exam establishes a record of the patient’s healthy retina and rules out pre-existing conditions that might increase risk.
Following the baseline evaluation, annual screenings are advised but typically do not begin until after five years of continuous drug use. This timeline is based on the low risk of toxicity during the initial years. For patients with major risk factors, such as kidney disease or concurrent use of tamoxifen, screenings may be initiated sooner.
Modern screening relies on advanced tests that can detect subtle changes long before a patient would notice vision problems. One primary tool is Optical Coherence Tomography (OCT), a non-invasive test that uses light waves to take cross-section pictures of the retina to identify early damage. Another standard test is the Humphrey Visual Field (HVF) test, which maps out any blind spots (scotomas) that can be an early indicator of toxicity.
Symptoms and Management of Damage
Hydroxychloroquine retinopathy is asymptomatic in its early stages. A person can have detectable retinal changes without experiencing any noticeable difference in their vision, which is why regular screening is necessary to detect damage before it affects sight.
When the condition progresses, patients may begin to experience a range of symptoms. These can include a blurring of their central vision, making activities like reading or driving difficult. Some individuals report the appearance of blind spots, or scotomas, near the center of their vision, along with difficulty seeing in low light and changes in color perception.
If definitive signs of retinal toxicity are confirmed, the standard management protocol is to discontinue the medication. This decision is made in consultation between the patient, their ophthalmologist, and the prescribing physician. The prescribing doctor will transition the patient to an alternative medication to continue managing their autoimmune condition.
The retinal damage caused by hydroxychloroquine is considered irreversible, and vision loss cannot be restored. Stopping the drug is effective at halting further progression of the damage and is the primary step to preserve remaining vision.