Diseases and Conditions

Will hydroxychloroquine hurt my eyes?

May 24, 2017
Will hydroxychloroquine damage my eyes?

I love hydroxychloroquine.  Honestly, I really do.  It’s simple, easy, it works, and for the most part it’s benign especially when compared to the rest of the medications I prescribe.  Rheumatologists use hydroxychloroquine (Plaquenil) to treat of lupus, mild cases of rheumatoid arthritis, and many other autoimmune diseases.

Now I said benign.  Well I actually said, “for the most part it’s benign”.  Allergic reactions are always a concern but the main concern I have with hydroxychloroquine is the possibility of developing eye toxicity.  More specifically, hydroxychloroquine maculopathy.  But before I continue, I think it’s important to go through some anatomy.

Anatomy of the Eye

The following is a simplified version of the human eye.  The cornea is the clear part of the eye that lets you focus light into your eye.  The iris regulates the amount of light you let into your eye.  The pupil is the dark part of the eye.  This is where light actually goes into the eye.  The lens focuses light so that it hits the retina just right and the retina actually senses light.  This info is then condensed onto the optic disc and then sent to the optic nerve then into your brain.

Where does hydroxychloroquine fit in?

Now this is the important part because this is where hydroxychloroquine can cause problems: the macula.  The macula is a specialized place on your retina that has cells that enable you to see fine details with high acuity.  We call these specialized cells cones and they are found in high density in this area.  The macula is then made up of the fovea, foveal avascular zone, parafovea, and the perifovea.  The following is a real life example courtesy of Danny Hope.

By Photograph: Danny Hope from Brighton & Hove, UK Diagram: User:Zyxwv99 [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons


Now the prospect of losing the ability to see things clearly sounds absolutely terrible. I’ve been wearing glasses since I was 13.  Without them, everything is blurry.  I can’t even imagine the blow to my quality of life, if I didn’t have my glasses.  Hydroxychloroquine is kind of like that.  Your vision becomes blurry, except glasses won’t help, and the vision loss is permanent.

So why would anyone go on this medication and why would your doctor even suggest it?

Well… because it’s actually a pretty good medication.  Just like most medications, you need to take it as safely as possible.  The American Academy of Ophthalmology released a statement last year about monitoring hydroxychloroquine.  Let’s go over these recommendations together!

Recommendations on Screening for Hydroxychloroquine Retinopathy (2016 Revision)

First of all, it’s still unclear how exactly hydroxychloroquine causes eye toxicity.  In a nutshell the outer layer of the retina gets damaged and then it deepens and spreads around the fovea.  People tend not to notice anything at this stage. Over time, if the medication is not stopped, the fovea becomes involved and visual acuity drops.  It’s also important to note that hydroxychloroquine can worsen even after stopping the medication.  If it’s caught early on, it probably won’t affect vision.  If there already was a lot of damage to begin with, then the risk is higher.  So the real question is what is the real risk of developing toxicity, what are the factors that increase that risk, and how often should you get screened by an ophthalmologist?

What is the real risk of developing hydroxychloroquine eye toxicity?

In the past, we thought the risk of developing eye toxicity from hydroxychloroquine was very low.  New data suggests otherwise.  Although the risk is still low, we were probably underestimating the risk.  Researchers following 2,361 people using hydroxychloroquine, found that about 7.5% of those people had eye toxicity.  The most important risk factors included the daily dose of hydroxychloroquine and duration of use.

People who took 4 to 5 mg/kg/day of hydroxychloroquine had a much lower cumulative risk as compared to people you took a higher dose: 1% risk in the first 5 years and less than 2% up to 10 years.  After 20 years the risk dramatically increased to 20%.

When I mean mg/kg/day, I mean the amount of drug for every kilogram of body weight over a 24 hour period.  To calculate the dosage of hydroxychloroquine you need to use your real weight, NOT your ideal weight.  For some medications, it’s the opposite.  Let’s say you were taking hydroxychloroquine 200 mg twice a day and then you started dieting and exercising, and then you shed a lot of weight.  You now may need to decrease your daily dose of hydroxychloroquine because your real weight decreased.  In the study, the researchers found that thin people tended to have more eye toxicity because they tended to get more than 4 – 5 mg/kg/day of hydroxychloroquine.


FYI When calculating your body weight to verify your hydroxychloroquine dose, you need to use metric.  This is not optional.

1 kilogram = 2.2 pounds


Other Significant Risks

Initially we thought hydroxychloroquine gets stored in fat cells.  In actuality, recent lab studies show that the medication is mostly stored in melanotic tissue, liver, and in the kidneys.  Muscle, fat, and other organs not so much.  That being said, people with severe kidney disease are at higher risk of developing eye toxicity.  These people may need more frequent eye testing and they may not need as high of a dose.

Other significant risks includes concurrent use of tamoxifen, which is a medication commonly used to help treat breast cancer.  The researchers found that there was a 5-fold increase of toxicity in people taking tamoxifen and hydroxychloroquine.  Why?  Tamoxifen itself can affect the retina, so maybe having both on board simultaneously isn’t such a great idea.

Finally, people with macular or retinal issues, like having macular degeneration, may also be at higher risk.  There wasn’t enough results to confirm this, but it kind of makes sense.  If he retina isn’t too hot to begin with, it’ll probably be difficult for the ophthalmologist to decide whether future changes are medication-related versus disease-related, in this case macular degeneration.  Do you need to stop hydroxychloroquine?  Or do you need to start ranibizumab (i.e., a medication FDA approved for macular degeneration)?

Screening Schedule

As I mentioned before, hydroxychloroquine eye toxicity is not reversible.  Once it happens, it happens.  So the trick is to catch it early.  Fortunately, the changes occur VERY slowly.  The American Academy of Ophthalmology recommends the following:

  • Obtain a baseline eye exam within the first year of starting hydroxychloroquine to document any complicating eye problem.
  • Annual screening beginning after 5 years of use.
  • Sooner if there are major risk factors.
  • Check the dose of hydroxychloroquine based on your weight at your doctor’s appointment.
  • Inform your doctor if there’s been any significant change in your health: significant weight loss (intentional or unintentional), kidney disease, or if you’ve been prescribed tamoxifen.

Now you may wonder why your rheumatologist insists on annual eye checks even though you’ve been on hydroxychloroquine for less than 5 years.  This is probably a matter of style.  Personally, I’m one of those rheumatologists that insists on annual eye checks.  I wouldn’t feel comfortable NOT seeing my ophthalmologist if I was taking a medication that had retinal toxicity.

Screening Tests

There are many different techniques to screen for toxicity.  I won’t go into specifics because, well, I’m not an ophthalmologist.  However, here is a list of techniques that the American Academy of Ophthalmology approved to screen for hydroxychloroquine eye toxicity.

  • Automated visual fields
  • Spectral-domain optical coherence tomography
  • Multifocal electroretinogram
  • Fundus autofluorescence
  • Microperimetry – newer test, possible value in future
  • Adaptive optics retinal imaging – newer test, possible value in future

These tests are not recommended for screening

  • Fundus examination
  • Time-domain optical coherence tomography
  • Fluorescein angiography
  • Full-field electroretinogram
  • Amsler grid
  • Color testing
  • Electro-oculogram

If you have any questions about these tests, please ask you ophthalmologist.

Conclusion

Hydroxychloroquine is truly wonderful and useful medication for the treatment of multiple different types of autoimmune diseases.  Although eye toxicity is a real danger, the risk is usually small especially in the short-term.  But like I said at the beginning, like medications you need to take it safely and responsibly.  To learn more about medication safety, please read my article regarding the 10 most frequently asked questions when starting methotrexate.

Please leave your comments below!


By Jessica Chapman, M.D.

References

https://commons.wikimedia.org/wiki/File:Schematic_diagram_of_the_human_eye_en.svg

https://commons.wikimedia.org/wiki/File:Macula.svg

Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF, American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016 Jun;123(6):1386-94.

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Will hydroxychloroquine hurt my eyes?
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Will hydroxychloroquine hurt my eyes?
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Hydroxychloroquine is a medication used to treat autoimmune diseases but it can damage the eyes. Should you take this medication and how do you monitor?
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RheumDoctor
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