| Many patients taking hydroxychloroquine (Plaquenil
®) for systemic lupus erythematosis, rheumatoid arthritis
and other inflammatory or dermatological conditions are referred
to us for monitoring. Concern for retinal toxicity, known to
occasionally occur with such treatment, prompts these referrals.
Without established criteria of toxicity prior to a stage when
some permanent vision loss is likely, interval monitoring is
aimed at early detection rather than prevention. It is understood
that the selection of hydroxychloroquine therapy itself is based
upon significant quality-of-life issues where the relative risks
and benefits of alternative therapies have been weighed. A document
circulated by the American Academy of Ophthalmology1 (Ophthalmology,
July 2002) emphasizes its current recommendations regarding
individuals treated with hydroxychloroquine. The mechanism
of hydroxychloroquine toxicity is poorly understood. While
hydroxychloroquine is metabolized by the liver and excreted
in the urine, slow and chronic damage to the eye’s retinal
photoreceptor cells may result from binding of the drug to
melanin pigment in the underlying retinal pigment epithelium.
Affinity for the center of the retina (macula) suggests also
a possible role of photo-interaction or other peculiarities
of cone metabolism in the macula (fig. 1). The end result
is so-called “bull’s eye” maculopathy, a
characteristic bilateral annular pattern of depigmentation
of the retinal pigment epithelium surrounding the macula.
Observant patients may report a relative blurred area near
the center of their vision (para-central scotoma), but more
often early symptoms are either disregarded or lacking. Once
paracentral scotomas and/or detectable bull’s eye maculopathy
develops, stoppage of the drug is not likely to be followed
by significant visual recovery. In fact, further deterioration
may continue for months and even years, perhaps due to melanin
binding. If drug exposure continues, retinal pigment epithelial
atrophy and functional consequences become more wide spread.
Most reports of hydroxychloroquine toxicity have occurred
when daily dosing exceeds 6.5 mg/kg (as might be the case
when a very slight built patient takes two 200mg tablets per
day, or in anyone taking more than two tablets daily) or in
patients where duration of treatment exceeds five years. Within
these limits, the incidence of toxicity is reported to be
exceedingly low. Regular monitoring of macular health in patients
treated with hydroxychloroquine is the accepted standard of
care.
In accordance with the American Academy of Ophthalmology
advisory, the following are our current clinical practice
recommendations:
- At the beginning of hydroxychloroquine treatment, a thorough
baseline evaluation including medical history, determination
of hydroxychloroquine dosage relative to lean body weight,
dilated ophthalmoscopy to determine the health of the retina,
fundus photography, color vision testing, visual fields
testing, Amsler grid testing (fig. 2), along with risk assessment
and counseling.
- For patients deemed to be “low-risk” (daily
dosage less than 6.5 mg / kg with no other potentially complicating
factors), during the first five years of therapy re-evaluation
at a minimum interval of one year.
- For patients at “higher risk” (daily dosage
greater than 6.5 mg / kg, pre-existing retinal disease,
hepato/renal disease, or greater than five years duration
of therapy), minimum six month interval re-evaluations.
Back to Publications
|
