Drug-induced uveitis
Journal of Ophthalmic Inflammation and Infection
Drug-induced uveitis
Nikolas JS London 2
Sunir J Garg 0
Ramana S Moorthy 1 5
Emmett T Cunningham Jr 3 4
0 MidAtlantic Retina, The Retina Service of Wills Eye Institute, Thomas Jefferson University , 840 Walnut Street, Suite 1020, Philadelphia, PA 19107 , USA
1 Associated Vitreoretinal and Uveitis Consultants, St. Vincent Hospital and Health Services , Indianapolis, IN 46260 , USA
2 Retina Consultants San Diego , 9850 Genesee Avenue, Suite 700, La Jolla, CA 92037 , USA
3 Department of Ophthalmology, Stanford University School of Medicine , Stanford, CA 94305-5101 , USA
4 Department of Ophthalmology, California Pacific Medical Center , San Francisco, CA 94115 , USA
5 Associate Clinical Professor of Ophthalmology, Indiana University School of Medicine , Indianapolis, IN 46202 , USA
A number of medications have been associated with uveitis. This review highlights both well-established and recently reported systemic, topical, intraocular, and vaccine-associated causes of drug-induced uveitis, and assigns a quantitative score to each medication based upon criteria originally described by Naranjo and associates.
Review
Introduction
Although most cases of uveitis are due to autoimmune
disorders or infections, medications are recognized as an
increasingly important cause of uveitis. A number of
medications encompassing various forms of
administration, including topical formulations, periocular and
intraocular injections, and systemic medications, have
been associated with uveitis. The recent availability of
treatments for neovascular diseases of the retina and
choroid with anti-vascular endothelial growth factor
(anti-VEGF) agents has increased the prevalence and
recognition of drug-induced uveitis. The mechanism(s)
underlying drug-induced uveitis are generally unclear,
although both inflammatory and toxic reactions have been
suggested to play a role [
1-3
]. As such, for each agent
summarized below, we only discuss the mechanism of
drug-induced uveitis when specific studies have provided
additional insight. This review highlights both
wellestablished and recently reported systemic, topical,
intraocular, and vaccine-associated causes of drug-induced
uveitis. Although many drugs have been reported as
causing uveitis, only those drugs with multiple
independent publications to help confirm causation were
further ranked. Using an algorithm originally proposed by
Naranjo and associates, we quantitatively describe the
association of various drugs to uveitis as ‘definite,’
‘probable,’ ‘possible,’ and ‘doubtful’ (Table 1) [
4
]. Naranjo
scores of 9 or higher imply a definite association, scores
of 5 to 8 a probable association, scores of 1 to 4 a
possible association, and scores of 0 make an association
doubtful. Table 2 lists the drugs most strongly associated
with uveitis. Table 3 provides a list of those reviewed in
the current paper and their likelihood of causing uveitis
based on the Naranjo scoring system. In addition, the
likelihood of causation per the Naranjo criteria is listed
in parentheses next to the name of the medication in each
subsection. Current updates regarding specific agents may
be found at www.eyedrugregistry.com.
Systemic medications
Cidofovir (Naranjo score 11, definite)
Cidofovir is an infrequently administered antiviral
medication initially utilized for the treatment of
cytomegalovirus (CMV) retinitis in patients with profound immune
suppression due to human immunodeficiency virus (HIV)/
acquired immune deficiency syndrome (AIDS). It
selectively inhibits viral DNA polymerase, preventing virus
replication. Cidofovir can be administered intravenously or
directly into the vitreous cavity through an intravitreal
injection. The efficacy of intravenous cidofovir for the
treatment of previously untreated CMV retinitis in patients
with HIV/AIDS has been demonstrated in a multicenter
randomized trial and in a dose-ranging study of cidofovir
in patients with HIV/AIDS and previously treated relapsing
CMV retinitis [
5,6
].
Compared to other treatments for CMV retinitis,
cidofovir has several advantages, including a long intracellular
half-life [
7
]. However, it is rarely used today due to several
important side effects, the most serious of which is
potentially irreversible nephrotoxicity. In addition, cidofovir has
been shown to induce a non-granulomatous anterior uveitis
in 17% to 89% of cases and hypotony in approximately 10%
of cases [
8-14
]. These side effects occurred more frequently
if patients received concomitant protease inhibitors, were
previously treated for CMV retinitis, had chronic or
recurrent retinitis, or had immune recovery [
13
].
Cidofovir2. Did the adverse event appear after the suspected drug was administered?
3. Did the adverse reaction improve when the drug was discontinued or a specific antagonist
was administered?
4. Did the adverse reaction reappear when the drug was readministered?
5. Are there alternative ca (...truncated)