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Corresponding author: Carsten
H. Meyer, MD, Department of Ophthalmology, Philipps University–
Marburg, Robert-Koch-Strasse 4,
35037 Marburg, Germany (e-mail:
[email protected]).
1. Rosai J, Dorfman RF. Sinus histiocytosis with
massive lymphadenopathy: a newly recognized
benign clinicopathological entity. Arch Pathol.
1968;87:63-70.
2. Foucar E, Rosai J, Dorfman RF. The ophthalmic manifestations of sinus histiocytosis with
massive lymphadenopathy. Am J Ophthalmol.
1979;87:354-367.
3. Lee-Wing M, Oryschak A, Attariwala G, Ashenhust M. Rosai-Dorfman disease presenting as bilateral lacrimal gland enlargement. Am J Ophthalmol. 2001;131:677-678.
4. Pivetti-Pezzi P, Colabelli-Gisoldi RA, Vitale A,
Baccari A, Pacchiarotti A. Relapsing bilateral uveitis and papilledema in sinus histiocytosis with
massive lymphadenopathy (Rosai-Dorfman
disease). Eur J Ophthalmol. 1995;5:59-62.
5. Silvestre JF, Aliaga A. Cutaneous histiocytosis
and chronic uveitis. Pediatr Dermatol. 2000;17:
377-380.
Voriconazole Treatment
of Fungal Scleritis and
Epibulbar Abscess
Resulting From Scleral
Buckle Infection
Fungal infections, both ocular and
systemic, can be difficult to treat.
Challenges include the difficulty of
diagnosis, possibly diminished host
immune response, drug resistance of
organisms, the difficulty of drug penetration, and the limited number of
antifungal agents.
Voriconazole (Vfend; Pfizer
Pharmaceuticals, New York, NY) is
a new triazole antifungal agent; potent and wide-ranging activity has
been demonstrated in vitro and in
clinical studies.1-6 In May 2002, oral
and intravenous formulations of
voriconazole were approved by the
US Food and Drug Administration
for primary treatment of acute invasive aspergillosis and for salvage
therapy for infections caused by Scedosporium apiospermum and Fusarium species. As with other azole
compounds, the primary mode of action of voriconazole is the inhibition of cytochrome P-450–mediated 14-␣-lanosterol demethylation,
which is an essential step in fungal
ergosterol biosynthesis.5
Based on a MEDLINE search, we
believe that this is the first case report of refractory fungal scleritis with
a nodular epibulbar abscess due to
scleral buckle infection that was successfully treated with voriconazole,
and the first report of intraocular concentration of voriconazole in a human following oral administration.
Report of a Case. A 65-year-old
immunocompetent woman sought
treatment for a hyperemic and tender left eye associated with an inferonasal epibulbar nodule. According to the patient, the nodule began
“like a pimple” but gradually grew
during the preceding 2 months.
During the past year, the patient
had undergone 3 procedures at another facility for recurrent retinal
detachments, including pars plana vitrectomy and a scleral buckling procedure. She had been given subconjunctival methylprednisolone acetate
at the conclusion of each operation,
and postoperative topical prednisolone acetate was continued for 2 to
3 months each time. On examination, visual acuity was hand motions OS. She was aphakic, and the
retina was attached, with areas of pre-
retinal fibrosis and chorioretinal scarring. Areas of peripheral scleral thinning were noted. The nodule was
only minimally mobile and slightly
tender, but the inferonasal sclera was
particularly tender and erythematous (Figure 1).
Surgical exploration revealed
that the nodule was an abscess. The
scleral buckle was initially not disturbed because of significant necrosis of the sclera and the risk of globe
rupture. Cultures yielded Aspergillus fumigatus, and topical 0.15% amphotericin B and oral ketoconazole
were initiated. After a lack of clinical response to a 4-week course of
therapy, itraconazole was substituted for ketoconazole in hopes of
improving intraocular penetration.
A continued lack of clinical improvement led to uncomplicated scleral
buckle removal 1 month later. During the next 4 months, despite multiple debridements and continued
use of topical amphotericin B and
oral itraconazole, the infection continued to spread counterclockwise
around the eye (Figure 2). After
learning of the investigational use of
voriconazole, we obtained institutional review board approval of voriconazole use on a compassionate basis. Other antifungal agents were
discontinued, and treatment with
oral voriconazole, 200 mg twice a
day, was begun. After 1 week of
treatment, ocular tenderness and
left-sided headache disappeared.
Redness of the eye improved during the next 3 months (Figure 3).
During the second month of
therapy, simultaneously acquired serum and intraocular fluid samples
were assayed for trough concentra-
Figure 1. The patient’s left eye at the initial examination shows an inferonasal epibulbar mass and hypertropia due to mass effect.
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Figure 2. After 6 months of conventional therapy and just prior to initiation of voriconazole therapy, infection has spread superiorly.
Figure 3. One month after initiation of voriconazole therapy, erythema and ocular tenderness have diminished.
Figure 4. One year after discontinuation of voriconazole therapy, the eye shows no evidence of recurrence, and the patient has undergone uncomplicated
secondary intraocular lens placement.
tion of voriconazole by Pfizer Central Research (Kent, England). The
serum concentration was 1.619 µg/
mL, and the intraocular concentration was 0.865 µg/mL. Voriconazole was discontinued after 4
months of treatment, when the eye
appeared to have fully recovered
from the fungal infection. During
24 months of follow-up, there was
no evidence of recurrence, and the
patient underwent uncomplicated
secondary intraocular lens implantation (Figure 4). She noted that
her onychomycosis had also improved markedly while she was
taking voriconazole.
Comment. The first report of the efficacy of voriconazole in the treatment of a human ocular fungal infection described a case of ulcerative
(REPRINTED) ARCH OPHTHALMOL / VOL 121, MAY 2003
736
keratitis caused by Fusarium solani.7
In that report, successful treatment required intravenous, oral, intracameral, and topical routes with voriconazole. All routes of administration were
well tolerated by the patient. In our
patient, oral treatment alone was effective, despite the usual difficulty in
treating scleritis with oral agents because of the relatively avascular nature of sclera. Intraocular concentra-
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tion of voriconazole was above the
MIC90 (minimum inhibitory concentration) of 0.5 µg/mL for A fumigatus reported in various studies.1-3,5
Voriconazole also has been shown to
be effective for endogenous Fusarium endophthalmitis8 and Paecilomyces lilacinus endophthalmitis.9
In larger clinical studies of systemic fungal diseases, the most commonly reported adverse effects of
voriconazole were transient visual
disturbances, including brightness,
blurring, light sensitivity, or altered
color perception.4-6 These visual abnormalities were reported in approximately 30% of patients receiving voriconazole, typically began 30 minutes
after dosing, and lasted about 30 minutes. Other adverse effects included
elevated liver enzyme levels and facial erythema.5,6
The ability to achieve effective
intraocular drug concentrations with
oral administration, the broad spectrum of antifungal activity, and the
relatively low level of systemic adverse effects suggest that voriconazole may have a wider role in the future for treatment of ocular fungal
infections.
Judy E. Kim, MD
Stephen L. Perkins, MD
Gerald J. Harris, MD
Milwaukee, Wis
The authors have no relevant financial interest in this article.
This study was supported in part
by unrestricted grant from Research to
Prevent Blindness, Inc, New York, NY.
This study was presented in part
as a poster at the Annual Meeting of
the Association for Research in Vision and Ophthalmology, Ft Lauderdale, Fla, May 6, 2002.
Corresponding author: Judy E.
Kim, MD, Department of Ophthalmology, Medical College of Wisconsin,
925 N 87th St, Milwaukee, WI 53226
(e-mail: [email protected]).
4.
5.
6.
7.
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9.
photericin B against filamentous fungi. J Antimicrob Chemother. 1998;42:741-745.
Ghannoum MA, Kuhn DM. Voriconazole: better chances for patients with invasive mycosis.
Eur J Med Res. 2002;7:242-256.
Denning DW, Ribaud P, Milpied N, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect
Dis. 2002;34:563-571.
Walsh TJ, Pappas P, Winston DJ, et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever.
N Engl J Med. 2002;346:225-234.
Reis A, Sundmacher R, Tintelnot K, Agostini H,
Jensen HE, Althaus C. Successful treatment of
ocular invasive mould infection (fusariosis) with
the new antifungal agent voriconazole. Br J Ophthalmol. 2000;84:932-933.
Borkowski LM, Lyon AT, Jampol LM, Weinberg DV. Endogenous Fusarium endophthalmitis [ARVO abstract]. Invest Ophthal Vis Sci. 2000;
41:S353.
Garbino J, Ondrusova A, Baligvo E, Lew D, Bouchuiguir-Wafa K, Rhoner P. Successful treatment of Paecilomyces lilacinus endophthalmitis
with voriconazole. Scand J Infect Dis. 2002;34:
701-703.
1. Murphy M, Bernard EM, Ishimaru T, Armstrong D. Activity of voriconazole (UK109,496) against clinical isolates of Aspergillus
species and its effectiveness in an experimental model of invasive pulmonary aspergillosis.
Antimicrob Agents Chemother. 1997;41:696698.
2. McGinnis MR, Pasarell L, Sutton DA, et al. In
vitro evaluation of voriconazole against some
clinically important fungi. Antimicrob Agents Chemother. 1997;41:1832-1834.
3. Johnson EM, Szekely A, Warnock DW. In vitro
activity of voriconazole, itraconazole, and am-
Correction
Author’s Name Misspelled. In the article titled “Pathogenesis of the Vitreous
Cloud Emanating From Subretinal Hemorrhage,” published in the January
issue of the ARCHIVES (2003;121:91-96), Dr Steven McCormick’s name was
misspelled in the byline and the affiliation footnote on page 91. The journal
regrets the error.
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