TABLE I.

Prevalence and Causes of Amblyopia, Young Adult Men in Singapore

Total N 122,596

Chinese N 95,393

Malay N 18,824

Indian N 8379

Cause of Amblyopia

P*

Anisometropia
Strabismic
Meridional
Form deprivation
Combination
Others
Any amblyopia

164
24
62
9
65
104
428

0.13
0.02
0.05
0.01
0.05
0.08
0.35

129
14
46
7
52
76
324

0.14
0.01
0.05
0.01
0.05
0.08
0.34

27
3
12
2
11
15
70

0.14
0.02
0.06
0.01
0.06
0.08
0.37

8
7
4
0
2
13
34

0.09
0.08
0.05
0.00
0.02
0.16
0.41

.18
.0004
.73
.63
.29
.13
.52

*P value is based on 2 test comparing racial/ethnic groups.

Successful Treatment of Fusarium

Endophthalmitis With Voriconazole
and Aspergillus Endophthalmitis With
Voriconazole Plus Caspofungin

higher compared with Chinese (0.01%) and Malays

(0.02%, P .0004).
Direct comparison of these findings with others13 is
problematic because of differences in study design,
population demographics, and diagnostic criteria of
amblyopia. Nonetheless, the overall prevalence of amblyopia was lower than other studies.13 The low prevalence in our study may partly be explained by a
national screening program, started in 1991, to detect
and treat amblyopia among Singaporean school children. All school children have annual visual acuity
checks at the beginning of their primary education (7
years).4 We have no data, however, to verify that this
program is effective in reducing amblyopia.
We observed little difference in the prevalence of
amblyopia among Chinese, Indian, and Malay men. The
minor racial/ethnic variation in the causes of amblyopia,
however, may possibly reflect racial/ethnic differences in
the frequency and impact of refractive errors and other
ocular disorders in Asian people.4

Marlene L. Durand, MD, Ivana K. Kim, MD,

Donald J. DAmico, MD,
John I. Loewenstein, MD, Ellis H. Tobin, MD,
Shalom J. Kieval, MD, Stephen S. Martin, MD,
Dimitri T. Azar, MD, Frederick S. Miller, III,
Brandon J. Lujan, MD, and Joan W. Miller, MD
To report successful treatment of exogenous
Fusarium and Aspergillus endophthalmitis with new
antifungal agents.
DESIGN: Interventional case report.
METHODS: Treatment of two cases is reviewed.
RESULTS: A 64-year-old man developed post-cataract
Fusarium moniliforme endophthalmitis. Infection persisted despite removal of the intraocular lens, three
vitrectomies, and five intravitreal injections of amphotericin. Inflammation resolved and vision improved from
20/80 to 20/40 on 6 months of oral voriconazole. A
55-year-old man developed post-cataract intraocular inflammation. After three vitrectomies and removal of the
intraocular lens, Aspergillus fumigatus endophthalmitis
was diagnosed. Intravitreal amphotericin and systemic
voriconazole were given, but one week later there were
PURPOSE:

REFERENCES

1. Brown SA, Weih LM, Fu CL, Dimitrov P, Taylor HR,

McCarthy CA. Prevalence of amblyopia and associated refractive errors in an adult population in Victoria, Australia.
Ophthalmic Epidemiol 2000;7:249 258.
2. Attebo K, Mitchell P, Cumming R, Smith W, Jolly N, Sparkes
R. Prevalence and causes of amblyopia in an adult population.
Ophthalmology 1998;105:154 159.
3. Ohlsson J, Villarreal G, Sjostrom A, Cavazos H, Abrahamsson
M, Sjostrand J. Visual acuity, amblyopia, and ocular pathology
in 12- to 13-year-old children in Northern Mexico. J AAPOS
2003;7:4753.
4. Seet B, Wong TY, Tan DTH, et al. Myopia in Singapore:
taking a public health approach. Br J Ophthalmol 2001;85:
521526.
5. Wong TY, Tielsch JM, Schein OD. Racial difference in the
incidence of retinal detachment in Singapore. Arch Ophthalmol 1999;117:379 383.

552

AMERICAN JOURNAL

Accepted for publication Mar 7, 2005.

From the Infectious Disease Service (M.L.D.) and the Department of
Ophthalmology (I.K.K., D.J.D.A., J.I.L., D.T.A., J.W.M.), Massachusetts
Eye and Ear Infirmary (MEEI), Boston, Massachusetts; Infectious Disease
Unit, Massachusetts General Hospital, Boston, Massachusetts (M.L.D.);
Albany Medical College, Albany, New York (E.H.T., S.J.K.); The
Aroostook Medical Center, Presque Isle, Maine (S.S.M.); Maine Medical
Center, Portland, Maine (F.S.M.III); and Department of Ophthalmology,
University of California at San Francisco, San Francisco, California
(B.J.L.).
Inquiries to Marlene L. Durand, MD, Infectious Disease Service,
Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA
02114; fax 617-726-7416; e-mail: mdurand@partners.org
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OPHTHALMOLOGY

SEPTEMBER 2005

FIGURE 1. Patient 1 with Fusarium endophthalmitis. This

fundus photograph illustrates the inferior vitreous debris observed in the left eye of the patient when he presented to the
Massachusetts Eye and Ear Infirmary.

FIGURE 3. Patient 2 with Aspergillus endophthalmitis. This

photograph, taken 9 days after the third vitrectomy, reveals a
persistent endothelial plaque in the superior aspect of the
cornea.

report excellent visual outcome in two cases by the use of

voriconazole, with and without caspofungin.
CASE 1:

FIGURE 2. Patient 2 with Aspergillus endophthalmitis. This

photomicrograph demonstrates the pathology of the lens capsule removed at the third vitrectomy. Arrows point to fungal
hyphae. Methenamine silver stain, 400 magnification.

early signs of recurrence. Intravenous caspofungin was

added and the eye improved. Caspofungin was continued
for 6 weeks and voriconazole for 6 months. Vision
improved from counting fingers to 20/80 at 6 months and
20/25 at 23 months.
CONCLUSION: Voriconazole is a promising new therapy
for Fusarium and Aspergillus endophthalmitis. Caspofungin may act synergistically with voriconazole in treating Aspergillus endophthalmitis. (Am J Ophthalmol
2005;140:552554. 2005 by Elsevier Inc. All rights
reserved.)

WO-THIRDS OF PATIENTS WITH MOLD ENDOPHTHALMI-

tis lose useful vision despite treatment.1,2 Older systemic antifungal agents rarely improve this outcome. We

VOL. 140, NO. 3

In 1999, a 64-year-old man developed left eye

(OS) intraocular inflammation 3 weeks after cataract
extraction with intraocular lens (CE/IOL) placement.
Inflammation persisted despite topical corticosteroids. At 2
months, he received vitrectomy and intravitreal antibiotics, including amphotericin (5 g); vitreous cultures grew
Fusarium moniliforme (identified by a mycology reference
laboratory). At 3 months, he was referred to the Massachusetts Eye and Ear Infirmary with OS acuity 20/30, 3
anterior chamber (AC) cells, moderate vitritis with filamentous debris inferiorly (Figure 1). Over the next 6
weeks, vitritis recurred despite IOL removal, two vitrectomies, and four intravitreal injections of amphotericin (5,
10, 5, 5 gs). Culture of the IOL and one vitreous sample
grew Fusarium. After another vitrectomy, the patient was
enrolled in a phase III trial and received voriconazole 300
mg po bid for 6 months. The vitreous remained clear, and
vision improved from 20/80 to 20/40. Two weeks after
stopping voriconazole, mild vitritis recurred. Vitreous cultures were negative, so voriconazole was not available per
trial protocol. The vitritis cleared on fluconazole 800 mg
po qd, which was subsequently tapered with vision returning to 20/40.

CASE 2: Six weeks after CE/IOL in 2003, a 55-year-old

man developed intraocular inflammation OS. This improved then recurred on topical corticosteroids. Vitrectomy at 3 months was nondiagnostic and he was referred
with acuity OS 20/300, hypopyon, and 4 aqueous cells.
Vitrectomy was again nondiagnostic. One week later,
hypopyon recurred and a new feathery mass appeared in
the superior AC. Vitrectomy and IOL removal was performed, and amphotericin (5 g) was injected. Culture of

BRIEF REPORTS

553

3. Hariprasad SM, Mieler WF, Holz ER, et al. Determination of

vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans. Arch Ophthalmol 2004;122:
42 47.
4. Breit SM, Hariprasad SM, Mieler WF, Shah GK, Mills MD,
Grand G. Management of endogenous fungal endophthalmitis
with voriconazole and caspofungin. Am J Ophthalmol 2005;
139:135140.
5. 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 (letter). Br J Ophthalmol 2000;84:932933.
6. Cornely OA, Schmitz K, Aisenbrey S. The first echinocandin:
caspofungin. Mycoses 2002;45(Suppl 3):56 60.
7. Marr KA, Boechk M, Carter RA, Kim HW, Corey L.
Combination antifungal therapy for invasive aspergillosis.
Clin Infect Dis 2004;39:797 802.

the mass grew Aspergillus fumigatus (culture confirmed by

reference laboratory). Pathology showed hyphae invading
the lens capsule and adjacent fibrovascular tissue (Figure 2).
Postoperatively, a white corneal endothelial plaque persisted
superiorly (Figure 3). He received intravitreal amphotericin
(5 g), topical amphotericin plus natamycin, and systemic
voriconazole (6mg/kg IV q12h 2 doses, then 200 mg po
bid). One week later, eye pain worsened and the endothelial plaque appeared larger. Intravitreal amphotericin (10
g) was injected and IV caspofungin was started (70 mg IV
day one, then 50 mg IV qd). Eye pain improved over the
next week, plaque size remained stable, a fourth vitrectomy
confirmed negative cultures, and intravitreal amphotericin
(10 g) was given. He was discharged on IV caspofungin
and voriconazole 200 mg po bid, plus topical amphotericin
OS. Caspofungin and topical amphotericin were stopped
at 6 weeks, voriconazole at 6 months. Vision OS improved
from counting fingers at discharge to 20/80 at completion
of therapy and 20/25 at 23 months after discharge, following epiretinal membrane peel and secondary IOL.
Voriconazole has replaced amphotericin as the treatment of choice for systemic Aspergillus infections, and it is
also active against Fusarium. It achieves good aqueous and
vitreous levels with oral administration (53% and 38% of
plasma levels, respectively).3 A recent report described
voriconazole treatment of five patients with Candida endophthalmitis, three of whom also received caspofungin.4
Mold infections are more difficult to cure than Candida
infections, but voriconazole has been used to treat endophthalmitis attributable to Paecilomyces lilacinus, Scedosporium
apiospermum, and Lecythophora mutabilis. A case identified
as Fusarium endophthalmitis on the basis of immunohistochemistry (cultures were negative) was also successfully
treated with voriconazole.5 Our first case demonstrates
successful treatment of culture-positive Fusarium endophthalmitis with voriconazole. Our second case demonstrates
successful treatment of Aspergillus endophthalmitis with
voriconazole and caspofungin. We are unaware of any
previous reports of Aspergillus endophthalmitis in which
this combination therapy was used. Caspofungin, the first
approved echinocandin, is active against Candida and
Aspergillus but not Fusarium. Caspofungins ability to penetrate the blood-eye barrier is unknown, but it was used
successfully to treat a case of post-cataract Acremonium
endophthalmitis that had failed amphotericin therapy.6
Caspofungin may act synergistically with voriconazole
against Aspergillus,7 and our second case supports this.

Rapid Diagnosis of Orbital Mantle

Cell Lymphoma Utilizing Fluorescent
In Situ Hybridization Technology
Robert Coffee, MD, MPH, John Lazarchick, MD,
Patricia Chvez-Barrios, MD, and
Gene Howard, MD
PURPOSE: We describe a patient with an orbital lymphoma
in which genetic analysis utilizing fluorescent in situ
hybridization (FISH) on a touch preparation of the
tumor identified the classic 11:14 translocation associated with a mantle cell lymphoma.
DESIGN: Clinicopathologic case report.
METHODS: A 76-year-old woman presented complaining
of ptosis and was found to have an orbital lesion suspected of being a lymphoproliferative malignancy. A
biopsy of the lesion was performed in the office, and the
sample was processed using a touch preparation technique.
RESULTS: Genetic analysis utilizing FISH on a touch
preparation of the tumor identified the classic 11:14
translocation associated with a mantle cell lymphoma.
CONCLUSIONS: FISH has become useful in the differential
diagnosis of lymphoproliferative lesions. The touch preparation method requires smaller amounts of tissue than
standard methods, and samples may be obtained in an office
setting. (Am J Ophthalmol 2005;140:554 556. 2005
by Elsevier Inc. All rights reserved.)
Accepted for publication Mar 12, 2005.
From the Department of Ophthalmology, Cullen Eye Institute, Baylor
College of Medicine, Houston, Texas (R.C.); Department of Pathology,
Medical University of South Carolina, Charleston (J.L.); Departments of
Pathology and Ophthalmology, Baylor College of Medicine (P.C.-B.);
and Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina (G.H.).
Inquiries to Robert Coffee, MD, MPH, Baylor College of Medicine,
One Baylor Plaza, MS 220, Houston, TX, 77030; fax: (713) 798-8763;
e-mail: rcoffee@bcm.tmc.edu

REFERENCES

1. Pflugfelder SC, Flynn HW Jr, Zwickey TA, et al. Exogenous

fungal endophthalmitis. Ophthalomology 1988;95:19 30.
2. Dursun D, Fernandez V, Miller D, Alfonso EC. Advanced
Fusarium keratitis progressing to endophthalmitis. Cornea
2003;22:300 303.

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