ArticlePDF Available

Abstract

Objectives: To report the outcomes of therapeutic corneal transplant for managing fungal keratitis that is refractory to medical treatment. Materials and methods: Retrospective data analyses of the medical records was performed on 17 patients who underwent a therapeutic corneal transplant for severe culture-proven fungal keratitis between October 2006 and August 2013. We evaluated demographics, fungal organism type, surgical data, recurrence presentation, disease course, follow-up, and graft status. Results: Mean patient age was 53.2 years (range, 33-81 y). The male/female ratio was 12/5. All patients had positive microscopic evaluation and positive culture results for fungal infection. The most common fungal agent was Fusarium sp. (35%). Nine patients reported a history of injury to the cornea and/or contact with plant material or soil. The mean best-corrected visual acuity at the initial visit was 2.45 logMAR unit (range, 0.52-3.10 logMAR unit). The mean follow-up was 14 months (range, 6-76 mo). Four patients underwent evisceration surgery because of graft lysis or uncontrolled recurrent disease. Recurrence of the fungal infection after corneal transplant was seen in 8 patients (47.05%). The graft rejection rate was 18.18%. At the final visit, 5 grafts were clear, 4 were translucent, and 2 were opaque. There were 2 phthisis bulbi owing to catastrophic disease. The mean final best-corrected visual acuity was 1.64 logMAR unit (range, 0.22-3.10 logMAR unit). Conclusions: Although therapeutic corneal transplant has a higher incidence of infection recurrence and graft failure, it continues to be an effective treatment for uncontrolled, refractory fungal keratitis cases to save the affected eye.
Abstract
Objectives: To report the outcomes of therapeutic
corneal transplant for managing fungal keratitis
that is refractory to medical treatment.
Materials and Methods: Retrospective data
analyses of the medical records was performed on
17 patients who underwent a therapeutic corneal
transplant for severe culture-proven fungal keratitis
between October 2006 and August 2013. We
evaluated demographics, fungal organism type,
surgical data, recurrence presentation, disease
course, follow-up, and graft status.
Results: Mean patient age was 53.2 years (range,
33-81 y). The male/female ratio was 12/5. All
patients had positive microscopic evaluation and
positive culture results for fungal infection. The
most common fungal agent was
Fusarium sp.
(35%).
Nine patients reported a history of injury to the
cornea and/or contact with plant material or soil.
The mean best-corrected visual acuity at the initial
visit was 2.45 logMAR unit (range, 0.52-3.10 logMAR
unit). The mean follow-up was 14 months (range,
6-76 mo). Four patients underwent evisceration
surgery because of graft lysis or uncontrolled
recurrent disease. Recurrence of the fungal infection
after corneal transplant was seen in 8 patients
(47.05%). The graft rejection rate was 18.18%. At the
final visit, 5 grafts were clear, 4 were translucent,
and 2 were opaque. There were 2 phthisis bulbi
owing to catastrophic disease. The mean final best-
corrected visual acuity was 1.64 logMAR unit
(range, 0.22-3.10 logMAR unit).
Conclusions: Although therapeutic corneal trans-
plant has a higher incidence of infection recurrence
and graft failure, it continues to be an effective
treatment for uncontrolled, refractory fungal
keratitis cases to save the affected eye.
Key words: Eye, Fungal keratitis, Penetrating corneal
transplant, Therapeutic corneal transplant.
Introduction
Infectious keratitis is one of the most significant causes
of ocular morbidity and blindness worldwide.1There
are various pathogens that lead to infectious keratitis
including bacteria, virus, protozoa, and fungus.
Fungal keratitis is reported to be up to 40% of all
microbial keratitis, especially in developing countries,
with species most commonly being Fusarium and
Aspergillus.2-4
Fungal keratitis usually follows a trauma or
prolonged steroid treatment.5The majority of the cases
occur in farmers. Warm and humid climate accelerates
the incidence of fungal infection.6Slit lamp
examination findings of fungal keratitis consist of
corneal ulceration with satellite lesions, patchy
deposits behind the cornea, and accompanying
hypopyon. In advanced cases, corneal perforation that
may lead to infection, ending with endophthalmitis,
can occur.7
When compared with other infectious keratitis
types, managing fungal keratitis is difficult.5Despite
recent development of antifungal agents, treating
fungal keratitis remains challenging. Therapeutic
corneal transplant is performed to manage fungal
keratitis patients who are unresponsive to maximal
medical therapy or have corneal perforations owing
to the infection.8,9
Copyright © Başkent University 2014
Printed in Turkey. All Rights Reserved.
Therapeutic Corneal Transplant for Fungal Keratitis
Refractory to Medical Therapy
Ozlem Barut Selver,1Sait Egrilmez,1Melis Palamar,1Mesut Arici,2
Suleyha Hilmioglu Polat,3Ayse Yagci1
From the 1Department of Ophthalmology; the 2Department of Pharmaceutical Technology; and
the 3Department of Microbiology, Ege University, Izmir, Turkey
Acknowledgements: The authors have no conflicts of interest to disclose, and there was no
funding for this study. The authors have no proprietary or commercial interest in any materials
discussed in this article.
Corresponding author: Melis Palamar, Assoc. Prof., Ege University Faculty of Medicine,
Department of Ophthalmology, 35040 Bornova, Izmir, Turkey
Phone: +90 232 388 14 69 Fax: +90 232 388 14 69 E-mail: melispalamar@hotmail.com
Experimental and Clinical Transplantation (2014)


In the literature, therapeutic corneal transplant has
been reported to range in 12% to 38% of fungal
keratitis.10-12 Here, we report our clinical results of
refractory fungal keratitis patients who underwent
therapeutic corneal transplant surgery to save the eye
and treat infection.
Materials and Methods
We retrospectively reviewed the medical records of
17 culture-proven fungal keratitis patients who
underwent therapeutic corneal transplant between
October 2006 and August 2013 at the Ophthalmology
Department, of the Ege University School of
Medicine, in Izmir, Turkey. (There were 35 culture-
proven fungal keratitis patients during this
period, and 17 of these patients underwent a
therapeutic corneal transplant.) The demographics,
fungal organism type, surgical data, recurrence rate,
disease course, best-corrected visual acuity values
(logMAR unit), graft outcome, graft rejection, and
additional surgeries (if any) were evaluated
(Table 1).
Upon arrival, and after obtaining the diagnostic
material for microbiological examination, all patients
were initiated hourly with topical vancomycin
(50 mg/mL) and ceftazidime (50 mg/mL) for
presumed bacterial keratitis, and hourly topical
fluconazole (2 mg/mL) and oral fluconazole 100 mg
twice daily for presumed fungal keratitis. The
treatment regimens were revised according to the
results of cultures and antibiogram. By the time
fungal keratitis was proven by culture, topical
vancomycin and ceftazidime drops were replaced
with topical moxifloxacin hydrochloride (Alcon
LenSx, Inc., Aliso Viejo, CA, USA) every 2 hours.
Topical fluconazole (2 mg/mL) for yeast and topical
voriconazole (10 mg/mL) for mold fungi were
chosen for topical treatment.
Eyes that were unresponsive to appropriate
antifungal treatment (any fungal keratitis that did
not regress or that showed progression despite
appropriate topical antifungal treatment was
considered unresponsive) or progressed to corneal
melting and perforation, underwent a therapeutic
corneal transplant. In all cases, the size of the
trephine was chosen to involve all of the diseased
corneal area, and the donor cornea was punched
0.25 mm larger than the recipient bed. Interrupted
suturation was performed by 10.0 monofilament
nylon sutures. In the evidence of purulent
materials and fibrotic membrane in the
anterior chamber, removal of these materials,
angle revision (if needed), and anterior chamber
irrigation with 0.2% fluconazole was performed.
Topical antifungal treatment was continued for at
least 3 months after surgery. Upon completed
epithelization after surgery, topical corticosteroids
4 times daily were started to prevent graft rejection.
Follow-ups were adjusted according to the
ophthalmologic examination findings of each
patient.
Ozlem Barut Selver et al/Experimental and Clinical Transplantation (2014) Exp Clin Transplant
Patient Sex Age Trauma Perfo- Hypo- Large Time to Graft Culture Result Initial Final Recur- Rejection Follow- Final Outcome
ration pyon Ulcer Tx (d) Size BCVA BCVA rence Up (mo)
(mm) (logMAR) (logMAR)
SK M 73 30 8.25
Aspergillus flavus
1.80 0.52 21 Translucent
JR F 65 ++58.25
Acremonium sp
3.10 +1Evisceration
IK M 79 +++2 7.75
Candida albicans
3.10 3.10 + 13 Translucent
YE F 46 ++1 7.75
Fusarium sp
3.10 + 0.2 Evisceration
AS M 48 +++ 6 7.75
Aspergillus terreus
3.10 +6Phthisis
ZA F 41 75 8.25
Acremonium sp
1.80 0.3 6 Clear
CK M 66 + 15 8.25
Aspergillus fumigatus
3.10 0.22 + 26 Clear
LY M 43 ++ 2 8.25
Aspergillus fumigatus
3.10 0.7 76 Translucent
ZC M 33 ++57.75
Penicillium sp
3.10 3.10 6 Clear
ZS F 49 4 7.75
Fusarium sp
1.00 0.4 6 Clear
CG M 81 ++ +9 7.75
Colletotrichum
1.80 3.10 6 Opaque
gloeosporioides
AO M 40 ++18.25
Acremonium sp
3.10 0.4 53 Clear
OV M 41 + 10 7.75
Acremonium
3.10 + 42 Phthisis
falciforme
HB M 63 6 7.75
Fusarium sp
3.10 + 1.5 Evisceration
LK M 28 + 45 7.75
Fusarium sp
0.70 3.10 ++10 Opaque
MAI M 47 40 8.25
Fusarium sp
0.52 3.10 + 72 Translucent
OC F 61 +77.75
Fusarium sp
3.10 17.5 Evisceration
 Patient Demographics and Outcomes
Abbreviations: BCVA, best corrected visual acuity; Time to tx, time interval between initiation and corneal transplant
Ozlem Barut Selver et al/Experimental and Clinical Transplantation (2014)
Results
The mean age of patients was 53.2 years (range, 33-81
y; 12 men, 5 women). The most common fungal
agent was Fusarium sp. (35%). Nine patients (52.9%)
reported a history of injury to the cornea and/or
contact with plant material or soil. One patient
receiving immunosuppressive agent had a medical
history of severe rheumatoid arthritis. The rest of the
patients were unable to provide a cause for their
infection. Four of 17 patients (23.52%) had corneal
perforation on the initial visit. Seven patients
(41.17%) had hypopyon and 4 patients (23.52%) had
a corneal infection expanding to the limbus on first
examination (Figure 1). The mean best-corrected
visual acuity on the initial visit was 2.45 logMAR
unit (range, 0.52-3.10 logMAR unit). Immediate
corneal transplant surgery (ie, 1-9 d) was performed
in cases with corneal perforation or excessive
fungal disease. The mean time in our cases between
the first visit and the surgery was 15.47 days (range,
1-75 d).
The mean follow-up was 14 months (range, 6-76
mo) for patients who did not undergo evisceration
surgery. Four patients (23.52%) underwent evis-
ceration surgery because of graft lysis or uncontrolled
recurrent disease. Recurrence of the fungal infection
after the corneal transplant was noted in 8 patients
(47.05%), and the outcomes of recurrence in each
patient are summarized in Table 2. Graft rejection
rate was 18.18%. The mean number of corneal
transplants for each patient was 1.18 (range, 1-3) and
anatomic success was maintained in 11 of 17 patients
(64.70%). During the final visit, 5 grafts were clear
(Figure 2), 4 were translucent, and 2 were opaque.
Two eyes ended up with phthisis bulbi because of
catastrophic infection and inflammation. The mean
final best-corrected visual acuity was 1.64 logMAR
unit (range, 0.22-3.10 logMAR unit).
Discussion
Fungal keratitis is one of the most devastating
ophthalmologic infections. The majority of the fungal
Patients With Recurrence Re-Keratoplasty Evisceration Number Treated With Medical
Recurrence Number Surgery Phthisis Bulbi Therapy Only
11-+--
21-+--
31---+
41--+-
521-+-
622+--
732---
83---+
 Slit Lamp Examination Photographs of the Patient (LK) Who Had a Large Corneal Infiltration With a Hypopyon on the First Examination 
The disease was unresponsive to antifungal treatment ), and the patient underwent a therapeutic corneal transplant to control the progressive disease  There
was a recurrence of infection 2 months after surgery 
 Slit Lamp Examination Photographs of the Patient (CK) Who Had a Large Corneal Ulceration and Infiltration on the First Examination 
The patient underwent a therapeutic corneal transplant for the disease, which was unresponsive to medical treatment . The graft was clear during the follow-
up (7 mo after the surgery), ; 1 year after surgery, .
 Recurrence Outcomes
keratitis cases have a history of injury to the cornea
and/or contact with plant material or soil.6In our
case series, trauma history was present in 52.94% of
the cases. The most commonly isolated pathogen in
this case series was Fusarium sp. (35%), which is in
agreement with the literature.13
With recent pharmaceutical developments, fungal
keratitis can be successfully controlled, especially
during the early stages of the disease, with
appropriate antifungal agents.14-22 However, cases
that are unresponsive to antifungal treatment require
a therapeutic corneal transplant surgery to control
the disease and save the eye. In the literature,
therapeutic penetrating corneal transplant has been
reported to range between 12% and 38% of fungal
keratitis.10-12 Nevertheless, this surgery has
disadvantages including a high incidence of graft
infection and failure.6,23-26 The graft survival rate for
therapeutic corneal transplant is related with the
type of infective agent, the severity of inflammation,
surgical timing, donor tissue quality, graft size, pre-
and postoperative medical treatment, and
perforation existence.27
Unless the cornea is perforated, therapeutic
corneal transplant is recommended to be performed
7 to 10 days after initiating antifungal drugs.
However, if there is a corneal perforation, corneal
transplant should be performed as soon as
possible.26 In cases with corneal perforation or
excessive fungal disease, we performed a corneal
transplant as soon as possible. The mean time in our
cases between the first visit and surgery was 15.47
days.
One of the most important causes of treatment
failure after therapeutic corneal transplant for fungal
keratitis is infection recurrence. In the literature, the
rate of fungal recurrence is reported to be between
5% and 14%.27,28 In this study, the recurrence rate
was found to be 47.05%, which is higher than the
values reported in the literature.27,28 Preoperative
hypopyon, corneal perforation, and corneal
infection expanding to the limbus increase the
recurrence rate of fungal keratitis after a corneal
transplant.29 In our group of patients, on initial
examination, 4 had a corneal perforation, 7 had a
hypopyon, and 4 had a corneal infection expanding
to the limbus. Moreover, as our clinic is a tertiary
center in the region, 8 patients (47.05%) were
referred to our clinic at the end stage of the disease—
using multiple antibiotics, antiviral, antifungal
agents, and steroids. This may be the major reason
for the higher recurrence rate and increased surgery
requirement among our cases. The surgery rate in
our series was 48.57% among all culture-proven
fungal keratitis patients, which is higher than that
reported in the literature.10-12
Graft rejection is an expected complication of
therapeutic corneal transplant surgery. The rejection
rate of therapeutic corneal transplant for fungal
keratitis is reported to be 29.60%, which is higher
than that of other keratitis types.6In this study, the
graft rejection rate was 18.18%, which is slightly
lower than that presented in the literature.6,25
A larger graft size (≥ 9.00 mm) provides an
opportunity to remove larger infected tissue with
high anatomic precision but less functional results.30
In this study, smaller graft size (≤ 8 mm) was chosen
for corneal transplant surgery, and this preference
might be the reason for the high recurrence rate and
low rejection rate in our cases.
In patients with preserved eyeballs, corneal graft
success was 81.81%, which is consistent with the
literature.6,25 In contrast with graft success, we found
a low visual recovery rate in our study group
(54.54%; 6 patients). Although improvement of
visual acuity after a therapeutic corneal transplant
for fungal keratitis is reported to be 88.5%,25
in our study, patients with no gain in visual
acuity had additional ocular problems
(mature cataract; 2 patients, chronic retinal
detachment; 1 patient), which are unrelated to their
corneal graft outcome, except for 2 patients with
opaque grafts.
In conclusion, early diagnosis and urgent
initiation of appropriate antifungal therapy are
critical to control fungal keratitis. Refractory
fungal keratitis is a therapeutic challenge, as it
may progress to corneal perforation and
fungal endophthalmitis. Moreover, concomitant
inflammation also may result in extensive iris
synechia, secondary glaucoma, and extrusion
of the intraocular contents.31-35 Therefore, if the
infection does not respond to proper medical
treatment, a therapeutic corneal transplant should
be considered as an alternative treatment option for
refractory fungal keratitis.6A therapeutic corneal
transplant also is an effective method for
visual rehabilitation and protection of the eye
with a proper timing of surgery in severe fungal
keratitis.
Ozlem Barut Selver et al/Experimental and Clinical Transplantation (2014) Exp Clin Transplant
Ozlem Barut Selver et al/Experimental and Clinical Transplantation (2014)
References
1. Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global
perspective. Bull World Health Organ. 2001;79(3):214-221.
2. Bharathi MJ, Ramakrishnan R, Meenakshi R, Padmavathy S,
Shivakumar C, Srinivasan M. Microbial keratitis in South India:
influence of risk factors, climate, and geographical variation.
Ophthalmic Epidemiol. 2007;14(2):61-69.
3. Sirikul T, Prabriputaloong T, Smathivat A, Chuck RS, Vongthongsri
A. Predisposing factors and etiologic diagnosis of ulcerative keratitis.
Cornea. 2008;27(3):283-287.
4. Foster CS. Fungal keratitis. Infect Dis Clin North Am. 1992;6(4):851-
857.
5. Reddy PS, Satyendran OM, Satapathy M, Kumar HV, Reddy PR.
Mycotic keratitis. Indian J Ophthalmol. 1972;20(3):101-108.
6. Xie L, Dong X, Shi W. Treatment of fungal keratitis by penetrating
keratoplasty. Br J Ophthalmol. 2001;85(9):1070-1074.
7. Liu Y, Jia H, Shi X, et al. Minimal trephination penetrating
keratoplasty for severe fungal keratitis complicated with hypopyon.
Can J Ophthalmol. 2013; 48(6):529-534.
8. Singh G, Malik SR. Therapeutic keratoplasty in fungal corneal ulcers.
Br J Ophthalmol. 1972;56(1):41-45.
9. Forster RK, Rebell G. Therapeutic surger y in failures of medical
treatment for fungal keratitis. Br J Ophthalmol. 1975;59(7):366-371.
10. Ti SE, Scott JA, Janardhanan P, Tan DT. Therapeutic keratoplasty for
advanced suppurative keratitis. Am J Ophthalmol. 2007;143(5):755-
762.
11. Ibrahim MM, Vanini R, Ibrahim FM, et al. Epidemiologic aspects and
clinical outcome of fungal keratitis in southeastern Brazil. Eur J
Ophthalmol. 2009;19(3):355-361.
12. Thew MR, Todd B. Fungal keratitis in far north Queensland, Australia.
Clin Experiment Ophthalmol. 2008;36(8):721-724.
13. Vajpayee RB, Gupta SK, Bareja U, Kishore K. Ocular atopy and
mycotic keratitis. Ann Ophthalmol. 1990;22(10):369-372.
14. Sheehan DJ, Hitchcock CA, Sibley CM. Current and emerging azole
antifungal agents. Clin Microbiol Rev. 1999;12(1):40-79.
15. Luttrull JK, Wan WL, Kubak BM, Smith MD, Oster HA. Treatment of
ocular fungal infections with oral fluconazole. Am J Ophthalmol.
1995;119(4):477-481.
16. Guzek JP, Roosenberg JM, Gano DL, Wessels IF. The effect of vehicle
on corneal penetration of triturated ketoconazole and itraconazole.
Ophthalmic Surg Lasers. 1998;29(11):926-929.
17. De Rosso JQ, Gupta AK. Oral itraconazole therapy for superficial,
subcutaneous, and systemic infections. A panoramic view. Postgrad
Med. 1999;Spec No:46-52.
18. O'Day DM. Orally administered antifungal therapy for experimental
keratomycosis. Trans Am Ophthalmol Soc. 1990;88:685-725.
19. Thakar M. Oral fluconazole therapy for keratomycosis. Acta
Ophthalmol (Copenh). 1994;72(6):765-767.
20. Prajna NV, O'Brien KS, Acharya NR, Lietman TM. Voriconazole for
fungal keratitis. Ophthalmology. 2013;120(9):e62-e63. doi:
10.1016/j.ophtha.2013.06.016.
21. Hariprasad SM, Mieler WF, Lin TK, Sponsel WE, Graybill JR.
Voriconazole in the treatment of fungal eye infections: a review of
current literature. Br J Ophthalmol. 2008;92(7):871-878.
22. Prajna NV, Krishnan T, Mascarenhas J, et al; and Mycotic Ulcer
Treatment Trial Group. The mycotic ulcer treatment trial: a
randomized trial comparing natamycin vs voriconazole. JAMA
Ophthalmol. 2013;131(4):422-429.
23. Claerhout I, Beele H, Van den Abeele K, Kestelyn P. Therapeutic
penetrating keratoplasty: clinical outcome and evolution of
endothelial cell density. Cornea. 2002;21(7):637-642.
24. Chen WL, Wu CY, Hu FR, Wang IJ. Therapeutic penetrating
keratoplasty for microbial keratitis in Taiwan from 1987 to 2001.
Am J Ophthalmol. 2004;137(4):736-743.
25. Xie L, Zhai H, Shi W. Penetrating keratoplasty for corneal
perforations in fungal keratitis. Cornea. 2007;26(2):158-162.
26. Yao YF, Zhang YM, Zhou P, Zhang B, Qiu WY, Tseng SC.
Therapeutic penetrating keratoplasty in severe fungal keratitis using
cryopreserved donor corneas. Br J Ophthalmol. 2003;87(5):543-
547.
27. Sony P, Sharma N, Vajpayee RB, Ray M. Therapeutic keratoplasty for
infectious keratitis: a review of the literature. CL AO J.
2002;28(3):111-118.
28. Ti SE, Scott JA, Janardhanan P, Tan DT. Therapeutic keratoplasty for
advanced suppurative keratitis. Am J Ophthalmol. 2007;143(5):755-
762.
29. Shi W, Wang T, Xie L, et al. Risk factors, clinical features, and
outcomes of recurrent fungal keratitis after corneal transplantation.
Ophthalmology. 2010;117(5):890-896.
30. Sharma N, Jain M, Sehra SV, et al. Outcomes of therapeutic
penetrating keratoplasty from a tertiary eye care centre in
northern India. Cornea. 2014;33(2):114-118.
31. Shah CV, Jones DB, Holz ER. Microsphaeropsis olivacea keratitis
and consecutive endophthalmitis. Am J Ophthalmol.
2001;131(1):142-143.
32. Wang MX, Shen DJ, Liu JC, Pflugfelder SC, Alfonso EC, Forster RK.
Recurrent fungal keratitis and endophthalmitis. Cornea.
2000;19(4):558-560.
33. Scott IU, Flynn HW Jr, Feuer W, et al. Endophthalmitis associated
with microbial keratitis. Ophthalmology. 1996;103(11):1864-1870.
34. Liesegang TJ. Fungal keratitis. In: Kaufman HE, Barron BA, Mcdonald
MB, eds. The Cornea. 2nd ed. Boston: Butterworth-Heinemann;
1998:219-245.
35. Mizunoya S, Watanabe Y. Paecilomyces keratitis with corneal
perforation salvaged by a conjunctival flap and delayed keratoplasty.
Br J Ophthalmol. 1994;78(2):157-158.
... Bu olgular zamanında ve etkin tedavi edilmezse progresif doku nekrozu, perforasyon ve göz kaybına ilerleyebilir (12)(13)(14)(15). Bazı olgularda medikal tedaviye yanıtsızlık nedeniyle kornea nakli uygulanması gerekebilir (16). Enfeksiyöz keratitler bakteriyel, fungal, viral ve paraziter olmak üzere dörde ayrılır. ...
... Fungal keratitler bakteriyel keratitlere göre daha yavaş ilerleyen bir tablo ile seyrederler. Bununla birlikte çoğunda tanıda gecikme söz konusu olduğundan görsel prognoz çok iyi değildir (16). Viral keratitler: En sık olarak Herpes simplex virüs enfeksiyonu nedeni ile ortaya çıkar. ...
... However, despite treatment, 12 to 38% of severe fungal keratitis require therapeutic corneal transplantation. (15) Intrastromal and intracameral injections of amphotericin B have been used as an alternative to conventional treatment in deep fungal keratitis to postpone or prevent therapeutic keratoplasty. Corneal transplantation is effective at controlling the infection, but therapeutic keratoplasty-especially if performed on large ulcers or very inflamed eyes-presents inferior results when compared to optic keratoplasty after healing. ...
... According to literature, 12% to 38% of fungal keratitis cases require corneal transplantation, even after adequate treatment. (15,16,19) In our study, 43 patients (65.1%) underwent therapeutic keratoplasty. Besides that, most patients ended-up with significant visual impairment even after infection eradication, and final visual acuity was less related to the causal agent and more related to lesion's severity/depth, with better outcomes in superficial cases. ...
Article
Full-text available
Purpose: To report etiological diagnosis, predisposing risk factors, therapeutic strategies and visual outcome of patients treated at the Department of Ophthalmology of Federal University of São Paulo. Methods: This is a retrospective, descriptive, and observational study from medical and laboratory records of the Department of Ophthalmology of Federal University of São Paulo, including all patients with culture proven fungal keratitis in 5 years, from October 2012 through October 2017. Results: There were 2260 fungi microbiologic test requests. Of these, 140 samples had positive cultures for fungi and sixty-six patients were followed at our clinic. Forty-five patients (68.2%) were men, and the mean age was 48.06 (±17.39) years. Fusarium spp. was the most frequently isolated fungus (32 cases; 48.5%), followed by Candida parapsilosis (12 cases; 18.2%). Thirty-four patients (51.5%) underwent intracameral injection of amphotericin B (5 µg per 0.1 ml). In 11 patients (32.3%), infection was eradicated after intracameral amphotericin B associated to topical antifungal treatment and, in 23 patients (67.7%), therapeutic keratoplasty was needed. No complication related to intracameral amphotericin B injection was observed in this series. Forty-three patients (65.1%) ended up with therapeutic keratoplasty. Three patients (4.5%) evolved to evisceration or enucleation. At the last follow-up visit, 53 patients (80.3%) had visual acuity worse than 20/200. Conclusion: Despite current antifungals drugs and distinct administration strategies, fungal keratitis remains challenging. Delayed antifungal therapy may explain poor clinical outcomes. Intracameral amphotericin B associated to topical antfungal treatment seems to be a safe and helpful alternative for non-responsive fungal keratitis. But it is important to formulate other treatment strategies, hence to improve patients’ outcomes, since most patients ended-up with significant visual impairment even after current treatment.
... An excellent anatomical or visual outcome has been reported with PKP in fungal keratitis in several studies; 5,6 however, there is a high incidence of postsurgical graft failure, rejection and recurrence of fungal infection. 7,8 To reduce the incidence of complications after PKP for fungal keratitis, minimal trephination PKP, equal to the size of the corneal ulcer, has been reported for severe fungal keratitis complicated with hypopyon and showed a very high rate of graft clarity (95%) after surgery; however, intraoperative graft edge irrigation and anterior chamber irrigation with antifungal agents were necessary with this method. 9 Deep anterior lamellar keratoplasty (DALK) has recently been carried out for the treatment of refractory fungal keratitis, and a higher cure rate and better visual outcome compared with those with PKP have been reported in several studies of infectious keratitis including fungal keratitis. ...
... A favorable clinical outcome was reported in PKPtreated fungal keratitis in several studies, in which the anatomical success rate was 76-88%. 7,22,23 However, higher rates of recurrent infection (14-78%) 7,22,23 and graft rejection (18-22%) 22,23 were also reported in these studies. Overall, a poor final visual outcome with an average best-corrected logMAR of (mean, 95% CI) 0.7 (0.4-1.0) was noted in fungal keratitis, including patients treated with PKP. ...
Article
Full-text available
Purpose: Fungal keratitis remains an important disorder because of difficulty in its diagnosis, and some patients do not respond to medical treatment using antifungal local and systemic agents. This study was carried out to determine the therapeutic value of air-assisted manual therapeutic deep anterior lamellar keratoplasty (TDALK) in the treatment of fungal keratitis not curable by antifungal chemotherapy. Methods: Seventeen patients (18 eyes) who were referred to Fukuoka University Hospital and treated surgically from January 2006 to April 2018, in whom a diagnosis of fungal keratitis was confirmed by typical clinical findings and microbiological or histological analysis of corneal specimens, and who were poorly responsive to topical and systemic antifungal medication, whereas the lesion had not resulted in corneal perforation, were enrolled in this study and were treated by air-assisted manual TDALK. Clinical outcomes including treatment course, therapeutic success rate, visual acuity outcomes and graft clarity rate were analyzed. Results: The most common pathogen was Fusarium, followed by Candida and Aspergillus. Beneficial therapeutic results (a clear or translucent graft) were achieved in 15 of 18 eyes (83%). There was no recurrence of infection and resulting visual acuity ≤0.15 logarithm of minimal angle of resolution unit was achieved in 15 eyes (83%). Intraoperative microperforation of Descemet's membrane (DM) was not observed in any patients. Conclusion: Air-assisted manual TDALK can be effective for treating severe fungal keratitis. In addition, air-assisted manual TDALK might be an alternative procedure to big-bubble DALK, because it can provide ambulatory vision and can preserve potentiality of vision with less risk of intraoperative perforation of DM.
... Because of the risk of rejection with large grafts in Acanthamoeba keratitis, corneal grafts must be kept to the minimum size required [113]. In cases of fungal keratitis, Selver et al. demonstrated that smaller grafts (< 8 mm) were associated with lower rejection rates, but higher recurrence rates possibly related to incomplete removal of infected tissue [151,152]. ...
Chapter
Full-text available
The focus of this chapter is to review the most recent advances in the diagnosis and treatment of contact-lens-related infectious keratitis, the most sight-threatening complication of contact lens wear. In the last decades, contact lenses technology has confronted several challenges, including the need for safer and more comfortable polymer materials. The development of high coefficient oxygen permeability (Dkt) and low-water content disposable contact lens translated into a significant improvement in ocular discomfort related to dry eye and allergic reactions, decreasing biofilm build-up on the external surface of the lens. Additionally, the emergence and boom-effect of corneal refractive surgery have also driven the development of better contact lens manufacturing. Despite these substantial technological advances, contact lens users continue to be at risk for developing corneal infections. We describe recent epidemiologic data, and advances in understanding the complex pathogenesis of the disease, including the clinical characteristics of the infectious process produced by bacteria, fungi, and protozoans. Finally, the recent development of diagnostic techniques and therapeutic regimens are discussed.
... Since the 1960 ′ s, topical Natamycin is the most effective medication for the treatment of fungal keratitis (Ansari et al., 2013). However, 12-38% of fungal keratitis cases will progress despite medical treatment, and requires surgical intervention such as penetrating keratoplasty (Selver, 2015) (Rogers et al., 2013). ...
Preprint
Full-text available
Research in the development of ophthalmic drug formulations and innovative technologies over the past few decades has been directed at improving the penetration of medications delivered to the eye. Currently, approximately 90% of all ophthalmic drug formulations (e.g. liposomes, micelles) are applied as eye drops. The major challenge of topical eye drops is low bioavailability, need for frequent instillation due to the short half-life, poor drug solubility, and potential side effects. Recent research has been focused on improving topical drug delivery devices by increasing ocular residence time, overcoming physiological and anatomical barriers, and developing medical devices and drug formulations to increase the duration of action of the active drugs. Researchers have developed innovative technologies and formulations ranging from sub-micron to macroscopic size such as prodrugs, enhancers, mucus-penetrating particles (MPPs), therapeutic contact lenses, and collagen corneal shields. Another approach towards the development of effective topical drug delivery is embedding therapeutic formulations in microdevices designed for sustained release of the active drugs. The goal is to optimize the delivery of ophthalmic medications by achieving high drug concentration with prolonged duration of action that is convenient for patients to administer.
... Since the 1960 ′ s, topical Natamycin is the most effective medication for the treatment of fungal keratitis (Ansari et al., 2013). However, 12-38% of fungal keratitis cases will progress despite medical treatment, and requires surgical intervention such as penetrating keratoplasty (Selver, 2015) (Rogers et al., 2013). ...
Article
Research in the development of ophthalmic drug formulations and innovative technologies over the past few decades has been directed at improving the penetration of medications delivered to the eye. Currently, approximately 90% of all ophthalmic drug formulations (e.g. liposomes, micelles) are applied as eye drops. The major challenge of topical eye drops is low bioavailability, need for frequent instillation due to the short half-life, poor drug solubility, and potential side effects. Recent research has been focused on improving topical drug delivery devices by increasing ocular residence time, overcoming physiological and anatomical barriers, and developing medical devices and drug formulations to increase the duration of action of the active drugs. Researchers have developed innovative technologies and formulations ranging from sub-micron to macroscopic size such as prodrugs, enhancers, mucus-penetrating particles (MPPs), therapeutic contact lenses, and collagen corneal shields. Another approach towards the development of effective topical drug delivery is embedding therapeutic formulations in microdevices designed for sustained release of the active drugs. The goal is to optimize the delivery of ophthalmic medications by achieving high drug concentration with prolonged duration of action that is convenient for patients to administer.
... Other studies suggested that smaller grafts might reduce the incidence of complications after penetrating keratoplasty, but the recurrence rate increased due to incomplete removal of infection sites [60]. ...
Article
Full-text available
Purpose The aim of this article is to introduce the recent advance on the studies of fungal keratitis published over past 5 years. Methods We performed literature review of articles published on PubMed, Google Scholar, CNKI and Web of Science relevant to the diagnosis, pathogenesis and novel treatment of fungal keratitis. Results Excessive inflammation can lead to stromal damage and corneal opacification, hence the research on immune mechanism provides many potential therapeutic targets for fungal keratitis. Many researchers discussed the importance of earlier definitive diagnosis and were trying to find rapid and accurate diagnostic methods of pathogens. Develop new drug delivery systems and new routes of administration with better corneal penetration, prolonged ocular residence time, and better mucoadhesive properties is also one of the research hotspots. Additionally, many novel therapeutic agents and methods have been gradually applied in clinical ophthalmology. Conclusion The diagnosis and treatment of fungal keratitis are still a challenge for ophthalmologist, and many researches provide new methods to conquer these problems.
... Collagen cross linking with antifungal agents' introduction in stroma of cornea has a promising outcome in fungal keratitis [7]. Therapeutic corneal transplant is an effective alternative for refractory fungal keratitis despite complications associated with it, like recurrence of infection and graft failure [8]. There is also convincing evidence of hydrogel based contact lenses and drug delivery system to decrease the contact lens induced fungal keratitis [9]. ...
Article
Full-text available
A prospective case study of patients presenting with clinically suspected keratitis was conducted at Al-Rehma Hospital, Sirte, Libya between January 2008 and November 2010. A total of 32.9% patients were identified with fungal keratitis, Aspergillus and Fusarium together accounted for 89.28% of cases. Males had higher predisposition as compared with females. Trauma (78.5%) was the major cause, vegetative injury alone constituting 60.7% of cases. Other most common identifiable risk factors were history of diabetes mellitus (17.8%), contact lens (21.4%) and corticosteroids (3.57%). Fungal keratitis still possesses a significant threat for increased ocular morbidity. The overall knowledge of fungal keratitis with its clinical determinants and risk factors, would aid in general awareness and prevention of complications associated with it.
Article
There are no standardized protocols or guidelines for the treatment of recurrent fungal keratitis after therapeutic keratoplasty. This study aimed to investigate the incidence of recurrent fungal keratitis after the primary keratoplasty and the visual outcome and prognosis after intervention for the recurrence.This was a retrospective study. Patients with recurrent fungal keratitis after lamellar keratoplasty (LK) or penetrating keratoplasty (PK) were treated with different antifungal regimens at Shandong Eye Hospital and Qingdao Eye Hospital between Januray 2004 and December 2015. The operative techniques included PK, focal excision, tectonic keratoplasty with a patch graft, lensectomy and vitrectomy, and combined operation. Patients were followed at 1, 2, and 3 months, and then every 6 months after surgery for 2 years. Best corrected visual acuity was assessed and recurrence was recorded. Good prognosis was defined as the presence of visual acuity.Fungal keratitis recurred in 112 of 1448 patients (112/1448, 7.7%) treated initially with PK or LK. The good prognosis rates for different sites of recurrent fungal keratitis were: overall, 93 of 112 (83.0%); recipient bed, 64 of 69 (92.8%); anterior chamber, 14 of 14 (100%); posterior segment, 10 of 16 (62.5%); and atypical, 5 of 13 (38.5%). There was no significant difference in the timing of recurrence between the good and poor prognosis groups (P = .518). Recurrence rates were similar between patients with PK (8.6%) and those with LK (6.0%; P > .05), but the good prognosis rate in patients with post-LK recurrence (96.8%) was higher than that in patients with post-PK recurrence (77.8%, P = .017).Individualized treatment according to recurrent sites of fungal keratitis can achieve a good prognosis in most patients.
Article
Fusarium keratitis is a destructive eye infection that is difficult to treat and results in poor outcome. In tropical and subtropical areas, the infection is relatively common and associated with trauma or chronic eye diseases. However, in recent years, an increased incidence has been reported in temperate climate regions. At the German National Reference Center, we have observed a steady increase in case numbers since 2014. Here, we present the first German case series of eye infections withFusariumspecies. We identifiedFusariumisolates from the eye or eye-related material from 22 patients in 2014 and 2015. Thirteen isolates belonged to theFusarium solanispecies complex (FSSC), 6 isolates belonged to theFusarium oxysporumspecies complex (FOSC), and three isolates belonged to theFusarium fujikuroispecies complex (FFSC). FSSC was isolated in 13 of 15 (85%) definite infections and FOSC in 3 of 4 (75%) definite contaminations. Furthermore, diagnosis from contact lens swabs or a culture of contact lens solution turned out to be highly unreliable. FSSC isolates differed from FOSC and FFSC by a distinctly higher MIC for terbinafine. Outcome was often adverse, with 10 patients requiring keratoplasty or enucleation. The use of natamycin as the most effective agent against keratitis caused by filamentous fungi was rare in Germany, possibly due to restricted availability. Keratitis caused byFusariumspp. (usually FSSC) appears to be a relevant clinical problem in Germany, with the use of contact lenses as the predominant risk factor. Its outcome is often adverse.
Article
Full-text available
To study the risk factors, clinical features, and treatment of recurrent fungal keratitis after corneal transplantation. Retrospective, interventional case series. Eight hundred ninety-nine patients (eyes) with fungal keratitis who underwent corneal transplantation at the Shandong Eye Institute between January 2000 and October 2008. Six hundred fourteen patients underwent penetrating keratoplasty (PK) and 285 patients underwent lamellar keratoplasty (LK). All patients failed to respond to topical and systemic antifungal drugs treatment before corneal transplantation. A trephine that was 0.5 mm larger in diameter than the infection area was used during PK or LK. Medical records of each patient were reviewed retrospectively. The species of pathogenetic fungi causing recurrence were analyzed. The clinical features, including recurrence time, position, symptom, and physical signs, were summarized. Based on clinical features, appropriate topical and systemic antifungal treatment was determined for all patients; some patients also received combined subconjunctival or intracameral injection of fluconazole. If there was treatment failure, a conjunctival flap or keratoplasty was performed. Species of pathogenetic fungi, clinical features, and apparent therapeutic effects. Fifty-seven patients (6.34%) experienced recurrence after corneal transplantation. There was no difference between PK (6.79%) and LK (5.96%) in recurrence rate (P = 0.883). A higher rate of recurrences was found in those with preoperative hypopyon (10.90%), corneal perforation (12.00%), corneal infection expanding to limbus (20.69%), or lens infection with extracapsular cataract extraction (50%; P<0.05). The 3 main kinds of recurrence were: (1) recurrent infection from recipient bed to graft, and once recurrent infection invaded the graft, the inflammation progressed more rapidly; (2) white mushroom-shaped hypopyon with anterior chamber recurrence; (3) infection in the posterior chamber and vitreous opacity on posterior segment recurrence. Location of recurrence was: recipient bed (70.18%), anterior chamber (7.02%), and posterior segment (22.81%). The overall cure rate was 82.46%, which included drug therapy (28.07%) and surgical treatment (54.39%). Hypopyon, corneal perforation, corneal infection expanding to limbus and lens infection are major risk factors for recurrence of fungal keratitis after corneal transplantation. Based on the clinical features of recurrence, appropriate treatment options can help to control the recurrent infection.
Article
The aim was to study the outcomes and results of therapeutic penetrating keratoplasty (Th PK) at a tertiary eye care hospital in northern India. In this retrospective interventional study, a cohort of 506 eyes that underwent a Th PK for microbial keratitis was evaluated. Th PK was performed in cases of recalcitrant microbial keratitis with impending perforation (descemetocele formation) or perforation (>3 mm). Medical records were reviewed for demographic details, risk factors, ulcer and perforation size, microbiological investigations, size of donor and recipient beds, postoperative complications, and anatomical and visual outcomes. Anatomical success was seen in 454 eyes (89.7%). Preoperatively, the corrected distance visual acuity was <3/60 in 495 eyes (97.8%); after performing the Th PK, the corrected distance visual acuity was <3/60 in 249 eyes (49.2%), 3/60 to 6/60 in 182 eyes (35.9%), and >6/60 in 75 eyes (14.8%). Eyes with smaller grafts (<9 mm) had better anatomical and visual outcomes compared with eyes with larger grafts (9-11 mm; P = 0.03 and >11 mm; P = 0.0). A higher success rate was achieved with pure bacterial or fungal organisms rather than with mixed infections. A higher incidence of secondary glaucoma was seen in eyes with perforated ulcers (29.36%; 111/378) than in eyes without perforation (11.71%; 15/128) (P <.01) and in eyes with larger graft sizes (>11 mm and 9-11 mm) than in eyes with smaller graft sizes (<9 mm) (P <0.01). Th PK has a definitive role in the management of severe and refractory keratitis with a high success in restoring anatomical integrity and providing useful vision. Better outcomes may be achieved with early intervention before perforation or limbal/scleral extension.
Article
To report outcomes after minimal trephination penetrating keratoplasty (PKP) in the treatment of severe fungal keratitis complicated with hypopyon. Retrospective case series. Series of 19 eyes in 19 patients with severe fungal keratitis complicated with hypopyon that received minimal trephination PKP. The host trephination was made equal to or smaller than the margin of the corneal lesion. Fluconazole (0.2%) was used to irrigate the trephined edge and anterior chamber during surgery, followed by irrigation of the anterior chamber with a 0.02% fluconazole solution after graft transplantation. Postoperative complications, graft rejection, transparency rate, and visual acuity were recorded. Patients were followed postoperatively for 18 to 34 months (mean 28.6 months). At 18 months after PKP, 18 grafts (94.7%) remained clear and 14 eyes (73.7%) had improved visual acuity. Three eyes (15.8%) with secondary glaucoma complications after PKP were treated with subsequent trabeculectomy. Recurrent infection was found in only 1 eye (5.26%) after transplantation and was successfully managed. Immune graft rejections were not observed in any patient during the follow-up period. The minimal trephination technique in combination with antifungal therapy was effective in the treatment of severe fungal keratitis with large corneal lesions and hypopyon.
Article
This is a commentary on article Sharma N, Chacko J, Velpandian T, Titiyal JS, Sinha R, Satpathy G, Tandon R, Vajpayee RB. Comparative evaluation of topical versus intrastromal voriconazole as an adjunct to natamycin in recalcitrant fungal keratitis. Ophthalmology. 2013 Apr;120(4):677-81.
Article
To determine the surgical outcomes of therapeutic penetrating keratoplasty (PKP) and its role in the management of microbial keratitis.
Article
Objective To compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis. Methods This phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400. Main Outcome Measures The primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty. Results A total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycin-treated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient = −0.18 logMAR; 95% CI, −0.30 to −0.05; P = .006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio = 0.42; 95% CI, 0.22 to 0.80; P = .009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient = −0.41 logMAR; 95% CI, −0.61 to −0.20; P < .001; odds ratio for perforation = 0.06; 95% CI, 0.01 to 0.28; P < .001), while non- Fusarium cases fared similarly (regression coefficient = −0.02 logMAR; 95% CI, −0.17 to 0.13; P = .81; odds ratio for perforation = 1.08; 95% CI, 0.48 to 2.43; P = .86). Conclusions Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases. Application to Clinical Practice Voriconazole should not be used as monotherapy in filamentous keratitis. Trial Registration clinicaltrials.gov Identifier: NCT00996736
Article
Fungal keratitis (FK) is a sight-threatening disease, more prevalent in developing regions. The present retrospective study was conducted in order to evaluate the epidemiologic and clinical aspects and the progression of FK in patients treated at two ophthalmologic reference centers in Southeast Brazil. The charts of patients with infectious keratitis treated between 2000 and 2004 were reviewed. For the 66 cases of FK confirmed by microbiological analysis, data related to patient, disease, and therapeutic approaches were obtained. Mean patient age was 40.7+/-16 years. Fifty-three were men and 13 were women. Ocular trauma occurred in 40% of cases (27). Previous medications taken by the patients were quinolone in 72.5% and antimycotics in 30%. Visual acuity (VA) at presentation was >0.3 in 16% and <0.1 in 74.5%. Penetrant keratoplasty was performed in 38% and evisceration in 15%. The causing agents were Fusarium sp in 67%, Aspergillus sp in 10.5%, and Candida sp in 10%. Medication alone resolved 39% of cases within a mean period of 24.5+/-12 days. Final VA was >0.3 in 28%, and <0.1 in 63%. Fungal keratitis presented as a disease with severe complications, predominantly among young males, and was mostly caused by filamentous fungi. The present information permits the establishment of preventive strategies. Reducing the time between onset and treatment and using more accessible specific medication would reverse the negative prognosis.
Article
Aboriginals and Torres Strait Islanders form a significant proportion of the population in far north Queensland and are at increased risk for many eye conditions. This study describes the pattern of fungal keratitis seen at Cairns Base Hospital, far north Queensland, Australia. A retrospective review of all cases of culture positive fungal keratitis presenting between 1998 and 2008. The records of 17 patients were reviewed for epidemiological, risk factor, microbiological, treatment and outcome data. The study included 16 eyes from 16 patients. Five (31.25%) patients were of Aboriginal and Torres Strait Islander descent. Pre-disposing factors were ocular trauma (n = 7) and contact lens wear (n = 3). No patients were on topical steroids at presentation. All patients grew filamentous fungi with Fusarium the most common isolate (50%). Aspergillus, Curvularia and Lasiodiplodia theobromae were the next most common accounting for two cases each. Two patients developed corneal perforations, whereas two required penetrating keratoplasty and one required evisceration. Eight patients had a visual acuity of 6/18 or better at presentation and this increased to 13 patients at final follow up. A significant proportion of the patients presenting to Cairns Base Hospital with fungal keratitis are Indigenous. The very high percentage of cases due to filamentous fungi is similar to other tropical regions of the world. The very low rates of Candida infection and steroid use prior to presentation are in contrast to studies from temperate areas such as Melbourne and Philadelphia.
Article
Medical treatment failure necessitated surgery in nine cases of fungal keratitis. Therapeutic surgery eliminated fungal infection in seven cases, and useful vision was retained in five out of six penetrating keratoplasties. In three cases Natamycin (Pimaricin) therapy rendered fungi non-viable, but two were demonstrable by histopathology. These results suggest that antifungal treatment should be applied for as long as possible before therapeutic surgery in order to improve the final visual outcome.
Article
As Jones has emphasized, the successful management of microbial keratitis, fungal or otherwise, necessitates five steps: (1) clinical suspicion and clinical diagnosis; (2) performing the proper laboratory procedures; (3) initiating antimicrobial therapy based on the results of laboratory studies; (4) modifying the initial therapy based on the clinical response; and (5) deciding correctly when and how to terminate therapy. Keratomycosis poses special diagnostic and therapeutic challenges for ophthalmologists because of its low incidence, and its resistance to treatment, because of the lack of antifungal agents with good penetration into the eye, and because of the difficulties in obtaining meaningful in vitro drug susceptibility results for fungal isolates. We believe, however, that ophthalmologists are now diagnosing keratomycosis earlier and treating it more effectively.