ORIGINAL ARTICLE

Minimal trephination penetrating keratoplasty for severe fungal keratitis complicated with hypopyon Yang Liu, MD, PhD,* Hui Jia, MD, PhD,* Xiaoru Shi, MD, PhD,* Jiao Wang, MD,* Yan Ning, MD,* Bing He, MD, PhD,* Chunmei Wang, MD,* Xiaodong Zheng, MD, PhD† ABSTRACT ● RÉSUMÉ Objective: To report outcomes after minimal trephination penetrating keratoplasty (PKP) in the treatment of severe fungal keratitis complicated with hypopyon. Design: Retrospective case series. Participants: Series of 19 eyes in 19 patients with severe fungal keratitis complicated with hypopyon that received minimal trephination PKP. Methods: 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. Results: 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. Conclusions: The minimal trephination technique in combination with antifungal therapy was effective in the treatment of severe fungal keratitis with large corneal lesions and hypopyon. Objet : Compte-rendu des résultats de la kératoplastie pénétrante thérapeutique (KPT) par trépanation de taille minimale pour le traitement de la kératite fongique sévère avec complication d’hypopion. Méthodes : Rétrospective d’une série de cas de 19 yeux de 19 patients qui, ayant une sévère kératite fongique avec une complication d’hypopion, ont reçu une KPT par trépanation de taille minimale. La trépanation de l’hôte était égale à ou plus petite que la marge de la lésion cornéenne. Le Fluconazole (0,2%) a servi à l’irrigation de la bordure trépanée et la chambre antérieure pendant la chirurgie, suivie de l’irrigation de la chambre antérieure avec une solution de fluconazole 0,02% après la transplantation de la greffe. Les complications postopératoires, le rejet des greffes, le degré de transparence et d’acuité visuelle ont été notés. Résultats : Les patients ont eu un suivi postopératoire de 18 à 34 mois (28,6 mois en moyenne). Puis, 18 mois après la KPT, 18 greffes (94,7%) étaient demeurées claires et 14 yeux (73,7%) avaient une acuité visuelle améliorée. Trois yeux (15,8%), qui eurent la complication d’un glaucome secondaire après la KPT, ont été soumis à une trabéculectomie ultérieure. Une infection récurrente a été notée dans un seul œil (5,26%) après la transplantation et a été traitée avec succès. Aucun rejet immunitaire des greffes n’a été noté chez les patients pendant la période de suivi. Conclusions : La technique de trépanation minimale, combinée avec la thérapie antifongique, a été efficace pour le traitement de la kératite fongique sévère avec de grandes lésions cornéennes et l’hypopion.

Fungal keratitis remains a serious blinding eye disease in China. In recent years, the incidence of corneal infection of fungal origin has been increasing because of the widespread use of antibiotics and inappropriate application of steroids.1,2 Fungal keratitis may manifest with a variety of clinical signs, often characterized by a fluffy border, small satellite lesions around the ulcer, and patchy or lumpy deposits behind the cornea; occasionally, viscous hypopyon may occur. In advanced cases, infection can progress to fungal endophthalmitis, especially when corneal perforation occurs.

A typical feature of fungal keratitis is its slow onset and gradual progression, often presenting as a relatively “quiet” eye, in contrast with bacterial keratitis. Its chronic course and concealed signs often puzzle clinicians, making early diagnosis difficult and often resulting in delayed treatment and poor prognosis. Fungal keratitis becomes much more difficult to treat once fungi enter the anterior chamber.3 Appropriate antifungal agents are effective in controlling early stages of the infection, whereas therapeutic penetrating keratoplasty (PKP) is the treatment of choice for intractable cases, with full-thickness corneal layers

From the *Department of Ophthalmology, First Hospital of Jilin University, Changchun, People’s Republic of China; and †Department of Ophthalmology, Ehime University School of Medicine, Toon City, Ehime, Japan

Can J Ophthalmol 2013;48:529–534 0008-4182/13/$-see front matter & 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2013.05.017

Originally received Oct. 12, 2012. Final revision May 24, 2013. Accepted May 30, 2013 Correspondence to Hui Jia, MD, Department of Ophthalmology, First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, P.R. China; [email protected] CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013

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Minimal trephination PKP for severe fungal keratitis—Liu et al. involved in restoring vision and salvaging the eye.4,5 In conventional PKP procedures, the recipient bed is prepared with a 0.25- to 1.0-mm larger trephination than the lesion edge to eliminate infected tissue.6 However, when the graft diameter exceeds 8.0 mm or the graft is eccentric, the rate of graft failure increases remarkably.3,4 The dilemma of choosing a smaller graft size to increase the chances of graft survival, over a larger graft to completely remove the fungal infection, remains a big hurdle for ophthalmologists.4 Furthermore, patients are often referred to our facility at a very advanced stage of infection, complicated with large corneal lesions and hypopyon. In cases like these, removing the entire lesion is difficult and impractical. Therefore, we report in this article a modified approach, namely, a minimal trephination PKP procedure, where the edge of the lesion is the cutting edge for trephination, and in some cases, the cutting edge was even smaller than the lesion size. This procedure was successfully performed between November 2007 and March 2009 on 19 eyes of 19 patients who suffered from severe fungal keratitis complicated with hypopyon.

METHODS This is a retrospective study of a consecutive case series, approved by the institutional ethics committee of First Hospital of Jilin University informed consent was obtained from each patient participating in this study. Inclusion criteria required that patients be diagnosed with severe fungal keratitis with hypopyon, unresponsive to antifungal chemotherapy, and that patients ultimately underwent PKP. All cases were confirmed with the diagnosis of fungal keratitis as described in the following section. The postoperative follow-up period was at least 18 months. Diagnostic methods

Confocal microscopy (NIDEK ConfoScan-4, Albignasego, Italy) was used to examine the cornea. Corneal scrapings were incubated and examined as wet mounts with potassium hydroxide before surgery in all patients. The corneal button and hypopyon specimens obtained during PKP were also subjected to potassium hydroxide– based smear and fungal culture for strain identification. Fungal presence in corneal scrapings, confocal microscopic imaging, or positive culture confirmed the diagnosis. Medical treatment before surgery

Before surgery, patients received hourly drops of 0.5% fluconazole (ShandongBausch Pharmaceutical, Jinan, China), and 5% natamycin (North China Pharmaceutical, Shijiazhuang, China), intermittent debridement of the ulcerative region, intravenous administration of fluconazole (Pfizer PGM, Pocé-sur-Cisse, France) 200 mg once daily, or oral itraconazole (Xian-Janssen Pharmaceutical,

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Table 1—Size of corneal lesion and trephination (mm) Case No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

Corneal Lesion

Recipient

Donor

                  

8.0 8.0 8.0 7.5 9.0 13  11.5 8.0 7.5 7.5 7.5 7.5 7.5 7.25 7.25 7.5 7.75 7.25 8.0 7.5

8.25 8.25 8.25 7.75 9.25 13  11.5 8.25 7.75 7.75 7.75 7.75 7.75 7.5 7.5 7.75 8.0 7.5 8.25 7.75

8.5 8.2 8.0 8.0 9.5 13 8.5 8.0 8.0 7.5 7.5 8.0 7.25 7.5 8.0 8.0 7.5 8.5 7.5

8.5 9.0 8.5 8.5 9.0 11.5 9.0 8.0 7.5 7.5 7.8 7.0 8.0 7.5 7.8 8.2 7.8 8.0 7.5

Xian, China) 200 mg daily for 5 to 10 days. The carbonic anhydrase inhibitor, methazolamide tablets (Hangzhou Aoyipolien Pharmaceutical, Hangzhou, China), were administered for cases with significantly thinned corneas to prevent perforation. In addition, 1% atropine ointment (Shengyang Xingqi Pharmaceutical, Shengyang, China) once daily, 0.1% pranoprofen (Senju Pharmaceutical, Fukusaki, Japan) bid and 0.3% levofloxacin (Santen Pharmaceutical, Shiga, Japan) tid eye drops were administered to extinguish inflammation and prevent bacterial co-infection. PKP was performed when corneal ulceration deteriorated or did not improve after intensified antifungal therapy. The average duration of antifungal treatment was 36 ⫾ 3.5 (range 31–42) days. Surgical procedure

Our minimal trephination PKP procedure was performed on all 19 eyes using a corneal allograft under local anaesthesia. For trephination, the cutting edge was made at a size equal to (5 eyes) or 0.25 to 0.5 mm smaller than (14 eyes) the margin of the corneal lesion. The diameter of the recipient corneal trephination ranged from 7.25 to 9.00 mm in 18 cases, and an oval-shaped graft (horizontal  vertical diameter ¼ 13 mm  11.5 mm) was made in 1 case because of the overly large lesion exceeding the corneal limbus (Table 1). When the diseased cornea was removed, purulent materials and fibrous membrane were observed on the corneal endothelium and at the anterior chamber angle. Purulent materials and fibrous membrane were carefully removed with fine forceps and subjected to smear test and culture. The anterior chamber angle and iris surface were then cleaned and irrigated carefully with 100 mL of 0.2% fluconazole. Residual necrotic portions and purulent material attaching to the groove of recipient beds were cleaned with forceps and irrigated with antifungals as well. The iris-lens diaphragm was preserved perfectly, and peripheral iridectomy was not performed during the surgery to minimize the

CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013

Minimal trephination PKP for severe fungal keratitis—Liu et al. possibility of fungal migration from the anterior chamber to the posterior chamber. A donor corneal button with a diameter 0.25 to 0.5 mm larger than recipient site was transplanted and secured in place with 16 interrupted 10–0 nylon sutures. The anterior chamber was then washed with 0.02% fluconazole again, with an aliquot of 0.5 mL also injected subconjunctivally at the end of the surgery. Postoperative treatment

After PKP, 5% natamycin drops were administered every 2 hours for 1 month along with oral itraconazole 200 mg daily for 2 weeks to prevent fungal recurrence. Topical 1% cyclosporine A (North China Pharmaceutical, Shijiazhuang, China) was applied qid; 1% atropine ointment, 0.1% pranoprofen, and 0.3% levofloxacin eye drops were administered as described earlier. Oral cyclosporine (5 mg/kg; North China Pharmaceutical, Shijiazhuang, China) was administered bid for 3 months. The blood level of cyclosporine was monitored biweekly along with liver and kidney functions. If no signs of fungal recurrence were present 2 weeks after PKP, topical and systemic steroids were administered. Topical 3% tobramycin and 1% dexamethasone ointment (Alcon-Couvreur n.v., Rijksweg, Belgium) were used tid for 4 weeks followed by 0.1% fluorometholone drops (Santen Pharmaceutical, Shiga, Japan) tid for 6 months, tapered over 1 year. Intravenous dexamethasone 10 mg daily was used for 1 week followed by 20 mg oral prednisone tapered over 4 weeks.

RESULTS From November 2007 to March 2009, 19 eyes of 19 patients met the inclusion criteria. There were 11 (57.9%) male patients and 8 (42.1%) female patients, with a mean age of 54.1 (range 31–72) years. Ten patients (52.6%) reported a history of eye injury, 8 of which were associated with agriculture materials and 2 were from foreign body invasion such as sand. No patients in this study were contact lens users. Before referral to our hospital, 1 patient had received long-term subconjunctival injections of corticosteroids because of a misdiagnosis of iridocyclitis. All 19 patients were transferred to us after unsuccessful treatment with antibiotics, antivirals, or antifungal drugs. On admission, the patients had ocular pain in the affected eyes combined with migraine, redness, and swelling of eyelids and ciliary congestion. Four patients had a best corrected visual acuity (BCVA) of light perception, and 15 patients had a BCVA of hand motion at 10 to 30 cm. Twelve patients had complications of secondary glaucoma before surgery. Apparent vitreous infection was not found in any case, as evidenced by ultrasound examination before surgery.

Table 1). The lesion was located at the central cornea in 17 eyes. Two eyes had overly large paracentral lesions exceeding the temporal corneal limbus. All affected eyes were complicated with hypopyon. All 19 eyes (100%) were smear-positive for typical fungal filaments, and 17 eyes (89.5%) also had positive detection by confocal microscopy. Hypopyon specimens on potato-dextrose agar were all positive for fungal pathogens and negative for bacteria. Fourteen specimens were identified as Fusarium (73.7%), 4 as Aspergillus (21.1%), and 1 as Candida albicans (5.2%).

Clinical features and microbiologic examinations

Graft clarity

The average size of corneal lesions ranged from 7.5  7.5 mm to 13  11.5 mm (horizontal  vertical diameter;

After surgery, average length of hospitalization was 19.5 ⫾ 5.7 (13–30) days. The average follow-up period was 28.6

Fig. 1 — Slit-lamp examination demonstrating preoperative and postoperative outcomes of a patient with fungal keratitis (Case 8). A, Intractable corneal ulceration did not respond to antifungal treatment for 40 days (lesions size: 8.0 mm  8.0 mm). B, Two weeks after minimal trephination penetrating keratoplasty (trephination size: 7.5 mm in diameter, graft size: 7.75 mm in diameter). C, Twenty-two months after suture removal showing a perfectly clear corneal graft without fungal recurrence. Final best corrected visual acuity was 20/20.

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Minimal trephination PKP for severe fungal keratitis—Liu et al. daily for 21 days and an hourly dose of 5% natamycin drops for 30 days. Topical and oral steroids were then administered as described earlier after the infection was successfully controlled. Immune graft rejections were not observed in any patient during the follow-up period. A summary of treatment comparisons for fungal keratitis in this study, along with those in the published literature, is presented in Table 2. Fig. 2 — Slit-lamp examination showing preoperative and postoperative view of another patient with fungal keratitis (Case 14). A, Large corneal ulcer of 7.5 mm  7.5 mm and apparent hypopyon can be appreciated. B, Clear graft at 9 months after minimal trephination penetrating keratoplasty. Best corrected visual acuity was 20/40 (trephination size: 7.25 mm in diameter, graft size: 7.5 mm in diameter).

⫾ 3.9 (18–34) months. During the follow-up period after PKP, the corneal grafts of all 19 patients except 1 (Case 19) were transparent with well-formed anterior chamber and minimal iris posterior synechiae (Figs. 1 and 2). The corneal transparency rate was 94.7% (18/19 eyes). The morphology of corneal endothelia in these 18 patients was normal showing uniformly sized cells of predominantly hexagonal shape. The average endothelial cell density of donor corneas before surgery, and at 1 and 6 months after PKP, was 2557.89 ⫾ 439.86, 2442.67 ⫾ 373.97, and 2317.72 ⫾ 477.02 cells/mm², respectively. Cell density in the recurrent case was 2531, 1324, and 1037 cells/mm², respectively; however, this corneal graft remained semitransparent at the final follow-up visit (18 months). Visual acuity

As mentioned earlier, the preoperative BCVA was either light perception or hand motion. At the final follow-up visit after surgery, 2 eyes had a BCVA of ≥20/40, 4 eyes were between 20/100 and 20/40, and 8 eyes were between 20/200 and 20/100. The BCVA of the remaining 5 eyes complicated with severe cataract before surgery did not change. Complications

Cataract complicated with infection was found in 14 eyes and was the primary factor affecting visual acuity in patients postoperatively. Cataract surgery was not performed during the PKP procedure and follow-up period. Trabeculectomy was performed in 3 eyes with secondary glaucoma on days 10, 17, and 28 after PKP, respectively, and no other patients required glaucoma medication. Fungal recurrence was observed in only 1 case (Case 19) who presented with purulent material at the cutting edge around the suture and in the anterior chamber on day 3 after surgery. The anterior chamber and recipient bed edge were immediately cleaned thoroughly and irrigated with 0.2% fluconazole again. Fungal hyphae were found in the purulent material from the trephined edge on smear test. This patient was prescribed oral itraconazole 200 mg

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DISCUSSION With the increasing incidence of fungal keratitis, clinical research in this area of ocular infection is becoming more important.7–9 Although a variety of antifungal agents are available in clinics,10,11 many cases still do not respond well to medication. Fungal resistance to antifungal agents and inappropriate or delayed diagnosis are some of the main reasons.2 The most frequently isolated strain in our cases was Fusarium (71.4%), similar to the rates reported by PérezBalbuena et al.,12 Ibrahim et al.,13 and Wang et al.14 In cases of serious fungal keratitis combined with hypopyon, it is possible that the hypopyon contains fungi even though the depth of the anterior chamber is normal and no apparent corneal perforation is detected. In this study, profuse hyphae were found in the anterior chamber along with purulent exudation on the endothelial layers in all cases who did not respond to intensive antifungal treatments. The positive rate of fungal culture from corneal lesions and hypopyon specimens was 100% in this study, which is higher than the 49.2% reported by Prajna et al.15 and Mahdy et al.8 This difference may be due to the fact that our patients were more severely infected and with a prolonged duration of corneal ulceration before referral to our hospital. Furthermore, our results indicated that fungi were likely to spread into the anterior chamber in severe and intractable cases. The decision for an earlier surgical approach seems to be crucial for saving the endothelial layer and increasing the chances of cure via a less invasive surgical approach such as lamellar keratoplasty. The conventional PKP procedure for infectious keratitis is to make the recipient bed 0.25 to 1.0 mm larger in diameter than the lesion edge to eradicate the infection and minimize the risk for recurrence.6,16 However, for severe cases with large corneal lesions, the area of trephination is often expanded to the very peripheral cornea or even to the limbus or sclera. This will increase postoperative complications such as a shallow anterior chamber, vulnerable angle, and high rejection rates, resulting in graft opacity, angiogenesis, secondary glaucoma, and, finally, leading to graft failure.16 In this study, we challenged this conventional rule, using the edge of the lesion as the cutting edge for trephination. Even so, in some cases, the cutting edge was slightly smaller than the lesion edge. Our results showed that the anterior chamber angle was well preserved and the

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Minimal trephination PKP for severe fungal keratitis—Liu et al. Table 2—Comparison of treatments for fungal keratitis in this study with those in the literature This Study Before MPKP Topical

Systemic During MPKP Irrigation

Cleaning Trephination size After MPKP Topical

Systemic Steroid n

Other Studies

0.5% fluconazole and 5% natamycin 0.1% pranoprofen 1% atropine sulfate Intravenous injection of fluconazole or oral itraconazole

0.5% fluconazole and 5% natamycin17 0.25% amphotericin B or 5% natamycin drops6,17,19 1% atropine sulfate17 Intravenous injection of fluconazole17 or oral itraconazole6

0.2% fluconazole solution followed by 0.02% fluconazole solution after graft was transplanted

0.2% fluconazole solution17

Clean completely the groove of recipient beds and anterior chamber Equal to or smaller than the infiltration area

0.02% fluconazole solution1 0.05% amphotericin B19 Clean completely anterior chamber17,19 Larger than the infiltration area6,17,19 0.5% fluconazole6,17,19 0.25% amphotericin B ointment6,17 1% cyclosporine A17

5% natamycin 0.1% pranoprofen 1% atropine sulfate 0.3% levofloxacin 1% cyclosporine A Oral cyclosporine A Oral itraconazole Topical and systemic*

Oral fluconazole17,19 Topical and systemic6,17

Medicine was administrated if no typical signs of fungal recurrence 2 weeks (average) after surgery.

risks for angiogenesis and postoperative immune rejection were minimized. In this study, none of the corneal allografts developed corneal allograft rejection during the follow-up period. The rejection rate is lower than 29.6%17 or 38.5%4 as previously reported by Xie et al. The rationale of our minimal trephination PKP procedure is that, as evidenced by our confocal microscopic studies (data not shown), most of the fungal hyphae were localized in the centre of corneal lesion and, if any exist, the residual few hyphae in the remaining host cornea can mostly be removed by scraping and debridement using microforceps in combination with irrigation of a high concentration of 0.2% fluconazole. Although recurrence was observed in 1 case 3 days after surgery, the infection was successfully controlled after anterior chamber irrigation with 0.2% fluconazole solution again and systemic application of antifungal agents. The corneal transparency rate in our study is 94.7%, which is higher than previously reported.18–20 One benefit is the absence of graft rejection in our cases. In addition, during the early period after PKP, administration of oral cyclosporine A, a potent T cell regulatory agent, may delay or reduce the occurrence of rejections. Further investigations are needed to elucidate the effect and proper dose of this medicine in severely infected cases after PKP. One limitation of this study was that we should be aware of the fact that extrapolation of these data from this study should be done carefully because we did not include a control group to show the effectiveness of PKP treatment only. Besides our minimal penetration PKP techniques, prolonged and aggressive administration of topical and systemic medication in this study may all contribute to the success of treatment in this study. The applicability and reproducibility of this technique need to be further studied. After removal of the lesions, 0.2% fluconazole irrigating solution was applied to the anterior chamber and the

residual lesion edge. This would be effective in preventing fungal recurrence after surgery.17 Lenses were untouched even in cases of cataract, and by protecting the iris–lens diaphragm, fungi were prevented from spreading into the vitreous cavity. When the donor cornea was transplanted, irrigation with a lower concentration of 0.02% fluconazole solution was used to prevent damage to the donor endothelium. The normal morphology of endothelium and low recurrence rates in our cases demonstrated that the appropriate application of fluconazole in a high concentration is safe and effective. Twelve eyes experienced secondary glaucoma before surgery and were treated with goniosynechialysis and cleaning of purulent materials in the anterior chamber and angles during surgery. Three patients experienced development of secondary glaucoma, and subsequent trabeculectomy was performed to control intraocular pressure. In summary, our study showed that our minimal trephination PKP technique was effective in managing severe fungal keratitis of large corneal lesions complicated with hypopyon. Furthermore, the combination of this modified PKP procedure and appropriate antifungal medication during and after the surgery are crucial for increased rates of graft survival and decreased rates of fungal recurrence.

Disclosure: The authors have no proprietary or commercial interest in any materials discussed in this article.

REFERENCES 1. Bharathi MJ, Ramakrishnan R, Vasu S, et al. Epidemiological characteristics and laboratory diagnosis of fungal keratitis. A threeyear study. Indian J Ophthalmol. 2003;51:315-21.

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Minimal trephination PKP for severe fungal keratitis—Liu et al. 2. Srinivasan M. Fungal keratitis. Curr Opin Ophthalmol. 2004;15: 321-7. 3. Cristol SM, Alfonso EC, Guildford JH, et al. Results of large penetrating keratoplasty in microbial keratitis. Cornea. 1996;15:571-6. 4. Xie L, Zhai H, Shi W. Penetrating keratoplasty for corneal perforations in fungal keratitis. Cornea. 2007;26:158-62. 5. Yao YF, Zhang YM, Zhou P, et al. Therapeutic penetrating keratoplasty in severe fungal keratitis using cryopreserved donor corneas. Br J Ophthalmol. 2003;87:543-7. 6. Shi W, Wang T, Xie L, et al. Risk factors, clinical features, and outcomes of recurrent fungal keratitis after corneal transplantation. Ophthalmology. 2010;117:890-6. 7. Li L, Wang Z, Li R, et al. In vitro evaluation of combination antifungal activity against Fusarium species isolated from ocular tissues of keratomycosis patients. Am J Ophthalmol. 2008;146:724-8. 8. Mahdy RA, Nada WM, Wageh MM. Topical amphotericin B and subconjunctival injection of fluconazole (combination therapy) versus topical amphotericin B (monotherapy) in treatment of keratomycosis. J Ocul Pharmacol Ther. 2010;26:281-5. 9. Pearce JW, Giuliano EA, Moore CP. In vitro susceptibility patterns of Aspergillus and Fusarium species isolated from equine ulcerative keratomycosis cases in the midwestern and southern United States with inclusion of the new antifungal agent voriconazole. Vet Ophthalmol. 2009;12:318-24. 10. Tu EY. Alternaria keratitis: clinical presentation and resolution with topical fluconazole or intrastromal voriconazole and topical caspofungin. Cornea. 2009;28:116-9.

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11. Yilmaz S, Ture M, Maden A. Efficacy of intracameral amphotericin B injection in the management of refractory keratomycosis and endophthalmitis. Cornea. 2007;26:398-402. 12. Pérez-Balbuena AL, Vanzzini-Rosano V, Valadéz-Virgen Jde J, et al. Fusarium keratitis in Mexico. Cornea. 2009;28:626-30. 13. Ibrahim MM, Vanini R, Ibrahim FM, et al. Epidemiologic aspects and clinical outcome of fungal keratitis in southeastern Brazil. Eur J Ophthalmol. 2009;19:355-61. 14. Wang L, Sun S, Jing Y, et al. Spectrum of fungal keratitis in central China. Clin Experiment Ophthalmol. 2009;37:763-71. 15. Prajna NV, Mascarenhas J, Krishnan T, et al. Comparison of natamycin and voriconazole for the treatment of fungal keratitis. Arch Ophthalmol. 2010;128:672-8. 16. Sony P, Sharma N, Vajpayee RB, et al. Therapeutic keratoplasty for infectious keratitis: a review of the literature. CLAO J. 2002;28: 111-8. 17. Xie L, Dong X, Shi W. Treatment of fungal keratitis by penetrating keratoplasty. Br J Ophthalmol. 2001;85:1070-4. 18. Killingsworth DW, Stern GA, Driebe WT, et al. Results of therapeutic penetrating keratoplasty. Ophthalmology. 1993;100: 534-41. 19. Ti SE, Scott JA, Janardhanan P, et al. Therapeutic keratoplasty for advanced suppurative keratitis. Am J Ophthalmol. 2007;143:755-62. 20. Xie LX, Zhai HL. Penetrating keratoplasty for treatment of fungal keratitis with corneal perforation. Zhonghua Yan Ke Za Zhi. 2005;41:1009-13.

CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013

Minimal trephination penetrating keratoplasty for severe fungal keratitis complicated with hypopyon.

To report outcomes after minimal trephination penetrating keratoplasty (PKP) in the treatment of severe fungal keratitis complicated with hypopyon...
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