March 2009.indd SQU MED J, APRIL 2009, VOL. 9, ISS. 1, PP. 59-62, EPUB 16TH MAR 2009 SUBMITTED - 23RD JUNE 08 REVISION REQ. 18TH NOV 08, REVISION RECD. 31ST JAN 09 ACCEPTED - 2ND FEB 09 A Retrospective Study of Fungal Corneal Ulcers in the South Sharqiyah Region in Oman *Thara Idiculla, George Zachariah, BR Keshav, Somansu Basu Department of Ophthalmology, Sur Regional Hospital, Sultanate of Oman *To whom correspondence should be addressed. Email: gorgtara@omantel.net.om C L I N I C A L A N D B A S I C R E S E A R C H باملنطقة الفطريات عن الناجت القرنية لتقرحات استعادية دراسه عمان في (جنوب) الشرقية سومانسو باسو كيشاف ، آر بي ، زكريا جورج ايديكولال ، ثارا . الفطريات عن الناجتة القرنية التقرحات عالج وطرق السائدة اهرية األحياء وحتديد عوامل االختطار ومعرفة احلدوث معدل امللخص: الهدف: دراسة 2004 إلى للفترة من يناير (عمان) صور مبستشفى قسم العيون في عوجلت للحاالت التي القرنية للتقرحات حتليلية استعادية دراسة هذه الطريقة: عوامل ملعرفة الفطريات عن الناجتة القرنية بالتقرحات الزرع) طريق (عن إصابتها ثبت وثالثني حالة الثنني الطبية امللفات مراجعة 2007 . مت ديسمبر . ــبب الفطريات بس %13.22 منها القرنية كان قرحة من 242 حالة تعاني بني للعالج. النتائج: من ــتجابة واالس اتبرية ونتائج الفحوص االختطار اجلزء األكبر من على (34%) يَّة اشِ والرَشَّ (50%) زَالَوِيَّة ِغْ امل الفطريات حازت . منها (31.38% ) الفطريات شكلت بالزرع موجبة 102 حالة ومن بني (25% ) في العني وإصابات احلاالت %31.25 من في املوضعي الستيرويد كاآلتي: استخدام فكانت االختطار عوامل أما . الفطري الهياليني الطيف الناجت التقرح (%0.15) . اخلالصة: يبقى ــي ــني ب االمفوتيريس مع لوحده أو (2%) كيتوكينازول لعالج ــتجابت اس (60.62%) أكثرية احلاالت . ــا منه الفطريات . االختطار عوامل العني أهم وإصابات املوضعية الستيرويد ــتقات ملش العشوائي االستخدام . البصري للعجز رئيسيا ــببا س عن الفطريات . احلاالت معظم في فعاال جدا واالمفوتيريسني بالكيتوكينازول العالج املوضعي كان . هذه املنطقة في انتشارا األكثر املسببات من اخليطية . الزرع مستنبتات ، ،الفطريات القرنية ،التهاب القرنية قرحة الكلمات: مفتاح ABSTRACT Objectives: To study the incidence, identify the risk factors and determine the predominant microorganisms and treat- ment regimen of fungal corneal ulcers. Methods: This was a retrospective analysis of corneal ulcers treated in the Ophthalmology Department of Sur Hospital, Oman, undertaken from January 2004 to December 2007. Medical and microbiology records of thirty two culture proven cases of fungal keratitis were reviewed for risk factors, laboratory findings and response to treatment. Results: Out of the total 242 corneal ulcers, 3.22 % were fungal. Among the 02 culture positive cases, 3.38 % were fungal isolates. Fusarium spp (50%) and Aspergillus spp (34.4%) predominated in the hyaline fungal spectrum. The important risk factors were topical steroid usage in 3.25 % of cases and ocular injury in 25 %. The majority of cases (90.62%) responded to 2% ketoconazole alone or in combination with 0.5% amphotericin B. Conclusion: Fungal ulcer remains one of the leading causes of visual disability. Indiscriminate use of topi- cal steroids and ocular trauma are the most important risk factors. Filamentous fungi are common aetiological agents in this region. Topical ketoconazole and amphotericin B were very effective for most of the cases. Key words: Corneal ulcer; Keratitis; Fungi; Culture media. Advances in Knowledge • Filamentous fungi are frequent causes of corneal ulcer in hot and dry climatic regions and it is imperative to keep a high level of suspicion. • Direct wet mount potassium hydroxide (KOH) preparation is an essential screening test in corneal ulcers. • Therapies with reconstituted antifungal agents are highly effective. • Treatment has to be continued for a minimum of three to four weeks. TH A R A I D I C U L L A , G E O R G E Z A C H A R I A H , K E S H AV A N D S O M A N S U B A S U 60 FUNGAL KERATITIS CAN POSE DIAGNOSTIC and therapeutic challenges for ophthalmolo-gists. Although fungi cause only 5 to 10% of all corneal infections, devastating ocular damage can occur if they are not diagnosed promptly and treated effectively. Through a defect in the epithelial barrier, fungi may gain access into the corneal stroma where they can cause tissue necrosis and a host inflamma- tory reaction. In addition, they may penetrate through an intact Descemet’s membrane. Once fungi reach the anterior chamber or spread to adjacent sclera, the in- fection becomes very difficult to control due to poor penetration of antimycotic agents. The pattern of mycotic keratitis varies with geo- graphic region according to the local climate.1 Corneal ulcers with an indolent course, stromal infiltrates with a dry texture and feathery borders, satellite lesions, immune ring infiltrates and unlevelled hypyon are highly suggestive of a fungal aetiology.2 In cases of a negative smear or culture and where there is a high suspicion for fungal keratitis, a corneal biopsy should be considered. In vivo confocal microscopy is a useful adjunct to slit lamp biomicroscopy for supplementing diagnosis in most cases and establishing early diagno- sis in many cases of non-responding keratitis. This is a non-invasive, high resolution technique which allows rapid detection of fungal hyphae in the cornea long be- fore laboratory cultures can give conclusive results.3 M E T H O D S Case records of all corneal ulcers presented to Oph- thalmolgy Department of Sur Hospital, Oman, in the four year study period from January 2004 to Decem- ber 2007, were analysed retrospectively. A proper his- tory regarding the events leading to ulcers was record- ed and all the patients were subjected to a thorough clinical and microbiological examination at the time of presentation. Corneal scrapings, from the edge and base of the ulcers were subjected to complete micro- biological examinations which included direct mi- croscopic examination by 10% potassium hydroxide (KOH) solution and inoculation into various culture media. The wet preparations of KOH were examined under low magnification (x100) initially and then un- der high magnification (x400). Corneal scrapings were transferred directly from spatula to agar media by a series of C-shaped cuts on the media. Three differ- ent media were utilised: blood agar, chocolate agar and Sabouraud’s dextrose agar with chlorampheni- col (SDA). The SDA plates were incubated at 25°c for three weeks. Most of the patients were admitted. Vis- ual acuity ranged from hand movement to 6/60. Only culture proven cases of fungal ulcers were included in this study and they were reviewed for risk factors, lab- oratory findings and response to treatment. The data obtained from the study were analysed using 95% level of confidence at 5% significance level. R E S U L T S There were a total of 242 cases of corneal ulcers in our study period of 4 years, out of which 13.32% (95% CI: 8.95% to 17.49%) were fungal. Among 102 culture pos- itive cases, 32 (95% CI: 22.37% to 40.37%) were fungal and 70 were bacterial. The remaining 140 cases were culture negative. Among the 32 fungal corneal ulcers, 19 (59.37%) were in male patients and 13 (40.63%) in female ones. The incidence was highest in the age group above 60 years (62.5%). Analysis of risk factors for fungal ulcers showed a history of steroid use in 10 patients, most in the eld- erly age group of 50-70 years. Five patients were on steroid treatment for unrelated eye problems and the remaining five were post operative cases on chronic steroid usage. The second commonest risk factor iden- tified was ocular injury with plant debris in 8 patients. Among this group, two were children in the age group 10-15 years; the remaining six patients were elderly in the age group 50-75 years. Preexisting corneal pathol- Application to Patient Care • There is a need to recognise the public heath risks of corneal ulcers and educate the community to prevent this avoidable cause of blindness. • The modifiable risk factors need to be understood to lessen the magnitude of fungal corneal ulcers. • Any superficial corneal injury, especially with vegetable matter, has to be properly attended to. • The application of native medicines and eye drops containing steroids should be avoided. A R E T R O S P E C T I V E S T U D Y O F F U N G A L C O R N E A L U L C E R S I N T H E S O U T H S H A R Q I YA H R E G I O N I N O M A N 61 ogy like corneal degenerative keratopathy and tracho- ma sequelae were seen in 6 patients in the age group 50-80 years. The use of topical traditional medications for minor eye diseases was another risk factor in 5 pa- tients, all in the age group 50-70 years. The remain- ing 3 patients had no predisposing factors. Three were three diabetic patients, but all of them had additional predisposing factors [Table 1]. In the laboratory investigations, the positive cul- tures obtained were corroborated with positive KOH results. In direct microscopy, branching and septate hyphae were identified in 24 cases (75%). Fusarium spp was the most common fungi isolated (50%) fol- lowed by Aspergillus spp (34.4%). Apart from filamen- tous fungi, 2 cases were yeast infection [Table 2]. T R E A T M E N T A N D O U T C O M E The initial treatment given was ketoconazole 2% drops hourly with 14 (43.75%) cases responding well. The re- maining 18 (56.25%) patients, who had unfavourable response after the third day, were given a combina- tion of 2% ketoconazole and 0.15% amphotericin B. Fresh preparations were reconstituted every third day. Daily examination was done with clinical documen- tation of the size, extent and anterior chamber reac- tion. Frequency of instillation was gradually tapered as the ulcers improved. Treatment was continued for a minimum period of three weeks. Six patients, who had lesions extending to the limbus and with thinning of cornea, were given oral ketoconazole 200mg twice daily for 7 days in addition to the combination drops. Twenty nine patients (95% CI: 80.53% to 100.73%) re- sponded well to this regimen. Visual acuity improved in 15 patients, while it remained the same in 12 pa- tients and deteriorated in 5 patients. The ulcers wors- ened in 3 patients and they were referred for further treatment to a tertiary centre. Patients who were on native medication presented late with extensive ulcers. These patients needed a longer period of treatment and their outcome was dense scarring. D I S C U S S I O N Even though fungal corneal ulcers are comparatively uncommon, they cause devastating ocular damage if not managed properly.2 Our study shows an incidence of fungal keratitis (13.22%) comparable with other studies. In a similar study conducted in a tertiary re- ferral centre in Baghdad, an 18.7% incidence of fungal keratitis was reported.4 Filamentous fungi like Fusari- um, Aspergillus and Pencillium were the predominant isolates in our study. World wide, Aspergillus is the most common cause of mycotic keratitis. Fusarium species are the most common cause of fungal cor- neal infection in the southern United States (45.76%), while Aspegillus species followed by Fusarium are the most common isolates in India.5,6,10 The Baghdad study showed Aspergillus in 56.8% and Fusarium in 27%.4 Our study shows a higher incidence of Fusari- um (50%) followed by Aspergillus (34.4%).This may be due to the fact that the Fusarium species is commonly found in soil and plants and most of our patients were from a rural background. When the risk factors were analysed, the highest risk factor noted was steroid usage (31.25%) followed by ocular trauma (25%). A similar study of fungal keratitis in Melbourne showed chronic steroid usage in 31.4% and ocular trauma in 37%.7 Corneal injury as- sociated with outdoor activities with plant or soil ma- terial is a high risk factor for fungal keratitis. In a study of fungal keratitis in northern Iran, trauma with plant debris and straws were noted in 28.6% of patients with fungal keratitis.8 Other predisposing factors noted were ocular surface disorders in 18.75% and use of na- tive medications in 15.62%. A study of fungal keratitis at Wills Eye Hospital, Pennsylvania, USA, reported chronic ocular surface disease in 41.7%.11 In a study from a rural area of India, usage of traditional medi- Table 1: Predisposing risk factors in fungal corneal ulcers Factors No. of cases Age group Percentage Confidence Interval Steriod use 10 50-70 years 31.25 95% CI: 15.19% to 47.31% Ocular injury 8 10-75 years 25.00 95% CI: 10% to 40% Preexisting corneal pathology 6 50-80 years 18.75 95% CI: 5.23% to 32.27% Topical traditional medications 5 50-70 years 15.62 95% CI: 3.05% to 28.21% TH A R A I D I C U L L A , G E O R G E Z A C H A R I A H , K E S H AV A N D S O M A N S U B A S U 62 cations like human milk, leafy extracts and oil were reported in 47% of corneal ulcer patients.12,13 Reconstituted topical 2% ketoconazole and 0.15% amphotericin B were very effective for most of the cases. Fresh preparations were reconstituted on every third day and instilled hourly as ready made antifun- gal drops were not available.4,9 Most cases of corneal ulcers presented in this study were already on topical antibiotics and this may explain the high percentage of culture negative cases. Filamentous fungi are common aetiological agents for fungal keratitis in our region. Hence this study is useful to institute appropriate em- pirical antifungal therapy based on this scenario. C O N C L U S I O N Fungal keratitis presents both diagnostic and man- agement challenges for the clinician. Infection due to filamentous fungi is a frequent cause of corneal blind- ness and remains as a major ophthalmological prob- lem. Corneal injuries need to be treated and managed properly. Indiscriminate use of steroid drops and the application of native medicines for unrelated eye prob- lems may provide an environment for fungal growth. A wet smear of 10% KOH preparation is an essential screening test for corneal ulcer.8 Mycotic lesions are often recalcitrant and require many weeks of medical treatment. Reconstituted antifungal drops are equally as effective as commercial antifungal drops which are not readily available in this region. It is imperative to maintain a high level of suspicion for fungal keratitis, so that appropriate therapy can be instituted imme- diately. C O N FL I C T O F I N T E R E ST : None declared S O U R C E O F F U N D I N G : Sur Hospital, Oman R E F E R E N C E S 1. Khairallah SH, ByrneKA, Tabbara KF. Fungal keratitis in Saudi Arabia. Doc Ophthalmol 1992; 79:269-76. 2. Kim MC, Karp CL. Managing fungal keratitis. Amer Acad Ophthalmol, Eye Net Magazine, March 2001. 3. Gupta N, Tandon R. Investigative modalities in infec- tious keratitis. Ind J Ophthalmol 2008; 56:209-13. 4. Al-Shakarachi F. Initial Therapy for suppurative micro- bial keratitis. BJO 2007; 91:1583-87. 5. Agarwal PK, Roy P, Das A, Banerjee A. Ind J Ophthal- mol 2001; 49:173-6. 6. Gopinathan U, Garg P, Fernandes M, Sharma S. The ep- idemiological features and laboratory results of fungal keratitis: a 10-year review at a referral eye care center in South India. Cornea 2002; 21:555-9. 7. Bhartiya P, Daniell M, Constantnou M. Fungal Kerati- tis in Melbourne. Clin Experiment Ophthalmol 2007; 35:124-30. 8. Shokohi T, Nowroozpoor-Dailami K, Moaddel-Haghighi T. Fungal Keratitis in patients with corneal ulcer in Sari, Northern Iran. Arch Iran Med 2006; 9:222-7. 9. Yavas GF, Oztürk F, Küsbeci T, Cetinkaya Z, Ermis SS, Kiraz N, et al. Antifungal efficacy of voriconazole, itra- conazole and amphotericin B in experimental fusarium solani keratitis. Graefes Arch Clin Exp Ophthalmol 2008; 246:275-9. 10. Chander J, Singla N, Agnihotri N, Arya SK. Keratomy- cosis in and around Chandigarh: a five-year study from a north Indian tertiary care hospital. Ind J Pathol Micro- biol 2008; 51:304-6. 11. Tanure MA, Cohen EJ, Sudesh S,Rapuano CJ,Laibson PR, et al. Spectrum of fungal keratitis at Wills Eye Hos- pital, Pennsylvania. Cornea 2000; 19:307-12. 12. Prajna V, Pillai MR, Manimegalai TK,Srinivasan M, et al. Use of traditional eye medicines by corneal ulcer pa- tients. Ind J Ophthalmol 1999; 47:15-18. 13. Bialasiewicz A, Shenoy R, Thakral A, Al-Muniri A, Shenoy U, Al-Mughairi Z. Microbial keratitis: A 4 year study of risk factors and traditional/complimentary medicines in Oman. Ophthalmologe 2006; 103:682-87. Species grown No of cases Percentage Confidence Interval Fusarium spp 16 50 % 95% CI: 32.68% to 67.32% Aspergillus spp 11 34.4% 95% CI: 17.92% to 50.84% Penicillium spp 3 09:4% 95% CI: -0.72 to 19.48% Candida spp 2 06.2% 95% CI: -2.14 to 14.64% Table 2: Fungal Culture: Species grown