Fungal corneal ulcer is more commonly in the countries which are developing. Fungal corneal ulcer is one of the main causes of visual loss in developing agrarian part of the world and is hard to manage. ¹ The corneal ulcer may worsen and lead to serious consequences like corneal staphyloma, descemetocele, endophthalmitis, perforation, and visual loss. ²

Fusarium and Aspergillus being the most common causes of fungal corneal ulcer and are highly immune to most antifungal drugs.³ the fungal hypha can penetrate the unscathed Descemet's membrane and quickly enters the anterior chamber. ²

The topical administration of azoles, like fluconazole and voriconazole, has been demonstrated to be secure for eye structures and has fair perforation into corneal tissue .⁴ The types of fungal species isolated in patients with microbial keratitis are as follows: .¹

Hyaline fungi: Fusarium solani, F. culmorum, Aspergillus flavus, A. fumigatus, A. terreus, A. Niger, and other Aspergillus spp.

Molds dematiaceous fungi: Curvularia lunata, Curvularia spp., Bipolaris incurvata, Exserohilum rosratum.

Yeasts Candida spp.

As soon as one is diagnosed with fungal keratitis, immediate empirical therapy is required. Fungal corneal ulcer is a challenging ocular infection for Ophthalmologist. Natamycin is only ophthalmic antimycotic drug that is readily present in various regions of the world including Pakistan. Topical fortified antimycotic agents made from already available antifungal injections and it play a crucial part in management of fungal keratitis patients.5 Amphotericin B is one of the wide-spectrum antimycotic drug. Topically it is efficacious for many cases of fungal keratitis.6

Topically strength of 0.05% in 5% dextrose (0.5 mg/ml) is used. ¹

Shih-Hao Tsai et al used fluconazole subconjunctivaly for management of intense mycotic corneal ulcer resistant to standard antimycotic medications and proved that it can be efficacious for intense fungal corneal ulcer and prevent early surgical intervention in acute phase of inflammation [7]. Fluconazole is an effective antifungal agent against most cases of fungal keratitis.8 It is proven by the researchers that subconjunctival injection of fluconazole or intrastromal injection of voriconazole is effective against fungal corneal ulcer.⁹ Fluconazole used as subconjunctivaly increase the potency of this medicine in management of mycotic corneal ulcer and has least side effects and it is also less hazardous for cornea and conjunctiva.¹⁰ Fluconazole 2mg/ml injected subconjunctivaly had lower rate of complications as compared to topical use of Amphotericin B and also has vast spectrum of antifungal coverage. ¹¹ Diagnosing corneal ulcer needs a detail history and complete ocular examination using slit-lamp biomicroscope. Sometimes only clinical signs are insufficient to diagnose an infection, but break in the corneal epithelium with staining on Fluorescein dye and stromal infiltrates should raise suspicion of infection until proven otherwise.

Polyenes are amphotericin B, nystatin and natamycin and it destroy the cell by attaching to the mycotic cell wall ergosterol and are efficacious against yeast and filamentous fungi. Amphotericin B is particularly useful against yeasts, but less effective against filamentous fungi; so it is the first line of choice against yeasts.12 Amphotericin B (0.15%) drops can be used alone or in combination with natamycin in resistance cases; but their penetration through an intact epithelium is less than natamycin .¹²

Azoles (imidazoles and triazoles) include ketoconazole, miconazole, fluconazole, itraconazole, econazole, and clotrimazole. Imidazoles and triazoles are synthetic chemical antifungal drugs. Azoles have good penetration in eye, so when it is given systemically they are helpful in management of ulcer caused by yeast and filamentous fungi.¹³

A prospective and follow-up study was conducted on 74 eyes of 74 patients with resistant corneal ulcers attending the outpatient clinic of department of Ophthalmology Ayub Teaching Hospital Abbottabad from January 2020 to June 2021. The patients were classified into two groups: group 1 included 37 eyes treated with topical amphotericin B (fungizone) eye drops at a concentration of 0.5% in 5% dextrose (0.5 mg/ml), prepared from the commercially available 50 mg vial with 5% dextrose dilution to obtain the 0.05% strength, every two hourly. For both categories topical 1% Cyclopentolate eye drops three times a day, 0.5% Moxifloxacin eye drops four times a day was used. Regular removal of the damaged tissue is done in both categories using keratome every 48 hours. Group 2 included 37 eyes treated with 1 ml subconjunctival injection having 0.5 ml of 2% lidocaine and 0.5 ml of fluconazole 2 ml made injectable form of fluconazole IV injection (Diflucan) injected every day for 10 injections and then every 48 hourly for another 10 injections. Fate of ulcer in both groups was documented in both eyes and results were compared.

The ages of subjects in both categories was from 20 to 80 years, with a mean age of 45 years; 46 patients (62%) were under 45 years of age and 28 patients (33%) were older than 45 years of age (Table 1). As regards sex, 54 cases (62%) were male and 21 subjects (28%) were female (Table 1).

On analyzing the occupation of the patients, it was found that 57 cases (76%) were farmers and 18 cases (24%) were from different occupations. A total of 57 patients complained of trauma with plant materials. No significant statistical difference was found in the origin of trauma in relation to developing fungal keratitis in both groups (P > 0.05) (Table II).

Table- I: Number and percent distribution of the patients based on sociodemographic data

Table- II: Number and percent distribution of the patients based on the origin of trauma data

The management of mycotic corneal ulcer is a difficult and hard task for ophthalmologists because the clinical signs are nearly similar in many cases, and many antifungal drugs are not readily available in many parts of the world.1 Common antifungal used in different eye setups are polyene (natamycin and amphotericin B) and azoles (ketoconazole, fluconazole, itraconazole, and miconazole).14 Numerous elements were found that elevate the risk of fungal corneal ulcer. A study was conducted on 48 eyes and they observe that 58% of subjects with resistant keratitis, in which 38% were diabetic, and 21% got plant injury.15 El-Sayed SH et al. reported that diabetes, plant eye injury and history of keratitis are the various predisposing elements for developing fungal keratitis.1 In our study, we found that diabetes mellitus and vegetative ocular trauma are the major risk factors for developing fungal corneal ulcer and we noted that 48% of the cases are diabetic and 76% cases have plant eye trauma. The present study conducted laboratory investigations to confirm the clinical diagnosis, same as Garg et al 16 who reported in their study that laboratory diagnosis is more supercilious to clinical identification in the treatment of fungal corneal ulcer.16 Our study revealed that microscopic examination of corneal smear show only 38% of subjects with positive fungal results, but another study showed the sensitivity and specificity of gram staining for corneal smear as much as 61%.17 In the present study decrease sensitivity of detecting microorganism on directs microscopic detection is due to very intense insertion of mycotic organisms in the cornea, so it was not found in the scrapped tissue. However, we found that the positive culture result was reported to be around 75% and it is more accurate than direct gram staining and our results was comparable to another study conducted by Nayak N who reported positive culture result to be 77.8%.18 The present study was performed to compare the use of topical amphotericin B eye drops with the use of subconjunctival fluconazole injection in the treatment of fungal corneal ulcer. Our study showed that fluconazole used subconjunctivaly may increase the effectiveness of this medicine in the management of fungal corneal ulcer and also increase the chance of least of side effects and hazardous for the corneal and conjunctival tissues. This is in agreement with that reported by Alsayed SH et al who stated that fluconazole 2mg/ml used subconjunctivaly has the advantage of decrease incidence of complication as compared to the local use of amphotericin B and wider antimycotic spectrum.1 Avunduk et al reported that fluconazole is one of the safe and effective drugs when used as subconjunctival injection. Subconjunctival use of fluconazole is more effective than systemic use.19 Our study showed high percentage (92%) of curing of corneal ulcers in group 2, which was treated with subconjunctival fluconazole, compared with group 1, which was treated with topical amphotericin B (29%). Yilmaz and Maden8 proved that subconjunctival fluconazole covers broader spectrum of fungi. Isipradit also showed that subconjunctival fluconazole was more effective compared with topical use.20

On the basis of the findings of the present study, it is concluded that fungal corneal ulcer is the most devastating ocular infection and is a challenge for diseased, doctors and community. Most common cause we identified is diabetes and vegetative eye trauma. Our study shows that subconjunctival injection of fluconazole was more efficacious than topical Amphotericin B eye drops, which is evident by effective healing of fungal keratitis and also less time to heal.

Disclaimer:
Nothing to declare.

Acknowledgement:
The author thank the department medical staffs for their help and support. They keep patient record properly and managed the data carefully which helped in completing this research.

Authors’ CONTRIBUTION:

^1,2,3 Conceptualized the study and contributed in the data collection and aided in drafting of the article, Active Participation in active methodology.

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