*4.2.4 Treatment*

The currently available antifungal drugs have multiple drawbacks such as poor ocular penetration, unpredictable bioavailability, and adverse effects associated with systemic medications [47]. Filamentous fungal keratitis is difficult to treat despite the use of topical and systemic antifungal agents and adjuvant surgery, such as corneal transplantation [61]. About one-third of fungal keratitis patients have pharmacological failure that required surgical interventions to get rid of infection [72]. Thus, early diagnosis of fungal keratitis is the most important determinant of their prognosis [56]. Topical corticosteroids are contraindicated in the treatment of fungal keratitis and also in the early postoperative therapeutic keratoplasty [72]. For filamentous fungi, the first-line drug is 5% natamycin, and the second-line drugs are 1% itraconazole and 2% Econazole [18]. There is evidence that natamycin is more effective than voriconazole in the treatment of filamentous fungal keratitis especially in Fusarium keratitis [74, 75]. *Candida keratitis* is usually initially treated with 0.15% amphotericin B followed by fluconazole eye drop if the first-line drug is not responsive [18]. The systemic antifungal agents, including oral ketoconazole, itraconazole, voriconazole, and posaconazole, are needed for severe keratitis or cases with extension beyond the anterior chamber [18, 43]. Seventy percent of Fusarium keratitis with deep lesion does not respond to sole medical treatment, and surgical intervention may be required [61]. More than 80% of Aspergillus keratitis responds to medical therapy alone; however, in deep keratitis, surgical intervention is needed [61]. For Candida keratitis, medical therapy generally has a favorable response, and the presence of deep lesions is not a major issue [61]. Severe fungal keratitis patients that are still smear-positive despite being pretreated with appropriate antifungal agents may benefit from aggressive multimodality therapy [76]. Various drugs and route of antifungal agents for fungal keratitis are available as listed below [9, 18, 47, 60, 61, 75, 77–79].


Surgical debridement of the epithelium and base of the fungal keratitis is crucial in the management because it debulks the organisms and enhances drug penetration into cornea [79]. Surgery for fungal keratitis, ranging from lamellar or penetrating keratoplasty to evisceration or enucleation, plays a role as an adjunct to medical therapy for initial management and when medical therapy fails or impending corneal perforation [51, 61, 79]. The prognosis of fungal keratitis is worse than bacterial keratitis [80]. The course is favorable with medical treatment in 50—70% of cases. A surgery is required in 30 to 54% of cases [80]. These infections may lead to loss of the globe in 10 to 25% of cases [80]. High risk of developing corneal perforation and the need to undergo therapeutic penetrating keratoplasty (TPK) are due to infiltrate size of more than 6.6 mm, an infiltrate involving the posterior one-third of the stroma, and the presence of a hypopyon [73]. Unfortunately, recurrence keratitis can occur approximately 6–7% after therapeutic keratoplasty [81]. Hypopyon, corneal perforation, and corneal infection expanding to limbus and lens infection are predominant risk factors for the recurrence of fungal keratitis after corneal transplantation [81]. After therapeutic keratoplasty, systemic and topical antifungal treatments should be used for 2 weeks routinely and possibly for 6 to 8 weeks in high-risk cases [81]. Generally, if no typical signs of recurrence were present 2 weeks after surgery, low-concentration topical steroids may be administered with caution [81].
