I. organic molecules. This ultimately leads tokilling of thefungus.

I.                   
Mycotic keratitis is an
important cause of corneal infection and ocular morbidity in the tropical and sub-tropical
countries and accounts for 1-45% of the total burden ofkeratitis.
98 Geographic variation has been noted in the incidence as well as
pattern of mycotic keratitis. Tropical countries witness a high incidence of
mycotic keratitis with filamentous fungi being the primary pathogen while in
temperate areas yeasts has beenprimarily  implicated.6,108,112 The two major concerns in management of mycotic keratitis is the lack
of availability of laboratory diagnostic tools fordetermination of drug
sensitivity of the pathogenic organism and poor ocular penetration resulting in
low bioavailability of the antifungal agents. This has motivated the
researchers to improvise the available treatment options for the management of
mycotic keratitis. There has been a paradigm shift in the management of mycotic
keratitis with the advent of new antifungal agents as well as novel drug
delivery system such as nano-particles. Other than the conventional mode of
topical and systemic treatment, intracameral and intrastromal injection of
antifungal agents have also been used with variable success rate incases with
deep and refractory keratitis.

II.                 
Antifungal agents for Mycotic Keratitis

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A.                
Classification

The antifungal agents can be categorisedbased on their
molecular structure and mechanism of action (Table1). They are broadly
classified as polyenes, azoles, pyrimidines, allylamines, echinocandins, heterocyclics
and others.

B.                 
Mechanism of Action

Polyenes are group of antifungal with multiple conjugated
double bonds and a heavily hydroxylated region on the ring opposite the
conjugated system. These are amphiphilic and acts by binding to sterols
(primarily ergosterol) present in the fungal cell wall. This binding leads to
formation of pores with alterated membrane permeability resulting in leakage of
vital cytoplasmic constituentssuch as monovalent ions (Na+/ K+/ H+/ Cl?) and
small organic molecules. This ultimately leads tokilling of thefungus. Human cells
are less sensitive to such changes as it has cholesterol instead of ergosterol.
However, at therapeutic doses, they may bind to human membrane cholesterol
leading to toxicity.5

Azoles acts by inhibiting the
enzyme lanosterol 14 ?-demethylase which is essential for conversionoflanosterol
to ergosterol. Depletion of ergosterolleads to death of the fungus due to altered
cell membrane permeability and cell lysis. 103Allylamines inhibit
squalene epoxidase, another enzyme required for ergosterol synthesis. The
mechanism of action of Echinocandinsinvolve inhibitionof glucan synthesis in
the cell wall by acting on the enzyme 1, 3-Beta-glucan synthase (Table 1).

C.                 
Routes of administration

The conventional treatment for mycotic keratitis
constitutes use of topical formulations. Systemic treatment, in the form of
oral antifungal, is used in cases with severe keratitis, perforated ulcer,
associated scleritis and endophthalmitis. Intrastromal and intracameral routed
of antifungal drug delivery has been used for cases of deep and recalcitrant
mycotic keratitis. Subconjunctival injection of antifungal agents has been used
with variable success. Nano-particle based drug delivery of antifungal agents
has recently gained a lot of attention. Drug eluting contact lenses, having the
advantage of continuous drug delivery to the ocular surface, are considered by
few in treatment of mycotic keratitis.