On the phylogenetic tree, fungi are closer to animals and plants than they are to bacteria. Like plants and animals, fungi are eukaryotes, have a separate membrane-bound nucleus, many membrane-bound organelles such as mitochondria, sterols in their cell membranes, DNA that contains noncoding regions, and 80S ribosomes (bacteria have 70S) (1). Fungi, like animals, need preformed organic compounds as energy sources. The ancestor of fungi may be a protozoan (1).

Fungi are helpful and harmful to humans. Fungi cause 70% of all major crop diseases. They were responsible for the Irish potato famine of the 1840s, which led to the starvation of 1 million people, and for Dutch elm disease and the American chestnut blight, which permanently altered U.S. hardwood forests. On the other hand, fungi have provided leavening for bread, fermentation of alcohol, and important therapeutic agents (penicillins, cephalosporins, aminoglycosides, amphotericin, cyclosporine).

Fungi are ubiquitous in the environment. Their spores can survive extremes of heat, cold, and desiccation, and are present in high concentration in the air. Outdoor and indoor air concentrations in temperate climates are typically 1500 and 1000 spores per cubic meter, respectively, although they may reach as high as 50,000 spores per cubic meter (2). Humans constantly breathe in fungal spores, and molds may be isolated from nasal mucus in 100% of randomly sampled individuals (3). Despite this, invasive fungal infections rarely develop in immunocompetent people.

The ocular surface is also exposed to fungi, but keratomycosis is rare. Fungi, particularly Candida species, are often part of the normal conjunctival flora (4). Fungi have been cultured from 24% of contact lens cases from asymptomatic cosmetic lens wearers, yet keratomycosis in a contact lens wearer is so rare as to be worthy of a case report (5,6). As in systemic fungal infections, fungi invade the ocular surface only when it is compromised, either from surface disease, topical steroid use, or trauma. Ocular trauma, especially involving vegetable matter, is the most common risk factor for keratomycosis and accounts for 50% of cases in most series. Trauma may be minor, and farmers who live in tropical climates are at particular risk.

Worldwide, fungal keratitis due to molds is one of the most common causes of infectious keratitis. Most cases occur in hot, humid climates. In India, Nepal, Bangladesh, Ghana, and Paraguay, fungi cause 20% to 60% of all infectious keratitis cases (Table 15-1). Keratomycosis is uncommon in temperate regions such as the northern United States and western Europe, where it accounts for at most 3% of keratitis cases (7,8). It is more common in the southern United States, and fungi cause 16% of microbial keratitis cases in Florida (9).

Fungi have a nucleus, membrane-bound organelles, a cell wall that contains chitin, and a cell membrane that contains ergosterol (mammalian cell membranes contain cholesterol). Fungal cells are larger than bacteria. Staphylococcus aureus is 1 μm in diameter, for example, whereas Candida is 4 to 6 μm.

Fungi take the form of either yeasts or molds. Yeasts are usually unicellular and grow by budding. In budding, the nucleus undergoes mitosis and a daughter cell pinches off to form a new cell containing the new nucleus. Molds, also called filamentous fungi, are composed of hyphae and are multicellular. Molds grow by extension and branching of hyphae. A hypha is a rigid tube that grows only at the tip. It contains cytoplasm that continuously moves toward the growing tip to supply it with materials for growth, leaving behind a vacuolated base that may undergo autolysis (Fig. 15-1). There is little difference between septate and aseptate hyphae because septa have pores through which cytoplasm and nuclei pass to reach the growing tip.

Although most fungi are always yeasts or always molds, some take either form depending on temperature. These
fungi are called dimorphic, and are yeasts in vivo and at 37°C but molds in the environment and at 25°C. They include the endemic mycoses (those that are geographically restricted): Histoplasma, Blastomyces, Coccidioides, and Paracoccidioides. None of them is an important cause of keratomycosis.

Fungi reproduce by spores. Spores may be sexual as a result of fusion of two cells followed by meiosis, or asexual (mitosis only). The asexual spores of medically important fungi are called conidia.

There are 250,000 species of fungi, although few are human pathogens (10). Until recently, the only effective antifungal for treating systemic fungal infections was amphotericin B, and the identity of the species of Candida or genus of mold seemed unimportant from a therapeutic standpoint. Now, with the advent of many new antifungal agents whose activity varies with fungal species, fungal identification has taken on new importance.

Although terminology is in flux, all fungi may be placed in seven phyla or groups: Oomycota, Chytridiomycota, Zygomycota, Ascomycota, Basidiomycota, and Deuteromycota. These groups are based on septation, growth, and reproductive characteristics. Deuteromycota, also called Fungi Imperfecta, include all fungi that reproduce only asexually. Most human pathogens, including the major agents of keratomycosis, are in this group (Table 15-2). Deuteromycetes include the yeasts Candida and Cryptococcus and the molds Aspergillus, Fusarium, Curvularia, Alternaria, and others. Deuteromycete molds are divided into the families Moniliaceae and Dematiaceae, based on the color of the unstained hyphae when viewed through a light microscope. Molds whose hyphae have white or light-colored walls are called hyaline fungi and are classified in the family Moniliaceae. Molds with brown or black-pigmented walls are dematiaceous fungi (family Dematiaceae). The pigment is due to melanin in the hyphal walls. Note that color does not refer to the color of the mycelial colonies growing on agar and visible to the unaided eye. Many hyaline molds form pigmented colonies, usually due to pigmented conidia.

In general, infections due to molds are much more difficult to diagnose and treat than are those due to yeasts. Candida, the major pathogenic yeasts, are as easy to Gram stain and culture as common bacteria and have similar media requirements. Molds require special media and incubation temperature, and may take days to grow. Even with optimal culture techniques, cultures from specimens infected with molds are often falsely negative, whereas this is rare in Candida infections. Ocular and systemic infections due to molds are also much more difficult to treat than are those due to Candida. A recent report noted that only 8% of 84 patients with endogenous Aspergillus endophthalmitis recovered useful vision, in contrast to the 76% to 100% vision recovery rates reported for patients with intraocular candidiasis (11). Similarly, attributable mortality from systemic Aspergillus infection (invasive pulmonary aspergillosis in bone marrow transplant recipients) is much higher than from candidemia (85% vs. 38%) (12).