Fungal Infections

• Heterotrophic eukaryotes: depend on exogenous food sources (either saprophytes or parasites)

• Yeasts: unicellular
• Moulds: branching filaments called mycelium, bear spores and grow as hyphae
• Long-lasting infections that can be difficult to treat
• Fungal infections are more common than bacterial
• Moulds are the most common fungal infection worldwide
• Aspergillus
• Fusarium 

• Candida albicans is the most common yeast infection
• Cataract surgery
• Corneal transplant
• Therapeutic CLs
• Steroids
• Immunosuppression
• Yeasts germinate to form pseudohyphae in the corneal stroma
• CL wear is the main risk factor in industrialised settings
• Fungi can reproduce sexually 
• Fungal keratitis presents as a feathery-edged infiltrate with satellite lesions

Candida albicans

• Normal commensal yeast
• Cultures on Sabouraud’s glucose media in 24-48 hours
• Candidaemia:
• GI surgery
• Prolonged IV antibiotics
• Indwelling catheters
• Diabetes
• Malignancy
• IV drug abuse
• Liver disease
• Alcoholism 
• A third of patients with candidaemia develop candidiasis
• 80% of patients with candidiasis have candidal chorioretinitis
• Also associated with candidal endophthalmitis (endogenous) in candidaemia
• Candidal infection of the oesophagus, trachea or lung is an AIDS-defining illness

Cryptococcus neoformans

• Yeast found in pigeon droppings
• Respiratory infections
• Chronic meningoencephalitis

Aspergillus (and Fusarium) keratitis

• Septate fungi
• Saprophytic mould (ie. filamentous)

• Spores (“conidia”) are dispersed in association with plant material or insects

• Opportunistic pathogen

• Mycelia spark an IgE mediated allergic response in the bronchi (type I hypersensitivity) or complement activation and polymorph infiltration (type II hypersensitivity)

• Aspergilloma: compact mass of mycelia

• If the corneal stroma is exposed (eg. following corneal injury) conidia germinate and hyphae penetrate the stroma

• Hyphae contain proteases eg collagenases that facilitate penetration through the stroma and into the AC (hypopyon)

• Pathophysiology relates to the inflammatory response causing tissue damage

• C-type lectins bind to cell wall components (beta-glucan and alpha-mannose) leading to chemotactic/inflammatory cytokine release

• Contact lens wear is the main risk factor

• Fungal biofilms are complexes of hyphae and extracellular carbohydrates with resistance to antimicrobials

• The deep penetration of hyphae makes antimycotics less effective. 
• Treatment options
• Natamycin
• Voriconazole
• Full thickness keratoplasty
• Enucleation

• Steroid use is risky as will cause hyphal growth if given before the infection is controlled

Histoplasma capsulatum

• Dimorph (may exist as a mould or a yeast)
• Soil yeast fungus, temperature dependent
• Inhaled and spreads haematogenously to the choroid
• Carried on birds feathers and bat droppings
• HLA-DRw2 and HLA-B7 associated.
• Presumed ocular histoplasmosis syndrome (POHS) is not truly an infectious process
• Hence anti-fungal therapy is not beneficial
• Histoplasmin skin antigen test is not sensitive/specific for POHS
• FFA useful
• POHS: immunologically mediated condition in those previously exposed
• Atrophic chorioretinal scars: CNV may form at macula
• PPA
• No vitritis

Mucoraceae

• Non-septate fungi: rhizopus, mucor, absidia

• Histopathology: non-septate fungi with wide angle branching (cp to Fusaria and Aspergillus which are septate fungi)

• Ubiquitous saphrophytic fungi in soil, air, ventilation systems, bodily orifices
• Usually phagocytosed by macrophages

• In acidic conditions of diabetes, metabolic acidosis or uraemia: spores can germinate and hyphae establish infection

• Causes orbital fungal infection: mucormycosis

• Most common route of orbital invasion is from an adjacent sinus

• Organisms disrupt blood vessels leading to ischaemia and black eschar

• Systemic antifungals are given eg. amphoteracin B
• Surgical debridement may be needed