Pythium insidiosum Keratitis: Past, Present, and Future

Abstract

Pythium insidiosum (PI) is an oomycete, a protist belonging to the clade Stramenopila. PI causes vision-threatening keratitis closely mimicking fungal keratitis (FK), hence it is also labeled as "parafungus". PI keratitis was initially confined to Thailand, USA, China, and Australia, but with growing clinical awareness and improvement in diagnostic modalities, the last decade saw a massive upsurge in numbers with the majority of reports coming from India. In the early 1990s, pythiosis was classified as vascular, cutaneous, gastrointestinal, systemic, and ocular. Clinically, morphologically, and microbiologically, PI keratitis closely resembles severe FK and requires a high index of clinical suspicion for diagnosis. The clinical features such as reticular dot infiltrate, tentacular projections, peripheral thinning with guttering, and rapid limbal spread distinguish it from other microorganisms. Routine smearing with Gram and KOH stain reveals perpendicular septate/aseptate hyphae, which closely mimic fungi and make the diagnosis cumbersome. The definitive diagnosis is the presence of dull grey/brown refractile colonies along with zoospore formation upon culture by leaf induction method. However, culture is time-consuming, and currently polymerase chain reaction (PCR) method is the gold standard. The value of other diagnostic modalities such as confocal microscopy and immunohistopathological assays is limited due to cost, non-availability, and limited diagnostic accuracy. PI keratitis is a relatively rare disease without established treatment protocols. Because of its resemblance to fungus, it was earlier treated with antifungals but with an improved understanding of its cell wall structure and absence of ergosterol, this is no longer recommended. Currently, antibacterials have shown promising results. Therapeutic keratoplasty with good margin (1 mm) is mandated for non-resolving cases and corneal perforation. In this review, we have deliberated on the evolution of PI keratitis, covered all the recently available literature, described our current understanding of the diagnosis and treatment, and the potential future diagnostic and management options for PI keratitis.

Keywords: Azithromycin; Keratitis; Leaf incarnation method; Linezolid; Parafungus; Pythium insidiosum; Therapeutic keratoplasty; Zoospore.

Fig. 1

Digital image of a patient with rapidly proliferative Pythium insidiosum keratitis. a At presentation (day 1)—5 × 6 mm central full-thickness infiltrate with trace hypopyon. b, c (day 7) Worsening of full-thickness infiltrate with rapid spread towards limbus and increase size and density of hypopyon despite topical medications. d Recurrence-graft infection noted 7 days following therapeutic penetrating keratoplasty, e 1 month following a regraft-diffuse congestion, stromal edema, and 360-degree superficial vascularization

Fig. 2

Digital culture images of Pythium insidiosum keratitis. a 5% sheep blood agar image depicting flat, gray-white colony at 37° (2nd day). b Dense cream-colored colony of Pythium on 5% sheep blood agar at 37° after 5 days. c White submerged colony on chocolate agar after 2 days. d Magnified view (× 10) of a small vesicle with numerous zoospore formation after 3 h of incubation using leaf incarnation method

Fig. 3

Digital image of a patient of Pythium insidiosum keratitis. a Depicting 6 × 8 mm full-thickness infiltrate with subepithelial infiltrates radiating up to the limbus. b No recurrence noted 2 weeks after therapeutic penetrating keratoplasty taking 1 mm larger host margin with intraoperative cryotherapy and alcohol

Fig. 4

Image depicting the proposed management algorithm for Pythium insidiosum keratitis