Understanding the science of fungal endophthalmitis - AIOS 2021 Sengamedu Srinivas Badrinath Endowment Lecture

Abstract

Fungal endophthalmitis is a potentially blinding condition. It is more often reported from Asia, including India. The incidence is lower than bacterial endophthalmitis. But it is relatively more challenging to treat than bacterial endophthalmitis. Many eyes may need therapeutic keratoplasty and/or evisceration. The current mainstays of treatment are vitrectomy irrespective of the presenting vision, intravitreal antifungal agents, and systemic therapy; additionally, the patients could require prolonged treatment with repeat vitreous surgeries and intravitreal injections. Difficulty in clinical diagnosis, delay in microbiological culture, and limited options of antifungal drugs make the treatment more difficult and less rewarding. Three common fungi causing endophthalmitis are Aspergillus, Fusarium, and Candida. The former two are molds, often identified in exogenous endophthalmitis, postoperative and traumatic; the latter is yeast and is more often identified in endogenous endophthalmitis. A faster diagnosis with newer molecular microbiological technologies might help institute treatment earlier than it is currently possible. A target trial using big data from different regions of the world might emulate a randomized clinical trial to design a definite treatment strategy. Given fewer antifungal drugs, one must be mindful of antifungal stewardship to prevent resistance to the existing drugs.

Keywords: Antifungal stewardship; endophthalmitis; fungus; microbiology; minimum fungicidal concentration; outcome; pathology; treatment.

Figure 1

Photomicrograph of exogenous fungal endophthalmitis (a) Perforated cornea (asterix) with dense inflammation (arrow) of intraocular structure (H and E; scanner view). (b) Histiocytes and multinucleate giant cells (arrow) with dense chronic infiltrate forming microabscess and scattered uveal pigments (H and E × 300). (c and d) Fungal hyphae and chlamydospores (PAS left and GMS right, ×400). (e and f) Microabscesses in vitreous with central fungal filaments (within the circle- PAS left × 300 and GMS, right × 300)

Figure 2

Photomicrograph of endogenous endophthalmitis. (a) Fragments of the choroid (arrow) and retina (arrowhead) densely infiltrated with inflammatory cells, extending into the vitreous cavity (H and E, ×200). (b) Fragments of fungal hyphae (within the circle) noted in the retina (H and E, ×300). (c and d) Suppurative inflammation of vitreous (asterix) with fungal hyphae, which are hyaline, thin, septate, and branched (PAS left × 300 and GMS right, ×400)

Figure 3

Fungal endophthalmitis. Presentation, treatment, and outcome. (a) Post cataract; (b) Traumatic; (c) Endogenous. Left-clinical and fundus view. (a) PVA: 20/100; Microbiology: Aspergillus niger. Treatment: three vitreous surgery, IOL explant, three intravitreal antifungals. FVA: 20/50. (b) PVA: FCF 2 meters. Microbiology: Aspergillus flavus. Treatment: two additional vitreous surgery, 14 intravitreal antifungal drugs. FVA: 20/60. (c) PVA: 20/500. Microbiology: Candida albicans. Treatment: Two vitreous surgery and three intravitreal antifungal drugs. FVA- final visual acuity, PVA- presenting visual acuity

Figure 4

Microbiology of common fungi; left-culture and right-microscopy. (a) Aspergillus flavus-culture and microscopy (Lactophenol Cotton Blue). (b) Candida albicans-culture and microscopy (Grams). (c) Fusarium solani-culture and microscopy (Lactophenol Cotton Blue)

Figure 5

Building target trial from real-world data