Recent Perspectives in the Management of Fungal Keratitis

Abstract

Mycotic keratitis is common in warm, humid regions with a varying profile of pathogenic fungi according to geographical origin, socioeconomic status, and climatic condition. Clinical diagnosis can be challenging in difficult cases and those refractory to treatment. Fungal hyphae on microscopic examination and culture isolation have been the gold standard in the laboratory diagnosis of fungal keratitis. A culture isolate of the aetiological fungus is essential to perform antifungal susceptibility testing. As the culture isolation of fungi is time-consuming, causing delays in the initiation of treatment, newer investigative modalities such as in vivo confocal microscopy and molecular diagnostic methods have recently gained popularity. Molecular diagnostic techniques now help to obtain a rapid diagnosis of fungal keratitis. Genomic approaches are based on detecting amplicons of ribosomal RNA genes, with internal transcribed spacers being increasingly adopted. Metagenomic deep sequencing allows for rapid and accurate diagnosis without the need to wait for the fungus to grow. This is also helpful in identifying new emerging strains of fungi causing mycotic keratitis. A custom-tear proteomic approach will probably play an important diagnostic role in future in the management of mycotic keratitis. Positive repeat cultures are being suggested as an important gauge indicative of a poor prognosis. Positive repeat fungal cultures help to modify a treatment regimen by increasing its frequency, providing the addition of another topical and oral antifungal agent along with close follow-up for perforation and identifying need for early therapeutic keratoplasty. The role of collagen crosslinking in the treatment of fungal keratitis is not convincingly established. Rapid detection by multiplex PCR and antifungal susceptibility testing of the pathogenic fungi, adopted into a routine management protocol of fungal keratitis, will help to improve treatment outcome. Early therapy is essential in minimizing damage to the corneal tissue, thereby providing a better outcome. The role of conventional therapy with polyenes, systemic and targeted therapy of antifungal agents, newer azoles and echinocandins in fungal keratitis has been widely studied in recent times. Combination therapy can be more efficacious in comparison to monotherapy. Given the diversity of fungal aetiology, the emergence of new corneal pathogenic fungi with varying drug susceptibilities, increasing the drug resistance to antifungal agents in some genera and species, it is perhaps time to adopt recent molecular methods for precise identification and incorporate antifungal susceptibility testing as a routine.

Immunosuppressed Patients with Clinically Diagnosed Invasive Fungal Infections: The Fungal Species Distribution, Antifungal Sensitivity and Associated Risk Factors in a Tertiary Hospital of Anhui Province

“…during invasive and ocular Candida infections holds a promising perspective particularly for immunosuppressed patients. 15 For instance, ophthalmic solutions containing hexamidine diisethionate 0.05% (Keratosept) or povidone-iodine 0.6% (IODIM ® ) have been evaluated to control ocular fungal infections with potent antimicrobial activities against Candida spp. as recently reported by Pinna et al [13][14][15] Moreover, many plant essential oils have increasingly been assessed to present promising broad-spectrum antifungal activities to overcome MDR Candida spp.…”

“…15 For instance, ophthalmic solutions containing hexamidine diisethionate 0.05% (Keratosept) or povidone-iodine 0.6% (IODIM ® ) have been evaluated to control ocular fungal infections with potent antimicrobial activities against Candida spp. as recently reported by Pinna et al [13][14][15] Moreover, many plant essential oils have increasingly been assessed to present promising broad-spectrum antifungal activities to overcome MDR Candida spp. and even filamentous fungi, including the essential oils from Ruta graveolens, Myrtus communis and Austroeupatorium inulaefolium.…”

“…3,11,12 Furthermore, emerging multidrugresistant fungi of clinical origin would be a fatal threat for the immunosuppressed inpatients and especially for those with transplantations or chemo-/radio-therapies if novel and strong antifungal agents are unavailable. [13][14][15] Recent studies on new potent antimicrobial drugs against multidrug-resistant Candida and filamentous fungi hold a promising perspective to overcome refractory and invasive fungal infections. [13][14][15][16][17][18] Given the widespread administration of clinically commonlyused antifungals including azoles to a large number of patients experiencing malignancy and transplantation, it is of significant importance to understand the changing trends of clinically diagnosed IFIs in terms of the fungal species stratifications, antifungal sensitivities and possible underlying azole-resistance mechanisms related to sterolΔ 5,6 desaturase (ERG3) and 14-ɑ-sterol demethylase (ERG11) genes, 19,20 as well as clinical characteristics and distinctive risk factors in combination with relevant clinical profiles.…”

Successful treatment of Candida albicans anterior chamber infection after penetrating keratoplasty

“… 9 , 14 , 15 A faster method of detecting donor fungal infection via PCR at the time of tissue harvesting is also being developed. 16 , 17 …”

A Review on Pathogens and Necessary Diagnostic Work for Bleb-Related Infections (BRIs)

“…Pan-bacterial PCR has been used as a complementary technique to traditional microbiologic culture, providing a concomitant increase in detection sensitivity of 21% [ 6 ]. Additionally, for the diagnosis of fungal endophthalmitis, pan-fungal PCR using internal transcribed spacer (ITS) primers is considered a highly sensitive method, as fungi are known to have low sensitivity yields in conventional methods [ 40 , 52 ].…”