Raj Nimmy, Vanathi Murugesan, Ahmed Nishat Hussain, Gupta Noopur, Lomi Neiwete, Tandon Radhika
Cornea, Lens & Refractive Surgery Services-Dr R P Centre for Ophthalmic Sciences, All India Institute for Medical Sciences, New Delhi 110029, India.
Ocular Microbiology Services-Dr R P Centre for Ophthalmic Sciences, All India Institute for Medical Sciences, New Delhi 110029, India.
J Fungi (Basel). 2021 Oct 26;7(11):907. doi: 10.3390/jof7110907.
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.
真菌性角膜炎在温暖、潮湿地区较为常见,根据地理来源、社会经济状况和气候条件的不同,致病真菌的种类也有所差异。在疑难病例和治疗效果不佳的病例中,临床诊断可能具有挑战性。显微镜检查发现真菌菌丝以及进行培养分离一直是真菌性角膜炎实验室诊断的金标准。分离出致病真菌的培养物对于进行抗真菌药敏试验至关重要。由于真菌的培养分离耗时较长,会导致治疗开始延迟,因此诸如活体共聚焦显微镜检查和分子诊断方法等新的检测手段近来越来越受到欢迎。分子诊断技术现在有助于快速诊断真菌性角膜炎。基因组学方法基于检测核糖体RNA基因的扩增子,越来越多地采用内部转录间隔区。宏基因组深度测序无需等待真菌生长即可实现快速准确的诊断。这对于识别引起真菌性角膜炎的新出现真菌菌株也很有帮助。定制的泪液蛋白质组学方法可能在未来真菌性角膜炎的管理中发挥重要的诊断作用。多次培养呈阳性被认为是预后不良的重要指标。多次真菌培养呈阳性有助于通过增加治疗频率来调整治疗方案,增加另一种局部和口服抗真菌药物,并密切随访角膜穿孔情况以及确定是否需要早期治疗性角膜移植术。胶原交联在真菌性角膜炎治疗中的作用尚未得到令人信服的确立。将多重PCR快速检测和致病真菌的抗真菌药敏试验纳入真菌性角膜炎的常规管理方案,将有助于改善治疗效果。早期治疗对于将角膜组织的损伤降至最低至关重要,从而获得更好的治疗结果。近年来,多烯类传统疗法、抗真菌药物的全身和靶向治疗、新型唑类和棘白菌素类在真菌性角膜炎中的作用已得到广泛研究。联合治疗可能比单一治疗更有效。鉴于真菌病因的多样性、具有不同药敏性的新角膜致病真菌的出现、某些属和种对抗真菌药物耐药性的增加,或许是时候采用最新的分子方法进行精确鉴定并将抗真菌药敏试验作为常规操作了。