Three factors are intricately entwined in ocular infection: the host, microorganisms, and the environment. Thus, ocular infection is more complicated than other ocular diseases, in which two factors are involved: the host and the environment. Therefore, various methods should be used to understand the pathogenesis and solve this complicated disease. In this report, we introduce our past and current approaches to ocular infection.
1. Herpes simplex virus keratitis
Herpes simplex virus (HSV) keratitis is based on a delicate balance of viral growth and immune reaction to vial antigens; however, a fundamental solution has not yet been achieved, and the clinical importance is high. The accumulation of basic research with the latest scientific methodology is essential to find a treatment for this disease. In an in vitro study, microarray analyses of mRNA in HSV-infected corneal epithelial and endothelial cells led to the discovery of the correlations between interferon regulatory factor 7 and indoleamine 2,3-dioxygenase 1 with immune reactions to HSV. In a previous in vivo study, using a mouse model, we used vaccination to control herpetic keratitis, analyzed the relationship between chemokine receptors and stromal inflammation, and evaluated the efficacy of a novel antiherpetic drug, amenamevir, against murine herpetic keratitis. As clinical research, real-time polymerase chain reaction (PCR) has been used for the diagnosis of HSV keratitis.
2. Cytomegalovirus corneal endotheliitis
Since the first report by Koizumi et al. in 2006, various cases and studies have been reported; however, the pathogenesis of this disease remains unknown. We previously reported that the amount of cytomegalovirus (CMV)-DNA in the anterior chamber is related to various clinical parameters, and in an in vitro study, CMV was shown to actually infect human corneal endothelial cells and trabecular meshwork cells, which induced various cell reactions, such as cytokine release. In addition, we determined that the induction of CD8-positive cytotoxic T-lymphocytes stimulated by CMV-infected corneal endothelial cells is suppressed in patients with CMV endotheliitis.
3. Multicenter study of fungal keratitis
The Japanese Association for Ocular Infection (JAOI) conducted a prospective multicenter observational study to determine the causative fungi and their drug sensitivity, clinical findings, and prognosis of fungal keratitis. In the study, gene analyses revealed various fungal species cause fungal keratitis, and in vitro sensitivity testing revealed the antagonistic effect of natamycin and azoles in some strains.
4. Application of artificial intelligence to corneal infection
Artificial intelligence (AI) has been applied to various ocular diseases, and the Japanese Ophthalmological Society will conduct AI studies. We have obtained relatively good results for the diagnosis of infectious keratitis by slit-lamp photographs using convolutional neural networks that previously learned from general images using the ImageNet database. Additionally, the diagnosis of infectious keratitis based on factors other than slit-lamp photographs, such as culture and real-time PCR, etc., using Random Forest, a machine learning algorithm, has been progressing. In the future, ensembles of both models will lead to highly accurate diagnosis of infectious keratitis by AI.
5. Prevention of postoperative endophthalmitis
Various methods have been used to prevent postoperative endophthalmitis. A JAOI multicenter study had shown that 3-day preoperative antibiotic instillation reduced the bacterial load in the conjunctiva; however, intraoperative iodine irrigation and intracameral antibiotic injection have been performed recently, and countermeasures against antimicrobial resistance has become a large issue. Therefore, we must reconsider the necessity of preoperative antibiotics. Our prospective study proved that timely intraoperative iodine irrigation can reduce the bacterial load in the conjunctiva as much as that by preoperative antibiotic instillation.
Various studies have been performed on issues associated with ocular infection, and we have participated continuously in some of these studies. Ocular infection will continuously provide us with important tasks to be solved in the future; therefore, we must confront this old and new menace to our vision and health with a wide range of approaches, from basic medicine to clinical medicine.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 124: 155-184, 2020.