Ocular mycoses, also called fungal eye infections or oculomycosis, are caused by various species of fungi that can affect different parts of the eye, such as the conjunctiva, cornea, eyelids, and margins, as well as the interior of the eye, which is clinically referred to as mycotic conjunctivitis, keratitis, blepharitis, and endophthalmitis, respectively. Although mycotic ocular infections are relatively rare, they can nonetheless lead to significant morbidity and vision loss1. Contrary to eye infections of bacterial etiology, epidemiological estimates of ocular mycoses are limited owing to diagnostic challenges. However, recent studies estimate the annual incidence of keratomycoses as 1,051,787 cases per annum, with the highest burden noticeable in Asia and African regions2,3. Further, the epidemiology of ocular mycoses varies based on geographic region, the demographics of the population, seasonal variations, and other innate predisposing factors4,5. The burden of ocular mycoses is particularly high in tropical and subtropical regions due to the high humidity supporting budding spores' growth and increased exposure to vegetative matter 6,7,8. Moreover, other factors such as impaired immunity resulting in cancer, HIV/AIDS, or diabetes, exposure to contaminated water through contact lens wear, ocular trauma or surgery, and long-term use of topical steroids or antibacterial drugs predispose ophthalmic patients to mycotic ocular infections8,9. Current estimates on the prevalence of ocular mycosis in Ghana are largely unknown.
A staggering number of fungal genera and species have been discovered as the cause of ocular mycoses, and the number is continually growing with regional variations9. While filamentous fungi (Fusarium, Aspergillus, Acremonium, and Penicillium species) are the predominant causative agents of oculomycosis in tropical and subtropical regions, yeast and yeast-like fungi (Candida, Cryptococcus, and Malassezia species) assumes a significant role in temperate regions8,9,10. Clinically, patients with ocular mycoses present with symptoms of eye pain, redness, tears, watery to thick mucus discharge, photophobia, and reduced visual acuity that are usually misconstrued by ophthalmic clinicians as bacterial infections. Such clinical misdiagnosis of suspected external ocular and periocular infections of fungi etiology may exacerbate corneal perforation and consequently implicate the middle and inner tunics of the eyes, resulting in panuveitis, endophthalmitis, or even loss of the eye7,11.
The duration of treatment of ocular fungi infections varies depending on the type of fungi species and the severity of the illness12. Such course of disease prognosis underscores accurate diagnosis and timely initiation of ophthalmic treatment. However, in resource-constrained settings such as Ghana, the lack of rapid molecular diagnostics and high throughput screening facilities offset most consulting ophthalmic clinicians to mainly rely on clinical features in diagnosing and managing oculomycosis. Specifically, eyecare professionals perform comprehensive patient history to collate patients’ symptoms and gross ophthalmic assessments by slit-lamp biomicroscopy, ophthalmoscopy, and visual acuity to recognize peculiar clinical signs and employ broad-spectrum antimicrobial treatment therapy 13,14,15. Such clinical practice results in an inability to establish etiologic agents before treatment and leaves a worrying dearth of evidence on ocular fungal isolates commonly implicated in oculomycosis among ophthalmic patients in Ghana14.
Furthermore, the prevailing deployment and utilization of extended-spectrum antimicrobials without establishing the microbial etiology in treating eye infections, including oculomycosis, may culminate into antimicrobial and multi-drug resistance (MDR)16. In developed countries, the growing concern of drug resistance and the concurrent negative consequences on the global economy and repercussions on patients’ overall quality of life has fostered the establishment of surveillance programs to combat antimicrobial resistance (AMR)17,18,19,20. Nonetheless, limited attention has been ascribed to AMR and MDR in developing countries such as Ghana, with a recurring practice of poor regulatory compliance and adherence to antimicrobial handling and use and limited accessibility of national antimicrobial policy guidelines21.
Of note, antifungal agents available for treating fungi infections such as oculomycosis include polyenes (natamycin, nystatin, and amphotericin B), allylamines (terbinafine), azoles (fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole) and echinocandins classes22. Contrary to the echinocandins, the polyenes, allylamines, and azole class of antifungal medications are readily available and commonly used by clinicians, including eyecare professionals, for managing fungi infections in Ghana23,24,25. Current trends in medical and public health space show an increasing AMR and MDR to clinically used antimicrobial agents such as antifungals. Nevertheless, there remains a paucity of evidence on the antifungal susceptibility status of commonly administered antifungal medications used by ophthalmic clinicians in Ghana.
Natural products represent a significant source of phytoconstituents with a promising propensity for development into novel drug therapies26. As a semi-arid region, Ghana is home to an array of medicinal plants traditionally utilized to treat various infections owing to their beneficial phytochemicals such as alkaloids, flavonoids, tannins, glycosides, saponins, triterpenoids, and phytosterols27,28. The vegetative parts of plants such as Aspilia Africana, Chromolaena odorata, Cinnamomum verum, Syzygium aromaticum, Senna alata are known for their antifungal activity29,30. However, the fungistatic and fungicidal potential of these medicinal plants against ocular microbes have not been previously studied. Our preliminary elucidation of the antifungal potential of these medicinal plants against ocular fungal isolates could gauge the bioprospecting of bioactive lead compounds with potential for clinical development into novel treatment therapy for oculomycosis.
Therefore, the primary objective of this study is to elucidate the fungal pathogens implicated in ocular and periocular infections among ophthalmic patients and ascertain the antifungal susceptibility of antifungal agents commonly used by clinicians to manage oculomycosis in Ghana. Additionally, the study aims to explore five different Ghanaian medicinal plants as potential source for leads bioactive compounds for treating oculomycosis. Altogether, the primary outcome of our study will provide regional specific estimates on the prevalence and commonly implicated fungi pathogen in ocular infections and importantly guide ophthalmic clinicians on their choice of antifungal agents to clinically manage oculomycosis. To this end, our completion of the secondary aim of the study remains critically essential to gauge translational studies in the discovery of novel effective antifungal therapies for oculomycosis.