Histological Effects of Intravitreal Injection of Antifungal Agents in New Zealand White Rabbits: An Electron Microscopic and Immunohistochemical Study.

Sofia Karachrysafi,Athanasios Karamitsos,Vasileios Karampatakis,Penelope Anastasiadou,Anastasia Komnenou,Theodora Papamitsou,Georgios Delis,Ioanna Dori,Sotiris Sotiriou,Maria Xioteli,Evangelia Kofidou,Antonia Sioga

doi:10.3390/ph13100267

Abstract

Fungal endophthalmitis is a serious and vision-threatening infection which requires an immediate and effective treatment approach. Our research aims to elucidate the histological effects of the intravitreal injection of the maximum safe dosage of voriconazole and micafungin on retina. Six albino New Zealand White Rabbits were used. In experimental animals, a solution of voriconazole (Group V) or micafungin (Group M) was intravitreally injected in the right eye, while in control animals, balanced salt solution was intravitreally injected in the left eye (Group C). Euthanasia was performed ten days post injection and the retina was removed and prepared for histological examination with a light and electron microscope. Eosin-hematoxylin staining did not reveal any pathological changes in any of the samples examined. The immunohistochemical staining for Tumor Necrosis Factor alpha (TNF-a) marker was detected as negative in all samples, while Interleukin 6 (IL-6) marker was detected as mild only in the group injected with voriconazole. Electron microscopy revealed several ultrastructural alterations in retinal layers in both groups of experimental animals. Histological retinal lesions, revealed with electron microscopy in the present investigation, raises the question of the safe usage of these antifungal agents in the treatment of fungal intraocular infections in the future.

Highlights

Fungal endophthalmitis is a serious and vision-threatening infection with increasing incidence during the last decades
We studied two immunological markers, Interleukin 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-a), in order to clarify the possible presence of inflammation in retina
Our research aims to elucidate the histological effects of the intravitreal injection of the maximum safe dosage of voriconazole and micafungin according to available literature on retina

Summary

Introduction

Fungal endophthalmitis is a serious and vision-threatening infection with increasing incidence during the last decades. Various factors, such as the use of corticosteroids, which facilitates the penetration of pathogens, and the spread of topical antibiotics, which create an environment of lower competition between microorganisms on the surface of the eye, are suggested as key factors for this increase [1]. Fungal endophthalmitis is a life-threatening infection, as well as a common complication of intraocular surgery (mainly after cataract surgery), the use of ophthalmic products and/or corticosteroids, and pharmaceuticals (mainly drugs), eye injuries, systemic fungal infections (mainly candidiasis and aspergillosis), and immunosuppressive entities (mainly Human Immunodeficiency Virus (HIV) infection) [2,3,4,5,6,7,8,9,10,11,12]. Antifungal drugs have lower efficacy due to their mechanism of action (usually antifungal agents with dose-dependent fungicidal action), lower tissue penetration, and less noisy nature of the infection [14]

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