Scientific and Regulatory Policy Committee Points to Consider: Fixation, Trimming, and Sectioning of Nonrodent Eyes and Ocular Tissues for Examination in Ocular and General Toxicity Studies

Abstract

A Working Group of the Society of Toxicologic Pathology’s Scientific and Regulatory Policy Committee conducted a technical and scientific review of current practices relating to the fixation, trimming, and sectioning of the nonrodent eye to identify key points and species-specific anatomical landmarks to consider when preparing and evaluating eyes of rabbits, dogs, minipigs, and nonhuman primates from ocular and general toxicity studies. The topics addressed in this Points to Consider article include determination of situations when more comprehensive evaluation of the globe and/or associated extraocular tissues should be implemented (expanded ocular sampling), and what constitutes expanded ocular sampling. In addition, this manuscript highlights the practical aspects of fixing, trimming, and sectioning the eye to ensure adequate histopathological evaluation of all major ocular structures, including the cone-dense areas (visual streak/macula/fovea) of the retina for rabbits, dogs, minipigs, and nonhuman primates, which is a current regulatory expectation for ocular toxicity studies. [Box: see text]

No side effects on rabbit retina or vitreous microenvironment by nd:YAG laser vitreolysis

“…A sample of undiluted vitreous humor (0.5 ml) was manually aspirated and immediately transferred to a sterile tube, which was stored at − 80 °C until the assay was performed. Then the eyes were enucleated cautiously to avoid probable globe violations and stored in Davidson’s fixative solution for 24 h [ 15 ].…”

“…2 A). A minimum of three retinal tissue sections were evaluated, with one of them exhibiting a visual streak [ 15 ]. The morphologies of the retinal pigment epithelium (RPE), photoreceptors, and ganglion cells were carefully examined.…”

Anti-brolucizumab immune response as one prerequisite for rare retinal vasculitis/retinal vascular occlusion adverse events

“…At necropsy, the eyes with bulbar conjunctiva and the kidneys were collected in 10% neutral-buffered formalin. After fixation, sectioning of the eyes was enhanced to include one vertical midsagittal section through the pupil and optic disc and one vertical sagittal section at the limbus in the nasal and temporal areas each ( 25 ). All tissues were processed by paraffin embedding and hematoxylin and eosin staining for light microscopy evaluation.…”

International consortium for innovation and quality: An industry perspective on the nonclinical and early clinical development of intravitreal drugs

“…Considerations for sampling, fixation, trimming of the eye in ocular toxicity studies were recently reviewed by the Scientific and Regulatory Committee of the Society of Toxicologic Pathology. 87 Extensive histopathological assessment of the eye is recommended for ocular toxicity studies conducted in nonrodent species. Trimming should capture all ocular and adnexal structures, including those that are speciesspecific as well as the retinal cone-dense areas (e.g., macula and fovea in nonhuman primates, and visual streaks in rabbits, dogs, and minipigs).…”

“…Considerations for sampling, fixation, and trimming of the eye in ocular toxicity studies were recently reviewed by the Scientific and Regulatory Committee of the Society of Toxicologic Pathology 87 …”