A Closer Look at Ocular Toxicity Studies
The eye and the ocular adnexa are common target organs in toxicology studies, but the appropriate evaluation of ocular tissues is a specialized endeavor. Compared to routine toxicity studies, ocular toxicity studies require methodological modifications at almost every stage from study design to the final pathology report.
EPL has extensive experience in the processing and evaluation of ocular tissues (eyes and ocular adnexa [eyelids, lacrimal glands, Harderian glands, nictitating membrane, etc.]). The following suggestions for ocular toxicity studies are based on this experience:
- At necropsy, careful handling, very rapid exenteration, and specialized fixatives such as modified Davidson’s solution are utilized. The left and right eyes and their adnexa should be identified and stored in separate labelled containers. The globes should be marked (with sutures, indelible ink, etc.) in such a manner that the superior-inferior and nasal-temporal aspects remain identifiable.
- Multiple sections (calottes) of each globe should be taken, and in many cases, multiple step-sections of each calotte are appropriate to ensure that the various eye regions (i.e., central, nasal, and temporal) are adequately sampled. Various eye sections should be placed on the glass slide in such a manner that the superior-inferior and nasal -temporal orientation is uniformly identifiable. EPL has developed special histology methods to trim, embed, and section eyes to ensure that this critically important orientation is maintained.
- Additional customized microscopic sections may also be required depending on the route of administration (e.g., topical, intravitreal, intracameral, juxtascleral, sub-Tenon, topical, or systemic).
- Gross observations are rarely visible in eyes at necropsy. In ocular toxicity studies, the appropriate correlation for a microscopic ocular lesion is often a clinical in-life ophthalmological finding rather than a gross necropsy observation.
- In many ocular studies one eye is treated and the other left untreated as a contralateral control. In these studies, the pathologist must record pathology findings separately for the left and right eyes. Tissue accountability and microscopic findings should be recorded at the level of major anatomic subsites of the eye, such as “cornea”, “lens”, “retina”, etc.
Margarita M. Gruebbel, DVM, PhD, DACVP