Emerging Imaging Technologies for Assessing Ocular Toxicity in Laboratory Animals

Nork, T. Michael; Rasmussen, Carol A.; Christian, Brian J.; Croft, Mary Ann; Murphy, Christopher J.

doi:10.1007/978-1-62703-164-6_3

Cited by 6 publications

(10 citation statements)

References 261 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This limitation is exacerbated in cases where the spectacle is opacified. By contrast, spectral domain optical coherence tomography (SD‐OCT) has a resolution of about 5 μm and can be used to obtain optical cross‐sections of the anterior segment in vivo with high scanning speed (26 kHz) and axial resolution …”

Section: Introductionmentioning

confidence: 99%

Spectral domain optical coherence tomography imaging of spectacular ecdysis in the royal python (Python regius)

Tusler

Maggs

Kass

et al. 2014

Veterinary Ophthalmology

Self Cite

View full text Add to dashboard Cite

Objective To describe using spectral domain optical coherence tomography (SD-OCT), digital slit-lamp biomicroscopy, and external photography, changes in the ophidian cuticle, spectacle, and cornea during ecdysis. Animals Studied Four normal royal pythons (Python regius). Procedures Snakes were assessed once daily throughout a complete shed cycle using nasal, axial, and temporal SD-OCT images, digital slit-lamp biomicroscopy, and external photography. Results Spectral domain optical coherence tomography (SD-OCT) images reliably showed the spectacular cuticle and stroma, subcuticular space (SCS), cornea, anterior chamber, iris, and Schlemm's canal. When visible, the subspectacular space (SSS) was more distended peripherally than axially. Ocular surface changes throughout ecdysis were relatively conserved among snakes at all three regions imaged. From baseline (7 days following completion of a full cycle), the spectacle gradually thickened before separating into superficial cuticular and deep, hyper-reflective stromal components, thereby creating the SCS. During spectacular separation, the stroma regained original reflectivity, and multiple hyper-reflective foci (likely fragments from the cuticular-stromal interface) were noted within the SCS. The cornea was relatively unchanged in character or thickness throughout all stages of ecdysis. Slit-lamp images did not permit observation of these changes. Conclusions Spectral domain optical coherence tomography (SD-OCT) provided excellent high-resolution images of the snake anterior segment, and especially the cuticle, spectacle, and cornea of manually restrained normal snakes at all stages of ecdysis and warrants investigation in snakes with anterior segment disease. The peripheral spectacle may be the preferred entry point for diagnostic or therapeutic injections into the SSS and for initiating spectacular surgery.

show abstract

Section: Introductionmentioning

confidence: 99%

Spectral domain optical coherence tomography imaging of spectacular ecdysis in the royal python (Python regius)

Tusler

Maggs

Kass

et al. 2014

Veterinary Ophthalmology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Characterization of standard or specialized ocular examination techniques used for in-life evaluation in ocular tolerability/dose range and pivotal ocular toxicity studies including basic principles, performance parameters, and use in ocular and other toxicity studies have been reviewed in greater detail elsewhere, 4,10,[56][57][58][59][60] and only a few practical points or recent developments will be covered in this article. Recent reviews of species anatomical differences in anterior segment that affect anterior chamber scoring systems, [61][62][63] which is a revision to the ocular scoring systems of McDonald-Shadduck and Hackett-McDonald, have greatly contributed to our understanding and standardization of ocular evaluation by ophthalmologists in ocular toxicity studies.…”

Section: Ocular In-life Parametersmentioning

confidence: 99%

Selected Aspects of Ocular Toxicity Studies With a Focus on High-Quality Pathology Reports: A Pathology/Toxicology Consultant’s Perspective

Short¹

2020

Toxicol Pathol

View full text Add to dashboard Cite

Ocular toxicity studies are the bedrock of nonclinical ocular drug and drug–device development, and there has been an evolution in experience, technologies, and challenges to address that ensures safe clinical trials and marketing authorization. The expectations of a well-designed ocular toxicity study and the generation of a coherent, integrative ocular toxicology report and subreports are high, and this article provides a pathology/toxicology consultant’s perspective on achieving that goal. The first objective is to cover selected aspects of study designs for ocular toxicity studies including considerations for contract research organization selection, minipig species selection, unilateral versus bilateral dosing, and in-life parameters based on fit-for-purpose study objectives. The main objective is a focus on a high-quality ocular pathology report that includes ocular histology procedures to meet regulatory expectations and a report narrative and tables that correlate microscopic findings with key ophthalmic findings and presents a clear interpretation of test article-, vehicle-, and procedure-related ocular and extraocular findings with identification of adversity and a pathology peer review. The last objective covers considerations for a high-quality ophthalmology report, which in concert with a high-quality pathology report, will pave the way for a best quality toxicology report for an ocular toxicity study.

show abstract

“…39,53 Intravitreal toxicity studies evaluate retinal function by electroretinography (ERG) and may include fluorescein angiography if retinal vessel changes are expected secondary to leakage or inflammation and confocal scanning laser ophthalmology of the retina if for fundus imaging and dynamic retinal angiography. 39,53 Intracameral toxicity studies evaluate corneal endothelium with specular microscopy, measure anterior chamber angle characteristics, track location and size of drug delivery systems with gonioscopy, and measure corneal thickness with pachymetry. 39,53 Intraocular toxicity studies conduct histopathology of up to 5 sections of the globe, optic nerve, and ocular adnexa.…”

Section: Intraocular Toxicity Study Design and Assessmentmentioning

confidence: 99%

“…39,53 Intracameral toxicity studies evaluate corneal endothelium with specular microscopy, measure anterior chamber angle characteristics, track location and size of drug delivery systems with gonioscopy, and measure corneal thickness with pachymetry. 39,53 Intraocular toxicity studies conduct histopathology of up to 5 sections of the globe, optic nerve, and ocular adnexa. The decision to evaluate systemic parameters including clinical pathology, organ weights, and a full list of systemic tissues for histopathology is based on the classification of the drug substance as an NME or reformulation and the detection of systemic exposure above the EC50 and/or clinical signs following intraocular injection.…”

Section: Intraocular Toxicity Study Design and Assessmentmentioning

confidence: 99%

“…52 Emerging technologies are also used, including photographic imaging to follow biodegradation of drug delivery systems and spectral-domain optical coherence tomography (SD-OCT) for providing cross-sectional or 3-dimensional images of the posterior segment for intravitreal studies or the anterior chamber for intracameral studies. 39,53 Intravitreal toxicity studies evaluate retinal function by electroretinography (ERG) and may include fluorescein angiography if retinal vessel changes are expected secondary to leakage or inflammation and confocal scanning laser ophthalmology of the retina if for fundus imaging and dynamic retinal angiography. 39,53 Intracameral toxicity studies evaluate corneal endothelium with specular microscopy, measure anterior chamber angle characteristics, track location and size of drug delivery systems with gonioscopy, and measure corneal thickness with pachymetry.…”

Section: Intraocular Toxicity Study Design and Assessmentmentioning

confidence: 99%

See 1 more Smart Citation

Toxicology Evaluation of Drugs Administered via Uncommon Routes: Intranasal, Intraocular, Intrathecal/Intraspinal, and Intra-Articular

Emami

Tepper²,

Short

et al. 2017

Int J Toxicol

View full text Add to dashboard Cite

As the need for nasal, ocular, spinal, and articular therapeutic compounds increases, toxicology assessments of drugs administered via these routes play an important role in human safety. This symposium outlined the local and systemic evaluation to support safety during the development of these drugs in nonclinical models with some case studies. Discussions included selection of appropriate species for the intended route; conducting nonclinical studies that closely mimic the intended use with adequate duration; functional assessment, if deemed necessary; evaluation of local tissues with special histological staining procedure; and evaluations of safety margins based on local and systemic toxicity.

show abstract

Emerging Imaging Technologies for Assessing Ocular Toxicity in Laboratory Animals

Cited by 6 publications

References 261 publications

Spectral domain optical coherence tomography imaging of spectacular ecdysis in the royal python (Python regius)

Spectral domain optical coherence tomography imaging of spectacular ecdysis in the royal python (Python regius)

Selected Aspects of Ocular Toxicity Studies With a Focus on High-Quality Pathology Reports: A Pathology/Toxicology Consultant’s Perspective

Toxicology Evaluation of Drugs Administered via Uncommon Routes: Intranasal, Intraocular, Intrathecal/Intraspinal, and Intra-Articular

Contact Info

Product

Resources

About