Optical coherence tomography (OCT) is an ophthalmic imaging technology that provides a cross sectional view of multiple ocular structures at near-cellular resolution.
The retina, vitreo-retinal interface, optic nerve, and portions of the choroid can all be examined in fine detail. Anterior segment OCT allows visualization of distinct corneal layers and structures in the iridocorneal angle. These capabilities make OCT a valuable imaging tool for diagnosing ocular diseases in the clinic, assessing the efficacy of treatments, and for evaluating the pharmacological and toxicological effects of drugs during clinical trials and in preclinical research.
As a research and clinical tool, OCT provides quantitative thickness and volumetric values for the central retina and is useful in the clinical diagnosis and longitudinal monitoring of various retinal lesions including macular edema, macular hole, and geographic atrophy. The quantitative nature of the measurement provides valuable biomarkers for investigating retinal diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration and other hereditary retinal degenerations like retinitis pigmentosa.
While OCT is just one of many imaging technologies available to researchers, it offers some unique advantages, particularly during the preclinical phase of development.
We’ve highlighted five of these advantages below.
1. OCT can help shape the design of your clinical study
The exceptionally high resolution and detail offered by OCT provides important insight the nature of retinal or anterior segment changes, or lack thereof, during preclinical animal studies.
This allows researchers to perform risk assessments, taking into account important structure/function relationships in the eye as well as important comparative anatomical considerations between laboratory species and humans. Furthermore, OCT data series can be obtained from all commonly used laboratory animal species: mice, rats, rabbits, mini-pigs, dogs, and non-human primates.
The effects on animal models can be assessed with the exact same technology used to evaluate humans. The same OCT instrumentation can be used from basic research to preclinical studies to clinical trials. Consistency in imaging instrumentation allows researchers/clinicians to determine the most efficacious imaging practices for the compound/disease being studied and use those through out all phases of clinical development, including post market surveillance, resulting in more focused use of resources.
2. OCT is non-invasive
Capturing clear images using OCT requires only a still subject and an open eye. In preclinical animal studies, this may necessitate the use of sedation or anesthesia, but no invasive tools or techniques are needed.
The noninvasive nature of OCT, along with its ability to acquire images in just seconds, means less stress for the animals and the ability to image a relatively large number of animals in a short period of time.
3. OCT facilitates interpretation of examination findings
OCT imaging provides valuable complementary data to a variety of other testing modalities, from functional electrophysiology testing required by the FDA to fundus photography and ophthalmic examination data.
As a complement to ophthalmic examination using traditional direct and indirect ophthalmoscopy, OCT imaging systems can reveal the affected cell layers within lesions and identify whether or not these effects may extend beyond what is observed ophthalmoscopically. Furthermore, OCT data allows identification of specific retinal structural changes that can provide insight into abnormal electrophysiology testing results.
4. OCT allows for longitudinal follow-up of localized doses
A number of gene- and cell-based drugs require a localized dose close to the site of interest. In ophthalmic research, this often requires sub-retinal injection or another specialized form of drug delivery that may affect structures within the eye.
Serial, non-invasive OCT scanning in each cohort of subjects provides data documenting ocular changes from the beginning of the study all the way to the end. Often, these studies support extended therapies that continue to take effect after a single dose. When used to observe an ocular area like the retina sequentially over several weeks or months, OCT may alleviate the need for interim sacrifices, allowing ongoing evaluation of progression or regression, reducing the number of animals needed to complete the study compared to traditional methods.
5. OCT can reveal lesions even before ophthalmic examination
Many changes in the outer retina cannot be detected during an ophthalmic examination until they grow into a larger lesion.
Monitoring OCT images in real-time is possible, and can potentially detect these lesions before they develop fully. While the area needed to be scanned may be vast, OCT technology is developing rapidly with faster scan times and new wide angle imaging modalities. If prior research has shown potential for lesions to exist in a particular area, OCT can be used to search those specific areas for smaller lesions earlier in the process. OCT can then be used to provide a clinically meaningful evaluation of progression or regression of the lesions over time. OCT may also be able to identify potentially sensitive biomarkers applicable to clinical settings.
This technique could be especially useful when:
Lesions are detected in high-dose groups, but not low-dose groups, or
When detecting lesions early in low-dose groups
In these scenarios, longitudinal evaluation using OCT can give researchers key insight into how lesions develop and the margins of safety throughout the study.
How new tools are improving OCT in preclinical research
No matter how advanced an imaging technique may be, its value to researchers is ultimately defined by how well data can be interpreted and correlated. This is true for OCT as it is for all other imaging technologies in use today. The field of OCT imaging is evolving rapidly with multiple commercially available OCT instruments with varying capabilities and specifications.
Analyzing ophthalmic images has traditionally been a laborious task, requiring hours of gathering, sorting, organizing, and examining images in varying file formats from multiple sites using different types of equipment.
Fortunately, new systems are making these challenges a thing of the past by allowing for centralized clinical trial management through a single tool. Rather than manage the process by hand, researchers can rely on automated systems to harmonize imaging equipment and media for faster, more accurate analysis.
EXCELSIOR’s Preclinical platform brings the advanced management capabilities of its flagship clinical trial system to the preclinical phases of development where image analysis plays a key role in advancing treatments to the next stage of development. Excelsior provides a platform that is instrument independent: images and data can be compiled and analyzed from all of the commercially available systems. This allows direct comparison of quantitative and qualitative data independent of which imaging system was used to acquire the data.
By providing a centralized hub for all preclinical activities, the EXCELSIOR Preclinical platform allows trial managers to funnel a variety of imaging data into a single system, eliminating the risks of human error while saving time in the process. This new tool, coupled with the extensive clinical and preclinical research experience from the Ocular Services On Demand (OSOD) and the EyeKor team members, allows the study sponsor to have high-resolution, quantitative, in vivo, and real-time assessment of the examined animal retinas during the entire course of the preclinical study.
EXCELSIOR’s customizable software is designed to help your team manage the full spectrum of preclinical study types and imaging modalities, coordinate findings with ophthalmic examination data, gather reports in real-time and receive seamless access to expert analysis. Contact our team today to learn how we can help you make more informed decisions during your preclinical research.