EyeKor, Inc., Announces Partnership with Ophthalmic Photographer's Society to Develop Clinical Trial Imaging Certification

EyeKor's partnership with the OPS aims to accelerate the startup process of pharmaceutical sponsored ophthalmic clinical trials and provide ongoing support for those trials in terms of the necessary imaging certification requirements.

MADISON, Wis. (PRWEB) November 03, 2017 -- EyeKor, Inc., announced today that it will collaborate with the Ophthalmic Photographers’ Society (OPS) to develop a Clinical Trial Imaging Certification Program for OPS members who are Certified Retinal Angiographers or Certified Optical Coherence Tomographers. This program aims to accelerate the startup process of pharmaceutical-sponsored ophthalmic clinical trials and provide ongoing support for those trials in terms of the necessary imaging certification requirements.

The use of Certified Clinical Trial Imaging professionals will greatly improve the quality of the specialized imaging required for ophthalmic clinical studies. Specifically, certified imaging professionals will be able to provide a more accurate evaluation of ophthalmic images, thereby enabling earlier evaluation of the data required for the determination of therapeutic success.

EyeKor is a Software-as-a-Service (SaaS) company providing image and data management solutions for ophthalmic clinical trials. As part of the collaboration, certified OPS photographers will use EXCELSIOR™, EyeKor’s 510(k)-cleared, cloud-based software platform, for both clinical and preclinical applications. The software platform will enable pharmaceutical sponsors and their contract research organization (CRO) partners to manage the ocular images and other data collected during their ophthalmic clinical trials and nonclinical studies, enhancing the efficiency and accuracy of data collection and interpretation. EXCELSIOR also allows leading scientists, principal investigators, CRO representatives, data managers, and reading center graders to access and track data in real time.

“We are very pleased to support our ophthalmic photographer partners in this way,” said Christopher J. Murphy, DVM, PhD, DACVO, and CEO of EyeKor. “Our collaboration is an important step for EyeKor in connecting the quality of imaging provided by the ophthalmic photographers with our sponsors, who bring ophthalmic therapeutics into the marketplace to benefit patients suffering from serious ocular diseases. We look forward to continuing our successful relationship.”

About the Ophthalmic Photographers Society: The Ophthalmic Photographers’ Society is a nonprofit organization dedicated to a highly specialized form of medical photography in the field of ophthalmology. The main objectives of the Society are to provide primary and continuing education in the field of ophthalmic photography, to set and maintain standards for the profession through multiple certification programs, and to promote scientific advancement in ophthalmic imaging technology. Members of the Ophthalmic Photographers' Society perform imaging of all structures of the eye using highly specialized equipment to increase the level of patient care and help to advance the science and practice of ophthalmology.

About EyeKor: EyeKor, Inc., is a Software-as-a-Service (SaaS) company that offers a complete spectrum of integrated ophthalmic clinical trial image data management and analysis services, from preclinical to clinical phases I through IV. EyeKor expertise encompasses a diverse array of ophthalmic testing methods including fundus photography and angiography, optical coherence tomography, fundus autofluorescence imaging, automated visual field testing, and electrophysiological testing. EyeKor’s cloud-based software application, EXCELSIOR™, was built specifically for supporting image data collection and management of ophthalmic preclinical studies and clinical trials. EXCELSIOR™ utilizes the latest web and imaging technologies for data standardization, analysis, grading and reporting. EXCELSIOR™ is cleared with the FDA as a Class II medical device, with specific indication for use for managing ophthalmic clinical trials.

The Advantages of Using OCT in Ophthalmic Preclinical Studies

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.

The 6 Phases of Ophthalmic Preclinical Research

The outcome of a clinical research program depends, in no-small part, on the decisions made during the preclinical phases of development. As with virtually all fields of pharmaceutical research, the goal of the ophthalmic preclinical process is to identify and elevate a lead candidate to advance into the next phases of research, or to eliminate a candidate in the research stage as early as possible to optimize R&D resources and efforts.

Since animal models can reproduce important pathologic aspects of human ocular diseases, they’re used in preclinical research to determine the efficacy of the novel therapies.

Those developing such therapies, however, should be well aware of important limitations associated with animal models. While it’s possible to model some parts of a human disease in a non-human species, many ophthalmic conditions – particularly those affecting the posterior segment – could present challenges for researchers.

To meet these challenges, EyeKor’s EXCELSIOR™ Preclinical platform gives researchers more power to see valuable results from their preclinical data. To set the stage for how these new systems can help, let’s briefly step back and run through each phase of the ophthalmic preclinical process step-by-step.

 

1. Initial Discovery & Formulation

Discovery of potential candidate therapies is the first step toward developing them into novel drugs. With most ophthalmic diseases, this typically begins with target identification, or selecting the particular pathogenesis mechanism of the disease that affects the part of the eye one intends to treat.

Target identification for ophthalmic preclinical trials can be carried out a number of ways; but most studies use in vitro enzymatic assays or binding and cell-based studies. Common tools used for these initial preclinical stages include mass spectroscopy and liquid chromatography. After these studies are reviewed, researchers can confirm (or refute) an interaction and choose a lead compound based on their findings.

Compounds that perform well in preliminary tests move into in vivo pharmacokinetic and efficacy studies for further evaluation.

2. Drug Metabolism and Pharmacokinetics (DMPK)

Once a lead compound is identified, researchers must then develop a drug formulation and delivery route that is capable of been administered in vivo, as investigated through Drug Metabolism studies. In ophthalmic drug development, this is often a challenging task as it requires researchers and study teams to consider many factors that may influence the results of preclinical studies or clinical trials.

Pharmacokinetic studies of ophthalmic drugs provide developers with important data for determination of both optimal dose and frequency of administration. These studies also provide a number of other key data points, including:

  • The maximum concentration of the drug inside specific ocular structures, like the retina (Cmax)
  • When Cmax is reached (Tmax)
  • How the body affects the characteristics of the drug

A strong PK study may facilitate “screening out” of many candidates that have made it to this level of testing. In today’s pharmaceutical landscape, therefore, researchers and study teams are conducting PK studies earlier and earlier to improve the selection process sooner.

3. Proof-of-Concept Studies

Proof-of-concept studies may have several goals, but among the most important is determining if the drug candidate exhibits expected results in a selected animal model, depending on known pathology and the drug’s mechanism of action. For ocular drug development, these studies involve testing animals in vivo and typically use multiple diagnostic imaging procedures. Imaging biomarkers, derived from the results of the imaging procedures through carefully planned imaging protocol and post-acquisition data analysis, are used to capture the treatment effects throughout the course of the studies.    

Ultimately, the results of the preclinical study should reflect what will be tested in humans during the clinical trial.

Clinical success is never assured, no matter how well a study is designed or conducted, and translatability between animal models and human patients is complicated by numerous factors However, better decision-making early in the development process, can maximize the predictive value of of preclinical results if moving forward into clinical trials.

4. GLP Toxicity Studies

Before moving into the next phase of preclinical development, manufacturers must first carry out GLP toxicity studies to the satisfaction of the FDA’s regulatory guidelines. It’s important to note that GLP toxicity studies will need to adhere to Good Laboratory Practices (GLP). Conducting animal toxicity studies to this quality system ensures study data is collected correctly and enough animals are tested to ensure the drug is both reasonably safe and effective.

GLP toxicity studies from at least two different species need to be conducted. Using similar imaging biomarkers to those used in proof-of-concept studies, and ultimately those will be used during the clinical trial stage, these studies are done to evaluate the treatments effectiveness in animal models.

EyeKor’s EXCELSIOR™ Preclinical platform shines in the proof-of-concept and toxicology studies steps––allowing researchers to gather, manage and interpret imaging data in concordance with the information gathered at earlier stages.

5. CMC Efforts

CMC efforts (chemistry, manufacturing and control), represent the first phase of IND-enabling studies. When a final formulation for clinical use is prepared, these efforts ensure that the product is stable, and that the production process is both scalable and achievable within GMP standards.

6. Submitting IND Application

After compiling preclinical results, it’s time to present findings to the FDA in both pre-IND and subsequent IND meetings.

The ultimate goal of these meetings is to design the clinical trial protocols based on the data gathered during every step of the preclinical process as they relate to dosage, frequency of administration and safety.

Perhaps the most important takeaway to remember when planning and carrying out the preclinical investigation process is to keep the final result in mind at all times. Don’t make short-term decisions. Instead, consider the entire development process and put all necessary quality control measures in place well ahead of time.

 

Are you looking to bridge the gap between a preclinical and clinical program for your new treatment? EyeKor’s EXCELSIOR™ Preclinical platform is a first-of-its kind FDA 501(k)-cleared, cloud-based software platform revolutionizing the way ophthalmic imaging data in preclinical investigations is managed.

This customizable software is designed to help your team manage the full spectrum of preclinical study types and imaging modalities, harmonize 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.

EyeKor EXCELSIOR™ Platform Improves Efficiency in Ocular Preclinical Research

Working in partnership with the renowned experts at Ocular Services On Demand LLC. (OSOD), EyeKor is excited to continue introducing its cloud-based preclinical platforms to the ocular preclinical research community. The EXCELSIOR™ Preclinical platform is designed to bridge the gap between the laboratory and the clinic, bringing a powerful array of comparative vision science and ophthalmic imaging services to those developing exciting new treatments.

The EXCELSIOR™ Preclinical platform brings the high efficiency and accuracy of EyeKor’s flagship clinical software to preclinical applications, harmonizing imaging data and research findings into one centralized database. The ocular exam module allows veterinary ophthalmologists to record both the clinical assessment and the  schematic drawing of lesion findings, and analyze them  side-by-side with ocular imaging data such as fundus photos and OCT. Real-time tabling and graphing function with DataBook, and access to expert analysis help study teams track, visualize and understand research data to make meaningful interpretations and informed decision-making each step of the way.

We look forward to offering the EXCELSIOR™ preclinical platform and other innovative research tools to those developing new treatments throughout the industry.

Implications for Ophthalmology of the Just-released FDA Draft Guidance on Imaging in Clinical Trials

The evolution of diagnostic imaging technologies across medicine has been rapid, and a number of companies seeking approval for novel drugs and devices have been using and want to use imaging data as study endpoints in clinical trials. To assist these companies, the U.S. Food and Drug Administration (FDA) recently released a new draft guidance on the use of images in clinical trials. The new draft document, “Clinical Trial imaging endpoint process standards: Guidance for industry,” if enacted as written, will have important implications for the conduct of ophthalmic clinical trials.

Designed to provide a clear path for clinical trial sponsors who want to use images as an endpoint in drug and device clinical trials, the guidance focuses on creating standards for image acquisition, display, archiving, and interpretation, all of which the FDA considers key elements when imaging is used in determining whether a drug or device has met its primary endpoint.

Imaging process standards aim to help trial sponsors ensure that images are obtained in a uniform manner that complies with a trial’s protocol and that allows fair comparison with images obtained with different devices by different people and at different centers; the guidance also calls for a verifiable audit trail to document the accuracy and reliability of the imaging process. Uniformity in image gathering, transmission, and interpretation is a critical aspect of ensuring a clinical trial’s ability to establish treatment effects and detect potential safety concerns.

Published in March 2015, the FDA draft guidance would revise the Standards for Clinical Trial Imaging Endpoints issued in August 2011. A number of key points have been clarified, including the need, in some cases, for an “imaging charter” that would detail trial-specific imaging process standards that would have to be in place prior to patient enrollment.

Trial-specific standards are particularly important in specialties like ophthalmology, where there are few specialty-wide standards for imaging.

One important aspect of this is that the draft guidance would require that any software used in image interpretation be FDA-approved or cleared, or undergo the arduous investigational device exemption (IDE) process. “If interpretation tools are to be used,” the guidance states, “the [imaging] charter should specify the use of FDA-approved computer-assisted interpretation tools. Alternatively, an unapproved (investigational) tool justified for use with a given imaging modality can be used in some situations if it is compliant with all applicable FDA regulations, including the investigational device exemption requirement” (p. 26, ll. 1048-52).

What this means is that sponsors of trials with imaging endpoints would have three options for compliance: use software already approved or cleared by the FDA-for ophthalmic image management and interpretation (currently, the only such software is EXCELSIOR™ by EyeKor, LLC); develop their own software and ensure that it meets the standards set in the IDE process; or use a single manufacturer’s already approved software, which may have limited capability to analyze data across multiple technology platforms—and ophthalmic trials regularly use data from multiple platforms.  

As a draft guidance, the document will evolve, and the FDA must still decide whether the proposal will be adopted in whole, in part, as amended, or not at all. But, for now, sponsors are strongly encouraged by the FDA to follow the guidance as closely as possible to make sure that their clinical trials don’t hit regulatory snags down the road.