ISOS: Conjunctival Hyperemia Quantization

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Purpose of the application

To describe a slit lamp-based imaging system and software that objectively and automatically quantifies conjunctival hyperemia. Conjunctival hyperemia is an important indicator of several ocular conditions including ocular surface inflammation, ocular irritation, and systemic disease. It is associated with increased blood volume in the anterior scleral, bulbar conjunctival and limbal vessels. Since conjunctival hyperemia is a consistent clinical sign of the ocular response to physiological and pathological stimuli, it has been considered an important endpoint in efficacy and safety trials for contact lenses, medications, as well as for evaluation of ocular toxicity of drugs, chemicals and pollutants. Thus, assessing the progression of conjunctival hyperemia is critically important for the treatment of patients with ocular disease.

Methods

The Imaging System for the Ocular Surface (ISOS) consisting of hardware and software components was developed to capture images and perform automated image analysis of conjunctival blood vessel morphology. It is a joint development between Novartis and ADCIS. A pilot study was conducted to obtain and analyze conjunctival images from patients with allergic conjunctivitis following allergen challenge. Manual image grading was performed on sets of images that were subsequently processed by image analysis. A statistical correlation of grading and image analysis results was performed, and a machine learning-based automatic hyperemia grading system was integrated in ISOS.

Results

Automatic image analysis using ISOS resulted in the ability to evaluate changes in a variety of morphological parameters of vessels that were not quantifiable to clinical observers (e.g. vessel dimensions such as diameter, total length, density), and correlate them with human grading. A machine learning-based system was developed in ISOS to mimic human grading and automatically quantify hyperemia from 35 morphological parameters. The automatic grading provided by ISOS was robust, highly correlated to manual image grading, and provided an objective hyperemia grade within a few seconds.

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Manual grades between 0 (no redness and 4)

Conclusion

This pilot study demonstrated that the ISOS suite represents a valuable tool for objective assessment of conjunctival hyperemia. ISOS minimized grading variations across images and provided clinically meaningful measurement of conjunctival hyperemia and insights into the progression of ocular hyperemia. ISOS was fast, reliable, accurate, and most importantly, eliminated human bias in assessing conjunctival hyperemia.

ISOS Architecture

Three types of users can interact with ISOS: Graders, Viewers and Reviewers.

  • A Grader is an expert in a field relevant to the project images who annotates each image to identify and comment about the objects that are significant to the Viewers. Typically, there will be multiple graders annotating the same image set. To avoid bias, ISOS only allows a Grader to see her/his own annotations.
  • A Viewer is someone who has a need for the information contained in the Graders' annotations, but is not provided with any capability to change the Graders' results. Viewers include computer programmers developing algorithms to automatically detect the graded objects, statisticians analyzing the results to better understand the causes and progressions of disease, and those monitoring the grading process.
  • A reviewer is someone who can see all the information (Grader's annotations, automatic measurements), export grades and measurements, perform queries on the image database and register images.

ISOS Capabilities

The ISOS software product has the following capabilities:

  • Capture images of the ocular surface
  • Store images and associated patient data in a database
  • Manually annotate objects of interest captured in image form, and save those annotations in a database so they can be accessed by others
  • Perform automatic image processing and save measurements in a database
  • Review manual and automatic grades
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Technical Specifications

ISOS is a stand-alone, software product that can be installed on any personal computer running Windows® XP or higher.

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Video tutorials

ISOS Grader
ISOS Reviewer
ISOS Viewer