Identification of Anterior Segment Structural Biomarkers in Glaucoma Following Pediatric Cataract Using Ultrasound Biomicroscopy

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This K23 application is submitted by Janet L. Alexander, MD, Assistant Professor in Ophthalmology and Pediatrics. My long-term goal is to become an independent clinical investigator focusing on clinical applications and innovations in ocular imaging to enhance the care of pediatric patients with ophthalmic disease. This K23 award will provide the mentored career development needed to gain in-depth expertise in study design, statistics (culminating in a Master’s of Science in Clinical Research), image analysis (though coursework and mentorship), and professional development. Glaucoma develops in more than one quarter of children with congenital cataracts in the 5 years following cataract surgery. Several structural risk factors for glaucoma following congenital cataract surgery (GFCCS) have been established including age, corneal size, and anatomic abnormalities of the sclera and ciliary body. Ultrasound biomicroscopy (UBM) has potential to revolutionize our understanding of these structural risk factors and many more. A critical gap in the field is our inability to utilize pre-operative data to anticipate GFCCS, to provide accurate personalized prognosis and earlier diagnosis and treatment. My overall goal is to determine the contribution of structural anatomy in the risk of GFCCS and offer clinicians a predictive risk profile for GFCCS at the time of cataract surgery (prior to disease onset) based on anterior segment structural features determined from UBM images. I hypothesize the structural risk factors (biomarkers) identified in pre-operative UBM images will reflect structural immaturity and correlate with GFCCS. We will test this hypothesis with the following Aims: 1) We will determine baseline quantitative structural characteristics among healthy subjects age 0-5 years using UBM images, 2) We will determine structural characteristics among subjects age 0-5 years with cataracts, to compare the cataract cohort to age-matched controls. The cataract cohort will be followed longitudinally to determine the structural biomarkers that correlate with development of GFCCS. My training efforts parallel these Aims and focus on gaining expertise in clinical research, biostatistics, image analysis, and professional development. In addition to didactic coursework, I will benefit from the close mentorship of Drs. Steven Bernstein and Bennie Jeng, and established leaders in each area of my intended expertise. The current study is important because identification of the specific measurable structural risk factors associated with GFCCS will aid clinicians in diagnosis and provide an immediate high yield potential target for treatment and prevention. Clinicians will identify structural features from UBM performed prior to cataract surgery to quantify risk for development of glaucoma. The results of the proposed research will provide the foundation for a future study examining interventions based on structural biomarkers for GFCCS. The ultimate goal of my research is to develop quantitative diagnostic tools to enhance clinical care for pediatric patients with anterior segment disease, leading to improved treatments and reduced childhood blindness.