Catherine Cukras MD, PhD, is a clinical researcher interested in understanding the retinal disease from clinical study to provide insights into disease pathogenesis and developing outcome measures for clinical trials.
Her area of expertise and interest focuses on degenerations of the outer retina. She is an investigator at the National Eye Institute at the National Institutes of health, in Bethesda MD, USA. The NIH Clinical center attracts large populations of people with rare retinal diseases which has enabled her to obtain wide exposure to uncommon retinal conditions. Her experience and training in the combined fields of medical retina and inherited retinal degenerations uniquely positions her to investigate retinal degenerations spanning monogenetic disease as well as age-related macular degeneration (AMD). Focused clinical study of these diseases in parallel will be mutually supportive.
Catherine grew up in New York and was a chemical engineering major at Princeton University. Early in her training she conducted research in cell biology and physiology during an MD/PhD at Washington University in St Louis, Missouri. After completing a residency in ophthalmology at the Scheie Eye Institute at the University of Pennsylvania, I conducted my medical retina fellowship training at the National Eye Institute which provided me not only with clinical training but also with training and experience in designing and conducting clinical trials. Specialization in medical retina allows her to continue research in physiology in the setting of studying retinal disease pathophysiology.
Outcome measures in AMD – the importance of functional and structural studies
While visual acuity has long been used as the primary end point for clinical trials in AMD, outcome development reflecting disease progression over earlier stages of disease could potentially increase the feasibility of clinical trials and allow for the identification of eyes with more severe cell dysfunction within early and intermediate categories of AMD.
Examination of pathologic features in intermediate AMD eyes demonstrate preferential loss of rod cells in the macula even in eyes with early disease compared with age-matched controls. Dark adaptation (DA) is one measure of visual function that has been identified to reveal abnormalities in non-advanced stages of AMD.
In an ongoing longitudinal study of over 100 patients with early to intermediate AMD, we investigate objective measures of dark adaptation and correlate them with ocular and patient features measures, such as visual acuity, and structural features obtained through multimodal imaging, as well as with the patient’s perceived difficulty in low luminance as assessed through responses on a questionnaire. In cross sectional study, an analysis of covariance demonstrated the variables which were correlated with dark adaptation measures include age, AMD group, and the presence of reticular pseudodrusen. We also find that the patient-reported functional deficits correlate with both reduced DA and reduced choroidal thickness. Longitudinal analysis demonstrates that across patients, we generally observed a decline in DA function over time, which correlated with patient-reported functional deficits, and is accelerated in eyes with greater AMD severity and especially in eyes with reticular pseudodrusen. The RIT prolongation as a measure of changing DA function may be a useful functional outcome measure in AMD clinical studies.