PROJECT SUMMARY Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. Although retinoblastoma is an aggressive cancer, early diagnosis and treatment may prevent visual impairment, and even improve mortality rates. This is particularly relevant for children at risk for retinoblastoma due to family history of the disease, which can be inherited in an autosomal dominant fashion. These children benefit fromea rly and frequent screening evaluations. Currently, RB diagnosis and management remains largely dependent upon ophthalmoscopic evaluation by expert clinicians. Ophthalmoscopy offers panretinal imaging, but suffers from a poor sensitivity to sub-millimeter (subclinical) tumors and a limited ability to monitor treatment response. Handheld optical coherence tomography (HH-OCT) offers the promise to address both of these needs, but technical deficiencies in imaging speed and axial range severely limit is clinica l utility. Recent innovations in circular-ranging methods, stretched-pulse mode-locked frequency comb lasers, and ultrawide handheld microscopes open new avenues for clinically meaningful deployments of HH-OCT in the management of Rb. In Aim 1, we will integrate these innovative technologies into a prototype instrument providing panretinal high- resolution three-dimensional imaging. In Aim 2, we will perform pilot imaging studies in sedated children undergoing RB screening. Study data will be used to assess the feasibility of panretinal imaging by HH-OCT in sedated children, to quantify RPE and ILM visibility as an image quality metric predictive of the instrument’s ability to detect subclinical tumors, and to confirm that the volume of all imaged tumors, regardless of size, can be calculated.