Pre-Laser Fundus images Post-Laser Fundus images Horizontal Caliper Vertical Caliper Pre-Laser OCT frames Post-Laser OCT frames * Figure 1: OCT guided localization and photocoagulation of invisible tumor. Horizontal Caliper identified the lateral extent of the tumor. Vertical Caliper identified point localization of the tumor. Point and lateral locations were identified in each of the pre-laser OCT frames that showed the tumor. Rectangular area (blue star) were plotted over pre-laser fundus images putting in consideration nearby vascular bifurcations (yellow stars) and upper and lower limits (green lines) corresponding to one frame below and above last ones (yellow box) with detected tumor. Post-laser fundus images can show retinal whitening in response to treatment. Post-laser OCT frames ensured complete tumor treatment. * Pre-Laser Fundus images Post-Laser Fundus images

Pre-Laser treatment Post-Laser treatment Final follow up * 45 days earlier Figure 2: OCT detection of subclinical tumors and scar recurrence. Upper row (yellow box): a small rounded invisible tumor (*) was missed in initial OCT scanning and diagnosed 45 days later when it attained a larger size. Laser was applied using the described technique and verified by post-laser OCT that showed tumor swelling, hyper-reflectiveness and shadowing. A flat scar can be seen within 2 months verified by OCT. Lower row (green box): a small tumor scar (*) within 2 disc diameters of the foveal center (yellow arrowhead) showed initial stability after treatment with the described laser technique followed by subclinical subtle recurrence 84 days later detected on OCT. It was treated with a single laser session verified by post-laser OCT. the scar is flat with pigmentary changes 1 year post laser. Pre-Laser treatment Post-Laser treatment Final follow up * *

Prenatal RB1 mutation detection Positive 100 % risk Negative 0 % risk Planned late preterm or early term delivery (36/37 weeks) No Screening required Figure 3: Flow chart showing proposed secondary prevention protocol for familial retinoblastoma. Clinical tumors at birth 20 % probability No clinical tumors at birth 80 % probability Manage per standard practice according to staging OCT-guided posterior pole screening No tumor detected Invisible tumor detected Clinical tumors detected OCT-guided localization and photocoagulation OCT guided tight follow up Every 2weeks for 3 months Every 3 weeks for 3 months Every 4 weeks for 6 months Invisible tumor/recurrence detected