Authors: Zhao Xun Feng¹, Alp Polat², Stephanie Kletke², Ashwin Mallipatna², Brenda Gallie². ¹Department of Ophthalmology, University of Ottawa, ²Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children.

Author Disclosures: Z. Feng: None. A. Polat: None. S. Kletke: None. A. Mallipatna: None. B. Gallie: None. 


Abstract Body: 

Purpose: Pathogenic RB1 allele inheritance predisposes children (termed H1) to early onset bilateral retinoblastoma. We update follow-up and apply a novel measure of treatment impact to H1 infants previously published (Ophthalmology 2016.123(12):2610-2617) that suggested planned early-term delivery facilitates less invasive therapy and better vision outcomes than spontaneous birth. 

Study Design: Retrospective, observational study. 

Methods: We updated follow-up from medical records of consecutive children with familial retinoblastoma born between 1996 and 2014 treated at SickKids. Cohort I spontaneously delivered neonates were examined within 1 week and confirmed to be H1. Cohort II infants were identified H1 by amniocentesis and scheduled for early-term delivery (36-38 weeks’ gestation). We developed a novel method to semi-quantitate outcome and long-term impact for retinoblastoma eyes. Perceived invasiveness and long-term impact of each therapy was assigned a score: 1, focal retinal therapy (cryotherapy, retinal laser); 3 , ocular chemotherapy (periocular, intravitreal); 7 , chemotherapy infusion (systemic, intra-arterial); 7 , eye conserving surgery (brachytherapy, tylectomy); 10 , response to failed attempted eye salvage (enucleation of first eye, external beam radiotherapy) and 20 , enucleation of the last eye. Total eye impact score is the sum of treatment impact scores required to achieve cure. 

Results: Studied were 42 eyes (21 children) (20 Cohort I and 22 Cohort II. All 42 eyes eventually demonstrated tumor, present at birth in 11/20 (55%) Cohort I vs 4/22 (18%) Cohort II (P=0.01). At first tumor appearance, 10/20 (50%) of Cohort I had stage Group A (cT1a) (small tumors not near fovea or optic nerve) vs 15/22 (68%) Cohort II ( P =0.23). Mean treatment impact score Cohort I was 14 (range, 1-31) vs 9 (range, 1-31) Cohort II ( P = 0.08). Focal retinal therapy alone achieved cure in 4/20 (20%) Cohort I vs 10/22 (45%) Cohort II ( P =0.08). Focal retinal therapy combined with ocular chemotherapy achieved cure in 7/20 (35%) Cohort I vs 12/22 (55%) Cohort II ( P =0.20). Failure of eye salvage occurred in 6/20 (30%) Cohort I vs 2/22 (9%) of Cohort II ( P =0.09). Mean LogMar vision was 1.1 (Snellen 20/250) Cohort I vs 0.1 (Snellen 20/40) Cohort II eyes ( P =0.02). Mean follow-up was Cohort I, 11.6 years and Cohort II, 12.2 years 

Conclusions: Children who inherit their parent’s pathogenic RB1 allele achieved cure with less invasive treatments and better vision if they have pre-natal molecular testing and planned early-term delivery which facilitated retinal evaluation prior to onset of first tumor.

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