• Ocular Pathology/Oncology, Pediatric Ophth/Strabismus

    This study validates that prenatal molecular testing enables the child to be delivered early, but full term, resulting in fewer and smaller tumors present at birth and a better chance at retaining vision.

    Children with an RB1 germline mutation may have retinoblastoma at birth, often in vision threatening locations like the posterior pole. Conventional postnatal screening recommends simply that infants with a family history of retinoblastoma be examined for tumor detection as soon as possible after birth and repeatedly for the first few years of life. The findings here indicate that early diagnosis from prenatal testing coupled with elective delivery at around 37 weeks gestation showed good ocular and visual outcomes, along with a chance for less invasive therapy.

    Investigators divided 20 children with familial retinoblastoma born between 1996 and 2014 into 2 cohorts. Cohort 1 included 8 spontaneously delivered neonates examined within 1 week of birth and confirmed postnatal to carry their family's RB1 mutant allele. Cohort 2 comprised of 12 infants identified by amniocentesis to carry their family's RB1 mutant allele. These infants were scheduled delivery between 36 to 38 weeks of gestation, with full retinal examination on day 1.

    Vision-threatening tumors were present in 4 of 8 infants in cohort 1 and in 3 of 12 infants in cohort 2. All infants eventually developed bilateral tumors before age 1. At the first treatment, 1 of 8 infants in cohort 1 had eyes in stage cT1a or cT0, the smallest and least vision-threatening tumors based on the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, compared with 8 of 12 infants in cohort 2 (P=0.02). Treatment course involved focal therapy, chemotherapy or radiation.

    Treatment success, defined as avoidance of enucleation, external-beam irradiation or both, was achieved in 3 of 8 children in cohort 1 compared with 11 of 12 children in cohort 2 (P=0.002). Additionally, more children in the second cohort achieved acceptable vision (better than 0.2 decimal) and useful vision (better than 0.1, legal blindness). The authors also confirm that the earliest tumors involve the perimacular region, threatening loss of central vision, whereas later-developing tumors tended to be peripheral, with less visual impact. Encouragingly, there were no complications related to early-term delivery.

    Although this study is limited by its small sample size and retrospective nature, it represents the largest cohort of children with retinoblastoma diagnosed prenatally. Based on the findings here, the authors show that prenatal molecular diagnosis facilitates anticipatory planning for both the child and family, offering a chance for better vision outcomes compared with conventional postnatal screening in familial retinoblastoma.