Main Outcome Measures
Abbreviations and Acronyms:AAOOP (American Association of Ophthalmic Oncologists and Pathologists)
|Relative of Proband||Pretest Risk for Mutant Allele (%)|
|Bilateral Proband (100)||Unilateral Proband (15)|
Ophthalmic Screening Guidelines
- 1.All children at elevated risk for retinoblastoma above the population risk require serial dilated fundus examination by an ophthalmologist with experience in retinoblastoma. Depending on the clinical setting and resources, this may be an ocular oncologist, pediatric ophthalmologist, retina specialist, or comprehensive ophthalmologist (grade D).
- 2.Early and frequent clinical screening is required for babies at elevated risk, and the examinations may be spaced out over time as children grow older (grade C).
- 3.We recommend screening for at-risk children from birth up to the age of 7 years. After age 7 years, no further screening of asymptomatic children is recommended, unless they are known to carry an RB1 mutation. We suggest that individuals who are known RB1 mutation carriers be followed indefinitely with examinations every 1 to 2 years after the age of 7 years. A single dilated fundus examination to evaluate for asymptomatic spontaneously regressed retinoblastoma or retinoma is recommended for all first-degree relatives of a retinoblastoma proband, including older siblings if the RB1 genetic status of the relatives is unknown (grade C).
- 4.Genetic counseling and testing clarify the risk for retinoblastoma in children with a family history of the disease and improve outcomes at reduced cost, justifying making testing available to all patients with a personal or family history of retinoblastoma. Genetic evaluation should be initiated whether the affected relative demonstrated unilateral or bilateral disease because both have a substantial risk of being heritable (grade C).
- 5.Stratifying children on the basis of their expected risk for retinoblastoma depending on their relationship to the affected family member and refining that risk by genetic testing as soon as possible in order to optimize care. Children at high risk for retinoblastoma require more frequent screening, which may include examinations under anesthesia (grade C).
- 6.It is recommended that genetic testing be performed at a Clinical Laboratory Improvement Amendments–certified laboratory (or similar certification in other countries) with experience in retinoblastoma genetic testing. Sensitivity of genetic testing may vary by laboratory, and post-test risk calculation by a genetics professional, taking into account the estimated laboratory sensitivity, will clarify the clinical risk category (high, intermediate, low, or population risk) for an individual child (grade B).
- 7.Decisions regarding examination method (examinations under anesthesia vs. nonsedated examination in the office) are complex and decided by the clinician in discussion with the child's family. The preference of the majority of the clinical centers contributing to this consensus statement is reflected in Figure 3. Individual centers make policy decisions on the basis of available resources and expert clinician preference. Examinations under anesthesia are strongly considered for any child who is unable to participate in an office examination sufficiently to allow thorough examination of the retina (grade D).
- 8.Examiners should be aware that young babies often present with tumors in the posterior pole, but the older the child is at the time retinoblastoma develops, the more likely the tumor location will be peripheral (grade B).
- 9.The schedules presented in Figure 3 are general guidelines and reflect a schedule for examinations of an at-risk child when no lesions of concern have been noted. It may be appropriate to examine some children more frequently (grade D).
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Financial Disclosure(s): The author(s) have made the following disclosure(s): A.H.S.: Consultant – Castle Biosciences Inc.
D.S.G.: Travel compensation and Co–principal investigator: Children's Oncology Group trial; Travel compensation and consultant – American Board of Ophthalmology; Consultant – AbbVie, Aura Biosciences, American Society of Clinical Oncology, Castle Biosciences; Grants – Housemann/Wilkins Foundation and Lois Kuss Fund for Glaucoma Research.
B.L.G.: Unpaid Medical Director of Ocular Oncology at Impact Genetics; Employed – Hospital for Sick Children; Expert testimony – legal cases; Grants pending – Retina Society; Travel expenses – SickKids, and reports a pension.
B.P.M.: Consultant to, holds stock in, and receives travel expenses – Aura Biosciences.
S.E.P.: Member of the Scientific Advisory Board – Baylor Miraca Genetics Laboratories; Grants pending – National Institutes of Health; Royalties – Antibody Users; Travel expenses – American Association of Cancer Research.
P.C.-B.: Employed – Houston Methodist Physician Organization; Grants pending – NASA; Payment for lectures – UT Houston Medical School Ophthalmology; Travel expenses – Children's Oncology Group.
Supported by a Lloyd Research Endowment Faculty Grant (A.H.S.) and by an unrestricted departmental grant from Research to Prevent Blindness (New York, NY).
HUMAN SUBJECTS: This study does not include human subjects/tissues.
Conception and design: Skalet, Gombos, Gallie, Kim, Shields, Marr, Plon, Chévez-Barrios
Data collection: Skalet, Gombos, Gallie, Kim, Shields, Marr, Plon, Chévez-Barrios
Analysis and interpretation: Skalet, Gombos, Gallie, Kim, Shields, Marr, Plon, Chévez-Barrios
Obtained funding: Not applicable
Overall responsibility: Skalet, Gombos, Gallie, Kim, Shields, Marr, Plon, Chévez-Barrios
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