• My Dashboard My Education Find an Ophthalmologist
  • Home
  • Coronavirus
  • For Ophthalmologists
    • Meetings
      • AAO 2022
        • Meeting Information
          • Past and Future Meetings
          • Mobile Meeting Guide
          • Contact Information
          • Annual Meeting News
          • Health and Safety
          • Policies and Disclaimers
        • Program
          • Program Highlights
          • Subspecialty Day
          • Virtual Meeting
          • Program Committees
          • CME
          • Meeting Archives
        • Expo
        • Registration
        • Hotels & Travel
          • Hotel Reservation Information
          • Chicago
          • International Attendees
          • Hotel Meeting Space
        • Presenter Central
          • Presenter Central
          • Abstract Selection Process
          • Submission Policies
          • Subject Classification/Topics
          • Instruction Courses and Skills Transfer Labs
          • Papers and Posters
          • Videos
          • Grand Rounds Symposium
          • Program Participant and Faculty Guidelines
          • Faculty Development Program
        • Exhibitors
          • Exhibitor Central
          • Exhibitor Portal Information
          • Exhibitor Prospectus
          • New Exhibiting Companies
          • Exhibitor Resources
          • International Exhibitors
          • Promotional Opportunities
          • Exhibitor Hotel Reservations
      • Mid-Year Forum
        • Registration and Travel
        • Congressional Advocacy Day
        • Advocacy Ambassador Program
        • Program
        • Schedule
        • Sponsored Attendees
        • News
      • Codequest
        • Codequest Instructors
        • Claim Codequest CME or CEU Credit
      • Eyecelerator
    • Clinical Education
      • COVID-19
      • Education
        • Browse All Education
        • Courses
        • Cases
        • Learning Plans
        • Interactive
        • Focal Points
        • Wills Eye Manual
        • Disease Reviews
        • Clinical Webinars
        • Diagnose This
        • Self-Assessments
        • Educational Centers
          • Glaucoma Education Center
          • Pediatric Ophthalmology Education Center
          • Laser Surgery Education Center
          • Myopia Resources
          • Oculofacial Plastic Surgery Center
          • Redmond Ethics Center
      • Journals
      • Guidelines
        • Browse All Practice Guidelines
        • Preferred Practice Patterns
        • Clinical Statements
        • Compendium Guidelines
        • Complementary Therapy Assessments
        • Medical Information Technology
        • Ophthalmic Technology Assessments
        • Patient Safety Statements
        • Choosing Wisely
        • Low Vision
        • Eye Care for Older Adults
        • Eye Disease Statistics
        • About the Hoskins Center
      • Video and Image Library
        • Browse All Videos
        • Clinical and Surgical Videos
        • Presentations and Lectures
        • 1-Minute Videos
        • Master Class Videos
        • Basic Skills Videos
        • Interviews
        • Images
        • Submit an Image
        • Submit a Video
      • Podcasts
        • Browse All Audio and Podcasts
        • Experts InSight
        • Ophthalmology Journal
      • News
        • Browse All Clinical News
        • Editors' Choice
        • Headlines
        • Current Insight
      • CME Central
        • Browse All CME Activities
        • Claim CME Credit and View Transcript
        • CME Planning Resources
        • Complete Your Financial Disclosure
        • Joint Sponsorship Portal
        • LEO Continuing Education Recognition Award
        • Safe ER/LA Opioid Prescribing
        • Check Your Industry Payment Records
      • MOC
      • Resident Education
        • Resident Education Home
        • Browse All Resident Content
          • Courses
          • Flashcards
          • Interactive Cases and Simulations
          • Videos
          • Webinars
        • OKAP and Board Exam Resources
          • OKAP Exam
          • Board Prep Resources
          • OKAP and Board Review Presentations
          • Study Flashcards
        • Cataract Master
        • Diversity and Inclusion Education
        • News and Advice from YO Info
        • Pediatric Ophthalmology Education Center
        • PGY-1 and PGY-2 Resources
        • Simulation in Resident Education
    • Membership
      • Join
      • Renew
      • Current Member
      • Volunteer
      • Physician Wellness
      • Member Directory
      • Member Obituaries
      • AAOE Membership
    • Advocacy
      • Advocacy News
      • Get Involved
        • Ways to Give
        • How to Get Involved
        • Congressional Advocacy
        • Support the Academy's Agenda
        • Research Legislation
        • Find Your Legislators
        • I Am an Advocate
        • Advocacy at Home
        • Advocate Tools
        • Best Practices for Advocating at Home
        • Social Media Toolkit
        • Letter to Editor
        • Town Hall Guide
        • Guide to Engaging With New Lawmakers
        • Resources
        • Attending a Political Fundraiser
      • OPHTHPAC
        • About Us
        • Join OPHTHPAC
        • OPHTHPAC Blog
      • Surgical Scope Fund
        • Support Surgery By Surgeons
        • Surgery By Surgeons Blog
    • Publications
      • EyeNet Magazine
        • Latest Issue
        • Archive
        • Subscribe
        • Advertise
        • Write For Us
        • Corporate Lunches
        • Contact
        • MIPS 2022
      • Focal Points
      • Ophthalmology
      • Ophthalmology Glaucoma
      • Ophthalmology Retina
      • YO Info
      • Scope
    • Subspecialties
      • Cataract/Anterior Segment
      • Comprehensive Ophthalmology
      • Cornea/External Disease
      • Glaucoma
      • Neuro-Ophthalmology/Orbit
      • Ocular Pathology/Oncology
      • Oculoplastics/Orbit
      • Pediatric Ophthalmology/Strabismus
      • Refractive Management/Intervention
      • Retina/Vitreous
      • Uveitis
    • IRIS Registry
      • About
      • Using the Registry
        • User Guide
        • Medicare Reporting
        • Maintenance of Certification
        • Non-EHR Reporting
      • Sign Up
        • Application Process
        • Why Participate
        • Once You've Applied: Getting Started
        • What Practices Are Saying About the Registry
      • Requirements
        • EHR Systems
        • Data & Technical Needs
      • Research
      • Registry Dashboard
      • News
      • Medicare & MIPS
    • Medicare Information
    • Diversity, Equity, and Inclusion
  • For Practice Management
    • Managing Your Practice
      • Managing Your Practice Topics
      • Coronavirus Resources
      • Reopening & Recovery
      • Practice Forms Library
      • Practice Management News and Advice
      • AAOE-Talk
      • Video Library
      • Ophthalmology Job Center
      • Benchmarking and Salary Tools
      • Academy Consultations
      • Consultant Directory
    • Coding
      • Coding Topics
      • Codequest Events
      • Ask the Coding Experts
      • Coding Updates and Resources
      • Coding for Injectable Drugs
      • EM Documentation
      • ICD-10-CM
      • Ophthalmic Coding Specialist (OCS) Exam
      • Retina
      • Savvy Coder
    • Webinars and Events
      • Annual Meeting
      • Codequest Courses
      • Mid-Year Forum
      • Webinar Recordings
    • IRIS Registry
      • Merit-Based Incentive Payment
    • Medicare and MIPS
      • MIPS
        • Quality
        • Promoting Interoperability
        • Improvement Activities
        • Cost
        • Avoid a Penalty
      • Resources
      • Medicare Participation Options
      • Medicare Advantage Plans
      • New Medicare Card
      • Provider Enrollment, Chain and Ownership System (PECOS)
    • Regulatory Compliance
      • HIPPA Resources
      • Office of Inspector General
      • Audits
      • OSHA
    • AAOE Membership
      • Join AAOE
      • Membership Benefits
      • Renew/Pay Dues
    • About AAOE
      • AAOE Board of Directors
      • AAOE Content Committee
      • Volunteer Opportunities
  • For Public & Patients
    • Eye Health A-Z
    • Symptoms
    • Glasses & Contacts
    • Tips & Prevention
    • News
    • Ask an Ophthalmologist
    • Patient Stories
    • No Cost Eye Exams
    • Español
      • A - Z de Salud Ocular
      • Síntomas
      • Anteojos y Lentes de Contacto
      • Consejos y Prevención
      • Noticias
      • Relatos de Pacientes
      • Exámenes de la vista sin costo
      • English
  • AAO 2022
    • Meeting Information
      • Past and Future Meetings
      • Mobile Meeting Guide
      • Contact Information
      • Annual Meeting News
      • Health and Safety
      • Policies and Disclaimers
    • Program
      • Program Highlights
      • Subspecialty Day
      • Virtual Meeting
      • Program Committees
      • CME
      • Meeting Archives
    • Expo
    • Registration
    • Hotels & Travel
      • Hotel Reservation Information
      • Chicago
      • International Attendees
      • Hotel Meeting Space
    • Presenter Central
      • Presenter Central
      • Abstract Selection Process
      • Submission Policies
      • Subject Classification/Topics
      • Instruction Courses and Skills Transfer Labs
      • Papers and Posters
      • Videos
      • Grand Rounds Symposium
      • Program Participant and Faculty Guidelines
      • Faculty Development Program
    • Exhibitors
      • Exhibitor Central
      • Exhibitor Portal Information
      • Exhibitor Prospectus
      • New Exhibiting Companies
      • Exhibitor Resources
      • International Exhibitors
      • Promotional Opportunities
      • Exhibitor Hotel Reservations
  • About
    • Who We Are
      • What We Do
      • About Ophthalmology
      • The Eye Care Team
      • Ethics and the Academy
      • History
      • Museum of Vision
      • Values
    • Governance
      • Council
      • Board of Trustees
      • Committees
      • Academy Past Presidents
      • Secretariats
      • Elections
      • Academy Blog
      • Academy Staff Leadership
    • Leadership Development
    • Awards
      • Laureate Recognition Award
      • Outstanding Advocate Award
      • Outstanding Humanitarian Service Award
      • International Blindness Prevention Award
      • Distinguished Service Award
      • Guests of Honor
      • Secretariat Award
      • Straatsma Award
      • Achievement Award Program
      • Artemis Award
      • EnergEYES Award
      • International Education Award
      • International Scholar Award
      • Commitment to Advocacy Award
      • Visionary Society Award
    • Financial Relationships
    • Policy Statements
    • Related Organizations
      • Subspecialty/Specialized Interest Society Directory
      • State Society Directory
      • Subspecialty/Specialized Interest Society Meetings
      • State Society Meetings
      • Resources for Societies
    • Year in Review
      • 2020 Year in Review
  • Foundation
    • About
      • 2020-2021 Annual Report
      • Annual Report Archives
      • News From the Chair
      • Foundation Staff
    • Our Impact
      • Partners for Sight
      • Donor Spotlights
      • Global Ophthalmic Community
      • Sponsorships
      • Patients and the Public
    • Giving Options
      • Our Supporters
      • Estate and Planned Giving
      • Ophthalmic Business Council
      • Parke Center Campaign
      • Minority Ophthalmology Mentoring Campaign
      • Museum of the Eye Campaign
    • Orbital Gala
      • Why Attend
      • Photo Recap
      • Corporate Support Opportunities
      • Tribute Gifts
      • Silent Auction
      • Corporate Sponsors
    • Donate
    • Museum of the Eye Campaign
      • Museum Supporters
  • Museum of the Eye
    • Visit
    • What's On
      • Museum Galleries
      • Special Exhibitions
      • Current Events
      • Past Events
    • Explore
      • Research and Resources
      • Collection Search
      • Previous Exhibits
      • Oral Histories
      • Biographies
    • Volunteer
    • Mailing List
    • Donate
    • About the Museum
      • Museum Blog
  • Young Ophthalmologists
    • YO Info
    • Learn to Bill
    • Engage with the Academy
  • Senior Ophthalmologists
    • Scope
    • Practice Transitions
  • International Ophthalmologists
    • Global Programs and Resources for National Societies
    • Awards
    • Global Outreach
  • Residents
  • Medical Students
×
Shop
Log In Create an Account
  • For Ophthalmologists
  • For Practice Management
  • For Public & Patients
  • Coronavirus
  • About
  • Foundation
  • Museum of the Eye
  • COVID-19
  • Journals
  • Education
    • Education
    • Courses
    • Cases
    • Learning Plans
    • Interactive
    • Focal Points
    • Wills Eye Manual
    • Disease Reviews
    • Clinical Webinars
    • Diagnose This
    • Self-Assessments
    • Education Centers
      • Glaucoma Education Center
      • Pediatric Ophthalmology Education Center
      • Laser Surgery Education Center
      • Oculofacial Plastic Surgery Center
      • Redmond Ethics Center
      • Myopia Resources
      • Thyroid Eye Disease Resources
  • Guidelines
    • Practice Guidelines
    • Preferred Practice Patterns
    • Clinical Statements
    • Ophthalmic Technology Assessments
    • Patient Safety Statements
    • Complementary Therapy Assessments
    • Compendium Guidelines
    • Medical Information Technology
    • Low Vision
    • Choosing Wisely
    • Eye Care for Older Adults
    • Eye Disease Statistics
    • About the Hoskins Center
    • Artificial Intelligence
    • Premium IOLs
    • Patient-Reported Outcomes with LASIK Symptoms and Satisfaction
  • Multimedia
    • Multimedia Library
    • Video
      • 1-Minute Videos
      • Presentations and Lectures
      • Master Class Videos
      • Basic Skills Videos
      • Clinical and Surgical Videos
      • Interviews
      • Resident Lectures
      • Submit a Video
      • YO Video Contest
    • Podcasts
      • Browse Podcast Archive
      • Experts InSight Podcast
      • Ophthalmology Journal Podcast
    • Images
      • Submit an Image
  • News
    • Clinical News
    • Editors' Choice
    • Headlines
    • Current Insight
  • CME
    • CME Central
    • Claim CME Credit and View Transcript
    • CME Planning Resources
    • Complete Your Financial Disclosure
    • Joint Sponsorship Portal
    • LEO Continuing Education Recognition Award
    • Safe ER/LA Opioid Prescribing
    • Check Your Industry Payment Records
  • MOC
  • Residents
    • Resident Education Home
    • Browse All Resident Content
      • Courses
      • Flashcards and Study Presentations
      • Interactive Cases and Simulations
      • Videos
      • Webinars
    • Cataract Master
    • Diversity and Inclusion Education
    • News and Advice from YO Info
    • OKAP and Board Exam Resources
      • OKAP Exam
      • Board Prep Resources
      • OKAP and Board Review Presentations
      • Study Flashcards
    • Pediatric Ophthalmology Education Center
    • PGY-1 and PGY-2 Resources
    • Resident Knowledge Exchange
    • Simulation in Resident Education
    • Clinical Education /
    • Book Excerpts /
    • Basic and Clinical Science Course - Excerpt
  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    6 Pediatric Ophthalmology and Strabismus

    Part II: Pediatric Ophthalmology

    Chapter 25: Disorders of the Retina and Vitreous

    Tumors

    Retinoblastoma

    Retinoblastoma is the most common malignant intraocular tumor of childhood and one of the most common pediatric solid tumors, with an incidence of 1:14,000–1:20,000 live births. It is equally common in both sexes and has no racial predilection. Retinoblastoma is a neuroblastic tumor and is therefore biologically similar to neuroblastoma and medulloblastoma. The tumor can be unilateral or bilateral; 30%–40% of cases are bilateral. In familial and bilateral cases, retinoblastoma is typically diagnosed during the first year of life; in sporadic unilateral cases, between 1 and 3 years of age. Approximately 90% of cases are diagnosed before 3 years of age; onset later than age 5 years is rare but can occur.

    The most common initial sign is leukocoria (white pupillary reflex), which is usually first noticed by the family and described as a glow, glint, or cat’s-eye appearance (Fig 25-24). The differential diagnosis of leukocoria is presented in Table 25-7. Approximately 25% of cases present with strabismus (esotropia or exotropia). Less common presentations include vitreous hemorrhage, hyphema, ocular or periocular inflammation, glaucoma, proptosis, and pseudohypopyon.

    Figure 25-24 Leukocoria of the right eye, which is visible in this family photograph of a 1-year-old girl with retinoblastoma.

    (Courtesy of A. Linn Murphree, MD.)

    Table 25-7 Differential Diagnosis of Leukocoria

    Diagnosis

    Diagnosis of retinoblastoma is usually based on its ophthalmoscopic appearance. Intraocular retinoblastoma can exhibit a variety of growth patterns. With endophytic growth, it appears as a white to cream-colored mass that breaks through the internal limiting membrane (Fig 25-25). Endophytic retinoblastoma is sometimes associated with vitreous seeding, in which individual cells or fragments of tumor tissue become separated from the main mass, as shown in Figure 25-26. Vitreous seeds may be few and localized or so extensive that the clinical picture resembles endophthalmitis. Occasionally, malignant cells enter the anterior chamber and form a pseudohypopyon.

    Exophytic tumors are usually yellow-white and occur in the subretinal space; the overlying retinal vessels are commonly larger in caliber and more tortuous (Fig 25-27). Exophytic retinoblastoma growth is often associated with subretinal fluid accumulation, which can obscure the tumor and closely mimic the appearance of an exudative retinal detachment suggestive of advanced Coats disease. Retinoblastoma cells have the potential to implant on previously uninvolved retinal tissue and grow, thereby creating an impression of multicentricity in an eye with only a single primary tumor.

    Large tumors often show signs of both endophytic and exophytic growth. Small retinoblastoma lesions appear as a grayish mass and are frequently confined between the internal and external limiting membranes. A third pattern, diffuse infiltrative retinoblastoma, is usually unilateral and nonhereditary. It is found in children older than 5 years. The tumor presents with conjunctival injection, anterior chamber seeds, pseudohypopyon, large clumps of vitreous cells, and retinal infiltration of tumor. Because no distinct tumor mass is present, diagnostic confusion with inflammatory conditions is common.

    Figure 25-25 Fundus photograph showing multiple endophytic retinoblastoma lesions, left eye.

    (Courtesy of A. Linn Murphree, MD.)

    Figure 25-26 Endophytic retinoblastoma with vitreous seeding.

    Figure 25-27 Exophytic retinoblastoma with overlying detached retina.

    Spontaneous regression of retinoblastoma is possible. It can be asymptomatic, resulting in the development of a benign retinocytoma, or it can be associated with inflammation and, ultimately, phthisis bulbi. In either case, the genetic implications are the same as for an individual with an active retinoblastoma.

    The most common retinal lesion simulating retinoblastoma is seen in Coats disease. The presence of crystalline material, extensive subretinal fluid, and peripheral vascular abnormalities—combined with the absence of calcium—suggests Coats disease. Astrocytic hamartomas and hemangioblastomas are benign retinal tumors that may simulate the appearance of small retinoblastomas. Both are usually associated with neuro-oculocutaneous syndromes (see Chapter 28).

    Evaluation of a patient with presumed retinoblastoma requires imaging of the head and orbits, which can confirm the diagnosis and assess for extraocular extension and intracranial disease. Computed tomography is discouraged because of the possible increased risk of secondary tumors due to radiation exposure. Magnetic resonance imaging and ultrasonography are recommended. More invasive tests are reserved for atypical cases. Aspiration of ocular fluids for diagnostic testing should be performed only under the most unusual circumstances because such procedures can disseminate malignant cells. Recently, however, it was demonstrated that cell-free tumor-derived DNA may be obtained from aqueous humor.

    The characteristic histologic features of retinoblastoma include Flexner-Wintersteiner rosettes, which are usually present, and fleurettes, which are less common. Both represent limited degrees of retinal cellular differentiation. Homer Wright rosettes are also frequently present but are less specific for retinoblastoma because they are common in other neuroblastic tumors. Calcification of varying extent is usually present.

    • Berry JL, Xu L, Murphree AL, et al. Potential of aqueous humor as a surrogate tumor biopsy for retinoblastoma. JAMA Ophthalmol. 2017;135(11):1221–1230.

    • de Graaf P, Göricke S, Rodjan F, et al; European Retinoblastoma Imaging Collaboration. Guidelines for imaging retinoblastoma: imaging principles and MRI standardization. Pediatr Radiol. 2012;42(1):2–14.

    Genetics

    The retinoblastoma gene (RB1) maps to a locus within the q14 band of chromosome 13 and codes for a protein, pRB, that suppresses tumor formation. For retinoblastoma to occur, both RB1 genes must have a mutation. Approximately 60% of retinoblastoma cases arise from somatic nonhereditary mutations of both alleles of RB1 in a retinal cell. These mutations generally result in unifocal and unilateral tumors. In the other 40% of patients, a germline mutation in 1 of the 2 alleles of RB1 either is inherited from an affected parent (10% of all retinoblastoma cases) or occurs spontaneously in 1 of the gametes. A second somatic mutation in a retinal cell is all that is necessary for retinoblastoma to develop; such cases are often multicentric and bilateral.

    Genetic counseling for families of retinoblastoma patients is complex (Table 25-8). Both parents and all siblings should be examined. In approximately 1% of cases, a parent may be found to have an unsuspected fundus lesion that represents a spontaneously regressed retinoblastoma (retinocytoma).

    Genetic testing for retinoblastoma is important for determining the risk of subsequent cancers (both retinoblastoma and other primary neoplasms) in the affected child and the risk of retinoblastoma in other family members. The probability of detecting the RB1 gene depends on many factors, including the capabilities of the molecular diagnostic laboratory, the presence of tumor tissue, and the ability to test other affected family members.

    Preimplantation genetic testing can be performed, and in vitro fertilization techniques have been used successfully to select embryos that are free from the germinal RB1 mutation.

    • Dhar SU, Chintagumpala M, Noll C, Chévez-Barrios P, Paysse EA, Plon SE. Outcomes of integrating genetics in management of patients with retinoblastoma. Arch Ophthalmol. 2011;129(11):1428–1434.

    Classification of retinoblastoma

    The International Classification of Retinoblastoma (ICRB; Table 25-9) is useful for predicting the success of chemoreduction and has superseded the Reese-Ellsworth classification, which was originally developed to predict globe salvage after external-beam radiotherapy. The American Joint Committee on Cancer (AJCC) also has a staging system for retinoblastoma that addresses both intraocular and extraocular disease (see BCSC Section 4, Ophthalmic Pathology and Intraocular Tumors).

    • Shields CL, Mashayekhi A, Au AK, et al. The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology. 2006;113(12):2276–2280.

    Table 25-8 Genetic Counseling for Retinoblastoma

    Table 25-9 International Classification of Retinoblastoma

    Treatment

    The management of retinoblastoma has changed dramatically over the past decade and continues to evolve. Many specialists may be involved, including ocular oncologists, pediatric ophthalmologists, geneticists, genetic counselors, pediatric oncologists, and radiation oncologists. External-beam radiation is seldom used to treat intraocular retinoblastoma because of its high association with development of craniofacial deformity and secondary tumors in the field of radiation. When the likelihood of salvaging vision is low, primary enucleation of eyes with advanced unilateral retinoblastoma is often performed to avoid the adverse effects of systemic chemotherapy. To prevent extraocular spread of the tumor, the surgeon should minimize manipulation of the globe and obtain a long segment of optic nerve. Small retinoblastoma tumors can often be treated with either laser photocoagulation or cryotherapy.

    Primary systemic chemotherapy (chemoreduction) followed by local therapy (consolidation) has been used to spare vision for larger tumors (Fig 25-28) and is often used in cases of bilateral retinoblastoma. Most studies of chemoreduction for retinoblastoma have used vincristine, carboplatin, and an epipodophyllotoxin. Others have added cyclosporine. Chemotherapy is rarely successful when used alone and often requires local therapy (cryotherapy, laser photocoagulation, thermotherapy, or plaque radiotherapy) as well. Adverse effects of chemoreduction treatment include low blood count, hair loss, hearing loss, renal toxicity, neurologic and cardiac disturbances, and possible increased risk for acute myelogenous leukemia.

    Figure 25-28 A, Left eye of an infant with bilateral retinoblastoma; 2 tumors straddle the optic nerve. B, After chemoreduction and laser consolidation, the tumors are nonviable. The child’s visual acuity was 20/25 at age 5 years.

    Intra-arterial chemotherapy has recently been reported as an alternative to systemic chemoreduction for unilateral retinoblastoma in group B, C, D, or E eyes. Chemotherapy is delivered via cannulation of the ophthalmic artery in single or multiple sessions. Many chemotherapy agents have been used; melphalan is the most common. Overall, the results show higher rates of globe salvage in eyes treated initially and in those that did not respond to prior treatments. Systemic complications include neutropenia and metastasis. Ocular complications include vascular occlusion, blepharoptosis, cilia loss, temporary dysmotility, and periocular edema in the distribution of the supratrochlear artery. There is concern about the radiation that is delivered during the procedure, especially for patients with germline RB1 gene mutations, who are at higher risk for malignant tumors.

    Intravitreal chemotherapy has been used for refractory and recurrent vitreous seeding from retinoblastoma. Periocular injections have been used for adjuvant chemotherapy.

    Treated retinoblastoma sometimes disappears altogether, but more often it persists as a calcified mass (type 1, or “cottage cheese,” pattern) or a noncalcified, translucent grayish lesion (type 2, or “fish flesh,” pattern), which may be difficult to distinguish from untreated tumor. Type 3 regression has elements of both types 1 and 2, and type 4 regression is a flat, atrophic scar. A child with treated retinoblastoma must be observed closely for new or recurrent tumor formation, with frequent examinations under anesthesia if necessary.

    Extraocular retinoblastoma, though uncommon in the United States, is still problematic in developing countries, primarily because of delay in diagnosis. The 4 major types are optic nerve involvement, orbital invasion, central nervous system (CNS) involvement, and distant metastasis. Treatment of extraocular retinoblastoma includes intensive multimodality chemotherapy, autologous hematopoietic stem cell rescue, and external-beam radiotherapy. Long-term disease-free survival is possible if the CNS is not involved; otherwise, the prognosis is usually poor.

    Patients with trilateral retinoblastoma have a primitive neuroectodermal tumor (PNET) of the pineal gland or parasellar region in addition to retinoblastoma. In patients with unilateral retinoblastoma, the risk of trilateral retinoblastoma has been less than 0.5%; in those with bilateral retinoblastoma, less than 5%–15%. However, the rate of trilateral retinoblastoma appears to be lower in patients treated with chemoreduction. Treatment usually involves a multimodal approach, and the prognosis is poor.

    • Abramson DH, Dunkel IJ, Brodie SE, Marr B, Gobin YP. Superselective ophthalmic artery chemotherapy as primary treatment for retinoblastoma (chemosurgery). Ophthalmology. 2010;117(8):1623–1629.

    • Shields CL, Alset AE, Say EA, Caywood E, Jabbour P, Shields JA. Retinoblastoma control with primary intra-arterial chemotherapy: outcomes before and during the intravitreal chemotherapy era. J Pediatr Ophthalmol Strabismus. 2016;53(5):275–284.

    Monitoring

    Identification of RB1 mutations is very useful in determining how frequently to monitor patients. Patients with unilateral tumors who have somatic mutations are not at risk for development of additional tumors (ocular or systemic). Patients who undergo globe salvage require frequent examinations to monitor for tumor recurrence. In these patients, examinations under anesthesia are typically performed every 4–8 weeks until age 3 years. Recurrence of retinoblastoma is common and can occur years after treatment.

    In patients with germline mutations, periodic MRI of the brain is performed to screen for CNS metastases and PNET, which have poor prognoses. Results of genetic testing can also help determine whether siblings need to be monitored. If genetic testing is not available, siblings should be monitored routinely during the first 2 years of life.

    Because of their risk of developing secondary malignancies, patients with germline mutations require long-term follow-up by oncologists and ophthalmologists. Nonocular tumors are common in these patients; the estimated incidence rate is 1% per year of life (eg, 10% prevalence by age 10 years, 30% by age 30 years). The incidence is higher among patients treated with external-beam radiation before 1 year of age. The most common secondary tumors (and the mean age at diagnosis) are PNET (2.7 years), sarcoma (13 years), melanoma (27 years), and carcinomas (29 years). For patients with second nonocular tumors, the risk of additional malignant tumors is even greater.

    • Correa ZM, Berry JL. Review of retinoblastoma. Pediatric Ophthalmology Education Center. April 28, 2016. Available at https://www.aao.org/disease-review/review-of-retinoblastoma.

    • Woo KI, Harbour JW. Review of 676 second primary tumors in patients with retinoblastoma: association between age at onset and tumor type. Arch Ophthalmol. 2010;128(7):865–870.

    Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

  • Most Commented
    Loading, please wait...
    There are no comments available.
    Most Viewed
    Loading, please wait...
    Most Viewed content is not available.
  • The Academy Store
    2022-2023 Basic and Clinical Science Course, Complete Print Set
    2022-2023 Basic and Clinical Science Course, Complete eBook Set
    2022-2023 Basic and Clinical Science Course, Complete Print and eBook Set
    2022-2023 Basic and Clinical Science Course, Residency Print Set
    2022-2023 Basic and Clinical Science Course, Residency eBook Set
    2022-2023 Basic and Clinical Science Course Complete Set
    2022-2023 Basic and Clinical Science Course Residency Set
    2022-2023 Basic and Clinical Science Course, Section 01: Update on General Medicine
    2022-2023 Basic and Clinical Science Course, Section 02: Fundamentals and Principles of Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 03: Clinical Optics and Vision Rehabilitation
    2022-2023 Basic and Clinical Science Course, Section 04: Ophthalmic Pathology and Intraocular Tumors
    2022-2023 Basic and Clinical Science Course, Section 05: Neuro-Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 06: Pediatric Ophthalmology and Strabismus
    2022-2023 Basic and Clinical Science Course, Section 07: Oculofacial Plastic and Orbital Surgery
    2022-2023 Basic and Clinical Science Course, Section 08: External Disease and Cornea
    2022-2023 Basic and Clinical Science Course, Section 09: Uveitis and Ocular Inflammation
    2022-2023 Basic and Clinical Science Course, Section 10: Glaucoma
    2022-2023 Basic and Clinical Science Course, Section 11: Lens and Cataract
    2022-2023 Basic and Clinical Science Course, Section 12: Retina and Vitreous
    2022-2023 Basic and Clinical Science Course, Section 13: Refractive Surgery
    The Technician Point System: How to Improve Practice Accountability and Bottom Line (Free Member Webinar)
    Transitioning Your Practice: Retiring, Selling or Buying a Practice (Free Member Webinar)
    How to Build a Patient-First Culture (Free Member Webinar)
    2022 IRIS Registry (Intelligent Research in Sight) Preparation Kit
    Advances in Medical and Surgical Management: The 2022 Update on Glaucoma
    Presbyopia-Correcting IOLs
    2022 Codequest - Multistate (Recorded March 29)
    2022 Codequest Virtual (Multistate)
    Retina Patient Education Video Collection
    Cataract and Refractive Surgery Patient Education Video Collection
 
  • Contact Us
  • About the Academy
  • Jobs at the Academy
  • Financial Relationships with Industry
  • Medical Disclaimer
  • Privacy Policy
  • Terms of Service
  • Help
  • For Advertisers
  • For Media
  • Ophthalmology Job Center

OUR SITES

  • EyeWiki
  • International Society of Refractive Surgery

FOLLOW THE ACADEMY

Medical Professionals

  • Facebook
  • Twitter
  • LinkedIn
  • YouTube

Public & Patients

  • Facebook
  • Twitter
  • Instagram
  • YouTube

Museum of the Eye

  • Facebook
  • Twitter
  • Instagram
  • YouTube
  • Trip Advisor
  • Yelp
© American Academy of Ophthalmology 2022