Retinoblastoma

Disease Description (Causes and Symptoms)

• Definition: Retinoblastoma is a childhood malignant tumor that develops from immature retinal cells in the retina. It occurs mainly in infants and young children.
• Causes·Pathophysiology:
  • The main causative gene is the RB1 gene (located at 13q14.1–14.2), and the “two-hit” mechanism, in which two abnormalities (two mutations) are required for tumor development, is well established.
  • Pathophysiologically, immature retinal cells fail to mature and continue to proliferate, forming a tumor.
  • Genetic classification: Approximately 60% are reported to be nonhereditary unilateral (one eye), approximately 15% hereditary unilateral, and approximately 25% hereditary bilateral.
  • Incidence: Approximately 1 in 15,000–20,000 births.
• Main symptoms:
  • Leukocoria (the pupil appears to reflect white light)
  • Reduced vision
  • Strabismus (exotropia, esotropia, etc.)
  • Enlargement or protrusion of the eyeball (buphthalmos, proptosis)
  • Abnormal pupillary response, eye pain·redness (in advanced cases)
  • Rarely, metastasis to tissues outside the eye (such as the orbit or brain) may occur

Treatment Methods and Precautions

• Treatment goals: Preservation of life, preservation of the eye, and preservation of vision when possible
• Standard treatment options (combined according to the tumor’s location, size, and presence or absence of metastasis):
  • Local treatment
    • Laser photocoagulation and cryotherapy: Suitable for small tumors
    • Local radiation (local plaque, etc.) — used on a limited basis
  • Systemic·local chemotherapy
    • Systemic chemotherapy (neoadjuvant or adjuvant therapy): Reduction of tumor size followed by local treatment
    • Intra-arterial chemotherapy: Injected directly into the eye, with high efficacy and low systemic toxicity (performed depending on the center)
    • Intravitreal chemotherapy injection: Used in cases of vitreous seeding or when local treatment is needed
  • Radiation therapy
    • External-beam radiation therapy is limited because of the risk of growth-related complications and secondary cancers, and is used selectively
  • Surgery
    • Enucleation: Performed when the tumor is extensive, vision preservation is impossible, or there is a threat to life
• Additional treatment·management
  • If systemic metastasis is suspected, bone marrow examination, cerebrospinal fluid examination, and systemic chemotherapy
  • Genetic testing (confirmation of an RB1 mutation) and genetic counseling
  • Fabrication of an ocular prosthesis·artificial eye (after enucleation)
• Precautions (management during and after treatment)
  • In hereditary cases, the risk of future secondary malignancies (such as osteosarcoma) is increased => long-term follow-up is necessary
  • Radiation therapy increases the risk of growth impairment and secondary cancers in young patients
  • Monitoring for systemic side effects of chemotherapy (myelosuppression, infection, etc.) is necessary
  • Psychosocial support and education for adapting to an artificial eye are necessary after enucleation

Checklist Before an Outpatient Visit (Including Items to Bring, Test Records, and Example Questions)

• Items to bring (recommended)
  • List of currently used medications (medication name·instructions for use·start date)
  • Past medical history and surgical records, family history (especially retinoblastoma or a history of cancer at an early age)
  • Results of previous tests (fundus photographs, ultrasound, CT/MRI, blood test results)
  • Record of symptom changes (when they began, which eye, photographs [photos of leukocoria] can be useful)
• Items that are useful to confirm in advance at the outpatient visit
  • Timing of symptom onset and pattern of progression (changes in vision, presence of strabismus, pain)
  • Information at birth and results of newborn screening tests
  • Whether siblings or first-degree relatives have related diseases
• Example questions to prepare before the outpatient visit (the patient·caregiver should take notes)
  • Is anesthesia required during the tests? What are the risks of anesthesia?
  • If the genetic test results are available, should family members also be tested?
  • For each treatment option, how likely is it that the eye and vision can be preserved?

Examples of General Questions to Ask the Doctor

• What is the treatment recommendation (standard) for this disease? Why do you recommend it for our child?
• Based on the current extent of the tumor, how likely is vision preservation?
• What tests are recommended, and how often should they be performed (what is the follow-up schedule)?
• What are the main side effects of chemotherapy or radiation therapy, and how can they be prevented?
• If the genetic test is positive, how will family screening and preconception counseling be conducted?

Examples of Disease-Specific Questions

• We have been advised to undergo enucleation. What conservative treatment alternatives (local treatment·local chemotherapy) are possible, and what are their success rates?
• If hereditary disease (an RB1 mutation) is confirmed, what is the risk of onset in future children (or siblings), and what schedule of recommended newborn/infant testing should be followed?

If you need additional information, please provide the test results currently available (fundus photographs·ultrasound·MRI, etc.) or family history, and we can help you prepare more specific consultation items and a list of questions.