Variability Wide Across Practices for Definitions of At-Risk Retinoblastoma

Nurse Looking At Girl During Cat Scan Exam
Nurse looking at little patient in preparing for CAT scan. Girl with female healthcare worker during tomography exam. They are at hospital.
The decision to offer adjuvant chemotherapy and radiotherapy depends on the definition of “high-risk” retinoblastoma, but this definition varies by practice.

A small yet far-reaching survey of clinicians who treat retinoblastoma found little uniformity exists in defining high-risk cases of the condition. Without an accepted definition and clearly defined characteristics, retinoblastoma remains challenging to treat uniformly, according to a report published in JAMA Ophthalmology.

The high-risk histopathologic features of retinoblastoma are used to determine the risk of systemic metastasis. However, among 27 oncologists and pathologists across 16 countries in 6 continents surveyed electronically, post laminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly named as high-risk signals for metastasis.

Researchers issued a 10-question survey to 27 clinicians from 24 retinoblastoma practices across 16 countries in 6 continents. The survey posed objective, yes-or-no questions, each with a free-text box for additional comments. The questions focused on what histopathologic factors clinicians looked for when determining whether a patient with retinoblastoma is at high-risk.

Of the respondents, 18 (67%) were ophthalmologists or researchers practicing ocular oncology, 2 (7%) were ocular pathologists, 3 (11%) were trained in both ocular oncology and pathology, and 4 (15%) were medical oncologists treating retinoblastoma; 5 respondents (19%) were from North America.

According to the study, high-risk features of retinoblastoma include:

  • Post laminar optic nerve infiltration (27 [100%])
  • Involvement of optic nerve transection (27 [100%])
  • Extrascleral tissue infiltration (27 [100%])
  • Massive (≥3 mm) choroidal invasion (25 [93%])
  • Microscopic scleral infiltration (23 [85%])
  • Ciliary body infiltration (20 [74%])
  • Trabecular meshwork invasion (18 [67%])
  • Iris infiltration (17 [63%])
  • Anterior chamber seeds (14 [52%])
  • Laminar optic nerve infiltration (13 [48%])
  • Combination of pre-laminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%])
  • Minor (<3 mm) choroidal invasion (5 [19%])
  • Prelaminar optic nerve infiltration (2 [7%])

The data revealed that the other histopathologic features considered high-risk by those surveyed include Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Further, 4 respondents (15%) said that the presence of more than 1 high-risk feature, particularly massive peripapillary choroidal invasion paired with post laminar optic nerve infiltration, should be considered “very high risk” for metastasis.

“Because the decision to offer adjuvant chemotherapy and radiotherapy depends on the definition of high-risk RB at each individual treatment center, this disparity translates into a wide variation in practice in the management of high-risk RB, with highly variable outcomes,” the study says.

The investigators note some limitations of their work, including that the survey was not validated and respondents had different backgrounds and opportunities to treat, follow-up, and study their patients.


Kaliki S, Shields CL, Cassoux N, et al. Defining high-risk retinoblastoma: a multicenter global survey. JAMA Ophthalmol. Published online November 11, 2021. doi:10.1001/jamaophthalmol.2021.4732