Skip to content

Focal therapy and brachytherapy

TL;DR — Focal therapy supplies local tumour destruction for small primary lesions and, more commonly, consolidates residual disease after chemotherapy. Laser/thermotherapy is suited to visible posterior lesions; cryotherapy reaches peripheral lesions through the sclera; plaque brachytherapy treats selected localised resistant or recurrent tumours. Modality choice depends on size, location, subretinal fluid and seeds. Local control must be reported with retinal damage, macular/optic-disc proximity, repeat procedures and final visual function.

Decision-relevant evidence

  • Transpupillary thermotherapy alone cured 84 of 91 small tumours (92%) treated as initial therapy in 22 eyes of 24 patients; mean initial tumour base was 0.67 disc diameters, the mean number of sessions was 1.7 and 64% needed only one session. Seven tumours (8%) required one to five salvage treatments and all were controlled without enucleation; 21 of 22 eyes (95%) were preserved (Abramson 2004, PMID 15121378).

  • Plaque brachytherapy in 208 tumours from 141 children gave Kaplan-Meier tumour control of 83% at one year and 79% at five years. Prior treatment had failed in 148 tumours (71%) and more than one prior method had failed in 72 (35%). One-year recurrence was 12% after primary plaque, 8% after prior chemoreduction, 8% after prior laser/thermotherapy/cryotherapy, 25% after prior external-beam radiotherapy and 34% after both chemoreduction and external-beam radiotherapy (Shields 2001, PMID 11713089).

  • Plaque radiation carries a measurable ocular cost: five-year Kaplan-Meier complication estimates in the same series were nonproliferative retinopathy 27%, proliferative retinopathy 15%, maculopathy 25%, papillopathy 26%, cataract 31%, glaucoma 11% and scleral necrosis 0%. Vitreous seeds, subretinal seeds and older age predicted recurrence (PMID 11713089).

  • Focal consolidation is what controls seeds, not chemotherapy alone. In 130 tumours in 52 eyes, adjuvant focal treatment was applied to 93% of retinal tumours and only 2% recurred over mean 17 months; adding focal treatment to six VEC cycles reduced vitreous-seed recurrence from 75% to 0% (P = 0.04) and subretinal-seed recurrence from 67% to 0% (P = 0.003). Enucleation or external-beam radiotherapy was avoided in 42% of the 52 eyes overall and ocular salvage reached 78% in the 36 Reese-Ellsworth group 5 eyes (Shields 1997, PMID 9400771).

  • In a prospective single-arm chemoreduction-plus-focal-therapy trial of 75 eyes in 47 children, event-free survival (event = enucleation and/or external-beam radiotherapy) was 74% at median 13 months; all 39 Reese-Ellsworth group 1–3 eyes avoided both, whereas 33% of six group 4 eyes and 53% of 30 group 5 eyes required them (Friedman 2000, PMID 10623688).

  • Failure after chemoreduction is common and stage-dependent: of 105 eyes, 10 (9.5%) were enucleated for unresponsive disease after two cycles and 42 of the remaining 95 (44.2%) recurred; external-beam radiotherapy was used in 27.4% and enucleation in 23.2% of those 95 eyes. Overall globe salvage was 69.5%, from 87.0% in Reese-Ellsworth groups I–IV to 36.1% in group V (Gündüz 2004, PMID 15465557).

  • Cycle number changed the need for radiotherapy in advanced eyes: external-beam irradiation was required in 12 of 16 eyes (75%) after two chemoreduction cycles versus 4 of 11 (36%) after six cycles in Reese-Ellsworth group V disease, although the difference was not statistically significant in that 27-eye series (Gündüz 1998, PMID 9869790).

  • Laterality, not only stage, tracks conservative-treatment success in a middle-income setting: in 84 Brazilian children treated with two to six chemotherapy cycles plus focal therapy with or without plaque, eye preservation without external-beam radiotherapy was achieved in 54% of bilateral versus 19% of unilateral cases (P = 0.003), and in Reese-Ellsworth IV–V disease 40.7% versus 0% (P = 0.012) — a contrast driven by the threshold for enucleating a unilateral advanced eye (Antoneli 2006, PMID 16794500).

  • Anatomical location sets the ceiling on what focal therapy can protect. In 47 eyes with primary macular retinoblastoma, local tumour control reached 96% and the globe was salvaged in every eye, but 36 eyes (77%) ended with foveal atrophy and 5 (11%) recurred (Chandra 2022, PMID 37006899).

  • Retinal detachment complicates a minority of globe-conserving courses: detachment developed in 10 eyes of 10 patients (5.92%) among 169 managed with globe-conserving treatment, evenly split between exudative and rhegmatogenous types, with median 15 weeks to resolution in the exudative group (Elaraoud 2019, PMID 30899845).

  • Cryotherapy remains part of the standard focal repertoire and is used for peripheral lesions and as needle-track sterilisation during intravitreal injection, but the retinoblastoma-specific record indexed for it here is a 1993 clinical-teaching article without an abstract, so no effect size is claimed from it (Shields 1993, PMID 8407173). Contemporary quantitative reporting of cryotherapy is embedded in multimodal series rather than in modality-specific cohorts (Ancona-Lezama 2020, PMID 33120616).

  • The one randomized study in this space compared the drugs preceding focal therapy, not the focal modalities themselves: 65 eyes in 55 children received two neoadjuvant cycles and then local treatment plus carboplatin chemothermotherapy, and two-year salvage without enucleation or external-beam radiotherapy was 23 of 33 eyes (69.7%) with vincristine-carboplatin versus 26 of 32 (81.2%) with etoposide-carboplatin (Lumbroso-Le Rouic 2016, PMID 26427984).

  • The evidence base is otherwise dominated by retrospective eye-level series, so selection by initial tumour geometry limits cross-modality comparisons (Nag 2024, PMID 38804799). A live PubMed search on 2026-09-01 for retinoblastoma with cryotherapy, thermotherapy, laser, brachytherapy or plaque restricted to randomized controlled trials returned one record — the Institut Curie chemotherapy comparison above — so as of that date no trial has randomised one focal modality against another, and every laser-versus-cryotherapy-versus-plaque comparison in this page is between non-randomised, geometry-selected groups.

Clinical and research frame

Domain Operational meaning Evidence boundary
Laser/thermotherapy Posterior visible small/residual tumour Macular and vascular thermal injury
Cryotherapy Peripheral lesion Scleral depression; retinal tear/detachment risk
Plaque brachytherapy Localised resistant/recurrent lesion Radiation retinopathy/optic neuropathy
Combination After systemic or arterial chemotherapy Repeated EUA and cumulative focal scars
Outcome Local control plus acuity/field Globe-only reporting is incomplete

Interpretation rules

  • Keep the child-level endpoints of survival and metastasis separate from the eye-level endpoint of globe salvage.

  • Report initial stage, laterality, heritability, prior treatment and follow-up; otherwise comparisons are not transportable.

  • A retrospective eye series estimates performance in selected eyes; it does not establish superiority over another route.

  • Absence of metastasis in a small series is a safety observation, not proof that risk is zero.

  • Treatment-era effects matter because external-beam radiotherapy, systemic chemotherapy, IAC and intravitreal therapy create different late-risk profiles.

  • Income stratum and access are effect modifiers, not background descriptors (Global Retinoblastoma Study Group 2022, PMID 35839812).

Evidence register

The following records were each retrieved live from PubMed E-utilities on 2026-09-01 and re-fetched live during the independent audit on the same date. Every identifier below resolved, and its author, year, journal and title matched the citation as written. Inclusion records the evidence base for this page; a register entry asserts that the record exists and is on topic, not that it supports a specific effect estimate.

PMID Year Study or review Role in this page
8407173 1993 Cryotherapy for retinoblastoma. Topic-resolved source (Shields 1993, PMID 8407173)
16139001 2005 Chemoreduction in the management of retinoblastoma. Topic-resolved source (Shields 2005, PMID 16139001)
33120616 2020 Modern treatment of retinoblastoma: A 2020 review. Topic-resolved source (Ancona-Lezama 2020, PMID 33120616)
38804799 2024 Retinoblastoma - A comprehensive review, update and recent advances. Topic-resolved source (Nag 2024, PMID 38804799)
35839812 2022 The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries. Topic-resolved source (Global 2022, PMID 35839812)
37667345 2023 Retinoblastoma: present scenario and future challenges. Topic-resolved source (Byroju 2023, PMID 37667345)
28620731 2017 Retinoblastoma. Topic-resolved source (Rao 2017, PMID 28620731)
16934146 2006 Retinoblastoma. Topic-resolved source (Aerts 2006, PMID 16934146)
16570739 2006 Retinoblastoma. Topic-resolved source (Melamud 2006, PMID 16570739)
8199450 1993 Retinoblastoma. Topic-resolved source (Abramson 1993, PMID 8199450)
22337189 2012 Retinoblastoma. Topic-resolved source (Mehta 2012, PMID 22337189)
2059954 1991 Retinoblastoma. Topic-resolved source (Servodidio 1991, PMID 2059954)
15763191 2005 Chemotherapy for retinoblastoma. Topic-resolved source (Chan 2005, PMID 15763191)
32206913 2020 [Retinoblastoma]. Topic-resolved source (Bornfeld 2020, PMID 32206913)
35584909 2023 Intra-arterial chemotherapy for retinoblastoma. Topic-resolved source (Carnevale 2023, PMID 35584909)
25473349 2014 Retinoblastoma: An overview. Topic-resolved source (Pandey 2014, PMID 25473349)
26679524 2016 [Retinoblastoma update]. Topic-resolved source (Aerts 2016, PMID 26679524)
28345569 2017 Recent advances and challenges in the management of retinoblastoma. Topic-resolved source (Chawla 2017, PMID 28345569)
39620227 2024 Prospects of anti-GD2 immunotherapy for retinoblastoma. Topic-resolved source (Zhang 2024, PMID 39620227)
24793631 2014 [Retinoblastoma: recent advances]. Topic-resolved source (Jehanne 2014, PMID 24793631)
27218786 2016 Therapeutic Options for Retinoblastoma. Topic-resolved source (Mendoza 2016, PMID 27218786)
37006899 2022 Primary Macular Retinoblastoma: Clinical Presentation and Treatment Outcomes. Topic-resolved source (Chandra 2022, PMID 37006899)
19477707 2009 Frontiers in the management of retinoblastoma. Topic-resolved source (Lin 2009, PMID 19477707)
25014750 2014 Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Topic-resolved source (Shields 2014, PMID 25014750)
30899845 2019 Management of retinal detachment in retinoblastoma with globe conserving treatment. Topic-resolved source (Elaraoud 2019, PMID 30899845)
19184307 2009 Prognostic factors and treatment outcomes of retinoblastoma in pediatric patients: a single-institution study. Topic-resolved source (Atchaneeyasakul 2009, PMID 19184307)
23508752 2013 [Diagnosis and treatment of retinoblastoma: current strategies for effective tumour control and preservation of vision]. Topic-resolved source (Temming 2013, PMID 23508752)
9400771 1997 Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. Topic-resolved source (Shields 1997, PMID 9400771)
17729249 2008 Outcomes of a two-drug chemotherapy regimen for intraocular retinoblastoma. Topic-resolved source (Zage 2008, PMID 17729249)
34000459 2021 Selective Ophthalmic Artery Chemotherapy with Melphalan in the Management of Unilateral Retinoblastoma: A Prospective Study. Topic-resolved source (Lumbroso-Le 2021, PMID 34000459)
15121378 2004 Transpupillary thermotherapy as initial treatment for small intraocular retinoblastoma: technique and predictors of success. Topic-resolved source (Abramson 2004, PMID 15121378)
17300564 2007 Outcomes in retinoblastoma, 1974-2005: the Children's Hospital, Westmead. Topic-resolved source (Berman 2007, PMID 17300564)
11713089 2001 Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors. Topic-resolved source (Shields 2001, PMID 11713089)
26349159 2015 [Available approaches to retinoblastoma therapy--literature review]. Topic-resolved source (Morawski 2015, PMID 26349159)
8906025 1996 Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Topic-resolved source (Murphree 1996, PMID 8906025)
9869790 1998 The outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma. Topic-resolved source (Gündüz 1998, PMID 9869790)
15465557 2004 Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation. Topic-resolved source (Gündüz 2004, PMID 15465557)
16794500 2006 Treatment of retinoblastoma patients with chemoreduction plus local therapy: experience of the AC Camargo Hospital, Brazil. Topic-resolved source (Antoneli 2006, PMID 16794500)
20714385 2010 Eye-preserving therapy in retinoblastoma: prolonged primary chemotherapy alone or combined with local therapy. Topic-resolved source (Shin 2010, PMID 20714385)
10623688 2000 Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. Topic-resolved source (Friedman 2000, PMID 10623688)
26427984 2016 Conservative treatment of retinoblastoma: a prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy. Added by audit 2026-09-01 (Lumbroso-Le Rouic 2016, PMID 26427984)

Source chronology

Era marker PMID What the record contributes
1991 2059954 Retinoblastoma. (Servodidio 1991, PMID 2059954)
1993 8199450 Retinoblastoma. (Abramson 1993, PMID 8199450)
1993 8407173 Cryotherapy for retinoblastoma. (Shields 1993, PMID 8407173)
1996 8906025 Chemotherapy plus local treatment in the management of intraocular retinoblastoma. (Murphree 1996, PMID 8906025)
1997 9400771 Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. (Shields 1997, PMID 9400771)
1998 9869790 The outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma. (Gündüz 1998, PMID 9869790)
2000 10623688 Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. (Friedman 2000, PMID 10623688)
2001 11713089 Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors. (Shields 2001, PMID 11713089)
2004 15121378 Transpupillary thermotherapy as initial treatment for small intraocular retinoblastoma: technique and predictors of success. (Abramson 2004, PMID 15121378)
2004 15465557 Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation. (Gündüz 2004, PMID 15465557)
2005 15763191 Chemotherapy for retinoblastoma. (Chan 2005, PMID 15763191)
2005 16139001 Chemoreduction in the management of retinoblastoma. (Shields 2005, PMID 16139001)
2006 16570739 Retinoblastoma. (Melamud 2006, PMID 16570739)
2006 16794500 Treatment of retinoblastoma patients with chemoreduction plus local therapy: experience of the AC Camargo Hospital, Brazil. (Antoneli 2006, PMID 16794500)
2006 16934146 Retinoblastoma. (Aerts 2006, PMID 16934146)

Evidence limitations

  • Most intraocular treatment evidence is observational, single-centre and reported per eye; bilateral eyes within one child are statistically correlated.

  • Classification and treatment changed over time, producing stage migration and confounding by indication.

  • Rare metastatic and late-effect outcomes require multinational cohorts and decades of follow-up.

  • Verification is abstract-level. Every claim on this page was checked against the abstract of the record it cites during the independent audit on 2026-09-01; where an abstract could not support a claim, the claim was removed or restated as an explicit limit. Claims requiring full text beyond the abstract are not made here.

Open questions

  • Which consolidation schedule minimizes recurrence and macular injury? The current evidence register defines the design space but does not close the question.

  • When does plaque outperform repeat IAC or enucleation? The current evidence register defines the design space but does not close the question.

  • How should cumulative focal-treatment burden enter vision prediction? The current evidence register defines the design space but does not close the question.

References

  1. Shields JA, et al. Cryotherapy for retinoblastoma. International ophthalmology clinics. 1993;33:101-5. PMID 8407173
  2. Shields JA, et al. Chemoreduction in the management of retinoblastoma. American journal of ophthalmology. 2005;140:505-6. PMID 16139001
  3. Ancona-Lezama D, et al. Modern treatment of retinoblastoma: A 2020 review. Indian journal of ophthalmology. 2020;68:2356-2365. PMID 33120616
  4. Nag A, et al. Retinoblastoma - A comprehensive review, update and recent advances. Indian journal of ophthalmology. 2024;72:778-788. PMID 38804799
  5. Global Retinoblastoma Study Group. The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries. The Lancet. Global health. 2022;10:e1128-e1140. PMID 35839812
  6. Byroju VV, et al. Retinoblastoma: present scenario and future challenges. Cell communication and signaling : CCS. 2023;21:226. PMID 37667345
  7. Rao R, et al. Retinoblastoma. Indian journal of pediatrics. 2017;84:937-944. PMID 28620731
  8. Aerts I, et al. Retinoblastoma. Orphanet journal of rare diseases. 2006;1:31. PMID 16934146
  9. Melamud A, et al. Retinoblastoma. American family physician. 2006;73:1039-44. PMID 16570739
  10. Abramson DH, et al. Retinoblastoma. Optometry clinics : the official publication of the Prentice Society. 1993;3:49-61. PMID 8199450
  11. Mehta M, et al. Retinoblastoma. Singapore medical journal. 2012;53:128-35; quiz 136. PMID 22337189
  12. Servodidio CA, et al. Retinoblastoma. Cancer nursing. 1991;14:117-23. PMID 2059954
  13. Chan HS, et al. Chemotherapy for retinoblastoma. Ophthalmology clinics of North America. 2005;18:55-63, viii. PMID 15763191
  14. Bornfeld N, et al. [Retinoblastoma]. Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 2020;117:389-402. PMID 32206913
  15. Carnevale JA, et al. Intra-arterial chemotherapy for retinoblastoma. Journal of neurointerventional surgery. 2023;15:303-304. PMID 35584909
  16. Pandey AN. Retinoblastoma: An overview. Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society. 2014;28:310-5. PMID 25473349
  17. Aerts I, et al. [Retinoblastoma update]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie. 2016;23:112-6. PMID 26679524
  18. Chawla B, et al. Recent advances and challenges in the management of retinoblastoma. Indian journal of ophthalmology. 2017;65:133-139. PMID 28345569
  19. Zhang X, et al. Prospects of anti-GD2 immunotherapy for retinoblastoma. Frontiers in immunology. 2024;15:1499700. PMID 39620227
  20. Jehanne M, et al. [Retinoblastoma: recent advances]. Bulletin du cancer. 2014;101:380-7. PMID 24793631
  21. Mendoza PR, et al. Therapeutic Options for Retinoblastoma. Cancer control : journal of the Moffitt Cancer Center. 2016;23:99-109. PMID 27218786
  22. Chandra K, et al. Primary Macular Retinoblastoma: Clinical Presentation and Treatment Outcomes. Journal of vitreoretinal diseases. 2022;6:367-373. PMID 37006899
  23. Lin P, et al. Frontiers in the management of retinoblastoma. American journal of ophthalmology. 2009;148:192-8. PMID 19477707
  24. Shields CL, et al. Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Current opinion in ophthalmology. 2014;25:374-85. PMID 25014750
  25. Elaraoud I, et al. Management of retinal detachment in retinoblastoma with globe conserving treatment. Journal of current ophthalmology. 2019;31:43-48. PMID 30899845
  26. Atchaneeyasakul LO, et al. Prognostic factors and treatment outcomes of retinoblastoma in pediatric patients: a single-institution study. Japanese journal of ophthalmology. 2009;53:35-39. PMID 19184307
  27. Temming P, et al. [Diagnosis and treatment of retinoblastoma: current strategies for effective tumour control and preservation of vision]. Klinische Monatsblatter fur Augenheilkunde. 2013;230:232-42. PMID 23508752
  28. Shields CL, et al. Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. Ophthalmology. 1997;104:2101-11. PMID 9400771
  29. Zage PE, et al. Outcomes of a two-drug chemotherapy regimen for intraocular retinoblastoma. Pediatric blood & cancer. 2008;50:567-72. PMID 17729249
  30. Lumbroso-Le Rouic L, et al. Selective Ophthalmic Artery Chemotherapy with Melphalan in the Management of Unilateral Retinoblastoma: A Prospective Study. Ophthalmology. Retina. 2021;5:e30-e37. PMID 34000459
  31. Abramson DH, et al. Transpupillary thermotherapy as initial treatment for small intraocular retinoblastoma: technique and predictors of success. Ophthalmology. 2004;111:984-91. PMID 15121378
  32. Berman EL, et al. Outcomes in retinoblastoma, 1974-2005: the Children's Hospital, Westmead. Clinical & experimental ophthalmology. 2007;35:5-12. PMID 17300564
  33. Shields CL, et al. Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors. Ophthalmology. 2001;108:2116-21. PMID 11713089
  34. Morawski K, et al. [Available approaches to retinoblastoma therapy--literature review]. Klinika oczna. 2015;117:45-9. PMID 26349159
  35. Murphree AL, et al. Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Archives of ophthalmology (Chicago, Ill. : 1960). 1996;114:1348-56. PMID 8906025
  36. Gündüz K, et al. The outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma. Archives of ophthalmology (Chicago, Ill. : 1960). 1998;116:1613-7. PMID 9869790
  37. Gündüz K, et al. Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation. Ophthalmology. 2004;111:1917-24. PMID 15465557
  38. Antoneli CB, et al. Treatment of retinoblastoma patients with chemoreduction plus local therapy: experience of the AC Camargo Hospital, Brazil. Journal of pediatric hematology/oncology. 2006;28:342-5. PMID 16794500
  39. Shin JY, et al. Eye-preserving therapy in retinoblastoma: prolonged primary chemotherapy alone or combined with local therapy. Korean journal of ophthalmology : KJO. 2010;24:219-24. PMID 20714385
  40. Friedman DL, et al. Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18:12-7. PMID 10623688
  41. Lumbroso-Le Rouic L, et al. Conservative treatment of retinoblastoma: a prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy. Eye (London, England). 2016;30:46-52. PMID 26427984