Treatment Paradigms in Radiation Maculopathy Treatment: What’s Next?

Main Article Content

Brittany E. Powell, MD Rachel A. Lieberman, MD Paul T. Finger, MD

Abstract

Radiation is the most common life and sight-sparing treatment for eye cancer patients. However, it can subsequently lead to a dose-dependent, progressive radiation vasculopathy, which results in retinopathy- or optic neuropathy-related vision loss. Before the advent of intravitreal drug therapy, laser destruction of the ischemic retina was found to be effective for select patients. However, in 2006, the anti-vascular endothelial growth factor bevacizumab was found to trigger regression and suppress radiation maculopathy and optic neuropathy. Anti-vascular endothelial growth factor drugs were administered initially to forestall vision loss in patients with clinically significant disease. Advancements in retinal imaging and a better understanding of their capabilities resulted in earlier intervention with anti-vascular endothelial growth factor treatment. Still, not all the radiation damage to the retina was reversible. To prevent this irreversible injury, periodic anti-vascular endothelial growth factor therapy was given to those patients at the highest risk of developing radiation-related maculopathy within six months of high-dose foveal plaque radiation therapy. This research found that treating patients before clinically evident radiation maculopathy prevented or delayed the onset of radiation maculopathy with preservation of vision. Other strategies to prevent vision loss due to progressive, recalcitrant retinopathy have included the off-label use of alternative therapeutic agents and polypharmacy with intravitreal steroids. These therapeutic agents should be evaluated in protocols where intervention can be guided by optical coherence tomography angiography as subclinical obliterative retinal microangiopathy appears to start at the time of or soon after ocular irradiation. Treatment strategies have evolved, especially as our understanding of the condition has improved. We propose that future protocols take advantage of new therapies, use advances in retinal imaging, and employ novel technologies to establish optimal treatment regimens.

Keywords: radiation retinopathy, radiation optic neuropathy, radiation maculopathy, anti-VEGF, drug, radiation dose, intravitreal, bevacizumab, ranibizumab, steroid

Article Details

How to Cite
POWELL, Brittany E.; LIEBERMAN, Rachel A.; FINGER, Paul T.. Treatment Paradigms in Radiation Maculopathy Treatment: What’s Next?. Medical Research Archives, [S.l.], v. 12, n. 9, sep. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5708>. Date accessed: 03 oct. 2024. doi: https://doi.org/10.18103/mra.v12i9.5708.
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Research Articles

References

1. Finger PT. Radiation therapy for orbital tumors: concepts, current use, and ophthalmic radiation side effects. Surv Ophthalmol. 2009;54(5):545-568. doi:10.1016/j.survophthal.2009.06.004
2. Finger PT. Radiation therapy for choroidal melanoma. Surv Ophthalmol. 1997;42(3):215-232.
3. American Brachytherapy Society - Ophthalmic Oncology Task Force. Electronic address: [email protected], ABS – OOTF Committee. The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma. Brachytherapy. 2014;13(1):1-14. doi:10.1016/j.brachy.2013.11.008
4. Finger PT, Chin KJ, Duvall G, Palladium-103 for Choroidal Melanoma Study Group. Palladium-103 ophthalmic plaque radiation therapy for choroidal melanoma: 400 treated patients. Ophthalmology. 2009;116(4):790-796, 796.e1. doi:10.1016/j.ophtha.2008.12.027
5. Melia M, Moy CS, Reynolds SM, et al. Quality of life after iodine 125 brachytherapy vs enucleation for choroidal melanoma: 5-year results from the Collaborative Ocular Melanoma Study: COMS QOLS Report No. 3. Arch Ophthalmol Chic Ill 1960. 2006;124(2):226-238. doi:10.1001/archopht.124.2.226
6. Miniati M, Fabrini MG, Genovesi Ebert F, et al. Quality of Life, Depression, and Anxiety in Patients with Uveal Melanoma: A Review. J Oncol. 2018;2018:5253109. doi:10.1155/2018/5253109
7. Quality of life assessment in the collaborative ocular melanoma study: design and methods. COMS-QOLS Report No. 1. COMS Quality of Life Study Group. Ophthalmic Epidemiol. 1999;6(1):5-17.
8. Finger PT, Chin KJ, Yu GP. Risk Factors for Radiation Maculopathy after Ophthalmic Plaque Radiation for Choroidal Melanoma. Am J Ophthalmol. 2010;149(4):608-615. doi:10.1016/j.ajo.2009.11.006
9. Finger PT. Tumour location affects the incidence of cataract and retinopathy after ophthalmic plaque radiation therapy. Br J Ophthalmol. 2000;84(9):1068-1070.
10. Hall EJ. Radiation dose-rate: a factor of importance in radiobiology and radiotherapy. Br J Radiol. 1972;45(530):81-97. doi:10.1259/0007-1285-45-530-81
11. Groenewald C, Konstantinidis L, Damato B. Effects of radiotherapy on uveal melanomas and adjacent tissues. Eye Lond Engl. 2013;27(2):163-171. doi:10.1038/eye.2012.249
12. Archer DB, Gardiner TA. Ionizing radiation and the retina. Curr Opin Ophthalmol. 1994;5(3):59-65.
13. Bawankar P, Barman M, Bhattacharjee H, Soibam R, Paulbuddhe V. Radiation retinopathy after external beam irradiation for nasopharyngeal carcinoma: A case report and review of the literature. Pract Radiat Oncol. 2018;8(6):366-368. doi:10.1016/j.prro.2018.03.010
14. Hsu CR, Tai MC, Chang YH, Chien KH. Rapid onset of radiation maculopathy after whole-brain radiation therapy: A case report. Medicine (Baltimore). 2016;95(39):e4830. doi:10.1097/MD.0000000000004830
15. Gliedman PR, Steinfeld AD. Radiation retinopathy. JAMA. 1987;257(6):780.
16. Brown GC, Shields JA, Sanborn G, Augsburger JJ, Savino PJ, Schatz NJ. Radiation retinopathy. Ophthalmology. 1982;89(12):1494-1501.
17. Gupta A, Dhawahir-Scala F, Smith A, Young L, Charles S. Radiation retinopathy: case report and review. BMC Ophthalmol. 2007;7:6. doi:10.1186/1471-2415-7-6
18. Bianciotto C, Shields CL, Pirondini C, Mashayekhi A, Furuta M, Shields JA. Proliferative radiation retinopathy after plaque radiotherapy for uveal melanoma. Ophthalmology. 2010;117(5):1005-1012. doi:10.1016/j.ophtha.2009.10.015
19. Kinyoun JL. Long-term visual acuity results of treated and untreated radiation retinopathy (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:325-335.
20. Young WC, Thornton AF, Gebarski SS, Cornblath WT. Radiation-induced optic neuropathy: correlation of MR imaging and radiation dosimetry. Radiology. 1992;185(3):904-907. doi:10.1148/radiology.185.3.1438784
21. Yousef YA, Finger PT. Optical coherence tomography of radiation optic neuropathy. Ophthalmic Surg Lasers Imaging Off J Int Soc Imaging Eye. 2012;43(1):6-12. doi:10.3928/15428877-20111129-09
22. Powell BE, Chin KJ, Finger PT. Early anti-VEGF treatment for radiation maculopathy and optic neuropathy: lessons learned. Eye Lond Engl. 2023;37(5):866-874. doi:10.1038/s41433-022-02200-5
23. Shields CL, Say EAT, Samara WA, Khoo CTL, Mashayekhi A, Shields JA. O Optical Coherence Tomography Angiography of the Macula after Plaque Radiotherapy of Choroidal Melanoma: Comparison of Irradiated Versus Nonirradiated Eyes in 65 Patients. Retina Phila Pa. 2016;36(8):1493-1505. doi:10.1097/IAE.0000000000001021
24. Fam A, Tomar AS, Finger PT. OCT-A evaluation of radiation vasculopathy following slotted plaque brachytherapy. Eur J Ophthalmol. 2022;32(4):2459-2568. doi:10.1177/11206721211044339
25. Horgan N, Shields CL, Mashayekhi A, Teixeira LF, Materin MA, Shields JA. Early Macular Morphological Change Following Plaque Radiotherapy for Uveal Melanoma. Retina. 2008;28(2):263-273. doi:10.1097/IAE.0b013e31814b1b75
26. Horgan N, Shields CL, Mashayekhi A, Shields JA. Classification and treatment of radiation maculopathy. Curr Opin Ophthalmol. 2010;21(3):233-238. doi:10.1097/ICU.0b013e3283386687
27. Finger PT. Laser photocoagulation for radiation retinopathy after ophthalmic plaque radiation therapy. Br J Ophthalmol. 2005;89(6):730-738. doi:10.1136/bjo.2004.052159
28. Argon laser photocoagulation for macular edema in branch vein occlusion. The Branch Vein Occlusion Study Group. Am J Ophthalmol. 1984;98(3):271-282. doi:10.1016/0002-9394(84)90316-7
29. Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. A randomized clinical trial. Branch Vein Occlusion Study Group. Arch Ophthalmol Chic Ill 1960. 1986;104(1):34-41. doi:10.1001/archopht.1986.01050130044017
30. A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. The Central Vein Occlusion Study Group N report. Ophthalmology. 1995;102(10):1434-1444.
31. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98(5 Suppl):823-833.
32. Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study findings. Ophthalmology. 1978;85(1):82-106. doi:10.1016/s0161-6420(78)35693-1
33. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology. 1981;88(7):583-600.
34. Materin MA, Bianciotto CG, Wu C, Shields CL. Sector laser photocoagulation for the prevention of macular edema after plaque radiotherapy for uveal melanoma: a pilot study. Retina Phila Pa. 2012;32(8):1601-1607. doi:10.1097/IAE.0b013e3182437e70
35. Vinores SA, Youssri AI, Luna JD, et al. Upregulation of vascular endothelial growth factor in ischemic and non-ischemic human and experimental retinal disease. Histol Histopathol. 1997;12(1):99-109.
36. Banai S, Shweiki D, Pinson A, Chandra M, Lazarovici G, Keshet E. Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis. Cardiovasc Res. 1994;28(8):1176-1179. doi:10.1093/cvr/28.8.1176
37. Maheshwari A, Finger PT. Laser treatment for choroidal melanoma: Current concepts. Surv Ophthalmol. 2023;68(2):211-224. doi:10.1016/j.survophthal.2022.05.002
38. Finger PT, Chin K. Anti–vascular endothelial growth factor bevacizumab (Avastin) for radiation retinopathy. Arch Ophthalmol. 2007;125(6):751-756.
39. Finger PT. Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin). Int J Radiat Oncol Biol Phys. 2008;70(4):974-977. doi:10.1016/j.ijrobp.2007.11.045
40. Finger PT. Anti-VEGF bevacizumab (Avastin) for radiation optic neuropathy. Am J Ophthalmol. 2007;143(2):335-338. doi:10.1016/j.ajo.2006.09.014
41. Finger PT, Chin KJ, Semenova EA. Intravitreal anti-VEGF therapy for macular radiation retinopathy: a 10-year study. Eur J Ophthalmol. 2016;26(1):60-66. doi:10.5301/ejo.5000670
42. Fallico M, Reibaldi M, Avitabile T, et al. Intravitreal aflibercept for the treatment of radiation-induced macular edema after ruthenium 106 plaque radiotherapy for choroidal melanoma. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol. 2019;257(7):1547-1554. doi:10.1007/s00417-019-04347-6
43. Pooprasert P, Young-Zvandasara T, Al-Bermani A. Radiation retinopathy treated successfully with aflibercept. BMJ Case Rep. 2017;2017. doi:10.1136/bcr-2017-220744
44. Skalet AH, Liu L, Binder C, et al. Quantitative OCT Angiography Evaluation of Peripapillary Retinal Circulation after Plaque Brachytherapy. Ophthalmol Retina. 2018;2(3):244-250. doi:10.1016/j.oret.2017.06.005
45. Skalet AH, Liu L, Binder C, et al. Longitudinal Detection of Radiation-Induced Peripapillary and Macular Retinal Capillary Ischemia Using OCT Angiography. Ophthalmol Retina. 2020;4(3):320-326. doi:10.1016/j.oret.2019.10.001
46. Chu Z, Lin J, Gao C, et al. Quantitative assessment of the retinal microvasculature using optical coherence tomography angiography. J Biomed Opt. 2016;21(6):066008. doi:10.1117/1.JBO.21.6.066008
47. Torkashvand A, Riazi-Esfahani H, Ghassemi F, et al. Evaluation of radiation maculopathy after treatment of choroidal melanoma with ruthenium-106 using optical coherence tomography angiography. BMC Ophthalmol. 2021;21(1):385. doi:10.1186/s12886-021-02140-w
48. Shah SU, Shields CL, Bianciotto CG, et al. Intravitreal Bevacizumab at 4-Month Intervals for Prevention of Macular Edema after Plaque Radiotherapy of Uveal Melanoma. Ophthalmology. 2014;121(1):269-275. doi:10.1016/j.ophtha.2013.08.039
49. Powell BE, Finger PT. Anti–VEGF Therapy Immediately after Plaque Radiation Therapy Prevents or Delays Radiation Maculopathy. Ophthalmol Retina. 2020;4(5):547-550. doi:10.1016/j.oret.2020.01.010
50. Kim IK, Lane AM, Jain P, Awh C, Gragoudas ES. Ranibizumab for the Prevention of Radiation Complications in Patients Treated with Proton Beam Irradiation for Choroidal Melanoma (An American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc. Published online 2016:19.
51. Shields CL, Dalvin LA, Chang M, et al. Visual Outcome at 4 Years Following Plaque Radiotherapy and Prophylactic Intravitreal Bevacizumab (Every 4 Months for 2 Years) for Uveal Melanoma: Comparison With Nonrandomized Historical Control Individuals. JAMA Ophthalmol. 2020;138(2):136. doi:10.1001/jamaophthalmol.2019.5132
52. Victor AA, Andayani G, Djatikusumo A, et al. Efficacy of Prophylactic Anti-VEGF in Preventing Radiation Retinopathy: A Systematic Review and Meta-Analysis. Clin Ophthalmol Auckl NZ. 2023;17:2997-3009. doi:10.2147/OPTH.S433531
53. Villegas NC, Mishra K, Steinle N, Liu W, Beadle B, Mruthyunjaya P. Intravitreal brolucizumab as treatment of early onset radiation retinopathy secondary to plaque brachytherapy for choroidal melanoma. Am J Ophthalmol Case Rep. 2022;27:101581. doi:10.1016/j.ajoc.2022.101581
54. Finger PT, Chin KJ. High-dose (2.0 mg) Intravitreal Ranibizumab for Recalcitrant Radiation Retinopathy. Eur J Ophthalmol. 2013;23(6):850-856. doi:10.5301/ejo.5000333
55. Brown DM, Boyer DS, Do DV, et al. Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial. Lancet Lond Engl. 2024;403(10432):1153-1163. doi:10.1016/S0140-6736(23)02577-1
56. Murray TG, Latiff A, Villegas VM, Gold AS. Aflibercept for Radiation Maculopathy (ARM Study): Year-2 Extension of a Prospective Clinical Study. J Vitreoretin Dis. 2021;5(3):232-238. doi:10.1177/2474126420958894
57. Kaplan RI, Chaugule SS, Finger PT. Intravitreal triamcinolone acetate for radiation maculopathy recalcitrant to high-dose intravitreal bevacizumab. Br J Ophthalmol. 2017;101(12):1694-1698. doi:10.1136/bjophthalmol-2017-310315
58. Wykoff CC, Abreu F, Adamis AP, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. The Lancet. 2022;399(10326):741-755. doi:10.1016/S0140-6736(22)00018-6