The Collaborative Ocular Melanoma Study (COMS) established iodine-125 plaque brachytherapy at a prescription of 85 Gy to the tumor apex as the gold standard for medium-sized uveal melanoma.1 This empirically derived dose was intended to maximize local tumor control while maintaining an acceptable rate of vision-threatening radiation complications. However, growing evidence suggests that the optimal dose may be lower, particularly for smaller tumors.
Prior to COMS, brachytherapy dosing varied widely, from <70 Gy to >100 Gy, with higher doses linked to increased complications such as radiation retinopathy, optic neuropathy, and neovascular glaucoma. COMS selected 85 Gy based on a therapeutic window suggested by clinical experience (70 Gy to 100 Gy), radiobiologic modeling indicating a tumor biologically effective dose (BED) of ~103 Gy, and practical delivery with standard plaque designs. The protocol prescribed 85 Gy to 5 mm depth for tumors ≤5 mm in height, a practice that may have resulted in overtreatment for the smaller tumors.1,2
Figure 1. A 56-year-old male undergoing a routine eye exam was found to have a choroidal melanoma in the left eye.
Evidence from Systematic Reviews
In 2017 our group conducted a systematic review of 15 studies (2,662 patients) and found no statistically significant relationship between apex dose and local recurrence rate in the 62.5 Gy to 104 Gy range.3 An increase in dose of 1 Gy was associated with only a 0.14% decrease in recurrence rate (P=.336). Importantly, several low-dose regimens, such as in Saconn et al’s 62.5 Gy series, achieved a local control rate comparable to COMS (9% vs 10.3%).4 Perez et al stratified 190 patients by dose quartiles (<65 Gy to >85 Gy) and found lack of association between higher dose and reduced recurrence, but did note greater ocular toxicity with higher doses.5
In an updated review from 2025 that included 20 studies and 3,316 patients, the regression slope between apex dose and recurrence remained weak (R²=.033, P=.397). Some low-dose series—such as Kheir et al’s 63 Gy regimen with custom-designed Eye Physics plaques—reported recurrence rates (~6%) comparable to standard 85 Gy COMS plaques,6 while offering better visual preservation. Plaque design may play a critical role: Eye Physics plaque design achieves greater dose conformality and reduces radiation to critical structures by 40% to 50% compared to COMS-design plaques.
The 2020 Ocular Oncology Study Consortium survey revealed that although most ocular oncology centers still prescribe 85 Gy per COMS standards, practice variation is common.7 Several centers reported intentionally reducing dose for small tumors (≤5 mm height) or when using plaques with different dosimetric characteristics. Prescription depth, plaque sizing, and dose rate (typically ~0.60 Gy/h) also varied. Importantly, an increasing proportion of centers now employ individualized 3D dosimetry and advanced intraoperative imaging to optimize plaque positioning—strategies that may allow safe dose reduction without compromising tumor control.
Figure 2. The dome-shaped, melanocytic lesion measured 9 mm x 9 mm x 2.8 mm and was situated in the inferonasal quadrant (A), accompanied by a shallow retinal detachment (B). A-scan ultrasonography revealed low to medium internal reflectivity. Episcleral plaque brachytherapy was recommended due to the tumor proximity—2.7 mm—to the optic disc margin, which increased the risk of radiation-induced optic neuropathy.
Clinical Case: Radiation Dose Optimization
The following case illustrates how plaque design can be optimized to reduce radiation exposure to critical structures such as the macula and optic nerve during treatment of ocular tumors.
A 56-year-old male, undergoing a routine eye exam for glasses, was incidentally found to have a choroidal melanoma in his left eye (Figure 1). The dome-shaped melanocytic tumor measured 9 mm x 9 mm x 2.8 mm and was located in the inferonasal quadrant, associated with a shallow retinal detachment (Figure 2). A-scan ultrasonography showed low to medium internal reflectivity. Episcleral plaque brachytherapy was recommended as the treatment approach. The tumor was 2.7 mm from the optic disc margin, and this proximity presented a significant risk for radiation-induced optic neuropathy.
Because the patient had 20/20 vision and was asymptomatic, he was highly motivated to minimize the risk of vision loss. He was ineligible for the COMPASS trial due to tumor thickness exceeding 2.5 mm and for the IDEAYA trial, which had closed enrollment.8
Radiation planning using an EP 917 plaque (IsoAid) with the standard apical dose of 85 Gy (Figure 3A) initially predicted a macular dose under 30 Gy, which disqualified him from the DRCR Retina Network’s Protocol AL, which requires a macular dose ≥30 Gy.8 To further reduce radiation exposure, the prescribed apical dose was lowered to 65 Gy. This adjustment decreased the optic disc dose from 44 Gy to 33 Gy—a 25% reduction—while maintaining adequate tumor coverage, as demonstrated by the isodose curves drawn closer to the tumor (Figure 3B).
Figure 3. Radiation treatment planning using an EP 917 plaque (IsoAid) considered apical doses of 85 Gy (A) and 65 Gy (B). Lowering the dose to 65 Gy decreased the radiation exposure to the optic disc from 44 Gy to 33 Gy, a 25% reduction, as illustrated by the isodose curves focusing closer to the tumor.
Clinical Considerations for Retina Specialists
Although ocular oncologists set brachytherapy treatment parameters, retina specialists frequently manage the resulting complications. Understanding radiation dose strategies and evolving clinical practices is essential for effective patient counseling and follow-up care. Current evidence indicates the following:
- For tumors 5 mm or less in height, prescribing 85 Gy to a fixed 5 mm depth may be unnecessarily high. Instead, the prescription point can be set at the tumor apical height, consistent with the American Brachytherapy Society guidelines.2
- Lower apical doses, around 60 Gy to 70 Gy, combined with advanced plaque designs, can maintain high rates of local tumor control while reducing toxicity.
- Local tumor recurrence is influenced by multiple factors—including tumor size, margin status, plaque positioning, and thoroughness of follow-up—with radiation dose accounting for only about 4% of the variation in recurrence rates.
Future Directions and Conclusion
The 85 Gy standard remains effective for most medium-sized tumors, but it is not necessarily optimal for all patients. Prospective randomized trials are needed to compare reduced-dose regimens—especially in small tumors—while leveraging modern imaging, 3D planning, and plaque technology. Future standards should balance tumor control with the need for visual preservation.
The assumption that “more is better” for brachytherapy dose in uveal melanoma is increasingly being challenged. For select patients, particularly those with smaller tumors and favorable anatomy, lower-dose regimens may offer equivalent control with fewer vision-threatening complications. A shift toward individualized dosing, informed by plaque design and modern dosimetry, could align local tumor control with functional outcomes—a shared priority for retinal specialists and ocular oncologists alike. RP
References
1. Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors. Arch Ophthalmol. 2006;124(12):1684-1693. doi:10.1001/archopht.124.12.1684
2. Meidenbauer K, Richards Z, Yupari RJ, et al. Outcomes for posterior uveal melanoma: validation of American Brachytherapy Society Guidelines. Brachytherapy. 2021;20(6):1226-1234. doi:10.1016/j.brachy.2021.05.165
3. Echegaray JJ, Bechrakis NE, Singh N, Bellerive C, Singh AD. Iodine-125 brachytherapy for uveal melanoma: a systematic review of radiation dose. Ocul Oncol Pathol. 2017;3(3):193-198. doi:10.1159/000455872
4. Saconn PA, Damato BE, Fernandes BF, et al. Local tumor control after iodine-125 episcleral plaque radiotherapy for choroidal melanoma. Ophthalmology. 2013;120(1):208-215.
5. Perez BA, Mettu P, Vajzovic L, et al. Uveal melanoma treated with iodine-125 episcleral plaque: an analysis of dose on disease control and visual outcomes. Int J Radiat Oncol Biol Phys. 2014;89(1):127-136. doi:10.1016/j.ijrobp.2014.01.026
6. Kheir WJ, Damato B, Tuncer S, et al. Outcomes of iodine-125 plaque brachytherapy with reduced radiation dose for uveal melanoma using Eye Physics plaques. Ocul Oncol Pathol. 2021;7(5):327-335.
7. Binder C, Mruthyunjaya P, Schefler AC, et al. Practice patterns for the treatment of uveal melanoma with iodine-125 plaque brachytherapy: Ocular Oncology Study Consortium Report 5. Ocul Oncol Pathol. 2020;6(3):210-218. doi:10.1159/000504312
8. Weinberger Y, Singh AD. Current trials in uveal melanoma: three promising treatments tested to prevent or mitigate the effects of radiation. Taiwan J Ophthalmol. 2025;15(1):130-134. doi:10.4103/tjo.TJO-D-24-00120