Brachytherapy; Choroidal melanoma; Multimodal imagingBraquiteràpia; Melanoma coroïdal; Imatge multimodalBraquiterapia; Melanoma coroideo; Imagen multimodalBackground: Choroidal melanoma is the most common primary intraocular malignancy, accounting for 90% of all uveal melanomas. Although radiation therapy (brachytherapy, proton beam and gamma knife) is a standard and effective treatment for choroidal melanomas, it carries a risk of vision-threatening complications such as cataract, optic neuropathy, and radiation retinopathy. A lesser-known complication is tumor-related lipid exudation (TRLE), characterized by subretinal and intraretinal lipid accumulation following radiotherapy, potentially resulting from radiation-induced vasculopathy and increased vascular permeability.
Case report: We report a case of a 61-year-old man with a long-standing choroidal nevus under observation for 15 years. Due to signs of growth and subretinal fluid detected on OCT, malignancy was suspected, and Ruthenium-106 brachytherapy was performed. One-month post-treatment, the patient developed progressive exudative retinal detachment with lipid exudation, despite preserved visual acuity. At the nine-month follow-up, worsening exudation and tumor growth were observed, prompting a second brachytherapy session and intravitreal aflibercept injections every eight weeks, leading to complete resolution of lipid exudation and restoration of retinal anatomy. Six months post-treatment, the tumor remained flat, and visual acuity improved to 20/20.
Conclusions: TRLE is an underrecognized complication of radiation therapy for choroidal melanoma, with risk factors including pre-radiotherapy subretinal fluid, increased tumour thickness, and Bruch’s membrane rupture. Studies suggest that anti-VEGF therapy may help mitigate exudative complications; however, its efficacy remains uncertain. This case highlights the importance of recognizing TRLE as a potential complication of brachytherapy and underscores the critical role of multimodal imaging in early diagnosis and monitoring, ensuring optimal treatment outcomes for patients with choroidal melanoma

Boixadera Espax, Ana

Buck Sainz-Rozas, Pablo

Garrido-Marín, Marta

Goncharova Simón, Tetiana

Oliver-Gutierrez, David

Ros-Sanchez, Elena

Zapata, Miguel Angel

BMC Ophthalmology

English

Scientia, Dipòsit d’Informació Digital del Departament de Salut

C A S E  R E P O R T Open Access© The Author(s) 2025. Open Access  This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit  h t t p : / / c r e a t i v e c o m m o n s . o r g / l i c e n s e s / b y - n c - n d / 4 . 0 /.Ros-Sanchez et al. BMC Ophthalmology          (2025) 25:467 https://doi.org/10.1186/s12886-025-04282-7BMC Ophthalmology*Correspondence:Elena Ros-Sanchezelena.rs9@gmail.com1Ophthalmology, Hospital Universitari Vall d’Hebron, Passeig de la Vall d’Hebron 129, Barcelona 08035, Spain2Ophthalmology, Innova Ocular Verte Barcelona, Barcelona, SpainAbstractBackground Choroidal melanoma is the most common primary intraocular malignancy, accounting for 90% of all uveal melanomas. Although radiation therapy (brachytherapy, proton beam and gamma knife) is a standard and effective treatment for choroidal melanomas, it carries a risk of vision-threatening complications such as cataract, optic neuropathy, and radiation retinopathy. A lesser-known complication is tumor-related lipid exudation (TRLE), characterized by subretinal and intraretinal lipid accumulation following radiotherapy, potentially resulting from radiation-induced vasculopathy and increased vascular permeability.Case report We report a case of a 61-year-old man with a long-standing choroidal nevus under observation for 15 years. Due to signs of growth and subretinal fluid detected on OCT, malignancy was suspected, and Ruthenium-106 brachytherapy was performed. One-month post-treatment, the patient developed progressive exudative retinal detachment with lipid exudation, despite preserved visual acuity. At the nine-month follow-up, worsening exudation and tumor growth were observed, prompting a second brachytherapy session and intravitreal aflibercept injections every eight weeks, leading to complete resolution of lipid exudation and restoration of retinal anatomy. Six months post-treatment, the tumor remained flat, and visual acuity improved to 20/20.Conclusions TRLE is an underrecognized complication of radiation therapy for choroidal melanoma, with risk factors including pre-radiotherapy subretinal fluid, increased tumour thickness, and Bruch’s membrane rupture. Studies suggest that anti-VEGF therapy may help mitigate exudative complications; however, its efficacy remains uncertain. This case highlights the importance of recognizing TRLE as a potential complication of brachytherapy and underscores the critical role of multimodal imaging in early diagnosis and monitoring, ensuring optimal treatment outcomes for patients with choroidal melanoma.Keywords  Choroidal melanoma,  Multimodal imaging,  Radiotherapy,  Brachytherapy,  Tumor-related lipid exudation, Case reportMultimodal imaging of tumour-related lipid exudation and exudative retinal detachment following brachytherapy in choroidal melanomaElena Ros-Sanchez1*, David Oliver-Gutierrez1,2, Paul Buck1, Tetiana Goncharova-Simón1, Marta Garrido-Marín1,  Miguel Ángel Zapata-Victori1 and Anna Boixadera1Page 2 of 6Ros-Sanchez et al. BMC Ophthalmology          (2025) 25:467 BackgroundChoroidal melanoma is a life-threatening malignancy, comprising 90% of all uveal melanomas. It predominantly affects Caucasians, with a mean age at diagnosis of 60 years. Major risk factors include fair skin, light-coloured eyes, and intermittent ultraviolet exposure [1, 2]. A cho-roidal nevus, present in 4% of Caucasians, is a significant precursor. DeSimone et al. identified several predictive features of malignant transformation, summarized in the mnemonic “To Find Small Ocular Melanoma Doing Imaging,” including tumour thickness > 2 mm, subretinal fluid, symptoms, orange pigment, melanoma hollow, and diameter > 5 mm [3].Treatment is tailored to tumour characteristics and patient factors, with radiotherapy being a standard approach for posterior uveal melanomas. Although effec-tive, all forms of radiation, including brachytherapy, pro-ton beam and gamma knife, are associated with potentially sight-threatening complications. These include anterior segment pathology, radiation-induced cataract (8–83% at 5 years), optic neuropathy (16%), and radiation retinopathy (10–63%, mean onset 25.6 months) [4, 5].A lesser-known but clinically relevant complication of radiation therapy is ‘tumour-related lipid exudation’ (TRLE), characterized by intraretinal or subretinal lipid accumulation with variable degrees of fluid exudation from the irradiated tumour [6].We present a case report of TRLE following brachy-therapy for choroidal melanoma, emphasizing the critical role of multimodal imaging in diagnosing and managing this rare complication.Case presentationA 61-year-old man was referred to the Retina Depart-ment due to signs of growth and potential malignant transformation of a choroidal nevus into choroidal mela-noma. He had been under follow-up for this nevus for the past 15 years. His systemic history included a colon neo-plasm treated five years prior, with complete remission, and type 2 diabetes mellitus with good systemic control. His best-corrected visual acuity (BCVA) was 20/20 in both eyes. The patient was asymptomatic and attended routine check-ups.On examination, the anterior segment was unremark-able. Right eye fundoscopy showed no abnormalities. Left eye fundoscopy revealed a superior-temporal amelanotic choroidal nevus measuring 7.5 × 5.2 in base and 2.5  mm in height. Optical coherence tomography (OCT) showed the presence of subretinal fluid (Fig. 1). Observation was decided. At the six month- follow-up visit, tumour growth was observed both on fundoscopy and B-scan ultraso-nography, with new dimensions of 9 × 8.66 in base and 3.52 mm in height, with persistent subretinal fluid (Fig. 2). Given these findings suggestive of malignancy suspecting Fig. 1 Left eye retinography showing an amelanotic choroidal nevus in the supero-temporal region. Left eye ultrasound shows an extension of 7.67 × 5.2 mm in base and 2.55 mm in height with melanoma hallow. OCT shows the choroidal nevus with associated subretinal fluid at its base Page 3 of 6Ros-Sanchez et al. BMC Ophthalmology          (2025) 25:467 the evolution to a choroidal melanoma, Ruthenium-106 brachytherapy (80 Gy to the apex) was performed.One month after the procedure, left eye BCVA remained 20/20. Fundoscopy showed a new Bruch’s membrane rup-ture, an exudative retinal detachment inferior to the lesion, accompanied by subretinal haemorrhage. Two months post-brachytherapy, visual acuity remained unchanged. The serous retinal detachment continued to expand, with persistent subretinal haemorrhage. At the nine-month follow-up, further progression was noted, including an increase in lesion thickness on ultrasonography, greater exudative retinal detachment, and the appearance of extensive subretinal lipid exudation with BCVA decreasing to 20/40 (Fig. 3). Based on these findings, a second brachy-therapy was scheduled, delivering 80 Gy to the apex, as it was deemed safe by the Radiation Oncology department in terms of the accumulated radiation dose to the sclera. An intravitreal aflibercept injection was administered at the brachytherapy plaque removal, followed by additional intravitreal aflibercept injections every 8 weeks until sub-retinal exudation decreased and visual acuity improved. Six months after the second brachytherapy, left eye BCVA improved to 20/20. Fundoscopic examination revealed a flat, amelanotic tumour with a thickness of less than 1 mm, as confirmed by ultrasound, with no signs of exudative retinal detachment and complete resorption of the lipid exudation (Fig. 4). OCT confirmed the absence of subreti-nal fluid. As a result, intravitreal therapy was discontinued, and the patient was scheduled for routine follow-up.Discussion and conclusionsBrachytherapy is an effective treatment modality for cho-roidal melanoma; however, like other forms of radiother-apy, it can lead to complications such as cataract, vitreous Fig. 2 Retinography of the left eye reveals an enlarging choroidal lesion in the supero-temporal region. Left eye ultrasound shows an extension of 9 × 8.66 mm in base and 3,52 mm in height. OCT shows no fluid in the macular region and an increase of the subretinal fluid at the base of the tumor Page 4 of 6Ros-Sanchez et al. BMC Ophthalmology          (2025) 25:467 haemorrhage, glaucoma, radiation retinopathy, macu-lopathy, and papillopathy [7]. A lesser-known complica-tion of this treatment is TRLE, which may result from radiation-induced vasculopathy of the tumour vessels or the release of pro-angiogenic cytokines. This would lead to increased vascular permeability of the tumour vessels, allowing extravasated fluid and lipids to move through the Bruch’s membrane and RPE into the subretinal space. The protective barrier of the Bruch’s membrane and RPE would help explain why the incidence of lipid exudation from choroidal tumours is low [8].Mills et al. investigated the associated risk factors for lipid exudation following plaque radiotherapy in uveal melanoma and found that 13% of cases treated with I-125 developed this complication, with an average onset of 10 months post-treatment. Young age, high serum low-den-sity lipoproteins, low serum high-density lipoproteins, high tumour thickness and exudative retinal detach-ment in the preoperative period constituted the most important risk factors. Moreover, they observed that the occurrence of TRLE was associated with poorer visual outcomes and an increased risk of neovascular glaucoma [6]. Subsequently, in a case-control study, Mashayekhi et al. examined the systemic and tumour characteristics predictive of development of TRLE following plaque radiotherapy for posterior uveal melanoma. TRLE developed in 8% of the treated eyes, with the primary risk factors identified as rupture of Bruch’s membrane, pos-terior tumour location closer to the optic nerve or fovea, larger tumour base, with radiation dose to the tumour base correlating with the extent of lipid exudation. Addi-tional factors included the absence of adjuvant therapy with transpupillary thermotherapy (TTT), and the pres-ence of pre-radiotherapy serous retinal detachment, as well as a transient increase in serous retinal detachment in the first months following treatment [8].Our case report involved a middle-aged man who pre-sented risk factors associated with TRLE, including the presence of subretinal fluid prior to radiotherapy and its progression in the first months following treatment, along with a new rupture of the Bruch´s membrane that appeared immediately after the first brachytherapy. Due to suspected tumour growth despite initial therapy, the patient underwent an additional treatment with Ruthe-nium-106 brachytherapy. Subsequently, intravitreal ther-apy with Aflibercept was administered to reduce both lipid exudation and exudative retinal detachment.Anti-VEGF therapy has been studied as a treatment for the resolution of exudative retinal detachment secondary to choroidal melanoma, with published studies primarily using Bevacizumab. In a retrospective study, Houston et al. evaluated the efficacy of intravitreal Bevacizumab as Fig. 3 Nine months after the first brachytherapy. Left eye retinography showing inferior exudative retinal detachment with an important lipid exudation surrounding the choroidal melanoma and extending to the inferior and nasal retinal periphery. OCT shows subretinal fluid approaching to the centre of the macula from the temporal posterior pole. Ultrasound shows an increase of tumour thickness to 4 mm and the Bruch´s membrane rupture Page 5 of 6Ros-Sanchez et al. BMC Ophthalmology          (2025) 25:467 an adjuvant therapy to plaque brachytherapy for choroi-dal melanoma, administering it immediately after plaque removal. They observed a 73% resolution rate in patients receiving combined therapy, with a mean resolution time of four months [9]. Additionally, a comparative study assessed the effectiveness of intravitreal triamcinolone versus intravitreal Bevacizumab for the treatment of large exudative retinal detachment secondary to uveal mela-noma. The study found a higher regression rate of reti-nal detachment (69%) in patients treated with intravitreal triamcinolone immediately after brachytherapy, with ste-roid-induced cataract being the most common complica-tion [10].In our case, the patient initially underwent brachy-therapy; however, a second brachytherapy was required within the first year due to tumour growth and exten-sive subretinal detachment and lipid exudation, indicat-ing insufficient local tumour control. Unlike previously reported cases, no immediate intravitreal anti-VEGF or triamcinolone treatment was administered, making Fig. 4 Left eye retinography shows resolution of inferior exudative retinal detachment and reduction of the lipid exudation. OCT shows resolution of subretinal fluid with retinal atrophy temporal to the fovea secondary to the brachytherapy Page 6 of 6Ros-Sanchez et al. BMC Ophthalmology          (2025) 25:467 it uncertain whether such an approach could have pre-vented the subsequent progression and significant exuda-tion observed in the following months.After the second brachytherapy, intravitreal anti-VEGF therapy with aflibercept was initiated every eight weeks. However, to date, no published studies have evaluated the use of aflibercept as an adjunctive therapy for the management of choroidal melanoma with associated exudative retinal detachment. Despite this, the patient showed a favourable response to aflibercept, with com-plete resolution of exudation. These findings suggest that aflibercept could be a potential adjunctive therapy in such cases, as its mechanism of action is similar to that of other anti-VEGF. While the resolution of exudation may be attributed largely to the anti-VEGF therapy, the fact that tumour growth occurred after the initial brachy-therapy also suggests that the second brachytherapy may have contributed to improve local tumour control and, consequently, to the resolution of TRLE.Regarding long-term vascular changes, some studies have assessed the effects of I-125 brachytherapy and TTT as primary treatments for choroidal melanoma. Pilotto et al. reported that retino-choroidal anastomoses devel-oped in 11% of patients treated with TTT, while none were observed in those treated with brachytherapy. These findings were associated with an increased risk of tumour recurrence [11]. In our case, fluorescein angiography has not yet been performed; thus, we cannot confirm the presence or absence of vascular anastomoses involv-ing the tumour. However, based on the aforementioned study, the risk would be expected to be relatively low.In conclusion, this case underscores the importance of recognizing TRLE as a potential complication of brachy-therapy for choroidal melanoma and highlights the cru-cial role of multimodal imaging in its early detection and monitoring. The successful resolution of the exudative retinal detachment following brachytherapy combined with intravitreal aflibercept suggests that the combined therapy may be a useful option in managing TRLE. How-ever, further studies are needed to better define its role. Case reports like this contribute valuable insights that help refine clinical decision-making and optimize treat-ment approaches for choroidal melanoma.AbbreviationsOCT  Optical coherence tomographyOCT-A  Optical coherence tomography – AngiographyTRLE  Tumour-related lipid exudationBCVA  Best-corrected visual acuityTTT  Transpupillary thermotherapyAuthors’ contributionsAB, MZ and MG were in charge of the patient and did the follow-up, collected the data. ER and DO wrote the manuscript. PB and TGSrevised and corrected the manuscript. All authors read and approved the final manuscript.FundingThis paper has no funding or grant support.Data availabilityAll data generated or analysed during this study are included in this published article.DeclarationsEthics approval and consent to participateNot applicable.Consent for publicationWritten informed consent was obtained from the patient for publication of this case report.Competing interestsThe authors declare no competing interests.Received: 14 April 2025 / Accepted: 17 July 2025References1. Shields CL, Manalac J, Das C, Ferguson K, Shields JA. Choroidal melanoma: clinical features, classification, and top 10 pseudomelanomas. Curr Opin Ophthalmol. 2014;25(3):177–85.2. Shah CP, Weis E, Lajous M, Shields JA, Shields CL. Intermittent and chronic ultraviolet light exposure and uveal melanoma: a meta-analysis. Ophthalmol-ogy. 2005;112(9):1599–607.3. Shields CL, Dalvin LA, Ancona-Lezama D, Yu MD, Di Nicola M, Williams BK Jr, Lucio-Alvarez JA, Ang SM, Maloney S, Welch RJ, Shields JA. Choroidal nevus imaging features in 3,806 cases and risk factors for transformation into melanoma in 2,355 cases: the 2020 Taylor R. Smith and victor T. Curtin lecture. Retina. 2019;39(10):1840–51.4. Shields CL, Cater J, Shields JA, Chao A, Krema H, Materin M, Brady LW. Com-bined plaque radiotherapy and transpupillary thermotherapy for choroidal melanoma: tumor control and treatment complications in 270 consecutive patients. Arch Ophthalmol. 2002;120(7):933–40.5. Wen JC, Oliver SC, McCannel TA. Ocular complications following I-125 brachy-therapy for choroidal melanoma. Eye (Lond). 2009;23(6):1254–68.  h t t p s : / / d o i . o r g / 1 0 . 1 0 3 8 / e y e . 2 0 0 9 . 4 3.6. Mills MD, Harbour JW. Lipid exudation following plaque radiotherapy for posterior uveal melanoma. Am J Ophthalmol. 2006;141(3):594–5.7. Summanen P, Immonen I, Kivelä T, Tommila P, Heikkonen J, Tarkkanen A. Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma. Br J Ophthalmol. 1996;80(8):732–9.8. Mashayekhi A, Tuncer S, Shields CL, Shields JA. Tumor-related lipid exudation after plaque radiotherapy of choroidal melanoma: the role of bruch’s mem-brane rupture. Ophthalmology. 2010;117(5):1013–23.9. Houston SK, Shah NV, Decatur C, Lonngi M, Feuer W, Markoe AM, Murray TG. Intravitreal bevacizumab combined with plaque brachytherapy reduces melanoma tumor volume and enhances resolution of exudative detach-ment. Clin Ophthalmol. 2013;7:193–8.10. Parrozzani R, Pilotto E, Dario A, Miglionico G, Midena E. Intravitreal triamcino-lone versus intravitreal bevacizumab in the treatment of exudative retinal detachment secondary to posterior uveal melanoma. Am J Ophthalmol. 2013;155(1):127–e1332.11. Pilotto E, Vujosevic S, De Belvis V, Parrozzani R, Boccassini B, Midena E. Long-term choroidal vascular changes after iodine brachytherapy versus transpupillary thermotherapy for choroidal melanoma. Eur J Ophthalmol. 2009;19(4):646–53.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Multimodal imaging of tumour-related lipid exudation and exudative retinal detachment following brachytherapy in choroidal melanoma

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Multimodal imaging of tumour-related lipid exudation and exudative retinal detachment following brachytherapy in choroidal melanoma

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