Post-brachytherapy tumor endoresection for treatment of toxic maculopathy in choroidal melanoma

Abstract

Purpose

Toxic tumor syndrome may occur when the irradiated choroidal melanoma releases cytokines, by exudation from irradiated ischemic tissue. We report our experience and outcomes in a series of post-brachytherapy tumor endoresection to mediate radiation complications.

Methods

Patients who underwent endoresection of a choroidal melanoma treated with iodine-125 plaque brachytherapy were evaluated. Baseline patient and tumor parameters were tabulated.

Results

Five patients underwent post-brachytherapy tumor endoresection with intraocular gas or silicone oil tamponade. Three of the five patients underwent concomitant phacoemulsification with intraocular lens placement. Initial tumor height ranged from 2.03–8.91 mm (mean 5.81 mm). Time between brachytherapy and endoresection ranged from 13–62 months (mean 26.8 months), and total follow-up time from brachytherapy ranged from 2.5–9.75 years (mean 5.2 years). Vision post-brachytherapy and pre-endoresection ranged from 20/30 to 20/400. Final visual acuity ranged from 20/70 to no light perception. One patient developed neovascular glaucoma. Radiation maculopathy increased in all patients. One patient developed metastasis at last follow-up. No patient developed exudative retinal detachment, none had local treatment failure, and none required enucleation.

Conclusion

Although tumor endoresection post-brachytherapy is a technically feasible procedure, all patients in our series experienced progressive radiation maculopathy with gradual visual decline.

Introduction

Radiation maculopathy post-brachytherapy is the primary cause of irreversible vision loss in patients with choroidal melanoma.^{1, 2, 3} Treatments with laser photocagulation,^{4, 5} steroids,^{6, 7, 8} and anti-vascular endothelial growth factor agents^{9, 10, 11, 12} do not offer a long-term solution.

Ischemia and exudative retinal detachment following the irradiation of large tumors has been described by Damato and others^{13, 14} to be a result of ‘toxic tumor syndrome'. This may involve the release of inflammatory cytokines, exudation from irradiated and incompetent vessels, and vascular endothelial growth factor from ischemic tissue. Transscleral local resection of residual tumor in patients with exudative retinal detachment and neovascular glaucoma following radiation may result in resolution of these complications by removing the source of toxic inflammatory mediators, which may contribute to the progression of maculopathy.

Materials and methods

The study was approved by the Institutional Review Board of the University of California, Los Angeles. The records of all patients with clinical diagnosis of choroidal melanoma treated with iodine-125 plaque brachytherapy who had tumor endoresection via pars plana vitrectomy were reviewed. All patients who had undergone tumor endoresection, had ultrasonographic evidence of tumor regression, and had expected radiation retinopathy were included. Surgeries were performed by the author.

Details of the radioactive plaque placement procedure have been described.^{15, 16, 17} Tumor endoresection was performed via a pars plana 20 gauge vitrectomy approach. In phakic cases, phacoemulsification with intraocular lens placement was performed in combination with vitrectomy, which included complete vitreous removal to the ora serrata. Endolaser was applied to the base of the tumor. The tumor and overlying retina were removed with the vitreous cutter to bare sclera. Intraocular cautery and elevation of intraocular pressure were used to achieve hemostasis. C3F8 gas or Silicone Oil 5000 centistokes was used for endotamponade.

Case reports

Case 1

A 36-year-old male with 20/20 vision was treated for a 6-mm choroidal melanoma. (See Table 1 for pre-plaque and pre-endoresection characteristics). After 5.2 years (62 months), his vision declined to 20/80 with exudates and cystoid macular edema, and foveal capillary drop-out on fluorescein angiography. At 4.42 years (53 months) after endoresection with C3F8 gas, the vision was 20/125, and there was cystoid edema, exudates, and hemorrhage in the macula. (See Table 2 for patient characteristics at final follow-up).

Table 1. Patient characteristics pre-plaque and pre-endoresection.

Case	Sex	Age (years)	Initial VA	Tumor height (mm)	Time to endoresection	Pre-endoresection	Pre-endoresection tumor height (mm)	Macula status pre-endoresection
					years (months)	VA		Clinical	FA
1	M	36	20/20	6	5.2 (62)	20/80	1.93	CME, exudates	Mild ischemia
2	M	50	CF	8.13	2.1 (25)	20/400	7.51	CME, exudates	N/A
3	M	68	20/30	2.03	1.1 (13)	20/25	2.17	Normal	CME
4	M	42	20/25	8.91	1.25 (15)	20/30	6.5	Normal	Mild ischemia
5	F	60	20/25	3.97	1.58 (19)	20/60	2.42	No viewa	No viewa

Abbreviations: CME, cystoid macular edema; FA, fluorescein angiogram; N/A, not available; VA, visual acuity.

^aPatient had advanced cataract.

Table 2. Patient characteristics at final follow-up.

Case	Endo surgery	Total follow-up years (months)	Exudative RD	NVG	Final VA	Final macular status	Metastasis
1	PPV C3F8	9.75 (117)	No	No	20/125	Diffuse CME, exudates, hemes	No
2	Phaco PPV SiO	5.92 (71)	No	No	NLP	Diffuse CME, exudates, vasc sclerosis	Yes
3	PPV C3F8	3.08 (37)	No	No	20/70	Moderate CME, exudates, hemes	No
4	Phaco PPV C3F8	4.75 (57)	No	Yes	CF	Diffuse CME, exudates, hemes	No
5	Phaco PPV C3F8	2.5 (30)	No	No	CF	Diffuse CME, exudates, hemes	No

Abbreviations: CF, counting fingers; CME, cystoid macular edema; Endo, endoresection; hemes, retinal hemorrhages; NLP, no light perception; NVG, neovascular glaucoma; phaco, phacoemulsification; PPV, pars plana vitrectomy; RD, retinal detachment; SiO, silicone oil 5000 centistokes; VA, visual acuity; vasc, vascular; C3F8, perfluoropropane gas.

Case 2

A 50-year-old male with counting fingers vision was treated for a 8.13-mm choroidal melanoma. After 2.1 years (25 months), his vision declined to 20/400 with exudates and cystoid macular edema. At 3.83 years (46 months) after combined cataract surgery and endoresection with silicone oil, the vision was no light perception, and there was diffuse cystoid edema, exudates, and vascular sclerosis of the retina. He developed metastasis of the lungs and liver.

Case 3

A 68-year-old male with 20/30 vision was treated for a 2.03-mm choroidal melanoma. After 1.1 years (13 months), his vision was 20/25 with fluorescein angiographic macular edema. Two years (24 months) after endoresection with C3F8 gas, the vision was 20/70, and there was moderate cystoid edema, exudates, and hemorrhage of the macula.

Case 4

A 42-year-old male with 20/25 vision was treated for a 8.91-mm choroidal melanoma with good tumor response to treatment (Figure 1). After 1.25 years (15 months), his vision was 20/30 with mild foveal capillary drop-out on fluorescein angiography. At 3.5 years (42 months) after combined cataract surgery and endoresection with C3F8 gas, the vision was counting fingers. He had diffuse cystoid edema, exudates, and hemorrhage of the macula (Figure 2). Three and a half years following endoresection surgery, he developed neovascular glaucoma, which was successfully controlled with pan-retinal laser photocoagulation and intravitreal bevacizumab injections.

Figure 1.

Macular photograph and mid-phase fluorescein angiogram 15 months after iodine-125 plaque brachytherapy for a 8.91-mm choroidal melanoma located in the inferonasal equatorial fundus (tumor not shown). Angiogram reveals foveal capillary drop-out. Ocular coherence tomography reveals trace thinning of the outer plexiform layer at the fovea. Vision is 20/30 (Case 4).

Figure 2.

Macular photograph of same patient demonstrating typical features of radiation maculopathy: exudates, peripapillary nerve fiber layer infarcts, retinal hemorrhages, and disk pallor 26 months (2.17 years) after tumor endoresection (41 months (3.42 years) after brachytherapy). Ocular coherence tomography reveals disorganization of photoreceptor outer segments, intraretinal fluid and exudates worse on the nasal side. Vision is counting fingers.

Case 5

A 60-year-old female with 20/25 vision was treated for a 3.97-mm choroidal melanoma with good tumor response to treatment. After 1.6 years (19 months), her vision declined to 20/60 with advanced nuclear sclerotic cataract. At 11 months after combined cataract and endoresection with C3F8 gas, the vision was counting fingers, and there was diffuse cystoid edema, exudates, and hemorrhage of the macula.

Discussion

The aim of this report was to evaluate the feasibility and outcomes of five cases where post-brachytherapy tumor endoresection was performed with mild signs of radiation retinopathy. There were no surgical complications. Over the 2.9 years (35.2 months), average follow-up after endoresection, clinical signs of radiation retinopathy progressed, and vision continued to deteriorate.

Based on the ‘toxic tumor syndrome' theory, we expected that debulking the residual-treated melanoma, while the visual acuity and macular status were minimally affected, might limit progression of radiation retinopathy. One could consider that the deterioration in vision might have been worse without endoresection. Endoresection post-irradiation of large tumors has been reported to resolve serous retinal detachment and neovascular glaucoma.^{13, 14} None of the cases in our series developed serous exudation. However, Case 4 developed neovascular glaucoma despite post-brachytherapy endoresection.

In summary, post-brachytherapy tumor endoresection is a technically feasible procedure. As macular status and vision continued to deteriorate after endoresection in this series, endoresection alone may not be sufficient to improve visual outcomes.

The author declares no conflict of interest.