Radiation-Induced Optic Neuropathy After Choroidal Metastasis

A 62-year-old Hispanic woman came to our clinic with an elevated mass in the choroid of her left eye that was diagnosed as a choroidal metastatic tumor. She underwent iodine-125 plaque brachytherapy with fine needle aspiration biopsy, performed by a retina specialist ocular oncologist at an academic center.

Two and a half years after her choroidal melanoma was stabilized, she again presented to our clinic, this time with acute onset of mild blur in her left eye.

CLINICAL FINDINGS

The patient’s VA was stable at 20/20 OD and 20/50 OS. She had no relative afferent pupillary defect. With finger counting, her visual fields were restricted in the superior and superonasal areas, as expected due to the location of the metastatic lesion. Extraocular motilities were smooth and full without diplopia. An anterior segment examination was significant for mild dry eye syndrome. IOPs were normotensive.

Dilated fundus examination revealed a swollen optic nerve in the left eye with a peripapillary flame-shaped hemorrhage and cotton wool spot superotemporal to the nerve. The nasal disc margins were blurred. The metastatic choroidal melanoma appeared to be stable. The right eye was significant for an epiretinal membrane (Figure 1).

Fluorescein angiography showed mild leakage in the optic nerve in the late phase, a blocking defect due to the retinal hemorrhage, and mild perivascular leakage of the superotemporal and superonasal vasculature (Figure 2).

A retinal nerve fiber layer (RNFL) OCT of the left eye showed a significantly elevated RNFL consistent with the clinical picture of a swollen nerve (Figure 3). High-definition 5-line raster OCT scan revealed intraretinal cystic spaces and thickened RNFL that was denser nasally than temporally, consistent with clinical appearance. Automated perimetry showed a stable superotemporal field defect consistent with the metastatic lesion and an enlarged blind spot that was consistent with optic neuropathy (Figure 4).

The patient was diagnosed with radiation-induced optic neuropathy (RION) and sent back to the retinal ocular oncologist immediately for further evaluation. At that time, observation every 3 months was recommended. The patient continues to be monitored.

DISCUSSION

Globe preservation strategies have led to increased use of plaque brachytherapy as a treatment for ocular melanoma. This has led to reports of an increased rate of secondary ocular complications, with optic neuropathy occurring in 22% of eyes in reports in the past 2 decades.^1,2

Radiation retinopathy and RION typically occur in patients treated with radiation for intraocular, orbital, cephalic, nasopharyngeal, and/or paranasal tumors. The dose of radiation applied and proximity of the radioactive therapy to the ocular structures increase the risk of developing secondary ocular complications such as keratitis, cataract, neovascular glaucoma, vitreous hemorrhage, macular edema, proliferative retinopathy, and optic neuropathy.³

Rose et al demonstrated changes in retinal microcirculation in eyes after radiation, with an increase in retinal oxygenation and reduction in blood flow.⁴ This is thought to be due to reduced demand for oxygen secondary to cell degeneration and tissue damage after radiation; vascular occlusion may also play a role due to endothelial cell loss. Specifically, RION may occur due to cell injury and subsequent cell death anterior and/or posterior to the lamina cribrosa.³ Prolonged optic nerve edema may lead to optic disc pallor due to neuronal degeneration and possibly devastating vision loss.^3,5

A review of the literature shows that RION occurs in up to 22% of patients by 5 years after radiotherapy,^2,3 although the risk may increase with larger tumors. Clinical features of RION include optic nerve edema, peripapillary cotton wool spots, hemorrhages, and subretinal fluid.³ Clinical symptoms of optic neuropathy may range from none to sudden onset of monocular vision loss.

The primary risk factor for RION has been related to radiation dosage.⁶ Other risk factors may include proximity of tumor to the optic disc and size of tumor.

Intravitreal triamcinolone acetonide, intravitreal bevacizumab, and panretinal photocoagulation have been shown to be beneficial treatments for radiation retinopathy, but there is no consensus on treatment for RION.³

A retrospective study in 2019 found no statistically significant difference in visual acuity or development of optic atrophy after RION between groups treated with intravitreal bevacizumab, triamcinolone, and/or dexamethasone compared with observation. Particularly, both the treatment and nontreatment groups developed optic atrophy after RION, suggesting that observation for a short period of time may be acceptable, as treatment will not change the outcome.⁷

Several treatment regimens for RION have been studied, including bevacizumab alone, triamcinolone alone, and the combination of both. Shields et al found that, after a single dose of intravitreal triamcinolone in patients with RION, visual acuity improved by 2 lines within 3 weeks and was sustained at 11 months, and optic disc hyperemia had resolved by 11 months.⁸ In another study, when patients were treated with bevacizumab alone, visual acuity improved in 64% and optic disc edema resolved in 100%.⁹ The combination of triamcinolone and bevacizumab also resulted in improvement in visual acuity.⁹ Importantly, the study demonstrated that patients with vision loss directly attributed to RION are likely to experience improvement in vision after treatment.⁹

These data support treatment for patients who experience acute decline in visual acuity due to RION and perhaps show support for treating patients to maintain vision and prevent vision loss.¹⁰ By contrast, Eckstein et al found that, with long-term follow-up of up to 55 months after RION, optic atrophy still occurred despite treatment.⁷

MORE DATA NEEDED

More data are needed on the long-term optic nerve implications of plaque brachytherapy for primary melanoma and choroidal metastases. Sustained effects of treatment remain largely unknown, as many patients will lose vision from concurrent radiation maculopathy, thus confounding the outcomes.

Prophylactic treatments for ischemic retinopathy such as panretinal photocoagulation and concurrent periocular triamcinolone acetonide have been considered, but ethical justification for treating all eyes has not been established at this time.