Treatment of Radiation Retinopathy with Intravitreal Injection of Ranibizumab (Lucentis®)

Introduction

Radiation retinopathy is an important complication of orbital radiotherapy or radiation exposure. The literature describes cases of radiotherapy treatment such as plaque radiotherapy for pathologies such as Graves’ ophthalmopathy, uveal or orbital tumors, and ocular metastases.¹

Radiation can damage cells and affect genetic material, with two types of radiation: electromagnetic radiation and particle emission radiation. Ionizing radiations are electromagnetic waves or particles that propagate with high speed and carrying energy, possibly electric and magnetic charge, and that, when interacting, can produce varied effects on matter (National Nuclear Energy Commission, 2009). Radiation is considered ionizing when it has the ability to ionize, the most known type of ionizing radiation is X-rays. The effect of radiation depends on factors such as total amount of radiation received, range of exposure, other associated damages, region affected and individual predisposition.

In radiation retinopathy, alterations occur that are dose dependent, occurring between 6 months to 3 years of exposure, with retinal damage and vasculopathy (exudate, retinal hemorrhage, intraretinal microangiopathy, retinal edema, neovascularization). Macular edema is a common cause of low visual acuity due to radiation retinopathy.

Vascular endothelial growth factor (VEGF) is produced by retinal cells such as Muller, glia and Retinal Pigmented Epithelium cells (EPR). It is a stimulator of proliferation and endothelial migration, responsible for neovascularization, intraretinal edema due to vascular extravasation and vascular injury.

Medications with anti-VEGF action have been used as a treatment for vascular pathology retininians, such as ranibizumab, which is a humanized antibody fragment that acts to inhibit all VEGF-A isoforms.^2–4

Case Report

A 26-year-old female, brown patient with a history of exposure to ionizing radiation for a period of 2 years as an X-ray technique, despite all protective measures regulated by law, developed myelodysplasia confirmed by Bone marrow biopsy and excluding other causes such as autoimmune diseases, neoplasia, viral, drug and exposure to other metals or chemical substances. She was referred for ophthalmologic evaluation for visual turbidity complaint. The patient had visual acuity of 20/80 in the right eye and 20/50 in the left eye.

The funduscopy showed bilateral pale papilla, with physiological digging, vessels with reduced caliber and some phantom vessels, macula with decreased foveal brightness, pale retina, RPE hyperplasia in the middle periphery (see Figures 1 and 2). The macular optical coherence tomography (StratusOCT) showed retinal thickening and cysts formation (see Figures 3–5). Visual field showed island of bilateral central vision (see Figures 6 and 7).

Figure 1 Color fundus photograph – right eye.

Figure 2 Color fundus photograph – left eye.

Figure 3 SD-OCT topcon – incidences and macular view. Right eye (previous anti-VEGF therapy).

Figure 4 SD-OCT topcon – incidences and macular view. Right eye (previous anti-VEGF therapy).

Figure 5 SD-OCT topcon – central macular thickness (CMT). Right eye = 703 µm, left eye = µm. Previous Anti-VEGF therapy.

Figure 6 Octopus 900 – perimeter – visual field – right eye.

Figure 7 Octopus 900 – perimeter – visual field – left eye.

The multifocal ERG (electroretinogram)/PEV (visual evoked potential)/EOG (electrooculogram) examinations was generally affected in both eyes according to the low acuity.

It was performed continuous intravitreal injection with ranibizumab (0.3mg/0,05mL) in 4- week intervals and monitoring with visual acuity and OCT. After performing nine monthly injections the visual acuity was improved for 20/40 in both eyes and decreased macular edema (see Figures 8 and 9).

Figure 8 Zeiss cirrus – SD-OCT – left eye. CMT = 387 µm (after anti-VEGF therapy).

Figure 9 SD-OCT topcon – right eye. CMT = 319 µm (after anti-VEGF therapy).

A case of systemic and ophthalmological manifestation related to tolerable exposure to ionizing radiation in both eyes is rare, not found in the literature similar reports. The improvement of macular edema with the use of intravitreal injection of anti-VEGF as observed was not permanent and did not have a determined number of intravitreal procedures necessary to stabilize the macular condition. Continuous treatment is necessary to maintain acuity improvement. Intravitreal Dexamethasone treatment was not performed due to pallor of the optic nerve and ischemic neuropathy of increased intraocular pressure risk of further injury.^5–9

Conclusion

There is still no curative treatment for pathologies related to exposure to ionizing radiation, requiring more studies with a larger number of patients and a longer follow-up. The patient maintains follow up in hematology and ophthalmology. Aplastic anemia and myelodysplasia are rare diseases with ophthalmic manifestations like vascular changes, retinal hemorrhages, and peripheral retinal ischemia. The systemic changes combined with radiation retinopathy explain the quickly progressing to low vision and concentric impairment of visual field.^10–12 The macular edema treatments with anti-VEGF (Ranibizumab) is promising, and the results depends on continuity what can increase the side effects.^13–17 The mechanisms of radiation protection are still the most effective in preventing radiation retinopathy, which do not have curative treatment.