Effect of intravitreal dexamethasone implant on the contralateral eye in recalcitrant radiation maculopathy.

Radiation maculopathy, a subset of significant radiation retinopathy, is one of the most common causes of visual loss following localized, regional, or whole-brain radiotherapy. Ozurdex (Allergan Inc., Irvine, CA, USA), a sustained-release intravitreal implant of 0.7 mg dexamethasone, has been used as an off-label treatment for treating recalcitrant radiation maculopathy. However, to the best of our knowledge, the beneficial effect of intravitreal dexamethasone in the contralateral eye in a patient with radiation maculopathy has not been described in the literature so far. In this case report, we report the efficacy of dexamethasone 0.7 mg intravitreal implant in recalcitrant radiation maculopathy which was refractory to intravitreal bevacizumab therapy. The patient showed good anatomical and functional outcomes in both the eyes after unilateral injection of intravitreal dexamethasone as evident by optical coherence tomography scans and fundus fluorescein angiography. It is noteworthy that the contralateral was not treated for 4 years. The case reveals systemic exposure of dexamethasone after intravitreal injection by demonstrating the bilateral effect after unilateral injection of intravitreal dexamethasone.

Introduction

Radiation maculopathy, a subset of significant radiation retinopathy, is progressive occlusive microangiopathy.[1] Different treatment modalities have been tried so far including focal laser photocoagulation, photodynamic therapy (PDT), intravitreal triamcinolone, and intravitreal anti-vascular endothelial growth factor agents with variable success results.[12]

Ozurdex (Allergan Inc., Irvine, CA, USA), a sustained-release intravitreal implant of 0.7 mg dexamethasone, provide controlled release of drug at a stable rate over a long period.[3] The implant has been approved for the treatment of macular edema following branch and central retinal vein occlusion, diabetic retinopathy, and noninfectious posterior uveitis.[4] However, it has been used as an off-label treatment for recalcitrant radiation maculopathy.[5]

Here, we report successful treatment of bilateral recalcitrant radiation maculopathy with intravitreal dexamethasone implant which was refractory to intravitreal bevacizumab treatment. In this case report, intravitreal dexamethasone showed good efficacy regarding central macular thickness (CMT) reduction and best-corrected visual acuity (BCVA) improvement in the injected eye, as well as good anatomical and functional outcomes in the contralateral eye (CMT and BCVA) which was not treated for 4 years. To the best of our knowledge, this advantageous effect of intravitreal dexamethasone in the contralateral eye in radiation maculopathy has not been described in the literature so far.

Case Report

A 58-year-old male patient presented to us with chief complaints of decreased vision in both eyes in 2007. His medical history revealed the diagnosis of primary central nervous system lymphoma in 2006 for which he was treated with methotrexate in combination with whole-brain radiation therapy (50 Gy in 25 fractions). He had no other systemic diseases. On presentation, in October 2007, his BCVA was 6/18 and 6/9 in the right eye and left eye, respectively. Fundus examination revealed hard exudates at the macula and cystoid macular edema (CME). Fundus fluorescein angiography revealed multiple microaneurysms with surrounding ischemia (early phases) and leakages corresponding to microaneurysms (late phases). Optical coherence tomography (OCT) confirmed the presence of CME with CMT of 356 μm and 320 μm in the right and left eyes, respectively. The temporal onset of the maculopathy in relation to the radiotherapy and the radiation dose delivered confirmed the diagnosis of radiation maculopathy.

The patient was treated with intravitreal bevacizumab (Avastin, Genentech Inc., South San Francisco, CA, USA) injections, two each in the right eye and left eye over 2 months. Despite the treatment, his BCVA remained 6/18 (right eye) and 6/9 (left eye). OCT showed a reduction of CME in both eyes. As there was no improvement in vision, the patient refused for further treatment. Eight months later, the patient again presented with the complaint of diminished vision. His BCVA dropped down to 5/60 and 6/18 in the right eye and left eye, respectively. There was an increase in hard exudates and macular fluid. With OCT, CMT was found to be 550 μm and 310 μm in the right and left eyes, respectively. He was treated with six intravitreal bevacizumab injections in the right eye and one in the left eye over next 2 years. His BCVA remained static at 5/60 and 6/12 in the right eye and left eye, respectively. Low-fluence PDT was performed to the left eye given subretinal hemorrhage in the left fovea probably due to an atypical CNVM associated with radiation retinopathy.[678] Visual acuity was maintained at 6/12 in the left eye postPDT. The CMT remained at 350 μm in the right eye and 305 μm in the left eye.

By August 2011, the patient had deteriorated to a vision of 3/60 in the right eye due to significant cataract. He underwent cataract surgery in the right eye following which his BCVA improved back to 5/60. However, the ischemic changes in the retina and macular edema persisted preventing any further improvement in vision. Even after four more intravitreal bevacizumab injections in the right eye, the patient's vision remained static at 5/60. The CMT was 320 μm in the right eye and 310 μm in the left eye [Figure 1a and b]. As there was recalcitrant macular edema and no improvement of vision even after 12 intravitreal injections of bevacizumab in the right eye [Figure 2a, b, e and f], the treatment was changed to intravitreal dexamethasone (Ozurdex, Allergan Inc., Irvine, CA, USA) implant in June 2012. The vision of the right eye improved to 6/24 and CMT reduced to 260 μm after the first injection of intravitreal dexamethasone in the right eye. After the second injection, the vision improved to 6/18 in the right eye with CMT of 259 μm. The vision in the left eye also showed improvement from 6/18 to 6/12 after the second injection, but with minimal reduction in CMT (294μm). He underwent two more Ozurdex injections in the right eye in the next 1 year. After the fourth injection, the CMT in both eyes showed marked reduction to 182 μm in the right eye and 192 μm in the left eye. The vision had improved to 6/18 in the right eye and 6/9 in the left eye. Clinically, there was disappearance of hard exudates with reduction of macular edema and microaneurysm [Figure 2c and d] which was confirmed with FFA [Figure 2g and h] and OCT [Figure 1c and d]. On his last follow-up in August 2014 (8 months after the fourth injection), the patient's BCVA was maintained at 6/18 in the right eye and 6/9 in the left eye with and normal foveal contour and no edema as confirmed on OCT.

Figure 1

Optical coherence tomography scans (a and b) before implantation intravitreal dexamethasone; (c and d) after implantation of intravitreal dexamethasone in the right eye showing a reduction in cystoid edema and normalization of foveal contour in both eyes

Figure 2

(a and b) Clinical picture and (e and f) fluorescein fundus angiography before implantation intravitreal dexamethasone showing hard exudates; (c and d) Clinical picture and (g and h) fluorescein fundus angiography after implantation of intravitreal dexamethasone in the right eye showing disappearance of the hard exudates in both eyes

Discussion

Radiation retinopathy is often used to broadly encompass all retinal vascular changes, including ischemic and/or proliferative retinopathy and maculopathy.[2] Radiation maculopathy is diagnosed when there is occurrence of retinal capillary bed changes, clinical retinal edema, exudation, nerve fiber layer infarction, or vascular sheathing within 3 mm of foveola.[2]

We opted for intravitreal bevacizumab when the patient was diagnosed radiation maculopathy. The patient was treated on pro re nata basis due to the cost constraint. As shown in Figure 3, we did not achieve significant anatomical and functional improvement in spite of extensive treatment with intravitreal bevacizumab over 6 years. Hence, we considered intravitreal dexamethasone as salvage treatment for radiation maculopathy. We observed dramatic improvement in visual acuity (right eye) after the first injection of intravitreal dexamethasone due to the resolution of macular edema [Figure 3]. Tarmann et al. and Bui et al. have also reported that intravitreal dexamethasone implant can be considered as an alternative treatment strategy for treating radiation maculopathy refractory to the previous intravitreal bevacizumab treatment.

Figure 3

Graph of (a) average central macular thickness and (b) vision from 2007 to 2014

The case also demonstrates the beneficial effect of intravitreal dexamethasone on the uninjected contralateral eye. There was a consistent response in the contralateral eye (left eye) with progressive improvement in visual acuity, CMT and hard exudates over 2 years when the patient was being treated with intravitreal dexamethasone injections in the right eye only. The effects of intravitreal preparations, such as bevacizumab, ranibizumab, and triamcinolone, on the contralateral eye, have been reported in the literature.[9101112] However, extensive literature search showed only one case report of improvement of contralateral eye function (without injections) followed by intravitreal dexamethasone in clinically significant diabetic macular edema.[13] The exact mechanism by which dexamethasone affects the contralateral eye has not been elucidated. The author postulated that the corticosteroid molecule may escape from the injected eye into systematic circulation and consequently enter contralateral eye where it counteracts pathological process and produces a beneficial effect.[13] Although this fellow eye effect is advantageous, it may raise safety issues as dexamethasone has various systemic and ocular adverse reactions.

Conclusion

This case report reveals the effectiveness of intravitreal dexamethasone implant in the treatment of radiation maculopathy in a patient who was recalcitrant to multiple intravitreal bevacizumab injections. It also points to the systemic exposure after intravitreal dexamethasone by revealing the bilateral effect after unilateral injection of intravitreal dexamethasone.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/ have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

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Conflicts of interest

There are no conflicts of interest.