NEW TREATMENTS IN RADIATION RETINOPATHY Marta S. Figueroa, MD, PhD,*†‡ Carolina Arruabarrena, MD,*† Marco Sales-Sanz, MD*†

Purpose: The purpose of this study was to present a case of radiation retinopathy and review of the literature on treatment options for the disease. Methods: A 28-year-old woman presented with bilateral visual acuity impairment. Four years before presentation, she was diagnosed with Hodgkin lymphoma affecting the left supraclavicular area and was treated with chemotherapy and radiotherapy, achieving complete remission. Bilateral radiation retinopathy with macular edema was diagnosed after the possibility of relapse was ruled out. Several treatments, including intravitreal bevacizumab and triamcinolone, laser photocoagulation, and surgery, have been used in an effort to resolve the macular edema and the tractional proliferative retinopathy. Result: Radiation tractional retinopathy was controlled with surgery and photocoagulation, and macular edema was resolved with a final visual acuity of 20/25 in both eyes. Conclusion: Radiation retinopathy is a complication that is devastating to the visual pathway. Historically, it has been refractory to treatment, but new options are now available. We review the most recent literature on radiation retinopathy treatment. RETINAL CASES & BRIEF REPORTS 5:171–174, 2011

From the *Division of Ophthalmology, Department of Vitreoretinal, Ramon y Cajal University Hospital, Madrid, Spain; the †Vitreoretinal Department, Vissum Madrid, Madrid, Spain; and the ‡Alcald de Henares University, Madrid, Spain.

Peripheral proliferative RR is traditionally treated with panretinal photocoagulation, but radiation maculopathy is a serious vision-threatening complication, which has no standard treatment.3 Several options have been tested with moderate success, including argon laser therapy,5,6 photodynamic therapy,7 intravitreal triamcinolone (TA),8 and bevacizumab.9–12 This article presents a case that required several therapies, and it reviews the most recent literature on RR treatment.

R

adiation retinopathy (RR) includes maculopathy, which consists of macular edema (ME) or macular ischemia, and peripheral retinopathy with edema, hemorrhages, microangiopathy, and neovascularization.1 Radiation retinopathy is a late complication of radiation therapy of ocular, nasal, or paranasal malignancies.2 The incidence of RR is influenced by a number of factors such as total dosage, daily fraction size, and preexisting medical conditions such as diabetes, hypertension, or previous chemotherapy treatment.3 One study reported its occurrence in 43.1% of 1,300 patients after 5 years of plaque radiotherapy treatment.4 Radiation retinopathy is associated with a slowly progressive angiopathy caused by endothelial cell loss, which leads to capillary occlusion with both vascular incompetence with exudation and neovascularization.1,2

Case Report A 28-year-old woman with bilateral visual acuity impairment was referred to us. Four years before presentation, she was diagnosed with Hodgkin lymphoma affecting the left supraclavicular area. She was treated with chemotherapy and cobalt-60 radiotherapy—15 sessions of 200 cGy per session for a total of 3,000 cGy—and achieved complete remission. Since treatment, there had been no evidence of tumor recurrence. On examination, visual acuity was 20/40 in the right eye and 20/ 30 in the left eye. The anterior segment and intraocular pressure were normal. Examination of the posterior segment showed exudative inferior retinal detachment with intraretinal exudation, hemorrhages, and microangiopathy (Figure 1). The fluorescein angiography showed severe retinal ischemia with retinal telangiectasias in the inferior retina of both eyes. Bilateral ME was also evident. Optical coherence tomography disclosed a macular thickness of 324 mm in the right eye and 574 mm in the left eye

The authors have no financial or commercial interests to disclose. Reprint requests: Carolina Arruabarrena, MD, Department of Vitreoretinal, Division of Ophthalmology, Ramo´ n y Cajal University Hospital, Carretera de Colmenar Viejo KM 9,100, 28034 Madrid, Spain; e-mail: [email protected]

171

172

RETINAL CASES & BRIEF REPORTS´  2011  VOLUME 5  NUMBER 2

Fig. 1. Pretreatment fundus appearance showing a bilateral exudative inferior retinal detachment with intraretinal exudation, hemorrhages, and microangiopathy.

C O L O R

(Figure 2). Once the possibility of a relapse had been ruled out, RR was diagnosed. After discussing the different therapeutic options with the patient, informed consent was obtained for intravitreal off-label injection of 1.25 mg bevacizumab in the right eye for 3 consecutive months. One month after the last intravitreal injection of bevacizumab, there were no complications but no anatomical or visual benefits. In view of these results, informed consent was obtained for the injection of 4 mg intravitreal TA in the left eye. One month after the TA injection, ME resolved but visual acuity remained unchanged. As a result of this good result in the left eye, the same treatment was recommended for the right eye in which ME resolved and visual acuity improved to 20/30 1 month after intravitreal TA (Figure 2). The only complication was an increase of intraocular pressure 1 week after the TA injections in both eyes requiring topical hypotensive treatment. Six months after the first examination, visual acuity was 20/25 in both eyes. However, proliferative retinopathy with inferior fractional retinal detachment developed in both eyes. Despite scattered laser retinal photocoagulation, the fibrovascular proliferation progressed. Surgery was proposed, and pars plana vitrectomy was performed in the right eye. The surgical procedure involved delaminating the fibrovascular proliferation, extending the peripheral laser photocoagulation to the ora serrata, and applying

C O L O R

cryotherapy to the detached inferior retina (Figure 3). Surgery in the left eye was performed 2 months later, but at that time, there was also a massive submacular exudation resulting in worsening of visual acuity to 20/70 (Figure 3). After discussing the different therapeutic options with the patient, surgical removal of the submacular exudation was performed (Figure 4) with a 39-gauge subretinal cannula (Visitec 5188, BD Medical - Ophthalmic Systems, Waltham, MA). No intra- or postoperative complication developed. After the surgery, no subfoveal exudation was evident (optical coherence tomography macular thickness = 275 mm) but visual acuity did not improve as a result of progression of the cataract. Written informed consent for phacoemulsification was obtained. Phacoemulsification was performed first in the right eye and 3 months later in the left eye. One month after phacoemulsification in the left eye, visual acuity was 20/30 in the right eye and 20/40 in the left eye, and no edema had recurred 5 months after surgery.

Discussion Several treatment strategies have been used for macular and peripheral RR, but no consensus exists about the best one. Until now, managing RR continues to be a challenge.

Fig. 2. Top, Pretreatment optical coherence tomography appearance. Left, Right eye. Right, Left eye. Middle, Pretreatment optical coherence tomography macular maps. Bottom, Resolution of ME in both eyes 1 month after intravitreal TA injection.

NEW TREATMENTS IN RR

173

Fig. 3. Left, Postoperative fundus appearance of the right eye. Right, Postoperative fundus appearance of the left eye.

Kinyoun et al5 treated 12 eyes (8 patients) with focal laser photocoagulation for radiation ME, and mean visual acuity improved from 20/100 to 20/75 by the final examination at a mean follow-up of 39 months. Visual acuity improved in eight eyes and the edema resolved in six eyes. However, Hykin et al, in a nonrandomized study comparing 19 treated eyes and 23 control subjects, reported only mild improvement after focal laser photocoagulation. Nevertheless, even these results did not persist for 2 years.6 Bakri and Beer used photodynamic therapy in a series of four patients with radiation maculopathy, but the results are difficult to analyze because one of the patients was not treated for the radiation ME itself but for the development of a choroidal membrane secondary to focal laser treatment for radiation ME. In the other three cases, only two achieved a modest improvement in visual acuity.7 The largest case series of intravitreal TA for radiation ME was reported by Shields et al.8 They studied 31 eyes and observed temporary visual acuity improvement after a single injection, but this improvement diminished during the follow-up, making repeated injections necessary to maintain the initial effect. Visual acuity

Fig. 4. Left, Massive submacular exudation. Right, Fundus appearance after surgical removal of the subfoveal exudation.

C O L O R improved by $2 lines in 68% of patients at 1 month, declining to 47% at 3 months and to 27% at 6 months. Known complications of intravitreal TA such as cataract progression and glaucoma appeared in 45% of eyes. In a similar fashion, ME and visual acuity improved in both eyes of our patient, but proliferative retinopathy progressed. Although no cataract developed after the intravitreal TA injection, intraocular pressure increased in both eyes. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits human vascular endothelial growth factor, a cytokine that has been implicated in the development of retinal neovascularization and ME in diabetic retinopathy and retinal vein occlusions. Intravitreal bevacizumab has been used off-label with good results in these diseases. Macular edema and neovascularization are also common findings in RR. Intravitreal bevacizumab has been used off-label in radiation ME for two reasons; first, because this condition has a certain similarity to diabetic ME, and second, because of the regression of radiation ME in a patient who had previously been treated with external beam radiation for a choroidal melanoma after the treatment of colorectal cancer with systemic bevacizumab.1,9,10

C O L O R

174

RETINAL CASES & BRIEF REPORTS´  2011  VOLUME 5  NUMBER 2

To date, four case series1,9–11 and two case reports12,13 have yielded favorable results of intravitreal bevacizumab for radiation ME secondary to brachytherapy for choroidal melanoma. Finger and Chin have reported two case series in the last year. The first case series consisted of 6 eyes of 6 patients who were treated with 1.25 mg intravitreal bevacizumab every 6 weeks to 8 weeks according to changes in visual acuity and macular thickness in optical coherence tomography.9 A mean of 2.8 injections was applied per patient during a mean follow-up of 4.7 months. Vision improved in two eyes and remained the same in four eyes despite ME resolution in all cases. The second case series consisted of 21 eyes of 21 patients. A mean of 3.8 injections was applied per patient during a mean follow-up of 7.8 months. Vision improved in 3 eyes, remained the same in 13 eyes, and worsened in 5 eyes.10 Mason et al1 reported 10 patients treated with a single intravitreal injection of bevacizumab. Six weeks after the injection, mean visual acuity improved from 20/100 to 20/86. Nevertheless, this mild improvement disappeared 4 months after treatment. Visual changes correlated with anatomical findings; ME resolved at 6 weeks, but this was followed by progressive deterioration to preoperative optical coherence tomography levels 4 months after the injection. No complications resulted from the injection. Both of the previously mentioned authors realized that although anatomical resolution occurred in almost all cases, only a small and temporary visual acuity improvement was achieved. They suggested that the radiationinduced capillary nonperfusion might be responsible for the minimal improvement in visual acuity. The last case series published included five patients, and only two of them showed slight visual acuity improvement after intravitreal bevacizumab injection. The authors hypothesized that only short-standing ME improves with bevacizumab.11 In our case, ME showed no resolution when treated with bevacizumab, but it did respond well to intravitreal TA, yielding substantial improvement in visual acuity. We agree with other authors that visual acuity improvement depends on the degree of macular ischemia, which was not severe in our case. Both eyes of our patient showed not only ME, but also severe inferior peripheral retinal ischemia. Despite laser panretinal photocoagulation, proliferative retinopathy with secondary fractional retinal detachment developed during the follow-up. This complication required pars plana vitrectomy to reattach the retina and to apply cryotherapy to the ischemic peripheral retina. In the left eye, because of the development of massive subretinal lipid exudation with visual

deterioration, submacular surgery was also performed. Although anatomical results were excellent, visual acuity did not improve after surgery as a result of cataract progression. In summary, radiation ME in our case did not respond to intravitreal bevacizumab. In contrast, intravitreal injection of TA was an effective treatment for radiation ME. Despite TA injection and panretinal laser photocoagulation, proliferative retinopathy developed, causing tractional retinal detachment and requiring a vitrectomy. This case illustrates the complexity of treating RR and shows that it usually requires multiple therapeutic strategies to stop its aggressive progression. Key words: bevacizumab, intravitreal triamcinolone, radiation retinopathy, radiation macular edema. References 1. Mason JO, Albert MA, Persaud TO, Vail RS. Intravitreal bevacizumab for radiation macular edema after plaque radio therapy for choroidal melanoma. Retina 2007;27:903–907. 2. Arriola-Villalobos P, Donate-Lopez J, Calvo-Gonzalez C, Reche-Frutos J, Alejandre-Alba N, Diaz-Valle D. Intravitreal bevacizumab (AvastinÒ) for radiation retinopathy neovascularization. Acta Ophthalmol Scand 2008;86:115–116. 3. Gupta A, Dhawahir-Scala F, Smith A, Young L, Charles S. Radiation retinopathy: case report and review. BMC Ophthalmol 2007;7:6. 4. Gunduz K, Shields C, Shields JA, Cater J, Freire J, Brady L. Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Arch Ophthalmol 1999;117:609—614. 5. Kinyoun JL, Zamber RW, Lawerence BS, Barlow WE, Arnold AM. Photocoagulation treatment for clinically significant radiation oedema. Br J Ophthalmol 1995;79:144–149. 6. Hykin PG, Shields CL, Shields JA, Arevalo JF. The efficacy of focal laser therapy in radiation-induced macular edema. Ophthalmology 1998;105:470–478. 7. Bakri SJ, Beer PM. Photodynamic therapy for maculopathy due to radiation retinopathy. Eye 2005;19:795–799. 8. Shields CL, Demirci H, Dai V, et al. Intravitreal triamcinolone acetonide for radiation maculopathy after plaque radiotherapy for choroidal melanoma. Retina 2005;25: 868–874. 9. Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (Avastin) for radiation retinopathy. Arch Ophthalmol 2007;125:751–756. 10. Finger PT. Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin). Int J Radiat Oncol Biol Phys 2008;70:974–977. 11. Gupta A, Muecke JS. Treatment of radiation maculopathy with intravitreal injection of bevacizumab (Avastin). Retina 2008; 28:964–968. 12. Solano JM, Bakri SJ, Pulido JS. Regression of radiationinduced macular edema after systemic bevacizumab. Can J Ophthalmol 2007;42:748–749. 13. Ziemssen F, Voelker M, Altpeter E, Bartz-Smith KU, Gelisken F. Intravitreal bevacizumab treatment of radiation maculopathy due to brachytherapy in choroidal melanoma. Acta Ophthalmol Scand 2007;85:579–580.

New treatments in radiation retinopathy.

The purpose of this study was to present a case of radiation retinopathy and review of the literature on treatment options for the disease...
421KB Sizes 2 Downloads 5 Views