Current treatments and preventive strategies for radiation retinopathy.

REVIEW URRENT C OPINION

Current treatments and preventive strategies for radiation retinopathy David Reichstein

Purpose of review Radiation retinopathy remains a devastating cause of visual morbidity in patients undergoing radiation for globe, orbit, and head and neck malignancies. This review discusses the recent efforts of several authors to treat radiation retinopathy once it has developed and efforts to prevent its development with early aggressive management. Recent findings Intravitreal anti-vascular endothelial growth factor agents and intravitreal steroid agents have been used to successfully treat radiation-induced macular edema and neovascular events secondary to radiation retinopathy. The visual outcomes, however, have varied. Recent work has been directed towards prevention of radiation retinopathy prior to its development. This has been done with preventive scatter laser and intravitreal bevacizumab therapy. Effective customization of radiation dose to the tumor has also reduced some collateral radiation damage. Preventive vitrectomy and silicone oil placement at the time of plaque brachytherapy may shield normal ocular structures from radiation injury. Summary Radiation retinopathy remains a major source of visual morbidity following radiotherapy for malignancies. Promising, albeit unproven, new therapies and preventive efforts may ameliorate the negative visual outcomes. Keywords radiation maculopathy, radiation optic neuropathy, radiation retinopathy

INTRODUCTION Radiation retinopathy remains a devastating cause of visual morbidity in patients undergoing radiotherapy for malignancies involving the globe, orbit, head, and neck. Radiation injury to the posterior segment involves microangiopathy of the small retinal vessels secondary to endothelial cell loss and capillary closure [1–3]. This vascular injury leads to predictable cascade of events that ultimately leads to macular edema (radiation maculopathy), optic neuropathy, and neovascularization [4,5]. Figure 1 demonstrates three examples of posterior segment complications of radiation therapy. Treatments of radiation retinopathy have been directed towards reduction of macular edema and neovascular events [6]. However, the results of therapies, whether with laser, steroids, or, more recently, antivascular endothelial growth factor agents, have been unpredictable. This article will review the efforts of authors who have treated the posterior segment morbidities of radiation. We will also outline more recent efforts of authors who have

attempted to prevent radiation retinopathy and its sequelae prior to its development.

LASER THERAPY Neovascularization secondary to radiation retinopathy can be controlled with laser therapy. Chaudhuri et al. [7] reported a case of neovascular radiation retinopathy that demonstrated complete regression of the new vessels within 2 weeks following pan retinal photocoagulation. Kinyoun et al. [8] then demonstrated complete resolution of radiationinduced neovascularization in 91% of 14 eyes following pan retinal photocoagulation. Photocoagulation technique was similar to that used in the Tennessee Retina, 345 23rd Ave, N #350, Nashville, TN 37203, USA Correspondence to David Reichstein, MD, Tennessee Retina, 345 23rd Ave, N #350, Nashville, TN 37203, USA. Tel: +1 615 983 6000; e-mail: [email protected] Curr Opin Ophthalmol 2015, 26:157–166 DOI:10.1097/ICU.0000000000000141

1040-8738 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.

www.co-ophthalmology.com

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Retinal, vitreous and macular disorders

KEY POINTS Radiation retinopathy, radiation optic neuropathy, and radiation-induced macular edema remain devastating sources of vision loss following radiation therapy for globe, and head and neck malignancies. Early treatments with laser therapy for radiation-induced macular edema had varying efficacies, but newer treatments with anti-VEGF therapies and steroid-based therapies may have remarkable results on retinal thickness and visual acuity. Preventive management with scatter laser and antiVEGF therapy for radiation-induced macular edema may reduce retinal swelling and improve visual acuity in the long term following radiation therapy.

ETDRS (500-micron burns scattered throughout the retinal periphery). The mean follow-up time for these eyes was 75 months. Unfortunately, it was seen that the prognosis for vision in these eyes was poor. Among the 14 eyes, 86% treated with pan retinal photocoagulation for proliferative disease had a final vision of 20/200 or worse [8]. Radiation retinopathy can cause capillary leakage with resultant macular edema. Macular edema involving the fovea is a major source of visual morbidity in patients with radiation retinopathy. Clinicians in the 1980s used focal laser therapy to treat radiation-induced macular edema. Kinyoun et al. [9] reported that focal laser was successful in preventing further vision loss in five eyes with macular edema. Axer-Siegel et al. [10] demonstrated that macular edema and exudates could be resolved with laser, but visual outcomes were only marginally improved. Kinyoun et al. demonstrated improvement in mean visual acuity following focal laser therapy for macular edema. They found that at final examination, visual acuity improved in 67% of eyes, and 50% of the eyes had complete resolution of macular edema [11]. Kinyoun [12] also demonstrated that with a mean follow-up of 113 months, eyes treated with macular focal laser had improved vision in comparison to untreated patients, when rates of optic neuropathy, macular ischemia, diabetes mellitus, and systemic hypertension were controlled. In contrast, Hykin et al. [13] found that focal laser led to a mild improvement in vision at 6 months following focal laser for radiationinduced macular edema, but there was no visual acuity difference at 2 years between patients who received focal laser therapy and matched untreated controls. Studies of macular laser for radiationinduced macular edema suffered from inconsistent 158


laser parameters and inconsistent follow-up. Patients with macular edema also have a vast range of ocular comorbidities including macular ischemia, optic neuropathy, cataract, and neovascularisation, making comparison between studies of focal laser difficult.

NONLASER THERAPIES Treatment of radiation retinopathy with hyperbaric oxygen has not been pursued extensively and results have been mixed. Stanford reported a case of severe radiation retinopathy following external beam radiation and hyperbaric oxygen for a frontal lobe meningioma. The authors postulated that the severity of retinopathy may actually have been worsened by hyperbaric oxygen [14]. In contrast, Borruat et al. [15] described a case of radiation-induced optic neuropathy causing a visual field defect 17 months following radiation of a left maxillary melanoma. The patient received 35 episodes of hyperbaric oxygen therapy and showed resolution of the visual field defect. The authors postulated that hyperbaric oxygen enhanced fibroblastic activity, collagen synthesis, and induced neovascularization, which led to reoxygenation of the damaged tissues [15]. The patient, however, also received systemic corticosteroids, which also can improve optic nerve swelling [16]. Radiation retinopathy following plaque brachytherapy can improve following hyperbaric oxygen without steroid administration, however [17]. Reports of radiation retinopathy treated with hyperbaric oxygen have waned recently. Gupta et al. [18] described a case of radiation retinopathy following whole brain radiotherapy for a temporal lobe medulloblastoma. The patient experienced visual acuity improvement following 8 months of pentoxifylline treatment. Pentoxifylline has the ability to increase blood flow by decreasing blood viscosity and increasing erythrocyte flexibility [18]. Pentoxifylline has not been studied in large series of radiation retinopathy, however.

PHOTODYNAMIC THERAPY Macular subretinal neovascularization complicating radiation retinopathy has been observed by Spaide et al. [19]. They reported a case of advanced radiation retinopathy with severe choroidal nonperfusion. Subretinal vascular dilations with resultant subretinal fluid, macular edema, and lipid were noted [19]. It is in similar cases that photodynamic therapy (PDT) may be effective. PDT is a two-step process in which systemic infusion of verteporfin is followed by irradiance of a 689-nm laser. Verteporfin Volume 26 Number 3 May 2015


Treating and preventing radiation retinopathy Reichstein

(a)

(b)

(c)

(d)

(e)

(f)

(g)

FIGURE 1. Three patients with posterior segment complications of radiation. (a) Radiation optic neuropathy developed 2 years following stereotactic radiotherapy of a choroidal metastasis. Note the regressed metastatic lesion involving the macula and optic nerve. Severe optic nerve swelling and disc hemorrhage occurred as a result of radiation optic neuropathy. (b) Improved optic nerve swelling and improved disc hemorrhage 1 month following intravitreal bevacizumab. Despite improved disc appearance, visual acuity remains finger counting. (c) Radiation retinopathy 5 years following plaque brachytherapy for a choroidal melanoma superotemporal to the optic nerve head. Note the regressed choroidal melanoma, macular cotton wool spots, and macular telangiectasia. An epiretinal membrane has also formed. (d) OCT of patients in (c) demonstrating lack of macular edema and epiretinal membrane. (e) Regressed juxtapapillary choroidal melanoma with radiation retinopathy and macular edema. A branch retinal vein occlusion has occurred. Note macular edema, cotton wool spots, multiple dot blot hemorrhages in the macula. (f) OCT demonstrating macular edema at the onset of severe vision loss. (g) OCT demonstrating reduced macular edema following three intravitreal injections of ranibizumab.

binds to the serum lipoproteins which are preferentially bound in choroidal neovascular membranes [20]. Bakri and Beer [21] reported a case of an

extrafoveal predominantly classic lesion of choroidal neovascularization at the edge of a laser scar placed for macular edema. Following three PDT treatments,




159


there was resolution of neovascularization and visual acuity of 20/20 [21]. Lee et al. [22] have demonstrated that idiopathic subretinal neovascularization can also be treated by a single session of PDT. Interestingly, Bakri and Beer [23] have demonstrated that PDT can ameliorate macular edema even in the absence of subretinal neovascularization. They hypothesized that verteporfin is taken up selectively in damaged blood vessels and consequently there is decreased vascular leakage after PDT. They admit that the mechanism for reduction in macular edema is unclear.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY Vascular endothelial growth factor (VEGF) and other inflammatory and vasculogenic factors have been implicated in the pathogenesis of radiationinduced macular edema and neovascularization [24]. For this reason, multiple authors have attempted treatment of radiation-induced macular edema, radiation-related neovascularization, and radiation optic neuropathy with anti-VEGF therapy. Mason et al. [25] demonstrated that a single injection of bevacizumab reduced mean foveal thickness and improved mean visual acuity 6 weeks after injection in patients with macular edema following plaque brachytherapy. Not surprisingly, 4 months following injection, mean visual acuity returned to pretreatment levels and foveal thickness increased [25]. Gupta and Muecke [26] demonstrated that the effect of a single injection of bevacizumab on macular edema 2 weeks after injection differed based upon the age of the patient and the duration of macular edema prior to treatment. Patients of older age and those with long-standing macular edema prior to treatment had less treatment effect [26]. Finger and Chin [27] demonstrated that injections of bevacizumab every 6–8 weeks following diagnosis of retinopathy improved or stabilized visual acuity in all treated patients with a mean follow-up of 4.7 months following first injection. They reported that continued treatment up to 18 months following initial injection could improve or stabilize visual acuity in the majority of the treated patients [28]. Studies have demonstrated that the treatment effect of a single treatment of bevacizumab could improve foveal thickness and visual acuity, whether the radioactive isotope utilized was iodine-125, palladium-103, or ruthenium-106 [26–29]. Shah et al. [30] demonstrated that prompt treatment of radiation maculopathy at the first signs of SD-OCT change with multiple injections of 160


bevacizumab could improve or stabilize visual acuity up to 54 months following initial treatment. They reported that 51% of patients had final visual acuity 20/50 or better. In contrast Mashayekhi et al. [31] demonstrated that four monthly injections of bevacizumab in patients with macular edema following plaque brachytherapy demonstrated decreased retinal swelling in 56% of patients, but vision improved in only 42% of the treated eyes. Why there is a variable treatment effect in patients with macular edema following bevacizumab treatment is unclear. Clearly, there is variability in the treatment regimens and follow-up times between several of the initial studies. An initial effect of bevacizumab followed by a resistance to its effects in some patients has also been described [32]. Variability in patient’s anti-VEGF requirements has been observed as well. Finger and Chin [33] demonstrated excellent response to 0.5 mg ranibizumab therapy in patients with macular edema in 2010. Later though, they found that some patients were recalcitrant to standard dose therapy. Among the recalcitrant patients, 70% had stable or improved visual acuity following monthly highdose (2.0 mg) ranibizumab therapy [34]. Anti-VEGF therapy is effective when radiation maculopathy is induced by external beam radiation as well. Gondo et al. [35] reported that a single treatment of bevacizumab improved visual acuity and reduced macular thickness in a patient who received external beam radiation for maxillary sinus cancer. Subrayan et al. [36] demonstrated a variable response in five patients who had radiationinduced macular edema following treatment of nasopharyngeal carcinoma. Three eyes demonstrated reduction in foveal thickness and improvement in vision, two eyes demonstrated worsened foveal thickness and decreased vision, and two eyes demonstrated worsened visual acuity despite improvement in foveal thickness [36]. Finger and Mukkamala [37] demonstrated variable effects of repeated bevacizumab on visual acuities of four eyes receiving therapy for macular edema secondary to external beam radiation of maxillary carcinoma, intraocular lymphoma, and adenoid cystic carcinoma of the orbit. The variable efficacy was likely secondary to the differing foveal exposures of the globe in different treatment regimens [37]. Jutley et al. [38] demonstrated excellent response to ranibizumab in a patient with radiation maculopathy following stereotactic radiotherapy for optic nerve meningioma who had previously demonstrated tachyphylaxis to bevacizumab. This indicated that some patients could respond to Volume 26 Number 3 May 2015



Ranibizumb, 0.5 mg

Bevacizumab, 1.25 mg q 4–8 weeks injections

Bevacizumab, 1.25 mg Single injection

Bevacizumab, 1.25 mg q 6–8 weeks injection

Ranibizumab, 0.5 mg

Bevacizumab, 1.25 mg 1–17 injections q 2–4months

Finger and Chin, 2010 [33]

Finger and Mukkamala, 2011 [37]

Gondo et al., 2011 [35]


Jutley et al., 2012 [38]

Shah et al., 2012 [30]

7 PRN injections

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Plaque brachytherapy

Stereotactic

Plaque brachytherapy

External beam therapy

External beam therapy


Proton beam irradiation


Yeung et al., 2010 [40] 4 monthly injections followed by PRN therapy

Macular edema

Macular edema

Macular edema

Optic neuropathy

Radiation injury type

21

5

1

6

10

1

1

Patients (#)

Macular edema

Macular edema

Optic neuropathy

Macular edema

Macular edema

Macular edema

7–9 months

1–12 months

2–18 months

2–24 weeks

2 months

2–8 months

4 months

1 month

5 months

Length of follow-up

159

1

14

1

1–54 months

13 months

4–39 months

12 months

4 eyes in 15–33 months 3 patients

5

Iris neovascularization 4

Macular edema

Macular edema

Stereotactic radiotherapy Vitreous hemorrhage



Arriola-Villalobos et al., 2008 [39]






Finger, 2008 [28]


Mason et al., 2007 [25]




Ziemssen et al., 2007 [29]


Radiotherapy type

Gupta and Muecke, Bevacizumab, 1.25 mg 1–2 injections 2008 [26]


Finger, 2007 [42]

Treatment regimen

Intravitreal agent, dose

Author, year


(Continued )

51% of patients maintain 20/50 or better

Decreased macular swelling and improved visual acuity following tachyphylaxis to bevacizumab

Improved optic nerve swelling in all patients, 9 patients with stable or improved vision

Decreased macular swelling and improved visual acuity

Improved visual acuity in 3 eyes

Decreased edema and improved visual acuity in all patients

Regression of NVI in all patients, recurrence of NVI in 1 patient

Improved or stable vision in 86% of patients

Reduction of macular edema in two patients with recent swelling

Decreased vitreous hemorrhage and reduction of NV

Decreased macular swelling, improved or stabilized visual acuity in all patients

Decreased macular swelling at 1 month with recurrence at 4 months

Decreased macular swelling and improved visual acuity

Improved nerve swelling and visual acuity

Results

Table 1. Previously published reports of antivascular endothelial growth factor agents for radiation-induced retinopathy, maculopathy, and optic neuropathy


161

162

Decreased edema in 56% of patients and improved VA in 42% of patients

STEROID THERAPY

Works not directly referenced in the text are appearing in bold in the left hand column.

Bevacizumab, 1.25 mg Monthly injection 4 Mashayekhi et al., 2014 [31]


Bevacizumab, 1.25 mg q 4 months injection External beam therapy Montero et al., 2014 [41]


ranibizumab after they had developed resistance to bevacizumab [38]. Anti-VEGF therapy appears effective in reducing the effects of radiation-related neovascularization as well as radiation maculopathy. Arriola-Villalobos et al. [39] demonstrated improvement of neovascularization in a patient who developed severe retinal neovascularization following stereotactic radiotherapy for adenoid cystic carcinoma. Neovascularization in this case improved more rapidly following bevacizumab therapy than following pan retinal photocoagulation [39]. Yeung et al. [40] reported that bevacizumab reduced iris neovascularization in four eyes following proton beam irradiation for choroidal melanoma. Iris neovascularization recurred in all patients within 12 months, however [40]. Lastly, Montero et al. [41] reported that recurrent vitreous hemorrhage secondary to proliferative radiation retinopathy could be reduced with recurrent bevacizumab therapy. Table 1 outlines recent published work on antiVEGF therapies for radiation retinopathy, radiation maculopathy, and radiation optic neuropathy.

4–6 months 36 Macular edema

6 months following Recurrent hemorrhage following last injection repeated injections 1 Vitreous hemorrhage

70% with stable or improved visual acuity despite failure to standard dose therapy 10 Recalcitrant macular edema Monthly injection Ranibizumab, 2.0 mg Finger and Chin, 2013 [34]

External beam therapy Bevacizumab, 1.25 mg Monthly injection Subrayan et al., 2013 [36]

External beam or plaque

12 months

7 eyes of 6–24 months 5 patients Macular edema

Variable response of macular edema and visual outcome

Variable efficacy of bevacizumab injections – all ultimately responsive to triamcinolone Multiple injections of bevacizumab followed by steroid therapy 5 macular edema Plaque and external beam Bevacizumab, 1.25 mg 1–2 injections Bakri and Larson, 2013 [32]

Table 1 (Continued)

Treatment regimen

Radiotherapy type Intravitreal agent, dose Author, year

Length of follow-up Patients (#) Radiation injury type

Results


Shields et al. [44] demonstrated that radiation maculopathy following brachytherapy for choroidal melanoma could be treated with intravitreal triamcinolone. They reported that a single intravitreal injection of 4.0 mg of triamcinolone acetonide could stabilize or improve visual acuity in 91% of patients 1 month following injection. However, only 45% of patients retained stable visual acuity 6 months following injection [44]. Among them, 10% also developed persistent glaucoma and cataract. Triamcinolone has been coupled with bevacizumab to treat radiation maculopathy. Shah et al. [45] reported stabilization of vision with combined triamcinolone and bevacizumab injection at a mean follow-up of 45.5 months following the development of radiation maculopathy. They found that only 5% of the patients required intraocular pressure (IOP) medications following treatment [45]. More recently, several groups have demonstrated beneficial effects of an intravitreal dexamethasone 0.7-mg implant on radiation-induced macular edema. Russo et al. [46] reported on a single patient who developed macular edema resistant to bevacizumab injection. This patient demonstrated improved visual acuity and decreased macular edema 1 month following dexamethasone implantation. The effects persisted at 5-month follow-up [46]. Baillif et al. [47] reported on five cases of macular edema following cobalt-60 plaque Volume 26 Number 3 May 2015



brachytherapy treated with dexamethasone implant. They reported a modest but sustained improvement in visual acuity and reduced macular edema 5 months following treatment. One patient developed sustained increase in IOP [47]. Tarmann et al. [48] found similar results in four patients with macular edema following plaque brachytherapy or gamma knife therapy. Each of these four patients had failed therapy with bevacizumab injection. All patients demonstrated decreased macular edema and two developed sustained improvement in visual acuity up to 17 weeks following dexamethasone implant injection [48]. The proposed methods of function for improvement in macular edema following steroid therapy are myriad. Some authors posit that steroids reduce the osmotic swelling of Muller’s cells, leading to improved functionality and reduction in macular edema [46]. Others have proposed that intravitreal steroids stabilize endothelial cell tight junctions, prevent leukocyte migration, and inhibit synthesis of prostaglandins, pro-inflammatory cytokines, and VEGF [47].

Table 2 outlines recent published work on steroid therapies for radiation retinopathy, radiation maculopathy, and radiation optic neuropathy.

PREVENTIVE EFFORTS Recent efforts have been directed towards prevention of radiation retinopathy and maculopathy. One focus of efforts has been efficient customization of radiation to the tumor. Murray et al. [49 ] reported that small and medium-sized choroidal melanomas could be controlled similarly when radiation was dosed to the apex of the tumor or to a prescription point of 5.0 mm. They demonstrated that those receiving radiation to 5.0 mm developed radiation retinopathy, radiation optic neuropathy, and visually significant cataract more often than those radiated to the apex of the tumor [49 ]. Finger and Kurli [50] demonstrated that sector laser photocoagulation placed over the tumor and the surrounding 2–3 mm around the tumor following plaque brachytherapy could prevent the development of macular edema. They found that of &&

&&

Table 2. Previously published reports of intravitreal steroid agents for radiation retinopathy, maculopathy, and optic neuropathy Author, year

Steroid agent, dose

Treatment regimen

Radiotherapy type

Radiation injury type

Shields et al., 2005 [44]

Triamcinolone acetonide, 4 mg

Single injection

Plaque Macular brachytherapy edema

Shields et al., 2006 [16]

Triamcinolone acetonide, 4 mg

Single injection

Russo et al., 2012 [46]

Dexamethasone implant, 0.7 mg

Single injection

Shah et al., 2013 [45]

Baillif et al., 2013 [47]

Patient Length of (#) follow-up Results 6 months

Visual acuity stable or improved in 91% of patients at 1 month and 45% in 6 months

Plaque Optic 9 brachytherapy neuropathy

6–19 months

visual acuity stable or improved in 7 patients, disk edema improved in 9 patients at mean follow-up 11 months


1

5 months

decreased retinal swelling and improved visual acuity

Combination 1–6 injections Plaque Macular triamcinolone triamcinolone, brachytherapy edema acetonide, 4 mg 1–26 injections and bevacizumab, bevacizumab 1.25 mg

25

10–54 months

Stable mean visual acuity at final follow-up; 36% with final vision 20/50 or better

Dexamethasone implant, 0.7 mg

Tarmann et al., Dexamethasone 2014 [48] implant, 0.7 mg

31

1–2 injections


5

2–9 months

Stable or improved visual acuity in all patients 2 months after, repeat injection required at 5 months for two patients

Single injection


4

14–17 weeks

Decreased retinal swelling in all patients at 2 weeks, but increased at final follow-up in all patients, persistent visual acuity improvement in 1 patient




163


16 patients treated with preventive laser, only 1 patient developed subsequent macular edema [50]. Materin et al. [51 ] demonstrated that sector laser photocoagulation in conjunction with sub-tenon triamcinolone injection 4 months following plaque brachytherapy led to a low number of patients developing macular edema at 12 and 24 months after radiation. These results indicate that some macular edema, specifically that driven by inflammation and VEGF, might be preventable with early intervention. Accordingly, Shah et al. [52 ] demonstrated that intravitreal bevacizumab injected at plaque removal and every 4 months following plaque could reduce rates of macular edema and poor visual acuity 2 years after plaque brachytherapy. Silicone oil placement at the time of plaque placement may reduce ocular radiation dose and consequently may reduce the severity of radiation retinopathy. Ahuja et al. [53 ] demonstrated in vitro &&

&&

&&

that silicone oil reduced the ocular radiation dose compared with water. They then performed plaque brachytherapy with pars plana vitrectomy and silicone oil placement at the time of plaque in three patients. They noted that in 10–24-month follow-up, no patient developed radiation retinopathy, implying that silicone oil could potentially shield ocular structures from the effects of radiation [53 ]. McCannel and McCannel [54] compared 20 consecutive patients who underwent concurrent I-125 plaque brachytherapy and vitrectomy with silicone oil with control patients who underwent plaque brachytherapy alone. They found that patients with vitrectomy and oil placement had better mean visual acuity and reduced average central macular thickness. However, patients undergoing plaque, vitrectomy, and oil placement had a significantly higher incidence of metastasis [54]. &&

Table 3. Published reports of preventive interventions employed to reduce radiation retinopathy, maculopathy, and optic neuropathy Author, year

Preventive intervention

Radiotherapy type

Radiation injury to prevent Patients (#)

Finger and Kurli, Sector laser 2005 [50] photocoagulation


Macular edema

Monroe et al., 2005 [56]

Hyperfractionation

Head and neck external Radiation beam therapy retinopathy

31 of 186 with radiation 46 with retinopathy nasopharyngeal CA, 64 with paranasal sinus CA, 69 with nasal cavity CA, 7 with palate CA

Materin et al., && 2012 [51 ]

Sector laser photocoagulation and ST triamcinolone


Macular edema

29

17% with macular edema at 12 month and 24% with macular edema at 24 months

Ahuja et al., && 2012 [53 ]

Pars plana vitrectomy and silicone oil


Radiation retinopathy

3

No radiation retinopathy at 10–24 months follow-up

McCannel, 2013 [55]

Tumor endoresection


Macular edema

5

Increased macular edema in all patients, 1 patient with neovascular glaucoma

Murray et al., && 2013 [49 ]

Radiation to apex of tumor


Radiation retinopathy, radiation optic neuropathy, cataract

55

Reduced radiation retinopathy, optic neuropathy, cataract in comparison to patients treated to 5.0 mm

McCannel and McCannel, 2013 [54]

Pars plana vitrectomy and silicone oil


Macular edema

20

Reduced abnormal macular findings and retinal thickening compared to matched controls

Shah et al., && 2014 [52 ]

Intravitreal bevacizumab Plaque brachytherapy at plaque removal and q 4 months after brachytherapy

Macular edema

292

Reduced incidence of retinal swelling at 2 years compared to controls

16

Results 1 patient with macular edema

Work not cited directly in the text is appearing in bold in the left hand column.

164


Volume 26 Number 3 May 2015



McCannel [55] had also evaluated the use of postbrachytherapy tumor endoresection. The rationale behind tumor endoresection is that the irradiated tumor may result in a ‘toxic tumor syndrome’ which involves release of inflammatory cytokines, exudation from irradiated and incompetent vessels, and release of VEGF. She found that there was no reduction in radiation maculopathy following tumor endoresection in any of the four patients followed. In addition, one patient developed neovascular glaucoma [55]. Table 3 outlines recent published work on preventive efforts for radiation retinopathy, radiation maculopathy, and radiation optic neuropathy.

CONCLUSION Radiation retinopathy continues to be a major cause of vision loss following radiation of malignancies of the globe, head, and neck. We have discussed therapeutic interventions that have ameliorated the effects of retinopathy to varying levels of success including laser therapy, anti-VEGF therapy, steroid therapy, and therapies such as hyperbaric oxygen and pentoxyfylline. More recently, authors have directed therapies towards the prevention of radiation retinopathy rather than treatment after signs that radiation damage have already occurred. Although promising, more work will be required to support the use of early aggressive therapy for the prevention of radiation retinopathy. Acknowledgements We would like to thank Ms Tara Farmer for her help in preparation of the figures of this study. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Brown GC, Shields JA, Sanborn G, et al. Radiation retinopathy. Ophthalmology 1982; 89:1494–1501. 2. Brown GC, Shields JA, Sanborn G, et al. Radiation optic neuropathy. Ophthalmology 1982; 89:1489–1493. 3. Archer DB, Amoaku WM, Gardiner TA. Radiation retinopathy: clinical, histopathological, ultrastructural and experimental correlations. Eye (Lond) 1991; 5:239–251. 4. Amoaku WM, Archer DB. Fluorescein angiographic features, natural course and treatment of radiation retinopathy. Eye (Lond) 1990; 4:657– 667.

5. Archer DB, Gardiner TA. Ionizing radiation and the retina. Curr Opin Ophthalmol 1994; 5:59–65. 6. Horgan N, Shields CL, Mashayekhi A, Shields JA. Classification and treatment of radiation maculopathy. Curr Opin Ophthalmol 2010; 21:233–238. 7. Chaudhuri PR, Austin DJ, Rosenthal AR. Treatment of radiation retinopathy. Br J Ophthalmol 1981; 65:623–625. 8. Kinyoun JL, Lawrence BS, Barlow WE. Proliferative radiation retinopathy. Arch Ophthalmol 1996; 114:1097–1100. 9. Kinyoun JL, Chittum ME, Wells CG. Photocoagulation treatment of radiation retinopathy. Am J Ophthalmol 1988; 105:470–478. 10. Axer-Siegel R, Kremer I, Ben-Sira I, Weiss J. Radiation retinopathy treated with the krypton red laser. Ann Ophthalmol 1989; 21:272–274; 276. 11. Kinyoun JL, Zamber RW, Lawrence BS, et al. Photocoagulation treatment for clinically significant radiation macular oedema. Br J Ophthalmol 1995; 79:144–149. 12. Kinyoun JL. Long-term visual acuity results of treated and untreated radiation retinopathy (an AOS thesis). Trans Am Ophthalmol Soc 2008; 106:325– 335. 13. Hykin PG, Shields CL, Shields JA, Arevalo JF. The efficacy of focal laser therapy in radiation-induced macular edema. Ophthalmology 1998; 105:1425–1429. 14. Stanford MR. Retinopathy after irradiation and hyperbaric oxygen. J R Soc Med 1984; 77:1041–1043. 15. Borruat FX, Schatz NJ, Glaser JS, et al. Visual recovery from radiation-induced optic neuropathy. The role of hyperbaric oxygen therapy. J Clin Neuroophthalmol 1993; 13:98–101. 16. Shields CL, Demirci H, Marr BP, et al. Intravitreal triamcinolone acetonide for acute radiation papillopathy. Retina 2006; 26:537–544. 17. Gall N, Leiba H, Handzel R, Pe’er J. Severe radiation retinopathy and optic neuropathy after brachytherapy for choroidal melanoma, treated by hyperbaric oxygen. Eye (Lond) 2007; 21:1010–1012. 18. Gupta P, Meisenberg B, Amin P, Pomeranz HD. 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Volume 26 Number 3 May 2015


New treatments in radiation retinopathy.

New treatments for diabetic retinopathy.

Preventive treatments for breast cancer: recent developments.

Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets.

CT radiation dose: current controversies and dose reduction strategies.

[Treatments strategies for intracranial cavernomas].

Thematic Selection: Strategies of Current Drugs and Alternative Treatments for Neurodegenerative Diseases.

[Radiation retinopathy].

Radiation retinopathy.

Radiation retinopathy.

[Current treatments for corneal neovascularization].

Current screening and treatments in retinopathy of prematurity in the US.

Current status of oral cancer treatment strategies: surgical treatments for oral squamous cell carcinoma.

Current and emerging treatments for severe asthma.

Current and future treatments for hepatocellular carcinoma.

Preventive strategies against poliomyelitis.

Preventive strategies in education: history, current practices, and future trends regarding substance abuse and pregnancy prevention.

Intraocular beta-radiation for proliferative vitreo-retinopathy.

A Review of Radiation-Induced Coagulopathy and New Findings to Support Potential Prevention Strategies and Treatments.

Gavin M. Wright: current treatments for NSCLC.

Current choice of treatments for neovascular AMD.

Current strategies for mobilome research.

Current and investigational drug strategies for glioblastoma.

Current and Next Generation Portable Screening Devices for Diabetic Retinopathy.