Radiation retinopathy is a slowly progressive, occlusive vasculopathy characterized by microvascular changes and microaneurysm formation associated with radiation-induced endothelial damage. It is a common finding after plaque radiotherapy for choroidal melanoma, occurring in 42% of patients at 5 years.1 Proliferative radiation retinopathy develops in 7% of eyes by 10 years after plaque therapy, and high-risk factors have been found to include young age and additional transpupillary thermotherapy.2
Choroidal neovascularization associated with radiation retinopathy after plaque radiotherapy has not been commonly reported. Spaide et al3 first described an atypical choroidal neovascularization with prominent saccular dilations seen on indocyanine green angiography (ICGA). We report, to our knowledge, the first case of intravitreal polypoidal choroidal neovascularization (PCNV) documented on swept-source optical coherence tomography (SS-OCT), spectral-domain optical coherence tomography (SD-OCT), and ultrawide-field fluorescein angiography (FA).
A 30-year-old woman was diagnosed with choroidal melanoma and received treatment with I-25 plaque radiotherapy followed by transpupillary thermotherapy for an 8- × 8-mm dome-shaped choroidal melanoma located superonasal to the optic nerve 5 years prior to presentation. She experienced good regression of the tumor but developed proliferative radiation retinopathy with macular edema. She received panretinal photocoagulation in conjunction with 16 treatments of intravitreal anti–vascular endothelial growth factor (VEGF) for recalcitrant macular edema, and her visual acuity fluctuated between 20/70 and 20/100 over the course of the prior 5 years.
More recently, she presented with recurrent episodes of decreasing visual acuity (five episodes in the last year) in the affected left eye. Visual acuity was 20/200. Ophthalmoscopy findings of vitreous hemorrhage with dehemoglobinized blood suggested recurrent vitreous hemorrhage secondary to uncontrolled proliferative radiation retinopathy. Recalcitrant macular edema was also present. Visualization of new vessels at the site of the regressed choroidal melanoma and chorioretinal scarring prompted SS-OCT using the DRI OCT-1 Atlantis 3D (Topcon Medical Systems, NJ), SD-OCT with the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany), and ultrawide-field FA with the Optos 200Tx (Optos, Dunfermline, Scotland) over the area. A comparative ultrawide-field color fundus photograph taken 3 years prior showed the lack of these new vessels (Figure 1).
Ultrawide-field color fundus photographs of the left eye. (A) Color fundus photograph taken 3 years prior to presentation showing the regressed choroidal melanoma with chorioretinal scarring superonasal to the optic nerve. There is no neovascularization within the scar. Sectoral panretinal photocoagulation scars extend slightly beyond the superonasal quadrant. (B) Color fundus photograph taken at presentation showing visible new vessels (white arrow) within the site of the regressed choroidal melanoma, with chorioretinal scarring superonasal to the optic nerve. There are panretinal photocoagulation scars throughout the posterior pole in all quadrants, and dehemoglobinised vitreous hemorrhage is visible in the inferior vitreous cavity.
SS-OCT and SD-OCT imaging demonstrated ring-shaped lesions resembling that of a polyp4 lying on the surface of area of atrophied chorioretinal tissue, within the subhyaloid and intravitreal space. The posterior hyaloid was elevated from the atrophied chorioretinal wall and split into several layers by the cluster of polypoidal lesions (Figure 2; video available at http://www.healio.com/OSLIRetina).
Swept-source optical coherence tomography (SS-OCT) of the polypoidal choroidal neovasculopathic lesion. (A) Near-infrared fundus image showing areas of hyper-reflectivity corresponding to the chorioretinal scars and a hyporeflective lesion within the scar corresponding to the saccular new vessels. (B) SS-OCT B-scan taken through the green line in A, showing the polypoidal lesion sitting on the area of chorioretinal scar, devoid of retinal tissue. The posterior hyaloid is elevated and split into layers by the cluster of polyps.
Early-phase FA revealed prominent saccular dilations resembling those of PCNV in the large zone of the chorioretinal scar where there was virtually no retinal or choroidal perfusion. Late-phase FA demonstrated leakage from these saccular choroidal neovasculopathic vessels. Comparative FA images of the same area taken 3 years earlier showed the lack of these new vessels (Figures 3 and 4).
Early-phase fluorescein angiography (FA) of the left eye. (A) FA taken 3 years prior to presentation showing a large zone of chorioretinal scarring devoid of retinal and choroidal vessels. (B) FA taken at presentation showing new vessels within the scar adjacent to the edge of the perfused tissue, appearing as saccular dilations (white circle). The neovascularization arises from presumed connections to the choroidal vessels at the edge of the scar (white arrow).
Late-phase ultrawide-field fluorescein angiography of the left eye taken at presentation, showing leakage from the polypoidal choroidal neovasculopathic vessels. There are also areas of leakage seen in the peripheral temporal and nasal retina.
Spaide et al3 documented the occurrence of saccular dilations in radiation retinopathy with ICGA; however, they termed this lesion an atypical choroidal neovascularization, under the assumption that PCNV is a specific process seen in older individuals of either Asian or African heritage, unrelated to radiation. We now understand that PCNV is a nonspecific process characterized by aneurismal dilations with interconnecting channels that may occur in a variety of conditions as a form of type 1 choroidal neovascularization.4 Hence, the term PCNV is appropriate in our case, which features the appearance of both saccular choroidal neovasculopathic vessels and interconnecting channels.
This case is unique because PCNV occurring within the vitreous cavity has never before been described. SD-OCT revealed the lack of any retinal tissue in the area of antecedent plaque radiotherapy; hence, the choroidal polypoidal neovasculopathic lesion normally situated below retinal tissue and above Bruch’s membrane4 is seen sitting on the surface of the atrophied tissue and inadvertently prolapsed within the vitreous space.
In this case, radiation-induced PCNV was well-demonstrated with SD-OCT and FA. FA was able to demonstrate the retinal vasculature and lack thereof. The saccular choroidal neovasculopathic vessels were well-demonstrated in the large zone that lacked both retinal and choroidal perfusion. Also present were presumed connecting vessels to the remnant choroidal vasculature adjacent to the edge of the chorioretinal scar. ICGA was not used in this case because it would not have been able to depict the retinal vasculature as well as FA. It could perhaps be useful to reveal more classic polyps at the choroidal level within the normal tissue adjacent to the treated tumor, but this was not likely because there was no indication of leakage in this area on the FA.
Although the origin of PCNV is somewhat unclear, it has been shown that the choroidal circulation, like the retina, is profoundly affected by radiation, with partial or total loss of choroidal vessels and vascular remodeling.5 It is probable that PCNV in the present case grew in response to ischemia, possibly through mediators such as VEGF. Similar growth patterns of saccular dilations have been reported in patients treated with radiation for choroidal neovascularization.6
The differential diagnosis of retinal macroaneurysm may be considered, but this is less likely because retinal artery macroaneurysms typically occur within the first three orders of arteriolar bifurcation and have a strong association with hypertension and arteriosclerotic vascular changes.7 The dilated, saccular vessels in this case occurred in the peripheral retina of a young patient with no systemic vasculopathic risk factors, and the ischemic drive in radiation retinopathy which is responsible for the formation of neovascular vessels supports the diagnosis of PCNV.
Although a previous report of focal laser photocoagulation to the area of neovascularization has been shown to result in cessation of exudation and subretinal fluid,3 the lack of any visual benefit for this patient who has concomitant recalcitrant macular edema prompted the initial course of observation. Focal laser and intravitreal anti-VEGF injections may be considered in the event of further recurrent vitreous hemorrhage.
- Gunduz K, Shields CL, Shields JA, Cater J, Freire JE, Brady LW. Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Arch Ophthalmol. 1999;117(5):609–614. doi:10.1001/archopht.117.5.609 [CrossRef]
- Bianciotto C, Shields CL, Pirondini C, et al. Proliferative radiation retinopathy after plaque radiotherapy for uveal melanoma. Ophthalmology. 2010;117(5):1005–1012. doi:10.1016/j.ophtha.2009.10.015 [CrossRef]
- Spaide RF, Borodoker N, Shah V. Atypical choroidal neovascularization in radiation retinopathy. Am J Ophthalmol. 2002;133(5):709–711. doi:10.1016/S0002-9394(02)01331-4 [CrossRef]
- Khan S, Engelbert M, Imamura Y, Freund KB. Polypoidal choroidal vasculopathy: simultaneous indocyanine green angiography and eye-tracked spectral-domain optical coherence tomography findings. Retina. 2012;32(6):1057–1068. doi:10.1097/IAE.0b013e31823beb14 [CrossRef]
- Takahashi K, Kishi S, Muraoka K, Tanaka T, Shimizu K. Radiation choroidopathy with remodeling of the choroidal venous system. Am J Ophthalmol. 1998;125(3):367–373. doi:10.1016/S0002-9394(99)80148-2 [CrossRef]
- Spaide RF, Leys A, Herrmann-Delemazure B, et al. Radiation- associated choroidal neovasculopathy. Ophthalmology. 1999; 106(12):2254–2260. doi:10.1016/S0161-6420(99)90524-9 [CrossRef]
- Pitkanen L, Tommila P, Kaarniranta et al. Retinal arterial macroaneurysms. Acta Ophthalmol. 2014;92(2):101–104. doi:10.1111/aos.12210 [CrossRef]