Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is a rare retinal vascular condition characterized by bilateral retinal artery vasculitis, arterial macroaneurysms occurring most commonly at the optic nerve head and at bifurcations of the retinal arteries, and neuroretinitis. Macular exudation and retinal neovascularization secondary to diffuse capillary nonperfusion can lead to progressive visual loss in some patients. Two cases of primary occlusion of branch retinal arteries have been described in patients previously diagnosed with IRVAN.1,2 We report a case of a previously healthy young woman who presented with branch retinal artery occlusion (BRAO) as a presenting feature of IRVAN syndrome.
A previously healthy 36-year-old Haitian-American woman was referred in May 2009 by her optometrist due to several weeks of decreased vision and flashes of light in her right eye (OD).
On examination, best-corrected visual acuity (BCVA) was 20/25 OD and 20/20 in the left eye (OS). Confrontation visual field testing revealed a superonasal field defect OD. Dilated fundus examination (DFE) OD showed aneurysms at the optic disc with cotton-wool spots and retinal whitening (Figure 1A). DFE OS showed aneurysms at the optic disc and peripapillary hard exudates (Figure 1E). Retinal venous sheathing was apparent in both eyes (Figures 1A and 1E). Fluorescein angiography (FA) showed evidence of BRAO of the inferotemporal retinal artery OD. Both optic discs were hyperfluorescent in the late phase (Figures 1C and 1G). Spectral-domain optical coherence tomography (SD-OCT) showed an epiretinal membrane (ERM) OD and OS and thickening of the outer nuclear layer in the area of retinal whitening OD (Figures 1D and 1H). Diagnostic studies to rule out systemic diseases were within normal limits, and she was diagnosed with stage 3 IRVAN. Both eyes were initially treated with panretinal photocoagulation (PRP). Follow-up at 6 months was complicated by vitreous hemorrhage OD, which was treated with pars plana vitrectomy (PPV) and additional PRP.
Multimodal retinal imaging at the first visit in May 2009. (A) Color fundus photograph of the right eye showing cotton-wool spots (yellow arrow heads), retinal whitening, retinal vein sheathing (white arrow heads), and aneurysmal dilations at the optic disc. (B,C) Intermediate-phase and late-phase fluorescein angiography (FA) of the right eye showing evidence of a branch retinal artery occlusion of the inferior temporal retinal artery, vessel tortuosity (white arrow), and disc hyperfluorescence. (D) Spectral-domain optical coherence tomography (SD-OCT) B-scan centered on the fovea of the right eye showing an epiretinal membrane (ERM) and vitreomacular traction. (E) Color fundus photograph of the left eye showing an ERM at the macula, hard exudates in the peripapillary region (red arrow head), retinal vein sheathing (white arrow heads), and aneurysmal dilations at the optic disc. (F,G) Mid-phase and late-phase FA of the left eye showing vessel tortuosity, staining consistent with vasculitis (white arrow), and disc hyperfluorescence. (H) SD-OCT B-scan centered on the fovea of the left eye shows an ERM and vitreomacular traction.
In June 2015, she presented with acute visual decline to 20/200+1 OS. BCVA remained 20/25 OD, and examination revealed signs consistent with history of BRAO (Figures 2A and 2B). DFE OS revealed new optic disc edema and retinal whitening along the superotemporal arcade consistent with an acute BRAO (Figure 2E). Neovascularization temporal to the macula was seen on FA (Figures 2F and 2G). SD-OCT showed cystoid macular edema with a lamellar hole and ERM (Figure 2H). She was treated with prednisone during a 2-week course, and BCVA OS improved to 20/30.
Multimodal retinal imaging from June 2015 when the patient presented with an acute branch retinal artery occlusion (BRAO) in the left eye. (A) Color fundus photograph of the right eye showing retinal striae, inferior altitudinal disc pallor, gliosis of aneurysms proximal to the optic disc, stenosis in a superonasal and inferotemporal vessel, retinal vein sheathing (white arrowheads), and previous panretinal photocoagulation (PRP). (B,C) Intermediate-phase and late-phase fluorescein angiography (FA) of the right eye showing retinal ischemia with capillary nonperfusion, pruning, and tortuosity of vessels in the inferotemporal quadrant (white arrows) and shunt vessels and anastomotic vessels between superotemporal and inferotemporal circulations consistent with an old BRAO. Signs of previous PRP are visible. (D) Spectral-domain optical coherence tomography (SD-OCT) B-scan of the right eye centered on the fovea demonstrating epiretinal membrane (ERM) and thinning of the inner retina. (E) Color fundus photograph of the left eye showing dilated vessels proximal to the optic nerve head, retinal whitening along the superotemporal arcade surrounding an acute BRAO in the superior macula, peripapillary hard exudates (yellow arrows), optic disc edema, and retinal vein sheathing. (F,G) Intermediate-phase and late-phase FA of the left eye showing dilated vessels proximal at the optic nerve head, superotemporal and inferotemporal aneurysms, peripheral capillary nonperfusion, two areas of neovascularization temporally (yellow arrowheads), and superotemporal blockage of dye secondary to the retinal thickening and swelling due to an acute BRAO. Signs of previous PRP are visible. (H) SD-OCT B-scan centered on the fovea of the left eye showing cystic retinal changes secondary to a lamellar hole and an ERM.
Since the first case series by Chang et al. in 1995, IRVAN syndrome has been recognized as a distinct disease entity.3 It is seen more frequently in young, healthy individuals with a predilection toward females. No initial insult or underlying systemic condition has been clearly linked to IRVAN. A single report of a patient with IRVAN syndrome who was positive for perinuclear antineutrophil cytoplasmic antibody and another case of concurrent antiphospholipid syndrome and IRVAN have been described suggesting an underlying systemic association.4,5 However, extensive systemic investigations have not revealed a definitive underlying systemic etiology.6
The rate and extent of disease progression is highly variable but follows a predictable pattern outlined in a staging system established by Samuel and colleagues.6 In stage 1 of the disease, macroaneurysms, macular exudation, neuroretinitis, and retinal vasculitis are the only findings. Capillary nonperfusion visible on fluorescein angiography especially at the periphery defines stage 2. Posterior segment neovascularization and vitreous hemorrhage follow in stage 3. Finally, stages 4 and 5 are characterized by anterior segment neovascularization and ultimately neovascular glaucoma, respectively. The major predisposing factors for visual loss are peripheral capillary nonperfusion leading to diffuse retinal ischemia, exudative retinopathy leading to macular edema, and neovascular sequelae including vitreous hemorrhage and neovascular glaucoma.3,6,7 Later stages are associated with worsening visual function.
Although there is no clear preferred treatment, several treatment options exist to control the clinical manifestations of IRVAN syndrome. The recommended treatment for patients with IRVAN syndrome with widespread retinal ischemia is PRP.8 IRVAN syndrome may be treated medically with systemic corticosteroid therapy, but there is currently no evidence to show its efficacy in reducing vasculitis or controlling ischemia and neovascularization. Intravitreal steroid implants9,10 and anti-VEGF therapies11 are promising treatments for IRVAN. PPV is indicated for patients who present with vitreous hemorrhage secondary to IRVAN.
We report a patient presenting with BRAO who was later diagnosed with IRVAN syndrome based on the six diagnostic criteria described by Chang et al.3 The patient's initial presentation was consistent with stage 3 IRVAN syndrome, which was confirmed by fundus and angiographic evidence of posterior segment neovascularization and vitreous hemorrhage. As such, she was treated with PRP and PPV. Her course was consistent with the findings of Samuel et al., who showed that most patients treated with PRP at this stage maintained stable visual acuity.6 There is evidence that PRP is most effective in maintaining stable vision and preventing disease progression if initiated early in the disease process, upon the first angiographic sign of widespread retinal nonperfusion and prior to the development of retinal neovascularization.6
BRAO is more common in IRVAN after laser photocoagulation of macroaneurysms;3,12 for this reason, previous studies have advised against direct laser of the macroaneurysms.6 However, BRAO is an unusual presenting symptom of IRVAN syndrome. To our knowledge, there are no definitive studies looking at why patients with IRVAN do not present more commonly with BRAO. We theorize that the location of macroaneurysms at the junction of the retinal artery tree might make it prone to spontaneous thrombosis. Nonetheless, IRVAN syndrome is a very rare disease, and more data and studies are needed to have a better understanding of the pathophysiology.
In conclusion, this case represents a growing subset of patients in the literature who have branch retinal vasculature occlusions on initial presentation or early in the disease course. Although IRVAN was first described and tends to be thought of as an obliterative disease of small retinal vessels, this group of patients suggests that damage to the larger vessels may be a previously unrecognized aspect of the disease process.
- Terrada C, Dethorey G, Ducos G, Lehoang P, Bodaghi B, Souied EH. Spontaneous branch artery occlusion in idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis syndrome despite panretinal laser photocoagulation of widespread retina nonperfusion. Acta Ophthalmol. 2011;89(6):e542–e543. doi:10.1111/j.1755-3768.2010.01972.x [CrossRef]
- Venkatesh P, Verghese M, Davde M, Garg S. Primary vascular occlusion in IRVAN (idiopathic retinal vasculitis, aneurysms, neuroretinitis) syndrome. Ocul Immunol Inflamm. 2006;14(3):195–196. doi:10.1080/09273940600657710 [CrossRef]
- Chang TS, Aylward GW, Davis JL, et al. Idiopathic retinal vasculitis, aneurysms, and neuro-retinitis. Ophthalmology. 1995;102(7):1089–1097. doi:10.1016/S0161-6420(95)30907-4 [CrossRef]
- Nourinia R, Montahai T, Amoohashemi N, Hassanpour H, Soheilian M. Idiopathic retinal vasculitis, aneurysms and neuroretinitis syndrome associated with positive perinuclear antineutrophil cytoplasmic antibody. J Ophthalmic Vis Res. 2011;6(4):330–333.
- Kurz DE, Wang RC, Kurz PA. Idiopathic retinal vasculitis, aneurysms, and neuroretinitis in a patient with antiphospholipid syndrome. Arch Ophthalmol. 2012;130(2):257–258. doi:10.1001/archopthalmol.2011.1363 [CrossRef]
- Samuel MA, Equi RA, Chang TS, et al. Idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis (IRVAN): New observations and a proposed staging system. Ophthalmology. 2007;114(8):1526–1529.e1. doi:10.1016/j.ophtha.2006.11.014 [CrossRef]
- Rouvas A, Nikita E, Markomichelakis N, Theodossiadis P, Pharmakakis N. Idiopathic retinal vasculitis, arteriolar macroaneurysms and neuroretinitis: Clinical course and treatment. J Ophthalmic Inflamm Infect. 2013;3(1):1. doi:10.1186/1869-5760-3-21 [CrossRef]
- Landers MB, Stefansson E, Wolbarsht ML. Panretinal photocoagulation and retinal oxygenation. Retina. 1982;2(3):167–175. doi:10.1097/00006982-198200230-00007 [CrossRef]
- Saatci AO, Ayhan Z, Takeş Ö, Yaman A, Söylev Bajin F. Single bilateral dexamethasone implant in addition to panretinal photocoagulation and oral azathioprine treatment in IRVAN syndrome. Case Rep Ophthalmol. 2015;6(1):56–62. doi:10.1159/000375481 [CrossRef]
- Empeslidis T, Banerjee S, Vardarinos A, Konstas A. Dexamethasone intravitreal implant for idiopathic retinal vasculitis, aneurysms, and neuroretinitis. Eur J Ophthalmol. 2012;23(5):757–760. doi:10.5301/ejo.5000301 [CrossRef]
- Karagiannis D, Soumplis V, Georgalas I, Kandarakis A. Ranibizumab for idiopathic retinal vasculitis, aneurysms, and neuroretinitis: favorable results. Eur J Ophthalmol. 2009;20(4):792–794.
- Russell SR, Folk JC. Branch retinal artery occlusion after dye yellow photocoagulation of an arterial macroaneurysm. Am J Ophthalmol. 1987;104(2):186–187. doi:10.1016/0002-9394(87)90015-8 [CrossRef]