Ophthalmic Surgery, Lasers and Imaging Retina

Case Report 

Management of IRVAN Syndrome With Observation

Madhi Basha, DO; Gary C. Brown, MD, MBA; Geremie Palombaro, DO; Carol L. Shields, MD; Jerry A. Shields, MD

Abstract

A 7-year-old girl with IRVAN (idiopathic retinal vasculitis, aneurysms, and neuroretinitis) syndrome was monitored for 9 years. The patient had symmetric multiple aneurysmal dilations, retinal vasculitis, and severe hard exudation in the macula bilaterally. Long-term visual acuity in her untreated right eye was 20/25. In the left eye, treated with laser panretinal photocoagulation and intravitreal vascular endothelial growth factor inhibitor therapy, visual acuity decreased to 20/200 from macular hard exudates and central fibrovascular tissue. Observation is a consideration in IRVAN syndrome if the vision remains good with hard exudation.

[Ophthalmic Surg Lasers Imaging Retina. 2014;45:e18–e22.]

From the Retina Service (MB, GCB, GP) and the Oncology Service (CLS, JAS), Wills Eye Hospital, Jefferson Medical College, Philadelphia, Pennsylvania; the Center for Value-Based Medicine, Flourtown, Pennsylvania (MB, GCB, GP); and the Philadelphia Retina Endowment Fund, Philadelphia, Pennsylvania (GCB).

The authors have no proprietary or financial interest in the materials presented herein.

Address correspondence to Gary C. Brown, MD, MBA, Mid-Atlantic Retina, 4060 Butler Pike, Plymouth Meeting, PA 19462; 800-332-6634; fax: 215-233-3222; email: gary0514@gmail.com.

Received: July 25, 2013
Accepted: November 22, 2013
Posted Online: April 28, 2014

Abstract

A 7-year-old girl with IRVAN (idiopathic retinal vasculitis, aneurysms, and neuroretinitis) syndrome was monitored for 9 years. The patient had symmetric multiple aneurysmal dilations, retinal vasculitis, and severe hard exudation in the macula bilaterally. Long-term visual acuity in her untreated right eye was 20/25. In the left eye, treated with laser panretinal photocoagulation and intravitreal vascular endothelial growth factor inhibitor therapy, visual acuity decreased to 20/200 from macular hard exudates and central fibrovascular tissue. Observation is a consideration in IRVAN syndrome if the vision remains good with hard exudation.

[Ophthalmic Surg Lasers Imaging Retina. 2014;45:e18–e22.]

From the Retina Service (MB, GCB, GP) and the Oncology Service (CLS, JAS), Wills Eye Hospital, Jefferson Medical College, Philadelphia, Pennsylvania; the Center for Value-Based Medicine, Flourtown, Pennsylvania (MB, GCB, GP); and the Philadelphia Retina Endowment Fund, Philadelphia, Pennsylvania (GCB).

The authors have no proprietary or financial interest in the materials presented herein.

Address correspondence to Gary C. Brown, MD, MBA, Mid-Atlantic Retina, 4060 Butler Pike, Plymouth Meeting, PA 19462; 800-332-6634; fax: 215-233-3222; email: gary0514@gmail.com.

Received: July 25, 2013
Accepted: November 22, 2013
Posted Online: April 28, 2014

Introduction

IRVAN (idiopathic retinal vasculitis, aneurysms, and neuroretinitis) syndrome is a rare retinal vascular inflammation characterized by the presence of retinal vasculitis, retinal aneurysmal abnormalities, and neuroretinitis.1–8 Visual loss occurs from sequelae due to proliferative retinopathic changes, severe macular hard exudation, macular edema, and/or retinal vascular occlusion. Treatment options advocated have included oral glucocorticosteroids, intravitreal vascular endothelial growth factor (VEGF) inhibitor injections, pars plana vitrectomy, and laser panretinal photocoagulation.2,3

Case Report

A healthy, asymptomatic 7-year-old girl presented with a chief complaint of floaters in the left eye and a referring diagnosis of capillary hemangioma of the optic disc bilaterally. The patient had no known medical problems and took no medications. Birth history revealed a full-term pregnancy with vaginal delivery and no neonatal complications. Pediatric history revealed normal development. A review of systems and medical, including formal neurological, examinations yielded no abnormal findings. There was no pertinent family medical or ophthalmic history.

Initial Presentation

Ophthalmic examination revealed best corrected visual acuity (BCVA) of 20/20–1 in the right eye and 20/25 in the left eye. Intraocular pressure was 12 mm Hg in both eyes. Anterior segment examination revealed 1+ white blood cells in the anterior vitreous cavity bilaterally. Posterior segment examination in both eyes revealed multiple dilated, aneurysmal abnormalities overlying the optic disc and in the peripapillary retina. Retinal vasculitis with sheathing on the optic disc and peripapillary retina was seen bilaterally, and pronounced hard exudates extended from the optic disc to the nasal fovea in both eyes (Figures 13). Macular edema was present with the hard exudates.

Fundus photograph of the right eye at initial presentation. BCVA was 20/25. Multiple retinal vascular aneurysmal abnormalities are present on the optic disc, and pronounced hard exudates are present in a circinate pattern, most pronounced temporal to the disc. Retinal edema was present within the area of circinate exudation.

Figure 1.

Fundus photograph of the right eye at initial presentation. BCVA was 20/25. Multiple retinal vascular aneurysmal abnormalities are present on the optic disc, and pronounced hard exudates are present in a circinate pattern, most pronounced temporal to the disc. Retinal edema was present within the area of circinate exudation.

Fundus photograph of the left eye at initial presentation. BCVA was 20/20. Retinal vascular aneurysmal abnormalities are present overlying the optic disc and along the superotemporal vascular arcade. Prominent hard exudation associated with retinal edema is present in the papillomacular bundle, extending slightly into the fovea.

Figure 2.

Fundus photograph of the left eye at initial presentation. BCVA was 20/20. Retinal vascular aneurysmal abnormalities are present overlying the optic disc and along the superotemporal vascular arcade. Prominent hard exudation associated with retinal edema is present in the papillomacular bundle, extending slightly into the fovea.

Fluorescein angiogram of the left eye (positive image) corresponding to Figure 2 initial presentation. The time was 8.5 minutes after injection of dye, and BCVA was 20/25. There is marked hyperfuorescence over the optic disc and peripapillary retina due to leakage of fluorescein dye from the arterial aneurysmal abnormalities.

Figure 3.

Fluorescein angiogram of the left eye (positive image) corresponding to Figure 2 initial presentation. The time was 8.5 minutes after injection of dye, and BCVA was 20/25. There is marked hyperfuorescence over the optic disc and peripapillary retina due to leakage of fluorescein dye from the arterial aneurysmal abnormalities.

A lumbar puncture revealed normal opening pressure, and magnetic resonance imaging and magnetic resonance angiography of the brain yielded normal findings. A fasting lipid panel, comprehensive metabolic panel, erythrocyte sedimentation rate, complete blood count, C reactive protein, and rheumatology consultation and work-up yielded normal findings.

The patient was diagnosed with IRVAN syndrome and was started on prednisone 40 mg orally daily. The oral corticosteroid had no visible effect on the retinal vasculitis and/or hard exudate in each eye; it was therefore discontinued several weeks later. At 6 months after baseline examination, BCVA decreased to 20/30–2 bilaterally. The patient underwent mid-peripheral panretinal laser photocoagulation to extensive peripheral non-perfusion in the left eye in conjunction with a 1.25 mg intravitreal bevacizumab injection, the latter to theoretically decrease retinal vascular leakage and macular edema.

BCVA in the left eye decreased to 20/100 by 3 months after the initial therapy and 20/200 by 6 months. Hard exudates coalesced centrally in the left macula but remained perifoveolar in the untreated 20/30 right eye.

Eighteen Months After Initial Presentation

At 18 months after presentation, BCVA in the right eye remained 20/30–2, despite circinate hard exudates surrounding the optic disc and impinging upon the foveola (Figure 4). Due to the poor visual result in the left eye, treatment was not undertaken in the right eye.

Fundus photograph of the right eye 18 months after initial presentation. BCVA was 20/30–1. The hard exudate has entered the fovea and is impinging upon the foveola. Retinal edema was present between the optic disc and hard exudate. No treatment was undertaken. The hard exudation in the left eye also progressed to this degree by approximately 6 months after initial presentation.

Figure 4.

Fundus photograph of the right eye 18 months after initial presentation. BCVA was 20/30–1. The hard exudate has entered the fovea and is impinging upon the foveola. Retinal edema was present between the optic disc and hard exudate. No treatment was undertaken. The hard exudation in the left eye also progressed to this degree by approximately 6 months after initial presentation.

BCVA in the left eye remained 20/200 despite five intravitreal bevacizumab injections for macular edema. A permanent central nodule of subretinal fibrosis developed in the left macula, initially associated with subretinal blood (Figure 5).

Fundus photograph of the left eye 18 months after initial presentation. BCVA was 20/200. There is a button of central gray subretinal fibrovascular tissue with subretinal blood inferior and nasal to it. The fibrovascular tissue was markedly hyperfluorescent with fluorescein angiography (Figure 6). It is uncertain whether this fibrovascular tissue, which occurred after coalescence of the severe hard exudation, derives it blood supply from the retinal vasculature and/or the choroidal vasculature. The hard exudate is in a resolution pattern with globoid deposits in the retina temporally, superiorly, and inferiorly.

Figure 5.

Fundus photograph of the left eye 18 months after initial presentation. BCVA was 20/200. There is a button of central gray subretinal fibrovascular tissue with subretinal blood inferior and nasal to it. The fibrovascular tissue was markedly hyperfluorescent with fluorescein angiography (Figure 6). It is uncertain whether this fibrovascular tissue, which occurred after coalescence of the severe hard exudation, derives it blood supply from the retinal vasculature and/or the choroidal vasculature. The hard exudate is in a resolution pattern with globoid deposits in the retina temporally, superiorly, and inferiorly.

Additional panretinal laser photocoagulation was performed in the left eye at 18 months. At this time, angiographic evidence of increased retinal capillary non-perfusion was evident to within 3 to 4 disc diameters from the temporal fovea (Figure 6).

Fluorescein angiogram of the left eye 18 months after initial presentation. Hyperfluorescence is present corresponding to the central macular button of fibrovascular tissue. Marked gray retinal capillary non-perfusion is present in the temporal and inferior periphery. Scatter laser photocoagulation is visible in the far temporal and inferotemporal periphery.

Figure 6.

Fluorescein angiogram of the left eye 18 months after initial presentation. Hyperfluorescence is present corresponding to the central macular button of fibrovascular tissue. Marked gray retinal capillary non-perfusion is present in the temporal and inferior periphery. Scatter laser photocoagulation is visible in the far temporal and inferotemporal periphery.

Nine Years After Initial Presentation

The right eye was never treated, and at 9 years after initial presentation, BCVA was 20/25. Most hard exudates had resolved spontaneously (Figure 7). Left eye vision was 20/200. No macular hard exudate was noted, although new small foci of hard exudate were present outside the macula (Figure 8).

Composite fundus photograph of the right eye 9 years after initial presentation. BCVA was 20/25. The majority of the hard exudates have resolved. No retinal edema was present within the macula. Hard exudates continued to further resolve in the macula, and BCVA remained 20/25 through 9 years of total observation. Note that the aneurysmal abnormalities overlying the optic disc have changed configuration and are less pronounced than at original presentation (Figure 1).

Figure 7.

Composite fundus photograph of the right eye 9 years after initial presentation. BCVA was 20/25. The majority of the hard exudates have resolved. No retinal edema was present within the macula. Hard exudates continued to further resolve in the macula, and BCVA remained 20/25 through 9 years of total observation. Note that the aneurysmal abnormalities overlying the optic disc have changed configuration and are less pronounced than at original presentation (Figure 1).

Composite fundus photograph of the left eye 9 years after initial presentation. BCVA was 20/200. Panretinal photocoagulation therapy, characterized by hyperpigmented burns, is visible temporally. The central button of fibrovascular tissue in the foveola is unchanged in size from 7.5 years prior (Figure 6), although preretinal bands now extend nasally from the fibrovascular button toward the optic disc. The macular hard exudates have resolved, but new discrete foci of hard exudation are present superior and inferior to the optic disc. The aneurysm along the superotemporal vascular arcade (Figures 2 and 3) has resolved.

Figure 8.

Composite fundus photograph of the left eye 9 years after initial presentation. BCVA was 20/200. Panretinal photocoagulation therapy, characterized by hyperpigmented burns, is visible temporally. The central button of fibrovascular tissue in the foveola is unchanged in size from 7.5 years prior (Figure 6), although preretinal bands now extend nasally from the fibrovascular button toward the optic disc. The macular hard exudates have resolved, but new discrete foci of hard exudation are present superior and inferior to the optic disc. The aneurysm along the superotemporal vascular arcade (Figures 2 and 3) has resolved.

Discussion

The association of bilateral retinal arteritis with multiple aneurysmal dilatations was first described by Kincaid and Schatz1 in 1983, while Chang et al2 were first to coin the acronym IRVAN in 1995. IRVAN predominantly affects the retinal arteries on the optic disc and in the posterior pole. As with our case, systemic pathology is generally not identified,1–7 although one reported case had a positive perinuclear antineutrophil cytoplasmic antibody (P-ANCA).8 The P-ANCA assay is positive in 10% of Wegener’s granulomatosis cases and 50% to 80% of polyarteritis nodosa patients.8 A case of increased intracranial pressure has also been documented.9

The vision-threatening features of IRVAN include macular edema, hard exudates in the central macular retina, and retinal capillary non-perfusion, which can lead to retinal neovascularization and vitreous hemorrhage.2,3 Retinal vascular occlusion has also be described.4

Oral prednisone does not seem to have therapeutic benefit, despite the suggestion of inflammation in the vitreous cavity.2,3 Panretinal photocoagulation has been shown to be effective in the management of retinal neovascularization,2,3 at times in combination with intravitreal anti-VEGF therapy.5 Therapy with intravenous infliximab, a monoclonal antibody against tumor necrosis factor alpha, has also been suggested to help decrease exudative maculopathy.6

Our case is unique in that with long-term follow-up of bilateral, symmetric, vision-threatening, exudative retinopathy, the treated eye became legally blind (20/200), while the untreated eye maintained good central vision (20/25). It has been noted that the aneurysmal abnormalities can change size and shape with time,9 as seen in our case in each eye. We believe these anatomical changes, possibly in association with clot formation, are responsible for decreasing the permeability of aneurysmal walls, with subsequent diminution in leakage of plasma into the retina. The hard exudate is then eventually removed by macrophages. While theoretical, it is possible that gradual removal of the hard exudate in the untreated eye decreased the chance of abrupt coalescence and deposition of hard exudate into the central fovea such as occurred in the treated eye. The role of the young age of our patient referent to most IRVAN cases1–9 is unclear in this regard.

We are uncertain why the hard exudates in the treated left eye encroached upon the central macula after therapy, especially because the laser panretinal photocoagulation was administered to the midperipheral retina. It has been demonstrated that midperipheral panretinal photocoagulation does not result in an increase in macular edema and/or hard exudation in eyes with proliferative diabetic retinopathy.10 Whether the bevacizumab therapy or a combination of laser photocoagulation and bevacizumab therapy contributed to the central exudation migration is also uncertain. Other ambiguities include whether there was any systemic cross-over effect of bevacizumab therapy from the treated eye to the untreated eye. It is also unknown whether laser photocoagulation and intravitreal bevacizumab therapy would have produced a favorable outcome in the untreated eye.

In summary, observation is a consideration if a patient with IRVAN syndrome manifests with macular hard exudation and the vision is good. It is unclear whether the exudative maculopathy encountered with IRVAN syndrome is benefitted or exacerbated by panretinal photocoagulation and/or intravitreal anti-VEGF therapy.

References

  1. Kincaid J, Schatz H. Bilateral retinal arteritis with multiple aneurismal dilatations. Retina. 1983;3(3):171–178. doi:10.1097/00006982-198300330-00005 [CrossRef]
  2. Chang TS, Aylward GW, Davis JL, et al. Idiopathic retinal vasculitis, aneurysms, and neuro-retinitis. Retinal vasculitis study. Ophthalmology. 1995;102(7):1089–1097. doi:10.1016/S0161-6420(95)30907-4 [CrossRef]
  3. Samuel MS, 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. doi:10.1016/j.ophtha.2006.11.014 [CrossRef]
  4. Venkatesh P, Verghese M, Davde N, Garg SPrimary vascular occlusion in IRVAN (idiopathic retinal vasculitis, aneurysms, neuroretinitis) syndrome. Ocular Immunology and Inflammation. 2006;14(3):195–196. doi:10.1080/09273940600657710 [CrossRef]
  5. Karagiannis D, Soumplis V, Georgalas I, Kandarakis A. Ranibizumab for idiopathic retinal vasculitis, aneurysms, and neuroretinitis: favorable results. Eur J Ophthalmol. 2010;20(4):792–794.
  6. Cheema RA, Al-Askar E, Cheema HR. Infliximab therapy for idiopathic retinal vasculitis, aneurysm, and neuroretinitis syndrome. J Ocul Pharmacol Ther. 2011;27(4):407–410. doi:10.1089/jop.2010.0189 [CrossRef]
  7. Nourinia R, Montahai T, Amooshashemi N, et al. Idiopathic retinal vasculitis, aneurysms and neuroretinitis syndrome associated with positive pernuclear antineutrophil cytoplasmic antibody. J Ophthalmic Vis Res. 2011;6(4):330–333.
  8. Hammond MD, Ward TP, Katz B, Subramanian PS. Elevated intracranial pressure associated with idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome. J Neuroophthalmol. 2004;24(3):221–224. doi:10.1097/00041327-200409000-00008 [CrossRef]
  9. Yeshurun I, Recillas-Gispert C, Navarro-Lopez P, Arellanes-Garcia L, Cervantes-Costs G. Extensive dynamics in location, shape, and size of aneurysms in a patient with idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. Am J Ophthalmol. 2003;135(1):118–120. doi:10.1016/S0002-9394(02)01823-8 [CrossRef]
  10. Blankenship GW. A clinical comparison of central and peripheral argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology. 1988;95(2):170–177. doi:10.1016/S0161-6420(88)33212-4 [CrossRef]

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