A Comprehensive Update on Retinal Vasculitis: Etiologies, Manifestations and Treatments

Abstract

Retinal vasculitis is characterized by inflammatory involvement of retinal arterioles, venules and/or capillaries and can be associated with a myriad of systemic and ophthalmic diseases. In this review, we have comprehensively discussed the etiologies, clinical manifestations, and presentations of retinal vasculitis. We have also included newer advances in imaging in retinal vasculitis such as OCTA and widefield imaging.

Keywords: eye; fluorescein angiography; ocular inflammation; retinal vasculitis; uveitis.

Figure 1

Schematic representation of the pathophysiology and influencing factors in retinal vasculitis. Highly simplified representation of the exogenous and endogenous factors that lead to an immune response in retinal vasculitis. Innate and acquired immunity as well as genetic factors result in vasculitis and subsequent tissue damage. Exogenous factors such as foreign antigens and infectious agents are processed by antigen-presenting cells, which result in B-cell activation. Endogenous antigens such as retinal S antigen can also result in immune stimulation and cytokine release. Both endogenous and exogenous antigen-mediated immune stimulation are controlled by genetic factors. Resultant cytokine release and antigen–antibody complexes result in tissue (endothelial) dysfunction, which is a hallmark of retinal vasculitis. HLA, human leukocyte antigen; HSP, heat shock protein; IL, interleukin; IRBP, interphotoreceptor retinoid binding protein; S-AG, retinal protein S-Ag.

Figure 2

The figure shows a patient (20-year-old Asian Indian male) with tubercular retinal vasculitis. Fundus examination (A) reveals optic nerve hyperemia with retinal vascular sheathing and few hemorrhages. Fluorescein angiography (B) reveals active optic nerve head inflammation and peripheral retinal vasculitis.

Figure 3

The figure is a fluorescein angiogram (FA) that shows a patient with multifocal retinitis and retinal vasculitis due to ocular syphilis. The FA shows multifocal retinal vasculitis involving the large vessels and multiple areas of hyperfluorescence due to retinitis lesions. There is mild disc hyperfluorescence as well.

Figure 4

The figure shows a patient with cat-scratch disease (bartonella-related retinitis). Fundus photographs of the right and left eye (A,B) reveal the presence of neuroretinitis in the right eye and a branch retinal arteriole occlusion in the left eye (yellow arrowheads). The optical coherence tomography of both the eyes (C,D) does not show macular edema. However, there is significant subretinal fluid in the right eye (C). The left eye (D) shows hyperreflectivity in the inner retina (yellow arrowhead), suggestive of arteriolar occlusion.

Figure 5

The figure shows a patient diagnosed with Whipple’s disease (A). The fluorescein angiography (B) shows subtle vascular leakage suggestive of focal vasculitis (yellow arrowheads).

Figure 6

Ultrawide-field imaging of a patient with varicella zoster-related acute retinal necrosis. The fundus photograph reveals extensive peripheral retinal necrosis resulting in whitening and edema, along with retinal arteritis. There is significant media haze due to the presence of vitreous inflammation and cells.

Figure 7

The slit-lamp biomicroscopy fundus photograph using 90 diopter lens shows a necrotizing retinochoroiditis lesion due to toxoplasmosis located nasally to the optic nerve head (white arrow). The active yellow-white lesion is located adjacent to a dull yellow scar, and there is associated retinal vasculitis and overlying vitritis.

Figure 8

Clinical photograph of 28-year-old male patient with Behcet’s syndrome shows presence of punched out aphthous ulcerations on the lip mucosa.

Figure 9

Fundus photograph of a 32-year-old patient with Behcet’s syndrome (only left eye shown) demonstrating occlusive retinal vasculitis leading to severe retinal and optic nerve atrophy. There is severe macular atrophy as well.

Figure 10

(A) 61-year-old woman with panuveitis associated with multiple sclerosis (MS) demonstrating granulomatous keratic precipitates on slit-lamp photography (A) and cystoid macular edema on optical coherence tomography (OCT) (B). Fluorescein angiography (FA) (C) depicts macular edema, optic disc leakage and vascular leakage of central and peripheral vessels. Furthermore, vitreous haze, indicated by a reduced visibility of the fundus best appreciated on peripheral FA and OCT images, is present.

Figure 11

A 39-year-old man with Susac’s syndrome demonstrating hyperintense infarcts in the corpus callosum referred to as “snowball lesions” (white arrows, (A)) and hyperintense lesions in the white matter (white arrows, (B)) on T2 flair weighted magnetic resonance tomography (MRI) images. Ophthalmologic findings include multiple branch retinal artery occlusions (black asterisk) in the right (C) and left eye (D). In addition, there are areas of focal arterial wall hyperfluorescence (black arrow) on fluorescein angiography (FA) of both eyes (C,D). Optical coherence tomography (OCT) of both eyes (right eye: (E), left eye: (F)) is unremarkable.

Figure 12

Figure shows the Chapel Hill classification of retinal vasculitis. (Permission obtained for reprint).

Figure 13

The figure shows fundus photograph of a patient with sarcoid-associated retinal vasculitis with exuberant retinal vessel sheathing, (A) suggestive of frosted branch angiitis. Fluorescein angiography (B) shows extensive retinal vascular leakage due to the intense inflammatory response.

Figure 14

Initial presentation of a 43-year-old female patient with birdshot chorioretinopathy. Fundus photography of the right (A) and left eyes (B) showing discrete yellowish ovoid choroidal lesions in the peripapillary and midperiphery area.

Figure 15

Swept-source OCT of the same patient with birdshot chorioretinopathy shown in Figure 14. Retina: B-scan shows retinal changes. There are intraretinal cysts and hyperreflective foci in outer layers. Optic nerve of the right eye shows reduced nerve fiber layer.

Figure 16

Fundus autofluorescence (FAF) and fluorescein angiography (FA) of the right and left eyes of the same patient with birdshot chorioretinopathy shown in Figure 14 and Figure 15. The FAF is shown in (A,B) (right and left eyes, respectively). Early phase (C,D) and late-phase FA (E,F) of both fundi demonstrate leakage of the optic discs, large vessel leakage, and capillary ferning. Note: floaters are partly impairing visualization.

Figure 17

Indocyanine green angiography (ICGA) of the patient with Birdshot chorioretinopathy described in Figure 14, Figure 15 and Figure 16 is shown. The ICGA of both fundi in the early phase (A,B), and the late phase (C,D) (right and left eyes, respectively) show numerous evenly distributed and symmetric hypocyanescent spots throughout the fundus of both eyes, suggestive of choroidal inflammation.