Retinal vasculitis is a diagnosis of inflammatory changes of the retinal arteries and/or veins consisting of vascular sheathing, vitreous cells, cotton-wool spots, and intraretinal hemorrhages.^1,2 It is a sight-threatening disease due to complications from macular edema, vascular occlusion, retinal ischemia, and neovascularization. Etiologies of retinal vasculitis include infectious, noninfectious (autoimmune/inflammatory), and neoplastic entities. Because it can be associated with systemic vasculitis or underlying systemic inflammatory diseases, a tailored but thorough investigation is indicated.

ETIOLOGIES

Infectious retinal vasculitis can be caused by syphilis, herpesviridae, toxoplasmosis, or tuberculosis.¹ Given the protean ocular manifestations of syphilis, which also include vitritis, chorioretinitis, neuroretinitis, optic neuritis, occlusive disease, and exudative retinal detachment, it should always be considered in cases of retinal vasculitis.³ Herpesviridae, specifically varicella zoster and herpes simplex types 1 and 2, can affect immunocompetent and immunocompromised individuals and result in rapidly progressive peripheral retinal necrosis with occlusive arteritis and varying levels of anterior-segment and vitreous inflammation.⁴ Cytomegalovirus causes a more indolent retinitis and is seen in immunocompromised patients. Congenital or acquired ocular toxoplasmosis is characterized by retinochoroiditis, anterior-segment inflammation, vitritis, and active fluffy white lesions adjacent to atrophic pigmented scars.⁴ Tubercular uveitis can present as serpiginous-like choroiditis and retinitis, with involvement of the retinal vasculature.⁵ Other infectious etiologies of retinal vasculitis include cat-scratch disease, Lyme disease, human T-cell lymphotropic virus type 1, and West Nile virus.

Noninfectious retinal vasculitis can be associated with primary systemic vasculitides, such as systemic lupus erythematosus, granulomatosis with polyangiitis, and Behçet disease, or with other systemic disease such as sarcoidosis.⁶ Lupus retinopathy involves vasculitis of the retinal capillaries and arterioles, sometimes with significant vaso-occlusive disease leading to ischemia and neovascularization.⁶ Testing for antiphospholipid antibodies in cases of retinal vasculitis can help elucidate the etiology. Granulomatosis with polyangiitis can have significant orbital involvement, as well as retinitis, chorioretinitis, macular edema, exudative retinal detachment, and retinal necrosis.⁷ Behçet disease presents as a panuveitis with a progressive retinal vasculitis.⁸ Ocular sarcoidosis, in addition to its anterior-segment manifestations, can present with “candle-wax dripping” segmental periphlebitis, retinochoroiditis, and choroidal nodules.⁹ Multiple sclerosis can present with optic neuritis and periphlebitis. Susac syndrome presents with retinal artery occlusions and can be diagnosed by the presence of white matter lesions in the corpus callosum.¹⁰ Patients have a triad of symptoms involving the brain, retina, and cochlea.

Retinal vasculitis can also present secondary to paraneoplastic syndromes, ocular lymphoma, and acute leukemia.¹ When other etiologies have been ruled out and there is a suspicion for malignancy, thorough systemic evaluation is recommended. And lastly, retinal vasculitis can present locally without evidence of systemic disease, such as in cases of birdshot chorioretinopathy (BSCR); idiopathic retinal vasculitis, aneurysms, and neuroretinitis; and Eales disease.

MULTIMODAL IMAGING

Multimodal imaging in retinal vasculitis utilizing fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and adaptive optics (AO) can be helpful in establishing diagnosis and severity and guiding therapy.^1,11 Fluorescein angiography can demonstrate vascular leakage and staining and can be used to evaluate the degree of arteritis or phlebitis.

Etiologies with both arterial and venous involvement include toxoplasmosis, Crohn disease, and granulomatosis with polyangiitis. Predominantly arteriolar involvement is seen in acute retinal necrosis, syphilis, and systemic lupus erythematosus, while predominantly venular involvement is seen in tuberculosis, sarcoidosis, multiple sclerosis, intermediate uveitis, Behçet disease, and BSCR. Other FA findings associated with retinal vasculitis include the presence of optic disc staining or leakage and macular edema. Furthermore, studies have shown that the use of ultrawidefield FA can provide better monitoring in patients with retinal vasculitis and lead to adjustments in treatment plans.¹² Fluorescein angiography can also demonstrate areas of occlusive vasculitis, ischemia, nonperfusion, and neovascularization, which can be treated with retinal laser photocoagulation.¹³

Dual angiography with FA and ICGA can help characterize diseases that also have choroidal involvement, such as sarcoidosis, BSCR, Vogt-Koyanagi-Harada disease, tuberculosis, acute retinal necrosis, and toxoplasmosis.³ In these etiologies, ICGA can reveal hypofluorescent areas or fuzzy or hypercyanescent choroidal vessels. Optical coherence tomography, enhanced depth imaging OCT, and OCT angiography can similarly aid in the management of patients with retinal vasculitis by demonstrating retinal and choroidal structural changes, such as retinal thickening, loss of normal retinal laminations, outer retinal changes, choroidal thickening, and changes in flow signal.^14,15 Lastly, AO can also be used to demonstrate vascular involvement in retinal vasculitis.¹⁶ It can demonstrate perivascular infiltrates and subclinical disease activity beyond that noted in ophthalmoscopy and FA.

INVESTIGATIONS

Investigations for retinal vasculitis should be thorough but tailored based on history and review of systems, ocular presentation, and systemic symptoms and signs.¹⁷ For unilateral retinal vasculitis with associated chorioretinal changes, an aqueous tap for PCR testing of herpes simplex virus, varicella zoster virus, cytomegalovirus, and toxoplasma should be performed. Laboratory workup informed by the clinical presentation may include complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, c-reactive protein, angiotensin-converting enzyme, antinuclear antibodies, myeloperoxidase, proteinase 3, antiphospholipid antibodies, complement testing, and urinalysis. Syphilis, tuberculosis, and human immunodeficiency virus testing should be included. Human leukocyte antigen testing, particularly for HLA-A29, HLA-B51, and HLA-B27, can be considered. Serum antibody testing for infections may be useful in certain situations but is often not diagnostic. Systemic imaging with chest radiograph, computed tomography of the chest, or central nervous system imaging is sometimes indicated. Collaboration with an internist, infectious disease specialist, or rheumatologist may be helpful.

TREATMENTS

The treatment of retinal vasculitis is dependent on etiology.¹² For infectious cases, treatment of the underlying infection is required and corticosteroids may be recommended. For noninfectious cases, initial therapy consists of systemic corticosteroids. Local steroid therapy with periocular or intravitreal administration may also be utilized. Complications from ischemia and neovascularization can be treated with intravitreal bevacizumab and/or retinal laser photocoagulation. A stepladder approach to achieving durable steroid-free remission is recommended for long-term management of retinal vasculitis. Steroid-sparing therapies, such as antimetabolites (azathioprine, methotrexate, and mycophenolate mofetil) and calcineurin inhibitors (cyclosporine A and tacrolimus) can be utilized. Alkylating agents are usually reserved for refractory cases. Biologics such as adalimumab, infliximab, and rituximab have also been effective in retinal vasculitis.¹⁸

CONCLUSION

Retinal vasculitis is a sight-threatening condition of infectious, noninfectious (autoimmune/inflammatory), or neoplastic etiologies. Imaging with FA, ICG, and OCT can be particularly helpful in its diagnosis and management. A tailored but thorough investigation is recommended due to its systemic associations. Treatment is aimed at the underlying etiology. RP

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