What is the pathology and pathogenesis of retinal vasculitis?

Pathology and Pathogenesis of Retinal Vasculitis

Retinal vasculitis is fundamentally an autoimmune inflammatory condition affecting retinal blood vessels, characterized by immune-mediated vessel wall inflammation that leads to vascular occlusion, retinal ischemia, and potentially irreversible vision loss through mechanisms involving type III hypersensitivity reactions, increased expression of intracellular adhesion molecules, and genetic susceptibility. 1, 2

Core Pathophysiologic Mechanisms

Immune-Mediated Inflammation

• The primary pathology involves inflammation of retinal arterioles, venules, and/or capillaries through autoimmune mechanisms 1, 3
• Type III hypersensitivity reactions drive the inflammatory cascade, with immune complex deposition in vessel walls 1
• Increased expression of intracellular adhesion molecules (ICAMs) facilitates leukocyte recruitment and vessel wall infiltration 1
• Evidence indicates that antecedent infection with microbes cross-reacting with putative retinal autoantigens may trigger the autoimmune response 2

Genetic and Immunologic Susceptibility

• HLA associations and cytokine polymorphisms influence genetic susceptibility to developing retinal vasculitis 2
• The condition represents an autoimmune process where the effector immune response targets retinal vascular structures 2

Pathologic Consequences and Tissue Damage

Vascular Occlusion and Ischemia

• Vessel wall inflammation leads to vascular occlusion and subsequent retinal hypoperfusion 4, 5
• The retina has dual blood supply: inner layers from retinal arteries, outer layers from choroidal vessels 6
• When hypoperfusion occurs, ischemia predominantly affects the inner retinal layers 6
• Experimental data shows retinal arteries can tolerate occlusion up to 97 minutes without damage, but severe irreversible damage occurs after 240 minutes 6

Classification by Vessel Involvement

• Retinal vasculitis is classified by the type of vessels involved (arterial, venous, or mixed) 1, 3
• Further subclassification distinguishes occlusive versus non-occlusive disease 1
• Behçet's disease, sarcoidosis, and multiple sclerosis predominantly cause venous involvement 4
• Systemic lupus erythematosus and necrotizing vasculitis more commonly cause arterial or mixed vasculitis 4

Vision-Threatening Sequelae

Direct Macular Damage

• Visual acuity becomes severely affected when macular involvement occurs through ischemia or edema 4, 5
• Macular ischemia represents a primary mechanism of permanent vision loss 5

Neovascular Complications

• Chronic retinal ischemia triggers neovascularization at the inner retinal surface and into the vitreous 5
• New vessel formation leads to vitreous hemorrhage, fibrovascular proliferation, and tractional retinal detachment 1, 5
• Neovascular glaucoma can develop from new vessels growing on iris and anterior chamber angle structures 7

Critical Clinical Distinctions

Giant Cell Arteritis as Emergency Etiology

• In patients over 50, GCA represents the most common non-embolic cause and constitutes an ophthalmologic emergency 6, 8
• GCA causes inflammatory disease of the proximal ocular artery with vessel wall thickening and occlusion 6
• This results in simultaneous ischemia of inner and outer retina plus optic disc 6
• Immediate high-dose corticosteroid treatment is critical to prevent vision loss in the fellow eye 6, 8

Systemic Disease Associations

• Behçet's disease shows strong association with posterior segment involvement requiring azathioprine and systemic corticosteroids 7
• The primary pathology in Behçet's-associated thrombosis is vessel wall inflammation, not thrombophilia 7
• Sarcoidosis, systemic lupus erythematosus, and multiple sclerosis represent other major systemic associations 4, 2

Common Pitfalls in Understanding Pathogenesis

• Failing to recognize that retinal vasculitis differs fundamentally from embolic retinal artery occlusion—the former involves inflammatory vessel wall disease while the latter involves mechanical obstruction 6
• Underestimating the rapidity of irreversible damage—the 240-minute threshold for severe retinal injury demands emergency evaluation 6
• Missing that vasculitis can cause vessel narrowing without embolus through pure inflammatory mechanisms 6
• Not appreciating that the inflammation itself, rather than secondary thrombosis, represents the primary therapeutic target requiring immunosuppression 7, 1