Clinicopathologic Case Ravi Patel MD MBA Julia Kofler MD Charleen Chu MD PhD

Brief History 69 year old African American Female Patient had extensive history of idiopathic intraocular inflammation. She progressed to where her vision was NLP from advanced glaucoma Initially 180 degrees of cyclophotocoagulation was attempted without reduction of pressure Eye then became painful and patient elected to proceed with enucleation (PHS09-28620)

Ciliary Body Depigmentation - Likely due to previous cyclophotocoagulation DISLOCATED IOL

Found in 27% of population, not believed to be clinically significant Cobblestone Degeneration

Extensive Optic Nerve Cupping Vascular Sheathing

Vascular Sheathing/Frosting Macular Edema

Discussion- Macular Edema Most commonly caused by retinal vascular disease from diabetes, hypertension and venous occlusive disease. In this patient it is most likely from chronic intraocular inflammation as macular edema is a well known complication of uveitis Other less common etiologies of macular edema include papilledema, choroidal neovascular membrane, macular degeneration, retinitis pigmentosa, toxic maculopathy, post-operative (Irwin-Gass Syndrome)

Treatment – Macular Edema Widely accepted is focal/grid photocoagulation Also accepted therapy is topical, periocular, intraocular or even systemic corticosteroids There is emerging evidence to suggest efficacy of intravitreal anti-VEGF therapy (bevacizumab) As a final resort, vitrectomy surgery is considered

Thickened Ciliary Body Epithelial Basement Membrane Highlighted by PAS stain Usually this membrane is barely visible. Becomes more prominent in inflammatory conditions, and more commonly diabetes mellitus.

Neovascularization of Iris Thin fibrovascular membrane on anterior iris surface

Discussion - Neovascularization Usually a sequellae of retinal ischemia, now thought to be VEGF mediated Commonly associated with diabetes mellitus, venous occlusive disease, carotid occlusive disease Less commonly due to chronic intraocular inflammation, sickle cell disease, intraocular neoplasm, ROP, uveitis-glaucoma-hyphema syndrome There is evidence to suggest treatment with anti-VEGF therapy and panretinal photocoagulation

Treatment-Neovascularization Optimal therapy is to control the underlying disease Ocular therapy revolves around improving oxygenation and reducing oxygen demand Customarily panretinal photocoagulation is employed Extrapolating from studies of macular degeneration patients with choroidal neovascularization, intravitreal anti-VEGF therapy has been helpful in promoting regression of neovascularization

Chronic Keratoconjunctivitis Chronic lymphocytic infiltrate into conjunctival epithelium, usually nonkeratinized stratified squamous epithelium

Keratic Precipitates Inflammatory aggregates on corneal endothelium

Chronic Iritis Chronic lymphocytic infiltrate into iris stroma

Chronic Choroiditis Mononuclear cells “small blue cells”

Retinal Vasculitis Lymphoplasmacytic Perivascular Inflammation 17

Discussion - Uveitis Any intraocular inflammation involving uveal tissue (iris, ciliary body, choroid) is termed uveitis. Disease is classified by which layers are affected, and chronicity. This is a multi-factorial disease which can be: Secondary to systemic infection Noninfectious from systemic inflammatory disease Idiopathic

Treatment - Uveitis Infectious Uveitis involves treating the underlying infection along with supportive periocular therapy Noninfectious Uveitis is usually managed using topical steroids and cycloplegics. Recurrent episodes or posterior uveitis typically involves the use of periocular or systemic immunosuppression

Peripheral Anterior Synechiae Segment represented by peripheral adhesion of iris tissue to cornea

Optic Nerve Cupping Paucity of Ganglion Cells Large Cup Posterior Bowing of Lamina Cribosa

Discussion - Glaucoma Secondary Angle Closure Glaucoma Due to neovascularization Due to intraocular inflammation Accepted theory is a fibrovascular membrane that “zips up” the angle thereby producing a resistance to aqueous outflow

Treatment - Glaucoma Topical antiglaucoma therapy is often employed (caution is used to avoid miotics and prostaglandin analogues as they can exacerbate inflammation) Second line therapy usually involve insertion of setons as trabeculectomies are subject to a high rate of failure.

Diagnosis: SECONDARY GLAUCOMA WITH INFLAMMATORY AND NEOVASCULAR CONTRIBUTIONS Contributing factors: Idiopathic chronic panophthalmitis Hypertension