UVEITIS By Dr. Ricky Mittal

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Anatomy of the Uvea:

Anatomy of the Uvea Pigmented structure between retina & sclera Nourishes most of the eye thru’ anterior & posterior ciliary vessels Involved in aqueous formation, aqueous outflow & control of accomodation Uvea includes Iris, Ciliary body & Choroid

Anatomy of the Uvea (IRIS):

Anatomy of the Uvea (IRIS) Anterior portion of uvea Divides anterior segment into anterior & posterior chambers Mainly vascular stroma along with melanocytes nerves, collagen, and hyaluronidase sensitive acid mucopolysaccharide Vascular supply – anterior and long posterior ciliary arteries – form major arterial circle – branch radially Blood vessels lack internal elastic lamina & have non fenestrated endothelial cells

Anatomy of the Uvea (IRIS):

Anatomy of the Uvea (IRIS) Anterior surface – interconnected fibroblasts with many ridges & crypts Pupillary aperture slightly inferonasal to center of iris Number & density of stromal melanocytes determines eye color

Anatomy of the Uvea (IRIS):

Anatomy of the Uvea (IRIS) Posterior portion of iris – muscles & epithelium Muscles – dilator & sphincter pupillae – regulate the amount of light entering the eye Sphincter – in posterior stroma – tightly arranged in a circle around pupil – innervated by parasympathetic nerves of 3 rd cranial N. nucleus Dilator muscles – radially oriented – anterior pigmented epithelial layer – innervated by sympathetic N.

Anatomy of the Uvea (IRIS):

Anatomy of the Uvea (IRIS) Anterior surface irregular Posterior surface – velvety smooth – composed of 2 layers of heavily pigmented columnar cells – absorbs light not entering pupil Iris pigmented epithelium continuous with pigmented & non pigmented layers of ciliary body

Anatomy of the Uvea (Ciliary body)_:

Anatomy of the Uvea (Ciliary body)_ Two parts – pars plicata, pars plana Pars plicata – 2mm long, 70 ciliary processes, arranged radially, zonular fibers of lens attached to ciliary processes along pars plana Ciliary processes – vascularised stromal core, covered with two layers of epithelium Epithelium – outer non pigmented, inner pigmented Zonulae occludens – blood aqueous barrier Non pigmented layer – aqueous secretion Arterial blood flow – regulates aqueous formation

Anatomy of the Uvea (Ciliary body)_:

Anatomy of the Uvea (Ciliary body)_ Pars plana – flat, 4mm long, between pars plicata & ora serrata, 3-4 mm behind limbus Lined by outer non pigmented epithelium & inner pigmented epithelium Non pigmented epithelium secretes acid mucopolysaccharides – main component of vitreous

Anatomy of the Uvea (Ciliary body)_:

Anatomy of the Uvea (Ciliary body)_ Adjacent to pars plicata – ciliary muscles Ciliary muscles – smooth non striated muscle Outer longitudinal attached to scleral spur Radial fibers – originate – middle ciliary body circular fibers – originate – inner ciliary body Supplied – parasympathetic – ciliary ganglion Ciliary muscle contraction – accomodation, aqueous outflow Miotics - Ciliary muscle contraction

Anatomy of the Uvea (Choroid):

Anatomy of the Uvea (Choroid) Between retina & sclera Extends from scleral spur to optic nerve Scleral attachment at vortex veins – characteristic shape of choroidal detachment Composed of vessels, fine connective tissue & melanocytes Pigmentation of choroid – no. of pigmented melanocytes

Anatomy of the Uvea (Choroid):

Anatomy of the Uvea (Choroid) Nourishes outer retina, portion of optic nerve, sole vascular supply to foveal area – cherry red spot in CRAO Cilioretinal artery from choroid in 15% - fovea High blood flow – low difference in arterial and venous blood oxygen levels Choriocapillaris – diffuse heat – incident light – retina Choroidal drainage by 4-7 vortex veins

Anatomy of the Uvea (Choroid):

Anatomy of the Uvea (Choroid) Choriocapillaris – continuous sheet of capillaries, 40 - 60 microns diameter, multiple fenestrations, leak fluorescein – choriodal blush on FFA Large & medium choroidal vessels – no fluorescein leakage Architecture of Choriocapillaris differs from area to area Choriocapillaris intimately associated with Bruch’s membrane & RPE – diseases of one tend to affect all these structures

Anatomy of the Uvea (Embryology):

Anatomy of the Uvea (Embryology) Sphincter and dilator muscles of pupil, pigmented epithelium of ciliary body, RPE – outer lamina of optic cup or neuroectoderm Pigment epithelium of iris, nonpigmented epithelium of ciliary body – inner lamina of optic cup Iris & choroidal stroma, melanocytes & ciliary musculature – neural crest Vascular endothelium - mesoderm

Uveitis:

Uveitis Inflammation of uveal tract or adjacent structures Key features – inflammatory cells in anterior chamber&/ vitreous cavity

Uveitis:

Uveitis Associated features Pain, redness, photophobia, blurred vision, floaters Localized infilteration of inflammatory cells (e.g. keratitic precipitates, iris nodules, retinochoroidal infilterates) Anterior or posterior synechiae Disc or macular edema, sheathing of blood vessels Secondary cataract or glaucoma

Uveitis (Epidemiology & pathogenesis:

Uveitis (Epidemiology & pathogenesis Numerous classification schemes based on Location (e.g. anterior, posterior) Course (acute, chronic, recurrent) Pathology (granulomatous, non granulomatous) Causative factors ( e.g. infectious, autoimmune, systemic, neoplastic diseases) International uveitis study group – based on anatomic location

Classification of uveitis:

Classification of uveitis International uveitis study group- anatomic based - classification of uveitis Anterior - Iritis - Anterior cyclitis - Iridocyclitis Intermediate uveitis ( formerly k/a pars planitis, posterior cyclitis, hyalitis, basal retinochoroiditis, peripheral uveitis) Posterior uveitis - focal, multifocal or diffuse choroiditis, chorioretinitis -retinochoroiditis or neurouveitis Pan uveitis

Epidemiology:

Epidemiology Anterior uveitis – 28 to 66% of all cases of uveitis Intermediate uveitis – 5 to 15% Posterior uveitis – 19 to 51% Panuveitis – 7 to 18% Large %age of uveitis cases are etiologically “idiopathic” Uveitis frequently associated other systemic conditions Detailed history and review of systems - indispensable in arriving at correct diagnosis

Uveitis (Ocular manifestations):

Uveitis (Ocular manifestations) Clinical manifestations depend on Primary site of involvement in eye Course ( acute or chronic) Presence of uveitis related complications

Uveitis (Ocular manifestations):

Uveitis (Ocular manifestations) Acute anterior uveitis severe Pain Redness Photophobia Blurred vision develops over a period of hours/ days Chronic uveitis Blurred vision Mild redness Little pain or photophobia

Uveitis (Ocular manifestations):

Uveitis (Ocular manifestations) Intermediate uveitis Floaters Impaired vision – CME Posterior uveitis Floaters Impaired vision – posterior pole involvement Panuveitis Any or all of these features

Uveitis ( clinical examination):

Uveitis ( clinical examination) Conjunctiva – ciliary flush, nodules (sarcoidosis) Cornea – keratitic precipitates (KPs), epithelial dendrites, geographic ulcers, stromal scarring, band shaped keratopathy

Keratitic precipitates (KPs):

Keratitic precipitates (KPs) Collection of inflammatory cells on endothelial surface Small KPs – non granulomatous uveitis Large (mutton fat) KPs - granulomatous uveitis More concentrated in lower part of cornea – normal convection currents of aqueous Diffuse distribution of KPs – Fuch’s heterochromic cyclitis, herpetic kerato-uveitis Fresh KPs – white & round Old KPs – crenated, shrunken & pigmented

Uveitis ( clinical examination):

Uveitis ( clinical examination) Sine qua non of anterior uveitis –cells & flare in anterior chamber Normally aqueous has no cells and very little proteins Uveitis – increased permeability – cells & proteins (plasmoid aqueous) in AC Cells & flare graded (0 to 4+) In long standing uveitis – cells more diagnostic of activity

Uveitis ( clinical examination):

Uveitis ( clinical examination) Iris in uveitis may show Anterior synechiae Posterior synechiae Koeppes nodules Bussaca nodules Engorgement of iris vessels Resulting in Loss of iris pattern Pupillary blockage Iris bomb’e Angle closure glaucoma

Uveitis ( clinical examination):

Uveitis ( clinical examination) Lens Cataract - complicated a) posterior subcapsular b) anterior subcapsular - steroid induced In cases of (lens induced) uveitis, hypermature cataract / lens rupture (+)

Uveitis ( clinical examination):

Uveitis ( clinical examination) Vitreous Cellular infiltrates Snowball opacities Fibrosis Cyclitic membrane

Uveitis ( clinical examination):

Uveitis ( clinical examination) Posterior segment Disc / macular edema Retinal vasculitis Perivascular exudates Focal / diffuse retinitis or choroiditis Pars plana exudates ( snow banking) Serous, tractional or rhegmatogenous retinal detachment Retinochoroidal atrophy Choroidal & retinal neovascularization

Uveitis ( clinical examination):

Uveitis ( clinical examination) Intraocular pressure - Low a) inflammation induced reduced aqueous production b) long standing uveitis or cyclitis induced ciliary body detachment – hypotony – phthiasis bulbi - high a) plugging of trabecular meshwork by inflammatory cells, KPs, plasmoid aqueous b) trabeculitis c) peripheral anterior synechiae d) pupillary blockage – posterior synechiae / exudates e) corticosteroid induced f) mydriatic induced angle closure glaucoma

Differential diagnosis of Uveitis:

Differential diagnosis of Uveitis Conjunctivitis Acute angle closure glaucoma Retinoblastoma Juvenile xanthogranuloma of iris Malignant lymphoma Neurofibroma Pigment “ cells ” in anterior chamber Pseudoexfoliation of lens Primary familial amyloidosis Reactive lymphoid hyperplasia Reticulum cell sarcoma

Causes of Uveitis:

Causes of Uveitis Unknown – majority Known – minority - infectious agents - trauma - autoimmune

Infectious agents:

Infectious agents Protozoal Bacterial Fungal Viral Helminthic infestations

Bacterial Infections:

Bacterial Infections Treponema pallidum Mycobacterium tuberculosis Mycobacterium leprae Leptospira  - hemoltytic streptococcus Gonococcus Listeria Borrelia burgdorferi (lyme disease) chlamydia

Viruses:

Viruses Ornithosis Lymphogranuloma Varicella zoster Herpes simplex Mumps Rubella Cytomegalovirus

Fungus:

Fungus Histoplasma capsulatum Candida spp. Blastomycosis Aspergillus Mucor Cryptococcus Coccidiodes immitus Sporotrichum schenkii Nocardia

Infestations & Parasites:

Infestations & Parasites Toxocara larvae Hookworm larvae Larva migrans (Ascaris) Ophalmomyiasis Filaria Toxoplasma Cysticercus Echinococcus Onchocerca

Traumatic uveitis:

Traumatic uveitis Lens induced - Phacoanaphylactic - Phakotoxic Sympathetic ophthalmitis

Autoimmune diseases:

Autoimmune diseases HLA antigen related diseases Microbe initiated diseases Tissue initiated

Investigations:

Investigations Of cause of uveitis ( depending on ocular and associated features - skin tests - x-rays - serology (culture/ antibodies) - diagnostic keratocentesis/ vitrectomy - tissue biopsy - polymerase chain reaction - electron microscopy

Investigations:

Investigations Clinical evaluation Fundus fluorescein angiography ultrasonography ICG angiography perimetry

Treatment:

Treatment Aims Early control of inflammation Treatment of cause Minimize complications of the disease & therapeutic regimen

Treatment:

Treatment Mydriatic and cycloplegic agents Corticosteroids topical periocular intraocular systemic NSAIDS Immunosuppressive/cytotoxic agents

Course & outcome:

Course & outcome Potentially blinding with serious complications Blindness may be caused by Band shaped keratopathy Cataract Glaucoma Cystoid macular edema Vitreous exudates/ membranes Retinal detachment Cyclitic membrane – chronic hypotony - phthiasis