Uveitis

Slide 1 · Uveitis

Clinicopathologic mechanisms, morphology and interpretation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Localize inflammation within the iris, ciliary body, choroid and adjacent retina.

Explain anterior-segment inflammatory signs and their structural consequences.

Distinguish sarcoid, infectious and sympathetic forms of uveitis.

Connect morphology to diagnosis while recognizing limits of individual signs.

Slide 3 · The uvea comprises three structures

Iris

Ciliary body

Choroid

Iris: Regulates the pupillary aperture.

Ciliary body: Forms aqueous humor and belongs to the anterior uvea.

Choroid: Richly vascular tissue between sclera and retina.

Schematic

Slide 4 · The choroid is exceptionally vascular

Vascular uveal bed

The choroid as one of the most richly vascularized tissues.

Inflammation in the choroid can be associated with clinically important retinal abnormalities.

Posterior uveitis therefore requires assessment beyond the visible anterior chamber.

Schematic

Slide 5 · Uveitis is an anatomic and clinical term

Broadly: Inflammation of one or more uveal tissues.

In routine clinical usage: A heterogeneous group of ocular or systemic inflammatory diseases.

Traumatic iritis and corneal-ulcer–associated iritis meet the broad definition but are not the whole clinical category.

Slide 6 · Multiple mechanisms produce uveal inflammation

Infectious agents may directly involve ocular tissues.

Systemic granulomatous disease may involve eye and retina.

Noninfectious immune responses may occur after ocular injury.

The mechanism cannot be inferred from anatomy alone.

Schematic

Slide 7 · Anatomic classification guides examination

Iris / anterior chamber

Vitreous / middle segment

Choroid and retina

Anterior: Inflammation centered in the anterior chamber.

Intermediate: Inflammation centered in the vitreous.

Posterior: Retina or choroid is the principal site.

Panuveitis: Inflammation involving all major ocular compartments without one predominant site.

Slide 8 · Chronic inflammation is clinically consequential

Chronic uveitis as a heterogeneous group of disorders.

Inflammatory exudates can damage structures even after the initiating trigger is absent.

Persistent inflammation may generate synechiae, cataract or glaucoma.

Slide 9 · A useful etiologic approach is not a single diagnosis

Define the predominant compartment and unilateral versus bilateral pattern.

Look for evidence of infection, systemic granulomatous disease and antecedent trauma.

A similar appearance may arise from different mechanisms.

Schematic

Slide 10 · Retinal abnormalities often accompany uveitis

Retina

Choroid

Retina and choroid are adjacent but anatomically distinct.

Inflammation in one frequently coexists with inflammation in the other.

Posterior-segment findings may drive visual loss even when anterior signs are modest.

Schematic

Slide 11 · Site and tissue response must be kept separate

Anatomic location: Anterior, intermediate, posterior or panuveitis.

Histologic reaction: Granulomatous or non-granulomatous pattern.

Etiologic category: Infectious, systemic inflammatory or ocular-specific immune response.

Slide 12 · The anterior chamber sits behind the cornea

Iris

Anterior chamber

Anterior boundary: Corneal endothelium.

Posterior boundary: Iris; Peripheral boundary: Angle and trabecular meshwork.

Inflammatory exudates accumulate in the chamber and may form adhesions.

Schematic

Slide 13 · Aqueous humor traverses the pupil

Iris

Anterior chamber

Aqueous flow

Ciliary processes produce aqueous humor into the posterior chamber.

Fluid flows through the pupil to reach the anterior chamber.

Aqueous outflow depends on patency of the anterior chamber angle.

Schematic

Slide 14 · Inflammatory exudate arises from ocular vessels

Acute corneal inflammation can provoke an exudative response from iris and ciliary-body vessels.

The exudate contains inflammatory cells and proteins.

A normally optically clear chamber becomes turbid.

Schematic

Slide 15 · Hypopyon reflects gravitational sedimentation

Iris

Anterior chamber

Settled leukocytes

Leukocytes may settle in the inferior anterior chamber.

The resulting white layer is visible clinically as a hypopyon.

Hypopyon reports inflammation but does not independently establish the responsible organism.

Schematic

Slide 16 · A hypopyon is not equivalent to endophthalmitis

Anterior-chamber hypopyon

Endophthalmitis

White leukocytic layer

Vitreous involvement

May be sterile

Inflammation extends into vitreous

Does not define etiology

Defines anatomic involvement

Hypopyon associated with an infected cornea seldom contains organisms.

Slide 17 · Slit-lamp “cells” indicate leukocytes

Discrete inflammatory cells scatter reflected light against a dark background.

The normal aqueous chamber should be optically clear.

Cells are evidence of an active inflammatory cellular response.

Slide 18 · Slit-lamp “flare” indicates proteinaceous exudate

Cells

Flare

Particulate inflammatory cells

Protein-rich aqueous haze

Discrete dots in slit beam

Diffuse light-scattering beam

Cellular recruitment

Increased vascular permeability

Breakdown of the normal aqueous barrier increases visible protein in chamber fluid.

Slide 19 · Keratic precipitates form on endothelium

Iris

Anterior chamber

Cell deposits on endothelium

Inflammatory cells can adhere to the posterior corneal surface.

These visible deposits are called keratic precipitates.

Their morphology may suggest granulomatous inflammation but does not prove an etiology.

Schematic

Slide 20 · “Mutton-fat” precipitates imply a granulomatous pattern

Sarcoid anterior uveitis may produce large, greasy-appearing keratic precipitates.

The precipitates evolve from an anterior-segment exudate.

They are a characteristic clinical clue, not a stand-alone sarcoidosis diagnosis.

Slide 21 · Synechiae are organized inflammatory adhesions

Iris

Anterior chamber

Iris–lens adhesion

Anterior synechiae: Iris adheres to cornea or angle structures.

Posterior synechiae: Iris adheres to anterior lens surface.

Location determines the mechanism of subsequent visual damage.

Schematic

Slide 22 · Anterior synechiae may obstruct outflow

An adhesion at the iridocorneal angle can cover trabecular meshwork.

Obstruction may elevate intraocular pressure.

Sustained pressure elevation can cause glaucomatous optic-nerve injury.

Schematic

Slide 23 · Posterior synechiae tether the iris to lens

Iris

Anterior chamber

Iris–lens adhesion

Chronic exudate encourages iris–lens adhesion.

Prolonged contact disrupts the normal interface of lens epithelium with aqueous humor.

The anatomic contact can stimulate metaplastic changes in the lens epithelium.

Schematic

Slide 24 · An anterior subcapsular cataract can result

Posterior synechiae may deprive adjacent lens epithelium of aqueous contact.

Fibrous metaplasia can yield an anterior subcapsular opacity.

The cataract is a secondary structural consequence of inflammation, not the uveitis itself.

Schematic

Slide 25 · Cycloplegia limits adhesion formation

Pharmacologic pupil dilation and cycloplegia as measures to reduce synechiae formation.

Maintaining iris mobility counters prolonged apposition.

This is a mechanistic complication-prevention principle, not a complete treatment algorithm.

Schematic

Slide 26 · Chronic inflammation can cause band keratopathy

Calcific band keratopathy results from calcium deposition near Bowman layer.

Chronic uveitis as one predisposing circumstance.

Corneal opacity then adds an anterior optical cause of impaired vision.

Slide 27 · Anterior damage follows predictable pathways

Leukocytes and protein enter the chamber → cells and flare.

Organization and contact → anterior or posterior synechiae.

Outflow obstruction or lens metaplasia → glaucoma or cataract.

Schematic

Slide 28 · Sarcoidosis is a systemic granulomatous cause

Sarcoidosis as an important cause of granulomatous uveitis.

Ocular disease may involve anterior and posterior segments.

Retinal signs reflect inflammation adjacent to, and within, posterior ocular tissues.

Slide 29 · Granulomatous uveitis spans both segments

Iris / anterior chamber

Vitreous / middle segment

Choroid and retina

Anterior: Exudate with large keratic precipitates.

Choroid: Granulomatous infiltrates can be present.

Retina: Perivascular inflammatory changes are prominent.

Slide 30 · Sarcoid choroiditis may contain granulomas

Retina (schematic)

Choroidal stroma

Granulomatous infiltrate

Granulomas can develop within the vascular choroid.

The lesion is anatomically posterior to the retina.

An explanatory schematic must not be confused with actual histology or fundus photography.

Schematic

Slide 31 · Retinal perivascular inflammation is central

Perivenous inflammatory deposits

Retinal vascular sheathing reflects inflammation along vessels.

In sarcoid uveitis, perivascular inflammation may be visible ophthalmoscopically.

The vessel-associated distribution helps distinguish it from isolated choroidal nodules.

Schematic

Slide 32 · “Candle wax drippings” describe vessel-associated exudates

Perivenous inflammatory deposits

Characteristic whitish perivascular deposits track along retinal veins.

The appearance is associated with sarcoid retinal periphlebitis.

It is a descriptive clinical sign and must be integrated with systemic and ocular data.

Schematic

Slide 33 · A posterior finding can inform systemic investigation

Choroidal granulomas and retinal periphlebitis provide a specific inflammatory pattern.

The pattern raises suspicion for ocular sarcoidosis.

Clinical and systemic assessment is needed to corroborate the suspected etiology.

Schematic

Slide 34 · Conjunctival biopsy may yield tissue confirmation

The conjunctiva is more accessible than deep posterior ocular tissues.

Demonstrating granulomatous inflammation can contribute to diagnosing ocular sarcoidosis.

Specimen selection and interpretation depend on clinical context and exclusion of alternative causes.

Schematic

Slide 35 · Granulomatous morphology is not a unique label

Granulomatous pattern

Etiologic diagnosis

What tissue does

Why it occurs

May recur in multiple diseases

Requires contextual evidence

Not synonymous with sarcoid

Not determined by one cell type

Sarcoidosis and sympathetic ophthalmia can both produce granulomatous uveitis.

Slide 36 · The 2019 IWOS consensus emphasizes exclusion

The revised ocular sarcoidosis framework begins by excluding other causes of granulomatous uveitis.

It integrates characteristic ocular signs with systemic assessment and biopsy information.

Consensus classifications support structured assessment; They do not replace clinicopathologic judgment.

Slide 37 · Ocular sarcoid can involve more than one tissue

Iris and ciliary body explain keratic precipitates and anterior inflammation.

Choroidal granulomas reflect stromal posterior inflammation.

Retinal periphlebitis produces the characteristic vascular fundus pattern.

Schematic

Slide 38 · Sarcoidosis: Trace the sign back to the tissue

Mutton-fat deposits → cells adhering to corneal endothelium.

Choroidal nodule → granulomatous inflammation in uveal stroma.

Candle-wax vascular sheathing → retinal perivascular inflammation.

Slide 39 · Case: Chronic granulomatous inflammation

A patient has anterior keratic precipitates and retinal venous sheathing.

Interpretation: The combined anterior/posterior pattern is compatible with ocular sarcoidosis.

Next step: A granulomatous pattern should prompt a search for corroborating systemic evidence and alternative causes.

Slide 40 · Sarcoidosis: What is and is not established

Established: Keratic precipitates, choroidal granulomas and retinal perivascular inflammation.

Not established by one ocular sign: Systemic sarcoidosis as the sole possible cause.

Appropriate inference: Compare findings and assess for mimics before etiologic attribution.

Slide 41 · Infectious posterior uveitis links compartments

Retina

Choroid

Infection may involve retina, choroid or both.

Inflammation in one compartment often accompanies inflammation in the adjacent compartment.

Describing the primary focus and associated uveitis improves anatomic precision.

Schematic

Slide 42 · Several infectious examples

Retinal toxoplasmosis with uveitis.

Cytomegalovirus retinitis in patients with AIDS.

Pneumocystis-associated uveal infection and mycobacterial choroiditis in AIDS.

Slide 43 · Toxoplasmosis commonly manifests as retinochoroiditis

Retina

Choroid

The retinal inflammatory focus is commonly accompanied by uveal inflammation.

Occasional associated scleritis.

The diagnostic target is the retinal lesion together with the surrounding ocular response.

Schematic

Slide 44 · Retinal inflammation may heal with a scar

Ocular toxoplasmosis can create a focal active retinal lesion.

After resolution, retinal scarring may remain.

Reactivation can threaten vision when central structures are involved.

Schematic

Slide 45 · Toxoplasma symptoms reflect inflammatory anatomy

Blurred or reduced vision indicates functional retinal or media involvement.

Photophobia, ocular discomfort and redness may accompany inflammation.

Clinical symptoms are not sufficiently specific to assign an infectious organism.

Slide 46 · CMV retinitis is an opportunistic setting

CMV retinitis in individuals with AIDS.

The immune status is part of the diagnostic context.

The textbook example emphasizes posterior retinal infection rather than isolated anterior iritis.

Slide 47 · Pneumocystis can involve the uvea

Pneumocystis as an example of infectious uveitis.

In patients with AIDS, the organism may produce uveal infection.

The named organism does not imply that every uveitis in immunocompromise is infectious.

Slide 48 · Mycobacterial infection may target the choroid

Mycobacterial choroiditis is included among AIDS-associated ocular infections.

A choroidal location may coexist with retinal inflammatory findings.

Infectious granulomatous disease is an important competing explanation for posterior ocular inflammation.

Slide 49 · Immune status changes the differential

Opportunistic retinal and choroidal infections must be considered in advanced immunosuppression.

Noninfectious inflammation remains possible.

The pathologic pattern and host context should be interpreted together.

Schematic

Slide 50 · Do not suppress inflammation before considering infection

Corticosteroid or immunosuppressive treatment may be appropriate in selected noninfectious uveitides.

Unrecognized infection changes the safety of that strategy.

Establishing infectious versus noninfectious etiology is therefore a clinically consequential distinction.

Slide 51 · Case: Posterior inflammation in advanced AIDS

A patient with advanced HIV-related immunosuppression develops a posterior retinal lesion.

Interpretation: Robbins explicitly lists CMV retinitis and other opportunistic posterior infections.

Next step: Organism-specific evaluation is required; The anatomic term “uveitis” is insufficient.

Slide 52 · Sympathetic ophthalmia is a bilateral panuveitis

Iris / anterior chamber

Vitreous / middle segment

Choroid and retina

The disease is noninfectious and granulomatous.

Both the previously injured and contralateral eye may be affected.

Diffuse uveal inflammation involves iris, ciliary body and choroid.

Slide 53 · A penetrating eye injury can precede disease

Exciting eye

Sympathizing eye

Antecedent ocular injury

Fellow eye becomes inflamed

Source of antigen exposure

Immune-mediated involvement

Also may show uveitis

Often prompts recognition

Sympathetic ophthalmia can follow penetration of one globe.

Slide 54 · Sequestered ocular antigens can become exposed

That retinal antigens are normally sequestered from systemic immune surveillance.

Penetrating trauma exposes these antigens.

Antigen access initiates an immune response rather than direct spread of an organism.

Schematic

Slide 55 · Conjunctival lymphatics provide an immune route

Antigens released after trauma may gain access to conjunctival lymphatics.

This connects sequestered ocular antigens with systemic immune recognition.

The model is a proposed mechanism; The precise antigenic targets are not settled.

Schematic

Slide 56 · Delayed hypersensitivity is the pathogenic model

A delayed hypersensitivity reaction after antigen exposure.

The response targets uveal tissues in both eyes.

This is a cell-mediated immune explanation for bilateral granulomatous inflammation.

Schematic

Slide 57 · Bilateral disease is not direct ocular spread

Exciting eye

Sympathizing eye

Shared immune response

Schematic

Slide 58 · The latency can be long

Symptoms may begin after a short interval or many years after injury.

Robbins specifies approximately 2 weeks to many years.

A remote trauma history remains diagnostically relevant.

Schematic

Slide 59 · Sympathetic ophthalmia has diffuse uveal granulomas

Retina (schematic)

Choroidal stroma

Granulomatous infiltrate

Histologic inflammation may be present throughout choroid, ciliary body and iris.

Granulomatous inflammation is the principal tissue pattern.

A localized posterior lesion alone would not convey the full pathologic distribution.

Schematic

Slide 60 · Pigmented material may occur within granulomas

Robbins Fig. 29.13 describes melanin pigment within uveal granulomas.

Pigment can reflect the involved pigmented ocular tissues.

The presence of pigment is a microscopic descriptor, not an organism or biomarker.

Slide 61 · The inflammatory cellular mixture has a pattern

Typical reported finding

Important qualification

Diffuse uveal granulomas

Not unique to this disease

Plasma cells usually absent

Not an absolute exclusion rule

Eosinophils may be present

Variable finding

Plasma cells as typically absent.

Slide 62 · Dalen–Fuchs nodules are an additional clue

The sympathetic-ophthalmia review describes sub–retinal pigment epithelial nodules.

They may correspond to yellow-white fundus spots.

They are not obligatory or pathognomonic; This detail supplements the Robbins extract.

Slide 63 · Treatment targets the systemic immune response

Systemic immunosuppressive agents as treatment.

The rationale is bilateral, immune-mediated inflammation.

Treatment choice and monitoring require specialist oversight and infection assessment.

Schematic

Slide 64 · Enucleation can supply diagnostic pathology

A blind eye may be removed and provide tissue for examination.

Robbins cautions that the enucleated blind eye is not necessarily the originally injured eye.

Gross history and microscopic distribution must be interpreted together.

Slide 65 · Compare sarcoidosis with sympathetic ophthalmia

Sarcoid-associated uveitis

Sympathetic ophthalmia

Systemic inflammatory setting

History of ocular penetration

Periphlebitis/candle-wax sign

Bilateral granulomatous panuveitis

Choroidal granulomas

Diffuse uveal granulomatous inflammation

Both may produce granulomatous anterior and posterior inflammation.

Slide 66 · Case: Delayed inflammation of the fellow eye

An eye develops granulomatous inflammation months after penetrating injury to the opposite eye.

Interpretation: Bilateral uveal involvement and delayed onset strongly suggest sympathetic ophthalmia.

Next step: Exclude competing granulomatous and infectious explanations before diagnosis.

Slide 67 · A disciplined evaluation starts with localization

Identify the dominant compartment: Anterior chamber, vitreous, retina/choroid or diffuse.

Describe granulomatous findings, vascular changes and structural complications.

Integrate immune status, systemic findings and trauma history before causal assignment.

Schematic

Slide 68 · Mechanism, morphology and context work together

Anterior synechiae link inflammation to impaired aqueous drainage.

Sarcoid periphlebitis links a retinal vascular sign to granulomatous disease.

Retinochoroiditis links posterior infection to adjacent uveal inflammation.

Sympathetic ophthalmia links penetrating trauma to bilateral immune disease.

Slide 69 · Five clinicopathologic conclusions

Uveitis is heterogeneous: Identify the involved tissue and mechanism.

Anterior chamber exudates can create synechiae, cataract and glaucoma.

Sarcoid produces choroidal granulomas and retinal periphlebitis.

Infection must be considered, particularly with immunosuppression.

Sympathetic ophthalmia is delayed bilateral granulomatous inflammation after ocular injury.

Slide 70 · Application: Do the signs establish etiology?

A patient shows mutton-fat keratic precipitates and bilateral posterior inflammation.

Interpretation: What evidence would favor sarcoidosis rather than sympathetic ophthalmia?

Next step: What infections must be considered before initiating immunosuppressive treatment?

Slide 71 · Selected references

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026; Ch. 29: The Eye.

Jabs DA et al. Standardization of Uveitis Nomenclature. Am J Ophthalmol. 2005.

Mochizuki M et al. Revised IWOS criteria. Br J Ophthalmol. 2019.

SUN Working Group. Classification criteria for the uveitides. Am J Ophthalmol. 2021.

Chu XK, Chan CC. Sympathetic ophthalmia review. J Ophthalmic Inflamm Infect. 2013.

CDC. Symptoms of Toxoplasmosis. 2024.