UVEITIC GLAUCOMAUVEITIC GLAUCOMA

TARIQ ALASBALI, MDTARIQ ALASBALI, MD..

POAGJUVENILE

PDSPXFHEMOLYTICPHACOLYTICINFLAMMATORY ↑ EVP

PUPILLARY BLOCK

PLATEAU IRIS

AXIAL SHALLOWING•CHOROIDAL EFFUSION•CHOROIDAL HE•AQ MISSDIRECTION•ROP•PHPV•CHOROIDAL MASS

PHACOMOROHICECTOPIA LENTISAPHAKICPSEUDOPHAKICINFLAMMATORY PSAQ MISSDIRECTIONSUBRETINAL MASS

PUSHING

PULLING

PERIPH SHALLOWINGIRIS CYSTCB CYSTCB SWELLING SULFA PRPCB INFLAMMATIONCB TUMOUR

PAS FORMATIONNVGINFLAMMATIONTRAUMATUMOUR RELATED

MEMBRANEGROWTHICEEPITH DOWNGROWTHFIBROUS INGROWTH

Uveitis Classifications

Anatomic Classification

Duration Classification

Uveitis Classifications

I) Anatomical Classification:• Anterior• Intermediate (Pars planitis 85%, MS, sarcoid,

TB, lyme, toxoplasmosis, toxocariasis, syphilis, IBD (children) lymphoma, Eale’s)

• Posterior• Panuveitis (ant + intermediate + post)

Anatomical Classification:

Q1: Which form of ocular inflammation (anatomical classification)

most frequently produces an IOP elevation?

A1: Anterior uveitis (chronic >>> acute)

Even glaucomas that result from other types of ocular inflammation are usually the consequence of secondary involvement of the anterior uveal tract.

Q2. What are typical IOPs in anterior uveitis?

A2. LOW secondary to CB shut down +/- increased uveoscleral outflow

Q2. What are typical IOPs in anterior uveitis?

Uveitis ClassificationsII) Duration Classification:

Acute: Usually anterior uveitis Sudden onset

Moderate ocular pain PhotophobiaBlurred vision IOP often

LOWER than other eye

Sub-acute: Often minimal symptoms often undetected till significant complications

Chronic: longer than 3 monthsMost likely to have ↑ IOP

Acute Anterior Uveitis

• 0.2% cumulative lifetime incidence in general population

• HLA-B27 positive – 50% of cases in white patients

(Lancet 1973; 2: 944)

– Younger age onset (median early 30s) (AJO 1995; 120:351)

– Male > female (AJO 1995; 120:351)

– Unilat or unilat alternating > bilat (AJO 1995; 120:351)

BEHÇET’S DISEASE

Idiopathic multisystem disease

More common in men

Occurs in 3rd - 4th decade

Associated with HLA-B5

Incidance: 1/100, 000 prevalence in USA 670/100,000 in Japan

BD is most prevalent (and more virulent) in the Mediterranean region, Middle East, and Far East, with an estimated prevalence of 1 case per 10,000 persons

BEHÇET’S DISEASE

Unknown Various bacteria and viruses

suggested No good evidence to suggest

any of them Tumour necrosis factor (TNF)

thought to be important

BEHÇET’S DISEASEAetiology

Oral aphthous ulceration – 100%

Genital ulceration – 90%

BEHÇET’S DISEASESystemic Involvement

Skin lesions – 80% Erythema

Nodosum

Acneiform

Uveitis 70% (inflam. of iris, ciliary body or choroid)

BEHÇET’S DISEASESystemic Involvement

CNS involvement – strokes

Major vessels SVC obstruction

Increased skin response to trauma

BEHÇET’S DISEASESystemic Involvement

Acute iritis Pain, redness & VA Flare Inflammatory cells

in anterior chamber KPs

Recurrent hypopyon(Fluid level of WBC)

BEHÇET’S DISEASEOcular Features

Marked inflammation of the eye

Retinal vasculitis and haemorrhage

Occlusive periphlebitis (venous sheathing & occlusion)

Cataract or glaucoma

BEHÇET’S DISEASEOcular Features

International criteria published in 1990 require

Oral ulcers 3 X /1 year + Any 2 of the following: 1. Recurrent genital ulcers2. eye lesions 3. Skin lesions4. Positive pathergy test 2mm plus papule developing over 24-48 hrs after

oblique insertion of a 20 gauge needle into skin.

BEHÇET’S DISEASEdiagnosis

Sarcoidosis

• Multisystem inflammatory disorder• Unknown origin• Young adults• Black• Histopathology: noncaseating granulomas• Systemic involvement: o Hilar lymphadenopathy,o Peripheral lymphadenopathy, o Cutaneous lesions

• 38-50% have ocular involvement (AJO 1978; 86:648 & Jpn

J Ophthalmol 1992; 36:452)

Sarcoidosis – Anterior Uveitis

• Most common ocular manifestation = chronic granulomatous uveitis

• Mutton fat KPs (15%) (AJO 1978; 86:648)

• Bilateral > unilateral

• Iris nodules (11.4-35%) (Ophthalmology 1986; 93: 511)

• AC angle nodules (49%) (Ophthalmology 1986; 93: 511)

• CB nodules (42%) (Ophthalmology 1986; 93: 511)

• Glaucoma in 11% with ocular sarcoid (AJO 1978; 86:648)

• Glaucoma in 34% with ocular sarcoid

(Jpn J Ophthalmol 2002;46:556-62 )

• Most common mechanism of glaucoma : - obstruction of TM with inflammatory debris or nodules

(Ann NY Acad Sci 1976; 278:445)

Other mechanisms: Inflammatory cell infiltration around the inner and outer walls

of Schlemm’s canalIris bombe with PAS formationNVI and NVA

Sarcoidosis – Anterior Uveitis

Posner Schlossman Syndrome

Fuch’s heterochromic iritis

PresentationAcute BOV, haloes, pain. Recurrent episodes

Asymptommatic. May have mild BOV

CellsMild inflammationIn AC, anterior vitreous

KPsFine, few, may be stellate

Small white stellate KPs, scattered diffusely

IrisHeterochromia ( diff stromal atrophy)Absence of posterior synechiae. Fine abnormal blood vessels on gonio

Other featuresCataract.

Posner Schlossman Syndrome

Fuch’s heterochromic iritis

Presentation

Acute BOV, haloes, pain. Recurrent episodes

Asymptommatic. May have mild BOV

CellsMild inflammation

In AC, anterior vitreous

KPsFine, few. May be stellate

Small white stellate KPs, scattered diffusely

IrisHeterochromia ( diff stromal atrophy)Absence of posterior synechiae. Fine abnormal blood vessels on gonio

Other features

Cataract.

Features• Described in 1948 by Posner and Schlossman

• “Glaucomatocylitic crisis” characterised by self-limited recurrent episodes of markedly elevated IOP with mild AC inflammation

•IOP elevation out of proportion to degree of AC inflammation

•Usually in adults 20-50 yrs

•Previously thought to be idiopathic, but postulated aetiologies include

oAbnormal vascular processoAutonomic defectoInfective: HSV, CMV

Posner Schlossman Syndrome

Fuch’s heterochromic iritis

Presentation

Acute BOV, haloes, pain. Recurrent episodes

Asymptommatic. May have mild BOV

CellsLow gradeIn AC, anterior vitreous

KPsFine, few (sometimes sentinel only)

Small white stellate KPs, scattered diffusely

IrisHeterochromia (diffuse stromal atrophy)Absence of posterior synechiae.Fine abnormal blood vessels on gonio

Other features

Cataract.

Features•Chronic unilateral (bilateral in 10%) iridocyclitis

•Classic triad ofo Iris heterochromiao KPso Cataract

•Low grade inflammation which does not usu req Rx

•Postulated aetiologyo Adrenergic dysfunctiono Infective cause: link between ocular toxoplasmosis and FHIo Immunologic theories

JIA

Monoarticular or pauciarticular or polyarticular. F>M RAF –ve ,ANA,HLA-B27. The most common systemic disease

associated with uveitis in children. Iridocyclitis in 30% of pauciarticular.

Arthritis then uveitis. Under treatment by ophthalmologists → PS +

PAS formation → closed angle glaucoma

Glaucoma===>14 -27% of JRA.

Infection (chronic endophthalmitis) Tumors (lymphoma, melanoma) Acute angle closure Neovascular glaucoma Secondary reaction to intraocular FB

Uveitis Masqueraders (i.e. cells in the AC with ↑ IOP but not uveitis)

First reported by:

Joseph Beer in -------- 1813Desmans in -------- 1821Mackenzie in -------- 1830

Glaucoma Associated with Uveitis

• Etiology of uveitis:• Topographic Types

Difference non-significant [P>0.05]

391391 eyeseyes F/U median 55 monthsF/U median 55 months

Neri P. J Glaucoma Neri P. J Glaucoma

2004;13:461-652004;13:461-65

ConclusionConclusion:: 1.1. Presence of glaucoma was associated with an increasing risk of visual loss. Presence of glaucoma was associated with an increasing risk of visual loss. 2.2. The incidence of glaucoma increased with time and similar among The incidence of glaucoma increased with time and similar among different types of uveitis. different types of uveitis.

IncidenceIncidence• 6.6% at 1 year• 11.2% at 4 years• 22.7% at 10 years

Secondary Glaucoma in Uveitis Secondary Glaucoma in Uveitis PatientsPatients

Clinical Entry Uveitis Secondary Glaucoma

Patients % Affected eyes (A) Eyes (B) B/A x 100 (%)

HTLV – 1 uveitis 194 17.7 260 4216.2

Vogt-Koyanagi-Harada’s disease 107 9.7 214 3516.4

Ocular toxoplasmosis 85 7.7 95 11 11.6

Sarcoidosis 71 6.5 129 4434.1

Behcet’s disease 55 5.0 96 2020.8

Herpetic anterior uveitis 22 2.0 23 7 30.4

HLA-B27-related acute anterior uvietis 21 1.9 25 520.0

Posner-Scholossman syndrome 10 0.9 10 10100*

Others 92 8.4 116 23 16.1

Idiopathic uveitis 442 40.2 636 9615.0

TOTAL 1099 100 1604 29318.3

*HTLV-I: human T-lymphotropic virus type1. HLA: human leukocyte antigen

Takahashi T et al. Jpn J Ophthalmol 2002;46:556-62

Glaucoma Associated with Uveitis

25% of uvetic patients: Ocular hypentensive

5-19% of uveitic patients: Develop S.G.

Risk factors for elevated IOP

in uveitis patients

1.1. ChronicityChronicity2.2. AgeAge3.3.CorticosterCorticoster

oidsoids4.4. ActivityActivity

Herbert H et al. J. Glaucoma 2004;13:96-99

JIA, and ANA JIA, and ANA positive positive uveitis uveitis without without evidence of evidence of arthritis.arthritis. seqandary glaucoma inseqandary glaucoma in children with uveitischildren with uveitis

Sijssens et al. Ophthalmology 2006;113:853-9

PATHOGENESIS

A. Biochemical and Cellular Changes in Aqueous Composition

B. Direct Involvement of the TMC. Corticosteroids Effects on the TMD. Morphologic Changes in the AC

Angle

1.1. ProteinsProteins

2.2. Inflammatory CellsInflammatory Cells

3.3. ProstaglandinsProstaglandins

4.4. Inflammatory Mediators (Cytokines) & Toxic Inflammatory Mediators (Cytokines) & Toxic AgentsAgents

A. Biochemical and Cellular Changes in Aqueous Composition

PATHOGENESISPATHOGENESIS

Normal aqueous content is 1% ofNormal aqueous content is 1% of

that in the serumthat in the serum1.1. ProteinsProteins

uveitis

permeability of blood-aqueous barrier (non-specific)

proteins in the aqueous (resembles undiluted resembles undiluted serum)serum)

PersistePersistentnt

Affects IOPAffects IOP

IndirectlyIndirectlyPost synechiae & PASPost synechiae & PAS

DirectlyDirectlyAqueous sludging, impeding outflowAqueous sludging, impeding outflow

A.A. Biochemical and Cellular Changes in Biochemical and Cellular Changes in Aqueous CompositionAqueous Composition

PATHOGENESISPATHOGENESIS

2.2. Inflammatory CellsInflammatory Cells

Affects IOPAffects IOP

IndirectlyIndirectlyBy releasing inflammatory mediators, altering TM cells size, function and extra-cellular matrix composition.

DirectlyDirectlyInfiltrate TM and SC causing mechanical blockage

3. Prostaglandins

Affects IOP Prostaglandins E1 & 2 IOP

Prostaglandins F2 α IOP

A.A. Biochemical and Cellular Changes in Biochemical and Cellular Changes in Aqueous CompositionAqueous Composition

PATHOGENESISPATHOGENESIS

4. Inflammatory Mediators (Cytokines) & Toxic

Agents

A.A. Biochemical and Cellular Changes in Biochemical and Cellular Changes in Aqueous CompositionAqueous Composition

PATHOGENESISPATHOGENESIS

Conventional rootConventional root

Interleukin-1Interleukin-1

B. Direct Inflammation of the TM Posner-sehlossman Syndrome Fuchs’ Uveitis Herpetic Keratouveitis

PATHOGENESISPATHOGENESIS

C. Effect of Corticosteroids on the TM 35% of normal population, moderate

responders 4-6% high responders (>15mmHg) 50% or more of POAG population, high

responders

PATHOGENESISPATHOGENESIS

Weireb RN et al. Invest Ophthalmol Vis Sci 1985;26:170-5Weireb RN et al. Invest Ophthalmol Vis Sci 1985;26:170-5Levin DS, et al. Am J Ophtalmol 2002;133:196-202Levin DS, et al. Am J Ophtalmol 2002;133:196-202

Affects IOPAffects IOP

Reduction of aqueous Reduction of aqueous outflow BYoutflow BY

1.1. Alteration in cell sizeAlteration in cell size2.2. Cytoskeletal Cytoskeletal

organizationorganization3.3. Extra-cellular matrix Extra-cellular matrix

depositiondeposition Veda J et al. Invest Ophthalmol Vis Sci 2003;44:4772-9Veda J et al. Invest Ophthalmol Vis Sci 2003;44:4772-9

Velota et al. Curr Opn Ophthalmol 2004;15:136-140Velota et al. Curr Opn Ophthalmol 2004;15:136-140

Increase the aqueous

production

Incidence of steroid responsiveness

HighHigh(%)(%)ModerateModerate(%)(%)NonNon(%)(%)

General General PopulationPopulation5535356060Pts With Pts With POAGPOAG9090101000Siblings of Siblings of pts with pts with POAGPOAG

303050502020

Offspring of Offspring of pts with pts with POAGPOAG

2525707055

PATHOGENESIS

D. Morphologic Changes in the Anterior Chamber Angle

Open Angle Uveitic Glaucoma

• Mechanical blockage to outflow pathways

• Chronic inflammatory damage to outflow pathways

• Trabeculitis• Steroid-induced

PATHOGENESIS

D. Morphologic Changes in the Anterior Chamber Angle

Angle Closure Uveitic Glaucoma

Uveitic Glaucoma

ManagementEvaluation

History & SymptomsVisual function (perimetry)Slit-lamp: Etiology cluesGonioscopy: ClassificationFundus biomicroscopy: Clues, C/D, NFLUBM: Iridocorneal angle, Ciliary body

Proper DiagnosisProper Diagnosis Proper DiagnosisProper Diagnosis

Uveitis Work Up

• CBC + differential• HLA• ESR + CRP• ACE, lysozyme• CXR +/- CT chest• FTA Abs + VDRL• TB skin test• Titers: toxocariasis, toxoplasmosis,

lyme

Management

Control Inflammation:

Undertreating

uveitis with corticosteroids to minimize IOP elevation at the expense of good control

of inflammation

isis

A A false false economyeconomy

Management

Medical therapy: Beta-blockers CA inhibitors Adrenergic agonists Prostaglandin analogues? Miotics - Avoid

Q3: What glaucoma drops have been associated with uveitis?

A3: Brimonidine (AJO 2000; 130:287)

Metipranolol (AJO 1997; 123:843)

prostaglandin analogues (Surv Ophthalmol 2002;

47 (suppl 1): S219)

Management

Surgical: Laser therapy

- Laser iridotomy (pupillary block)- ALT – ineffective (avoid it)

Filtering surgeryFiltering surgery - Trabeculectomy with - Trabeculectomy with antimetaboliteantimetabolite - Non-penetrating glaucoma - Non-penetrating glaucoma surgerysurgery

- Tube surgery- Tube surgery- Goniotomy- Goniotomy

Cyclodestructive Cyclodestructive proceduresprocedures

Management

Surgical:Trabeculectomy with anti metabolites

Up to now is the procedure of choice Success rates variable (30%-78% after 5

years)

HypotonyHypotony & & cataractcataract formation were significant complicationsformation were significant complications..

Towler HMA et al. Ophthalmology 2000;107:1822-28Ceballos EM et al. J Glaucoma 2002;11:189-196

Tube Surgery in Uveitic Tube Surgery in Uveitic GlaucomaGlaucoma

* Ahmad Glaucoma Valve* Ahmad Glaucoma Valve :: (14 (14 eyes, 21 eyes)eyes, 21 eyes)

Success Rates ------ 57% to 94% at 1 yearSuccess Rates ------ 57% to 94% at 1 year

* Molteno Implant:* Molteno Implant: (40 eyes)(40 eyes) - - Success Rates: ------ 87% at 5 yearsSuccess Rates: ------ 87% at 5 years ------ 77 % at 10 years------ 77 % at 10 years - - Corneal decompensation ------- 27%Corneal decompensation ------- 27%

Mata AD et alMata AD et alOphthalmology 1999;11:2168-72Ophthalmology 1999;11:2168-72

Ceballos EMCeballos EMJ. Glaucoma 2002; 11:189-96J. Glaucoma 2002; 11:189-96

Cyclophotocoagulation in Uveitic Glaucoma

Should be used with caution in patients with uveitis.

Already inflammed ciliary body• Exacerbate the inflammation• Higher risk of profound hypotony• Visual loss and phthysis bulbi is a significant risk.

Murphy CC et al. Br J Ophthalmol 2003;87:1252-7

Rate of hypotony in uveitic eyes was 19%Rate of hypotony in uveitic eyes was 19%

Aside…DDx Krukenberg Spindle• PDS

– Young– Myopic– Male– 10% have glaucoma– ↑ risk RD

• Trauma• Iris infarction (e.g. zoster, ACG)• Tumor• Uveitis

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