UVEITIC GLAUCOMA

UVEITIC GLAUCOMA
TARIQ ALASBALI, MD.
POAG
JUVENILE
PDS
PXF
HEMOLYTIC
PHACOLYTIC
INFLAMMATORY
↑ EVP
PUPILLARY BLOCK
PLATEAU IRIS
WITHOUT
WITH
PUPILLARY BLOCK
PUPILLARY BLOCK
PHACOMOROHIC
ECTOPIA LENTIS
APHAKIC
PSEUDOPHAKIC
INFLAMMATORY PS
AQ MISSDIRECTION
SUBRETINAL MASS
PUSHING
AXIAL SHALLOWING
•CHOROIDAL EFFUSION
•CHOROIDAL HE
•AQ MISSDIRECTION
•ROP
•PHPV
•CHOROIDAL MASS
PERIPH SHALLOWING
IRIS CYST
CB CYST
CB SWELLING
SULFA
PRP
CB INFLAMMATION
CB TUMOUR
PULLING
PAS FORMATION
NVG
INFLAMMATION
TRAUMA
TUMOUR RELATED
MEMBRANEGROWTH
ICE
EPITH
DOWNGROWTH
FIBROUS 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?
Q2. What are typical IOPs in anterior uveitis?
A2. LOW secondary to CB shut down +/increased uveoscleral outflow
Uveitis Classifications
II) Duration Classification:
Acute:
Usually anterior uveitis
Moderate ocular pain
Blurred vision
Sudden onset
Photophobia
IOP often LOWER than other eye
Sub-acute:
Often minimal symptoms
often undetected till significant complications
Chronic: longer than 3 months
Most 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
BEHÇET’S DISEASE
 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
Aetiology
 Unknown
 Various bacteria and viruses
suggested
 No good evidence to suggest any
of them
 Tumour necrosis factor (TNF)
thought to be important
BEHÇET’S DISEASE
Systemic Involvement
 Oral aphthous
ulceration – 100%
 Genital ulceration –
90%
BEHÇET’S DISEASE
Systemic Involvement
 Skin lesions – 80%
 Erythema Nodosum
 Acneiform
 Uveitis 70% (inflam.
of iris, ciliary body or
choroid)
BEHÇET’S DISEASE
Systemic Involvement
 CNS involvement – strokes
 Major vessels
SVC obstruction
 Increased skin response to trauma
BEHÇET’S DISEASE
Ocular Features
 Acute iritis
 Pain, redness & VA
 Flare
 Inflammatory cells in
anterior chamber
 KPs
 Recurrent hypopyon
(Fluid level of WBC)
BEHÇET’S DISEASE
Ocular Features
 Marked inflammation of
the eye
 Retinal vasculitis and
haemorrhage
 Occlusive periphlebitis
(venous sheathing &
occlusion)
 Cataract or glaucoma
BEHÇET’S DISEASE
diagnosis
International criteria published in 1990 require
Oral ulcers 3 X /1 year
+
Any 2 of the following:
1.
2.
3.
4.
Recurrent genital ulcers
eye lesions
Skin lesions
Positive pathergy test
2mm plus papule developing over 24-48 hrs after oblique insertion of
a 20 gauge needle into skin.
Sarcoidosis
•
•
•
•
•
•
o
o
o
Multisystem inflammatory disorder
Unknown origin
Young adults
Black
Histopathology: noncaseating granulomas
Systemic involvement:
Hilar lymphadenopathy,
Peripheral lymphadenopathy,
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)
Sarcoidosis – Anterior Uveitis
•
•
•
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 canal
Iris bombe with PAS formation
NVI and NVA
Posner Schlossman
Syndrome
Fuch’s heterochromic
iritis
Presentation
Acute BOV, haloes,
pain. Recurrent
episodes
Asymptommatic. May have
mild BOV
Cells
Mild inflammation
In AC, anterior vitreous
KPs
Fine, few, may be
stellate
Small white stellate KPs,
scattered diffusely
Iris
Heterochromia ( diff stromal
atrophy)
Absence of posterior
synechiae.
Fine abnormal blood vessels
on gonio
Other features
Cataract.
Posner
Schlossman
Syndrome
Presentation
Acute BOV,
haloes, pain.
Recurrent
episodes
Cells
Mild
inflammation
KPs
Fine, few.
May be
stellate
Iris
Other
features
Fuch’s heterochromic
iritis
Features
• Described in 1948 by Posner and
Asymptommatic.
May
Schlossman
have mild BOV
• “Glaucomatocylitic crisis” characterised
by self-limited recurrent episodes of
markedly elevated IOP with mild AC
In
AC, anterior vitreous
inflammation
•IOP elevation out of proportion to degree
of AC inflammation
Small white stellate KPs,
scattered diffusely
•Usually in adults 20-50 yrs
Heterochromia ( diff
stromal atrophy)
Absence of posterior
synechiae.
Fine abnormal blood
vessels on gonio
•Previously thought to be idiopathic, but
postulated aetiologies include
oAbnormal vascular process
Cataract.
oAutonomic defect
oInfective: HSV, CMV
Posner
Schlossman
Syndrome
Fuch’s heterochromic
iritis
Presentation
Acute BOV,
haloes, pain.
Recurrent
episodes
Asymptommatic. May
have mild BOV
Cells
Low grade
In AC, anterior vitreous
KPs
Fine, few
(sometimes
sentinel only)
Iris
Other features
Features
•Chronic unilateral (bilateral
in 10%) iridocyclitis
•Classic triad of
o Iris heterochromia
o KPs
o Cataract
Small white stellate KPs,
scattered diffusely
•Low grade inflammation
which does not usu req Rx
Heterochromia (diffuse
stromal atrophy)
•Postulated aetiology
Absence of posterior
o Adrenergic dysfunction
synechiae.
o Infective cause: link
Fine abnormal blood
between ocular
vessels on gonio
toxoplasmosis and FHI
o Immunologic theories
Cataract.
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.
Uveitis Masqueraders
(i.e. cells in the AC with ↑ IOP but not
uveitis)
 Infection (chronic endophthalmitis)
 Tumors (lymphoma, melanoma)
 Acute angle closure
 Neovascular glaucoma
 Secondary reaction to intraocular FB
GLAUCOMA ASSOCIATED WITH
UVEITIS
First reported by:
Joseph Beer in -------- 1813
Desmans in -------- 1821
Mackenzie in -------- 1830
Glaucoma Associated with Uveitis
391 eyes
F/U median 55 months
• Etiology of uveitis:
Incidence Types
• Topographic
• 6.6% at 1 year
Difference
non-significant
• 11.2%
at 4 years [P>0.05]
• 22.7% at 10 years
Conclusion:
1. Presence of glaucoma was associated with an increasing risk of visual loss.
2. The incidence of glaucoma increased with time and similar among
different types of uveitis.
Neri P. J Glaucoma
2004;13:461-65
Secondary Glaucoma in Uveitis
Patients
Clinical Entry
Uveitis
Patients
HTLV – 1 uveitis
194
Vogt-Koyanagi-Harada’s disease
107
Ocular toxoplasmosis
85
Sarcoidosis
71
Behcet’s disease
55
Herpetic anterior uveitis
22
HLA-B27-related acute anterior uvietis 21
Posner-Scholossman syndrome
10
Others
92
Idiopathic uveitis
442
TOTAL
1099
Secondary Glaucoma
%
Affected eyes (A)
17.7
9.7
7.7
6.5
5.0
2.0
1.9
0.9
8.4
40.2
100
260
214
95
129
96
23
25
10
116
636
1604
Eyes (B)
42
35
11
44
20
7
5
10
23
96
293
B/A x 100 (%)
16.2
16.4
11.6
34.1
20.8
30.4
20.0
100*
16.1
15.0
18.3
*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.
2.
3.
4.
Chronicity
Age
Corticosteroids
Activity
Herbert H et al. J. Glaucoma
2004;13:96-99
JIA, and ANA
positive uveitis
without evidence
of arthritis.
seqandary glaucoma in
children with uveitis
Sijssens et al. Ophthalmology
2006;113:853-9
PATHOGENESIS
A. Biochemical and Cellular Changes in Aqueous
Composition
Proteins
B. 1.Direct
Involvement of the TM
Inflammatory CellsEffects on the TM
C. 2.Corticosteroids
ProstaglandinsChanges in the AC Angle
D. 3.Morphologic
4. Inflammatory Mediators (Cytokines) & Toxic Agents
PATHOGENESIS
A. Biochemical and Cellular Changes in Aqueous
uveitis
Composition
Normal aqueous
content is 1% of
permeability of blood-aqueous
barrier
(non-specific) that in the serum
1. Proteins
proteins in the aqueous (resembles undiluted serum)
Persistent
Affects IOP
Indirectly
Directly
Post synechiae & PAS
Aqueous sludging, impeding outflow
PATHOGENESIS
A. Biochemical and Cellular Changes in Aqueous
Composition
2. Inflammatory Cells
Affects IOP
Indirectly
Directly
By releasing inflammatory mediators,
Infiltrate TM and SC causing
altering TM cells size, function and
mechanical blockage
extra-cellular matrix composition.
PATHOGENESIS
A. Biochemical and Cellular Changes in Aqueous
Composition
3. Prostaglandins

Affects IOP
 Prostaglandins E1 & 2
 Prostaglandins F2 α
IOP
IOP
PATHOGENESIS
A. Biochemical and Cellular Changes in Aqueous
Composition
4.
Inflammatory Mediators (Cytokines) & Toxic Agents
Interleukin-1
Conventional root
PATHOGENESIS
B. Direct Inflammation of the TM



Posner-sehlossman Syndrome
Fuchs’ Uveitis
Herpetic Keratouveitis
PATHOGENESIS
Affects IOP
C. Effect of Corticosteroids on the TM



Increase the aqueous
production
35% of normal population, moderate responders
Reduction of aqueous outflow BY
4-6% high
responders (>15mmHg)
50% or more of POAG population, high responders
1.
2.
3.
Alteration in cell size
Cytoskeletal organization
Extra-cellular matrix deposition
Weireb RN et al. Invest Ophthalmol Vis Sci 1985;26:170-5
Levin
et Invest
al. AmOphthalmol
J OphtalmolVis
2002;133:196-202
Veda JDS,
et al.
Sci 2003;44:4772-9
Velota et al. Curr Opn Ophthalmol 2004;15:136-140
Incidence of steroid
responsiveness
High(%)
Moderate(%)
Non(%)
5
35
60
Pts With
POAG
90
10
0
Siblings of pts
with POAG
30
50
20
Offspring of
pts with POAG
25
70
5
General
Population
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
Management
 Evaluation
Proper Diagnosis
Proper Diagnosis
 History & Symptoms
 Visual function (perimetry)
 Slit-lamp: Etiology clues
 Gonioscopy: Classification
 Fundus biomicroscopy: Clues, C/D, NFL
 UBM: Iridocorneal angle, Ciliary body
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
is
A false economy
Management
 Medical therapy:
 Beta-blockers
 CA inhibitors
 Adrenergic agonists
 Prostaglandin analogues?
 Miotics - Avoid
Q3: What glaucoma drops have been
associated with uveitis?
A3: Brimonidine
Metipranolol
prostaglandin analogues
(AJO 2000; 130:287)
(AJO 1997; 123:843)
(Surv Ophthalmol 2002; 47 (suppl 1): S219)
Management
Surgical:
 Laser therapy
- Laser iridotomy (pupillary block)
- ALT – ineffective (avoid it)

Filtering surgery
- Trabeculectomy with antimetabolite
- Non-penetrating glaucoma surgery
- Tube surgery
- Goniotomy

Cyclodestructive procedures
Management
Surgical:
 Trabeculectomy with anti metabolites
 Up to now is the procedure of choice
 Success rates variable (30%-78% after 5 years)
Hypotony & cataract
formation were significant complications.
Towler HMA et al. Ophthalmology 2000;107:1822-28
Ceballos EM et al. J Glaucoma 2002;11:189-196
Tube Surgery in Uveitic Glaucoma
* Ahmad Glaucoma Valve : (14 eyes, 21 eyes)
Success Rates ------ 57% to 94% at 1 year
Mata AD et al
Ophthalmology 1999;11:2168-72
* Molteno Implant: (40 eyes)
- Success Rates: ------ 87% at 5 years
------ 77 % at 10 years
- Corneal decompensation ------- 27%
Ceballos EM
J. 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.
Rate of hypotony in uveitic eyes was 19%
Murphy CC et al. Br J Ophthalmol
2003;87:1252-7
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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