PRIMARY OPEN ANGLE GLAUCOMA (POAG)

DR KALPANA SANGWANPOST GRADUATE

DEPARTMENT OF OPHTHALMOLOGYGMC HALDWANI

Glaucoma

Chronic, progressive optic neuropathy caused by a group of ocular conditions which lead to damage of the optic nerve with loss of visual function

IOP is the major risk factor

Normal tension glaucoma

PRIMARY OPEN ANGLE GLAUCOMA(POAG)

• K/a Chronic simple glaucoma

• Most prevalent of all glaucoma

• Affects both sexes equally

POAG

• An IOP >21 mmHg

• Glaucomatous optic nerve damage

• An open normal appearing anterior chamber angle

• Characteristic visual field loss

• Absence of signs of secondary glaucoma or a non-glaucomatous cause for the optic neuropathy

GENETICS• Mutations at 15 loci in the human genome..GLC1A to

GLC1O• 4 susceptible genes have been identified• MYOC gene (chromosome 1q21-q31), coding for the

glycoprotein myocilin that is found in the trabecular meshwork and other ocular tissues• OPTN gene on chromosome 10p, which codes for

optineurin• WDR36 gene on chromosome 5q22 • NTF4 gene on chromosome 19q13.3.

Among them MYOC is the most frequently mutated gene in POAG

Risk factors

• IOP• Age• Race• Family history• Diabetes Mellitus• Myopia

Changes in IOP

• IOP >21 mm Hg on more than one occasion

• Circardian variation of IOP >8 mm Hg

• Asymmetry of IOP >5 mm Hg between two eyes

AGE

• Advanced age is an important risk factor for the presence of POAG. • The Baltimore Eye Survey found that the prevalence of

glaucoma increases dramatically with age• Particularly among blacks, exceeding 11% in those aged

80 years or older• Visual field defects were 7 times more likely to develop in

patients aged 60 yrs or older

RACE

• Black race is another important risk factor for POAG

• The prevalence of POAG is 3 to 4 times greater in blacks than in others.

POSITIVE FAMILY HISTORY

Positive family history is also a risk factor for glaucoma.

The Baltimore Eye Survey found that the relative risk of having POAG is increased approximately 3.7-fold for individuals who have a sibling with POAG

ASSOCIATED DISORDERS•MYOPIA

BEAVER DAM STUDY showed that myopia was a significant risk factor for glaucoma prevalence

ROTTERDAM STUDY high myopia (>-4 D) was associated with a hazard ratio of 2.31 for development of incident glaucoma.

The concurrence of POAG and myopia may complicate both diagnosis and management.

………..

• Disc evaluation is particularly complicated in the presence of myopic fundus changes

• Myopia-related retinal changes can cause visual field abnormalities apart from any glaucomatous process.

• High refractive error may also make it difficult to perform accurate perimetric measurement and to interpret visual field abnormalities.

DIABETES

Role is controversialThe Beaver Dam study ,The Blue mountain study found an

association btw diabtes & POAG While Rotterdam study ,Framingham study & Barbados

study didn’t find any association.

CVS DISEASE

• Associations between POAG and blood pressure or perfusion pressure of the eye have been reported. • Systemic hypertension, with its possible microcirculatory

effects on the optic nerve, may increase susceptibility to glaucoma .• Lower systolic perfusion pressure, lower systolic blood

pressure, and cardiovascular disease history are risk factors for glaucoma progression

RETINAL VENOUS OCCLUSION

• Patients with CRVO may present with elevated IOP and glaucoma

OTHER ASSOCIATED CONDITIONS

• Sleep apnea• Thyroid disorders• Hypercholestrolemia• Migraine• Raynauds phenomena

Patho-physiology

Pathogenesis of rise in IOP

• Rise in IOP occurs due to decrease in the aqueous outflow• Reduced aqueous outflow facility occurs due to failure of

aqueous outflow pump mechanism• Thickening and sclerosis of trabecular meshwork with

faulty collagen tissue• Narrowing of intertrabecular spaces• Deposition of amorphous material in the juxta-

canalicular space• Collapse of schlemm’s canal and absence of giant

vacuoles in the cells lining it

Pathogenesis of glaucomatous optic neuropathy

1.Ischaemic theorySuggests that poor blood perfusion of ONH causes ischaemia and resultant loss of optic nerve fibres 2.Mechanical theory Suggests that weakness of supporting tissues of optic nerve head makes it susceptible to mechanical deformation by IOP with resultant nerve fibre damage

3. Immune theory Increased incidence of paraproteinemia and auto

antibodies and antiglutathione S-transferace antibodies

Cause retinal ganglion cell apoptosis

4. Apoptotic theory Genetically programmed destruction of retinal

ganglion cells may play a part in the pathogenesis

Clinical features• Usually asymptomatic until a significant visual

field loss has occurred

• Eye ache, headache, coloured haloes

• Delayed dark adaptation time

• Frequent changes of presbyopic(near) glasses

• Raised IOP & fluctuations in IOP

Base line information

• History: Ocular, Systemic, Family history, History of medication• Pupillary reaction• Slit lamp bio-microscopy: Anterior segment to rule outo 2° causes- shallow

anterior chamber, pseudoexfoliation syndrome, inflammation

Fundus evaluation to rule out lesions which can cause visual field defects

Applanation tonometry and Diurnal variation test

• CCT > 555µm: false high IOP < 540µm: false low IOP

• Gonioscopy

• Perimetry: Automatic static threshold perimetry

• Provocative Tests: Water drinking test

DIAGNOSIS

• Primary open angle glaucoma (POAG)IOP(>21 mm of Hg) associated with definite glaucomatous optic

disc cupping and visual field changes

• Ocular hypertension or glaucoma suspectIOP constantly more than 21 mm of Hg but no optic disc or

visual field changes

• Normal tension glaucoma (NTG)Typical glaucomatous disc cupping with or without visual field

changes is associated with an intraocular pressure constantly below 21 mm of Hg

NTG(NORMAL TENSION GLAUCOMA)

• The term normal tension glaucoma (NTG), also referred to as low tension glaucoma is labelled:

Typical glaucomatous disc changes with or without visual field defectsIOP constantly below 21 mm of HgNOTE: IOP reduction of at least 30% is associated with protection of visual field and nerve status in NTG

Pathogenesis

• It is believed to result from chronic low vascular perfusion, which makes the optic nerve head susceptible to normal IOP• Multifactorial disease• Higher prevalence of vasospastic disorders such as

migraine headache and Raynaud phenomenon, ischemic vascular diseases, autoimmune diseases, and coagulopathies

………

• Some authorities have separated normal-tension glaucoma into 2 groups based on disc appearance:

Senile sclerotic group with shallow, pale sloping of the neuroretinal rim (primarily in older patients with vascular disease)

Focal ischemic group with deep, focal notching in the neuroretinal rim

POAG vs NTG

• NRR -thinner, especially inferiorly and infero-temporally, in persons with NTG

• The visual field defects in normal-tension glaucoma tend to be more focal, deeper, and closer to fixation, especially early in the course of the disease

• Optic disc hemorrhages are more common among patients with NTG

DIFFERENTIAL DIAGNOSIS1.HIGH PRESSURE GLAUCOMAS• POAG• GLAUCOMA with intermitent rise in iop• Previous episodes of glaucoma

2.Non glaucomatous optic neuropathies• Congenital optic disc anomalies• Acquired optic neuropathies

GLAUCOMA SUSPECT

• An individual who has optic nerve or nerve fiber layer defect suggestive of glaucoma (enlarged cup- disc ratio, asymmetric cup-disc ratio, notching or narrowing of the neuroretinal rim, a disc hemorrhage, or suspicious alteration in the nerve fiber layer) in absence of VF defects

• A visual field abnormality consistent with glaucoma in absence of ONH changes

• SWAP & FDT perimetry have a good role in detecting early glaucomatous visual function loss

OCULAR HYPERTENSTION

• IOP constantly more than 21 mm of Hg• But no optic disc or visual field changes

Triad of abnormalities in disc, field and intraocular pressure (IOP) for the diagnosis of glaucoma.

Optic nerve head changes

• Asymmetry of CDR >0.2

• A localized notch or thinning of NRR

• Enlarged CDR >0.5 in vertical axis

• Superficial disc hemorrhages

• Shift of vessels to nasal side

• Bayonetting

• Para-papillary atrophy

• Lamellar-dot sign

Non-specific signs of glaucomatous damage. (A) Inferior baring of circumlinear blood vessels; (B) inferior bayoneting; (C) collaterals; (D) loss of nasal neuroretinal rim; (E) lamellar dots; (F) disc haemorrhage

Anderson’s criteria

On static perimetry, glaucomatous field loss is considered significant if:

1. Analysis of glaucoma hemi-field test is abnormal in 2 consecutive occasions

2. 3 contiguous non-edge points on the pattern deviation plot within Bjerrum area have a probability of < 5% of being in normal population, one of which have a probability of < 1%

3. Pattern standard deviation (PSD) should have a probability of < 5% confirmed on two consecutive tests

Visual field abnormalities

• Initially observed in Bjerrum area, 10- 25° from fixation• Correlate with abnormalities seen on optic nerve head• Field defects:

1. Paracentral scotomas2. Nasal step3. Siedel scotoma4. Arcuate scotoma5. Double arcuate or ring scotoma6. End-stage or near total defect with only a residual temporal island of vision

Grading of glaucomatous damage• MILD DAMAGEMinimal cuppingNasal step / Para-central

stepMD < -6dB

• MODERATE DAMAGEThinning of NRRArcuate scotomaMD < -12dB

• SEVERE DAMAGEMarked cuppingExtensive visual field

loss including defects within central 5 degree

MD > -12dB

• END STAGEGross cuppingSmall residual field

TREATMENT

MEDICAL MANAGEMENT

LASER

SURGICAL

Principle of treatment

• Usually start with MEDICAL THERAPY.

• Before starting the treatment - Assess each eye individually, inform patients

• Start treatment in worse eye first

• Set TARGET IOP

Target IOP depends upon

• IOP at which damage has occurred

• Severity of Visual Field damage

• Rate of progression of damage

• Age and Life Expectancy

TARGET IOP

• Level at which damage doesn’t develop or already existing damage doesn’t progress• Progression may be slow & it may take 3-5 yrs to find a

safe IOP level for an individual

• Target IOP must be updated during follow ups by monitoring progression of structural & visual field abnormalities

• Target IOP must be </=25% of the untreated level

• Target IOP should be lower esp if the patient has• Advanced glaucoma• Several Risk factors• Long life expectancy• Aggressive glaucoma

• Central corneal thickness(CCT): Patients with thin corneas having been identified as a major risk factor for patients with ocular hypertension

……………..

• In most cases, reducing the IOP by 20% to 30% from baseline is recommended• Target IOP in • Middle to high teens (mm Hg) for eyes with minimal

damage (e.g., early neural rim thinning without visual field loss), • Low to middle teens for eyes with moderate damage

(e.g., cupping to the disc margin in one quadrant with early field loss)• High single digits to low teens for eyes with

advanced damage (e.g., extensive cupping and field loss).

Classification• Drugs decreasing AQUEOUS PRODUCTION Beta-blockers Alpha-2-agonists Carbonic anhydrase inhibitors• Drugs increasing TRABECULAR OUTFLOW

ParasympathomimeticsNon selective agonistsProstamides

• Drugs increasing UVEOSCLERAL OUTFLOWAlpha-2-agonistsProstaglandins & Prostamides

I Line II Line III Line

Rationale for drugs Combinations

• Do not combine drugs of same pharmacological group

• More than two drugs usually not recommended

• If first line of drugs is not effective or tachyphylaxis occurs-change drug rather than adding another drug

LASERS IN POAG

• Outflow Enhancement • Laser Trabeculoplasty

• Inflow reduction• Cyclophoto-coagulation (in end stage

disease)

LASER TRABECULOPLASTY

• Uncontrolled glaucoma despite maximal tolerated medical therapy particularly in elderly

• Avoidance of poly-pharmacy (>2 drugs)• Avoidance of surgery

• Poor compliance

• Mechanism of action outflow facility by causing shrinkage of trabecular meshwork

Surgery in POAGIndications:• Failure of medical therapy

• Anticipated progressive damage or intolerably high IOP

• Combined with cataract procedure (phacotrabeculectomy)

• Primary therapy

• Poor compliance

SURGERIES• Penetrating filtration surgeries

• TRABECULECTOMY

• Non-penetrating filtration surgery(NPFS)• Deep Sclerectomy• Visco-canalostomy

Recent advances in glaucoma surgeries

I. The Ex-Press mini glaucoma shunt

II. Nonpenetrating Ab Externo Schlemm’s Canaloplasty

III. Ab Interno Devices: The Trabeculotome and Micro-bypass Stent

IV. The Gold Microshunt: A Suprachoroidal Device

NEUROPROTECTION

• Anti Oxidants• Calcuim Channel Blockade• Glutamate Blockade• Anti Apoptosis Agents• Neurotropins• Heat Shock Proteins• Nitric Acid Synthase Protection

Overview of Guidelines from Glaucoma Clinical Trials

•Ocular Hypertension Study: Risk factors for development of POAG1. Older age2. Higher IOP3. Greater pattern standard deviation4. Thinner central corneal thickness5. Larger vertical cup-disc ratio

Collaborative Normal Tension Glaucoma Study:

Risk factors for progression

1. Female gender2. Recurrent disc hemorrhages3. History of migraines

Early Manifest Glaucoma Treatment Trial:

• Risk factors for progression

1. Higher IOP 2. Exfoliation3. Older age4. Bilateral disease5. Worse mean deviation on VF6. Recurrent disc hemorrhages

The Collaborative Initial Glaucoma Treatment Study (CIGTS)

1. Medical therapy was as effective as trabeculectomy

2. Quality of life surveys were similar with the two groups, with the exception of more local symptoms with trabeculectomy

The Advanced Glaucoma Intervention Study (AGIS)

1. African Americans had less progression with initial laser treatment while Caucasians had better outcomes with trabeculectomy

2. Higher IOP fluctuation was associated with VF progression

3. Reduced risk of progression was noted with IOP consistently below 18 mm Hg or largely below 14 mm Hg.

…………..

• Glaucoma Laser Treatment Trial (GLT)Initial laser trabeculoplasty was as effective as

medical therapy

• Flurouracil Filtering Surgery StudyThe success of trabeculectomy was improved with

post-operative use of 5FU