PRIMARY OPEN ANGLE GLAUCOMA

BHAVISHYA KEERTHI ANNA VALDER

OPEN ANGLE GLAUCOMA

Aka: chronic simple glaucoma (CSG) and primary open angle glaucoma (POAG)

Angle Anatomy

Open angle Glaucoma

Open angle glaucoma, is a multifactorial condition characterized by damage to and loss of optic nerve axons, resulting most commonly in loss of peripheral aspect of the visual field, which may progress to loss of central vision.

PREVALENCE AND INCIDENCE OF POAG

Population-based studies show that the prevalence of POAG ranges from 0.4% to 8.8% in those older than age of 40.  On average, POAG is found in 1.9% of white and 0.58% of Asian populations. In black populations however, the prevalence is significantly higher at 6.7%. The significantly higher rates observed in Western African populations probably reflect a fundamental risk factor associated with race


Ethnicity

Ethnicity affects both the chance of an individual developing glaucoma and the prognosis of his or her diseas


Genetics Polygenic inheritence Three causative genes found: MYOC (myocilin); OPTN (optineurin); and WDR36 (WD repeat domain 36)


OTHER FACTORS
MYOPES DIABETICS CIGARETTE SMOKING HIGH BLOOD PRESSURE THYROTOXICOSIS


mechanism

ELEVATED INTRAOCULAR PRESSURE

The IOP is subject to normal diurnal fluctuation of 3 to 6 mmHg. Diurnal variation of more than 8mmHg is unusual and should raise suspicion for glaucoma. The most common diurnal pattern is an early morning peak. The early morning peak has been correlated with the endogenous adrenocortical steroid level.


CELLULAR MECHANISMS OF GANGLION CELL DEATH

Studies suggest that elevated IOP may trigger cellular events leading to apoptosis. One hypothesis is that elevated IOP impairs the retrograde axonal transport of essential neurotrophic factors and in turn triggers apoptosis of the retinal ganglion cell.

Glutamate and Calcium influx

Ischemia can produce excess levels of extracellular glutamate, cell death through a complex series of cellular events that involves glutamate receptors and Ca+ + influx into the cell.  ed glutamate in the vitreous have been demonstrated in glaucomatous monkeys and humans. It is unclear whether the accumulation of vitreal glutamate is a primary or secondary process in glaucoma.


VASCULAR CONSIDERATIONS Proponents of the vascular theory argue that microvascular changes in the optic nerve head are responsible for glaucomatous optic nerve damage. Blood supply to the prelaminar and laminar areas of the optic nerve is derived from the peripapillary choroid and short posterior ciliary arteries.

Effect of Glaucoma

Effect of Glaucoma

Effect of Glaucoma

Effect of Glaucoma

symptoms
ASYMPTOMATIC MILD HEADACHE & EYEACHE DEFECT IN VISUAL FIELD FREQUENT CHANGES IN PRESBYOPIC GLASSES DELAYED DARK ADAPTATION


SIGNS
ANTERIOR SEGMENT SIGN Anterior segment- N, pupil reaction sluggish, cornea- hazy


IOP CHANGES Exaggeration of N diurnal variation, IOP falls during evening IOP >5mmHg suspicious & >8mmHg diagnostic


Optic disc changes in Glaucoma

Notching of neuroretinal rim, Pallor, Splinter haemorrhage, Progressive enlargement , vertical elongation, Asymmetry (between the left & right eyes), Nasal displacement of central retinal vessels, baring of lamina cribrosa.
 

Atrophy of the Retinal Nerve Fibre Layer may be detectable using the green ( red-free) light of the slit lamp biomicroscope


Early Glaucomatous Changes

Vertically oval cup- d/t selective loss of neural rim tissue in sup & inf pole Asymmetry of the cup- diff of >0.2 Large cup- 0.6 or more d/t concentir expansion Splinter hages-on/ near optic disc margins Pallor areas Atrophy of retinal nerve fiber layers- seen with red free light


ASYMMETRY OF THE CUP

Cup-to-disk ratio

Disc Haemorrhage

ATROPHY OF RETINAL NERVE FIBER LAYER

Disk

Cup

C/D: 0.3 C/D: 0.7

E-11 Normal and Cupped Disc

NORMAL

CUPPED DISC

ENLARGED CUP

ADVANCED GLAUCOMATOUS CHANGES

MARKED CUPPING-cup size 0.7-0.9 THINNING OF NEURORETINAL RIMcrescetric shadow next to the disc margin NASAL SHIFTING OF THE RETINAL VESSELS- BAYONETTING SIGN- edges overhang course of the vessels as they climb the sides of the cup is hidden Pulsations of the retinal arterioles- IOP is very high LAMELLAR DOT SIGN-d/t atrophy of the nerves


Glaucomatous cupping

GLAUCOMA
The histology of glaucomatous optic nerve Glaucomatous: cupping:
Normal:

VISUAL FIELD DEFECT

NORMAL

Paracentral scotoma

Arcuate scotoma

Nasal step

Tubular field

Progression of glaucomatous damage

INVESTIGATIONS
TONOMETRY DIURNAL VARIATION TEST GONIOSCOPY DOCUMENTATION OF OPTIC DISC CHANGES SLIT LAMP EXAMINATION PERIMETRY NERVE FIBRE LAYER ANALYZER PROVOCATION TEST- water drinking test OPTICAL COHERENCE TOMOGRAPHY CONFOCAL SCANNING LASER TOPOGRAPHY


SOPHISTICATED OFFICE EQUIPMENT

GLAUCOMA- INVESTIGATIONS

How do we measure IOP? Applanation

Tonopen Schiotz Air Non-contact

INTRAOCULAR PRESSURE
VERY EASY TO DO- PORTABLE INSTRUMENTS POOR SENSITIVITY AND SPECIFICITY NORMAL- 20 mmHg OR LESS MEASURED BY: APPLANATION TONOMETER- NOT PRACTICAL FINGER PALPATION- INACCURATE


APPLANATION TONOMETRY

SCHIOTZ TONOMETER
ADVANTAGES: INEXPENSIVE PORTABLE EASY TO USE READILY AVAILABLE DISADVANTAGES: NOT THE MOST ACCURATE REQUIRES TOPICAL ANESTHETIC

Tonometry

Schiotz

Applanation

GLAUCOMA
Goldmann applanation tonometer

Tonopen

Optic Nerve

OPHTHALMOSCOPY
EASY; QUICK REQUIRES OPHTHALMOSCOPE PICKS UP DEFINITIVE GLAUCOMA ( A LATE STAGE)- MAY BE TOO LATE TO HAVE MUCH BENEFIT INTER-OBSERVER VARIABILITY NORMAL C:D RATIO- 0.3 OR LESS THAN 0.2 DIFFERENCE (STEREO VIEWS ARE BEST (NOT PRACTICAL)


PERIPHERAL VISUAL FIELD TESTING

PICKS UP LATER GLAUCOMA REQUIRES EXPENSIVE EQUIPMENTDIFFICULT TO PERFORM- NOT PRACTICAL FOR SCREENING OPTIC NERVE ANALYSIS- PICKS UP PROBLEMS EARLIER (REQUIRES EXPENSIVE EQUIPMENT AND TECHNNICAL SUPPORT)- NOT PRACTICAL FOR SCREENING


AUTOMATIC PERIMETER (VISUAL FIELD TESTING)

GLAUCOMA
Goldmann perimeter Glaucoma visual fields

THE VISUAL FIELD

Humphrey automated perimetry

Diagnosis

Diagnosis of Glaucoma  The diagnosis of glaucoma is based upon; 1. Intraocular pressure ( IOP ) and its measurement. (tonometry) [can be defined as IOP greater than 21mmHg where the optic disc and visual field are normal.] 2. Optic disc examination. 3 Visual Field examination (perimetry)


1. New or worsening optic-nerve damage 2. Worsening visual field loss 3. OHTA

Topical Drug

-adrenergic-antag PG analogues Carbonic anhydrase inhibitors Adrenergic agonists Cholinergic agonists

Laser trabeculoplasty

Reduce humor production

Surgery

new route for aqueous humor

Diagnosis and Management of Primary Open Angle Glaucoma

Target Pressure

. A useful clinical concept is that each eye treated for glaucoma has a target pressure, this is based upon a general assessment of each individual patients disease burden.


30% to 50% reduction of the pressure at which damage occurs ?



GLAUCOMA
Treatment

Medical Miotics  Beta-blockers  Carbonic anhydrase inhibitors  Prostaglandin analogues  Alpha-2 agonists


Surgical
 Argon

laser trabeculoplasty  Trabeculectomy  Filtering procedure  Cyclocryotherapy  Cyclolaser ablation  Iridotomy

Medical management of glaucoma 1. Beta-adrenergic antagonists: -inhibiting cAMP production in ciliary epithelium -=> decrease aqueous humor secretion 20-50 % => decrease IOP 20-30 % - peak 2-3 hours - non selective beta-antigonist: carteolol, levobunolol, timolol maleate selective beta1 antigonist: betaxolol - side effect: bronchospasm, bradycardia, heart block, lower BP CNS depression, punctate keratitis, impotence, allergy

2 Cholinergic-Agonist Drugs:
Direct-acting cholinergic agonists: carbachol, Pilocarpine, Side effects:  Induced myopia  Pupillary constriction  Bradycardia, hypotension  Nausea, cramps, diarrhea  Salivation, tremor


Medical management of glaucoma 3 Parasympathomimetic agents: - Direct-acting cholinergic agents: affect the motor endplates pilocarpine Indirect-acting cholinergic agents:inhibit enzyme acethylcholinesterase echothiophate iodide - Contraction of the longitudinal ciliary muscle => increase outflow => decrease IOP 15-25 % - Reduced uveoscleral outflow - Disrupt the blood-aqueous barrier - associated retinal detachment - induced myopia

Medical management of glaucoma 4 Carbonic anhydrase inhibitors: - Direct antagonist activity on ciliary epithelial carbonic anhydrase => decrease aqueous humor - Systemic CAI: Acetazolamide ( 62.5 mg gid ) decrease IOP 15-20 % Methazolamide ( 25-30 mg bid,tid ) side effect: ( dose relate ) acidosis, depression, numbness, renal stone, hypokalemia bone marrow depression - Topical CAI: Dorzolamide, Brinzolamide, Sulfonamide decrease IOP 14-17 % side effect: bitter taste, punctate keratopathy

Medical management of glaucoma 5 Adrenergic agonist: - Nonselective Alpha agonist : epinephrine Dipivefrin conventional and uveoscleral outflow IOP 15-20 % side effect: headache, BP, tachycardia, arrhythmia adrenocchrome deposits at the conjunctival and cornea pupillary dilation, allergic blepharoconjunctivitis cystoid macular edema - Relative selective Alpha agonist : Alpraclonidine Brimonidine aqueous production uveoscleral outflow IOP 20-30 %

PG-F2 Analogues
Latanoprost (Xalatan) 0.005% (once a day) Action: Increases uveoscleral outflow Side effects:  Muscle and joint pain  Redness  Foreign body sensation  Dark the iris (10%) (green-brown, bluebrown)  Eyelashes longer, thicker, heavily pigmented C/I: cataract, uveitis, herpes and severe asthma


Medical management of glaucoma 6. Combined medication: - Cosopt: timolol maleate 0.5% + dorzolamide 2% - Advantage: less confusion increase compliance

Adjunctive therapy:
Reduce vascular risk factors  Regular aerobic exercise  Passo MS, Am J Ophtalmol 1987;103:754-57  Stop smoking ? ...No controlled data  Control of HTA, diabetes, vasospasm,  Postural hypotension, big nocturnal dip,...

Surgical theraphy for glaucoma Trabeculectomy: - Indication: - Failed maximum medication - progressive glaucomatous optic neuropathy - Relative contraindication: - blind eye - rubeosis iridis - active iritis - Less successful in younger, aphakia, pseudophakia uveitis glaucoma, black, previously failed filtering

Trabeculectomy

Trabeculectomy

GLAUCOMA Surgical treatment of glaucoma

Argon laser trabeculoplasty Filtration procedures

GLAUCOMA Filtration blebs

Take home messages:

IOP is one of the main risk factor 4 step diagnosis method Earlier diagnosis Be careful for potential side effects Look for the compliance