PRIMARY OPEN ANGLE GLAUCOMA

BHAVISHYA KEERTHI ANNA VALDER

OPEN ANGLE GLAUCOMAAka: chronic simple glaucoma (CSG) and primary open angle glaucoma (POAG)

Angle Anatomy

Open angle GlaucomaOpen 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 POAGPopulation-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 FACTORSMYOPES DIABETICS CIGARETTE SMOKING HIGH BLOOD PRESSURE THYROTOXICOSIS

mechanism

ELEVATED INTRAOCULAR PRESSUREThe 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 influxIschemia 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

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

SIGNSANTERIOR 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 GlaucomaNotching 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 ChangesVertically 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 CUPCup-to-disk ratio

Disc Haemorrhage

ATROPHY OF RETINAL NERVE FIBER LAYERDisk

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

GLAUCOMAThe histology of glaucomatous optic nerve Glaucomatous: cupping:Normal:

VISUAL FIELD DEFECT

NORMAL

Paracentral scotoma

Arcuate scotoma

Nasal step

Tubular field

Progression of glaucomatous damage

INVESTIGATIONSTONOMETRY 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? ApplanationTonopen Schiotz Air Non-contact

INTRAOCULAR PRESSUREVERY 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 TONOMETERADVANTAGES: INEXPENSIVE PORTABLE EASY TO USE READILY AVAILABLE DISADVANTAGES: NOT THE MOST ACCURATE REQUIRES TOPICAL ANESTHETIC

Tonometry

Schiotz

Applanation

GLAUCOMAGoldmann applanation tonometer

Tonopen

Optic Nerve

OPHTHALMOSCOPYEASY; 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 TESTINGPICKS 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)

GLAUCOMAGoldmann perimeter Glaucoma visual fields

THE VISUAL FIELDHumphrey 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 ?

GLAUCOMATreatment

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 AnaloguesLatanoprost (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 glaucomaArgon 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