This document provides an overview of primary open-angle glaucoma (POAG). It discusses the pathophysiology of raised intraocular pressure in POAG, risk factors, genetics, clinical presentation, investigations including tonometry and gonioscopy, and management principles. POAG is the most common type of glaucoma and results from obstruction of aqueous outflow, leading to optic nerve damage and visual field loss. Family history, older age, higher IOP levels, and conditions like myopia and diabetes increase risk. Genetic factors and changes in the trabecular meshwork contribute to outflow obstruction in POAG.

1. Topic presentation- POAG
Dr.Lhacha Wangdi
R3, JDWNRH/KGUMSB
2016

2. Objectives
Aqueous formation and drainage system
Glaucoma overview
POAG:
 Pathophysiology of raised IOP
 Glaucomatous optic neuropathy
 Clinical manifestation
 Investigations and interpretation of the results
 Management principles

3. Aqueous humor
Formation:
 Aqueous is secreted by the bilayer ciliary epithelium
at the pars plicata of ciliary body

4. Aqueous production
Three Mechanism
1. Ultrafiltration
ultrafiltration of plasma through the fenestrated capillaries
into the ciliary stroma
2. Active transport (main mechanism)
Number of solutes are actively transported from
ultrafiltrated across the CE(PE+NPE) into the PC
3. Simple diffusion
Passive transport of H2O to PC facilitated by the Osmotic
gradient created by active transport

5. Active transport
 Three mechanism:
1. Loading of major ions/solutes occurs through the Basolateral
membrane (BLM) of PE
 Na-K-2cl and Na-HCO3 cotransporter / Na/H+ counter exchanger=
uptake of of Na+, K+, CL- from stroma to PE coupled with anti-transport
of H+ and HCO3- by Na/H+ and CL-/HCO3 antiports located in BLM of
PE
2. Active transport of Na+ by Na+,K+ ATPase located at the BLM of
NPE
3. Shifting of fluid and solutes from PE to PC is facilitated by the
concentration gradient

7. Aqueous dynamics
 Secretion of aqueous balanced with drainage
 Secretion flow rate:2-3 uL/min.
 Aqueous volume(AC+PC)= (200ul+60ul)=260ul
 Maintains IOP of 11-21mmHg (average=16mmHg)
 Diurnal variation – morning rise( 7.mmHg is
considered normal upper limit)
 Asymmetry of IOP >4mmHg is significant

8. Aqueous flow
1. Passes from PC to AC via pupil
2. About 90% of aqueuos flows through Trabecular
meshwork which drain through Schlemm canal to
episcleral vein
10% of aqueuos drain
through Uveoscleral route
across the face of ciliary
body into the
suprachoroidal spaces

9. Ctn..
Angle structure
1. Schwalbe line (SL)
2. Trabecular meshwork(TM)
3. Schlemm’s canal(SC)
4. Scleral spur(SS)
5. Anterior border of the ciliary
body(CB)
1. (where its longitudinal fibers insert
into the scleral spur)
6. Iris (I)

10. Trabecular meshwork (TM)
TM
 Circular spongework of connective tissue lined by
trabeculocytes
 Triangular in cross section.
 Apex at Schlemm’s canal
 Base formed by the scleral spur and the Ciliary body

11. Trabecular meshwork
3 parts:
1. Uveal
 Contains large and circular cordlike trabeculae
 Diameter of pores-70pm in diameter
2. Corneoscleral
 Series of thin, flat, perforated connective tissue sheets arranged in
a laminar pattern
 Pores-35pm in diameter (moderate resistance
3. Juxtacanalicular
 Pericanalicular connective tissue-a multilayered collection of cells
forming a loose network-
 Pores -7pm in diameter (highest resistance to flow)

12. Glaucoma
Definition:
Glaucoma is a group of acute and chronic, progressive,
multifactorial optic neuropathies in which intraocular pressure
(IOP) and other contributing factors are responsible for a
characteristic, acquired loss of retinal ganglion cell axons leading
to atrophy of the optic nerve with demonstrable visual field defects
The word glaucoma came from the ancient Greek word glaucosis,
meaning clouded or blue-green hue, most likely describing a
patient having corneal edema or rapid evolution of a cataract
precipitated by chronic elevated pressure

13. Glaucoma
When to suspect?
1. Glaumatous optic neuropathy
2. Characteristic visual field loss
3. Raised IOP
Other clinical signs will depend on the Type of
glaucoma

14. Glaucoma
Classification
Congenital Acquired
Angle closure Open angle
Primary Secondary
Acute Chronic

16. Primary open angle glaucoma
(POAG)
Definition:
 Multifactorial optic neuropathy that is chronic and
progressive with a characteristic acquired visual field
loss in presence of open anterior chamber angle.
Commonly bilateral disease of adult onset
Characteristics:
1. Primary glaucomatous optic neuropathy
2. >IOP 21mmHG at some stage
3. Characteristic visual field loss
4. Absence of secondary cause of glaucoma

17. POAG variants
Primary open-
angle glaucoma
(POAG)
Not associated with known ocular or
systemic disorders that cause increased
resistance to aqueous outflow or damage
to optic nerve;
usually associated with elevated IOP
Normal-tension
glaucoma ( NTG)
Considered in continuum of POAG;
terminology often used when IOP is not
elevated
Juvenile open-
angle
glaucoma (JOAG)
Terminology often used when open-angle
glaucoma diagnosed at young age (typically 4-
35 years of age)

18. Ocular
hypertension
Normal optic disc and visual field
associated with elevated I O P
Glaucoma
suspect
Suspicious optic disc or visual field
regardless of I O P

20. POAG
Epidemiology:
 Prevalence of 6% in white populations, 16% in black
populations and around 3% in Asian populations.
 Most common type of glaucoma
 Globally:
Glaucoma affects more than 67 million persons worldwide
10%, or 6.6 million, are estimated to be blind
Glaucoma is responsible for 14% of all blindness

21. POAG
Risk factors:
 The higher the IOP/Asymmetry of IOP of 4 mmHg or
more
 Older age
 More common in black individuals than in whites
 Genetics
 Steroid usages
 Diabetes mellitus
 Myopia
 Contraceptive pill
 Vascular disease
 Translaminar pressure gradient.
 Large discs

22. Genetics of POAG
Inheritance:
Most POAG pedigrees do not show a simple Mendelian
pattern of inheritance- largely unknown
A minority of POAG pedigrees do demonstrate a Mendelian
pattern of inheritance:
1. Autosomal recessive- commonest type
2. Autosomal dominant pedigrees have also been described, with
a degree of penetrance varying from 60% to 100%
3. Rare pedigrees showing possible sex linked inheritance have
been reported

23. Genetics of POAG
Molecular genetic:
 Gene expression analysis has found out 26 genetic
loci in the region of the long arm of chromosome 1,
1q21-q31 associated with POAG
 Out of these only three gene has been discovered till
date:
1. Myocilin (MYOC)
2. Optineurin
3. WDR36

25. Ctn..
MYOC(myocilin)-Most studied gene:
Also called TIGR(trabecular meshwork induced glucocorticoid
response protein)
Normally myocilin protein is secreted by TM cells into aqueous
Mutated myocilin protein is not secreted and retained within TM
cells:
 Interferes with TM function
 Causes TM cell death
 Obstruction of aqueous drainage- raised IOP

26. Ctn…
Optineurin &WDR36:
 It is expressed in a variety of ocular tissues,
including the ciliary body, TM, and retina.
 Itsrole in glaucoma pathogenesis is still unclear

27. Pathogenesis of raised IOP in PAOG
Mechanism:
 Complex
 Main mechanism:
 Obstruction of aqueous through open angle
 Pathological changes in the angle structures
 Cause of aqueous obstruction: Multifactorial:
 Genetic
 Aging
 Race
 Ocular risk
 systemic risk factors
 Drugs

28. Ctn…
Thickening and sclerosis of trabecular
meshwork with faulty collagen tissue
Narrowing of intertrabecular spaces
Deposition of amorphous material in the
juxtacanalicular space
Collapse of schlemm’s canal and
absence of giant vacuoles in the cells
lining it
Reduced aqueous outflow facility occurs due to failure
of aqueous outflow pump mechanisms:

29. Pathogenesis of raised IOP in POAG
obstruction of
aqueous outflow
High risk
groups
Transforming growth factors (TGFs)
• Inhibition of epithelial cell growth
• excessive amounts of extracellular matrix
materials - GAGs
Alteration of TM:
• increase in extracellular matrix and
an accumulation of “plaque
material.”
• Thickening of basement
membrane
• disrupt TM cell actin
microfilaments
Thickening of juxtacanalicular
connective tissue
Decreased in Pores and giant vacuoles in
the inner wall endothelium of the
Schlemm canal
Collapse of the Schlemm Canal
Alterations of the
Intrascleral Channels
• due to a swelling of
glycosaminoglycans in
the adjacent sclera

30. Steroid responsiveness
“Steroid Responder”
 Around one in three individuals develop some
degree of elevation of IOP in response to a course
of potent topical steroid
“Non-responders”
 IOP is not affected by steroid

31. Steroid responder
Mechanisms:
1. Glycosaminoglycans Theory:
Cortico — steroids stabilize the lysosome membrane of TM
cells► reduced catabolic enzyme►reduces GAGs
catabolism► increased polymerised form of GAGs► increases
resistance to aqueous outflow.
2. Phagocytosis Theory:
Suppress the phagocytic activity of endothelial cells lining the
trabecular►buildup of material that could account for the
amorphous layer in the juxtacanalicular connective tissue
meshwork
3. Cyclic-Adenosine Monophosphate Theory:
Altering cyclic-adenosine monophosphate- mechanism poorly
defined

32. Glaucomatous optic neuropathy
Pathogenesis:
1. Direct mechanical
damage to retinal nerve
fibres
2. Ischaemic damage
3. Common pathways of
damage
1 2
3

33. MECHANICAL
mechanical pressure on the
lamina cribrosa
mechanical pressure on the
lamina cribrosa
altering capillary blood flow
backward displacement and
compaction of the laminar plates
narrows the openings through which
the axons pass
GANGLION CELL DEATH

34. VASCULAR
rise in intraocular
pressure
mechanical pressure on
the lamina cribrosa
decrease the capillary
blood flow
mechanical compression
of vessels at the lamina
cribrosa
GANGLION CELL
DEATH

35. POAG- clinical menefestation
The Silent thief of sight

36. Clinical features
 Symptoms:
 Insidious and asymptomatic disease
 Gradual painless loss of vision
 Mild headache, eye ache
 Visual field defect(SCOTOMA)
 Frequent change in presbyopic glasses
 Delayed dark adaptation
 Significant loss of vision and blindness

37. Ctn…
Specific enquiry:
Refractive status(e.g myopia)
Causes of secondary glaucoma
(trauma/surgery/inflammation/tumour)
Family history- glaucoma
Past medical history-Asthma, heart failure/migraine and
Raynaud phenomenon, DM/HTN.
Drugs -Steroids/OCP/beta blockers
Social history- smoking/alcohol/nutrition-diet
Allergies

38. Examination
Work up:
1. Visual acuity
2. Pupils-
regularity/reaction/asymetry/RAPD/APD
3. Color vision assessment
4. Visual field- confrontation test
5. Slit lamp examination- detail examination of
anterior segment/fundus

39. Visual field examination
Screening tests …
Confrontational visual field testing
Amsler grid (assesses the central 10° the
visual field ) .
Quantitative measurements using manual or
automated perimetry

40. Cnt..
Anterior segment:
 Corneal haze
 AC depth and any reaction
 Pupil- syniechae
 Evidences of secondary
cause

42. Ctt..
The van Herick method: gross estimation
 Uses the slit lamp alone to estimate the AC angle
width:

43. Funduscopy
• Fundus :
1. Optic disc
assessment
2. Parapapillary
changes
3. Vessels
4. Nerve fiber

44. Optic disc- surface anatomy
Around the optic cup is neuroretinal rim (NRR):
• Pink and sharp peripheral margin
• Contain nerve axon
• Broad inferior rim followed by superior> nasal>temporal ( ISNT
rule)
Disc:
 Vertically oval Vertical diameter-1.8mm
Horizontal diameter- 1.5 mm
 Pale center area-physiological cup
 Horizontally oval
 Free of nerve axon(cup)-0.3mm
 Normal CDR= 0.4
Inferior
superior
Nasal temporal

45. Glaucomatous Optic neuropathy
Glaucomatous damages in three regions:
(a) the optic nerve head
(b) the peripapillary area and
(c) the retinal nerve fibre layer.
There are specific sings and non specific signs

46. Ctn…
Optic nerve:
Specific signs:
 Focal ischaemic discs
 Myopic disc with glaucoma
 Sclerotic discs
 Concentrically enlarging discs

47. Focal ischaemic – inferior notch and disc
haemorrhage
myopic;
sclerotic
concentrically enlarging

48. Glaucomatous ON
Nonspecific signs glaucomatous damages:
 Disc haemorrhages
 Baring of circumlinear blood vessels
 Bayoneting
 Collaterals
 Loss of nasal NRR
 The laminar dot sign
 ‘Sharpened edge’ or ‘sharpened rim’

49. baring of inferior circumlinear
blood vessel
bayoneting of blood vessels
collateral vessels
loss of nasal neuroretinal rim and laminar
dot sign

50. Ctn…
Peripapillary changes
1. Alpha (outer) zone is characterized by
superficial retinal pigment epithelial changes
2. Beta (inner) zone is characterized by
chorioretinal atrophy

51. Ctn..
Retinal nerve fibre layer
1. Localized wedge-shaped defects and
2. Diffuse defects that are larger and have
indistinct borders

52. INVESTIGATIONS
1. Tonometry
2. Central corneal thickness(CCT)
3. Diurnal variation test
4. Gonioscopy
5. Perimetry to detect the visual field defects
6. Nerve fibre layer analyzer (NFLA)
7. Provocative tests
Water drinking test

53. TONOMETRY
The intraocular pressure (IOP) is measured with
the help of an instrument called tonometer
 Indentation tonometery
Schiotz tonometer
 Applanation tonometry
Goldmann tonometer
Perkin’s applanation tonometer
Pneumatic tonometer
Pulse air tonometer
Tono-Pen
Rebound tonometry - icare
Schiotz
tonometer

54. Technique of Schiotz
tonometry
Technique of applanation
tonometry
End point of applanation tonometry. (A)
too small; (B) too large; (C) end point.

55. Gonioscopy
The technique of biomicroscopic examination of
the angle of the anterior chamber using a
goniolens.
The angle structures seen from behind forward
are:
1. Root of the iris
2. Ciliary body band
3. Scleral spur
4. Trabecular meshwork
5. Schwalbe’s line

56. Schaffer’s grading
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Grade 4 (35–45°) is the widest angle, the ciliary body can be visualized.
Grade 3 (25–35°) is an open angle, scleral spur is visible.
Grade 2 (20°) is an angle in which the trabeculum but not the scleral spur can be
seen.
Grade 1 (10°) is a very narrow angle in which only the Schwalbe line and perhaps
the top of the trabeculum can be identified.
Slit angle is one in which there is no obvious iridocorneal contact but no angle
structures can be identified.
Grade 0 (0°) is closed due to iridocorneal contact.

57. Visual field defects
Relative paracentral scotoma
Roenne’s nasal step
Seidel scotoma
Arcuate scotoma
Double arcuate / ring scotoma
End stage / near total field defect

58. A paracentral
scotoma- loss of
nerve fibers
ininferotemporal
retina
The arcuate
scotoma-10-
20° from
fixation-
Bjerrum
scotoma
Nasal step
Altitudinal defect
Advanced glaucomatous
V. Field loss

59. SEIDEL SCOTOMA
starts at the poles of the blind spot , arches over the macular
area without reaching the horizontal meridian nasally

60. Treatment of PAOG
Medical
LASER
Surgery

61. Management
Principle:
 Determine TARGET PRESSURE – Reduction of IOP
by at least 30% appears to have the best chance of
preventing optic nerve damage
 Starting drugs-Monocular Therapeutic Trial (MTT)
 Reexamination in 3 to 6 weeks to check for
effectiveness.
 Exception to MMT:
IOP > 40 mm Hg
impending loss of central fixation),

62. MEDICAL
 MECHANISM
 Decreased aqueous production
 Increased facility of outflow (trabecular / uveoscleral)
 Intraocular osmotic fluid reduction

63. Anti-glaucoma drugs
# Agents Mechanism of action Drugs
1 Prostaglandins enhancement
of uveoscleral aqueous
outflow
Latanoprost(0.005%) - OD
Travoprost(0.04%) -OD
Bimatoprost(0.03%) -OD
Tafluprost(0.04%) -OD
2 Beta-
blockers
block β receptors in
ciliary processes
aqueous production
Timolol (0.25%/0.5%)-BD
Betaxolol(0.25%,0.5%) -BD
Levobunolol(0.5%)-BD
Carteolol(1%, 2%) -BD
Metipranolol(0.1%, 0.3%, 0.6%)-BD
3 carbonic
anhydrase
inhibitors
Inhibition of carbonic
anhydrase- reduce
aqueous production
Dorzolamide(2%) –BD-TDS
Brinzolamide (1%)-BD-TDS
T-Acetazolamide (250mg),BD-QID
T-Dichlorphenamide(50mg) BD-TDS
T-Methazolamide(50 mg) BD-TDs

64. # Agents Mechanism of action Drugs
4 Alpha-2
agonists
Ocular alpha-2 receptor stimulation
decreases aqueous synthesis
via an effect on the ciliary
epithelium, and increases
uveoscleral outflow.
Brimonidine(0.2%)BD-TDS dosage
Apraclonidine (0.5%,1%)BD-TDS
Clonidine (0.125%,0.25%) BD
5 Miotics cholinergic agonists-reduce IOP by
contraction of the ciliary muscle,
also opens angle by miosis
Pilocarpine 0.5%, 1%, 2%, or 4%
solution as four times
Carbachol(0.75%,1.5%,3%)BD-TDS
dosage
6 Osmotic
agents
lower IOP by creating an osmotic
gradient so that
water is ‘drawn out’ from the
vitreous into the blood
Mannitol IV(20% solution1-2g/kg
over 20-30 minutes,
Glycerol is an oral agent (1 g/kg
body weight or 2 ml/kg
body weight of a 50% solution)
Isosorbide is a metabolically inert
oral agent

65. Prostaglandin Side affects
Systemic :
1. Upper respiratory tract symptoms (flu like )
2. Headache and precipitation of migraine in
susceptible individuals
3. Muscle and joint pains
4. Skin rash

66. Prostaglandin side affects
Ocular Side Effects
1. Conjunctival hyperaemia and foreign body sensation
2. Eyelash lengthening, thickening, hyperpigmentation, increase
in number
3. Iris hyperpigmentation
4. Increase in severity and recurrence of herpetic keratitis
5. Anterior uveitis
6. Cystoid macular edema

67. Beta- blocker side effects
Systemic
1. Cardiovascular effects – bradycardia, arrhythmia,
heart failure, syncope
2. Respiratory reactions – bronchospasm and airway
obstruction, especially in asthmatics
3. CNS effects – depression, anxiety, confusion,
drowsiness, disorientation
4. Others – nausea, diarrhoea, decreased libido, skin
rashes, alopecia

68. Beta-bockers
Ocular side affects:
 Conjuctival hyperaemia
 Superficial punctate keratopathy
 Corneal anaesthesia
1. Contraindications:
 Bronchial asthma
 Chronic obstructive pulmonary disease
 Heart blocks
 Congestive heart failure
 Cardiomyopathy

69. Carbonic anhydrase inhibiters
Systemic side affects:
1. Paraesthesias, numbmness, lethargy, depression,
malaise
2. Metabolic acidosis, hypokalemia, increased serum urate
level
3. Urinary frequency
4. Anorexia, cramps, flatulence, weight loss, diarrhoea
5. Sulfonamide related – blood dyscrasias, renal calculi,
steven-Johnson syndrome
Topical agents are less likely to induce systemic side
effects

70. LASER THERAPY
Argon laser trabeculoplasty
Selective laser
trabeculoplasty

71. Surgical
TRABECULECTOMY:
Involves creation of fistula between angle of anterior
chamber and sub Tenon’s space

72. Trabeculectomy
Indications:
Failure of conservative therapy to achieve adequate
IOP control.
Avoidance of excessive polypharmacy
Progressive deterioration despite seemingly adequate
IOP control (including poor compliance with medical
treatment).
Patient preference

73. DRAINAGE SHUNTS
Shunts using episcleral explants
Glaucoma Drainage Devices(GDD)= creates
communication between AC and sub tenon
space

74. THANK YOU