PRIMARY OPEN ANGLE GLACOMA -PATHOGENESIS AND MANAGEMENT

1. PRIMARY OPEN ANGLE
GLAUCOMA (POAG)
DR KALPANA SANGWAN
POST GRADUATE
DEPARTMENT OF OPHTHALMOLOGY
GMC HALDWANI

2. 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

3. PRIMARY OPEN ANGLE
GLAUCOMA
(POAG)
• K/a Chronic simple glaucoma
• Most prevalent of all glaucoma
• Affects both sexes equally

4. 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

6. 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

7. Risk factors
• IOP
• Age
• Race
• Family history
• Diabetes Mellitus
• Myopia

8. 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

9. 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

10. 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.

11. 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

12. 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.

13. ………..
• 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.

14. DIABETES
Role is controversial
The 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.

15. 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

16. RETINAL VENOUS OCCLUSION
• Patients with CRVO may present with elevated IOP and
glaucoma

17. OTHER ASSOCIATED CONDITIONS
• Sleep apnea
• Thyroid disorders
• Hypercholestrolemia
• Migraine
• Raynauds phenomena

18. Patho-physiology

19. 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

22. Pathogenesis of glaucomatous
optic neuropathy
1.Ischaemic theory
Suggests 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

23. 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

24. 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

25. 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

26. • CCT > 555µm: false high IOP
< 540µm: false low IOP
• Gonioscopy
• Perimetry: Automatic static threshold perimetry
• Provocative Tests: Water drinking test

27. 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 suspect
IOP 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

28. 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 defects
IOP constantly below 21 mm of Hg
NOTE: IOP reduction of at least 30% is associated with
protection of visual field and nerve status in NTG

29. 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

30. ………
• 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

31. 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

32. DIFFERENTIAL DIAGNOSIS
1.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

33. 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

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

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

36. 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

37. • Bayonetting
• Para-papillary atrophy
• Lamellar-dot sign

38. 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

39. 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

40. Visual field
abnormalities
• Initially observed in Bjerrum area, 10- 25° from fixation
• Correlate with abnormalities seen on optic nerve head
• Field defects:
1. Paracentral scotomas
2. Nasal step
3. Siedel scotoma
4. Arcuate scotoma
5. Double arcuate or ring scotoma
6. End-stage or near total defect with only
a residual temporal island of vision

41. Grading of glaucomatous
damage
• MILD DAMAGE
Minimal cupping
Nasal step / Para-central
step
MD < -6dB

42. • MODERATE DAMAGE
Thinning of NRR
Arcuate scotoma
MD < -12dB

43. • SEVERE DAMAGE
Marked cupping
Extensive visual field
loss including defects
within central 5 degree
MD > -12dB

44. • END STAGE
Gross cupping
Small residual field

45. TREATMENT
MEDICAL MANAGEMENT
LASER
SURGICAL

46. 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

47. Target IOP depends
upon
• IOP at which damage has occurred
• Severity of Visual Field damage
• Rate of progression of damage
• Age and Life Expectancy

48. 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

49. • 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

50. ……………..
• 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).

51. Classification
• Drugs decreasing AQUEOUS PRODUCTION
Beta-blockers
Alpha-2-agonists
Carbonic anhydrase inhibitors
• Drugs increasing TRABECULAR OUTFLOW
Parasympathomimetics
Non selective agonists
Prostamides
• Drugs increasing UVEOSCLERAL OUTFLOW
Alpha-2-agonists
Prostaglandins & Prostamides

53. I Line II Line III Line

58. 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

59. LASERS IN POAG
• Outflow Enhancement
• Laser Trabeculoplasty
• Inflow reduction
• Cyclophoto-coagulation (in end stage
disease)

60. 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

62. Surgery in POAG
Indications:
• Failure of medical therapy
• Anticipated progressive damage or intolerably high IOP
• Combined with cataract procedure
(phacotrabeculectomy)
• Primary therapy
• Poor compliance

63. SURGERIES
• Penetrating filtration surgeries
• TRABECULECTOMY
• Non-penetrating filtration surgery(NPFS)
• Deep Sclerectomy
• Visco-canalostomy

64. 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

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

66. Overview of Guidelines from
Glaucoma Clinical Trials
• Ocular Hypertension Study:
Risk factors for development of POAG
1. Older age
2. Higher IOP
3. Greater pattern standard deviation
4. Thinner central corneal thickness
5. Larger vertical cup-disc ratio

67. Collaborative Normal Tension
Glaucoma Study:
Risk factors for progression
1. Female gender
2. Recurrent disc hemorrhages
3. History of migraines

68. Early Manifest Glaucoma
Treatment Trial:
• Risk factors for progression
1. Higher IOP
2. Exfoliation
3. Older age
4. Bilateral disease
5. Worse mean deviation on VF
6. Recurrent disc hemorrhages

69. 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

70. 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.

71. …………..
• Glaucoma Laser Treatment Trial (GLT)
Initial laser trabeculoplasty was as effective as
medical therapy
• Flurouracil Filtering Surgery Study
The success of trabeculectomy was improved with
post-operative use of 5FU