POAG,NTG,OHTN

1.  Dr.Rakshya Basnet
 2nd year resident
 LEI,NAMS
PRIMARY OPEN ANGLE
GLAUCOMA
1

2. LAYOUT
 Introduction
 Epidemiology
 Risk factors
 Genetics
 Pathophysiology
 Clinical features
 management
2

3. Introduction
Primary open-angle glaucoma (POAG)
considered as a:
Chronic, progressive, anterior optic neuropathy
leading to damage of retinal ganglion cells and
optic nerve with corresponding visual field
changes
3

4. Characterised by
 Glaucomatous optic nerve damage
 Visual field loss
 Open angles
 No obvious causative ocular or systemic
conditions
 IOP may be elevated above statistically
‘normal’ range, reflecting reduced aqueous
humor outflow facility
4

5. Epidemiology: The POAG
Burden
 POAG: most common form of glaucoma
 global prevalence of glaucoma was 3.54% with POAG
prevalence being 3.05%
 Incidence of POAG 2.4 million persons per year
 Blindness prevalence for all types of glaucoma was >8million
with 4 million caused by POAG
5

6. Prevalence:
 Western Europe / United States: 0.5–1%
( above age 40)
 Baltimore eye survey: 1.29%
(whites),4.3%(black)
6

7. POAG: Epidemiology
 Nepal blindness survey(1981) reported glaucoma
related blindness to account for 3.2% of total blindness
in Nepal
 Another study from 2006-2010 in 50+ age group
reported it to be 4% of total blindness
8

8.  Bhaktapur Glaucoma study revealed an
incidence of 1.80( age and sex standardized)
and POAG of 1.26 accounting for 685 of total
glaucoma patients(2012)
 POAG is more common in males, Gurung
community(2.05x) and was associated with HTN
and DM(2013)
9

9. Risk factors
 Demographic
 Ocular
 systemic
10

10. Demographic risk factors
 Race(African, caribbean,
hispanic,chinese,asian )
 Age: increases with age
 Gender
 Family history
20–25% of POAG
13% in monozygotic and dizygotic twin
25% of the siblings of patients with POAG
Socioecomonic factors
11

11. Ocular risk factors
 Intraocular pressure
 Nerve fiber layer thickness
 Myopia
 Peri-papillary atrophy
 Translaminar pressure gradient
 Corneal thickness and hysteresis
12

12. Systemic risk factors
 Diabetes
 Hypertension
 low perfusion pressure
 migraine
 thyroid disease
 Sleep apnea
 Hypercholesterolemia
 Raynaud phenomenon
 Cigarette smoking,alcohol,caffeine
 OCP and menopause
13

13. GENETICS OF POAG
GENE LOCI INHERITANCE AGE OF ONSET
GLC1A (Myocilin) 1q23-25 DOMINANT JUVENILE/ADUL
T
GLC1B 2 cen-q13 DOMINANT ADULT
GLC1C 3q21-21 DOMINANT ADULT
GLC 1D 8 q23 DOMINANT ADULT
GLC1E
(Optineurin)
10q15-14 DOMINANT ADULT
POAG/NTG
GLC1F 7q35 DOMINANT ADULT
Phenotypic expression 3% for GLC1A, 5% GLC1E, others very low
14

14.  Genetic investigation done if
1. 3 or more first degree relatives from 2
generations are affected
2. research purpose
15

15. Pathophysiology
1. Mechanism(s) of IOP elevation
i. Diminished aqueous humor outflow
facility
ii. Altered corticosteroid metabolism
iii. Dysfunctional adrenergic control
iv. Abnormal immunologic processes
v. Oxidative damage
vi. Other toxic influences
2. Mechanism(s) of progressive optic nerve
16

16. i.Diminished aqueous humor outflow
facility
17

17. i.Diminished aqueous humor outflow
facility
Site of resistance : Juxtacanalicular tissue
Theories
 Obstruction of TM by foreign material
 Loss of trabecular endothelial cells
 Reduction in pore density and size in inner
wall endothelium of Schlemm’s canal
 Loss of giant vacuoles
 Loss of normal phagocytic activity
 Disturbance of neurologic feedback
mechanisms
18

18. PATHOPHYSIOLOGY CONTD.
ii.Altered corticosteroid metabolism.
1. Increased plasma levels of cortisol
2. Increased suppression of plasma cortisol with
different doses of exogenous dexamethasone
3. Continued suppression of plasma cortisol by
dexamethasone despite concomitant administration
of phenytoin
4. Disturbed pituitary adrenal axis function
5. Increased inhibition of mitogen –stimulated
lymphocyte transformation by glucocorticoids
19

19. Researchers postulated that endogenous
corticosteroids affects trabecular function
by
 altering PG metabolism
 GAG catabolism
 released of lysosomal enzymes
 synthesis of cyclic adenosine
monophosphate
20

20. PATOPHYSIOLOGY CONTD.
iii. Dysfunctional adrenergic control
Patients with POAG had:
1. A greater IOP reduction after the administration
of topical epinephrine;
2. A greater response to epinephrine or
theophylline in inhibiting mitogen stimulated
lymphocyte transformation;.
21

21. PATHOPHYSIOLOGY CONTD.
iv. Abnormal immunologic process
 Increased level of gamma globulin and plasma
cells found in the TM of patient with POAG.
 High prevalence of antinuclear antibodies.
.
22

22. v. Oxidative damage
TM cells contain Glutathione which may protect
endothelial cells from effect of H2O2 and other
reactive oxygen molecules
vi.Other toxic influences
TGF β₂ involvement, plasminogen activator
inhibitor
23

23. Mechanisms of Glaucomatous
optic neuropathy
 What is the primary site of glaucomatous
injury?
 What factors contribute to ganglion/axonal
injury?
 Precisely how do ganglion cells die?
24

24. Primary site
25

25. Primary site
 ONH itself – specifically sclera lamina of
ONH
 Histological studies  ON cupping includes
the loss of all three elements of the disc –
axons, blood vessels and glial cells
 Inner retina : damage to retinal ganglion cell
(RGC) and astroglial populations.
26

26. What Injures Ganglion Cells?
 Ganglion Cell Susceptibility
 Intraocular pressure level
 Vascular nutrition of the optic disc
 neurotoxicity
How Do Ganglion Cells Die? “ Apoptosis ”
27

27. PATHOGENESIS : GLAUCOMA
 Elevated IOP can either lead to
 Direct Mechanical compression
 Vascular perfusion of optic nerve head
28

28. PATHOGENESIS :
GLAUCOMA
MECHANICAL PRESSURE
29

29. 30

30. PATHOGENESIS : GLAUCOMA
RGC axon compression reduce axonal transport
trophic factors  RGC death by trophic
insufficiency
31

31. PATHOGENESIS :
GLAUCOMA
VASCULAR PERFUSION
32

32. Precisely how do ganglion cells
die?
33

33. 34

34. CLINICAL FEATURES:
SYMPTOMS
 Asymptomatic until significant visual field loss
has occurred
 Asymmetric progression
 Mild headache and eyeache
 Reading and close work increasing difficulty
frequent change in presbyopic glasses
 Delayed dark adaptation
 Haloes may be noted, if there is a sudden severe
rise of IOP, due to corneal edema
35

35.  Past medical and ocular history
 Surgical history
 Family history
 Current medication history
 Social history
 Allergic history
36

36. CLINICAL FEATURES:SIGNS
Early phase : Normal anterior segment findings
Late stage: Sluggish pupillary reflex(APD±) and
minimal corneal haziness
OPTIC DISC CHANGES:
 1. Specific signs:
 Optic disc cupping
 Vertical elongation of cup
 Large optic cup (CDR 0.7 or more)ISNT rule not obeyed
 Asymmetry of optic cup (difference of CDR 0.2 or more)
 Progressive enlargement of optic cup
 Focal signs:
 Notching of rim (NRR ), Regional pallor, Splinter hemorrhage,
Nerve fiber layer thinning
37

37. CLINICAL FEATURES:SIGNS
2. Less specific signs
 “Lamellar dot” sign
 Nasalization of vessels
 Peripapillary crescent
 Baring of circumlinear vessels
38

38. CLINICAL FEATURES: SIGNS
TONOMETRY
 Goldmann applanation  gold standard
 Wider fluctuation of IOP than normal
39

39. USE OF 24 HOUR MONITORING OF
IOP
 Diagnosis of POAG
 Explaining progressive damage despite
apparent good pressure control
 Evaluating efficacy of therapy
 Distinguishing NTG from POAG.
40

40. CLINICAL FEATURES: SIGNS
GONIOSCOPY
41

41. CLINICAL FEATURES: SIGNS
GONIOSCOPY
 Open angle, grossly normal
 More iris processes, high insertion of iris root,
more trabecular pigmentation
 Greater than normal degree of segmentation in
the pigmentation of the meshwork
 to rule out angle-closure or secondary causes of
IOP elevation, such as angle recession,
pigmentary glaucoma
42

42. VISUAL FIELD ABNORMALITIES
 Central visual acuity normal.
 Peripheral field loss progressive and finally
involves central field.
Subtle measures of visual dysfunction e.g.
contrast sensitivity, color vision and motion
perception are useful early indicators.
43

43. INVESTIGATIONS
PACHYMETRY
 NTG-thin corneas
 Goldmann applanation tonometry values hold
accurate for CCT of 530-545μm
 May induce error in measurement
50

44. SWAP (short wavelength automated
perimetry)
INVESTIGATIONS
51

45. INVESTIGATIONS
Frequency doubling perimetry

53

46. IMAGING STUDIES
Fundus photography
54

47. IMAGING STUDIES
Confocal scanning laser ophthalmoscopy
55

48. IMAGING STUDIES
Optical coherence tomography
56

49. IMAGING STUDIES
Scanning laser polarimetry
57

50. MANAGEMENT
58

51. TREATMENT: WHEN TO
TREAT?
 Triad of visual field loss, optic nerve cupping, and
elevated IOP, or is at high risk of developing them
 Progressive cupping without detectable visual field
loss
 visual field loss
 Episodes of corneal edema caused by elevated
IOP
 A vascular occlusion associated with increased IOP
 Asymmetric POAG
59

52. Management
Options:
 Medical
 Laser
 Surgery
Aim:
• To prevent Nerve fibre loss
• To prevent any further visual field deterioration
• To retain the quality of life of the Patient
60

53. MEDICAL THERAPY
 First line: prostaglandin analogues or nonselective
β-blocker(MONOTHERAPY)
65

54.  For typical glaucoma patient, 2 or 3 medications
would be maximum suggested before resorting
to laser or incisional surgery
66

55. MEDICAL THERAPY
 Failure:
 Inadequate control of IOP
 Progressive visual field loss or optic nerve cupping
 Appearance of an optic nerve hemorrhage
 Intolerable side effects of medication
 Demonstrated (or admitted) poor compliance with
therapy
67

56. SURGERY
 medical treatment and laser surgery are
inadequate to control POAG
 Controls IOP in approximately 80–90% of
patients
68

57. PROGNOSIS
 Lifetime chance of blindness in both eye is 5-10%
 Avg. period from diagnosis to death is ~15 yrs
 Determined by advanced damage at diagnosis, non
compliance, ethnic origin
69

58. Glaucoma suspect
70

59. Glaucoma Suspects
Type I
Normal intraocular pressure, no damage
 Strong family history of glaucoma
 Retinal vascular occlusion
 Exfoliative syndrome
 Angle recession
 Pigmentary dispersion syndrome
 Narrow angles
 Uveitis
 History of halos
71

60. Type 2
Normal intraocular pressure, possible
damage
 Thin corneas
 Suspicious optic disc
 Suspicious nerve fiber layer defects
 Suspicious visual field
 Reduced psychophysical function
72

61. GLAUCOMA SUSPECTS
TYPE III
 High intraocular pressure, no damage
 OCULAR HYPERTENSION
73

62. TYPE IV
High intraocular pressure, possible damage
 Peripheral anterior synechiae and narrow
angles
 Notch or local rim narrowing of optic nerve
 Early arcuate scotoma or paracentral scotoma
74

63. Follow up
• Every 6-12 months
• Visual field 6-18 months
• Tonometry and ophthalmoscopy every 1 or 2
years up to age 60, with increasing frequency
over age 60
76

64. Ocular
hypertension
77

65. OCULAR HYPERTENSION
 Occurs in 4–10% of population over age 40
 Clearly far more prevalent than POAG
78

66. Distuinguishing with POAG
 Signs of early damage
1. Focal notching
2. Assymetry of cupping
3. Optic disc hemorrage
4. Nerve fiber layer defect
5. Subtle visual field defect
79

67. Early damage detection by:
Newer modalities such as
 short-wavelength automated perimetry
 frequency-doubling perimetry
 confocal laser ophthalmoscopy
 Pattern electroretinogram
80

68. OHTS(Ocular Hypertension Treatment
Study)
-40-80 years
-IOP 24-32mm Hg
-observation or treatment group
9.5% of observation group developed
glaucoma 4.4% of treated group did
81

69. OCULAR HYPERTENSION
Treatment should be reserved for
 patients who demonstrate early damage
 Who are thought to be at high risk for developing
glaucoma
82

70. PROGRESSION TO POAG
Prospectively proven risk factors
 Thin corneas (<535 microns)
 Elevated intraocular pressures
 Increasing age
 Vertical cupping of optic nerve (>0.6)
 Increased pattern standard deviation on threshold perimetry
83

71. INDICATIONS FOR
TREATMENT
 If IOP is 30 mmHg or greater
 IOP in mid-to-upper 20s + one or more risk factors
 one-eyed patient
 young patient
84

72.  Unreliable visual fields / optic disc assessment
 Patient who is content with treatment
 Patient who desires treatment
 Vascular occlusion in either eye
85

73. NORMAL TENSION
GLAUCOMA
86

74. NORMAL TENSION
GLAUCOMA
 Typical glaucomatous optic disc cupping
 visual field loss
 normal IOP
 open angles
 absence of any contributing ocular or specific
systemic disorders
87

75. NORMAL TENSION
GLAUCOMA
PATHOGENESIS
 Hereditary increased vulnerability of optic nerve
 Vascular disease may only reduce optic nerve
resistance to pressure-induced damage
88

76. Vascular disease
-migraine
-Raynaud phenomenon
-Systemic hypotension
-carotid insufficiency
-hypercoagulability
-hypertension
89

77. PATHOGENESIS OF NTG
CONTD.
IMMUNOLOGIC BASIS
-autoantibody level found to be higher
90

78. PATHOGENESIS OF NTG
CONTD.
 Sleep disorders associated risk factor
 Mutations in optineurin gene
E50K mutation in optineurin gene
more severe disease &progressive course than NTG
patients without this mutation
91

79. Clinical features
 History
-Migraine & Raynaud phenomenon
-episodes of shock
-head injury or eye injury
-medications
92

80.  IOP higher than 15 mmHg twice likely to progress
over 2 yrs
 Wide variation in 24-hour IOP and with disc
hemorrhage greater risk of progression
 Most cases of normal-tension glaucoma are
detected because of optic disc cupping
93

81. SUBGROUPS OF NTG
 Senile sclerotic group with shallow, pale ,sloping
of NRR ( In older with vascular disease)
 Focal ischemic group with deep ,focal notching in
NRR
94

82. EXAMINATION :NTG
 Ocular examination should include:
 IOP measurement at different times of day & evening,in
sitting & supine position
 Ausculation & palpation of carotid A. reveal obstructive
disease
95

83. ONH findings
96

84. investigations
97

85. Indication for neuroimaging
 Age < 50 yrs
 New onset or increase of headcahe
 Localizing neuro symptoms
 Color vision abnormalities
 Highly asymmetric cupping
 NRR pallor
 Lack of disc and visual field correlation
98

86. TREATMENT OF NTG
100

87. TREATMENT
 Lowering IOP is main thrust of treatment
 IOP to be lowered by 30% which significantly
reduced incidence of future progression
 Disorders such as anemia, arrhythmia, and
congestive heart failure should be treated to
prevent ischemia of optic nerve
101

88.  If untreated pressures are in high teens, then
a target of 15 mmHg or less is reasonable
 If untreated pressures are in mid teens, then
one should aim for pressures in the 10–12
mmHg range
TREATMENT OF NTG CONTD.
102

89. Medical therapy
 Dipivefrinsuperior to timolol in preventing
visual field progression despite similar pressure-
lowering effects
 Brimonidineneuroprotective effects
independent of its pressure-lowering ability
104

90.  Betaxolol compared with timolol, has been
shown to have some direct
neuroprotective characteristics, as well
as to produce increased blood circulation
around optic nerve
105

91.  Dorzolamide improve blood flow velocity in
vicinity of optic nerve
 Laser trabeculoplasty limited benefit in
normal-tension glaucoma but may be worth
trying in patients who are reluctant to undergo,
or are high-risk candidates for surgical
intervention
106

92.  Trabeculectomy lowers pressure and
seems to slow but not necessarily stop
progression of condition
 Patients who have had successful
trabeculectomy seem to do better if they
also receive systemic calcium channel
blocking agents
107

93. RECENT MODALITIES:TREATMENT
OF NTG
 serotonin antagonist :Naftidrofuryl  improves
visual acuity and visual field performance in normal-
tension glaucoma.
 Calcium channel blocking agents increase
optic nerve function and improve blood flow to
nerve
 Nilvadipine, a calcium channel blocker, improved
blood flow around optic nerve in patients with
normal-tension glaucoma
108

94.  Systemic calcium channel blockers help in
improvement in contrast sensitivity &
improvement of indirect measures of blood flow
 Nimodipine-like agent, Brovincamine shows
prevention of visual field progression
109

95. Risk factors for progression
 diabetes mellitus
 positive family history
 female gender
 disc hemorrhage
 increased systolic blood pressure
 history of systemic hemorrhage
110

96. BIBLIOGRAPHY
 Diagnosis & therapy of glaucomas,8th edition
Becker-Shaffer’s
 Glaucoma ,section 10
BCSC,AAO,2016-2017
 Clinical ophthalmology,7th edition
Jack. J. Kanski
 Myron yanoff & jay S Duker ophthalmology(5th
edition)
 Text book of Glaucoma,4th edition
M. Bruce Shields
111

97. 112