Glaucoma

1. Glaucoma
Ocular Pathology & Microbiology
Dr Ian Pacey
UNIVERSITY OF
BRADFORD

2. ¨‘a group of progressive ocular diseases
with various aetiologies that ultimately
result in a rather consistent optic
neuropathy’
¨‘usually with a characteristic loss of
visual function’
Definition
Glaucoma (Greek: grey / opaque)

3. Primary Open Angle Glaucoma
Angle-Closure Glaucoma
Overview
The next two lectures will cover basic
¨pathophysiology
¨symptoms
¨signs
¨management of...

4. Ocular Anatomy
¨Anterior angle
¨The optic nerve
head
¨Aqueous
production &
outflow
Background
You should have revised your notes on:
V.O.A.
¨Gonioscopy
¨Optic nerve head
analysis
¨Tonometry
¨Perimetry

5. ¨adult onset
¨an open angle of normal appearance
¨glaucomatous optic nerve head damage
¨visual field loss
Definition
Primary Open Angle Glaucoma (POAG)
often associated with
¨raised intra-ocular pressure (IOP)
secondary =
no more on angle POAG

6. ¨­ age = ­ resistance to aqueous outflow
¨= increased IOP
¨results in damage to ganglion cell axons at
optic nerve head, by
? mechanical: stretching of lamina cribrosa
? vascular: ¯ perfusion pressure of disc BVs
Pathophysiology
Traditionally:
Effectively the ability of O
2

etc to go BV to nerve
? reduced prod of aqu
but overall incr IOP

7. Characteristic disc damage
¨fibres in inferior (& superior) neuroretinal
rim (NRR)
¨? larger axons affected first
¨? up to 40% nerve fibre loss before
measurable visual function loss
Pathophysiology
However,
¨NB current definition does not include IOP!
i.e. NTG. But IOP still
relevant ACG & >30
affects appearance of
disc & visual field
more later SWAP, motion

8. ¨Quigley (1996)
67million people world-wide affected by 2000!
¨Overall prevalence ~1.5 to 3%
¨not gender dependent
How relevant?
Prevalence
¨the proportion of the population with the
disease at a point in time
?true - not counted

9. How relevant?
Race
(prevalence)
¨Caucasians ~ 1.5 to 2%
¨Asian ~ 3 to 5%
¨Afro-Caribbean ~ 6 to 8%
disease starts younger
higher presenting IOP
more severe disc changes
more resistant to Tx, \ worse prognosis
not great deal of data

10. How relevant?
Age
¨prevalence increases with age
¨>60 yrs SIX times more likely than <60
from Baltimore study
why this point? all dead?

11. OH:
¨none really
? prev brought back for re-checks
¨high myopia - 2 to 3x more likely
perhaps ‘cos myopes have more eye exams?
¨(retinal vein occlusion)
The Case History
Symtoms:
¨NONE!
sometimes ‘something not right’

12. The Case History
FH:
¨Definite genetic link
recently gene loci discovered
¨13-47% of POAG are familial
¨5 to 20x prevalence for +’ve FH
¨Baltimore Eye Study (odds ratio)
siblings 3.69
parents 2.17
children 1.12
‘mum went blind’ - 4x risk of getting
POAG
most quote 8-10x risk
good ‘cos unbiased
population study

13. The Case History
GH:
¨Diabetes
previously 2.8x risk for POAG
?due to hospital based studies
No assoc. (Baltimore, Barbados, Beaver Dam)
Slight assoc. (Rotterdam, Blue Mountains)
¨Poor peripheral circulation (eg Reynauds)
¨Systemic hypertension
rise in BP = rise in IOP but not incr. risk of POAG
Therefore probably <2.8 but still there
cold hands/feet/nose/ears & migraine

14. The Case History
GH:
¨Perfusion pressure (PP)
(diastolic) BP minus IOP
LOW PP associated with prevalence of POAG
<30 mmHg have SIX TIMES risk >50 mmHg
‘nocturnal dippers’ at increased risk
<60yr & ÝBP less risk POAG than age-match controls
>70yr & ÝBP higher risk POAG controls
‘dippers’ those who’s BP
drops dramatically at night.
often recently Tx systemic
hypertensives
initially incr BP helps perfusion, but not when
secondary vascular changes have occured

15. Intra-Ocular Pressure

16. ¨?increases with age
not in Japanese!
¨diurnal variation 3-6 mmHg (>10 suspect)
¨inter-ocular difference <5 mmHg
¨IOP reduced by exercise, accommodation
¨IOP increased by drinking, lying down
Intra-Ocular Pressure
‘Normal’ IOP
¨mean = 16 mmHg
¨distribution skewed towards higher IOP

17. ¨progression slowed by reducing IOP
¨eye with higher IOP progresses faster
Intra-Ocular Pressure
Increased IOP is a risk factor for POAG
¨prevalence increases with IOP

18. Intra-Ocular Pressure
Problem
¨overlap between
normal and POAG’s
IOP
¨~50% of POAG have
IOP <22mmHg
¨large no. have Ý IOP
with no POAG

19. DO NOT use as diagnosis on its own
Intra-Ocular Pressure
measure on all pts: increase over time = suspect

20. ¨raised IOP in the absence of optic nerve
head changes or visual field defects
Prevalence
¨ Framingham Study ~25% !
Conversion to POAG
¨ incidence 1% per year
Refer IOP > 30 mmHg (GOLDMANN)
Ocular Hypertension
Definition
made up?!
ie after 10 years 1/10th will
have converted

21. Optic Nerve Head - normal
Disc size and shape
¨size variation 1:7 in
normal Caucasians
¨inner margin of
Elschnig’s Ring
¨vertically oval

22. Optic Nerve Head - normal
Disc size and shape
Afro-Caribbean higher prevalence of POAG due to
larger discs & cups Þ more susceptible to damage

23. Optic Nerve Head - normal
Neuroretinal Rim (NRR)
¨size varies according to disc size
¨shape = ISNT rule
I
S
NT

24. Optic Nerve Head - normal
Optic cup
¨3 dimensional pale depression in disc
usually horizontally oval
¨size varies according to disc size
¨three main ‘normal’ types
dimple with small central cup
punched out with larger/deeper cup
sloping temporal wall
possibly absent in small discs

25. Optic Nerve Head - normal
Optic cup
¨watch confusion
b/w pallor &
cupping ?
many pallor=cupping. glauc cupping increases & pallor same (?
ageing too). if pallor>cup suspect neurological lesion

26. Optic Nerve Head - normal
Optic cup:disc ratio
¨with Volk & S/L can use beam height
1.5mm
1mm
C:D = ??

27. Optic Nerve Head - normal
Optic cup:disc ratio
¨C:D larger horizontally
¨larger ratios in larger discs
¨average is 0.3-0.4
¨less than 5% ‘normals’ have >0.65
¨asymmetry of <0.2 in 96% of ‘normals’

28. Optic Nerve Head - normal
Peripapillary atrophy
¨potential confusion for CD ratios

29. Optic Nerve Head - POAG
Changes to NRR
¨progressive thinning of NRR
¨general enlargement of CD ratio
ISNT rule no longer applies
generally results in vertical elongation of cup
usually asymmetrical
¨focal
Increased depth of cupping
¨‘saucerisation’ in small discs
¨Laminar Dot signweak diagnostic tool

30. Optic Nerve Head - POAG
General enlargement of CD ratio
PPA
nearly end stage
Not ISNT: Sup thinning?

31. Optic Nerve Head - POAG
CD asymmetry
Not ISNT: Sup thinning?

32. Optic Nerve Head - POAG
Loss of NRR (notching)

33. Optic Nerve Head - POAG
Baring of blood vessels
¨early specific sign of glaucoma
¨circumlinear vessel usually supported by
NRR
¨elongation of cup leaves vessel hanging in
‘mid-air’

34. Optic Nerve Head - POAG
Baring of blood vessels

35. Optic Nerve Head - POAG
Nasal shift of disc vessels
¨said to indicate
glaucomatous
changes
¨can occur in
large C:D’s!

36. Optic Nerve Head - POAG
Bayonet sign
¨vessel has ‘Z’
appearance at
edge of cup
¨rarely seen in
normals

37. Optic Nerve Head - POAG
Splinter haemorrhages
¨flame shaped at
margin
¨mostly Inf Temp
& Sup Temp
¨associated with
nerve fibre defect
¨more in NTG?

38. Optic Nerve Head - POAG
Focal changes to vasculature

39. Nerve Fibre Layer (NFL)
Normal
¨ganglion axons appear as silver striations
¨easiest to see in young, darkly pigmented fundi,
using a bright ‘red-free’ light
¨NFL defects seen in <3% normals
POAG
¨defects seen easiest <2DD from edge of disc
¨usually ‘wedge’ or ‘slit’ defects
¨appear as dark bands radiating out

40. Optic Nerve Head - normal
NFL defect
splinter haem

41. Heidelberg Retinal Tomograph (HRT)

42. HRT

43. Problem
¨Time consuming & subjective
But,
¨often now ‘automated’
¨normal visual field less variable than discs
¨used to gauge success of management
Visual Fields
‘Measures’ what trying to save!

44. Visual Fields
The basis

45. ¨patient reliability (False
+’ve and -’ve responses
& fixation errors)
¨ptosis, lens artefacts
¨learning
¨fatigue
¨cataracts
Visual Fields
Problems for measurement

46. ¨Paracentral scotomas
¨Arcuate scotomas (Bjerrum)
¨Nasal steps
¨Temporal wedges
Localised vs Diffuse
¨the argument rages
¨diffuse probably not due to glaucoma
Visual Fields
‘Typical’ defects

47. Paracentral
scotoma

48. Arcuate scotoma
(Bjerrum)

49. Nasal step

50. SWAP
¨Short-wavelength Automated Perimetry
¨POAG selective damage to SWS ‘pathway’
FDT
¨Frequency Doubling Technology
¨illusion based around M-pathway
Visual Fields
New techniques:

51. When to treat?
¨IOP > 30, irrespective of other risks
¨IOP > 24, if have other risks
¨Any IOP if evidence of optic nerve damage
Management
Following your referral
¨Ophthalmologist confirms diagnosis!

52. ¨Medical
¨Surgical
Both aim to
1.Reduce IOP
2.Prevent optic nerve damage
3.Preserve vision
4.Remain healthy!
Management
Then two potential courses of action

53. ¨Miotics (eg Pilocarpine, 4x day)
Improve trabecular outflow
s/e: ciliary spasm, brow ache, VF constriction + others
¨ Adrenaline (and pro-drugs, 2x day)
ßaqueous inflow & Ý trab outflow
s/e: elevated BP, tachycardia, arrhythmia, h/a, anxiety
stinging, hyperaemia, deposits, mydriasis,
maculopathy
Medical Management
Eye drops of various types
original

54. ¨Carbonic anhydrase inhibitors (Dorzolamide, 3x)
ßaqueous secretion
s/e: parasthesia, nausea, urinary frequency, diarrhoea,
transient myopia
Medical Management
¨Beta-blockers (eg Timolol, 2x day)
Mainstay for ~20 years, various types
ßIOP by reducing aqueous secretion
s/e: bradycardia, arrhythmia, ßBP, heart failure, asthma
dry eye syndrome
newer

55. ¨Future:
Neuroprotection?
Medical Management
¨Prostaglandin analogues
Latanoprost (Xalatan): 1x day at night
increase uveoscleral outflow
more potent than b-blockers
s/e: mild conjunctival hyperaemia, mild punctate
keratopathy, ocular irritation & increased iris
pigmentation (about 20% of pts with mixed colour
irides)
newer

56. ¨Argon Laser Trabeculoplasty
Laser the trabecular meshwork (TM)
scars/contractions open TM
problem effect decreases over time
¨Trabeculectomy
produce a fistula to allow aqueous to drain into
subconjunctival space
seen as a ‘filtration bleb’
Surgical Management
Aim to facilitate aqueous outflow

57. Surgical Management
Trabeculectomy

58. CH: remember Age, Race, FH
Exam: need to measure IOP, do Fields and
carefully examine the disc
Use ALL THREE to decide to refer
Counsel the Pt that it is usually a very slow
progression
Summary
POAG is asymptomatic until late

59. Hitchings (2000) Fundamentals of clinical ophthalmology:
Glaucoma. BMJ Books.
LIB:S617.74.007.681 HIT
Fingeret (2001) Primary care of the glaucomas. McGraw-
Hill.
LIB:S617.74.007.681 LEW
Kanski (1996) Glaucoma: a colour manual of diagnosis
and treatment. Butterworth-Heinemann.
LIB:S617.74.007.681 KAN
References
Web based case studies
http://arapaho.nsuok.edu/~odce/htdocs/glaucoma/glaucoma_cases.html
+ numerous others