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Glaucoma and OCT – Are
Macula Scans More Valuable
than Disc Scans?
Jason Higginbotham Bsc (Hons) MCOptom FBDO
Glaucoma and OCT – Are Macula Scans More
Valuable than Disc Scans?
Glaucoma clinic – lets go back 25 years!
Look for the following:
1. Raised Intra Ocular Pressure (IOP)
2. Glaucomatous Field Loss
3. High CD Ratio, disc Pallor, deep cups, nasal shift of vessels,
bayonetting and so on
4. Px symptoms and family history
5. Narrow angles
6. Secondary markers (E.g. Krukenberg’s spindles)
A Classic View?
Open angle glaucoma
Do we measure IOP?
IOP is still considered the biggest risk factor for Glaucoma.
Do we measure it?
NO!? We estimate it. Often we are a long way off. Only two devices
measure actual IOP – The Reichert Ocular Response Analyser and the
Oculus Corvis ST.
OCT has shown a much higher rate of normal and low tension
glaucoma cases. IOP is important still, but how relevant?
Oculus Corvis
Are Fields reliable?
I’d like to say yes, but the subjective nature of these tests and the
affects of tilted discs and optic disc drusen (for example) can possibly
affect the results – as can happen on OCT disc scans.
What about pre-perimetric glaucoma?
What are RNFL fibres?
In glaucoma, up to 50% of retinal nerve
fibres are lost before a visual field defect
becomes manifest with full threshold
automated static perimetry (Quigley et al
1989)
Definition of Glaucoma
Glaucoma: a group of diseases of the optic nerve which result in a
loss of retinal ganglion cells in a characteristic pattern of optic
neuropathy
Glaucoma is a group of eye diseases that cause progressive damage
of the optic nerve at the point where it leaves the eye to carry visual
information to the brain. - World Glaucoma Association
The American Academy of Ophthalmology now defines glaucoma as
“a group of diseases with certain features including an intraocular
pressure that is too high for the continued health of the eye.”
What actually occurs in Glaucoma and where?
Studies have shown that the actual process at play is RGC (Retinal
Ganglion Cell) body shrinkage followed by RGC body death taking
place.
This has been shown to be due to cellular apoptosis caused either by
ischaemia or by excitotoxicity (glutamate in the vitreous). IOP may
cause release of glutamate as a traumatic response and glutamate is
toxic to RGC’s.
However, papers also suggest bringing down the IOP in normal
tension glaucoma patients is effective at slowing progress of the
disease.
Theories of Damage
What actually occurs in Glaucoma and where?
What actually occurs in Glaucoma and where?
We now have two main theories:
Selective Damage Theory versus
Reduced Redundancy Theory
It’s probable that a ‘bit of both’ are at play!
However, it’s the RGC that dies off in all cases. But the axonal death
may bring about the RGC death, or does it?
The Ganglion Cell Complex
The Ganglion Cell Complex (GCC) is the innermost five layers of the
retina (ILM, RNFL, GCL, IPL and INL).
Easier to measure as a whole than just the GCL or GCL and IPL.
GCC tends to shrink before obvious change at the disc, but there are
cases where this doesn’t occur.
Lots of evidence to suggest that ganglion cell body shrinkage takes
place first. Does axonal damage occur later – if so, the RNFL may be
intact or appear so for longer and might not manifest on eye
examination.
Normal GCC
GCC thinner in Glaucoma
The Ganglion Cell Complex
With the added ‘G Chart’,
Ganglion Cell Complex
thickness can be assessed
against the normative data.
Notice that now the scale
only represents half a bell
curve. Where the GCC is
thicker, this is represented
in white as there is no
known pathology of GCC
hyperplasia.
G Chart
The Ganglion Cell Complex
Normative Scales
Disc scans – RNFL measurement
Disc RNFL Analysis
Macula Scans versus Disc Scans
It is well known that Macula scans are more repeatable, accurate
and reliable than Disc scans.
Macula scans are easier to repeat and compare due to greater
fixation stability and ease of scan overlay.
Disc scans are more prone to subtle positioning errors, fixation loss
and opto-kinetic nystagmus.
Disc Drusen, Tilted Disc, Peripapillary ERM’s and papilloedema all
affect the accuracy and repeatability of disc scans.
Progression analysis
• Spotting Glaucoma early is one of the most
important uses of OCT and is certainly one area
where Optometrists come into their own within
Primary care and also in Community
Ophthalmology and Secondary care.
• We can use the software to analyse if there is
any progression in loss of Ganglion Cell Complex
(GCC) at the Macula or Retinal Near Fibre Layer
(RNFL) thickness at the Optic Nerve Head (ONH).
• Superior / Inferior step analysis as well as R/L
comparison are always important too.
GCC Progression R Eye
RNFL Progression R Eye ONH
This 44 year old patient
attended a clinic. They had
evident disc cupping in both
eyes with some palour.
Our suspicions would already be
aroused by the discs, but the
IOP’s were not raised.
A Late Stage Example. Case 1.
• The right visual
field shows an
arcuate scotoma,
with blind spot
enlargement in
the left eye.
The field loss becomes more obvious when we look at the RNFL layer
thickness deviation maps against the normative data.
You can see the evidence of loss of RNFL particularly in the Right Eye
which corresponds perfectly with the field plot on the previous page.
R L
The ETDRS chart
shows minor
thinning of the retina
inferior to the
Macula in the right
eye.
The G Chart, however, shows considerable inferior thinning and loss of
the Ganglion Cell Complex across the inferior Macula. The shape from
the deviation map is typically arcuate and matches the field loss very
closely. Note the nasal step and the horizontal mid line.
Example Case 2
84 Year Old Female
Drop in vision RE. Family history of Glaucoma.
IOP’s RE 17 mmHg LE 20 mmHg. CCT 512 microns.
Visual Fields inconclusive, poor compliance.
VA RE 6/24 distorted. LE 6/9 .
OH – Bilat IOL’s. FOH – Mother Glaucoma. GH – Good.
Arthritis. Meds – Anti inflammatories. FMH – Nil.
No headaches or other Sx. Driver. Retired, but does
voluntary work part time!
Example Case 3
61 Year Old Male
No visual complaints.
IOP’s RE 19 mmHg LE 18 mmHg. Corrected IOP’s.
Visual Fields show minor initial loss of sensitivity RE.
VA RE 6/6 LE 6/6 OH – No Ops. FOH – None
GH – Good. Meds – None. FMH – Nil.
No headaches or other Sx. Driver. Accountant.
Uses PC a lot. Plays golf and goes to the gym.
Example Case 4
65 Year Old Female
Noticed poor vision LE. A few headaches. No eye ache.
No haloes. Reading difficult.
Corrected IOP’s RE 22 mmHg LE 23 mmHg.
Visual Fields RE: Full 26 dB, LE: Early inferior arcuate
loss 24 dB. Slightly narrow angles OU.
VA RE 6/6- LE 6/9
OH – Good. No Ops. FOH – Sister Glaucoma.
GH – Hypertension. Meds – Anti hypertensives and
statins. FMH – Father heart attack.
Driver. Retired.
Example Case 5
72 Year Old Female
Night driving difficult. No headaches. No pain or other
ocular symptoms.
IOP’s RE 13 mmHg LE 13 mmHg.
Visual Fields full right and left. 24-2 screening.
VA RE 6/6- LE 6/6-
OH – Early lens opacities. No Ops. FOH – Mother went
blind; AMD. GH – Arthritis and IBS Meds – Anti
inflammatories. FMH – Nil. Driver. Retired. Uses PC and
likes to read.
Potential Errors with Macula Scans
There are circumstances where the reliability and accuracy of
Macula scans is slightly reduced. These include:
• High myopes. Some cases show overall retinal thinning, whereas
occasionally, the GCC alone seems thinned in some myopes.
• Epi retinal membranes (ERM’s) can affect the overall retinal
thickness and make accurate assessment of GCC difficult.
• Presence of over underlying pathology, particularly where a
large regional increase in overall retinal thickness occurs, such as
CSR (central serous retinopathy).
Potential for the future
As higher resolution devices become available with longer
wavelength infra red lasers and greater tissue penetration, then it
will be likely that better repeatability of scans will occur and more
effective scan imaging even with dense lens opacities might
become possible.
As whole eye OCT is being developed, it may not be too long before
such device can offer assessment of more eye parameters in one
full glaucoma plot.
Many devices have software which can or will incorporate visual
field plots and other test results.
Earliest Glaucoma detection
There is no doubt that OCT can detect glaucomatous damage much
earlier than visual fields and other older techniques.
However, it is possible to detect even earlier changes that OCT’s
might not.
Modern ERG / VEP tests can detect extremely subtle alterations in
the speed of response in the visual system and the speed of
depolarisation in the process of ‘seeing’.
There is a new device which makes these tests much quicker and
easier than before.
The Diopsys Nova and Argos systems
Tabletop
Cart
ERG and VEP for early glaucoma detection
Structure
Fundus Photograph
(Subjective)
Function
Visual Field
(Subjective)
ERG and VEP for early glaucoma detection
Structure Function
Optical Coherence Tomography
(Objective)
ERG
(Objective)
ERG and VEP for early glaucoma detection
Electrical activity of the retina
ERG
Pattern ERG
Flash ERG • Objective/functional assessment for early to
moderate disease patients
• First technology to assess cell sickness, not cell
death
• Early diagnosis = early treatment
• Additional information to assist the doctor to make
a more informed decision to either treat or follow
the patient
• Assists the doctor in determining whether
treatment is working or not
• Like OCT, Electrophysiology is a multi faceted
technology which offers clinical benefits for
glaucoma, retina, and anterior segment
• Glaucoma
• Multiple Sclerosis
• Ischemic Optic Neuropathy
• Traumatic Brain Injury
• Amblyopia
• Other Neuropathies
MAIN INDICATIONS
Visual Evoked Potential (VEP)
ERG and VEP for early glaucoma detection
Age (years): 75
Gender: Male
Complaint: Blurry vision, OD<OS
Personal History: Hypertension, COAG
(Dorzolamide, Timolol)
Family History: CVA
Allergies: No known allergies
Uncorrected VA OD: 20/50
Uncorrected VA OS: 20/50
Refraction OD: -1.50 x 94
Refraction OS: +1.00 -0.50 x 92
BCVA OD: 20/20
BCVA OS: 20/20
Case 1: ERG correlates with visual fields and RNFL
assessment
IOP OD (mmHg): 19
IOP OS (mmHg): 17
Pupil OD: PERRL, negative APD
Pupil OS: PERRL, negative APD
Anterior Segment OD: Pseudophakic
Anterior Segment OS: Pseudophakic
Fundus Exam OD: CD ratio 0.6
Fundus Exam OS: CD ratio 0.6
Diagnosis: COAG
Visual Fields: Outside normal limits (OS worse then OD)
RNFL thickness: outside normal
limits OS worse then OD
PERG: outside normal limits
OS worse then OD
PERG correlates with visual field and RNFL
assessment
When used in conjunction with other diagnostic
modalities PERG can offer another valuable tool
to help the doctor treat or follow a patient.
Case 1 Conclusion
Case 2: VEP
Glaucoma Suspect
Reason for test:
Standard test are unreliable
Patient Work-Up
Gender Male
Age 70
Ethnicity White
Complaints/Symptoms None
Family History Mother & Grandmother glaucoma
IOP (mmHg) OD 23
IOP (mmHg) OS 21
Pachymetry (µm) OD 506
Pachymetry (µm) OS 507
Refraction OD Plano
Refraction OS Plano
BCVA OD 20/25
BCVA OS 20/25
Preliminary Diagnosis Glaucoma Suspect
Visual Field Results
Humphrey 24-2 shows a slight depression in the inferior Blind Spot OD, and
borderline GHT findings although this field was somewhat unreliable. OS
without defect.
HRT Result
VEP Result
Shows increased latency in
low & high contrast OD,
and normal amplitude &
latency OS.
Diagnosis and Treatment:
“Having the ability to obtain a new objective measurement of optic nerve function by
performing a VEP has helped significantly in the decision to treat this patient for early POAG.”
Dr. Farrell Tyson
Initiated treatment with Lumigan 0.01 % OU
Follow up visit one month later, IOP’s were 18 and 16 (acceptable level for patient)
Will follow at quarterly intervals
Conclusion: VEP Aids in Decision To Treat
In summary
We must use ALL the information available to us to hopefully
produce more effective and early diagnosis of glaucoma.
As well as the ‘usual’ information, OCT provides massively useful
data, especially the macula scans and the GCC progression.
New versions of old technology, like ERG/VEP can aid in the earliest
diagnoses, in differential diagnosis and in follow up / treatment
analysis.
In summary
Be aware of the potential limitations of devices.
Consider follow up examinations where immediate referral might
not be necessary.
Each piece of data or scan results are pieces in a diagnostic jigsaw
puzzle.
Thank you for Listening.
References
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References

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Glaucoma and OCT – Are Macula Scans More Valuable than Disc Scans

  • 1. Glaucoma and OCT – Are Macula Scans More Valuable than Disc Scans? Jason Higginbotham Bsc (Hons) MCOptom FBDO
  • 2. Glaucoma and OCT – Are Macula Scans More Valuable than Disc Scans? Glaucoma clinic – lets go back 25 years! Look for the following: 1. Raised Intra Ocular Pressure (IOP) 2. Glaucomatous Field Loss 3. High CD Ratio, disc Pallor, deep cups, nasal shift of vessels, bayonetting and so on 4. Px symptoms and family history 5. Narrow angles 6. Secondary markers (E.g. Krukenberg’s spindles)
  • 3. A Classic View? Open angle glaucoma
  • 4.
  • 5. Do we measure IOP? IOP is still considered the biggest risk factor for Glaucoma. Do we measure it? NO!? We estimate it. Often we are a long way off. Only two devices measure actual IOP – The Reichert Ocular Response Analyser and the Oculus Corvis ST. OCT has shown a much higher rate of normal and low tension glaucoma cases. IOP is important still, but how relevant?
  • 7. Are Fields reliable? I’d like to say yes, but the subjective nature of these tests and the affects of tilted discs and optic disc drusen (for example) can possibly affect the results – as can happen on OCT disc scans. What about pre-perimetric glaucoma? What are RNFL fibres? In glaucoma, up to 50% of retinal nerve fibres are lost before a visual field defect becomes manifest with full threshold automated static perimetry (Quigley et al 1989)
  • 8. Definition of Glaucoma Glaucoma: a group of diseases of the optic nerve which result in a loss of retinal ganglion cells in a characteristic pattern of optic neuropathy Glaucoma is a group of eye diseases that cause progressive damage of the optic nerve at the point where it leaves the eye to carry visual information to the brain. - World Glaucoma Association The American Academy of Ophthalmology now defines glaucoma as “a group of diseases with certain features including an intraocular pressure that is too high for the continued health of the eye.”
  • 9. What actually occurs in Glaucoma and where? Studies have shown that the actual process at play is RGC (Retinal Ganglion Cell) body shrinkage followed by RGC body death taking place. This has been shown to be due to cellular apoptosis caused either by ischaemia or by excitotoxicity (glutamate in the vitreous). IOP may cause release of glutamate as a traumatic response and glutamate is toxic to RGC’s. However, papers also suggest bringing down the IOP in normal tension glaucoma patients is effective at slowing progress of the disease.
  • 10. Theories of Damage What actually occurs in Glaucoma and where?
  • 11. What actually occurs in Glaucoma and where? We now have two main theories: Selective Damage Theory versus Reduced Redundancy Theory It’s probable that a ‘bit of both’ are at play! However, it’s the RGC that dies off in all cases. But the axonal death may bring about the RGC death, or does it?
  • 12. The Ganglion Cell Complex The Ganglion Cell Complex (GCC) is the innermost five layers of the retina (ILM, RNFL, GCL, IPL and INL). Easier to measure as a whole than just the GCL or GCL and IPL. GCC tends to shrink before obvious change at the disc, but there are cases where this doesn’t occur. Lots of evidence to suggest that ganglion cell body shrinkage takes place first. Does axonal damage occur later – if so, the RNFL may be intact or appear so for longer and might not manifest on eye examination.
  • 13. Normal GCC GCC thinner in Glaucoma
  • 14. The Ganglion Cell Complex With the added ‘G Chart’, Ganglion Cell Complex thickness can be assessed against the normative data. Notice that now the scale only represents half a bell curve. Where the GCC is thicker, this is represented in white as there is no known pathology of GCC hyperplasia. G Chart
  • 15. The Ganglion Cell Complex Normative Scales
  • 16. Disc scans – RNFL measurement Disc RNFL Analysis
  • 17. Macula Scans versus Disc Scans It is well known that Macula scans are more repeatable, accurate and reliable than Disc scans. Macula scans are easier to repeat and compare due to greater fixation stability and ease of scan overlay. Disc scans are more prone to subtle positioning errors, fixation loss and opto-kinetic nystagmus. Disc Drusen, Tilted Disc, Peripapillary ERM’s and papilloedema all affect the accuracy and repeatability of disc scans.
  • 18. Progression analysis • Spotting Glaucoma early is one of the most important uses of OCT and is certainly one area where Optometrists come into their own within Primary care and also in Community Ophthalmology and Secondary care. • We can use the software to analyse if there is any progression in loss of Ganglion Cell Complex (GCC) at the Macula or Retinal Near Fibre Layer (RNFL) thickness at the Optic Nerve Head (ONH). • Superior / Inferior step analysis as well as R/L comparison are always important too.
  • 21. This 44 year old patient attended a clinic. They had evident disc cupping in both eyes with some palour. Our suspicions would already be aroused by the discs, but the IOP’s were not raised. A Late Stage Example. Case 1.
  • 22. • The right visual field shows an arcuate scotoma, with blind spot enlargement in the left eye.
  • 23. The field loss becomes more obvious when we look at the RNFL layer thickness deviation maps against the normative data. You can see the evidence of loss of RNFL particularly in the Right Eye which corresponds perfectly with the field plot on the previous page. R L
  • 24. The ETDRS chart shows minor thinning of the retina inferior to the Macula in the right eye. The G Chart, however, shows considerable inferior thinning and loss of the Ganglion Cell Complex across the inferior Macula. The shape from the deviation map is typically arcuate and matches the field loss very closely. Note the nasal step and the horizontal mid line.
  • 25. Example Case 2 84 Year Old Female Drop in vision RE. Family history of Glaucoma. IOP’s RE 17 mmHg LE 20 mmHg. CCT 512 microns. Visual Fields inconclusive, poor compliance. VA RE 6/24 distorted. LE 6/9 . OH – Bilat IOL’s. FOH – Mother Glaucoma. GH – Good. Arthritis. Meds – Anti inflammatories. FMH – Nil. No headaches or other Sx. Driver. Retired, but does voluntary work part time!
  • 26.
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  • 34. Example Case 3 61 Year Old Male No visual complaints. IOP’s RE 19 mmHg LE 18 mmHg. Corrected IOP’s. Visual Fields show minor initial loss of sensitivity RE. VA RE 6/6 LE 6/6 OH – No Ops. FOH – None GH – Good. Meds – None. FMH – Nil. No headaches or other Sx. Driver. Accountant. Uses PC a lot. Plays golf and goes to the gym.
  • 35.
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  • 40. Example Case 4 65 Year Old Female Noticed poor vision LE. A few headaches. No eye ache. No haloes. Reading difficult. Corrected IOP’s RE 22 mmHg LE 23 mmHg. Visual Fields RE: Full 26 dB, LE: Early inferior arcuate loss 24 dB. Slightly narrow angles OU. VA RE 6/6- LE 6/9 OH – Good. No Ops. FOH – Sister Glaucoma. GH – Hypertension. Meds – Anti hypertensives and statins. FMH – Father heart attack. Driver. Retired.
  • 41.
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  • 47. Example Case 5 72 Year Old Female Night driving difficult. No headaches. No pain or other ocular symptoms. IOP’s RE 13 mmHg LE 13 mmHg. Visual Fields full right and left. 24-2 screening. VA RE 6/6- LE 6/6- OH – Early lens opacities. No Ops. FOH – Mother went blind; AMD. GH – Arthritis and IBS Meds – Anti inflammatories. FMH – Nil. Driver. Retired. Uses PC and likes to read.
  • 48.
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  • 53. Potential Errors with Macula Scans There are circumstances where the reliability and accuracy of Macula scans is slightly reduced. These include: • High myopes. Some cases show overall retinal thinning, whereas occasionally, the GCC alone seems thinned in some myopes. • Epi retinal membranes (ERM’s) can affect the overall retinal thickness and make accurate assessment of GCC difficult. • Presence of over underlying pathology, particularly where a large regional increase in overall retinal thickness occurs, such as CSR (central serous retinopathy).
  • 54. Potential for the future As higher resolution devices become available with longer wavelength infra red lasers and greater tissue penetration, then it will be likely that better repeatability of scans will occur and more effective scan imaging even with dense lens opacities might become possible. As whole eye OCT is being developed, it may not be too long before such device can offer assessment of more eye parameters in one full glaucoma plot. Many devices have software which can or will incorporate visual field plots and other test results.
  • 55. Earliest Glaucoma detection There is no doubt that OCT can detect glaucomatous damage much earlier than visual fields and other older techniques. However, it is possible to detect even earlier changes that OCT’s might not. Modern ERG / VEP tests can detect extremely subtle alterations in the speed of response in the visual system and the speed of depolarisation in the process of ‘seeing’. There is a new device which makes these tests much quicker and easier than before.
  • 56. The Diopsys Nova and Argos systems Tabletop Cart
  • 57. ERG and VEP for early glaucoma detection Structure Fundus Photograph (Subjective) Function Visual Field (Subjective)
  • 58. ERG and VEP for early glaucoma detection Structure Function Optical Coherence Tomography (Objective) ERG (Objective)
  • 59. ERG and VEP for early glaucoma detection Electrical activity of the retina ERG Pattern ERG Flash ERG • Objective/functional assessment for early to moderate disease patients • First technology to assess cell sickness, not cell death • Early diagnosis = early treatment • Additional information to assist the doctor to make a more informed decision to either treat or follow the patient • Assists the doctor in determining whether treatment is working or not • Like OCT, Electrophysiology is a multi faceted technology which offers clinical benefits for glaucoma, retina, and anterior segment
  • 60. • Glaucoma • Multiple Sclerosis • Ischemic Optic Neuropathy • Traumatic Brain Injury • Amblyopia • Other Neuropathies MAIN INDICATIONS Visual Evoked Potential (VEP) ERG and VEP for early glaucoma detection
  • 61. Age (years): 75 Gender: Male Complaint: Blurry vision, OD<OS Personal History: Hypertension, COAG (Dorzolamide, Timolol) Family History: CVA Allergies: No known allergies Uncorrected VA OD: 20/50 Uncorrected VA OS: 20/50 Refraction OD: -1.50 x 94 Refraction OS: +1.00 -0.50 x 92 BCVA OD: 20/20 BCVA OS: 20/20 Case 1: ERG correlates with visual fields and RNFL assessment
  • 62. IOP OD (mmHg): 19 IOP OS (mmHg): 17 Pupil OD: PERRL, negative APD Pupil OS: PERRL, negative APD Anterior Segment OD: Pseudophakic Anterior Segment OS: Pseudophakic Fundus Exam OD: CD ratio 0.6 Fundus Exam OS: CD ratio 0.6 Diagnosis: COAG
  • 63. Visual Fields: Outside normal limits (OS worse then OD)
  • 64. RNFL thickness: outside normal limits OS worse then OD PERG: outside normal limits OS worse then OD
  • 65. PERG correlates with visual field and RNFL assessment When used in conjunction with other diagnostic modalities PERG can offer another valuable tool to help the doctor treat or follow a patient. Case 1 Conclusion
  • 66. Case 2: VEP Glaucoma Suspect Reason for test: Standard test are unreliable Patient Work-Up Gender Male Age 70 Ethnicity White Complaints/Symptoms None Family History Mother & Grandmother glaucoma IOP (mmHg) OD 23 IOP (mmHg) OS 21 Pachymetry (µm) OD 506 Pachymetry (µm) OS 507 Refraction OD Plano Refraction OS Plano BCVA OD 20/25 BCVA OS 20/25 Preliminary Diagnosis Glaucoma Suspect
  • 67. Visual Field Results Humphrey 24-2 shows a slight depression in the inferior Blind Spot OD, and borderline GHT findings although this field was somewhat unreliable. OS without defect.
  • 69. VEP Result Shows increased latency in low & high contrast OD, and normal amplitude & latency OS.
  • 70. Diagnosis and Treatment: “Having the ability to obtain a new objective measurement of optic nerve function by performing a VEP has helped significantly in the decision to treat this patient for early POAG.” Dr. Farrell Tyson Initiated treatment with Lumigan 0.01 % OU Follow up visit one month later, IOP’s were 18 and 16 (acceptable level for patient) Will follow at quarterly intervals Conclusion: VEP Aids in Decision To Treat
  • 71. In summary We must use ALL the information available to us to hopefully produce more effective and early diagnosis of glaucoma. As well as the ‘usual’ information, OCT provides massively useful data, especially the macula scans and the GCC progression. New versions of old technology, like ERG/VEP can aid in the earliest diagnoses, in differential diagnosis and in follow up / treatment analysis.
  • 72. In summary Be aware of the potential limitations of devices. Consider follow up examinations where immediate referral might not be necessary. Each piece of data or scan results are pieces in a diagnostic jigsaw puzzle.
  • 73. Thank you for Listening.
  • 74. References 1. E A Ansari, J E Morgan and R J Snowden Glaucoma: squaring the psychophysics and neurobiology Br J Ophthalmol 2002 86: 823-826 2. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239-57. 3. Neville N Osborne, John P M Wood, Glyn Chidlow, Ji-Hong Bae, Jose Melena and Mark S Nash Ganglion cell death in glaucoma: what do we really know? Br J Ophthalmol 1999 83:980-986 4. J E Morgan Selective cell death in glaucoma: does it really occur? Br J Ophthalmol 1994 78: 875- 880 5. Quigley HA, Sanchez RM, Dunkelberger GR, L'Hernault NL, Baginski TA. Chronic glaucoma selectively damages large optic nerve fibres. Invest Ophthalmol Vis Sci. 1987 Jun;28(6):913-20. 6. Chaturvedi N, Hedley-Whyte ET, Dreyer EB. Lateral geniculate nucleus in glaucoma. Am J Ophthalmol. 1993 Aug 15;116(2):182-8. 7. Silverman SE, Trick GL, Hart WM Jr. Motion perception is abnormal in primary open-angle glaucoma and ocular hypertension. Invest Ophthalmol Vis Sci. 1990 Apr;31(4):722-9. 8. Merigan WH. Chromatic and achromatic vision of macaques: role of the P pathway. J Neurosci. 1989 Mar;9(3):776-83. 9. Glovinsky Y, Quigley HA, Dunkelberger GR. Retinal ganglion cell loss is size dependent in experimental glaucoma. Invest Ophthalmol Vis Sci. 1991 Mar;32(3):484-91.
  • 75. 10. Merigan WH, Byrne CE, Maunsell JH. Does primate motion perception depend on the magnocellular pathway? J Neurosci. 1991 Nov;11(11):3422-9. 11. Willis A, Anderson SJ. Effects of glaucoma and aging on photopic and scotopic motion perception. Invest Ophthalmol Vis Sci. 2000 Jan;41(1):325-35. 12. Quigley HA. Identification of glaucoma-related visual field abnormality with the screening protocol of frequency doubling technology. Am J Ophthalmol. 1998 Jun;125(6):819-29. 13. Pamela A. Sample, Ph.D., James D.N. Taylor, M.D., Genaro A. Martinez, Moshe Lusky, M.D., Robert N. Weinreb, M.D. Short-wavelength Colour Visual Fields in Glaucoma Suspects at Risk. American Journal of Ophthalmology Volume 115, Issue 2, February 1993, Pages 225–233 14. Johnson C. Early Losses of Visual Function in Glaucoma. Optometry & Vision Science: June 1995 - Volume 72 - Issue 6 - ppg 359-370 15. Sample PA, Johnson CA, Haegerstrom-Portnoy G, Adams AJ. Optimum parameters for short- wavelength automated perimetry. J Glaucoma. 1996 Dec;5(6):375-83. 16. Quigley HA, Dunkelberger GR, Green WR. Chronic human glaucoma causing selectively greater loss of large optic nerve fibres. Ophthalmology. 1988 Mar;95(3):357-63. 17. Grieshaber MC, Mozaffarieh M, Flammer J. What is the link between vascular dysregulation and glaucoma? Surv Ophthalmol. 2007 Nov;52 Suppl 2:S144-54. 18. Renu Agarwal, Suresh K Gupta, Puneet Agarwal, Rohit Saxena and Shyam S Agrawal Current concepts in the pathophysiology of glaucoma Indian J Ophthalmol. 2009 Jul-Aug; 57(4): 257–266. References
  • 76. 19. Jonathan Denniss MOptom(Hons) MCOptom and Professor David Henson PhD FCOptom ; The Structure–Function Relationship in Glaucoma: Implications for Disease Detection Optometry in Practice Vol 10 (2009) 95–104 20. Andreas Schulze, Julia Lamparter, Norbert Pfeiffer, Fatmire Berisha, Irene Schmidtmann, Esther M. Hoffmann Diagnostic ability of retinal ganglion cell complex, retinal nerve fibre layer, and optic nerve head measurements by Fourier domain optical coherence tomography. Graefe's Archive for Clinical and Experimental Ophthalmology; July 2011, Volume 249, Issue 7, pp 1039-1045 21. Donald C. Hood, Brad Fortune, Maria A. Mavrommatis, Juan Reynaud, Rithambara Ramachandran, Robert Ritch, Richard B. Rosen, Hassan Muhammad, Alfredo Dubra, and Toco Y. P. Chui. Details of Glaucomatous Damage Are Better Seen on OCT En Face Images Than on OCT Retinal Nerve Fiber Layer Thickness Maps. IOVS; October 2015: Vol. 56 No. 11 pp 6208-6216 22. Zhiyong Yang, Andrew J. Tatham, Robert N. Weinreb, Felipe A. Medeiros, Ting Liu, Linda M. Zangwill Diagnostic Ability of Macular Ganglion Cell Inner Plexiform Layer Measurements in Glaucoma Using Swept Source and Spectral Domain Optical Coherence Tomography. PLOS ONE NEED OI: 10.1371/journal.pone.0125957 May 15, 2015 23. B. Anguelov K. Petrova Diagnostic accuracy of the parameters from ganglion cell complex map, evaluated with SD-OCT in primary open-angle glaucoma. Ophthalmology in Russia. — 2014. — Vol. 11, No 3. — P. 28–32 24. Diane L. Wang, Ali S. Raza, Carlos Gustavo de Moraes, Monica Chen, Paula Alhadeff, Ravivarn Jarukatsetphorn, Robert Ritch, and Donald C. Hood Central Glaucomatous Damage of the Macula Can Be Overlooked by Conventional OCT Retinal Nerve Fiber Layer Thickness Analyses. TVST: 2015 Vol. 4 No. 6 Article 4 References
  • 77. 24. Na Rae Kim, MD, Samin Hong, MD, PhD, Ji Hyun Kim, MD, Seung Soo Rho, MD, Gong Je Seong, MD, PhD, and Chan Yun Kim, MD, PhD Comparison of Macular Ganglion Cell Complex Thickness by Fourier-Domain OCT in Normal Tension Glaucoma and Primary Open-Angle Glaucoma. J Glaucoma Volume 22, Number 2, February 2013 pp 133 – 139 25. Donald C. Hood, Ali S. Raza, Carlos Gustavo V. de Moraes, Jeffrey M. Liebmann, Robert Ritch Glaucomatous damage of the macula. Progress in Retinal and Eye Research (2012), http:// dx.doi.org/10.1016/j.preteyeres.2012.08.003 26. Ivan Marjanovic The History of Detecting Glaucomatous Changes in the Optic Disc. http://dx.doi.org/10.5772/52470 27. Charanjit Kaur, Wallace S Foulds, Eng-Ang Ling Hypoxia-ischemia and retinal ganglion cell damage. Clinical Ophthalmology 2008:2(4) 879–889 28. Dr. Valsa Stephen MS DO DNB, Dr. Arup Chakrabarti MS DO, Dr. Sonia Rani John DNB, Dr. Meena Chakrabarti MS DO DNB OCT in Glaucoma. Kerala Journal of Ophthalmology Vol. XIX, No. 2 pp 183 – 190 29. Paolo Carpineto, MD, Marco Ciancaglini, MD, Eduardo Zuppardi, MD, Gennaro Falconio, MD, Emanuele Doronzo, MD, Leonardo Mastropasqua, MD Reliability of Nerve Fiber Layer Thickness Measurements Using Optical Coherence Tomography in Normal and Glaucomatous Eyes. Ophthalmology Volume 110, Number 1, January 2003 190 – 195 30. Graham Lakkis BScOptom Grad Cert OcTher FACO The ganglion cell complex and glaucoma. Pharma March 2014 pp 28-32 References
  • 78. 31. Quigley HA, Dunkelberger GR, Green WR. Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol 1989; 107: 453-464. 32. Feng L et al. Sustained ocular hypertension induces dendritic degeneration of mouse retinal ganglion cells that depends on cell type and location. Invest Ophthalmol Vis Sci 2013 7; 54: 2: 1106-1117. 33. Fortune B, Cull GA, Burgoyne CF. Relative course of RNFL birefringence, RNFL thickness and retinal function changes after optic nerve transection. Invest Ophthalmol Vis Sci 2008; 49: 10: 4444-4452. 34. Glovinsky Y, Quigley HA, Pease ME. Foveal ganglion cell loss in size dependent experimental glaucoma. Invest Ophthalmol Vis Sci 1993: 34395-34400. 35. Garas A, Vargha P, Hollo G. Reproducibility of retinal nerve fibre layer and macular thickness measurement with RTVue-100 OCT. Ophthalmology 2010; 117: 4: 738-746. 36. Pierro L, Gagliardi M et al. Retinal fibre layer thickness reproducibility using 7 different OCT instruments. Invest Ophthalmol Vis Sci 2012; 53: 9: 5912-5920. 37. Sung KS et al. Macula assessment using OCT for glaucoma diagnosis. Br J Ophthalmol 2012; 96: 12: 1452-1455. 38. Kotowski J et al. Glaucoma discrimination of segmented SD-OCT macular scans. Br J Ophthalmol References

Notes de l'éditeur

  1. IOP would be seen as the key risk factor and there would be two potential causes of damage from that IOP – Mechanical and Vascular. Everything would be disc centred in terms of investigations and ultimately consultants in the clinic of the past would have been thinking about the health or otherwise of the patients’ RNFL at the ONH (Optic Nerve Head). But, what is the RNFL? How much RNFL can we lose before it manifests as a field loss? If mechanical were the only cause, why would there be cases of NTG (normal tension glaucoma) and LTG (low tension glaucoma).
  2. At 4300 frames per second, the high speed Scheimpflug camera on the Corvis allows for full understanding of the Corneal hysteresis as well as size and structure. This allows for pneumo tonometry to provide full analysis of the real IOP as well as better prediction of ectactic disease and follow up of treatments like CXL (Corneal Cross Linking).
  3. Of course visual fields are important and reducing IOP is aimed solely at reducing the speed and extent of visual field loss progression. The Early Manifest Glaucoma Trial showed that there is a 10% decrease in the risk of worsening visual field loss (visual field progression) for every 1 mmHg reduction in IOP.
  4. The definition seems to have changed back and forth slightly over recent decades. Ultimately, Glaucoma is an Optic Neuropathy. How and why that occurs is certainly not yet fully known. According to World Health Organisation data (2002), worldwide glaucoma accounts for 12% of cases of blindness which makes it the second leading cause of blindness after cataract (48%).
  5. It is important to remember that apoptosis is often a useful mechanism in the body. For example, 50% of the RGC’s naturally die off during the visual system’s development by apoptosis and it is clear that some mechanism of insult and subsequent secondary neuro toxin release leads to the unnecessary programmed cell death encountered in glaucoma.
  6. The overriding premise still in existence is that intra ocular pressure (IOP) is the main cause of glaucoma (Cioffi and Van Buskirk 1994; see other references at the end of the lecture). Most sources suggest a mechanical and a vascular element to how the IOP causes physical damage to tissue and may lead to the release of neuro toxins. Basically, Selective Damage Theory states that the larger retinal nerve fibres are most affected by raised IOP (whether mechanical or vascular mechanisms). All RNFL fibres are affected to some extent, but it appears that the larger fibres are affected the most and at a greater rate. There is some damage to the RGC axonal flow. Reduced redundancy depends on the number, spread and commonality of different RGC’s. There are more Red ON RGC’s than there are Blue ON RGC’s. In glaucoma, all RGC’s reduce in number, but the proportion of blue RGC’s lost is much higher; this leads to blue on yellow defects occurring earlier in many cases. Note SWAP programme on the Humphrey field analyser.
  7. In either case, a patient can lose 50% of their superior and inferior nerve fibre bundles or GCC before this manifests as a field loss and up to 40% of their papillo macular region of nerve fibres or GCC before this manifests as a field loss. So, until the patient has perimetric glaucoma (if normal tension), they may not be referred and we could be sending them to the eye department to ‘rescue what’s left’ of their retinal/optic nerve neural tissue. So, is glaucoma a disease of the optic nerve or the retina or essentially both?
  8. The Ganglion Cell Complex is a clinically recognised ‘layer’ of the Retina. It represents the innermost five layers of the Retina. These are the ILM (Inner Limiting Membrane), the RNFL (Retinal Nerve Fibre Layer), the GCL (Ganglion Cell Layer), the IPL (Inner Plexiform Layer) and the INL (Inner Nuclear Layer). The GCC has been clinically proven to be the only layers of the Retina affected by Glaucoma and so some devices measure this against Normative data. Other OCT’s try to measure the GCL alone or the GCL and IPL together to assess Glaucoma risk. Note also the Superior / Inferior comparison. This is useful as no RNFL fibres cross the midline, and usually, the inferior GCC is thicker than the superior. This also allows us to assess symmetry WITHIN the eye. If there is a considerable asymmetry between superior and inferior areas, this can be a sign of pathology. Symmetry is an important differential diagnostic tool on many occasions. It is important to remember that the IPL, GCL and RNFL are in fact all part of the same large cells, whose Nuclei lie within the Ganglion Cell Layer. Damage to the cell body tends to occur first and thus the GCC starts to reduce in thickness at the Macula first. Often, the axons of the Ganglion Cells (the RNFL) remain intact within the RNFL at the disc for some time after the cell body has started to die/shrink within the GCL. Hence, the RNFL at the disc can take longer to show loss of tissue than found within the GCC at the Macula.
  9. Imagine a Bell curve coming out of the page / screen based on the colour scale above. The top of the bell is the centre of the Green on the Normative Database Scale. It is important to note that even if the map is all red, it could still be normal for that patient. However, it is less likely that it is normal where the map is all red. Of course, there may be cases where despite being all green, the patient is still abnormal as well.
  10. As well as comparing Retinal thickness and GCC with a normative database, OCT’s also compare RNFL thickness with normative data. There are several ways in which this can be assessed. On the right we have what is often referred to as a Disc Circle Scan. This is a 360 degree panoramic scan around a 3.4 mm circumference circle around the ONH (Optic Nerve Head). The OCT compares the RNFL thickness at all points around this circle to normative data and produces what is often called a TSNIT or ONH Profile map. The black line represents the patients RNFL ONH profile and this is overlaid over normative profiles. The same normal distribution and standard deviations apply and once again, there is no known condition where there is too much RNFL, so we only have colours for thinning of RNFL and white for anything thicker. We can also measure average RNFL thickness across the whole Optic Disc compared to normative data or to the Superior and Inferior Bundles, the ISNT rule (TSNIT) or even Clock hour for more refined analysis (for notching for example). OCT’s will always measure the CD ratio’s higher than clinicians do. This is because the OCT can see where Bruch’s Membrane ends and we cannot. We see the cup the same size as the OCT generally, but because we see the disc as being larger, we get a smaller CD ratio.
  11. Although there are also sources of error for Macula scans, these are fewer in number and severity. This means that repeatability of disc scans is lower than that of macula scans and as such, if you can measure RNFL via the GCC at the macula, you are more likely to get an accurate result that can be repeatably and reliably measured time and again.
  12. Such analysis is also useful for assessing if there is any progressive loss or increase in overall Retinal thickness at the posterior pole. This may help in assessing the rate of progress of Ischaemic Retinopathies, Macula Oedema or the effect of Lucentis treatment for example. Most software for OCT’s allows complex analysis over time of tissue thickness change. Most software carries out statistical analysis over time to measure if change is due to pathology, age or isn’t significant at all (i.e. within the normal repeatability limits of the device).
  13. Glaucoma Progression Macula. Notice the progressive loss of Ganglion Cell Layer / GCC in this patients Right Eye. The graph produced by the OCT helps us determine if change is occurring and there is obvious loss of tissue. Notice the very evident Inferior / Superior difference. This progression may help us to decide upon a correct course of referral if this were only over a short period. In this particular case, this is from a Px already under Treatment and the progression will help the Ophthalmologist direct a more aggressive treatment protocol to try and prevent further tissue loss.
  14. Glaucoma Progression Disc. This is the same eye! Notice there is less dramatic loss of RNFL tissue initially, but latterly the same Superior / Inferior difference can be seen. This is because recent studies have shown that loss of the Ganglion Cell Complex (ILM, RNFL, GCL, IPL and INL) can pre-date ONH RNFL loss and can be an excellent pre-clinical sign of Glaucomatous change and can help us to avoid field loss by starting Glaucoma treatment prior to this taking place. GCL / RNFL loss can help identify Glaucoma up to eight years before clinical signs such as field loss manifest. A Px can lose 50% of the GCC Superiorly and Inferiorly and 40% of the Papillo-Macula Bundle before this might manifest as a field loss! Diagnosing Glaucoma via field screening means we are often rescuing what is left of the Optic Nerve when we start treatment, where as with OCT, we can help to prevent or slow the field loss from occurring.
  15. Notice the Asymmetry WITHIN the eye, showing loss inferiorly only. With Glaucoma, we can see that only the GCC is affected initially. The overall Retinal thickness, even in later stages of GCC loss is relatively unchanged in thickness as outer layers are unaffected. Thus, if a patient has considerable loss of total Retinal thickness, the pathology may be less likely to be linked to Glaucoma or Optic Neuropathy. However, note that two conditions may co exist in some cases and there may be loss of total Retinal thickness as well as independent loss of GCC thickness in the same eye.
  16. Currently, many practitioners still rely on subjective examinations of structure versus function. The inherent problems with subjective assessments and testing mean that these are not the most effective ways of diagnosing glaucoma. For instance, even with FDT (M theory / selective damage and reduced redundancy), a large amount of RGC / RNFL loss will have occurred before any clinically significant visual field loss will have manifested. Evaluation of disc photographs, even with red free and other manipulation is likely to only find active and established glaucomatous damage.
  17. As previously mentioned, OCT offers a more objective and reliable early detection of glaucoma through tissue measurement and progression analysis for example. Add to this the even earlier detection sensitivity and specificity of ERG and VEP and practitioners should be able to correctly identify glaucoma suspects long before any subjective signs or patient symptoms arise (whether his be HTG – high tension glaucoma, NTG – normal tension glaucoma or LTG – low tension glaucoma). Also, if a subject has IOH – intra ocular hypertension, such devices should allow differential diagnosis from HTG and may assist the clinician’s decision making on control of IOH.
  18. Pattern ERG assesses RGC function / dysfunction. This is excellent for detection of glaucoma and maculopathies. Flash ERG is more suited to detection of AMD, DR, Diabetic macula oedema, CRVO and CRAO. Flash ERG can be done with fixed luminance flicker and multi luminance flicker.
  19. VEP helps to diagnose optic nerve and visual pathway pathologies as opposed to retinal. Again, glaucoma can be diagnosed this way.