This document discusses the diagnosis of pre-perimetric glaucoma. It begins by defining pre-perimetric glaucoma as optic nerve abnormalities seen on structural tests with normal visual fields. It then discusses the need for early diagnosis before functional changes occur. Various functional tests are described like standard automated perimetry, short wavelength automated perimetry, frequency doubling technology, and others. Structural tests like confocal scanning laser ophthalmoscopy, optical coherence tomography, and their principles are summarized.

1. DIAGNOSIS OF PRE-
PERIMETRIC GLAUCOMA
PRESENTOR - DR. SADHWINI M H
MODERATOR – DR. ANITHA S MAIYA

2. DEFINITION
• POAG - a chronic, progressive, anterior optic neuropathy that
is accompanied by a characteristic cupping and atrophy of the
optic disc, visual field loss, open angles, and no obvious
causative ocular or systemic conditions
• Pre-perimetric glaucoma is characterized by optic nerve
abnormalities with normal visual fields.
• Moderate glaucoma - visual field abnormalities in one
hemifield, not within 5 degrees of fixation.
• Severe glaucoma - involves visual field abnormalities in both
hemifields or loss within 5 degrees of fixation

4. NEED FOR EARLY DIAGNOSIS
Studies have proved that structural changes in glaucoma (ONH ,
RNFL) preceed functional changes
This has a great potential value in delaying and avoiding
progression of the disease

5. • Glaucoma diagnosis and monitoring require both :
Functional Structural
analysis analysis
- Standard Automated - Ophthalmoscopy
Perimetry (SAP) - Photography
* SWAP * CSLO
* FDT *SLP
* High pass resolution *OCT
perimetry
* Motion detection
perimetry

6. FUNCTIONAL TESTS
• The gold standard of modern functional assessment of
glaucoma is
Standard automated white-on-white perimetry
Disadvantage :
Does not show an abnormality until between 25-50% of ganglion
cells have been lost

7. BASIS OF NEWER TESTS
• Target a subset of ganglions that are fewer in number with
specific function that are disturbed earlier and have less
redundancy. eg : SWAP , FDT
• Tests having less noise ( more reliable 1st test with less variability
between tests ) eg : FDT , HRP
• Modern computer algorithms to reduce noise eg : SITA
• Modern algorithms to better interpret from standard test what is
real and what is noise eg : Neural network interpretation ,
Glaucoma Progression Analysis.

9. COLOR VISION
• CV impaired in glaucoma
• Aquired ON disorders affect Blue-Yellow & Red-Green
targeted to detect also affected
glaucomatous damage by inherited defects
• Ishihara chart – not effective for blue-yellow spectrum
• Anomaloscope
• Hardy-Ritter-Rand color plates
• Farnsworth D-100
• Farnsworth D-15
• Insensitive, non specific, time consuming, difficult to interpret

10. SHORT WAVELENGTH AUTOMATED PERIMETRY
• Principle : It tests blue cone mechanism (short wavelength) and
the small bistratified ganglion (konio) cells that carry this
information.
• Stimulus – blue-violet (440 nm), Goldmann size 5
• Background – bright yellow (500nm)
• Brightness is gradually increased in randomly spaced trials
until stimulus is seen appoximately 50% of the time.
• Threshold determination is same as in full threshold SAP

11. • SITA has been adapted to SWAP – less time, less fatigue, less
threshold variability
• STATPAC is available – probability of abnormality at each tested
point.
• Output of SWAP is similar to that of SAP
• GHT – most useful parameter to detect early damage – Sn & Sp

12. REVIEW OF SWAP
ADVANTAGES
• Early detection
• Tracks progression
• Most perimeters can be modified
to perform it
• Familiar format on result
• SITA makes it more user friendly
• Abnormalities mapped well
compared to that found
structurally
• Can be correlated with
abnormalities of laser scanning of
ON & NFL with thin corneas
DISADVANTAGES
• Learning curve
• Takes 20-30 mins/eye
• Lot of noise
• Defects are steeper and larger
than SAP,FDT
• Greater long term fluctuation
than SAP
• Affected by lens opacities and
refractive errors.
• Not suitable for moderate
/severe defect

13. SWAP is considered abnormal if :
On atleast 2 examinations,
PSD is abnormal at worse than 1% level
GHT is outside normal limits
One hemifield cluster with sensitivity <1% level
2 hemifield clusters <5% level
4-5 abnormal points (0.05%) on pattern deviation plot

15. FREQUENCY DOUBLING PERIMETRY/TECHNOLOGY
• Principle :It targets the function of M ganglion cells that carry
information such as flicker and motion. Easy to detect as they
have little redundancy.
• Stimulus – low-frequency sinusoidal grating(0.25
cycles/degree) that undergoes rapid reversal of light bars to
dark bars at 50 times/second (25 hz)
• Gratings are projected onto different parts of visual field and
at each location , projected at different levels of contrast
between light and dark bars
• Lower contrast at which grating is seen as grating – better Sn.

16. • Rapid
reversal
optical illusion
no. of light &
dark bars are
twice than
actual
Hence the
name double
frequency

17. • FDT 1 tested 17 sectors of central 30º (C-30)
• FDT 2 projects smaller gratings in 64 sectors similar to the 24-
2 or 30-2 of SAP.This is the Humphrey matrix.
• Has 2 general algorithms similar to SAP , screening mode
(suprathreshold test - fast) and full threshold mode (10
mins/eye)
• ZEST is a new algorithm, uses Bayesian logic. It can cut testing
time in half without affecting accuracy. Practical & useful

18. • Accurately
predicts
location of
future SAP
defects
• Defects on FDT
can correlate
with structural
abnormality
found on HRT,
OCT, GDX
• Combination of
SWAP & FDT –
better

19. REVIEW OF FDT
ADVANTAGES
• Small size – portable –
community screening
• Relatively insensitive to refractive
error upto 6D
• Faster than SAP
• Early diagnosis
• Sn-85%, Sp-90% for earl
glaucoma
• Shorter learning curve than SAP
• Can be used in children >5y
• Reading disabilities have no effect
on result.
DISADVANTAGES
• Affected by media opacity
• False positives possible
especially with first field
• Screening tests do not pick
up all glaucomatous defects
• Ability to detect
progression is not yet
proven

20. HIGH PASS RESOLUTION PERIMETRY
• Described by Frisen in 1987
• Principle – measurement of resolution over the extent of the
visual field which is a function of P ganglion cells.
• Stimuli – ring with bright core and dark border of different
sizes shown in 50 locations within central 30º, while fixating
on a central target.
• Smaller the ring perceived – higher is the resolution at that
part of retina
• Contrast can also be varied

21. • Advantages – early
diagnosis , suitable
for monitoring
progression , more
sensitive to IOP
induced damage ,
more repeatable and
less time consuming
than SAP
• Affected by media
opacities
• Useful in OHT
• Sn & Sp for early
glaucoma – 85%
• Correlates with
defects on SAP, OCT,
HRT

22. MOTION DETECTION PERIMETRY
• Principle – it tests motion detection which is a function of M
ganglion cells
• Measures ability to detect a coherent shift in a position of dots
in a circular area against a background of non-moving dots.
• Advantage – picks up a small subset of abnormal ocular
hypertensive eyes
• Disavantage – with current testing abilities , it is less reliable
than SWAP or FDT.

23. A magnified view of the target shows 50% of the dots are moving in random
directions and 50% are moving coherently. X – fixation target

24. ELECTROPHYSIOLOGICAL TESTS
• To eliminate the errors of psychophysical tests
• MULTIFOCAL ERG – electrodes on cornea held by soft contact
lens
• MULTIFOCALVEP – electrodes on scalp in and around occipital
lobe region
• Glaucomatous damage – decreased amplitude of signal.
• Abnormalities coincide with that of SAP, structural analysis
• To assess visual function in glaucoma & to detect eye with high
risk of progression

25. STRUCTURAL TESTS
• Gold standard of structural analysis of glaucoma :
Ophthalmoscopy
Slit lamp biomicroscopy
Stereo photos of optic nerve head.
Disadvantages :
• Dependent on the skill and expertise of the observer
• High intra-observer and inter-observer variability

26. CONFOCAL SCANNING LASER OPHTHALMOSCOPY
(HRT)
• CSLO is an imaging technology.
• Heidelberg RetinaTomography is
the major commercially
available instrument that uses
this technology.
• 3 generations – HRT, HRT 2
HRT 3
• Gives 3D images – high resolution
• Principle – spot illumination & spot
detection

27. • Stimulus - 670 micron Diode laser
• Conjugate pinholes placed in front of light source & light detector – allows
only light originating from a determined focal plane
• Sequential sections are obtained by moving the depth of the focal plane
through the whole depth of the tissue being studied.
• Oscillating mirrors redirect the laser beam to x and y axis , along a plane of
focus that is perpendicular to the optic axis (z).Thus a bi-dimensional
image is obtained at each focal plane

28. • As device changes focal plane , other bi-
dimensional optical sections of the optic
nerve are obtained
• Total of 64 sections , equivalent to a depth
of 4 mm
• Each optical section is composed of 384 x
384 points. Each one of these points has an
x, y & z value to locate it in space.
• The amount of light or ‘reflectance’ along
the z-axis is measured at each scanned
point, and the more intense the light is at a
given point, the higher (closer to the
surface) this is.The peak intensity along
the z-axis is assumed to correspond to the
ILM

29. • Once image is taken , operator
delineates the optic nerve contour
line over the reflectance or
topography image.
• Reference plane – 50 microns
posterior to the mean height along
a 6o arc of contour line at temporal
inferior sector.
• HRT3 provides ONH stereometric
analysis without manual
delineation of disc.
• Stereometric parameters are calculated by the machine and analysed by AI
classifier – RelevanceVector Machine (RVM).Then a Glaucoma Probability
Score is created.
• HRT3 has a larger, diverse normative database.

30. COMPONENTS OF HRT REPORT
A. PATIENT DATA
B.TOPOGRAPHY IMAGE C.REFELCTION IMAGE
D.MEAN HEIGHT
CONTOUR GRAPH
E.HORIZONTAL
HEIGHT PROFILE
F.VERICAL
HEIGHT PROFILE
G.STEREOMETRIC
ANALYSIS
H.MOORFIELDS
REGRESSION
ANALYSIS

31. PATIENT DATA
• Provides information on exam type (initial
report/baseline/follow-up), patient demographic information
(patient name , age, gender, ethnicity, etc.), and basic image
information including image focus position, and whether
astigmatic lenses were used during acquisition.

32. TOPOGRAPHY IMAGE
• On left upper corner
• A false color image
• Color coded map
• Superficial areas – darker
• Deep areas – lighter
• Red – cup
• Blue, green – NRR
• Blue – sloping rim Green – non sloping
rim

33. REFLECTANCE IMAGE
• On right upper corner in u/l report,
below topography image in OU
report
• Brighter areas – higher reflectance
– cup
• Darker areas – less reflectance
• Valuable in locating and drawing
the contour line around the disc
margin
• Reflectance image is overalid with
MRA andclassified as ;

34. HORIZONTAL & VERTICAL
HEIGHT PROFILE
• Height profile along the white
line in the topography image.
• The subjacent reference line
(red) indicates the location of
the reference plane
(separation between cup and
NRR).
• The two black lines
perpendicular to the height
profile denote the borders of
the disc as defined by contour
line.
• A smooth trace – better
quality trace.

35. MEAN CONTOUR HEIGHT GRAPH
• Graphical representation of retinal height along the contour
line & of RNFL thickness
• Green line – retinal height. Red line – reference place
• Green contour line should never go below red reference plane .
If it does, then contour line is likely not in proper position
• T-TS-NS-N-NI-TI-T
• Normal contour – DOUBLE HUMP - humps correspond to the
superior and inferior NFL, which are normally thicker

36. STEREOMETRIC ANALYSIS
• HRT2 – 14 parameters
• HRT3 – 6 parameters only
• Each value is designated as;
• If the SD is greater than 40
μm, the test should be
repeated to improve
reproducibility or the results
should be interpreted with
caution.

37. MOORFIELDS REGRESSION
ANALYSIS (MRA)
• Based on normative database of 112
caucasian subjects with refractive error
<6D & disc size 1.2-2.8sq.mm
• A predicted rim area line/disc area line was
obtained after plotting the ratio values

38. • Also shown on reflectance image
• Classification is written at the bottom of the graph –
classifies disc based on the worst classified sector
• Sn – 84.3%, Sp – 96.3%

39. GLAUCOMA PROBABILITY SCORE
• New software included in HRT3
• Based on construction of a 3D model
of ONH & RNFL by using 5
parameters – cup size & depth, rim
steepness, horizontal & vertical
RNFL
• Employs artificial intelligence:
RelevanceVector Machine and
derives probability of glaucoma of
scanned eye
Probability ≤ 28% -WNL
Probability ≥ 28% - BL
Probability ≥ 64 % - ONL

40. HRT can
differentiate
between normal &
early glaucomatous
eyes with a
sensitivity of 79%
to 87% & specificity
of 84 to 90%

41. TOPOGRAPHIC CHANGE ANALYSIS
• Statistical method to compare topographic values of
superpixels over time.
• Calculates P values of difference in height between 2 points to
be caused by chance.
• P>0.005 – high probability of change caused by chance
• P<0.005 – change did not occur by chance
• Automatically done after 3 scans – 1 baseline, 2 F/U
• Uses raw topographic values – independent of contour
delineation
• Display occurs as a probability map with reflectivty maps
overlaid with color coded superpixels that had significant P
values of change
• Red – depression. Green - elevation

42. TREND
ANALYSIS

43. QUALITY INDICATORS
• Even luminance.
• Sharp borders of topography and reflectance images
• Good centration of the disc
• Manufacturers’ classification by standard deviation-
 < 10 – Excellent
 11 – 20 –Very good
 21 – 30 – Good
 31 – 40 – Acceptable
 41 – 50 – Poor
 > 50 –Very poor.

44. REVIEW OF HRT
STRENGTH
• No pupil dilatation
• Rapid 3-D data of ONH
• Software available for
longitudinal change analysis
LIMITATIONS
• Operator draws contour line
(except in HRT 3)
• Reference plane affects data
outcome
• Blood vessels often included in
rim area
• Less useful for analysis of
macula or RNFL

45. OPTICAL COHERENCE TOMOGRAPHY
(OCT)
• It is an imaging technology that
measures intensity and echo-time delay
of back scattered and back reflected
light from scanned tissues
• Developed in 1991
• High resolution cross-sectioanal
imaging of ONH, RNFL, Macula
• Generations – OCT 1, 2, 3 (Stratus),
Spectral
• Light source - 820 or 850nm Diode laser
Principle – low coherence interferometry & the ability to
differentiate retina layers depending on different time delay of
their reflections

46. • High reflectivity tissues (white and red colours) – NFL , RPE
and Choriocapillaris
• Low reflectivity tissues (blue and black colours)-
Photoreceptor layer , choroid , pockets of fluid
• Advantage : can scan RNFL , ONH and Macula
• Resolution – 8 -10 microns

47. PERIPAPILLARY RNFL SCAN
• 3.4mm circular scan aroundONH
• RNFL curve starts with temporal quadrant & continues
clockwise in RE, counterclockwise in LE
• Thickness values are provided for 4 quadrants & each clock
hours
• Classification based on normative database is colour coded
• green –WNL
• yellow – Borderline
• red – ONL
• Average RNFL is also established

49. MACULAR SCAN
• 6 linear scans in a spoke pattern, spaced 300– each linear scan
of length 3/6mm
• Fast Macular scan uses 128/256/528 A scans for each radial
linear scan divided to 9 sectors

50. GCC=GCIPL+RNFL

51. ONH SCAN
• Six linear scans (length = 4mm) in a ‘spoke’ fashion is
obtained
• Automatically defines ONH margins at the end of RPE layer
(blue cross). Straight line is drawn joining the blue crosses
• Reference plane – parallel line drawn 150 microns anterior to
the previous line
• Tissues above reference plane – rim ( red )
• Tissues below – cup (contour – green and edge – yellow )
• One radial scan is yellow denoting the axis of cross-sectional
image in the prinout

52. • A – type of report
• B – patient & scan information
• C – singleOCT image
• D – single scan analysis
parameters
• E – signal strength
• F – overall analysis parameters
• G – plot of radial scans with
selected scan indicated by
yellow lines
• H – fundus image showing
placement
• I – times at which radial scan
was last modified
• J – physician interpretation

53. QUALITY INDICATORS
• Proper centration
• Signal strength value ≥ 6 – good quality scan
• Homogeneity of RNFL scan.
• OCT algorithm which measures RNFL between 2 white lines
should not fail to follow limit of RNFL (otherwise ‘dropout’ is
seen)

54. REVIEW OF OCT
ADVANTAGES
• Highest axial resolution
• c/s image can be compared
with histology slides
• Rapid data on RNFL , ONH and
macula
• ONH margin determined by
device.
• No need for pupil dilation
• Detects different pathologies
• Easy to operate, safe
DISADVANTAGES
• Limited normatve database
• Data are originate dfrom
only 1 set of scans
• Limited programs for
longitudinal evaluation
glaucomatous progression

56. SCANNING LASER POLARIMETRY
(GDX)
• Scanning laser polarimetry is an imaging
technology to measure peripapillary
RNFL thickness
• GDX is a device that uses this technology
• Latest generation- GDXVCC (variable
corneal compensator)
• Principle – Birefringence
• Phenomenon of double refraction where
a ray of light when incident on a
birefringent material is split by
polarization into 2 ways taking slight
different paths

57. • In the retina, the parallel
arrangement of the
microtubules in retinal ganglion
cell axons causes a change in
the polarization of light passing
through them.
• The change in the polarization
of light is called retardation
• The retardation value is
proportionate to the thickness
of the RNFL

58. • Technique :
• 780 nm Diode laser
• The scan is obtained by the use of an ellipse centered over the
ONH as seen in reflectance map.
• Data is displayed as colour coded grids representing different
levels of retardation and therefore RNFL thickness.

59. • VCC stands for variable corneal
compensator, which was created
to account for the variable corneal
birefringence in patients
• Uses the birefringence of Henle’s
layer in the macula as a control
for measurement of corneal
birefringence

60. GDX PRINT OUT

61. • PATIENT DATA : Patient data and quality score: the patient’s
name, date of birth, gender and ethnicity are reported. An
ideal quality score is from 7 to 10
• FUNDUS IMAGE :The fundus image is useful to check for
image quality. GDXVCC uses 16000 data points to construct
this image. Reflectance image of posterior pole 200x 200

62. • The Calculation Circle IsThe
Area Found BetweenTheTwo
Concentric Circles, Which
MeasureThe (TSNIT) And
Nerve Fiber Indicator (NFI)
Parameters
• By ResizingThe Calculation
Circle And Ellipse,The
Operator Is AbleTo Measure
BeyondA Large Peripapillary
Atrophy Area

63. RNFL THICKNESS MAP
• A color-coded format from blue to red.
• Hot colors like red and yellow mean
high retardation or thicker RNFL
• Cool colors like blue and green mean
low retardation / thinner RNFL
• A healthy eye has yellow and red colors
in the superior and inferior regions
representing thick RNFL regions and
blue and green areas nasally and
temporally representing thinner RNFL
areas.
• In glaucoma, RNFL loss will result in a
more uniform blue appearance

64. TSNIT MAP
• TSNIT displays the RNFL thickness values along the
calculation circle.
• Normal eye - typical ‘double hump’ pattern
• healthy eye there is good symmetry between theTSNIT
graphs of the two eyes and the two curves will overlap
• in glaucoma, one eye often has more advanced RNFL loss and
therefore the two curves will have less overlap

65. DEVIATION MAP
• Reveals the location and magnitude of RNFL defects over the
entire thickness map
• Compared to the age-matched normative database
• Dark blue squares - RNFL thickness is below the 5th percentile
of the normative database
• Light blue squares - deviation below the 2% level
• Yellow - deviation below 1%
• Red - deviation below 0.05%.

67. TSNIT PARAMETERS
• Also color coded based on P
values

68. NERVE FIBRE INDICATOR (NFI)
• An indicator of likehood that an eye has galucoma.
• Calculated using an advanced form of neural network, called a
SupportVector Machine (SVM)
• Output values range from 1 –100
• 1-30 -> low likelihood of glaucoma
• 31-50 -> glaucoma suspect
• 51+ -> high likelihood of glaucoma

69. SERIAL ANALYSIS
• Serial Analysis can
compare up to four
exams
• The Deviation from
Reference Map displays
the RNFL difference,
pixel by pixel, of the
followup exam
compared to the
baseline exam

70. QUALITY ASSESSMENT
• Appropriate focusing and illumination of retina.
• Ellipse must be centered over ONH
• No atypical scans in retardation maps ( normal vertical bow-tie
appearance, due to thicker RNFL superiorly and inferiorly, is
absent)
• Quality score :
7-10 – ideal score
Device provides an ‘ok’
if alignment, fixation
and refraction are right

71. REVIEW OF GDX
STRENGTH
• No pupil dilatation
• Rapid data on RNFL
• Large normative database
LIMITATIONS
• Only RNFL information
• Corneal surgery will induce
error (if noVCC)
• Macular pathology impedes
GDX
• NFI – proprietary value

72. CONCLUSION
• Proven advantages in early diagnosis and monitoring of
glaucoma
• Limitations :
 Disability to capture all nuances of appearance as in stereo-
photographs
 Cannot discriminate glaucoma in difficult optic discs ( high
myopia , tilted optic disc)
Hence , these modalities cannot replace the gold standards of
functional and structural tests but can definitely compliment
them in clinician’s decision making process.

73. REFERENCES
• Becker – Shaffer’s Diagnosis andTherapy of the Glaucomas –
5th edition
• Yanoff and DukerTextbook of Ophthalmology – 5th edition
• Practical Perimetry – Bhartiya, Ariga, Puthuran, George
• Glaucoma Imaging - Antonio Ferreras
• The Glaucoma Book – Paul N Schacknow, John R Samples