1. Preperimetric glaucoma is characterized by optic nerve abnormalities detected through imaging and testing, even though standard visual field tests are still normal. 2. Electrophysiological tests like pattern electroretinography (PERG) and multifocal visual-evoked potentials (mfVEP) can detect early ganglion cell damage before visual field loss occurs. 3. Imaging technologies like confocal scanning laser ophthalmoscopy (CSLO), optical coherence tomography (OCT), and scanning laser polarimetry provide structural evaluation of the optic nerve head and retina to diagnose and monitor glaucoma progression.

1. PREPERIMETRIC GLAUCOMA
DR. PRAKRITI YAGNAM .K
Moderator : DR.CH.MOHAN RAO

2. • Introduction :
• Glaucoma diagnosis and management requires assessment of both structure and
function of optic N. and ganglion cell layer
• Preperimetric glaucoma is characterized by optic nerve abnormalities with normal
visual fields
• Early diagnosis has greater potential in delaying and avoiding progression of the
disease

4. Analysis of glaucoma :
Structural. Functional
Ophthalmoscopy SAP , SWAP , FDT
Photography. HPRP , MDP
CSLO. Electrophysiological tests
OCT
SLP

5. Electrophysiology :
• All psychophysical tests are subjective and performance is
depends on physical and emotional status of the patient
• Like fatigue , emotional upset , anxiety , physical discomfort ,
extraneous noise and movement
• Therefore objective tests have been developed
1. Pattern ERG
2. Multifocal ERG
3. Multifocal VEP

6. ERG :
• Uses electrode on cornea held in place with soft contact lens
• Picks electric signals by retinal cells following stimulation of light
• As electric signal is faint , mass response is recorded ( of whole retina )
• Addition of computer to this technique allowed rapid stimulation , randomization of location of
stimuli and averaging of responses from many stimuli
• So amplitude of faint signal from one point of retina can be amplified

7. Pattern ERG :
• Similar to standard bright flash ERG – recordings are made from entire retina
• Stimulus – Reverse checkboard pattern
• Signal comes largely from retinal ganglion cells which forms the negative part
• Some part comes from amacrine , bipolar and inner retinal cells which form the positive part

8. In glaucoma :
• Reduced amplitude is seen in ocular hypertensives and with suspicious optic nerves
• Probably detects early diffuse damage to ganglion cells rather than focal damage
• Amplitude is reduced in 87 % of confirmed open angle glaucoma patients and 57 % of ocular
hypertensive patients

10. Correlation :
• It correlated well with mfVEP findings , optic nerve cupping and visual field loss in most patients with
glaucoma
• Abnormal PERG correlated well with ocular hypertensives with risk factors for development of
glaucoma such as thin corneas , African heritage , positive family history
• It may be more sensitive than perimetry in detecting either deterioration or improvement and could
be used in the future as an objective way to monitor effect of treatment

11. Summary :
• Can be used as early warning system for glaucomatous damage and possibly to detect those
eyes at high risk for progression
• Superiority over any others remains to be demonstrated

12. Multifocal ERG :
• mfERG changes are ascribed to the ganglion cell layer and also from inner plexiform layer
• Experimental studies showed that
• Elevated IOP showed evidence on mfERG of ganglion cell dysfunction which was confirmed by
Histopathological correlation
• Clear difference between normal and glaucomatous monkeys were demonstrated with mfERG

14. Multifocal VEP :
• It is basically a EEG
• Reads faint electric signals from visual cortex using skin electrodes over back of the
head
• Like ERG can detect large scale problems in visual system from optic nerve to visual
cortex
• Improvements in stimuli and averaging of signals allowed stimulation of specific parts of
the retina and representation of those specific parts in the signals measured from visual
cortex

15. Experimental studies revealed that
• Pattern stimulation of different parts of visual field using multifocal pseudo randomly alternated
pattern stimuli scaled in size to match their respective representation in visual cortex
able to identify loss of signal in areas of scotomata as seen in SAP
• Correlation of mfVEP in ocular hypertensives monkeys with histopathological damage to ganglion
cells is found

16. • Linear relationship is found between degree of
defect on mfVEP and depth and breadth of
scotomata on SAP with both correlating with
estinmated number of ganglion cells lost
• Graham and co workers stimulated 60 sites within
central 25 degree of visual field and amplitude and
latency defects of mfVEP correspond with visual
field defects in eyes with glaucoma
• But recent studies revealed that latency defects are
less reliable

18. • Sensitivity of mfVEP for all glaucomas – 97.5%
early glaucomas - 95%
• Based on SAP specificity is 92 %
• Based on optic nerve analysis sensitivity mfVEP = SAP
specificity mfVEP > SAP

19. Summary :
• Test time – 20 minutes
• Electrode potential is critical in obtaining good results
• Children > 5 years can give reliable , repeatable results
• Media opacities may give false positive results
• Small pupils result in reduced amplitude
• Dilated pupils may increase latency and mask borderline abnormalities

20. Uses :
• As a functional test in patients who are unable to perform accurate threshold perimetry
• In very elderly or infirm patients
• In children
• Unable to concentrate people
• Developmentally disabled
• Assessment of suspected malignancy

21. Optic nerve imaging :
• Characteristic optic nerve appearance in glaucoma results from structural glaucomatous changes which
usually precede functional deterioration
• Structural evaluation of optic nerve head and retina are key to diagnosis and follow up of glaucoma
patients
• There are predominantly three imaging technologies which complement slit lamp bio microscopy and
stereo photos of ONH

22. They are :
• Confocal scanning laser ophthalmoscopy ( CSLO ). - HRT
• Optical coherence tomography ( OCT )
• Scanning laser polarimetry - GDX

23. • Scans that are studied are Optic Nerve Head ( ONH ) , Retinal Nerve Fibre Layer ( RNFL ) and macula
• ONH - HRT and OCT
• RNFL - OCT and GDX
• Macula - OCT

24. • All technologies work differently and have their strengths and limitations as well as
different measures of reliability
• Ultimate goal is to improve the early diagnosis of glaucoma and detection of glaucoma
progression

25. Confocal Scanning Laser Ophthalmoscopy :
• CSLO is the imaging technology and HRT ( Heidelberg Retinal Tomograph ) is the major
commercially available instrument that utilizes this imaging system to study the eye
• HRT has three generations - HRT 1 , 2 and 3

26. Principle :
• Spot illumination and spot detection
Technique :
• CSLO is capable of obtaining 30 images of optic disc by acquiring high resolution images along the
optic axis ( Z – axis ) and perpendicular to it ( X and Y axes )
• Conjugated pinholes are placed in front of the light source and light detector

28. • Light originating from the determined focal plane is allowed to reach the detector
• Sequential sections are obtained by moving the depth of the focal plane through the whole
depth of the tissue

29. Instrument :
• Light source - 670 microns diode laser
• Oscillating mirrors in the device redirect laser beam to X , Y
and Z axes
• Bidimensional image 15 * 15 degree is obtained at each
plane
• Each one represents an optical section of optic nerve
• Each optical section is composed of 384 * 384 points
• Each point has X ( horizontal ) , Y ( vertical ) , Z ( depth )
value to locate it in space

30. • Total 64 sections each done with 1/16 mm. depth
interval are obtained and used to create a 3D image of
the optic nerve
• Total 64 sections are equivalent to 4mm. Depth

31. • The more intense or reflectance the light is along Z axis at a given point the closer to the surface
this is
• Peak intensity corresponds to internal limiting membrane that overlies the retina and optic disc
• A matrix of retinal height measurements is then created to form a topographical map of 384 *
384 height measurements of retinal and optic nerve surface
• Average of three scans – mean topography map

32. • Once the image is taken operator delineates the optic nerve contour line over it
• Points at external edge of disc border are placed and machine draws best fit ellipse to delineate
the disc
• Now a reference plane is created at 50 microns posterior to the mean height along a six minute
arc of the contour line at temporal inferior sector
• Structure above the reference plane and within the contour line is considered to be rim
• Anything below the reference plane is cup

34. Analysis :
• It is done by
 Computation of stereometric parameters
 Classification of eye
 Comparison to previous examinations

35. • Classification of eye is done by Moorefield’s regression analysis or other discriminatory method in HRT 2
• Neural network analysis in HRT 3

36. In HRT 3
3D model of ONH is created
Five optic N. parameters are created
Analysed with relevance vector machine ( artificial intelligence classifier )
Glaucoma Probability Score ( GPS ) is created
• HRT 3 is equipped with larger and more diverse normative database than its predecessor

37. HRT report :
• They are three types - Initial , follow up and OU report
Components :
• Patient data
• Topography image
• Reflectance image
• Retinal surface height variation graph

38. 5. Vertical and horizontal interactive analysis
6. Stereometric analysis
7. Moorefields regression analysis
8. Glaucoma probability score

40. 1. Patient data :
• Name , age , sex , date of birth , patient ID , date of examination
2. Topography image :
• Located on left upper corner of printout
• It is a false color image
• More superficial areas are darker and deeper areas are lighter
• Red indicates cup , blue and green indicate rim - blue indicates sloping rim

42. 3. Reflectance image :
• Right upper corner of unilateral report or below topography image on a bilateral report
• Also a false image
• Brighter areas are high reflectance areas like cup
• Overlaid with Moorefield analysis and classified as WNL , borderline and ONL

43. 4. Retinal surface height variation graph :
• Graphical representation of retinal height along contour line and thickness of nerve fibre layer
• Red line - reference plane Green line - Retinal height
• From left to right graph represents thickness of T , T-S , N-S , N , N-I , T-I and T sectors
• As the thickness of normal retina is irregular contour line will appear as what is known as the double
hump
• The hills or humps correspond to superior and inferior NFL which are normally thicker than the rest of
the retina

45. 5. Vertical and horizontal interactive analysis :
• This is the Optic N. retinal surface height horizontal and vertical
cross sections
• Smooth trace represents better quality
• Ragged trace – poor quality
• Provides information of disc steepness , presence of sloping etc…

46. 6. Stereometric analysis :
• 14 parameters are used in HRT 2
 Disc , cup and rim area Maximum cup depth
 Cup and rim volume Cup shape measure
 Cup / disc ratio Height variation contour
 Linear cup / disc ratio Mean RNFL thickness
 Mean cup depth RNFL cross sectional area
 Reference height

47. • In HRT 3 six parameters are
used
 Cup / disc area ratio
 Cup shape measure
 Rim area
 Rim volume
 Height variation contour
 Mean RNFL thickness

48. • Each value is designated as
 Within Normal Limits
 Borderline
 Outside Normal Limits
After comparing to a normative database

49. 7. Moorefields regression analysis :
• It is based on normative database of 112 Caucasian subjects with refractive error < 6 D and disc size
within range of 1.2 – 2.8mm.
• Rim area below 99.9 % of prediction interval. - outside normal limit. - red
95 to 99.9 % - borderline. - yellow
>. 95 % - within normal limits. - green
• Both global assessment and all six sectors are studied

50. • Moorfield's classification is also shown over reflectance image as green checkmark , yellow
exclamation point or red cross
• The classification of optic nerve is written at bottom of the graph
• MRA classifies disc based on Worst classified sector

51. 8. Glaucoma probability score :
• A 3D mode of Optic nerve layer and peripapillary RNFL is created using five parameters
 Cup size
 Cup depth
 Rim steepness
 Horizontal and vertical RNFL

52. • They are compared to predetermined normal and glaucoma model using AIC and RVM
• Probability of glaucoma for scanned eye :
p < or = 28 %. - WNL
p > 28 % - Borderline
p. > or = 64 % - Outside normal limits

54. Evaluating scan quality :
Good quality indicators. - Even luminance
Sharp border of topography and reflectance image
Good centration of disc
• SD – Standard deviation – measurement of variability of same pixel values among three different
scans

55. Classification based on SD :
< 10 – poor
11 to 20 - very good
21 to 30. - good
31 to 40. - acceptable
41 to 50. - poor
> 50. - very poor
• But poor scan can have low SD if variability is small among three scans

56. Strengths :
• Rapid and simple to operate
• 3D representation of optic nerve done without pupillary dilatation
• Used in Ocular Hypertensive Treatment Study so large amount of
data is available
Limitations :
• Inter observer variability because reference plane is drawn by the
operator
• Measurements can be affected by blood vessels on the disc ( Nasal
border is difficult to identify because of crowding of blood vessels)

57. • Can overestimate rim area in smaller discs and vice versa
• Not appropriate for macula or RNFL study
• Occasionally severely damaged eyes may appear normal and vice versa
Patients perspective :
• Experience is similar to slit lamp examination
• More comfortable than fundus photo because luminance of diode laser is 100 times lower than that of
the digital fundus flash camera
• Time is less than 7 seconds and safe to eye

58. Conclusion :
• Best parameters which can be compared are cup shape measurement , rim area and cup volume
• MRA – sensitivity is 84.3 % and specificity is 96.3 %
• Axial resolution is 300 microns and transverse 10 microns

61. OCT :
• Imaging technology that performs high resolution , cross sectional imaging of ONH , RNFL and
macula
• Measures intensity and echo time delay of back scattered and back reflected light from the
scanned tissues
Principle :
• Low coherence and interferometry

64. Technique :
Light source - super luminiscent diode laser beam ( 820 or 850 nm. )
directed to a partially reflecting mirror
splits light into two beams
mirror placed at a distance directed towards the eye
back reflected light
coherent light - compared

66. • The back reflected light from eye consists of multiple echoes with information about distance and
thickness of intraocular tissues
• Reference mirror is moved and other intraocular structures are measured
• 20 maps are created based on interference signal
• Map is color coded
white and red - areas with high reflectivity
blue and black - lower reflectivity

67. • High reflectivity layers. - NFL , RPE and choriocapillaris
• Low reflectivity layers - Photoreceptor layer , choroid and fluid pockets
Features :
• It has three generations – 1 , 2 and 3 or stratus OCT and OCT spectral
• Has the best axial resolution of the three imaging modalities
• OCT 3 has a resolution of 8 – 10. microns and the latest ultra high resolution has about 3 – 4
microns axial resolution
• Newer technologies include spectral domain and fourier domain they shoe higher resolution

68. Different scanning modalities :
 Peripapillary scan - for RNFL
 Macular scan
 ONH scan

70. Peripapillary scan :
• 3.4mm. Circular scan to measure thickness of RNFL is done
• Curve is obtained by opening up the scan
• Starts with temporal quadrant and continues clockwise in right eye and counter clockwise in left eye
• Values are provided for four quadrants and for 12 clock hours
• Classified as WNL – green , Borderline - yellow and outside normal limits. - red
• Average RNFL thickness is also established

72. In the report :
• It includes RNFL thickness curves for both eyes
• It is drawn as a black line on a graph featuring thickness in microns of different areas ( T , S ,N and I )
• Normal RNFL curve has double hump appearance
• Color coding done
• Divided into 12 clock hours and four quadrants

74. • False color cross sectional image is shown for both eyes with signal strength specified for each image
• Average thickness is calculated and appears at the the bottom of the thickness measurement table
• The thickness values are also color coded

75. Macular scan :
• Six linear scans in a spoke like pattern done spaced 30 degree apart
• Length of the linear scans are 3 mm. or 6mm. Longer ones are used commonly
• Fast macular scan utilizes 128 A scans for each radial linear scans. Can choose 256 or even 512 A scans
• Color coding : Blue - thinner retina
Yellow , green , red - thicker

77. • Macular thickness map and map with quantitative measurements in nine sectors is derived from
macular scan
• Map depicted is a cross sectional one along one of the radial scans

78. In the report :
• Thickness map provides cross sectional image of the retina along with signal strengths with
background shaded areas representing normative database
• Retinal thickness measurement is also provided
• Map analysis includes two maps , one with qualitative and one with quantitative thickness
measurements
• Measurements for nine macular scans are shown as well as thickness measurements for centre of
the scan and total macular volume

80. ONH scan :
• Star or spoke pattern is used
• Length of linear scan – 4mm.
• OCT automatically defines ONH margin as endings of RPE with blue cross
• Straight line is drawn connecting the crosses and parallel line is drawn 150 microns anterior to this
line
• Analogous to the reference plane in HRT
• Anything above the line is rim and below is cup

81. In the report :
• Area of rim is red
• Contour is traced in green
• Edge is traced in yellow
• Information of all six radial scans is used for the contour of ONH
• One of the radial scan is yellow and it represents the axis of cross sectional image in the printout

83. Fast scans :
• Available with OCT – 3
• Time efficient , obtained in 1.92 seconds
• Reduction of error caused by patients movement or loss of fixation done thus accuracy is
improved
• RNFL and ONH parameters are proved to be superior than macular parameter in discriminating
normal from glaucoma patients

84. Quality assessment :
1. Peripapillary circular scan centration
• Decentration of scan can account for inaccurate measurements of RNFL. thickness
• If circle is displaced inferiorly superior sector will be thicker and inferior sector thinner
• RNFL closer to the disc will be thicker

85. 2. Signal strength value :
> / = 6 - good quality
<5. - poor quality
3. Homogenecity of RNFL scan - loss of reflectivity in the scan is less than ideal and can affect
the overall quality
4. OCT algorithm : white line used to delineate RNFL fails to follow limits and dropout can
be seen in cross sectional image

86. Strengths :
• Most versatile ancillary image technique used in ophthalmology
• Best axial resolution of all imaging devices that they can be compared to histopathological slides
• Only technology capable of comparing ONH , macula and RNFL
• Detects early glaucomatous changes as well
• Easy to operate , safe and can obtain image without pupillary dilatation

87. Limitations :
• Normative database and its limited sampling density reduces its tranverse resolution
spectral OCT provides higher resolution
• OCT data are originated from one set of scans and not a series of set of scans as in HRT
• Current OCT devices have not yet developed robust progression for longitudinal evaluation of
glaucomatous progression as in HRT

88. Patient perspective :
• Similar to slit lamp examination
• Will see different light patterns - glowing red scan pattern
red landmark spot
green fixation target
• If patient has cataract green light may appear as white or yellow
• If eye is blind then using of external fixation wand for the fellow eye is done

89. Scanning laser polarimetry :
• Device used commonly is GDX
Principle :
• Birefringence
• Utilised to measure peripapillary RNFL thickness
• The main birefringent intraocular tissues are cornea , lens and retina
• The change in the polarization of light is called retardation which can be quantified

90. • In the retina parallel arrangement of microtubules in ganglion cells cause a change in the polarization of
light passing through them
• This retardation value is proportional to the RNFL thickness
GDX :
• The latest generation is the GDX variable corneal compensator
• Uses a diode laser ( 780 nm. ) to obtain measurements along a 15 * 15 area of retina

91. • Birefringence around fovea arises from the Henles layer in macula and is known to be uniform
• No compensation for anterior segment gives rise to non uniform pattern at fovea due to birefringence
of cornea and hourglass pattern indicates axis and magnitude of uncorrected corneal birefringence
• This is corrected by VCC – Variable Corneal Compensator
• Now recently ECC – Enhanced Corneal Compensator is being developed

92. Components of GDX report :
1. Patient data and quality score 8. TSNIT parameters
2. Fundus image 9. NFI
3. RNFL thickness map
4. TSNIT graph
5. TSNIT symmetry graph
6. TSNIT comparison and serial analysis graphs
7. Deviation from normal map

94. 1. Patients data and quality score :
• Patients name , date of birth , gender , ethnicity are reported at the top of the page
• Ideal quality score is from 7 to 10
2. Fundus image :
• Reflectance image of posterior pole
• Measures the T – S – N – I – T and Nerve Fibre Indicators ( NFI ) parameters

96. 3. RNFL Thickness map :
• Red and yellow - high retardation or thicker RNFL
• Blue and green. - low retardation or thinner RNFL
• Typical scan pattern - vertical bow tie. - thicker RNFL superiorly and inferiorly
4. TSNIT graph :
• Patients RNFL thickness as a black line drawn over a shaded area of normality based on normative
database of over 500 eyes

98. 5. TSNIT symmetry graph :
Overlays the individual TSNIT graphs for right and left eye
6. TSNIT comparison and serial analysis graph :
Compares two or more scans of same eyes obtained on different visits
7. Deviation from normal map :
Comparison between patient’s RNFL thickness and normative database

99. • Dark blue squares - Below 5 th percentile
• Light blue – deviation below 2%
• Yellow - below 1%
• Red – below 0.05%

101. 8. TSNIT parameters :
 TSNIT average ( average thickness values on calculation circle )
 Superior average ( average of pixels in superior 120 degree of calculation circle )
 Inferior average ( along inferior 120 degree )
 TSNIT standard deviation
 Inter eye symmetry

103. 9. NFI :
• Indicator of likelihood that the eye has glaucoma
• Higher the NFI , more likely the patient has glaucoma
< 30 - low likelihood of glaucoma
30 to 50 - glaucoma suspect
> 50. - high likelihood of glaucoma

105. Quality assessment :
• Focusing and illumination must be appropriate
• ONH must be inside a black square while obtaining a scan
• Motion artifacts decrease the quality of the scan
• Ellipse must be centred on ONH
• Quality score must be between 7 – 10
• Also device provides “ OK ” for alignment , fixation and refraction

106. • Presence of atypical scans in retardation map causes
 Over all thickness is increased
 Thickness axis is tilted
 Thickness is along radial lines through periphery of the scan

107. Strengths :
• Rapid and simple imaging of peripapillary RNFL
• No pupillary dilatation is required
Limitations :
• Provides only RNFL data
• Corneal surgery induces error in measurement but corrected by VCC
• Macular pathology is likely to impede GDX scanning as VCC calculation is dependent on intact Henles
layer

108. Patient’s perspective :
• Takes less than one second time
• Will see afield of thin horizontal red line and on one side of the field patient will see short , bright ,
blinking red horizontal lights similar to equal sign

109. Conclusion :
• Cannot differentiate in high myopic or tilted discs
• Should not be regarded as replacing a skilled ophthalmologist’s capacity to evaluate but aids in decision
making
• Quality and reliability need to be assessed before interpreting them

110. THANK YOU !!!