1. Intra-eye RNFL and MT Asymmetry for the Discrimination of POAG and NTG
Safal Khanal, OD
Clinical and Research Optometrist, Kathmandu, Nepal
Dr. Pinakin Gunvant Davey, Western University of Health Sciences, USA
Dr. Lyne Racette, Indiana University, USA
Dr. Madhu Thapa, Institute of Medicine, Nepal

2. Understanding glaucoma
A spectrum of diseases
Differ in clinical presentation,
pathophysiology and treatment.
a group of diseases of ON NOT the IOP…..
Describing Feature
OR (????...)
Defining Feature
Slow progressive degeneration of RGCs and axons

3. Structural vs functional loss
Visual function loss preceded by structural damage
60% of eyes approximately six years before any detectable VF defects (Soliman MA, et al, 2002)
Assessment of ONH and surrounding RNFL essential
Damage to optic disc a/w abnormal RNFL appearance
Objective measures gaining popularity for early pick up
OHTS
41.7% of patients with OHT reached visual end point before structural one.
Reasons?????

4. Continuum of OAG- NTG and POAG
OAG- Early pick up difficulty and when to initiate treatment
2 distinct IOP based clinical entities
High tension
Normal tension
Various risk factors- vascular and perfusion abnormalities
Differences
Greater prevalence of Disc Hge
Higher peak 24 hour IOP
Deeper and steeper sided VFDs closer to macula
Rate of progression, hematovascular
Thinner NRR

5. Rationale….. Imperative to note objective difference b/w NTG and POAG
Well established diagnostic ability of RNFL and macular thickness
Asymmetry – a well known characteristic of POAG
VF asymmetry- GHT, NRR width asymmetry
Problems with raw measurements
Superior diagnostic ability parameters ???

6. Aims and Objectives General Specific
Evaluate the performance of RNFL and MT asymmetry parameters in variants of OAG.
Specific
RNFL and MT asymmetry in POAG, NTG and normal
MT asymmetry (POAG v NTG v Normal)
RNFL thickness asymmetry ((POAG v NTG v Normal)
MT vs RNFL thickness asymmetry

7. Methodology Study design prospective, cross sectional, hospital based
Subjects
90 (30 consecutive healthy subjects, NTG and POAG), Age and gender matched
A part of Glaucoma Research Project at BP Koirala Lions Center for Ophthalmic Studies, Kathmandu, Nepal

8. Methodology
Complete ophthalmic examination including pachymetry, SAP and OCT
Inclusions
Age> 35 years; open angles;
good-quality scans (SNR >35);
reliable SAP performed at ± 1 month from OCT imaging;
RE within a ± 5 sph, with < ± 3 cylinder
Exclusions
BCVA< 20/60,
ocular conditions interfering with obtaining reliable visual fields (VFs) or good quality retinal scans, significant PPA
Unreliable VF test with three attempts
Pts with any ophthalmic or neurologic conditions resulting in SAP defects

9. Methodology Glaucomatous eyes Study groups POAG NTG Healthy subjects
a glaucomatous VFD confirmed by 2 reliable VF exams; appearance of a glaucomatous optic disc with typical loss of NRR (CDR, >0.7; intereye cup asymmetry, >0.2; or NRR notching, focal thinning, disc hemorrhage, or vertical elongation of the optic cup)
Study groups
POAG
IOP before treatment exceeding 21mm Hg based on 3 measurements on different days
NTG
untreated peak IOP lower than 21mm Hg on repeated 3 measurements taken at different times on separate visits during clinical follow-up
Healthy subjects
Age and gender matched normal subjects

10. Methodology SAP OCT Normal strategy on OCTOPUS 301
A reliable VF test : < 33% FL; < 20% FP and FN.
Hodapp, et al criteria for VF defect
Global indices obtained in the second examination were included
SAP was performed by the same operator in all cases
OCT
SD-OCT Spectralis HRA+OCT (Heidelberg Engineering)
Posterior pole asymmetry scan protocol
Intraeye RNFL and macular thickness asymmetry calculated as absolute difference between superior and inferior hemispheres of the eye
Image quality scores of at least 60

11. Results Normal (n = 30) NTG (n = 30) POAG (n = 30) P Age (yrs)
Normal (n = 30)
NTG (n = 30)
POAG (n = 30) P
Age (yrs)
47.00 ± 8.16
50.97 ± 10.03
52.00 ± 9.58
0.10*
Sex (M/F)
14/16
12/18
0.89¶
BCVA (logMAR)
0.07 ± 0.10
0.05 ± 0.10
0.09 ± 0.12
0.40*
Refractive error (D)
+0.26 ± 0.53
+0.16 ± 0.73
+0.33 ± 0.56
0.07*
MD (dB)
0.38± 0.82
3.10 ± 0.87
5.88 ± 4.07
<0.001ǂ
LV (dB)
2.68 ± 0.90
8.49 ± 3.59
23.4 ± 16.2
*One way ANOVA analysis
¶ Chi-square test
ǂ One way ANOVA analysis using Games-Howell adjustment for pairwise comparisons
NTG=normal tension glaucoma; POAG=primary open angle glaucoma; BCVA=best corrected visual acuity; MD=mean deviation; LV= loss variance

12. <.001 Normal (n=30) NTG POAG *P1 *P2 *P3 Sup RNFL thickness 138.9
Normal
(n=30)
NTG
POAG
*P1
*P2
*P3
Sup RNFL thickness
138.9
(133.0 to 144.8)
106.3
(101.0 to 111.7)
81.3
(73.0 to 89.7)
<.001
Inf RNFL thickness
141.9
(137.5 to 146.3)
117.3
(111.0 to 123.7)
73.7
(64.4 to 83.1)
Avg RNFL thickness
109.8
(106.7 to 112.9)
85.4
(81.8 to 89.1)
64.3
(58.9 to 69.7)
I/S RNFL thickness differencea
9.8
(6.9 to 12.7)
14.73
(10.6 to 18.8)
16.33
(11.4 to 21.3)
0.187
0.056
0.837
Sup macular
thickness
293.4
(290.5 to 296.2)
276.9
(272.8 to 280.9)
259.8
(255.4 to 264.1)
Inf macular
289.2
(282.2 to 296.3)
275.2
(271.3 to 279.2)
253.4
(248.8 to 258.1)
I/S macular
thickness diffb
2.0
(1.6 to 2.3)
4.5
(3.3 to 5.1)
7.2
(5.1 to 9.3)
<0.05
<0.01
Total macular thickness
291.3
(287.0 to 295.6)
276.0
(272.1 to 279.9)
256.6
(252.3 to 260 8)

15. Comparison groups Normal - POAG Normal – NTG NTG-POAG AROC P1 Sn/Sp P2
Comparison groups
Normal - POAG
Normal – NTG
NTG-POAG
AROC P1
Sn/Sp P2 P3
Superior RNFL thickness
0.989
<.001
100/90
0.940
90/90
0.811
62/90
Inferior RNFL thickness
0.999
0.876
69/90
0.917
80/90
Average RNFL thickness
1.000
100/100
0.979
93/90
0.900
76/90
I/S RNFL thickness differencea
0.644
.061
37/90
0.626
.091
30/90
0.533
.662
13/90
Superior macular thickness
0.997
0.889
67/92
0.854
53/90
Inferior macular thickness
0.878
0.911
67/90
I/S macular thickness differenceb
0.882
80/93
0.893
68/90
0.818
71/90
Total macular thickness
0.972
0.872
73/90
0.894
66/90

16. NTG

17. POAG

18. Discussion
Paucity of data regarding effectiveness of structural asymmetry measurements
Sullivan-Mee, et al
evaluated the diagnostic capabilities of intereye and intraeye differences in RNFL thickness and macular thickness for identifying early POAG
Concluded, although structural asymmetry parameters performed well, further study is indicated to validate the results.

19. Discussion MT asymmetry RNFL thickness asymmetry
a diagnostic capability comparable to RNFL thickness and MT parameters while discriminating subjects with NTG from POAG as well as normal subjects.
RNFL thickness asymmetry
lowest AROC as well as the least sensitivity for identifying subjects with NTG from normal (AROC=0.626, sensitivity=30%); POAG from normal (AROC=0.644, sensitivity=37%) and NTG from POAG (AROC=0.662, sensitivity=13%).
AROCs exceeded for all the studied parameters except for intra-eye RNFL thickness asymmetry.
RNFL thickness asymmetry could not statistically discriminate NTG from POAG (p=.837).
MT asymmetry adequately showed a distinction between NTG and POAG (p<.001).
MT Asymmetry measurement were higher in POAG compared to NTG.

20. Discussion Agreement with Sullivan Mee, et al’s study (2013)
RNFL thickness asymmetry demonstrated the worst diagnostic capability of any study parameter.
Intra-eye macular thickness asymmetry as one of the best parameters for identifying early glaucoma.
Intra-eye RNFL thickness asymmetry parameter had the lowest area under ROC and the least sensitivity of all the parameters in our study.

21. Discussion Um, et al (2012) Study groups
Asymmetry in hemifield MT, similar diagnostic performance to  sectoral RNFL thickness.
Study groups
Um and associates- GS, early and advanced glaucomas
This study – NTG and POAG
Further strengthens the role of MT asymmetry in being a pivotal potential clinical marker for glaucoma diagnosis.

22. Conclusion
The intra-eye MT asymmetry holds significant potential as a distinguishing parameter for NTG and POAG.
MT asymmetry could provide global indices of structural damage much in the way that the GHT provides for assessing the functional damage.
POAG showed a greater MT asymmetry than NTG with no difference in RNFL thickness asymmetry
Further studies needed to validate results in larger samples with diverse glaucoma study groups.

23. Acknowledgements….
Thank you for your attention!!!!!