Intra-eye RNFL and MT Asymmetry for the

Discrimination of POAG and NTG

Safal Khanal, ODClinical and Research Optometrist, Kathmandu, Nepal

safalkhanal@iom.edu.np

Dr. Pinakin Gunvant Davey, Western University of Health Sciences, USADr. Lyne Racette, Indiana University, USADr. Madhu Thapa, Institute of Medicine, Nepal

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

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?????

• 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

Continuum of OAG- NTG and POAG

Rate of progression, hematovascular

Thinner NRR

Deeper and steeper sided VFDs closer to

macula

Greater prevalence of Disc Hge

Higher peak 24 hour IOP

• 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 ???

Rationale…..

• General– 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

Aims and Objectives

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

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

Methodology

• Glaucomatous eyes – 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

Methodology

• SAP– 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

Results

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 14/16 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 <0.001ǂ

*One way ANOVA analysis¶ Chi-square testǂ One way ANOVA analysis using Games-Howell adjustment for pairwise comparisonsNTG=normal tension glaucoma; POAG=primary open angle glaucoma; BCVA=best corrected visual acuity; MD=mean deviation; LV= loss variance

Normal(n=30)

NTG(n=30)

POAG(n=30)

*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 <.001 <.001

Inf RNFL thickness141.9

(137.5 to 146.3)117.3

(111.0 to 123.7)73.7

(64.4 to 83.1)<.001 <.001 <.001

Avg RNFL thickness

109.8 (106.7 to 112.9)

85.4 (81.8 to 89.1)

64.3 (58.9 to 69.7)

<.001 <.001 <.001

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)

<.001 <.001 <.001

Inf macular thickness

289.2 (282.2 to 296.3)

275.2 (271.3 to 279.2)

253.4(248.8 to 258.1)

<.001 <.001 <.001

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 <.001 <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)

<.001 <.001 <.001

Comparison groups

Normal - POAG Normal – NTG NTG-POAG

AROC P1 Sn/Sp AROC P2 Sn/SpAROC P3 Sn/Sp

Superior RNFL thickness 0.989 <.001 100/90 0.940 <.001 90/90 0.811 <.001 62/90

Inferior RNFL thickness0.999 <.001 100/90 0.876 <.001 69/90 0.917 <.001 80/90

Average RNFL thickness 1.000 <.001 100/100 0.979 <.001 93/90 0.900 <.001 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 <.001 100/90 0.889 <.001 67/92 0.854 <.001 53/90

Inferior macular thickness 0.999 <.001 100/90 0.878 <.001 80/90 0.911 <.001 67/90

I/S macular thickness differenceb 0.882 <.001 80/93 0.893 <.001 68/90 0.818 <.001 71/90

Total macular thickness 0.972 <.001 100/90 0.872 <.001 73/90 0.894 <.001 66/90

0 20 40 60 80 100

0

20

40

60

80

100

100-Specificity

Sen

sitiv

ity

I/S Macular thickness asymmetryI/S RNFL thickness asymmetry

AROC1 = 0.893AROC2 = 0.626

1

2

NTG

0 20 40 60 80 100

0

20

40

60

80

100

100-Specificity

Sensitiv

ity

I/S Macular thickness asymmetryI/S RNFL thickenss asymmetry

AROC1=0.882AROC2=0.644

1

2

POAG

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.

Discussion

• MT 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 0.800 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.

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.

Discussion

• Um, et al (2012)– 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.

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.

Acknowledgements….

Thank you for your attention!!!!!