Intra-eye RNFL and MT Asymmetry for the Discrimination of POAG and NTG Safal Khanal, OD Clinical and Research Optometrist, Kathmandu, Nepal safalkhanal@iom.edu.np Dr. Pinakin Gunvant Davey, Western University of Health Sciences, USA Dr. Lyne Racette, Indiana University, USA Dr. 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?????

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

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 ???

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

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 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

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

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

<.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)

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

NTG

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 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 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) 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.

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!!!!!