1. Association between Glaucomatous Visual Field defects and Morphological Changes of Optic Nerve Head following Acute IOP Elevations
Tin A Tun,1,2 Eray Atalay,1 Mani Baskaran,1,3 Monisha E Nongpiur,1,4 Hla M Htoon,1,3 Ching-Yu Cheng,1,3,4 Tin Aung,1,3,4 Nicholas G. Strouthidis,1,5,6 Michaël J.A. Girard,1,2
1Singapore Eye Research Institute and Singapore National Eye Centre, 2Biomedical Engineering, National University of Singapore, Singapore, 3Duke-NUS Medical School, Singapore, 4National University of Singapore, Singapore, 5NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK, 6Discipline of Clinical Ophthalmology and Eye Health, University of Sydney, Sydney, NSW, Australia.
WGCSUB-1849
P-WT-352
Introduction
The injury to the retinal ganglion cell axons occurs on optic nerve head (ONH) particularly at lamina cribrosa (LC) at the onset and during the course of glaucoma.1
Whether structure changes such as retinal nerve fiber layer thinning, cupping of ONH (posterior displacement of LC), thinning of neuroretinal rim (or minimum rim width [MRW]) precede functional loss (mean deviation [MD] or visual field index [VFI]) is ongoing.2, 3
The relationship between functional loss and structural changes of ONH to acute IOP elevations may be useful as a prognostic biomarker4
Aim
To evaluate the association between visual field loss and acute IOP induced changes of ONH
Methods
Standard automated perimetry - Reliability criteria < 33% fixation loss, <15% false-positive error rate, and no false-negative error rate
IOP was raised twice (0.64 N [82.5 g] and then 0.9 N [95 g]) by using an ophthalmo-dynamometer at lower eye lid.5 (Fig 1)
Before and during acute IOP elevations, IOP was measured with Tonopen (Reichert Inc., Depew, USA)
and ONH images were taken with Spectral domain OCT (Spectralis, Heidelberg Engineering, Germany) and post-processed by using adaptive compensation.
Figure 1. Acute IOP elevations with
an ophthalmodynamometer
Figure 2. Measurement of LCD and MRW
from BMO reference plane
Bruch’s membrane opening (BMO) area is defined as the area of anterior most boundary of the neural canal and commonly is the narrowest part of the neural canal. 6 (Fig 2)
LCD is defined as the distance from the BMO reference plane to anterior LC surface.6 (Fig 2)
MRW is defined as the shortest distance from the BMO points to the retinal ILM6 (Fig 2)
Results
91 Chinese subjects (3 with POAG, 45 with PACG and 23 normal controls)
Anterior LC surface
Figure 3. Dynamic Structural changes of ONH to acute IOP elevations
Table 1. Association between functional loss and MRW at baseline or at acute IOP elevations
We adjusted age, gender and baseline IOP in the models analysed for IOP elevations
Figure 3. Plots showing the relationships between glaucomatous visual field defects and lamina cribrosa displacement at the 1st IOP elevation
A greater percentage change of ΔLCD was significantly associated with worse MD (β=-0.7, P<0.01) or with worse VFI (β=-0.61, P<0.01) in POAG eyes. However, this association was not found in PACG eyes.
At the 2nd IOP elevation, a significant association was found between a greater percentage decrease in ΔMRW in inferior-temporal sector and total deviation (dB) of corresponding superior-nasal visual field cluster (ρ=-0.55, P<0.01) in POAG eyes.
Conclusion
Although ONH’s structural changes induced by acute IOP elevations were associated with visual field loss in POAG eyes, no association was observed in the PACG group.
This suggests a differential impact of mechanical compression (by IOP) on the two groups of primary glaucoma.
References
Quigley HA, Addicks EM, Green WR, Maumenee AE. Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage. Arch Ophthalmol (Chicago, Ill 1960). 1981;99(4):
Harsha L. Rao, Linda M. Zangwill RNW. Structure function relationship in glaucoma using RTVue spectral domain optical coherence tomography Harsha. Arch Ophthalmol. 2011;129(7):145.
Muth DR, Hirneiß CW, Fitzke FW, RA. H, M. M-F, FA. M. Structure–Function Relationship Between Bruch’s Membrane Opening–Based Optic Nerve Head Parameters and Visual Field Defects in Glaucoma. Investig Opthalmology Vis Sci. 2015;56(5):3320.
Quigley H, Arora K, Idrees S, et al. Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change Assessed by Optical Coherence Tomography in Glaucoma Eyes. Investig Opthalmology Vis Sci. 2017;58(5):2566.
Tun TA, Thakku SG, Png O, et al. Shape changes of the anterior lamina cribrosa in normal, ocular hypertensive, and glaucomatous eyes following acute intraocular pressure elevation. Investig Ophthalmol Vis Sci. 2016;57(11):
PACG (n=45)
POAG (n=23)
MRW MD
VFI β
P value
Baseline
0.3
0.04
0.33
0.03
0.57
<0.01
0.62
At 1st IOP elevation
0.15
0.14
0.37
0.42
-0.54
At 2nd IOP elevation
0.34
0.2
0.19
0.55
-0.62
MRW
LCD
BMO
Mean (SD) or n (%)
Characteristics
PACG (n=45)
POAG (n=23)
Normal (n=23)
P value
Age, years
68.4 (6.2)
65.05 (7.7)
60.32 (5.65)
<0.05*
Gender, female
18 (40%)
5 (21.7%)
16 (69.6%)
<0.01Ϯ
IOP at baseline, mmHg
16.76 (3.19)
18.65 (3.26)
16.68 (2.15)
<0.05‡
Central corneal thickness, µm
(35.38)
(32.24)
(30.95)
<0.05§
Axial length, mm
23.27 (1.33)
24.56 (1.51)
24.25 (1.29)
0.02||
Mean deviation of SAP, dB
-5.64 (3.87)
-6.08 (5.56)
-2.02 (1.42)
0.02*
Visual field index of SAP, %
88.09 (10.76)
85.91 (13.68)
97.52 (1.9)
<0.02*
Baseline LCD, µm
(123.84)
482.5 (144.62)
(83.87)
0.04#
Baseline BMO area, mm2
2.41 (0.45)
2.54 (0.67)
2.19 (0.38)
0.06
Baseline MRW, µm
(54.12)
(54)
(42.38)
<0.01*
LC visibility, % of BMO area
86.6 (10.92)
76.06 (17.34)
76.41 (13.43)
<0.01$
Author Disclosure: None.
Grants: TA: National Medical Research Council (NMRC/STAR/0023/2014); NGS: National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology; MG: an NUS Young Investigator Award (NUSYIA_FY13_P03; R ) and the Ministry of Education, Academic Research Funds, Tier 1 (R )
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