Visual field progression in glaucoma

2011

Estimating the overall significance of deterioration with permutation analysis of point-wise linear regression
North American Perimetry Society Meeting 2011

Neil OLeary, Balwantray Chauhan, Paul Artes

Background: Detecting Change

Glaucoma change probability Point-wise linear regression Global indices not very sensitive (Chauhan et al IOVS 1990, Artes et al IOVS 2011)

Point-wise Linear Regression

Point-wise linear regression (PLR) is a method to measure visual field change

Much previous research

Criteria for PLR

Title Authors Year Slope(dB/y) Pvalue Improvement Filter Analysis Points Location Exclusionofexams Followup/Exam frequency
Remarks Spatially consistent, localized visual field loss before and after disc hemorrhage De Moraes CGV et al. 2009 < -1.0 0.01 no yes 1 non-edge points (f d i t (for edge points < -2.0 dB/y) First 2 VF in patients unfamiliar 6.7y / 6 - 12m At least 5 VF

Pointwise linear regression analysis for detection of visual field progression with absolute versus corrected threshold sensitivities

Manassakorn A et al.

2006

< -1.0

0.01

yes

no

In the same GHT location

Reliability

7.3y / -

Visual Field Progression in Glaucoma: Total Versus Pattern Deviation Analyses

Artes PH et al.

2005

< -1.0

0.05

yes

no

range

range

First VF (red learning effects). Two-omitting method

9y / 6m

At least 5 VF

Pointwise linear regression for evaluation of visual field outcomes and comparison with the Nouri-Mahdavi K et al. advanced glaucoma intervention study methods

2005

< -1.0

0.01

yes

no

1 or 2

2 points, 2 cluster, 2 Two-omitting method hemifield, 2 GHT

At least 3y / 6m

At least 3y FU. At least 7 VF.

Pointwise linear progression criteria and the detection of visual field change in a glaucoma trial.

Wilkins MR et al.

2006

< -1.0

0.01

yes

no

Anywhere. 2 or 3 cluster hemifield. 2 1, 2, 3, cluster GHT. 2 PNFB 4 or 5 cluster. 2 ONH derived cluster.

16m / 3-4m

At least 6 VF

Examination of Different Pointwise Linear Regression Methods for Determining Visual Field Progression

Gardiner SK et al.

< -1.0

0.01

no

no

non-edge points (for edge points < -2.0 dB/y)

No (no random selection)

Standard criteria. Comparrison with different ones.

Frequency of testing for detecting visual field progression Early detection of visual field progression in glaucoma: a comparison of PROGRESSOR and STATPAC 2 Visual field progression: comparison of HumphreyStatpac2 and pointwise linear regression analysis

Gardiner SK et al.

2002

< -1.0

0.01

no

no

Any y non-edge points (for edge points < -2.0 dB/y) non-edge points (for edge points < -2.0 dB/y)

No (no random selection)

Play with frequency

Viswanathan AC et al.

1997

< -1.0

0.01

no

no

Reliability

/ 4m

MacNaught AI et al.

1996

< -1.0

0.01

no

no

No (no random selection)

5.6y / 4.2m

Play with P value

Properties
Many strategies with many criteria...not simple!

Properties not well-defined: specificity and sensitivity

Aims
Develop a method to infer a simple, single, overall statistical significance of the observed pattern of sensitivity deterioration from PLR Show that significance level of this method produces an equivalent false positive level Compare hit t and specificity to other PLR C hit-rate d ifi it t th criteria for progression

Methodology
Perform PLR Combine p-values Permute test sequence Permutation of PLR: PoPLR!

PoPLR: Combining Evidence

RA Fisher

Providing statistical significance since 1925!

PoPLR: Assessing the Evidence

Combine evidence from different locations into a single statistic Test statistic S for observed sequence q Derive the significance of this statistic

Significance: Permutation
Permute sequence of VF tests and calculate test statistics under re-ordering
1 2 3 4 5 6 7 8

S
7 3 8 1 5 4 6 2

Sp

Repeat 5000 times for series: 5000 Sp

Significance: Permutation
Distribution of permuted test statistics (Sp)

Position of observed sequence S (3498 out of 5000: p = 0.30)

Significance: Permutation
Distribution of permuted test statistics (Sp)

Position of observed sequence S (4756 out of 5000: p = 0.05)

Permutation analyses of point-wise linear regression point wise

Experiment: Clinical Data

Measuring Specificity in Real Data

Removing any trends Shuffling time sequence

y p y Sensitivity and Specificity of Other Methods

Se ensitivity

Specificity

g y Measuring Relative Sensitivity in Real Data

H Hit Rat te

At Fixed Specificity Hit Rate Hi R A > Hit Rate B Hi R Sensitivity A > Sensitivity B

Specificity

Data
Median Baseline MD (dB) Baseline Age (years) -3.0 67 IQR -6.3, -1.2 59, 75

Results: Specificity of Method

5 exams

Results: Specificity of Method

8 exams

Results: Specificity of Method

Final exam

Results: Hit Rate

5 exams

Results: Hit Rate

5 exams

Results: Hit Rate

8 exams

Results: Hit Rate

Final exam

Conclusions
PoPLR provides a single, simple, overall estimate of statistical significance for visual field progression Specificity is accurate in population and in individual I di id li d t each patients own data h ti t d t Individualised to Adaptable

Bal

Paul

Alexandre Reis

Marcelo Nicolela

Paul Rafuse

Lesya Shuba esya S uba

Ray LeBlanc y