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Transcript
Non-contact Specular Microscopy for
Evaluation of Corneal Endothelium in
Early Fuchs’ Endothelial Corneal
Dystrophy
Jianyan Huang1, MD, PhD; Tudor Tepelus1, PhD;
Cristina Modak1, PhD; Vikas Chopra1,2, MD; Srinivas R
Sadda1,2, MD; Olivia L Lee1,2, MD
1 Doheny
Image Reading Center, Doheny Eye Institute, Los Angeles, California, USA;
2 Department of Ophthalmology, David Geffen School of Medicine, University of
California Los Angeles. Los Angeles, USA
1
Financial Disclosure
Dr. Sadda
•Consultant: Allergan, Genentech, Regeneron, Optos, Carl Zeiss Meditec
•Research Grant Support: Optos, Carl Zeiss Meditec, Allergan, Genentech
Dr. Chopra
•Consultant: Allergan
•Research Grant Support: Allergan
Dr. Lee
•Consultant: Allergan
•Research Grant Support: Allergan
All other authors
•Nothing to disclose
2
Introduction
Early Fuchs endothelial corneal dystrophy (FECD) is characterized by asymmetrical,
bilateral, slowly progressive formation of guttata in the absence of clinically significant
corneal edema. Progression of cornea guttata proceeds from the center of the cornea
and spreads to the periphery. Endothelial cell attrition rises with increasing number and
size of the guttate lesions. Eventually, edema of the corneal epithelium and stroma
appears, causing blurred vision.
Accurately assess the cornea endothelial cell density is clinically helpful to estimate the
health of the endothelium, but also can track the progression of FECD longitudinally.
Specular microscopy can provide a non-invasive morphological analysis of the corneal
endothelial cell layer to detect the early FECD patients and a variety of analysis programs
are available to determine corneal endothelial cell density (ECD) and morphometry.
The purpose of this study is to describe the use of non-contact specular microscopy to
obtain accurate endothelial cell measurements with Center method or Flex Center
method in the face of varying guttata density.
3
Methods
Using the Konan NSP 9900 specular microscope, three images of the
central corneal endothelium were captured in each eye of normal control
and early FECD affected eyes. All the eyes had no history of corneal or
intraocular surgery, ocular trauma, keratitis or uveitis.
Patient and subject information
Group
Age (years)
Number
Gender
Control
61.1±15.4
49 eyes (25 subjects)
13 female 12 male
FECD
60.3±14.5
39 eyes (24 patients)
13 female 11 male
4
Methods
Corneal endothelial cell analysis using both the Center method and Flex
Center method was performed by 2 certified graders. Measurements of
ECD, coefficient of variation (CV) and hexagonality (HEX) were then
calculated using Konan CellChek software.
Guttata surface area in each image was quantified by ImageJ, an image
analysis software.
Variation in ECD values was determined based on the % error and
relative standard deviation. Absolute error <5% was considered
acceptable agreement.
𝐶𝐷 𝑣𝑎𝑟𝑖𝑎𝑡𝑖𝑜𝑛 % 𝑒𝑟𝑟𝑜𝑟 =
𝐶𝐷𝐻𝐼𝐺𝐻 − 𝐶𝐷𝐿𝑂𝑊
× 100 < 5%
𝐶𝐷𝐿𝑂𝑊
Results were expressed as means ± standard deviations. Statistical
analyses were performed using SPSS ver. 13.0. Statistical methods
employed include paired t test, independent t test, Spearman correlation
and one way ANOVA.
5
Results
The mean values of endothelial parameters obtained by both Center and Flex Center
methods in normal corneas and early FECD-affected corneas.
Normal
corneas
(n=49)
FECD
affected
corneas
(n=39)
P*
FECD
affected
corneas
Frame#1
FECD
affected
corneas
Frame#2
FECD
affected
corneas
Frame#3
P**
ECD
2669±261
2322±537
0.001
2339±583
2308±603
2324±539
0.949
CV
34±4
29±4
<0.001
29±6
29±5
29±5
0.398
HEX
59±5
59±7
0.973
57±12
61±13
59±10
0.454
Center method
Flex center method
ECD
2664±261
2267±583
0.001
2275±579
2264±596
2267±584
0.906
CV
36±4
35±5
0.297
35±6
33±6
34±4
0.638
HEX
58±6
60±6
0.112
59±7
62±10
60±7
0.806
* Comparisons between the normal corneas and FECD affected corneas were made by paired t test.
** Comparisons among the 3 different images from the same FECD affected corneas were made by one way
ANOVA.
6
Results
Correlation of overall guttata area with endothelial parameters in FECD-affected
cornea.
Center method
Flex center method
Spearman correlation
coefficient
P
ECD
-0.340
0.001
CV
-0.314
0.001
HEX
-0.174
0.069
ECD
-0.433
<0.001
CV
-0.152
0.014
HEX
-0.055
0.665
7
Results
Agreement between Center method and Flex center method based on
differences in the number (NUM) of identified cells applied to the
calculation of ECD.
NUM
Percentage of Error ≥5%
≤ 10
56.25 (9/16)
10< NUM ≤ 15
25 (3/12)
15< NUM ≤ 20
50 (3/6)
20< NUM ≤ 30
20 (2/10)
>30
12.3 (9/73)
Total
22.2 (26/117)
8
Results
Three representative eyes with early FECD, showing the ungraded specular
image and the same image manually graded by Center and Flex center
methods. (INP: input dots by grader).
Frame
#1
#2
#3
9
Conclusions
In early FECD, both Center and Flex center methods
can be used to reliably determine ECD.
ECD values are lower in FECD-affected corneas than in
control eyes.
The overall guttata has a negative correlation with ECD
value, but is unrelated to CV and HEX.
10
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