Objectives: The aim of this study was to train and validate deep learning algorithms to quantitate relative amyloid deposition (RAD; mean amyloid deposited area per stromal area) in corneal sections from patients with familial amyloidosis, Finnish (FAF), and assess its relationship with visual acuity. Methods: Corneal specimens were obtained from 42 patients undergoing penetrating keratoplasty, stained with Congo red, and digitally scanned. Areas of amyloid deposits and areas of stromal tissue were labeled on a pixel level for training and validation. The algorithms were used to quantify RAD in each cornea, and the association of RAD with visual acuity was assessed. Results: In the validation of the amyloid area classification, sensitivity was 86%, specificity 92%, and F-score 81. For corneal stromal area classification, sensitivity was 74%, specificity 82%, and F-score 73. There was insufficient evidence to demonstrate correlation (Spearman’s rank correlation, –0.264, p = 0.091) between RAD and visual acuity (logMAR). Conclusions: Deep learning algorithms can achieve a high sensitivity and specificity in pixel-level classification of amyloid and corneal stromal area. Further modeling and development of algorithms to assess earlier stages of deposition from clinical images is necessary to better assess the correlation between amyloid deposition and visual acuity. The method might be applied to corneal dystrophies as well.

1.
Weiss
JS
,
Møller
HU
,
Aldave
AJ
,
Seitz
B
,
Bredrup
C
,
Kivelä
T
, et al.
IC3D classification of corneal dystrophies—edition 2
.
Cornea
.
2015
Feb
;
34
(
2
):
117
59
.
[PubMed]
0277-3740
2.
Meretoja
J
: Familial systemic paramyloidosis with lattice dystrophy of the cornea, progressive cranial neuropathy, skin changes and various internal symptoms. A previously unrecognized heritable syndrome. Ann Clin Res
1969
[cited 2018 Aug 16];1:314–24.
3.
Kiuru-Enari
S
,
Haltia
M
. Hereditary gelsolin amyloidosis; in : Handbook of clinical neurology.
2013
, pp 659–681.
4.
Nikoskinen
T
,
Schmidt
EK
,
Strbian
D
,
Kiuru-Enari
S
,
Atula
S
.
Natural course of Finnish gelsolin amyloidosis
.
Ann Med
.
2015
;
47
(
6
):
506
11
.
[PubMed]
0785-3890
5.
Rothstein
A
,
Auran
JD
,
Wittpenn
JR
,
Koester
CJ
,
Florakis
GJ
.
Confocal microscopy in Meretoja syndrome
.
Cornea
.
2002
May
;
21
(
4
):
364
7
.
[PubMed]
0277-3740
6.
Rosenberg
ME
,
Tervo
TM
,
Gallar
J
,
Acosta
MC
,
Müller
LJ
,
Moilanen
JA
, et al.
: Corneal morphology and sensitivity in lattice dystrophy type II (familial amyloidosis, Finnish type). Invest Ophthalmol Vis Sci
2001
[cited 2017 Jun 13];42:634–41.
7.
Maury
CP
,
Kere
J
,
Tolvanen
R
,
de la Chapelle
A
.
Finnish hereditary amyloidosis is caused by a single nucleotide substitution in the gelsolin gene
.
FEBS Lett
.
1990
Dec
;
276
(
1-2
):
75
7
.
[PubMed]
0014-5793
8.
Levy
E
,
Haltia
M
,
Fernandez-Madrid
I
,
Koivunen
O
,
Ghiso
J
,
Prelli
F
, et al.
: Mutation in gelsolin gene in Finnish hereditary amyloidosis. J Exp Med
1990
[cited 2018 Aug 16];172:1865–7.
9.
de la Chapelle
A
,
Tolvanen
R
,
Boysen
G
,
Santavy
J
,
Bleeker-Wagemakers
L
,
Maury
CP
, et al.
Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187
.
Nat Genet
.
1992
Oct
;
2
(
2
):
157
60
.
[PubMed]
1061-4036
10.
Kivelä
T
,
Tarkkanen
A
,
Frangione
B
,
Ghiso
J
,
Haltia
M
: Ocular amyloid deposition in familial amyloidosis, Finnish: an analysis of native and variant gelsolin in Meretoja’s syndrome. Invest Ophthalmol Vis Sci
1994
[cited 2018 Aug 16];35:3759–69.
11.
Meretoja
J
.
Comparative histopathological and clinical findings in eyes with lattice corneal dystrophy of two different types
.
Ophthalmologica
.
1972
;
165
(
1
):
15
37
.
[PubMed]
0030-3755
12.
Kivelä
T
,
Tarkkanen
A
,
McLean
I
,
Ghiso
J
,
Frangione
B
,
Haltia
M
:
Immunohistochemical analysis of lattice corneal dystrophies types I and II.
Br J Ophthalmol
1993
[cited 2017 Jun 13];77:799–804.
13.
Mattila
JS
,
Krootila
K
,
Kivelä
T
,
Holopainen
JM
.
Penetrating keratoplasty for corneal amyloidosis in familial amyloidosis, Finnish type
.
Ophthalmology
.
2015
Mar
;
122
(
3
):
457
63
.
[PubMed]
0161-6420
14.
Guo
Y
,
Liu
Y
,
Oerlemans
A
,
Lao
S
,
Wu
S
,
Lew
MS
.
Deep learning for visual understanding: A review
.
Neurocomputing
.
2016
;
187
:
27
48
. 0925-2312
15.
Bychkov
D
,
Turkki
R
,
Haglund
C
,
Linder
N
,
Lundin
J
. Deep learning for tissue microarray image-based outcome prediction in patients with colorectal cancer. In:
Gurcan
MN
,
Madabhushi
A
, editors
.
International Society for Optics and Photonics
.
2016
. p.
979115
.
16.
Esteva
A
,
Kuprel
B
,
Novoa
RA
,
Ko
J
,
Swetter
SM
,
Blau
HM
, et al.
Dermatologist-level classification of skin cancer with deep neural networks
.
Nature
.
2017
Feb
;
542
(
7639
):
115
8
.
[PubMed]
0028-0836
17.
Gulshan
V
,
Peng
L
,
Coram
M
,
Stumpe
MC
,
Wu
D
,
Narayanaswamy
A
, et al.
Development and Validation of a Deep Learning Algorithm for Detection of Diabetic Retinopathy in Retinal Fundus Photographs
.
JAMA
.
2016
Dec
;
316
(
22
):
2402
10
.
[PubMed]
0098-7484
18.
Ting
DS
,
Cheung
CY
,
Lim
G
,
Tan
GS
,
Quang
ND
,
Gan
A
, et al.
Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes
.
JAMA
.
2017
Dec
;
318
(
22
):
2211
23
.
[PubMed]
0098-7484
19.
Brown
JM
,
Campbell
JP
,
Beers
A
,
Chang
K
,
Ostmo
S
,
Chan
RV
, et al.;
Imaging and Informatics in Retinopathy of Prematurity (i-ROP) Research Consortium
.
Automated Diagnosis of Plus Disease in Retinopathy of Prematurity Using Deep Convolutional Neural Networks
.
JAMA Ophthalmol
.
2018
Jul
;
136
(
7
):
803
10
.
[PubMed]
2168-6165
20.
Janowczyk
A
,
Madabhushi
A
.
Deep learning for digital pathology image analysis: A comprehensive tutorial with selected use cases
.
J Pathol Inform
.
2016
Jul
;
7
(
1
):
29
.
[PubMed]
2229-5089
21.
Cruz-Roa
A
,
Basavanhally
A
,
González
F
,
Gilmore
H
,
Feldman
M
,
Ganesan
S
, et al.
 Automatic detection of invasive ductal carcinoma in whole slide images with convolutional neural networks. In:
Gurcan
MN
,
Madabhushi
A
, editors
.
International Society for Optics and Photonics
.
2014
. p.
904103
.
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