Purpose: The aim of this study was to evaluate risk factors for the development of retinal pigment epithelium (RPE) atrophy in patients with neovascular age-related macular degeneration (nAMD). Procedures: This post hoc analysis of the prospective RESPONSE study includes 52 therapy-naive nAMD patients without baseline RPE atrophy, who were treated with ≥9 anti-vascular endothelial growth factor (VEGF) injections for ≥3 years. RPE atrophy was assessed via multimodal imaging. Baseline aqueous VEGF and serum complement levels (C3d/C3) were measured. Risk factors for atrophy development were evaluated via logistic regression analysis. Results: Atrophy onset was significantly associated with the duration of nAMD (mean 5.34 years; odds ratio = 1.83, p = 0.012). Anti-VEGF injection number, age, C3d/C3 ratio, baseline intraocular VEGF, or delay to the first treatment had no influence on RPE atrophy. Conclusions: The duration of treatment-requiring nAMD was identified as primary risk factor for the onset of concomitant RPE atrophy after commencing therapy. Targeting concomitant atrophy in nAMD patients might improve the long-term prognosis of the disease.

1.
Ferris
FL
 3rd
,
Wilkinson
CP
,
Bird
A
,
Chakravarthy
U
,
Chew
E
,
Csaky
K
, et al.;
Beckman Initiative for Macular Research Classification Committee
.
Clinical classification of age-related macular degeneration
.
Ophthalmology
.
2013
Apr
;
120
(
4
):
844
51
.
[PubMed]
0161-6420
2.
Charbel Issa
P
,
Chong
NV
,
Scholl
HP
.
The significance of the complement system for the pathogenesis of age-related macular degeneration - current evidence and translation into clinical application
.
Graefes Arch Clin Exp Ophthalmol
.
2011
Feb
;
249
(
2
):
163
74
.
[PubMed]
0721-832X
3.
Fritsche
LG
,
Igl
W
,
Bailey
JN
,
Grassmann
F
,
Sengupta
S
,
Bragg-Gresham
JL
, et al.
A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants
.
Nat Genet
.
2016
Feb
;
48
(
2
):
134
43
.
[PubMed]
1061-4036
4.
Rosenfeld
PJ
,
Brown
DM
,
Heier
JS
,
Boyer
DS
,
Kaiser
PK
,
Chung
CY
, et al.;
MARINA Study Group
.
Ranibizumab for neovascular age-related macular degeneration
.
N Engl J Med
.
2006
Oct
;
355
(
14
):
1419
31
.
[PubMed]
0028-4793
5.
Campbell
JP
,
Bressler
SB
,
Bressler
NM
.
Impact of availability of anti-vascular endothelial growth factor therapy on visual impairment and blindness due to neovascular age-related macular degeneration
.
Arch Ophthalmol
.
2012
Jun
;
130
(
6
):
794
5
.
[PubMed]
0003-9950
6.
Abdelfattah
NS
,
Zhang
H
,
Boyer
DS
,
Sadda
SR
.
Progression of Macular Atrophy in Patients with Neovascular Age-Related Macular Degeneration Undergoing Antivascular Endothelial Growth Factor Therapy
.
Retina
.
2016
Oct
;
36
(
10
):
1843
50
.
[PubMed]
0275-004X
7.
Grunwald
JE
,
Daniel
E
,
Huang
J
,
Ying
GS
,
Maguire
MG
,
Toth
CA
, et al.;
CATT Research Group
.
Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials
.
Ophthalmology
.
2014
Jan
;
121
(
1
):
150
61
.
[PubMed]
0161-6420
8.
Sarks
JP
,
Sarks
SH
,
Killingsworth
MC
.
Evolution of geographic atrophy of the retinal pigment epithelium
.
Eye (Lond)
.
1988
;
2
(
Pt 5
):
552
77
.
[PubMed]
0950-222X
9.
Channa
R
,
Sophie
R
,
Bagheri
S
,
Shah
SM
,
Wang
J
,
Adeyemo
O
,
Sodhi
A
,
Wenick
A
,
Ying
HS
,
Campochiaro
PA
:
Regression of choroidal neovascularization results in macular atrophy in anti-vascular endothelial growth factor-treated eyes.
Am J Ophthalmol
2015
;159:9-19 e11-12.
10.
Lois
N
,
McBain
V
,
Abdelkader
E
,
Scott
NW
,
Kumari
R
.
Retinal pigment epithelial atrophy in patients with exudative age-related macular degeneration undergoing anti-vascular endothelial growth factor therapy
.
Retina
.
2013
Jan
;
33
(
1
):
13
22
.
[PubMed]
0275-004X
11.
Xu
L
,
Mrejen
S
,
Jung
JJ
,
Gallego-Pinazo
R
,
Thompson
D
,
Marsiglia
M
, et al.
Geographic atrophy in patients receiving anti-vascular endothelial growth factor for neovascular age-related macular degeneration
.
Retina
.
2015
Feb
;
35
(
2
):
176
86
.
[PubMed]
0275-004X
12.
Abdelfattah
NS
,
Al-Sheikh
M
,
Pitetta
S
,
Mousa
A
,
Sadda
SR
,
Wykoff
CC
, et al.;
Treat-and-Extend Age-Related Macular Degeneration Study Group
.
Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly versus Treat-and-Extend Ranibizumab: findings from the TREX-AMD Trial
.
Ophthalmology
.
2017
Feb
;
124
(
2
):
215
23
.
[PubMed]
0161-6420
13.
Bhisitkul
RB
,
Mendes
TS
,
Rofagha
S
,
Enanoria
W
,
Boyer
DS
,
Sadda
SR
,
Zhang
K
: Macular atrophy progression and 7-year vision outcomes in subjects from the ANCHOR, MARINA, and HORIZON studies: the SEVEN-UP study. Am J Ophthalmol
2015
;159:915-924 e912.
14.
Grunwald
JE
,
Pistilli
M
,
Daniel
E
,
Ying
GS
,
Pan
W
,
Jaffe
GJ
, et al.;
Comparison of Age-Related Macular Degeneration Treatments Trials Research Group
.
Incidence and Growth of Geographic Atrophy during 5 Years of Comparison of Age-Related Macular Degeneration Treatments Trials
.
Ophthalmology
.
2017
Jan
;
124
(
1
):
97
104
.
[PubMed]
0161-6420
15.
Chakravarthy
U
,
Harding
SP
,
Rogers
CA
,
Downes
SM
,
Lotery
AJ
,
Culliford
LA
, et al.;
IVAN study investigators
.
Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial
.
Lancet
.
2013
Oct
;
382
(
9900
):
1258
67
.
[PubMed]
0140-6736
16.
Binder
DR
,
Herring
IP
,
Zimmerman
KL
,
Pickett
JP
,
Huckle
WR
.
Expression of vascular endothelial growth factor receptor-1 and -2 in normal and diseased canine eyes
.
Vet Ophthalmol
.
2012
Jul
;
15
(
4
):
223
30
.
[PubMed]
1463-5216
17.
Grisanti
S
,
Tatar
O
.
The role of vascular endothelial growth factor and other endogenous interplayers in age-related macular degeneration
.
Prog Retin Eye Res
.
2008
Jul
;
27
(
4
):
372
90
.
[PubMed]
1350-9462
18.
Marneros
AG
,
Fan
J
,
Yokoyama
Y
,
Gerber
HP
,
Ferrara
N
,
Crouch
RK
, et al.
Vascular endothelial growth factor expression in the retinal pigment epithelium is essential for choriocapillaris development and visual function
.
Am J Pathol
.
2005
Nov
;
167
(
5
):
1451
9
.
[PubMed]
0002-9440
19.
Stewart
MW
.
The expanding role of vascular endothelial growth factor inhibitors in ophthalmology
.
Mayo Clin Proc
.
2012
Jan
;
87
(
1
):
77
88
.
[PubMed]
0025-6196
20.
Hoerster
R
,
Muether
PS
,
Sitnilska
V
,
Kirchhof
B
,
Fauser
S
.
Fibrovascular pigment epithelial detachment is a risk factor for long-term visual decay in neovascular age-related macular degeneretion
.
Retina
.
2014
Sep
;
34
(
9
):
1767
73
.
[PubMed]
0275-004X
21.
Muether
PS
,
Hermann
MM
,
Viebahn
U
,
Kirchhof
B
,
Fauser
S
.
Vascular endothelial growth factor in patients with exudative age-related macular degeneration treated with ranibizumab
.
Ophthalmology
.
2012
Oct
;
119
(
10
):
2082
6
.
[PubMed]
0161-6420
22.
Schick
T
,
Ersoy
L
,
Hoyng
CB
,
Kirchhof
B
,
Liakopoulos
S
.
Phenotype Characteristics of Fellow Eyes in Patients With Early Onset of Neovascular Age-Related Macular Degeneration
.
Invest Ophthalmol Vis Sci
.
2015
Nov
;
56
(
12
):
7269
73
.
[PubMed]
0146-0404
23.
Smailhodzic
D
,
Klaver
CC
,
Klevering
BJ
,
Boon
CJ
,
Groenewoud
JM
,
Kirchhof
B
, et al.
Risk alleles in CFH and ARMS2 are independently associated with systemic complement activation in age-related macular degeneration
.
Ophthalmology
.
2012
Feb
;
119
(
2
):
339
46
.
[PubMed]
0161-6420
24.
Holz
FG
,
Sadda
SR
,
Staurenghi
G
,
Lindner
M
,
Bird
AC
,
Blodi
BA
, et al.;
CAM group
.
Imaging Protocols in Clinical Studies in Advanced Age-Related Macular Degeneration: Recommendations from Classification of Atrophy Consensus Meetings
.
Ophthalmology
.
2017
Apr
;
124
(
4
):
464
78
.
[PubMed]
0161-6420
25.
Bradley
DT
,
Zipfel
PF
,
Hughes
AE
.
Complement in age-related macular degeneration: a focus on function
.
Eye (Lond)
.
2011
Jun
;
25
(
6
):
683
93
.
[PubMed]
0950-222X
26.
Schick
T
,
Steinhauer
M
,
Aslanidis
A
,
Altay
L
,
Karlstetter
M
,
Langmann
T
,
Kirschfink
M
,
Fauser
S
:
Local complement activation in aqueous humor in patients with age-related macular degeneration.
Eye (Lond)
2017
27.
Muether
PS
,
Hoerster
R
,
Hermann
MM
,
Kirchhof
B
,
Fauser
S
.
Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration
.
Graefes Arch Clin Exp Ophthalmol
.
2013
Feb
;
251
(
2
):
453
8
.
[PubMed]
0721-832X
28.
Wu
Z
,
Luu
CD
,
Ayton
LN
,
Goh
JK
,
Lucci
LM
,
Hubbard
WC
, et al.
Optical coherence tomography-defined changes preceding the development of drusen-associated atrophy in age-related macular degeneration
.
Ophthalmology
.
2014
Dec
;
121
(
12
):
2415
22
.
[PubMed]
0161-6420
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