ARVO 2014 Annual Meeting Abstracts 335 Real life management of

ARVO 2014 Annual Meeting Abstracts
335 Real life management of retinal disease
Tuesday, May 06, 2014 11:00 AM–12:45 PM
Hall SB Paper Session
Program #/Board # Range: 3061–3067
Organizing Section: Retina
Program Number: 3061
Presentation Time: 11:00 AM–11:15 AM
Baseline characteristics of over 10,000 patients enrolled into the
LUMINOUS study
Christopher S. Brand. Ophthalmology, Royal Hallamshire Hospital,
Sheffield, United Kingdom.
Purpose: To describe baseline characteristics of over 10,000 patients
recruited in the LUMINOUS study
Methods: LUMINOUS is a 5-year multicenter, prospective study
to evaluate long-term safety, effectiveness, treatment patterns, and
health-related quality of life in patients treated in routine clinical
practice with 0.5 mg ranibizumab (RBZ) in wet age-related macular
degeneration [wAMD], diabetic macular edema [DME], retinal vein
occlusion [RVO], and myopic choroidal neovascularization [mCNV]
(depending on local approval). Consenting adult patients are enrolled
irrespective of whether or not they were previously treated with RBZ
and/or any other ocular therapy. Patients are excluded if they are
participating in any other study that includes administration of any
investigational drug, or have had systemic or ocular treatment with
any vascular endothelial growth factor inhibitor other than RBZ, 90
days prior to study enrolment. The study is planned to recruit 30,000
patients from approximately 600 sites in 41 countries worldwide
Results: As of December 2013, baseline data were available
for 10,071 patients. Demographic data are shown in table 1 and
comorbidities in table 2. In total, 7914 (78.6%) patients were
previously treated with RBZ (T1), 1891 (18.8%) patients did not
have any prior treatment (T2), and 266 (2.6%) were previously
treated with other ocular therapies (T3; the pre-treatment status refers
to the primary treated eye). Here we present the data of T1 and T2
groups. The baseline mean visual acuity (VA) letter score of the
study eye was higher in the T1 group than the T2 group across all
indications (wAMD: 55.6 vs 46.4; DME: 55.3 vs 40.8; BRVO: 52.9
vs 37.3; CRVO: 45.2 vs 38.9). Mean central retinal thickness (CRT;
mm) of the study eye at baseline was lower in T1 than T2 across all
indications (wAMD: 265.6 vs 347.3; DME: 371.5 vs 429.3; BRVO:
328.8 vs 456.5; CRVO: 365.9 vs 555.4)
Conclusions: LUMINOUS includes patients with more diverse
demographics than reported for the pivotal trials and is more
representative of real world wAMD, DME and RVO patients.
Previous treatment with RBZ was associated with higher VA and
lower CRT at baseline than in the group without prior treatment
across indications
Baseline demographic data
Baseline comorbidities
Commercial Relationships: Christopher S. Brand, Allergan (C),
Allergan (F), Allergan (R), Bayer (C), Merck, Sharp and Dohme
(MSD) (R), Novartis (C), Novartis (F), Novartis (R), Pfizer (F),
Quark (F)
Clinical Trial: NCT01318941
Program Number: 3062
Presentation Time: 11:15 AM–11:30 AM
Ranibizumab in the real world clinical setting: results from the
one year interim analysis of the LUMINOUS study
Paul Mitchell. Ophthalmology, University of Sydney, Sydney, NSW,
Australia.
Purpose: To present one year data from the first cohort of wet age
related macular degeneration (wAMD) patients recruited in the
LUMINOUS study
Methods: LUMINOUS is an ongoing 5-year prospective,
multinational, observational study across all approved indications of
ranibizumab, designed to evaluate long-term safety, effectiveness,
treatment patterns, and health-related quality of life outcomes in
patients treated with ranibizumab 0.5 mg in routine clinical practice.
The study aims to enroll 30,000 patients from approximately 600
sites in 41 countries worldwide. Of the 2163 patients recruited prior
to or on 1st March 2012, 97.6% had wAMD, 1.7% diabetic macular
edema and 0.6% retinal vein occlusion. Here, we present the one
year safety and effectiveness data for the wAMD cohort (n=2112),
of whom 1829 patients had previous ranibizumab treatment (T1),
and 275 patients had no prior ranibizumab treatment (T2). 8 patients
were previously managed with other ocular treatments (pre-treatment
status defined by the primary treated eye)
Results: At baseline, mean age was 79.2 years, 61.7% were female,
93.0% were Caucasian. Mean visual acuity (VA), as early treatment
diabetic retinopathy study (ETDRS) letter scores, was higher and
central retinal thickness (CRT) was lower for T1 than T2 at baseline
(letter scores 60.3 and 52.4, CRT 255.0 and 339.7 mm, respectively).
There were no new safety findings reported at the end of the first
year, with low rates of ocular (0.4% [T1]; 1.1% [T2]) and non-ocular
serious adverse events (8.26% [T1]; 4.73% [T2]). Low rates of
endophthalmitis (0.11% [T1]; 0.36% [T2]), cerebrovascular accident
(0.22% [T1]; 0.36% [T2]) and myocardial infarction (0.66% [T1];
0% [T2]) were observed. None of the 37 deaths during the first
year of the study (1.7%) were suspected to be related to study drug/
injection procedure. At year one, T2 group letter score gain was 4.1
letters, whilst the T1 group maintained their initial higher baseline
level VA (-1.1 letter score change). T1 and T2 groups received a
mean of 5.2 injections over 7.4 and 7.5 visits, respectively
Conclusions: The outcomes from the first year follow up of
LUMINOUS wAMD patients in real-world settings reinforce the
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
well-established efficacy and safety profile of ranibizumab. No new
safety findings were observed in this first one year interim analysis of
the LUMINOUS study
Commercial Relationships: Paul Mitchell, Abbott (C), Abbott
(R), Allergan (C), Allergan (R), Bayer (C), Bayer (R), Novartis (C),
Novartis (R)
Clinical Trial: NCT01318941
Program Number: 3063
Presentation Time: 11:30 AM–11:45 AM
Patients undergoing treatment for wet age-related macular
degeneration in one eye rarely present for an unscheduled
emergent office visit when they develop wet AMD in their second
eye.
Sabrina Prabakaran1, 2, Steven M. Cohen1, 2. 1Morsani College of
Medicine, USF, Tampa, FL; 2Retina Vitreous Associates of Florida,
Tampa, FL.
Purpose: Patients with wet AMD in one eye are at risk of developing
wet AMD in the second eye and are advised to present immediately
should vision changes occur. This study is to determine if patients
who are being treated regularly for wet age-related macular
degeneration (AMD) in one eye present for an unscheduled emergent
office visit when they develop wet AMD in their second eye.
Methods: This is a retrospective interventional case series. Charts
of patients undergoing treatment for wet AMD between January 1,
2010 and December 31, 2012 were reviewed to identify patients who
developed new onset wet AMD in the fellow eye. Patients who were
being examined less frequently then every 3 months and who had less
than 6 month follow-up from initiation of therapy in the second eye
were excluded.
Results: Twenty-five patients developed incident wet AMD in their
second eye while undergoing treatment in their first eye and also met
the inclusion criteria. At the time of development of wet AMD in the
second eye, the first eye was being treated on average, every 8 weeks.
Nine patients were being treated with bevacizumab and 16 with
ranabizumab. Only two (8%) of the patients made an unscheduled
emergency visit with the onset of wet AMD in their second eye. Prior
to the development of wet AMD, the second eye had the better visual
acuity in 14 (56%) patients, and had symptoms of vision change in 19
(76%) of patients.
Conclusions: Patients with unilateral wet AMD, who are at high
risk of developing wet AMD in their second eye, rarely present for
an unscheduled emergent office visit when they develop wet AMD
in their second eye. This finding supports more frequent screening
of patients with dry AMD who are at high risk of progressing to wet
AMD.
Commercial Relationships: Sabrina Prabakaran, None; Steven
M. Cohen, None
Program Number: 3064
Presentation Time: 11:45 AM–12:00 PM
Real-world observations of ranibizumab treatment for
neovascular age-related macular degeneration in patients from
Africa, Asia and the Middle East: Final results from the UNVEIL
study
Naresh Yadav1, Shelley diTommaso2, Hakyoung Kim3, Kgaogelo
Legodi4, Mohamed M. Mahgoub5, Viktoria Mester6, Eddy Wu2.
1
Narayana Nethralaya, Bangalore, India; 2Novartis Pharma
AG, Basel, Switzerland; 3Ophthalmology, Kangnam Sacred
Heart Hospital, Hallym University, Seoul, Republic of Korea;
4
Ophthalmology, Medforum Medi-clinic, Pretoria, South
Africa; 5Ophthalmology, Ain Shams University, Cairo, Egypt;
6
Ophthalmology, Samaya Specialized Center, Abu Dhabi, United
Arab Emirates.
Purpose: The UNVEIL study was a multicenter, 12-month,
prospective, non-interventional study that evaluated the effectiveness
and safety profile of ranibizumab in the treatment of neovascular
age-related macular degeneration (nAMD) during real-life clinical
practice, in patients from Egypt, India, United Arab Emirates,
Lebanon, Kuwait, Philippines, South Africa and South Korea.
Methods: Patients were treated with ranibizumab (0.5 mg) for
nAMD according to their usual local treatment practices. The primary
study endpoint was the mean change in best-corrected visual acuity
(BCVA) from baseline to month 3 (ETDRS letters). Secondary
endpoints included the mean change in BCVA from baseline to month
12; the mean change in central retinal thickness (CRT) at 3 and 12
months, and the number of adverse events (AEs). Results are reported
as the mean ± standard deviation and ‘n’ denotes the number of
treated eyes.
Results: A total of 901 nAMD patients (age 67 ± 12.07 years)
participated in the study and 505 patients completed the study. BCVA
was 62.3 ± 22.59 letters at baseline (n = 842). This increased by 8.0
± 13.87 (n = 667, p<0.001) and 7.5 ± 16.26 letters (last observation
carried forward [LOCF], n = 768, p<0.001) at months 3 and 12,
respectively. CRT was 350.5 ± 142.38 mm at baseline (n = 678) and
decreased by 97.3 ± 134.98 (n = 444, p<0.001) and 88.6 ± 141.21
mm (LOCF, n = 460, p<0.001) at months 3 and 12, respectively. The
mean number of injections per treated eye during the loading phase
(months 0-2) and maintenance phase (months 3-12) was 2.3 ± 0.73
(n = 906) and 1.6 ± 1.19 (n = 444), respectively. AEs were reported
in 69 patients (7.7%) with 27 patients (3%) reporting ocular-related
AEs. Fifteen serious AEs were observed in 12 patients (1.3%). One
serious AE, retinal hemorrhage, was suspected to be injection related.
Conclusions: This is the first large-scale, multicenter, real-life study
to investigate the effectiveness and safety profile of ranibizumabtreated nAMD patients across these countries. Despite the wide
variations in healthcare infrastructures and a relatively lower mean
injection number than published observational studies from Western
societies, real-life ranibizumab treatment resulted in significant gains
in vision, morphological improvements, and a low incidence of AEs.
Commercial Relationships: Naresh Yadav, Novartis Pharma AG
(F); Shelley diTommaso, Novartis Pharma AG (E); Hakyoung
Kim, Novartis Pharma AG (F), Novartis Pharma AG (R); Kgaogelo
Legodi, Novartis Pharma AG (F), Novartis Pharma AG (R);
Mohamed M. Mahgoub, Novartis Pharma AG (F), Novartis Pharma
AG (R); Viktoria Mester, Novartis Pharma AG (F), Novartis Pharma
AG (R); Eddy Wu, Novartis Pharma AG (E)
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
Program Number: 3065
Presentation Time: 12:00 PM–12:15 PM
Real World Vision Outcomes in DME Treated with Anti-VEGF
Injections – An Analysis of EMR Data From a Large Health
System
Joanna Campbell1, Ashley L. Cole7, Arghavan Almony2, Herbert
Ingraham3, Nancy M. Holekamp4, 5, Steven Marks3, Hitesh
Chandwani1, Jonathan W. Kowalski1, Szilard Kiss6. 1GHOSR,
Allergan, Irvine, CA; 2Carolina Eye Associates, Southern Pines,
NC; 3Ophthalmology, Geisinger Health System, Danville, PA;
4
The Pepose Vision Institute, Chesterfield, MO; 5Ophthalmology,
Washington University School of Medicine, St Louis, MO;
6
Ophthalmology, Weill Cornell Medical College, New York, NY;
7
CHDA, Allergan, Irvine, CA.
Purpose: Prior studies have demonstrated less frequent anti-vascular
endothelial growth factor (anti-VEGF) utilization in retinal diseases
in clinical practice compared with landmark randomized controlled
trials (RCTs). The purpose of this study is to further assess real-world
vision outcomes for anti-VEGFs in the treatment of Diabetic Macular
Edema (DME).
Methods: This is a retrospective study of electronic medical records
from an integrated health system in the United States. Eyes of DME
patients receiving initial treatment with intravitreal ranibizumab
or bevacizumab from Jan 2007 to May 2012 were included, with
corrected visual acuity (CVA) from 20/40-20/400 at index treatment
(baseline) and ≥2 visits within the 12-month follow-up. Data from
missing visits (but not invalid data at visits) were imputed by last
observation carried forward (LOCF). Snellen visual acuities were
converted to the Early Treatment Diabetic Retinopathy Study
(ETDRS) scale using a published algorithm. The number of antiVEGF injections, change in CVA from baseline, and proportions of
eyes improving or losing ≥2 or ≥3 lines were assessed at 12 months.
Analyses were performed on observed and LOCF data.
Results: One hundred and three eyes met the inclusion criteria with
mean (SD) CVA of 53.8 (15.0) letters at baseline. Eighty-two eyes
had a follow-up visit at 6 months, with 77 eyes at 12 months. At 12
months: the mean number of anti-VEGF injections was 2.7; mean
change in CVA was 5.4 letters (LOCF); proportions of eyes gaining
≥2 and ≥3 lines were 28.9% and 24.1% (LOCF); and the proportions
of eyes losing ≥2 and ≥3 lines were 14.5% and 10.8%, respectively.
Outcomes in the observed population were similar to LOCF (Table
1).
Conclusions: In this large health care system retrospective study,
frequency of intravitreal injections and subsequent visual acuity
improvement in clinical practice are lower than reported in landmark
RCTs like RISE/RIDE. Prior studies demonstrating less frequent
DME anti-VEGF injections than in RCTs hypothesized that vision
improvement might also be lower. This study links less frequent
anti-VEGF injections to less visual acuity improvement. Additional
research is needed to assess factors that may affect utilization of antiVEGF injections, and patient characteristics that may affect vision
outcomes such as underlying diabetes control.
Table 1. DME Vision Outcomes at 12 Months
Commercial Relationships: Joanna Campbell, Allergan Inc (E);
Ashley L. Cole, Allergan Inc (E); Arghavan Almony, Allergan
Inc (C); Herbert Ingraham, Geisinger Health System (E); Nancy
M. Holekamp, Allergan Inc (C), Allergan Inc (R), Genentech (C),
Genentech (R), Regeneron (C), Regeneron (R); Steven Marks,
Geisinger Health System (E); Hitesh Chandwani, Allergan Inc (E);
Jonathan W. Kowalski, Allergan Inc (E); Szilard Kiss, Alimera
(C), Alimera (R), Allergan (F), Allergan Inc (C), Allergan Inc (R),
Genentech (C), Genentech (F), Genentech (R), Regeneron (C),
Regeneron (F), Regeneron (R)
Program Number: 3066
Presentation Time: 12:15 PM–12:30 PM
United Kingdom Neovascular AMD Database study: Time to
reactivation after a pause in treatment - outcomes from 92,000
intravitreal ranibizumab injections
Pearse A. Keane1, Martin McKibbin3, Aaron Y. Lee1, Usha
Chakravarthy2, Robert Johnston4, Catherine A. Egan1, Dawn A. Sim1,
Javier Zarranz-Ventura5, Adnan Tufail1. 1NIHR Biomedical Research
Centre for Opht, Moorfields Eye Hospital NHS Foundation Trust,
London, United Kingdom; 2Ctr for Vascular & Vision Sciences,
Queen’s University, Belfast, United Kingdom; 3Ophthalmology,
St. James’s University Hospital, Leeds, United Kingdom; 4Retinal
Service, Cheltenham General Hospital, Cheltenham, United
Kingdom; 5Retina Service, Bristol Eye Hospital, Bristol, United
Kingdom.
Purpose: To study time to reactivation in eyes that have not required
treatment for 3, 6, 9 and 12 months in a very large cohort of patients
and to evaluate visual outcomes in these eyes.
Methods: Participating centres collected clinical data using an
electronic medical record (EMR) system, with automatic extraction
of anonymized data to a database. Up to 5 years of data were
collected from each centre. Centres using EMR systems that collected
a minimum standard data set for eyes receiving ranibizumab therapy
for nAMD including visual acuity (ETDRS), were invited to submit
data, which were remotely extracted, anonymized and analyzed.
Patients were treated with 3 loading injections at monthly intervals
and then followed with a prn retreatment regimen.
Results: A total of 92,976 ranibizumab treatment episodes from
12952 treated eyes associated with over 300000 clinic visits were
collated from treatment naive eyes within a month of starting the
study. The dataset was explored to identify eyes that had a treatment
free interval of 6,9,or 12 months and Kaplan Meier graphs were
generated to explore the time to reactivation after this pause. The time
to reactivation for the 20th and 50th centile was 2.07/9.62 months
in the 6 month, 3.69/15.84 months in the 9 month and 5.90/22.49
months in the 12 month group.
Conclusions: EMR has the potential to collate very large volumes
of high quality data rapidly. This study provides times to reactivation
that have been clinically stable for certain length of time. These
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
outcomes will help inform rationale design of treat-and-extend
regimes and guide follow up intervals patients should be reviewed at
who have remained stable for a certain period.
Commercial Relationships: Pearse A. Keane, None; Martin
McKibbin, None; Aaron Y. Lee, None; Usha Chakravarthy, None;
Robert Johnston, Medisoft (E); Catherine A. Egan, None; Dawn
A. Sim, None; Javier Zarranz-Ventura, None; Adnan Tufail,
Alcon (C), Allergan (C), Bayer (C), Heidelberg Engineering (C),
Novartis (C), Oculogics (C), Pfizer (C), Roche (C), Thrombogenics
(C)
Program Number: 3067
Presentation Time: 12:30 PM–12:45 PM
The Home Monitoring of the Eye (HOME) Study: Potential
implication of Findings on Management of Intermediate AMD
Patients
Alexander J. Brucker. Scheie Eye Institute, Philadelphia, PA.
Purpose: To determine whether home monitoring with the
ForeseeHome device (Notal Vision Ltd, Israel), using hyperacuity
visual field and telemonitoring, results in earlier detection of agerelated macular degeneration–associated choroidal neovascularization
(CNV), when compared with standard care.
Methods: 1,970 participants age 53 to 90 years at high risk of
developing CNV were screened. Of these, 1520 participants with
a mean age of 72.5 years were enrolled in the HOME study at 44
AREDS2 clinical centers and randomized to two arms.
Instructions were provided to participants in both arms for selfmonitoring vision at home followed by report of new symptoms to
the clinic. Participants in the device arm were also asked to perform
daily device testing. When prompted by changes in device test
results the device monitoring center contacted clinical centers, which
contacted participants for examination.
The primary outcome was the difference in best-corrected visual
acuity between baseline and detection of CNV. CNV events were
determined by investigators using FA and OCT. A secondary outcome
compared the productivity of various alerting modalities in detecting
CNV.
Results: Mean follow-up was 1.4 years between July 2010 and April
2013. At the prespecified interim analysis, 82 participants progressed
to CNV, 51 in the device arm and 31 in the standard care arm.
Participants in the device arm had a smaller decline in visual acuity
from baseline to CNV detection (median, -4 letters; interquartile
range [IQR], -11.0 to -1.0 letters) compared with standard care
(median, -9 letters; IQR, -14.0 to -4.0 letters; P = 0.021). The
Data and Safety Monitoring Committee recommended early study
termination for efficacy. During the analysis period, participants in
the device arm had 263 device alert visits, 55 visits prompted by
symptoms and an estimated 1802 standard care office visits. CNV
was diagnosed at 26, 11 and 14 of these visits, respectively. CNV
events were diagnosed at 10%, 20%, and 0.8% of device alerts,
symptom alerts and standard care visits, respectively.
Conclusions: Persons at high risk for CNV benefit from the home
monitoring strategy for earlier detection of CNV. The productivity of
an office visit prompted by a device alert is far greater than a routine
office visit in identifying new onset CNV
Commercial Relationships: Alexander J. Brucker, None
Support: Notel Vision
Clinical Trial: NCT 01010997
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.