A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-related Macular Degeneration (HARBOR)

NCT ID: NCT00891735

Last Updated: 2013-01-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1097 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-31

Study Completion Date

2012-08-31

Brief Summary

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This is a Phase III, multicenter, randomized, double-masked, dose-comparison study of the efficacy and safety of ranibizumab injection administered intravitreally to patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Results are presented for the first 12 months of the study.

Detailed Description

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Conditions

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Age-related Macular Degeneration

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Ranibizumab 0.5 mg monthly

Patients received ranibizumab 0.5 mg monthly administered intravitreally for 24 months.

Group Type EXPERIMENTAL

Ranibizumab

Intervention Type DRUG

Sterile solution for intravitreal injection.

Ranibizumab 2.0 mg monthly

Patients received ranibizumab 2.0 mg monthly administered intravitreally for 24 months.

Group Type EXPERIMENTAL

Ranibizumab

Intervention Type DRUG

Sterile solution for intravitreal injection.

Ranibizumab 0.5 mg as-needed (pro re nata [PRN])

Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 21 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.

Group Type EXPERIMENTAL

Ranibizumab

Intervention Type DRUG

Sterile solution for intravitreal injection.

Ranibizumab 2.0 mg as-needed (pro re nata [PRN])

Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 21 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.

Group Type EXPERIMENTAL

Ranibizumab

Intervention Type DRUG

Sterile solution for intravitreal injection.

Interventions

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Ranibizumab

Sterile solution for intravitreal injection.

Intervention Type DRUG

Other Intervention Names

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Lucentis

Eligibility Criteria

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Inclusion Criteria

* For sexually active women of childbearing potential, agreement to the use of an appropriate form of contraception (or abstinence) for the duration of the study.


* Best corrected visual acuity (BCVA), using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, of 20/40-20/320 (Snellen equivalent).
* Choroidal neovascularization (CNV) lesions with classic CNV component, occult CNV, or with some classic CNV component were permissible.
* Total area of lesion \< 12 disc area or 30.48 mm\^2.

Exclusion Criteria

* History of vitrectomy surgery, submacular surgery, or other surgical intervention for age-related macular degeneration (AMD) in the study eye.
* Prior treatment with Visudyne(R), external-beam radiation therapy, or transpupillary thermotherapy (TTT) in the study eye.
* Previous intravitreal drug delivery (eg, intravitreal corticosteroid injection, anti-angiogenic drugs, or device implantation) in the study eye.
* Previous treatment or participation in a clinical trial involving anti-angiogenic drugs (Avastin(R), anecortave acetate, protein kinase C inhibitors, etc), in the non-study eye within 3 months of Day 0 (first day of treatment). The patient may not have received Lucentis(R) or Macugen(R) in the non-study eye within 7 days of Day 0.
* Treatment with Visudyne(R) in the non-study eye \< 7 days preceding Day 0.
* Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either \> 50% of the total area of the lesion or \> 1 disc area (2.54 mm\^2) in size.
* Subfoveal fibrosis or atrophy in the study eye.
* CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia.
* Retinal pigment epithelial tear involving the macula in the study eye.
* Any concurrent intraocular condition in the study eye (eg, cataract or diabetic retinopathy) that, in the opinion of the investigator, could either: Require medical or surgical intervention during the 24-month study period to prevent or treat visual loss that might result from that condition; or if allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity (BCVA) over the 24-month study period.
* Uncontrolled blood pressure.
* Atrial fibrillation not managed by patient's primary care physician or cardiologist within 3 months of screening visit.
* History of stroke within the last 3 months of screening visit.
* History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications.
* Current treatment for active systemic infection.
* Active malignancy.
* History of allergy to fluorescein, not amenable to treatment.
* Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals).
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

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Phoenix, Arizona, United States

Site Status

Tucson, Arizona, United States

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Arcadia, California, United States

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Beverly Hills, California, United States

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Campbell, California, United States

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Chico, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Mountain View, California, United States

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Oakland, California, United States

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Palm Desert, California, United States

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Poway, California, United States

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Sacramento, California, United States

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San Francisco, California, United States

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San Francisco, California, United States

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Santa Ana, California, United States

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Santa Barbara, California, United States

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Torrance, California, United States

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Ventura, California, United States

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Westlake Village, California, United States

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Aurora, Colorado, United States

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Colorado Springs, Colorado, United States

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Golden, Colorado, United States

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Danbury, Connecticut, United States

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Hamden, Connecticut, United States

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New Haven, Connecticut, United States

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New London, Connecticut, United States

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Altamonte Springs, Florida, United States

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Boynton Beach, Florida, United States

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Fort Lauderdale, Florida, United States

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Fort Myers, Florida, United States

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Palm Beach Gardens, Florida, United States

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Pensacola, Florida, United States

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Stuart, Florida, United States

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Tampa, Florida, United States

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Tampa, Florida, United States

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Winter Haven, Florida, United States

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Augusta, Georgia, United States

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‘Aiea, Hawaii, United States

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Chicago, Illinois, United States

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Oak Park, Illinois, United States

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Indianapolis, Indiana, United States

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Shawnee Mission, Kansas, United States

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Wichita, Kansas, United States

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Lexington, Kentucky, United States

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Paducah, Kentucky, United States

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Portland, Maine, United States

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Baltimore, Maryland, United States

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Hagerstown, Maryland, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Worcester, Massachusetts, United States

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Jackson, Michigan, United States

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Edina, Minnesota, United States

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St Louis, Missouri, United States

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Lincoln, Nebraska, United States

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Las Vegas, Nevada, United States

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Lawrenceville, New Jersey, United States

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New Brunswick, New Jersey, United States

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Northfield, New Jersey, United States

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Teaneck, New Jersey, United States

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Vauxhall, New Jersey, United States

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Great Neck, New York, United States

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Lynbrook, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Shirley, New York, United States

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Asheville, North Carolina, United States

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Charlotte, North Carolina, United States

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Beachwood, Ohio, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Camp Hill, Pennsylvania, United States

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Huntingdon Valley, Pennsylvania, United States

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Johnstown, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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West Mifflin, Pennsylvania, United States

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Greenville, South Carolina, United States

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Ladson, South Carolina, United States

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West Columbia, South Carolina, United States

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Rapid City, South Dakota, United States

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Nashville, Tennessee, United States

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Abilene, Texas, United States

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Austin, Texas, United States

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DeSoto, Texas, United States

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Houston, Texas, United States

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McAllen, Texas, United States

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San Antonio, Texas, United States

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Temple, Texas, United States

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The Woodlands, Texas, United States

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Salt Lake City, Utah, United States

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Richmond, Virginia, United States

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Virginia Beach, Virginia, United States

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Milwaukee, Wisconsin, United States

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Casper, Wyoming, United States

Site Status

Countries

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United States

References

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Tong N, Fan W, Su L, Ebraheem A, Uji A, Marion K, Sadda S. RELATIONSHIP BETWEEN OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS AND NUMBER OF INTRAVITREAL RANIBIZUMAB INJECTIONS IN EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN THE HARBOR STUDY. Retina. 2024 Oct 1;44(10):1696-1703. doi: 10.1097/IAE.0000000000004171.

Reference Type DERIVED
PMID: 39287532 (View on PubMed)

Kim S, Stockwell A, Qin H, Gao SS, Sagolla M, Stoilov I, Wuster A, Lai P, Yaspan BL, Jeanne M. Rare CIDEC coding variants enriched in age-related macular degeneration patients with small low-luminance deficit cause lipid droplet and fat storage defects. PLoS One. 2023 Apr 20;18(4):e0280484. doi: 10.1371/journal.pone.0280484. eCollection 2023.

Reference Type DERIVED
PMID: 37079518 (View on PubMed)

Adrean SD, Chaili S, Hill L, Amador-Patarroyo MJ. PATTERNS OF SUBRETINAL AND/OR INTRARETINAL FLUID RECURRENCE IN PATIENTS WHO RECEIVED AS-NEEDED RANIBIZUMAB THERAPY IN THE HARBOR TRIAL. Retina. 2023 Apr 1;43(4):624-631. doi: 10.1097/IAE.0000000000003708. Epub 2022 Dec 21.

Reference Type DERIVED
PMID: 36729084 (View on PubMed)

Staurenghi G, Cozzi M, Sadda S, Hill L, Gune S. Characteristics that Correlate with Macular Atrophy in Ranibizumab-Treated Patients with Neovascular Age-Related Macular Degeneration. Ophthalmol Retina. 2023 Apr;7(4):300-306. doi: 10.1016/j.oret.2022.11.002. Epub 2022 Nov 11.

Reference Type DERIVED
PMID: 36372347 (View on PubMed)

Lally DR, Hill L, Amador-Patarroyo MJ. Subretinal Fluid Resolution and Visual Acuity in Patients with Neovascular Age-Related Macular Degeneration: A HARBOR Post Hoc Analysis. Ophthalmol Retina. 2022 Nov;6(11):1054-1060. doi: 10.1016/j.oret.2022.05.026. Epub 2022 May 30.

Reference Type DERIVED
PMID: 35654363 (View on PubMed)

Sheth V, D'Rozario M, Gune S, Blotner S. Fluctuations in central foveal thickness and association with vision outcomes with anti-VEGF therapy for nAMD: HARBOR post hoc analysis. BMJ Open Ophthalmol. 2022 Mar 9;7(1):e000957. doi: 10.1136/bmjophth-2021-000957. eCollection 2022.

Reference Type DERIVED
PMID: 35342822 (View on PubMed)

Freund KB, Staurenghi G, Jung JJ, Zweifel SA, Cozzi M, Hill L, Blotner S, Tsuboi M, Gune S. Macular neovascularization lesion type and vision outcomes in neovascular age-related macular degeneration: post hoc analysis of HARBOR. Graefes Arch Clin Exp Ophthalmol. 2022 Aug;260(8):2437-2447. doi: 10.1007/s00417-022-05586-w. Epub 2022 Mar 3.

Reference Type DERIVED
PMID: 35239009 (View on PubMed)

Pawloff M, Bogunovic H, Gruber A, Michl M, Riedl S, Schmidt-Erfurth U. SYSTEMATIC CORRELATION OF CENTRAL SUBFIELD THICKNESS WITH RETINAL FLUID VOLUMES QUANTIFIED BY DEEP LEARNING IN THE MAJOR EXUDATIVE MACULAR DISEASES. Retina. 2022 May 1;42(5):831-841. doi: 10.1097/IAE.0000000000003385.

Reference Type DERIVED
PMID: 34934034 (View on PubMed)

Holekamp NM, Sadda S, Sarraf D, Guymer R, Hill L, Blotner S, Spicer G, Gune S. Effect of Residual Retinal Fluid on Visual Function in Ranibizumab-Treated Neovascular Age-Related Macular Degeneration. Am J Ophthalmol. 2022 Jan;233:8-17. doi: 10.1016/j.ajo.2021.06.029. Epub 2021 Jul 18.

Reference Type DERIVED
PMID: 34289338 (View on PubMed)

Javaheri M, Hill L, Ghanekar A, Stoilov I. Changes in Treatment-Naive Pigment Epithelial Detachments Associated With the Initial Anti-Vascular Endothelial Growth Factor Injection: A Post Hoc Analysis From the HARBOR Trial. JAMA Ophthalmol. 2021 Feb 1;139(2):219-223. doi: 10.1001/jamaophthalmol.2020.5130.

Reference Type DERIVED
PMID: 33331859 (View on PubMed)

Sadda SR, Abdelfattah NS, Lei J, Shi Y, Marion KM, Morgenthien E, Gune S, Balasubramanian S. Spectral-Domain OCT Analysis of Risk Factors for Macular Atrophy Development in the HARBOR Study for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2020 Oct;127(10):1360-1370. doi: 10.1016/j.ophtha.2020.03.031. Epub 2020 Apr 2.

Reference Type DERIVED
PMID: 32402555 (View on PubMed)

Khurana RN, Chang L, Day BM, Ghanekar A, Stoilov I. Timing of Peak Vision Gains in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab. Ophthalmol Retina. 2020 Aug;4(8):760-766. doi: 10.1016/j.oret.2020.02.011. Epub 2020 Feb 27.

Reference Type DERIVED
PMID: 32387055 (View on PubMed)

Li E, Donati S, Lindsley KB, Krzystolik MG, Virgili G. Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2020 May 5;5(5):CD012208. doi: 10.1002/14651858.CD012208.pub2.

Reference Type DERIVED
PMID: 32374423 (View on PubMed)

Khurana RN, Hill L, Ghanekar A, Gune S. Agreement of Spectral-Domain OCT with Fluorescein Leakage in Neovascular Age-Related Macular Degeneration: Post Hoc Analysis of the HARBOR Study. Ophthalmol Retina. 2020 Nov;4(11):1054-1058. doi: 10.1016/j.oret.2020.04.016. Epub 2020 Apr 28.

Reference Type DERIVED
PMID: 32353536 (View on PubMed)

Patel Y, Miller DM, Fung AE, Hill LF, Rosenfeld PJ. Are Dilated Fundus Examinations Needed for OCT-Guided Retreatment of Exudative Age-Related Macular Degeneration? Ophthalmol Retina. 2020 Feb;4(2):141-147. doi: 10.1016/j.oret.2019.09.006. Epub 2019 Sep 18.

Reference Type DERIVED
PMID: 31735634 (View on PubMed)

Khurana RN, Chang LK, Hill LF, Ghanekar A, Stoilov I. The Value of Prior Response to Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration: A HARBOR Subanalysis. Ophthalmol Retina. 2020 Jan;4(1):13-18. doi: 10.1016/j.oret.2019.06.008. Epub 2019 Jul 5.

Reference Type DERIVED
PMID: 31416763 (View on PubMed)

Nassisi M, Lei J, Abdelfattah NS, Karamat A, Balasubramanian S, Fan W, Uji A, Marion KM, Baker K, Huang X, Morgenthien E, Sadda SR. OCT Risk Factors for Development of Late Age-Related Macular Degeneration in the Fellow Eyes of Patients Enrolled in the HARBOR Study. Ophthalmology. 2019 Dec;126(12):1667-1674. doi: 10.1016/j.ophtha.2019.05.016. Epub 2019 May 29.

Reference Type DERIVED
PMID: 31281056 (View on PubMed)

Hallak JA, de Sisternes L, Osborne A, Yaspan B, Rubin DL, Leng T. Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration: Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2019 Jul 1;137(7):738-744. doi: 10.1001/jamaophthalmol.2019.0868.

Reference Type DERIVED
PMID: 31021381 (View on PubMed)

Sarraf D, London NJ, Khurana RN, Dugel PU, Gune S, Hill L, Tuomi L. Ranibizumab Treatment for Pigment Epithelial Detachment Secondary to Neovascular Age-Related Macular Degeneration: Post Hoc Analysis of the HARBOR Study. Ophthalmology. 2016 Oct;123(10):2213-24. doi: 10.1016/j.ophtha.2016.07.007. Epub 2016 Aug 23.

Reference Type DERIVED
PMID: 27566855 (View on PubMed)

Frenkel RE, Shapiro H, Stoilov I. Predicting vision gains with anti-VEGF therapy in neovascular age-related macular degeneration patients by using low-luminance vision. Br J Ophthalmol. 2016 Aug;100(8):1052-7. doi: 10.1136/bjophthalmol-2015-307575. Epub 2015 Nov 5.

Reference Type DERIVED
PMID: 26541435 (View on PubMed)

Busbee BG, Ho AC, Brown DM, Heier JS, Suner IJ, Li Z, Rubio RG, Lai P; HARBOR Study Group. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013 May;120(5):1046-56. doi: 10.1016/j.ophtha.2012.10.014. Epub 2013 Jan 23.

Reference Type DERIVED
PMID: 23352196 (View on PubMed)

Other Identifiers

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GX01511

Identifier Type: OTHER

Identifier Source: secondary_id

FVF4579g

Identifier Type: -

Identifier Source: org_study_id

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