Clinical trial NCT05850520: A Study to Learn How Well a Higher Amount of Aflibercept Given as an Injection Into the Eye Works and How Safe it is in People With Reduced Vision Due to Swelling in the Macula, Central Part of the Retina Caused by a Blocked Vein in the Retina (Macula Edema Secondary to Retinal Vein Occlusion)
Official title: Randomized, Double-Masked, Active-Controlled, Phase 3 Study of the Efficacy and Safety of Aflibercept 8 mg in Macular Edema Secondary to Retinal Vein Occlusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Macular Edema Secondary to Retinal Vein Occlusion
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2023-05-09
Enrollment: 892
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Researchers are looking for a better way to treat people who have macular edema secondary to retinal vein occlusion (RVO).

In people with RVO, a blood vessel that carries blood away from the retina (vein) becomes blocked. The retina is the very back part of the eye. The blocked vein causes fluid and blood to leak into the retina and thereby causes a swelling of the macula (the center of the retina responsible for fine vision). This swelling is called macular edema.

When a vein in the retina is blocked, the levels of a protein called vascular endothelial growth factor (VEGF) rises. VEGF helps the growth of new blood vessels. This can lead to macular edema and may cause the vision to become blurry.

The study treatment intravitreal (IVT) aflibercept is given as an injection into the eye. It works by blocking VEGF and this can help repair vision problems related to RVO. IVT aflibercept is already available and is prescribed by doctors as the standard of care treatment for macula edema secondary to RVO. Standard of care is a treatment that medical experts consider most appropriate for a disease.

Standard of care is given every 4 weeks in people with macula edema secondary to RVO. While repeated injections of aflibercept may prevent worsening of vision, it may place a burden on the patient. However, a higher amount (8 mg) compared to the standard of care (2 mg) of IVT aflibercept is being tested in studies. This higher amount could be given less often. The amount of IVT aflibercept given is measured in milligrams, also known as mg.

The main purpose of this study is to learn how well a higher amount of the study treatment aflibercept works in people with macular edema secondary to RVO. To answer this, researchers will measure changes in vision called best corrected visual acuity (BCVA) in the study participants between study start and after 36 weeks of treatment. Changes will then be compared between those participants who received the higher amount of IVT aflibercept and those that received standard of care.

To learn how safe the study treatment is in the participants, the researchers will count the number of participants from study start and up to 64 weeks later that have:

* adverse events
* serious adverse events

"Adverse events" are any medical problems that the participants have during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think they might be related to the study treatments. An adverse event is considered "serious" when it leads to death, puts the participants' lives at risk, requires hospitalization, causes disability, causes a baby being born with medical problems or is otherwise medically important.

Dependent on the treatment group, the participants will either receive the higher amount of aflibercept or standard of care as an intravitreal injection for up to 60 weeks. The study will consist of a test (screening) phase, a treatment phase and an end of study phase. Each participant will be in the study for up to 64 weeks.

One visit to the study site is planned during the screening phase, followed by visits approximately every 4 weeks (16 in total) during treatment and one visit at the end of the study.

During the study, the study doctors and their team will:

* check patients' eye health using various eye examination techniques
* measure patients' eye vision (BCVA)
* take blood and urine samples
* do physical examinations
* check vital signs
* examine heart health using electrocardiogram (ECG)
* do pregnancy tests in women of childbearing age

In addition, participants will be asked to fill a questionnaire on vision-related quality of life.


Eligibility criteria: Inclusion Criteria:

* Adult ≥18 years of age (or country's legal age of adulthood if the legal age is \>18 years) at the time of signing the informed consent.
* Treatment-naïve macular edema involving the foveal center secondary to RVO (BRVO, HRVO, or CRVO) diagnosed within 16 weeks (112 days) before the screening visit in the study eye.
* Early Treatment Diabetic Retinopathy Study BCVA letter score of 73 to 24 (20/40 to 20/320) at screening and baseline visits in the study eye.

Decrease in BCVA determined to be primarily the result of RVO in the study eye.

* Mean CST ≥300 μm on optical coherence tomography (OCT) if excluding Bruch's membrane (e.g., Cirrus or Topcon) or ≥320 μm if including Bruch's membrane (e.g., Heidelberg Spectralis), confirmed by the reading center at the screening visit and by the site at baseline visit in the study eye.
* Capable of giving signed informed consent form (ICF) by study participant or legally acceptable representative, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
* US participants will be required to have a Health Insurance Portability and Accountability Act (HIPAA) authorization; in other countries, as applicable according to national laws.
* Women of childbearing potential (WOCBP) or men who are sexually active with partners of childbearing potential must agree to use highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last administration of study intervention. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for participation in clinical studies and fulfil the conditions set on Section 10.4.2.

Exclusion Criteria:

* Concurrent disease that causes substantial decrease of BCVA, is expected to limit BCVA recovery or is likely to require medical or surgical intervention during the study in the study eye.
* Presence or history of the following ocular conditions:

  1. Advanced age-related macular degeneration (neovascular AMD or geographic atrophy) in the study eye.
  2. Diabetic macular edema or diabetic retinopathy, defined in diabetic participants as diabetic retinopathy lesions outside the area of the vein occlusion in the study eye and anywhere in the retina in the fellow eye.
  3. Anterior segment neovascularization, vitreous hemorrhage, retinal detachment in the study eye.
  4. Vitreomacular traction, epiretinal membrane or structural damage to the macula that is considered by the Investigator to significantly affect central vision or preclude improvement in vision in the study eye.
  5. Macular hole of stage 2 and above in the study eye.
  6. Myopia of a spherical equivalent of at least 8 diopters prior to any refractive or cataract surgery in the study eye.
  7. Corneal transplant or corneal dystrophy in the study eye.
  8. Idiopathic or autoimmune uveitis in the study or in the fellow eye.
* Presence of the following ocular conditions at screening or baseline visit:

  1. Significant media opacities, including cataract, that interfere with BCVA, or imaging assessments (e.g., fundus photography \[FP\], OCT) in the study eye.
  2. Aphakia, or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium-aluminum-garnet \[YAG\] posterior capsulotomy performed more than 30 days before the screening visit), in the study eye.
  3. Uncontrolled glaucoma (defined as IOP \>25 mmHg despite treatment with anti-glaucoma medication); or history or likely future need of glaucoma surgery in the study eye.
  4. Intraocular inflammation/infection (including trace, or above, cells in the anterior chamber and/or vitreous) within 12 weeks (84 days) of the screening visit in the study or in the fellow eye.
  5. Extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in the study or in the fellow eye.
* Uncontrolled blood pressure (defined as systolic \>160 mmHg or diastolic \>95 mmHg) at the screening visit or baseline visit.
* Uncontrolled diabetes mellitus, defined by hemoglobin A1c (HbA1c) \>12% at the screening visit.
* History of cerebrovascular accident or myocardial infarction within 24 weeks (168 days) before the screening visit or between screening and baseline visits.
* Renal failure requiring dialysis, or renal transplant at screening or potentially during the study.
* Any prior or concomitant ocular or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for RVO in the study eye.
* Previous administration of systemic anti-angiogenic medications for any condition.
* Prior treatment of the study eye with any of the following drugs (any route of ophthalmic administration) or procedures:

  1. Anti-angiogenic drugs at any time including investigational therapy (e.g., with anti-angiopoietin/anti-VEGF bispecific monoclonal antibodies).
  2. Previous use topical steroids within 4 weeks (28 days) from the screening visit, or intraocular or periocular steroids within 16 weeks (112 days) from the screening visit, or steroid implants at any time.
  3. Previous treatment with intraocular or periocular implant, gene therapy, or cell therapy at any time.
  4. Treatment with ocriplasmin at any time.
  5. Vitreoretinal surgery (including scleral buckling) at any time.
  6. Any intraocular surgery, including cataract surgery, within 12 weeks (84 days) before the screening visit.
  7. Previous treatment with retinal laser photocoagulation.
* Prior treatment of the fellow eye with any of the following:

  a. Gene therapy, or cell therapy in the fellow eye at any time.
* Participation in other clinical studies requiring administration of investigational treatments (other than vitamins and minerals) at the time of screening visit, or within 30 days or 5 half-lives of administration of the previous study intervention, whichever is longer.

Primary outcomes:
measure: Change from baseline in BCVA measured by the ETDRS letter score at Week 36
timeFrame: At Week 36
Secondary outcomes:
measure: Number of active injections from baseline to Week 64
timeFrame: From baseline to Week 64
measure: Number of active injections from baseline to Week 36
timeFrame: From baseline to Week 36
measure: Change from baseline in BCVA measured by the ETDRS letter score at Week 44
timeFrame: At baseline, week 44
measure: Change from baseline in BCVA measured by the ETDRS letter score at Week 64
timeFrame: At baseline, week 64
measure: Number of participants gaining at least 15 letters in BCVA from baseline at Weeks 36 and 64
timeFrame: From baseline at week 36 and week 64
measure: Number of participant achieving an ETDRS letter score of at least 69 (approximate 20/40 Snellen equivalent) at Weeks 36 and 64
timeFrame: At week 36 and week 64
measure: Participant having no IRF and no SRF in the center subfield at Weeks 36 and 64 (yes/no)
timeFrame: At week 36 and week 64
measure: Change from baseline in CST at Weeks 36 and 64
timeFrame: At baseline, week 36 and week 64
measure: Change from baseline in NEI VFQ 25 total score at Weeks 36 and 64
timeFrame: At baseline, week 36 and week 64
measure: Number of participant with TEAEs and SAEs through Weeks 36 and 64
timeFrame: Through weeks 36 and 64
measure: Participants dosed only Q8W through Week 36 in the 8 mg Q8W group
timeFrame: Through weeks 36
measure: Participants having last treatment intervals ≥12 or of 16 weeks at Week 64
timeFrame: At week 64
measure: Participants having next intended interval ≥12 or of 16 weeks at Week 64
timeFrame: At week 64
measure: Systemic exposure to aflibercept as assessed by plasma concentrations of free, adjusted bound and total aflibercept from baseline through Weeks 36 and 64
timeFrame: From baseline through weeks 36 and 64
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Retina Consultants of Orange County - Fullerton
state: California
city: Long Beach
country: United States
facility: South Coast Retina - Long Beach
state: California
city: Mountain View
country: United States
facility: Northern California Retina Vitreous Associates - Mountain View Office
state: California
city: Palm Springs
country: United States
facility: Southern California Desert Retina Consultants - Palm Springs Office
state: California
city: Pasadena
country: United States
facility: Azul Vision Pasadena
state: California
city: Redlands
country: United States
facility: Retina Consultants of Southern California
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado, PC
state: Colorado
city: New London
country: United States
facility: New England Retina Associates
state: Connecticut
city: Deerfield Beach
country: United States
facility: Rand Eye Institute
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute - Fort Myers
state: Florida
city: Largo
country: United States
facility: The Eye Institute of West Florida
state: Florida
city: Melbourne
country: United States
facility: Florida Eye Associates - Melbourne Main Office
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute - Orlando
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute - Pensacola
state: Florida
city: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of Florida - Saint Petersburg
state: Florida
city: Stuart
country: United States
facility: East Florida Eye Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease - Winter Haven
state: Florida
city: Marietta
country: United States
facility: Marietta Eye Clinic
state: Georgia
city: Elmhurst
country: United States
facility: Retina Associates - Elmhurst
state: Illinois
city: Oak Forest
country: United States
facility: University Retina and Macula Associates
state: Illinois
city: Lenexa
country: United States
facility: Retina Associates - Lenexa
state: Kansas
city: Baltimore
country: United States
facility: Retina Care Center
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants | Hagerstown, MD
state: Maryland
city: Hagerstown
country: United States
facility: Mid Atlantic Retina Specialists - Hagerstown
state: Maryland
city: Grand Rapids
country: United States
facility: Vitreo-Retinal Associates, PC
state: Michigan
city: Saint Louis Park
country: United States
facility: RCM - St. Louis Park Retina Clinic
state: Minnesota
city: Las Vegas
country: United States
facility: Retina Consultants of Nevada - Summerlin
state: Nevada
city: Bloomfield
country: United States
facility: Retina Center of New Jersey
state: New Jersey
city: New Brunswick
country: United States
facility: NJ Retina - New Brunswick
state: New Jersey
city: Teaneck
country: United States
facility: NJ Retina | Teaneck
state: New Jersey
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico - Albuquerque - Retina Center
state: New Mexico
city: Great Neck
country: United States
facility: Long Island Vitreoretinal Consultants - Great Neck
state: New York
city: Hauppauge
country: United States
facility: Vitreoretinal Consultants of NY - Hauppauge
state: New York
city: Lynbrook
country: United States
facility: Ophthalmic Consultants of Long Island
state: New York
city: Rochester
country: United States
facility: Retina Associates of Western New York
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill (UNC) | Ophthalmology
state: North Carolina
city: Blue Ash
country: United States
facility: Cincinnati Eye Institute - Blue Ash
state: Ohio
city: Dublin
country: United States
facility: Midwest Retina - Main Office
state: Ohio
city: Salem
country: United States
facility: Retina Consultants, LLC
state: Oregon
city: Philadelphia
country: United States
facility: Mid Atlantic Retina - Philadelphia / Wills Eye Hospital
state: Pennsylvania
city: Florence
country: United States
facility: Palmetto Retina Center, LLC - Florence
state: South Carolina
city: Ladson
country: United States
facility: Retina Consultants of South Carolina - Ladson
state: South Carolina
city: Memphis
country: United States
facility: Charles Retina Specialists - Germantown
state: Tennessee
city: Austin
country: United States
facility: Austin Retina Associates - Central
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas - Bellaire
state: Texas
city: Fort Worth
country: United States
facility: Texas Retina Associates
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates - Northwest
state: Texas
city: San Antonio
country: United States
facility: Retina Consultants of Texas - San Antonio Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Rocky Mountain Retina Consultants - Main Office
state: Utah
city: Fairfax
country: United States
facility: The Retina Group of Washington | Fairfax
state: Virginia
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Albury
country: Australia
facility: Eyeclinic Albury Wodonga
state: New South Wales
city: Parramatta
country: Australia
facility: Marsden Eye Surgery Center
state: New South Wales
city: Strathfield
country: Australia
facility: Strathfield Retina Clinic
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Eye Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Retina Clinic
state: New South Wales
city: Westmead
country: Australia
facility: Sydney West Retina Pty Ltd
state: New South Wales
city: Adelaide
country: Australia
facility: Adelaide Eye and Retina Centre
state: South Australia
city: Hobart
country: Australia
facility: Hobart Eye Surgeons
state: Tasmania
city: East Melbourne
country: Australia
facility: Centre for Eye Research
state: Victoria
city: Nedlands
country: Australia
facility: Lion Eye Institute
state: Western Australia
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt am Wörthersee
state: Kärnten
city: Linz
country: Austria
facility: Konventhospital Barmherzige Brüder Linz
state: Oberösterreich
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Steiermark
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Wien
country: Austria
facility: Hanusch-Krankenhaus Wien
city: Sofia
country: Bulgaria
facility: SEHAT Pentagram
city: Sofia
country: Bulgaria
facility: Specialized Hospital For Active Treatment of Eye Diseases Zora
city: Varna
country: Bulgaria
facility: Spec. Hosp. of Ophthalm. Disease for Active Treatment Varna
city: Hefei
country: China
facility: The Second Hospital of Anhui medical university
state: Anhui
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou Aier Eye Hospital
state: Guangdong
city: Hebei
country: China
facility: Hebei eye hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Shijiazhuang General Hospital
state: Hebei
city: Henan
country: China
facility: Henan Provincial Eye Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech.
state: Hubei
city: Changchun
country: China
facility: Eye Center of the second Bethune Hospital, jinlin University
state: Jilin
city: Shenyang
country: China
facility: The Fourth People's Hospital of Shenyang
state: Liaoning
city: Shenyang
country: China
facility: Aier Eye Hospital (LIAONING)
state: Liaoning
city: Ningxia
country: China
facility: People's Hospital of Ningxia Hui Autonomous Region - Opthalmology
state: Ningxia
city: Shanxi
country: China
facility: Shanxi Eye Hospital
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hosp., Shandong Univ.
state: Shandong
city: Chengdu
country: China
facility: Aier Eye Hospital (Chengdu)
state: Sichuan
city: Hangzhou
country: China
facility: ZheJiang Provincial People's Hospital
state: Zhejiang
city: Jinhua
country: China
facility: Dongyang People's Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Aier Intech Eye Hospital
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Beijing
country: China
facility: Capital Medical University (CMU) - Beijing Tongren Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital CAMS
city: Chongqing
country: China
facility: Chongqing Aier Ophthalmology Hospital
city: Lanzhou
country: China
facility: Lanzhou University - The Second Hospital (The Second Clinical Medical College of Lanzhou University)
city: Tianjin
country: China
facility: Tianjin Medical University Eye Hospital
city: Hradec Kralove
country: Czechia
facility: Fakultní Nemocnice Hradec Kralové
city: Ostrava
country: Czechia
facility: Fakultní nemocnice Ostrava
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnice
city: Praha 10
country: Czechia
facility: Fakultní nemocnice Královské Vinohrady - Urologická klinikay
city: Praha 2
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
city: Praha 4
country: Czechia
facility: Lexum a.s., Evropska ocni klinika
city: Praha 5
country: Czechia
facility: Axon Clinical, s.r.o.
city: Tallinn
country: Estonia
facility: AS Ida-Tallinna Keskhaigla - Oftalmoloogiakeskus
city: Tallinn
country: Estonia
facility: Dr. Kai Noor Silmakabinet OÜ
city: Tartu
country: Estonia
facility: Sihtasutus Tartu Ülikooli Kliinikum - Silmakliinik
city: Paris
country: France
facility: Centre Hospitalier National d'Ophthalmologie Quinze-Vingt
state: Cedex 12
city: Bordeaux
country: France
facility: Clinique Rétine Tourny
city: Bordeaux
country: France
facility: CHU Bordeaux - Hopital Pellegrin - Ophtalmologie
city: Creteil Cedex
country: France
facility: Hôpital Intercommunal - Créteil Cedex
city: Dijon
country: France
facility: CHU Dijon - Hopital Francois Miterrand
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Marseille
country: France
facility: Centre d'Ophtalmologie - Paradis-Monticelli
city: Nantes
country: France
facility: Clinique Jules Verne - Nantes
city: Paris
country: France
facility: Centre d'ophtalmologie de l'Odéon
city: Paris
country: France
facility: Centre Ophthalmologie d'Imagerie et de Laser
city: Paris
country: France
facility: AP-HP - Hopital Lariboisiere
city: Strasbourg
country: France
facility: CM Wolff
city: Tours
country: France
facility: Centre Ophtalmologique Transparence - Tours
city: Tbilisi
country: Georgia
facility: LTD "IQ Clinic"- Ophthalmology
city: Tbilisi
country: Georgia
facility: LTD "Chichua Medical Center MZERA"
city: Sulzbach
country: Germany
facility: Knappschaftskrankenhaus Sulzbach
state: Saarland
city: Bonn
country: Germany
facility: Uniklinik Bonn / Eye Clinic
city: Heidelberg
country: Germany
facility: Uni Heidelberg / Augenklinik
city: Ludwigshafen
country: Germany
facility: Klinikum d. Stadt Ludwigshafen - Ophthalmology
city: Muenster
country: Germany
facility: St. Franziskus-Hospital Münster - Eye Center
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Budapest
country: Hungary
facility: University of Semmelweis/ Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Budapesti Bajcsy-Zsilinszky Korhaz es Rendelointezet
city: Budapest
country: Hungary
facility: Budapest Retina Associates
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Pecs
country: Hungary
facility: Ganglion Medical Center
city: Szeged
country: Hungary
facility: SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont
city: Beer Sheva
country: Israel
facility: Clalit Health | Soroka Medical Center - Internal Medicine Department
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center | Internal Medicine Department
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital Ein Kerem
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center | Beilinson Hospital - Internal Medicine C Department
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Assuta Medical Centers - HaShalom
city: Zerifin
country: Israel
facility: Shamir Medical Center (Assaf Harofeh)
city: Torrette
country: Italy
facility: Azienda Ospedaliero Universitaria Delle Marche - Clinica Oculistica
state: Ancona
city: Roma
country: Italy
facility: Azienda Ospedaliera Policlinico Universitario Tor Vergata - Patologie Retiniche
state: Lazio
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oculistica
state: Lazio
city: Roma
country: Italy
facility: Fondazione G.B.Bietti Per Lo Studio E La Ricerca In Oftalmologia
state: Lazio
city: Milano
country: Italy
facility: ASST Fatebenefratelli Sacco
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Milano
country: Italy
facility: Ospedale San Raffaele s.r.l.
state: Lombardia
city: Nagakute
country: Japan
facility: Aichi Medical University Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Narita
country: Japan
facility: International University of Health and Welfare Narita Hospital
state: Chiba
city: Sakura
country: Japan
facility: Toho University Sakura Medical Center
state: Chiba
city: Yoshida
country: Japan
facility: University of Fukui Hospital
state: Fukui
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Koriyama
country: Japan
facility: Southern Tohoku Eye Clinic
state: Fukushima
city: Maebashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Amagasaki
country: Japan
facility: Hyogo Prefectural Amagasaki General Medical Center
state: Hyogo
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Nishinomiya
country: Japan
facility: Hyogo Medical University Hospital
state: Hyogo
city: Mito
country: Japan
facility: Kozawa Eye Hospital and Diabetes Center
state: Ibaraki
city: Toride
country: Japan
facility: Matsumoto Eye Clinic
state: Ibaraki
city: Kita-gun
country: Japan
facility: Kagawa University Hospital
state: Kagawa
city: Kawasaki
country: Japan
facility: Medical corporation Eiwakai Dannoue Ophthalmology clinic
state: Kanagawa
city: Kawasaki
country: Japan
facility: St. Marianna University Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
city: Matsumoto
country: Japan
facility: Shinshu University Hospital
state: Nagano
city: Tokorozawa
country: Japan
facility: National Defense Medical College Hospital
state: Saitama
city: Otsu
country: Japan
facility: Shiga University of Medical Science Hospital
state: Shiga
city: Fujieda-shi
country: Japan
facility: Shida Eye Clinic
state: Shizuoka
city: Chiyoda-ku
country: Japan
facility: Nihon University Hospital
state: Tkyo
city: Bunkyo-ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Chofu
country: Japan
facility: Chofu Eye Clinic
state: Tokyo
city: Hachioji
country: Japan
facility: Tokyo Medical University Hachioji Medical Center
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Tokyo Metropolitan Institute for Geriatrics and Gerontology
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Tokiwadai Muranaka Eye Clinic
state: Tokyo
city: Meguro-ku
country: Japan
facility: National Hospital Organization Tokyo Medical Center
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital
state: Tokyo
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Chuo
country: Japan
facility: University of Yamanashi Hospital
state: Yamanashi
city: Akita
country: Japan
facility: Akita University Hospital
city: Fukuoka
country: Japan
facility: Hayashi Eye Hospital
city: Fukuoka
country: Japan
facility: Murakami Karindoh Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Miyazaki
country: Japan
facility: University of Miyazaki Hospital
city: Nagasaki
country: Japan
facility: Japanese Red Cross Nagasaki Genbaku Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Saitama
country: Japan
facility: Japanese Red Cross Saitama Hospital
city: Toyama
country: Japan
facility: Toyama University Hospital
city: Wakayama
country: Japan
facility: Japanese Red Cross Wakayama Medical Center
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
state: Seoul Teugbyeolsi
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: St. Mary Hospital
city: Seoul
country: Korea, Republic of
facility: Kim's Eye Hospital
city: Riga
country: Latvia
facility: Department of Ophthalmology
city: Riga
country: Latvia
facility: Riga East Clinical University Hospital "Gailezers"
city: Kaunas
country: Lithuania
facility: Hospital of LT University of Health Sciences Kaunas Clinics
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Bandar Puncak Alam
country: Malaysia
facility: Hospital Al-Sultan Abdullah, UiTM | Opthalmology
state: Selangor
city: Shah Alam
country: Malaysia
facility: Hospital Shah Alam | Ophthalmology
state: Selangor
city: Shah Alam
country: Malaysia
facility: Hospital Selayang
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: OasisEye Specialists
city: Bydgoszcz
country: Poland
facility: Prywatna Klinika Okulistyczna OFTALMIKA
city: Bydgoszcz
country: Poland
facility: Specjalistyczny Osrodek Okulistyczny Oculomedica
city: Gdansk
country: Poland
facility: Profesorskie Centrum Okulistyki
city: Katowice
country: Poland
facility: Gabinet Okulistyczny Prof. Edward Wylegala
city: Krakow
country: Poland
facility: Centrum Medyczne Dietla 19 Sp. z o.o.
city: Krakow
country: Poland
facility: Centrum Medyczne PROMED
city: Olsztyn
country: Poland
facility: Centrum Diagnostyki i Mikrochirurgii Oka Lens
city: Rzeszow
country: Poland
facility: Osrodek Chirurgii Oka prof. Zagorskiego Sp. z o.o.
city: Walbrzych
country: Poland
facility: Centrum Medyczne Piasta 47
city: Coimbra
country: Portugal
facility: AIBILI
city: Coimbra
country: Portugal
facility: Espaco Medico de Coimbra
city: Lisboa
country: Portugal
facility: CHLC - Hospital dos Capuchos - Servico de Oftalmologia
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario de Sao Joao | Polo Porto - Centro de Investigacao e Ensaios Clinicos
city: Porto
country: Portugal
facility: Centro Hospitalar Vila Nova de Gaia e Espinho | Unit 1 - Clinical Research Center
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical hospital center Zvezdara
city: Novi Sad
country: Serbia
facility: Klinicki centar Vojvodine
city: Banska Bystrica
country: Slovakia
facility: Fakultna Nemocnica s poliklinikou F.D.Roosevelta
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava, Nemocnica Ruzinov
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava, Nem. Sv. Cyrila a Metoda
city: Nitra
country: Slovakia
facility: Fakultna nemocnica Nitra
city: Trencin
country: Slovakia
facility: Fakultna nemocnica Trencin
city: Zvolen
country: Slovakia
facility: Specialized hospital for ophthalmology OPHTAL
city: Santiago de Compostela
country: Spain
facility: Instituto Oftalmologico Gomez-Ulla S.L. - Oftalmologia
state: A Coruña
city: Sant Cugat del Valles
country: Spain
facility: Hospital General de Catalunya - Oftalmologia
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta De Hierro De Majadahonda - Oftalmologia
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron - Servei d'Oftalmologia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra CUN
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega - Oftalmologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet - Oftalmologia
city: Lausanne
country: Switzerland
facility: RétinElysée
state: Vaud
city: Bern
country: Switzerland
facility: Inselspital Universitätsspital Bern
city: Bern
country: Switzerland
facility: Berner Augenklinik am Lindenhofspital
city: Binningen
country: Switzerland
facility: Vista Klinik
city: Lausanne
country: Switzerland
facility: University Eye Hospital Jules Gonin
city: Chiangmai
country: Thailand
facility: Chiangmai University
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Ankara
country: Turkey
facility: Ankara Etlik City Hospital | Ophthalmology
city: Ankara
country: Turkey
facility: SBU Gulhane Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Ankara Numune Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Aydin
country: Turkey
facility: Adnan Menderes Universitesi Tip fakultesi
city: Bilkent Ankara
country: Turkey
facility: Ankara Bilkent Sehir Hastanesi
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: Leicestershire
city: Frimley
country: United Kingdom
facility: Frimley Park Hospital NHS
state: Surrey
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
state: Tyne And Wear
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: West Midlands
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
state: West Yorkshire
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust | St James's University Hospital - Oncology
state: West Yorkshire
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire Eye Hospital Hull and East Yorkshire
state: York
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: York
country: United Kingdom
facility: York Teaching Hospital
Study officials:
References: