Central Retinal Vein Occlusion With Macular EdemaPhase 3CoRaLaIINCT04444492
Combination of Ranibizumab and Targeted Laser Photocoagulation
A Phase 3 study testing Ranibizumab Injection and Laser photocoagulation in people with Central Retinal Vein Occlusion With Macular Edema, run by University of Giessen at 12 sites in 2 countries.
Trial summary
Intravitreal injections of Ranibizumab will be applied in all patients according to treatment guidelines. The experimental group will receive additional targeted laser photocoagulation of the peripheral areas of capillary non-perfusion (up to 4 laser treatments within 1st year of the study). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Central Retinal Vein Occlusion With Macular Edema
- What is being tested?
- Ranibizumab Injection and Laser photocoagulation
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 25 Aug 2020to 30 Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of macular edema due to central retinal vein occlusion foveal thickness > 250 μm (measured by OCT)
- Age > 18 years
- Written informed consent of the patient
- BCVA score in the study eye between 24 letters (20/320) and 78 letters (20/25) measured in ETDRS chart
- History of CRVO no longer than 6 months
- Presence of capillary non-perfusion in peripheral retina larger than 5 disc areas documented in ultra wide-field fluorescein angiography
- Ability and willingness to attend all scheduled visits and assessments
Who cannot join
- CRVO with ischemic maculopathy defined as diameter of the foveolar avascular zone larger than 2 optic disc diameters
- Macular edema due to another etiology than retinal vein occlusion (e.g. diabetic maculopathy, uveitis, age related macular degeneration, Irvine-Gass syndrome)
- History of idiopathic central serous chorioretinopathy
- Presence of vitreoretinal interface disease (e.g. vitreomacular traction, epiretinal membrane), either on clinical examination or in OCT
- An eye that, in the investigator's opinion, would not benefit from resolution of macular edema, such as eyes with foveal atrophy, dense pigmentary changes, or dense subfoveal hard exudates
- Aphakia in the study eye
Show all 18Show fewer
- Scatter laser photocoagulation or macular photocoagulation in the study eye prior to study entry
- Intraocular or periocular injection of steroids in the study eye prior to study entry
- Previous use of an anti-VEGF drug in the study eye
- Cataract surgery or any other intraocular surgery in the study eye within 3 months prior to study entry
- Uncontrolled glaucoma (defined as intraocular pressure ≥ 30 mm Hg despite treatment with maximal anti-glaucoma medications)
- History of stroke, myocardial infarction, transient ischemic attacks within 3 months prior to the study
- Pregnancy (positive urine pregnancy test) or lactation
- The presence of active malignancy, including lymphoproliferative disorders.
- History of allergy to fluorescein or any component of the ranibizumab formulation
- Active intraocular infection
- Participation in another simultaneous interventional medical investigation or trial
- Women with child bearing potency without effective contraception (i. e. implants, injectables, combined oral contraceptives, some IUDs or vasectomised partner) during the conduct of the trial.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
Germany11 sites
Universitätsklinikum Klinik für Augenheilkunde Freiburg
Freiburg im Breisgau, 79106
Universitätsklinikum Gießen, Klinik und Poliklinik für Augenheilkunde
Giessen
Hannover MHH Universitätsklinik für Augenheilkunde
Hanover, 30625
University Hospital of Leipzig Department of Ophthalmology
Leipzig, 04103
Klinikum der Stadt Ludwigshafen Augenklinik
Ludwigshafen, 67063
Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg Klinik für Augenheilkunde
Marburg, 35043
Ludwig-Maximilians-Universität München, Augenklinik
München
Augenzentrum am St. Franziskus-Hospital Münster
Münster, 48145
Universitätsklinikum Tübingen, Department für Augenheilkunde
Tübingen
Universitätsklinikum Ulm, Klinik für Augenheilkunde
Ulm
Augen-OP-Zentrum Zschopau, Praxis für Augenheilkunde
Zschopau
Austria1 site
Medizinische Universität Innsbruck, Klinik für Augenheilkunde und Optometrie
Innsbruck, 6020
About this study
Official title: Long-term Need of Ranibizumab Injections With or Without Early Targeted Peripheral Laser Photocoagulation for Treatment of Macular Edema Due to Central Retinal Vein Occlusion
Intravitreal injections of Ranibizumab will be applied in all patients according to treatment guidelines. The experimental group will receive additional targeted laser photocoagulation of the peripheral areas of capillary non-perfusion (up to 4 laser treatments within 1st year of the study). Based on the long-term observation after CoRaLa I study an importantly shorter duration of treatment and a relevant reduction of the total number of re-injections in RL patients is expected.
Read the detailed description
Retinal vein occlusion (RVO) is the second most common retinal vascular disease leading to visual impairment. Main cause for visual impairment in CRVO (Central Retinal Vein Occlusion) is macular edema (ME) while neovascularization of the retina and/or the anterior segment is the most serious complication leading to vitreous hemorrhage, retinal detachment and neovascular glaucoma. In serious cases loss of vision is imminent. To date, no causal treatment has been proven to be effective in large trials. Intravitreal injections of drugs that inhibit the vascular endothelial growth factor (VEGF) and other inflammatory factors are the current treatments of choice for ME due to CRVO. Two different anti-VEGF drugs (ranibizumab and aflibercept), and a biodegradable dexamethasone implant are approved by the EMA (European Medicines Agency). Based on data from confirmatory studies anti-VEGF-drugs are recommended as a treatment of first choice in patients with RVO. All intravitreal drugs provide only a temporary effect with need for re-treatment for recurrences of ME. Mean number of ranibizumab application needed in CRVO patients was found to be 7.4 to 10.2 injections in 12 months. A significant number of CRVO patients require treatment over several years. Need for repetitive treatments and ophthalmic controls are a major burden for patients (and their relatives who are required for driving the patients to ophthalmologists) despite of only few adverse events and generally well-tolerated injections. Endophthalmitis is the most severe ocular complication which can be eye-sight-threatening. The more injections are administered, the higher is the cumulative risk of complications. Due to high costs (>1000 € per injection) treatment with repeated injections over years is of significant socio-economic importance, too. Therefore, treatments concepts which would lead to permanent reduction of ME and/or significantly reduce the number of re-injections over long-term periods are the major currently unmet need in patients with RVO.
Until now, several studies evaluated the impact of the additional pan-retinal laser photocoagulation in patients undergoing the anti-VEGF-treatment for the ME due to retinal vein occlusions. However, most of the studies are limited by retrospective design, small number of evaluated patients or lack of the randomization. None of the available prospective randomized studies had sufficient power to finally clarify the benefit of the additional laser treatment. Therefore, there is an unmet need for a large randomized, prospective, multicentric trials.
The proposed study will be the first sufficiently powered trial evaluating the long-term effect of targeted laser photocoagulation performed selectively (targeted) in peripheral areas of non-perfusion in combination with standard anti-VEGF treatment (ranibizumab injections) on the duration of the required intravitreal treatment over time period of 2 years.
- Being tested
- Ranibizumab Injection, Laser photocoagulation
- Keywords
- retinal vein occlusion
- Medical subject headings
- Retinal Vein Occlusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ranibizumab InjectionDrug
Also called Lucentis
initial three injections of Ranibizumab - afterwards pro re nata monthly
Laser photocoagulationDevice
Areas of capillary non-perfusion will be treated with photocoagulation upto 4 times
| Study group | Role | What they receive |
|---|---|---|
| Ranibizumab+Laser-arm | Experimental | Ranibizumab injections and additional targeted laser Receives: Drug: Ranibizumab Injection; Device: Laser photocoagulation |
| Ranibizumab-arm | Active comparator | Only Ranibizumab injections Receives: Drug: Ranibizumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy endpoint is the time to treatment success
Time from randomisation until the date of last criteria-based intravitreal injection in case that thereafter a treatment-free period for (at least) 6 months was observed.
Measured: up-to 29 months
Secondary outcomes (3)
Best corrected visual acuity (BCVA)
Best corrected visual acuity (BCVA) in number of ETDRS letters (Early Treatment of Diabetes Retinopathy Study) per visit
Measured: Month 29
Central subfield thickness (CST)
Central subfield thickness (CST) measured by OCT per visit
Measured: Month 29
Number of ranibizumab injections
Number of ranibizumab injections required until treatment success and up to the end of Observation.
Measured: Month 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2020
- Study start25 Aug 2020
- Primary completion30 Nov 2027 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Retinal Vein Occlusion With Macular EdemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Giessen
- Sponsor type
- University, hospital or other
- Collaborators
- University of Leipzig
- Responsible party
- Sponsor
- Investigators
- Matus Rehak, Professor, Study director, Department of Ophthalmology Justus-Liebig-Universität Giessen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04444492
- Sponsor's protocol ID
- CoRaLaII
- Acronym
- CoRaLaII
- Status last verified
- May 2026
- First submitted
- 19 Jun 2020
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-term Need of Ranibizumab Injections With or Without Early Targeted Peripheral Laser Photocoagulation for Treatment of Macular Edema Due to Central Retinal Vein Occlusion
- ClinicalTrials.gov ID
- NCT04444492
- Acronym / sponsor ID
- CoRaLaII / CoRaLaII
- Keywords
- retinal vein occlusion
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University of GiessenUniversity, hospital or other
- Collaborators
- University of Leipzig
- Study start
- 25 Aug 2020 (actual)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 30 Nov 2027 (estimated)
- First posted
- 23 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Intravitreal injections of Ranibizumab will be applied in all patients according to treatment guidelines. The experimental group will receive additional targeted laser photocoagulation of the peripheral areas of capillary non-perfusion (up to 4 laser treatments within 1st year of the study). Based on the long-term observation after CoRaLa I study an importantly shorter duration of treatment and a relevant reduction of the total number of re-injections in RL patients is expected.
Detailed description
Retinal vein occlusion (RVO) is the second most common retinal vascular disease leading to visual impairment. Main cause for visual impairment in CRVO (Central Retinal Vein Occlusion) is macular edema (ME) while neovascularization of the retina and/or the anterior segment is the most serious complication leading to vitreous hemorrhage, retinal detachment and neovascular glaucoma. In serious cases loss of vision is imminent. To date, no causal treatment has been proven to be effective in large trials. Intravitreal injections of drugs that inhibit the vascular endothelial growth factor (VEGF) and other inflammatory factors are the current treatments of choice for ME due to CRVO. Two different anti-VEGF drugs (ranibizumab and aflibercept), and a biodegradable dexamethasone implant are approved by the EMA (European Medicines Agency). Based on data from confirmatory studies anti-VEGF-drugs are recommended as a treatment of first choice in patients with RVO. All intravitreal drugs provide only a temporary effect with need for re-treatment for recurrences of ME. Mean number of ranibizumab application needed in CRVO patients was found to be 7.4 to 10.2 injections in 12 months. A significant number of CRVO patients require treatment over several years. Need for repetitive treatments and ophthalmic controls are a major burden for patients (and their relatives who are required for driving the patients to ophthalmologists) despite of only few adverse events and generally well-tolerated injections. Endophthalmitis is the most severe ocular complication which can be eye-sight-threatening. The more injections are administered, the higher is the cumulative risk of complications. Due to high costs (>1000 € per injection) treatment with repeated injections over years is of significant socio-economic importance, too. Therefore, treatments concepts which would lead to permanent reduction of ME and/or significantly reduce the number of re-injections over long-term periods are the major currently unmet need in patients with RVO.
Until now, several studies evaluated the impact of the additional pan-retinal laser photocoagulation in patients undergoing the anti-VEGF-treatment for the ME due to retinal vein occlusions. However, most of the studies are limited by retrospective design, small number of evaluated patients or lack of the randomization. None of the available prospective randomized studies had sufficient power to finally clarify the benefit of the additional laser treatment. Therefore, there is an unmet need for a large randomized, prospective, multicentric trials.
The proposed study will be the first sufficiently powered trial evaluating the long-term effect of targeted laser photocoagulation performed selectively (targeted) in peripheral areas of non-perfusion in combination with standard anti-VEGF treatment (ranibizumab injections) on the duration of the required intravitreal treatment over time period of 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ranibizumab+Laser-arm | Experimental | Drug: Ranibizumab Injection, Device: Laser photocoagulationRanibizumab injections and additional targeted laser |
| Ranibizumab-arm | Active comparator | Drug: Ranibizumab InjectionOnly Ranibizumab injections |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of macular edema due to central retinal vein occlusion foveal thickness > 250 μm (measured by OCT)
- Age > 18 years
- Written informed consent of the patient
- BCVA score in the study eye between 24 letters (20/320) and 78 letters (20/25) measured in ETDRS chart
- History of CRVO no longer than 6 months
Key exclusion criteria (18 listed)
- CRVO with ischemic maculopathy defined as diameter of the foveolar avascular zone larger than 2 optic disc diameters
- Macular edema due to another etiology than retinal vein occlusion (e.g. diabetic maculopathy, uveitis, age related macular degeneration, Irvine-Gass syndrome)
- History of idiopathic central serous chorioretinopathy
- Presence of vitreoretinal interface disease (e.g. vitreomacular traction, epiretinal membrane), either on clinical examination or in OCT
- An eye that, in the investigator's opinion, would not benefit from resolution of macular edema, such as eyes with foveal atrophy, dense pigmentary changes, or dense subfoveal hard exudates
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ranibizumab InjectionAlso: Lucentisinitial three injections of Ranibizumab - afterwards pro re nata monthly | Drug | Ranibizumab+Laser-arm, Ranibizumab-arm |
| Laser photocoagulationAreas of capillary non-perfusion will be treated with photocoagulation upto 4 times | Device | Ranibizumab+Laser-arm |
Primary outcome
Efficacy endpoint is the time to treatment success
Time frame: up-to 29 months
Time from randomisation until the date of last criteria-based intravitreal injection in case that thereafter a treatment-free period for (at least) 6 months was observed.
3 secondary outcomes
Best corrected visual acuity (BCVA)
Time frame: Month 29
Central subfield thickness (CST)
Time frame: Month 29
Number of ranibizumab injections
Time frame: Month 29
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matus Rehak, Professor study director
Department of Ophthalmology Justus-Liebig-Universität Giessen
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ranibizumab Injection and Laser photocoagulation in people with Central Retinal Vein Occlusion With Macular Edema, run by University of Giessen at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy endpoint is the time to treatment success (time frame: up-to 29 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.