Navigated Laser In Branch Retinal Vein Occlusion Study

NCT03651011 | Completed

• 2 other identifiers: NIRVANAS-20170084
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief Summary

Branch retinal vein occlusion (BRVO) is often complicated by macular edema, possibly leading to severe visual loss or blindness. Treatment is repeated, intravitreal injections of vascular endothelial growth factor (VEGF)-inhibitors like aflibercept. The treatment is effective, but a need for repetitive injections is a concern for patients as well as society due to risk of side effects, regular hospital visits and the price of the drug. Former treatment included macular grid pattern photocoagulation, but this technology was limited by a poorer visual outcome for the patient and a higher risk of side effects, including central visual loss. A novel laser delivery system, called navigated laser photocoagulation, has proven effective, safe and precise, and has shown promising results in stabilising the effect of the VEGF-inhibitor treatment in similar diseases. Thus, in a 12-month prospective, randomized 1:1 study of 60 patients with BRVO and macular edema the investigators aim to (1) Examine the treatment response of patients treated with intravitreal aflibercept (Eylea®) and navigated retinal laser (Navilas®)(Group 1) as compared to patients treated with intravitreal aflibercept only (Group 2), and (2) Identify non-invasive retinal biomarkers (retinal oxygen saturation, macular ischemia and retinal vascular arteriolar and venular calibre) for successful treatment outcome.

Conditions

Branch Retinal Vein Occlusion; Macular Edema

Keywords

Branch Retinal Vein Occlusion; Navigated laser photocoagulation; Macular Edema; Oximetry; Retinal vascular caliber measurements; Microperimetry

Outcome Measures

Primary Outcomes (1)

• Patients with additional need for anti-VEGF after loading phase

  Percentage of patients in Groups 1 and 2 that receive additional intravitreal aflibercept after the loading phase

  Month 3 to Month 12

Secondary Outcomes (7)

• Additional need for anti-VEGF after loading phase

  Month 3 to Month 12

• Change in BCVA according to treatment regimen

  Month 12

• Effect on macular edema according til treatment regimen

  Month 12

• Retinal oxygen saturation

  Baseline

• Macular ischemia (area of FAZ)

  Baseline

Study Arms (2)

Aflibercept + Navigated laser

ACTIVE COMPARATOR

Patients will receive intravitreal aflibercept at M0, M1 and M2 (loading phase) and in addition receive navigated retinal laser photocoagulation at M3. Patients will receive aflibercept according to pro re nata regimen from M3-M12.

Drug: Aflibercept Injection [Eylea]; Procedure: Navigated laser photocoagulation

Aflibercept only

ACTIVE COMPARATOR

Patients will receive intravitreal aflibercept at M0, M1 and M2 (loading phase). Patients will receive aflibercept according to pro re nata regimen from M3-M12.

Drug: Aflibercept Injection [Eylea]

Interventions

Aflibercept Injection [Eylea] DRUG

Intravitreal injection 2 mg Eylea every 4 weeks M0-M2 (loading phase). M3-M12: continue in a pro re nata treatment regimen.

Aflibercept + Navigated laser; Aflibercept only

Navigated laser photocoagulation PROCEDURE

Navigated laser photocoagulation planned from flourscein angiography.

Also known as: Navilas

Aflibercept + Navigated laser

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with BRVO with foveal center-involved macular edema in the study eye.
• Best-corrected visual acuity (BCVA) 35-80 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (0.1-0.8 Snellen equivalent) in the study eye at baseline (BL).
• Age ≥18 years.
• Central retinal thickness \> 300 μm in the study eye at BL.
• Onset ≤ 6 months prior to the study.

You may not qualify if:

• Active retinal or iris neovascularizations in the study eye at any time.
• Cataract, vitreous hemorrhage or other clouding conditions that prevent retinal laser photocoagulation in the study eye at M3.
• Prior anti-VEGF treatment or macular laser photocoagulation in the study eye.
• Macular edema and/or increased retinal thickness due to other potential causes than BRVO
• Uncontrolled hypertension (blood pressure ≥ 160/110 mmHg).

Sponsors & Collaborators

• Odense University Hospital: lead
• Danske Regioner: collaborator
• Synoptik-Fonden: collaborator
• Toyota-Fonden: collaborator
• AP Moeller Foundation: collaborator
• Yamagata University: collaborator
• Queen's University, Belfast: collaborator
• Zealand University Hospital: collaborator
• Region Sjællands og Region Syddanmarks forskningspulje: collaborator

Study Sites (2)

Department of Ophthalmology, Odense University Hospital

Odense, Danmark, 5000, Denmark

Location

Department of Ophthalmology, Zealand University Hospital

Roskilde, 4000, Denmark

Location

Related Publications (18)

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  PMID: 2417579 BACKGROUND

• Brown DM, Campochiaro PA, Bhisitkul RB, Ho AC, Gray S, Saroj N, Adamis AP, Rubio RG, Murahashi WY. Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study. Ophthalmology. 2011 Aug;118(8):1594-602. doi: 10.1016/j.ophtha.2011.02.022.

  PMID: 21684606 BACKGROUND

• Pielen A, Mirshahi A, Feltgen N, Lorenz K, Korb C, Junker B, Schaefer C, Zwiener I, Hattenbach LO; RABAMES Study Group. Ranibizumab for Branch Retinal Vein Occlusion Associated Macular Edema Study (RABAMES): six-month results of a prospective randomized clinical trial. Acta Ophthalmol. 2015 Feb;93(1):e29-37. doi: 10.1111/aos.12488. Epub 2014 Jul 8.

  PMID: 25042729 BACKGROUND

• Clark WL, Boyer DS, Heier JS, Brown DM, Haller JA, Vitti R, Kazmi H, Berliner AJ, Erickson K, Chu KW, Soo Y, Cheng Y, Campochiaro PA. Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: 52-Week Results of the VIBRANT Study. Ophthalmology. 2016 Feb;123(2):330-336. doi: 10.1016/j.ophtha.2015.09.035. Epub 2015 Oct 30.

  PMID: 26522708 BACKGROUND

• Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol. 2008 Apr;126(4):513-8. doi: 10.1001/archopht.126.4.513.

  PMID: 18413521 BACKGROUND

• Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7. doi: 10.1056/NEJM199412013312203.

  PMID: 7526212 BACKGROUND

• Noma H, Minamoto A, Funatsu H, Tsukamoto H, Nakano K, Yamashita H, Mishima HK. Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. 2006 Mar;244(3):309-15. doi: 10.1007/s00417-004-1087-4. Epub 2005 Aug 13.

  PMID: 16133018 BACKGROUND

• Geirsdottir A, Palsson O, Hardarson SH, Olafsdottir OB, Kristjansdottir JV, Stefansson E. Retinal vessel oxygen saturation in healthy individuals. Invest Ophthalmol Vis Sci. 2012 Aug 13;53(9):5433-42. doi: 10.1167/iovs.12-9912.

  PMID: 22786895 BACKGROUND

• Lin LL, Dong YM, Zong Y, Zheng QS, Fu Y, Yuan YG, Huang X, Qian G, Gao QY. Study of retinal vessel oxygen saturation in ischemic and non-ischemic branch retinal vein occlusion. Int J Ophthalmol. 2016 Feb 18;9(1):99-107. doi: 10.18240/ijo.2016.01.17. eCollection 2016.

  PMID: 26949618 BACKGROUND

• Hardarson SH, Stefansson E. Oxygen saturation in branch retinal vein occlusion. Acta Ophthalmol. 2012 Aug;90(5):466-70. doi: 10.1111/j.1755-3768.2011.02109.x. Epub 2011 Apr 21.

  PMID: 21518303 BACKGROUND

• Grauslund J, Hodgson L, Kawasaki R, Green A, Sjolie AK, Wong TY. Retinal vessel calibre and micro- and macrovascular complications in type 1 diabetes. Diabetologia. 2009 Oct;52(10):2213-7. doi: 10.1007/s00125-009-1459-8. Epub 2009 Jul 18.

  PMID: 19618163 BACKGROUND

• Broe R, Rasmussen ML, Frydkjaer-Olsen U, Olsen BS, Mortensen HB, Hodgson L, Wong TY, Peto T, Grauslund J. Retinal vessel calibers predict long-term microvascular complications in type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987). Diabetes. 2014 Nov;63(11):3906-14. doi: 10.2337/db14-0227. Epub 2014 Jun 9.

  PMID: 24914239 BACKGROUND

• Youm DJ, Ha MM, Chang Y, Song SJ. Retinal vessel caliber and risk factors for branch retinal vein occlusion. Curr Eye Res. 2012 Apr;37(4):334-8. doi: 10.3109/02713683.2011.629070. Epub 2012 Feb 10.

  PMID: 22324736 BACKGROUND

• Techniques for scatter and local photocoagulation treatment of diabetic retinopathy: Early Treatment Diabetic Retinopathy Study Report no. 3. The Early Treatment Diabetic Retinopathy Study Research Group. Int Ophthalmol Clin. 1987 Winter;27(4):254-64. doi: 10.1097/00004397-198702740-00005. No abstract available.

  PMID: 3692707 BACKGROUND

• Kozak I, Oster SF, Cortes MA, Dowell D, Hartmann K, Kim JS, Freeman WR. Clinical evaluation and treatment accuracy in diabetic macular edema using navigated laser photocoagulator NAVILAS. Ophthalmology. 2011 Jun;118(6):1119-24. doi: 10.1016/j.ophtha.2010.10.007. Epub 2011 Jan 26.

  PMID: 21269701 BACKGROUND

• Tomkins-Netzer O, Ismetova F, Bar A, Seguin-Greenstein S, Kramer M, Lightman S. Functional outcome of macular edema in different retinal disorders. Prog Retin Eye Res. 2015 Sep;48:119-36. doi: 10.1016/j.preteyeres.2015.05.002. Epub 2015 May 23.

  PMID: 26014685 BACKGROUND

• Liegl R, Langer J, Seidensticker F, Reznicek L, Haritoglou C, Ulbig MW, Neubauer AS, Kampik A, Kernt M. Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema. PLoS One. 2014 Dec 26;9(12):e113981. doi: 10.1371/journal.pone.0113981. eCollection 2014.

  PMID: 25541960 BACKGROUND

• Frederiksen KH, Pedersen FN, Vergmann AS, Yang D, Laugesen CS, Vestergaard JP, Sorensen TL, Cheung CY, Kawasaki R, Peto T, Grauslund J. Predictive value of retinal oximetry, optical coherence tomography angiography and microperimetry in patients with treatment-naive branch retinal vein occlusion. Int J Retina Vitreous. 2023 Jun 28;9(1):38. doi: 10.1186/s40942-023-00468-7.

  PMID: 37381014 DERIVED

MeSH Terms

Conditions

Retinal Vein Occlusion; Macular Edema

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Macular Degeneration; Retinal Degeneration

Study Officials

• Katrine H Frederiksen, PhD-student

  Research Unit of Ophthalmology, University of Southern Denmark

  PRINCIPAL INVESTIGATOR

• Jakob Grauslund, DMSci,PhD

  Research Unit of Ophthalmology, University of Southern Denmark

  STUDY DIRECTOR

• Torben L Sørensen, DMSci

  Dept. of Ophthalmology, Zealand University Hospital

  STUDY CHAIR

• Jesper P Vestergaard, MD

  Dept. of Ophthalmology, Odense University Hospital

  STUDY CHAIR

• Inger C Munch, PhD

  Dept. of Ophthalmology, Zealand University Hospital

  STUDY CHAIR

• Tunde Peto, PhD

  Queen's University, Belfast, England

  STUDY CHAIR

• Ryo Kawasaki, PhD

  Yamagata, University, Japan

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 24, 2018
• First Posted: August 29, 2018
• Study Start: August 10, 2018
• Primary Completion: October 5, 2021
• Study Completion: October 5, 2021
• Last Updated: April 20, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)