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CompletedNCT01710839WAVEUpdated Sep 8, 2017Results posted

Widefield Angiography Guided Targeted-retinal Photocoagulation Combined With Anti VEgf Intravitreal Injections for the Treatment of Ischemic Central Retinal Vein Occlusion, Hemi Retinal Vein Occlusion, and Branch Retinal Vein Occlusion

A Phase 4 interventional study of 0.5mg Ranibizumab and Targeted Pan Retinal Photocoagulation in Central Retinal, Hemi Retinal & Brach Retinal Vein Occlusions, sponsored by Charles C Wykoff, PhD, MD. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-09-08.

Sponsored by Charles C Wykoff, PhD, MD · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

To see if Lucentis 0.5mg combined with Targeted Pan Retinal photocoagulation will decrease the total number of intravitreal injections in a year for ischemic central retinal vein occlusion, hemi-retinal vein occlusions and branch retinal vein occlusions compared to standard of care

Read the detailed description

The WAVE trial is a phase IV, open label, 12-month trial of intravitreal ranibizumab 0.5 mg in patients (n=30) with ischemic CRVO, HRVO and BRVO who have been previously treated with ranibizumab or any other anti-VEGF intravitreal injection therapy, who are incomplete responders to 2 or more consecutive intravitreal anti-VEGF injections in the past 4 months. Randomization is 1:4, 1=control, ranibizumab only, 4=treatment arm. In total, 6 subjects will be randomized to control and 24 randomized to treatment arm.

Cohort 1- 24 Subjects previously treated Patients will receive 6 doses of ranibizumab 0.5 mg, followed by PRN intravitreal injection of ranibizumab 0.5 mg based on pre-defined retreatment criteria for up to 11 total injections.

Wide field angiography guided peripheral targeted-retinal photocoagulation (TRP), will be divided into 2 sessions if needed, one at the 2 weeks post injection visit and another later at M4/V7, if repeat wide field angiogram indicates areas not sufficiently treated in the first TRP session

Cohort 2- 6 Subjects, previously treated patients will receive 6 doses of ranibizumab 0.5 mg, followed by PRN intravitreal injection of ranibizumab 0.5 mg based on pre-defined retreatment criteria for up to 11 total injections.

02

Conditions studied

  • Central Retinal, Hemi Retinal & Brach Retinal Vein Occlusions

Keywords

  • CRVO
  • BRVO
  • HRVO
  • Macular edema
  • vein occlusion
03

In context

Retinal Vein Occlusion

282 studies on the registry are indexed under Retinal Vein Occlusion; 27 are open to participants now.

This study's enrollment of 30 is below the median of 49 across 211 interventional studies indexed under Retinal Vein Occlusion.

Browse Retinal Vein Occlusion studies →

Lead sponsor

Charles C Wykoff, PhD, MD is the lead sponsor of 3 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age > 18 years
  • Visual acuity between 20/25 and 20/800, ETDRS best corrected visual acuity
  • Ability to provide written informed consent and comply with study assessments for the full duration of the study

Patients previously treated with any ITV anti-VEGF:

  • With at least 2 consecutive monthly intravitreal injections of anti-VEGF medications with presence of persistent or recurrent macular edema in the past 4 months

Exclusion criteria

Exclusion Criteria:

  • IOP over 30 mm Hg
  • Any previous retinal laser photocoagulation to the study eye
  • Previous intravitreal injection in the study eye of any corticosteroid treatment
  • Previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery)
  • Intracapsular cataract extraction
  • Any previous radiation treatments to head/neck that the principal or sub investigator feels is clinically relevant
  • Inability to assess iris or angle neovascularization (corneal opacity precluding gonioscopy)
  • Significant cardiovascular disease or cancer that would prevent follow-up visits or completion of the 12 month study
  • Significant diabetic retinopathy in the fellow eye (diabetic macular edema, proliferative diabetic retinopathy, or high-risk non-proliferative diabetic retinopathy)
  • Participation in another simultaneous medical investigator or trial
  • Ocular disorders or concurrent disease in the study eye that may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention, including history of retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., DME, AMD, ocular histoplasmosis, or pathologic myopia)
  • Structural damage to the center of the macula in the study eye prior to CRVO, HRVO and BRVO likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s)
  • Vitreomacular traction or clinically significant epiretinal membrane in the study eye evident biomicroscopically or by OCT (vitreomacular attachment OK)
  • Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye) or current treatment for serious systemic infection
  • Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia (For patients who have had refractive or cataract surgery in the study eye, preoperative spherical equivalent refractive error of more than -8 diopters myopia is not allowed)
  • Uncontrolled Blood pressure: defined as systolic pressure > 180mmHg and/or diastolic pressure of >110 mm Hg (sitting) during the screening period
  • Uncontrolled diabetes mellitus
  • Renal failure requiring dialysis or renal transplant
  • Pregnancy (positive pregnancy test) or lactation
  • Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
  • History of other disease, metabolic dysfunction, physical examination finding, or other findings giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications
  • History of allergy to fluorescein, not amenable to treatment
  • Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed by the principal investigator (PI) and/or the sub-investigator.
  • History of allergy to humanized antibodies or any component of the ranibizumab formulation
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    Targeted Pan Retinal laser combined with 0.5mg ranibizumab

    Cohort 1 (n=24), previously treated with at least 2 consecutive or more intravitreal injections of any anti-VEGF agent with persistent or recurrent macular edema will receive 6 loading doses of 0.5 mg ranibizumab followed by PRN treatment with ranibizumab 0.5 mg; after receiving the first loading dose of ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) based on 200° wide field angiography with possibility of a second session of TRP at M4/M7, if non-perfusion persists based on angiogram.The 200°wide field angiography will indicate areas of peripheral ischemia which will be selectively treated, preserving areas of more perfused retina.

    Drug: 0.5mg Ranibizumab · Procedure: Targeted Pan Retinal Photocoagulation

  • Active comparator
    Ranibizumab 0.5mg

    Cohort 2 (n=6), previously treated with at least 2 consecutive or more intravitreal injections of any anti-VEGF agent with persistent or recurrent macular edema will receive 6 loading doses followed by PRN monthly treatment with ranibizumab 0.5 mg.

    Drug: 0.5mg Ranibizumab

Interventions

  • Drug0.5mg Ranibizumab

    intravitreal injections

    Also known as: Lucentis

  • ProcedureTargeted Pan Retinal Photocoagulation

    Targeted Pan Retinal Photocoagulation based on wide field angiography

    Also known as: PRP, Pan Retinal Photocoagulation, TRP, Pan Laser

06

What researchers measure

Primary outcomes

  1. Total Number of Intravitreal Injections Over a 12 Month Period

    Assess the number of intravitreal injections over 12 months.

    Time frame: 12 months

  2. Visual Acuity

    Evaluate the mean change from baseline in ETDRS best-corrected visual acuity at 12 months. The ETDRS protocol is a widely accepted international standard for macular laser photocoagulation treatment. A higher score represents better functioning.

    Time frame: 12 month period

Secondary outcomes

  1. Retinal Ischemia

    Quantify change in area of perfused and ischemic retina.

    Time frame: 12 month period

  2. Foveal Avascular Zone

    Assess change in foveal avascular zone area and largest diameter, measured during the early phase of the angiogram

    Time frame: 12 months

  3. Adverse Events

    Incidence and severity of adverse events (ocular and non-ocular).

    Time frame: 12 months

  4. Neovascularization of the Iris, Optic Nerve and Elsewhere

    Percent of patients that develop neovascularization of the iris, optic nerve and/or elsewhere.

    Time frame: 12 months

  5. Central Foveal Outcome

    Mean change in Central Foveal Volume on High Resolution OCT.

    Time frame: 12 months

  6. Aqueous VEGF Levels

    VEGF, other cytokines and ranibizumab levels in aqueous and serum samples at randomization and at the exit or early termination visit.

    Time frame: 12 Months

  7. Visual Field

    Goldman Visual Field changes at 6 and 12 months from baseline. Goldmann perimetry is a method used to map a patient's field of vision (central and peripheral). Changes will be assessed by manual digital quantification of GVF plots.

    Time frame: 6 and 12 Months

07

Results

Posted Apr 11, 2017

Participant flow

Participant flow — Overall Study
MilestoneTargeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mg
Started246
Completed230
Not completed16

Outcome measures

PrimaryTotal Number of Intravitreal Injections Over a 12 Month Period

Assess the number of intravitreal injections over 12 months.

Time frame:
12 months
Reported as:
Mean · injections
Total Number of Intravitreal Injections Over a 12 Month Period
injectionsTargeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mg
Total Number of Intravitreal Injections Over a 12 Month Period8.7 (5 to 12)9.5 (7 to 12)
PrimaryVisual Acuity

Evaluate the mean change from baseline in ETDRS best-corrected visual acuity at 12 months. The ETDRS protocol is a widely accepted international standard for macular laser photocoagulation treatment. A higher score represents better functioning.

Time frame:
12 month period
Reported as:
Mean · ETDRS BCVA Letters
Visual Acuity
ETDRS BCVA LettersTargeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mg
Visual Acuity14.9 ± 3.410.7 ± 4.4
SecondaryRetinal Ischemia

Quantify change in area of perfused and ischemic retina.

Time frame:
12 month period

No measurements were reported for this outcome.

SecondaryFoveal Avascular Zone

Assess change in foveal avascular zone area and largest diameter, measured during the early phase of the angiogram

Time frame:
12 months

No measurements were reported for this outcome.

SecondaryAdverse Events

Incidence and severity of adverse events (ocular and non-ocular).

Time frame:
12 months
Reported as:
Count of participants · Participants
Adverse Events
ParticipantsTargeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mg
Notable Ocular Events172
Serious Non-Ocular Events20
SecondaryNeovascularization of the Iris, Optic Nerve and Elsewhere

Percent of patients that develop neovascularization of the iris, optic nerve and/or elsewhere.

Time frame:
12 months
Reported as:
Number · percentage of patients
Neovascularization of the Iris, Optic Nerve and Elsewhere
percentage of patientsTargeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mg
Neovascularization of the Iris, Optic Nerve and Elsewhere8.330
SecondaryCentral Foveal Outcome

Mean change in Central Foveal Volume on High Resolution OCT.

Time frame:
12 months
Reported as:
Mean · cubic millimeters
Central Foveal Outcome
cubic millimetersTargeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mg
Central Foveal Outcome-0.15 ± .21-0.15 ± .20
SecondaryAqueous VEGF Levels

VEGF, other cytokines and ranibizumab levels in aqueous and serum samples at randomization and at the exit or early termination visit.

Time frame:
12 Months

No measurements were reported for this outcome.

SecondaryVisual Field

Goldman Visual Field changes at 6 and 12 months from baseline. Goldmann perimetry is a method used to map a patient's field of vision (central and peripheral). Changes will be assessed by manual digital quantification of GVF plots.

Time frame:
6 and 12 Months
Reported as:
Mean · square degrees
Visual Field
square degreesTargeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mg
Month 6-1269 ± 180102 ± 423
Month 12-1628 ± 353-1875 ± 326

Adverse events

Collected over 12 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Targeted Pan Retinal Laser Combined With 0.5mg Ranibizumab—2/24 (8.3%)17/24 (70.8%)
Ranibizumab 0.5mg—0/6 (0%)2/6 (33.3%)
Most frequent serious events
Most frequent serious events
EventTargeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mg
Hemorrhoids with rectal bleedingVascular disorders1/240/6
BradycardiaCardiac disorders1/240/6
Most frequent other events
Most frequent other events
EventTargeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mg
Visual distortionEye disorders8/240/6
Glaucoma suspectEye disorders1/241/6
Cataract progressionEye disorders3/241/6
Posterior vitreous detachmentEye disorders3/240/6
Vitreous hemorrhageEye disorders1/240/6
Epiretinal membraneEye disorders1/240/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)Targeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mgTotal
Mean64.1 (43 to 80)63.8 (56 to 77)64.1 (43 to 80)
Sex: Female, Male
Sex: Female, Male(Participants)Targeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mgTotal
Female11415
Male13215
RVO Subtype
RVO Subtype(Participants)Targeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mgTotal
CRVO13417
BRVO9211
HRVO202
Prior Anti-VEGF Injections
Prior Anti-VEGF Injections(injections)Targeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mgTotal
Mean10.2 (2 to 34)10.0 (2 to 41)10.1 (2 to 41)
ETDRS BCVA Letters
ETDRS BCVA Letters(ETDRS BCVA Letters)Targeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mgTotal
Mean51.7 (7 to 77)55.3 (29 to 71)52.4 (7 to 77)
Central Retinal Thickness
Central Retinal Thickness(micrometers)Targeted Pan Retinal Laser Combined With 0.5mg RanibizumabRanibizumab 0.5mgTotal
Mean525 (224 to 1240)471 (272 to 910)514 (224 to 1240)
08

Study locations

3 sites
  • Retina Consultants of Houston/The Medical Center
    Houston, Texas 77030, United States
  • Retina Consultants of Houston
    Katy, Texas 77494, United States
  • Retina Consultants of Houston
    The Woodlands, Texas 77384, United States
09

References and documents

Publications

  • Armaly MF. Ocular pressure and visual fields. A ten-year follow-up study. Arch Ophthalmol. 1969 Jan;81(1):25-40. doi: 10.1001/archopht.1969.00990010027005. No abstract available. PubMed 5763217 ↗
  • Boyd SR, Zachary I, Chakravarthy U, Allen GJ, Wisdom GB, Cree IA, Martin JF, Hykin PG. Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion. Arch Ophthalmol. 2002 Dec;120(12):1644-50. doi: 10.1001/archopht.120.12.1644. PubMed 12470137 ↗
  • Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY; CRUISE Investigators. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010 Jun;117(6):1124-1133.e1. doi: 10.1016/j.ophtha.2010.02.022. Epub 2010 Apr 9. PubMed 20381871 ↗
  • Campochiaro PA, Brown DM, Awh CC, Lee SY, Gray S, Saroj N, Murahashi WY, Rubio RG. Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study. Ophthalmology. 2011 Oct;118(10):2041-9. doi: 10.1016/j.ophtha.2011.02.038. Epub 2011 Jun 29. PubMed 21715011 ↗
  • A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. The Central Vein Occlusion Study Group N report. Ophthalmology. 1995 Oct;102(10):1434-44. PubMed 9097789 ↗
  • Natural history and clinical management of central retinal vein occlusion. The Central Vein Occlusion Study Group. Arch Ophthalmol. 1997 Apr;115(4):486-91. doi: 10.1001/archopht.1997.01100150488006. Erratum In: Arch Ophthalmol 1997 Oct;115(10):1275. PubMed 9109757 ↗
  • Christen WG, Glynn RJ, Manson JE, Ajani UA, Buring JE. A prospective study of cigarette smoking and risk of age-related macular degeneration in men. JAMA. 1996 Oct 9;276(14):1147-51. PubMed 8827967 ↗
  • Conn G, Bayne ML, Soderman DD, Kwok PW, Sullivan KA, Palisi TM, Hope DA, Thomas KA. Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2628-32. doi: 10.1073/pnas.87.7.2628. PubMed 2320579 ↗
  • Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino JJ, Siegel NR, Leimgruber RM, Feder J. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest. 1989 Nov;84(5):1470-8. doi: 10.1172/JCI114322. PubMed 2478587 ↗
  • Connolly DT, Olander JV, Heuvelman D, Nelson R, Monsell R, Siegel N, Haymore BL, Leimgruber R, Feder J. Human vascular permeability factor. Isolation from U937 cells. J Biol Chem. 1989 Nov 25;264(33):20017-24. PubMed 2584205 ↗
  • de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992 Feb 21;255(5047):989-91. doi: 10.1126/science.1312256. PubMed 1312256 ↗
  • Hayreh SS, Klugman MR, Podhajsky P, Kolder HE. Electroretinography in central retinal vein occlusion. Correlation of electroretinographic changes with pupillary abnormalities. Graefes Arch Clin Exp Ophthalmol. 1989;227(6):549-61. doi: 10.1007/BF02169451. PubMed 2483144 ↗
  • Fan W, Fleming A, Hemert JV, Wykoff CC, Brown DM, Robertson G, Wang K, Falavarjani KG, Sadda SR, Ip M. RETINAL VASCULAR BED AREA IN EYES WITH RETINAL VEIN OCCLUSION ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY: WAVE Study. Retina. 2022 Oct 1;42(10):1883-1888. doi: 10.1097/IAE.0000000000003549. PubMed 35976232 ↗
  • Wykoff CC, Ou WC, Wang R, Brown DM, Cone C, Zamora D, Le RT, Sagong M, Wang K, Sadda SR; WAVE Study Group. Peripheral Laser for Recalcitrant Macular Edema Owing to Retinal Vein Occlusion: The WAVE Trial. Ophthalmology. 2017 Jun;124(6):919-921. doi: 10.1016/j.ophtha.2017.01.049. Epub 2017 Mar 18. No abstract available. PubMed 28318636 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 8, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01710839
Lead sponsor
Charles C Wykoff, PhD, MD
Collaborators
Genentech, Inc.
Responsible party
Charles C Wykoff, PhD, MD (Deputy Director of Research, Greater Houston Retina Research) — Sponsor-investigator
First posted
Oct 19, 2012
Start date
Oct 2012
Primary completion
Oct 2015
Completion
Oct 2015
Results posted
Apr 11, 2017
Last update
Sep 8, 2017

Study contacts

Charles C Wykoff, PhD, MD
principal investigator · Retina Consultants Houston

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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