search
Back to results

A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients (EVOKE)

Primary Purpose

Keratoconus

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% with UV light
Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% without UV light
Sponsored by
Joseph B. Ciolino, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Keratoconus focused on measuring Corneal Crosslinking, Penetrating Keratoplasty, Deep Anterior Lamellar Keratoplasty

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Willing and able to provide written informed consent.
  • Willing and able to comply with study assessments for the full duration of the study.
  • Age ≥18 years but ≤50 years
  • History of keratoconus (without a previous transplant) requiring a penetrating keratoplasty
  • Willing to commit to not having further cross-linking, corneal relaxing incisions, intacs, or corneal laser vision correction during the course of the study

Exclusion Criteria:

  • Age < 18 years >50
  • Inability to provide written informed consent and comply with study assessments for the full duration of the study
  • Participation in another simultaneous interventional medical investigation or trial

Systemic

  • History of Stevens-Johnson syndrome or ocular pemphigoid
  • Signs of current infection, including fever and current treatment with antibiotics
  • Pregnancy (positive pregnancy test) or lactating
  • Pre-menopausal sexually active women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method)

Recipient Eye

  • Corneal or ocular surface infection within 30 days prior to study entry
  • History of previous cross-linking
  • History of previous corneal transplant
  • Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
  • Ocular or periocular malignancy
  • Lid abnormalities that in the opinion of the investigator could confound the study results and these include clinically significant ectropion, lagophthalmos, cicatrization, entropion, and rosacea
  • Neurotrophic cornea
  • Monocular
  • Uncontrolled glaucoma
  • Glaucoma filtering devices or trabeculectomies

Sites / Locations

  • Massachusetts Eye and Ear Infirmary

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Ex vivo cross linking of donor corneal tissue

Non-cross-linked donor corneal tissue for keratoplasty

Arm Description

Treatment Arm: The donor corneal tissue used in the PK or DALK procedures will previously undergo ex vivo crosslinking.

Control Arm: The donor corneal tissue used in the PK or DALK procedures will not previously undergo ex vivo crosslinking.

Outcomes

Primary Outcome Measures

• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery.
• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery

Secondary Outcome Measures

• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
Manifest cylinder astigmatism at 130 weeks post-surgery
Manifest cylinder astigmatism at 130 weeks post-surgerykeratometry, anterior mean keratometry, posterior mean keratometry
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgery
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgerypermeable contact lens.

Full Information

First Posted
October 5, 2020
Last Updated
January 12, 2023
Sponsor
Joseph B. Ciolino, MD
search

1. Study Identification

Unique Protocol Identification Number
NCT04584125
Brief Title
A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients
Acronym
EVOKE
Official Title
A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2023 (Anticipated)
Primary Completion Date
May 1, 2028 (Anticipated)
Study Completion Date
November 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Joseph B. Ciolino, MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized clinical trial will assess corneal astigmatism and visual outcomes in participants who have undergone corneal transplantation for keratoconus with ex vivo cross-linked donor corneal tissue versus participants who have undergone corneal transplantation for keratoconus with non-cross-linked donor corneas. Crosslinking is a procedure that stabilizes the biomechanical properties of the cornea; as a result, the cornea stiffens. It has been shown that this procedure stabilizes the cornea of patients with keratoconus or corneal ectasias. The FDA currently approves crosslinking for patients with progressive keratoconus and corneal ectasia following refractive surgery. Ex vivo crosslinking of donor corneal tissue for patients with keratoconus undergoing PK or DALK could stabilize the cornea and reduce the risk of high astigmatism and improve vision in patient with keratoconus.
Detailed Description
The 15 clinical sites are expected to recruit cumulatively 216 cases over 18 months. Eligibility is assessed during a routine examination by an investigator. Informed consent will be obtained prior to collecting any information that is not part of usual care. Patients who meet all inclusion criteria and none of the exclusion criteria will be given the opportunity to participate in the study. Participants will be randomly assigned to the treatment group (cross-linked corneal tissue) or control group (non-cross-linked corneal tissue that has been exposed to riboflavin, but no ultraviolet light). The investigator will request a cadaveric cornea from the study's central eye bank CorneaGen, which will prepare the cadaveric cornea. Participants will receive the cross-linked donor tissue or control donor tissue during surgery. Clinical sites, including surgeons, and participants will be masked to treatment assignment. Participants will be followed up post-operatively by the site investigators as per the standard of care. This will include visits at 1 Day, 1 Week, 1 Month, 6 Months, 1 Year, 1.5 Years, 2 Years, and 2.5 Years post-surgery. Some participants may need to be seen more regularly for routine care. The investigators will monitor for systemic and ocular adverse events at all follow-up visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Keratoconus
Keywords
Corneal Crosslinking, Penetrating Keratoplasty, Deep Anterior Lamellar Keratoplasty

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The study is a multicenter, double-masked, parallel, and randomized study with a subsequent follow-up period of 30 months. 216 subjects (of any race or gender) who have keratoconus (between the ages of 18 and 50) will sign the consent for their first PK or DALK surgery in the study eye. Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be given the opportunity to participate in the study. Subjects will either randomized to the treatment group (crosslinked corneal tissue) or control group (non-crosslinked corneal tissue that has been exposed to riboflavin, but no ultraviolet light).
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
216 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ex vivo cross linking of donor corneal tissue
Arm Type
Experimental
Arm Description
Treatment Arm: The donor corneal tissue used in the PK or DALK procedures will previously undergo ex vivo crosslinking.
Arm Title
Non-cross-linked donor corneal tissue for keratoplasty
Arm Type
Sham Comparator
Arm Description
Control Arm: The donor corneal tissue used in the PK or DALK procedures will not previously undergo ex vivo crosslinking.
Intervention Type
Drug
Intervention Name(s)
Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% with UV light
Other Intervention Name(s)
PHOTREXA VISCOUS
Intervention Description
A wavelength of 365 nm ultraviolet A light will be used to direct 5.4 J/cm2 using a beam diameter of 9.5mm to treat the de-epithelialized corneal surface of a donor cornea for 30 minutes. Every 2 minutes, the UV light will be used while another drop of riboflavin is applied on top of the donor cornea.
Intervention Type
Drug
Intervention Name(s)
Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% without UV light
Other Intervention Name(s)
PHOTREXA VISCOUS
Intervention Description
The corneal tissue for the control arm will be treated the same as the crosslinked tissue except that it will not be exposed to ultraviolet light. The donor cornea will be placed on an artificial anterior chamber maintainer and the epithelium will be removed mechanically. Riboflavin solution (0.1% riboflavin and 20% dextran supplied in a sterile, single-dose container) will be applied to the cornea every 2 minutes for 30 minutes.
Primary Outcome Measure Information:
Title
• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery.
Description
• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery
Time Frame
130 weeks
Secondary Outcome Measure Information:
Title
• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
Description
• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
Time Frame
130 weeks
Title
Manifest cylinder astigmatism at 130 weeks post-surgery
Description
Manifest cylinder astigmatism at 130 weeks post-surgerykeratometry, anterior mean keratometry, posterior mean keratometry
Time Frame
130 weeks
Title
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
Description
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
Time Frame
130 weeks
Title
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgery
Description
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgerypermeable contact lens.
Time Frame
130 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Willing and able to provide written informed consent. Willing and able to comply with study assessments for the full duration of the study. Age ≥18 years but ≤50 years History of keratoconus (without a previous transplant) requiring keratoplasty Willing to commit to not having further cross-linking, corneal relaxing incisions, intacs, or corneal laser vision correction during the course of the study Exclusion Criteria: Age < 18 years >50 Inability to provide written informed consent and comply with study assessments for the full duration of the study Participation in another simultaneous interventional medical investigation or trial Systemic History of Stevens-Johnson syndrome or ocular pemphigoid Signs of current infection, including fever and current treatment with antibiotics Pregnancy (positive pregnancy test) or lactating Pre-menopausal sexually active women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method) Recipient Eye Corneal or ocular surface infection within 30 days prior to study entry History of previous cross-linking History of previous corneal transplant Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively Ocular or periocular malignancy Lid abnormalities that in the opinion of the investigator could confound the study results and these include clinically significant ectropion, lagophthalmos, cicatrization, entropion, and rosacea Neurotrophic cornea Monocular Uncontrolled glaucoma Glaucoma filtering devices or trabeculectomies
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joseph B Ciolino, MD
Phone
(617) 573-3938
Email
Joseph_Ciolino@MEEI.HARVARD.EDU
First Name & Middle Initial & Last Name or Official Title & Degree
Ellen Fitzgerald
Phone
617-573-6971
Email
Ellen_Fitzgerald@MEEI.HARVARD.EDU
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph B Ciolino
Organizational Affiliation
Massachusetts Eye and Ear
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts Eye and Ear Infirmary
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Ciolino, MD
Phone
617-573-5575
Email
Joseph_Ciolino@meei.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is not a plan to make individual participant data (IPD) available.
Citations:
PubMed Identifier
6230745
Citation
Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984 Jan-Feb;28(4):293-322. doi: 10.1016/0039-6257(84)90094-8.
Results Reference
background
PubMed Identifier
17568202
Citation
Tan DT, Por YM. Current treatment options for corneal ectasia. Curr Opin Ophthalmol. 2007 Jul;18(4):284-9. doi: 10.1097/ICU.0b013e3281a7ecaa.
Results Reference
background
PubMed Identifier
30196480
Citation
Yoshida J, Murata H, Miyai T, Shirakawa R, Toyono T, Yamagami S, Usui T. Characteristics and risk factors of recurrent keratoconus over the long term after penetrating keratoplasty. Graefes Arch Clin Exp Ophthalmol. 2018 Dec;256(12):2377-2383. doi: 10.1007/s00417-018-4131-5. Epub 2018 Sep 8.
Results Reference
background
PubMed Identifier
8131410
Citation
Bechrakis N, Blom ML, Stark WJ, Green WR. Recurrent keratoconus. Cornea. 1994 Jan;13(1):73-7. doi: 10.1097/00003226-199401000-00012.
Results Reference
background
PubMed Identifier
7004192
Citation
Abelson MB, Collin HB, Gillette TE, Dohlman CH. Recurrent keratoconus after keratoplasty. Am J Ophthalmol. 1980 Nov;90(5):672-6. doi: 10.1016/s0002-9394(14)75135-9.
Results Reference
background
PubMed Identifier
18471635
Citation
Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg. 2008 May;34(5):796-801. doi: 10.1016/j.jcrs.2007.12.039.
Results Reference
background
PubMed Identifier
12719068
Citation
Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1.
Results Reference
background
PubMed Identifier
21320951
Citation
Kelly TL, Williams KA, Coster DJ; Australian Corneal Graft Registry. Corneal transplantation for keratoconus: a registry study. Arch Ophthalmol. 2011 Jun;129(6):691-7. doi: 10.1001/archophthalmol.2011.7. Epub 2011 Feb 14.
Results Reference
background
PubMed Identifier
12867398
Citation
Thompson RW Jr, Price MO, Bowers PJ, Price FW Jr. Long-term graft survival after penetrating keratoplasty. Ophthalmology. 2003 Jul;110(7):1396-402. doi: 10.1016/S0161-6420(03)00463-9.
Results Reference
background
PubMed Identifier
16570014
Citation
Williams KA, Esterman AJ, Bartlett C, Holland H, Hornsby NB, Coster DJ. How effective is penetrating corneal transplantation? Factors influencing long-term outcome in multivariate analysis. Transplantation. 2006 Mar 27;81(6):896-901. doi: 10.1097/01.tp.0000185197.37824.35.
Results Reference
background
PubMed Identifier
19104411
Citation
Williams KA, Lowe M, Bartlett C, Kelly TL, Coster DJ; All Contributors. Risk factors for human corneal graft failure within the Australian corneal graft registry. Transplantation. 2008 Dec 27;86(12):1720-4. doi: 10.1097/TP.0b013e3181903b0a.
Results Reference
background
PubMed Identifier
1565452
Citation
Williams KA, Roder D, Esterman A, Muehlberg SM, Coster DJ. Factors predictive of corneal graft survival. Report from the Australian Corneal Graft Registry. Ophthalmology. 1992 Mar;99(3):403-14. doi: 10.1016/s0161-6420(92)31960-8.
Results Reference
background
PubMed Identifier
3287939
Citation
Binder PS. The effect of suture removal on postkeratoplasty astigmatism. Am J Ophthalmol. 1988 Jun 15;105(6):637-45. doi: 10.1016/0002-9394(88)90057-8.
Results Reference
background
PubMed Identifier
2665502
Citation
Limberg MB, Dingeldein SA, Green MT, Klyce SD, Insler MS, Kaufman HE. Corneal compression sutures for the reduction of astigmatism after penetrating keratoplasty. Am J Ophthalmol. 1989 Jul 15;108(1):36-42. doi: 10.1016/s0002-9394(14)73257-x.
Results Reference
background
PubMed Identifier
3554571
Citation
Swinger CA. Postoperative astigmatism. Surv Ophthalmol. 1987 Jan-Feb;31(4):219-48. doi: 10.1016/0039-6257(87)90023-3.
Results Reference
background
PubMed Identifier
3319412
Citation
Troutman RC, Lawless MA. Penetrating keratoplasty for keratoconus. Cornea. 1987;6(4):298-305. doi: 10.1097/00003226-198706040-00013.
Results Reference
background
PubMed Identifier
1923353
Citation
Price FW Jr, Whitson WE, Marks RG. Progression of visual acuity after penetrating keratoplasty. Ophthalmology. 1991 Aug;98(8):1177-85. doi: 10.1016/s0161-6420(91)32136-5.
Results Reference
background
PubMed Identifier
10387463
Citation
Riddle HK Jr, Parker DA, Price FW Jr. Management of postkeratoplasty astigmatism. Curr Opin Ophthalmol. 1998 Aug;9(4):15-28. doi: 10.1097/00055735-199808000-00004.
Results Reference
background
PubMed Identifier
9487761
Citation
Sporl E, Huhle M, Kasper M, Seiler T. [Increased rigidity of the cornea caused by intrastromal cross-linking]. Ophthalmologe. 1997 Dec;94(12):902-6. doi: 10.1007/s003470050219. German.
Results Reference
background
PubMed Identifier
21420606
Citation
de Sanctis U, Eandi C, Grignolo F. Phacoemulsification and customized toric intraocular lens implantation in eyes with cataract and high astigmatism after penetrating keratoplasty. J Cataract Refract Surg. 2011 Apr;37(4):781-5. doi: 10.1016/j.jcrs.2011.01.015.
Results Reference
background
PubMed Identifier
16814052
Citation
Rajan MS, O'Brart DP, Patel P, Falcon MG, Marshall J. Topography-guided customized laser-assisted subepithelial keratectomy for the treatment of postkeratoplasty astigmatism. J Cataract Refract Surg. 2006 Jun;32(6):949-57. doi: 10.1016/j.jcrs.2006.02.036.
Results Reference
background
PubMed Identifier
9049932
Citation
Arenas E, Maglione A. Laser in situ keratomileusis for astigmatism and myopia after penetrating keratoplasty. J Refract Surg. 1997 Jan-Feb;13(1):27-32. doi: 10.3928/1081-597X-19970101-09.
Results Reference
background
PubMed Identifier
8624832
Citation
Belmont SC, Lazzaro DR, Muller JW, Troutman RC. Combined wedge resection and relaxing incisions for astigmatism after penetrating keratoplasty. J Refract Surg. 1995 Nov-Dec;11(6):472-6. doi: 10.3928/1081-597X-19951101-14.
Results Reference
background
PubMed Identifier
2683795
Citation
Girard LJ. Corneal compression sutures for the reduction of astigmatism after penetrating keratoplasty. Am J Ophthalmol. 1989 Nov 15;108(5):614. doi: 10.1016/0002-9394(89)90455-8. No abstract available.
Results Reference
background
PubMed Identifier
1889216
Citation
Fronterre A, Portesani GP. Relaxing incisions for postkeratoplasty astigmatism. Cornea. 1991 Jul;10(4):305-11. doi: 10.1097/00003226-199107000-00005.
Results Reference
background
PubMed Identifier
16814049
Citation
Bochmann F, Schipper I. Correction of post-keratoplasty astigmatism with keratotomies in the host cornea. J Cataract Refract Surg. 2006 Jun;32(6):923-8. doi: 10.1016/j.jcrs.2006.02.013.
Results Reference
background

Learn more about this trial

A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients

We'll reach out to this number within 24 hrs