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

NCT ID: NCT04584125

Last Updated: 2023-01-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

216 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-01

Study Completion Date

2028-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Keratoconus

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Ex vivo cross linking of donor corneal tissue

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

Group Type EXPERIMENTAL

Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% with UV light

Intervention Type DRUG

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.

Non-cross-linked donor corneal tissue for keratoplasty

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

Group Type SHAM_COMPARATOR

Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% without UV light

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% with UV light

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

Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% without UV light

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

PHOTREXA VISCOUS PHOTREXA VISCOUS

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Joseph B. Ciolino, MD

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Joseph B. Ciolino, MD

Associate Professor of Ophthalmology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Joseph B Ciolino

Role: PRINCIPAL_INVESTIGATOR

Massachusetts Eye and Ear

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Joseph B Ciolino, MD

Role: CONTACT

(617) 573-3938

Ellen Fitzgerald

Role: CONTACT

617-573-6971

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Joseph Ciolino, MD

Role: primary

617-573-5575

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 6230745 (View on PubMed)

Tan DT, Por YM. Current treatment options for corneal ectasia. Curr Opin Ophthalmol. 2007 Jul;18(4):284-9. doi: 10.1097/ICU.0b013e3281a7ecaa.

Reference Type BACKGROUND
PMID: 17568202 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30196480 (View on PubMed)

Bechrakis N, Blom ML, Stark WJ, Green WR. Recurrent keratoconus. Cornea. 1994 Jan;13(1):73-7. doi: 10.1097/00003226-199401000-00012.

Reference Type BACKGROUND
PMID: 8131410 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7004192 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18471635 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12719068 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21320951 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12867398 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16570014 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19104411 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1565452 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3287939 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2665502 (View on PubMed)

Swinger CA. Postoperative astigmatism. Surv Ophthalmol. 1987 Jan-Feb;31(4):219-48. doi: 10.1016/0039-6257(87)90023-3.

Reference Type BACKGROUND
PMID: 3554571 (View on PubMed)

Troutman RC, Lawless MA. Penetrating keratoplasty for keratoconus. Cornea. 1987;6(4):298-305. doi: 10.1097/00003226-198706040-00013.

Reference Type BACKGROUND
PMID: 3319412 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1923353 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10387463 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9487761 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21420606 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16814052 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9049932 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8624832 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2683795 (View on PubMed)

Fronterre A, Portesani GP. Relaxing incisions for postkeratoplasty astigmatism. Cornea. 1991 Jul;10(4):305-11. doi: 10.1097/00003226-199107000-00005.

Reference Type BACKGROUND
PMID: 1889216 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16814049 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2020P002132

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

McNeel Eye Center Corneal Crosslinking Study
NCT02921009 ACTIVE_NOT_RECRUITING NA
Corneal Tissue Inlay for Keratoconus
NCT02649738 ACTIVE_NOT_RECRUITING NA
Prevelance of Keratoconus
NCT04092426 UNKNOWN