Exploratory Clinical Research for the Evaluation of Human GMP Collagen Implants (Humabiologics) in the Treatment of Corneal Melting.
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All trials for Patients With Severe Corneal Melting All trials of 3D collagen implant printed under GMP conditions.
-Summary
Participants will be invited to participate in this clinical study because they have a severe corneal melting. An eye disease characterized by the progressive loss of the transparent tissue that covers the eye (the cornea). This condition can cause pain, vision loss, and risk of eye perforation. Furthermore, in some cases, the response to standard treatments is inadequate.
A piece of 3D-printed human collagen will be implanted on the affected surface of the eye in order to reinforce and protect it and prevent its progression to perforation.
The collagen piece is biocompatible, flexible, and transparent, designed to integrate naturally with the eye's tissues. Since it does not require a complete transplant or a human donor at the time of surgery, it reduces the risks of rejection and complications associated with other more invasive techniques.
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+Detailed description
The 3D-printed collagen will be used in clinical research as a biocompatible graft for the treatment of severe corneal melting, providing structural support and promoting epithelial regeneration without the need for more invasive transplants.
+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| Only Group A. 3D collagen implant printed under GMP conditions. | Experimental | Device: 3D collagen implant printed under GMP conditions. | Group A. 3D collagen implant printed under GMP conditions. |
- 3D collagen implant printed under GMP conditions. (Device): Given its exploratory nature, the study does not propose an equivalence threshold compared to standard treatments, but rather seeks to confirm the safety and clinical viability of the implant. It is expected that 3D-printed collagen will provide superior stromal support, with greater transparency and stability than other reconstructive techniques, such as amniotic membrane, conjunctival flaps, or tectonic grafts.
+Outcome measures
Primary outcomes
- Incidence and severity of adverse reactions to evaluate the safety and biocompatibility of 3D-printed collagen in the corneal stroma of patients with severe corneal melting. [During 12 months after the surgery]: Incidence and severity of adverse reactions (safety and biocompatibility)
- Biocompatibility assessment: potential complications associated with the implant evaluated by slit lamp biomicroscopy [During 12 months after the surgery]: Biocompatibility assessment by slit lamp biomicroscopy
* Epithelial status: Not assessable , Reason: Lens /Tarsorrhaphy/ Edema or Other // Assessable : Epithelial defect present: Yes /No, Size of defect (if assessable) mm², Edges: Regular/ Irregular
* Overall corneal edema: Mild /Moderate / Severe
* Infiltrate: No /Yes (describe)
* Vascularization (scale 0-3)
* Secretion: Absent /Mild /Moderate / Profuse
* Signs of infection: No / Yes (describe)
- Potential complications associated with the implant evaluated by Optical Coherence Tomography (OCT) [During 12 months after the surgery]: Biocompatibility assessment by OCT:
* If the graft is present: Integration (Adequate/Partial/Displacement/ Graft edema/ Partial resorption) // Minimum thickness ( µm)
* If the graft is no longer present: ( Graft not visible/resorbed)
Secondary outcomes
- Determine the rate and time of corneal epithelial re-epithelization after implantation [During 12 months after the surgery]: Corneal re-epithelization rate and time measured with fluorescein staining. This will be measured as the area of the epithelial defect expressed in mm², which will allow both the rate of re-epithelialization and the time to complete closure to be calculated.
- Determine the rate and time of corneal epithelial re-epithelialization after implantation [During 12 months after the surgery]: Corneal thickness achieved in the area of corneal thinning by melting using Optical Coherence Tomography (OCT). This will be measured in μm.
- Compare the inflammatory response with conventional treatments (amniotic membrane, conjunctival flap, adhesives) [During 12 months after the surgery.]: Slit lamp biomicroscopy, evaluating:Presence and degree of conjunctival hyperemia (scale of 0 to 3) and Stromal edema (scale 0-3)
- Compare the inflammatory response with conventional treatments (amniotic membrane, conjunctival flap, adhesives) [During 12 months after the surgery]: Slit lamp biomicroscopy, evaluating:
Loss of transparency (standardized subjective scale 0-3)
- Compare the inflammatory response with conventional treatments (amniotic membrane, conjunctival flap, adhesives) [During 12 months after the surgery]: Slit lamp biomicroscopy, evaluating:
Presence of keratic precipitates, cells, and flare in the anterior chamber, if applicable.
- Compare the inflammatory response with conventional treatments (amniotic membrane, conjunctival flap, adhesives) by photograph [During 12 months after the surgery]: 2\. Photograph of the anterior segment at each visit to document changes and allow for masked evaluation by external experts .
- Quality of life scales: Visual quality and symptom questionnaires: Ocular Surface Disease Index (OSDI) [12 months since surgery]: The questions are responsed as Scale: 0 = None of the time, 1 = Some of the time, 2 = Half of the time, 3 = Most of the time, 4 = All of the time. According to the sum total of the questions: Severity Levels: Normal (0-12), Mild (13-22), Moderate (23-32), Severe (33-100)
- Quality of life scales: Visual quality and symptom questionnaires: National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) [12 months since surgery]: High Scores (close to 100): Indicate little to no impairment in that specific area of life.
Low Scores (closer to 0): Indicate significant difficulty or dependency caused by poor vision.
- Quality of life scales: Visual quality and symptom questionnaires: Eye pain and discomfort scales [12 months since surgery]: Visual Analogue Scale (VAS) from 0 to 10 : Mild ( from 0 to 2), Moderate (from 3 to 7) and severe (from 8 to 10)
- Quality of life scales: Visual quality and symptom questionnaires: Eye pain and discomfort scales: Symptom Likert scale [12 months since surgery]: (0 = none, 4 = very severe) to assess burning, photophobia, foreign body sensation, and tearing.
+Eligibility
Sex: All, ages: 18 Years to any
Inclusion Criteria:
1. Age over 18 years.
2. Patients who, after receiving detailed information about the design, purpose, risks, and implications of the study, and about their right to withdraw at any time without repercussions, give their informed written consent.
3. Confirmed diagnosis of severe corneal melting.
4. Absence of response to conventional non-surgical treatments, which must include:
* Intensive antibiotic, antifungal, or antiviral treatment according to etiology.
* Anti-inflammatory or immunomodulatory eye drops (such as corticosteroids, cyclosporine, tacrolimus).
* Intensive lubrication and/or autologous serum.
* Use of therapeutic contact lenses.
* The patient must not have responded satisfactorily to these measures and must show progression or persistence of the ulcer, thinning, and structural risk.
The absence of response is not defined by a specific number of treatments, but by the lack of clinical improvement or progression of the condition despite having received several of these measures appropriately. In particular, progression of the epithelial defect, worsening stromal thinning, or the appearance of signs of perforation risk will be considered an absence of response, which would justify surgical intervention.
5. If the patient has previously undergone surgical procedures or received other implants (such as amniotic membrane, conjunctival flap, or Tenon's graft), this will be included if there is documented clinical progression without sufficient functional or structural recovery, and provided that there are no surgical alternatives with documented superior efficacy in their specific situation.
Exclusion Criteria:
1. Pregnancy or breastfeeding.
2. Refusal to participate in the study.
3. Presence of active eye infection.
4. Systemic diseases that may affect healing.
5. Known hypersensitivity to collagen compounds.
6. Any circumstance that, in the investigator's opinion, makes the patient's participation in the clinical research inadvisable.
+Locations (1)
| Facility | City | Country | Status |
|---|
| Hospital Universitario Ramón y Cajal | Madrid, Madrid | Spain | Recruiting |
+Publications
- Stokking M, Cadenas-Martín M, Martín-González AI, Fernández-Ferrer A, Arnalich-Montiel F, De Miguel MP. (2025). Three-dimensional-printed collagen scaffold with limbal stem cells derived from adipose-derived mesenchymal stem cells for the treatment of limbal stem cell deficiency. Int J Bioprinting, 11(6), 407-429. doi:10.36922/IJB025290293
- Deshmukh R, Stevenson LJ, Vajpayee R. Management of corneal perforations: An update. Indian J Ophthalmol. 2020 Jan;68(1):7-14. doi: 10.4103/ijo.IJO_1151_19. PMID 31856457
- 10. Koenig KR, et al. "Biomaterials for corneal regeneration: Current perspectives." J Biomed Mater Res. 2020.
- Vajpayee RB, Singhvi A, Sharma N, Sinha R. Penetrating keratoplasty for perforated corneal ulcers: preservation of iris by corneal debulking. Cornea. 2006 Jan;25(1):44-6. doi: 10.1097/01.ico.0000177834.85507.28. PMID 16331040
- Korah S, Selvin SS, Pradhan ZS, Jacob P, Kuriakose T. Tenons Patch Graft in the Management of Large Corneal Perforations. Cornea. 2016 May;35(5):696-9. doi: 10.1097/ICO.0000000000000808. PMID 26989954
- Hick S, Demers PE, Brunette I, La C, Mabon M, Duchesne B. Amniotic membrane transplantation and fibrin glue in the management of corneal ulcers and perforations: a review of 33 cases. Cornea. 2005 May;24(4):369-77. doi: 10.1097/01.ico.0000151547.08113.d1. PMID 15829790
- Solomon A, Meller D, Prabhasawat P, John T, Espana EM, Steuhl KP, Tseng SC. Amniotic membrane grafts for nontraumatic corneal perforations, descemetoceles, and deep ulcers. Ophthalmology. 2002 Apr;109(4):694-703. doi: 10.1016/s0161-6420(01)01032-6. PMID 11927426
- Lee SH, Tseng SC. Amniotic membrane transplantation for persistent epithelial defects with ulceration. Am J Ophthalmol. 1997 Mar;123(3):303-12. doi: 10.1016/s0002-9394(14)70125-4. PMID 9063239
- Sii F, Lee GA. Fibrin glue in the management of corneal melt. Clin Exp Ophthalmol. 2005 Oct;33(5):532-4. doi: 10.1111/j.1442-9071.2005.01076.x. PMID 16181285
- Lagoutte FM, Gauthier L, Comte PR. A fibrin sealant for perforated and preperforated corneal ulcers. Br J Ophthalmol. 1989 Sep;73(9):757-61. doi: 10.1136/bjo.73.9.757. PMID 2804032
- Setlik DE, Seldomridge DL, Adelman RA, Semchyshyn TM, Afshari NA. The effectiveness of isobutyl cyanoacrylate tissue adhesive for the treatment of corneal perforations. Am J Ophthalmol. 2005 Nov;140(5):920-1. doi: 10.1016/j.ajo.2005.04.062. PMID 16310475
+Investigators
- Francisco Arnalich-Montiel, MD, Study director, Hospital Ramón y Cajal. Servicio de Oftalmología. Ctra. de Colmenar Km 9,100. 28034 Madrid
- María P. De Miguel, MD, Principal investigator, Instituto de Investigaciones Sanitarias del Hospital Universitario La Paz, IdiPAZ, Madrid