Corneal UlcerNCT05940376
Topical Insulin in Neurotrophic Keratopathy After Diabetic Vitrectomy
An observational study of Corneal Ulcer and Neurotrophic Corneal Ulcer, run by Benha University at 1 site in Egypt.
Trial summary
Various treatment options have been proposed in managing NK such as preservative-free lubrication (PF-L), withdrawal of epitheliotoxic medication, prophylactic antibiotics, applying of bandage contact lenses, using hemoderivatives 8, topical insulin, recombinant nerve growth factor (rNGF) or epidermal growth factor… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corneal Ulcer, Neurotrophic Corneal Ulcer, Diabetes Mellitus
- What is being tested?
- rapid acting insulin
- How many people
- 30 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Jul 2023to 15 Aug 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult diabetic patients (18 years of age) with neurotrophic keratopathy developing within 21 days after diabetic vitrectomy.
Who may be able to join
- Adult diabetic patients (18 years of age) with neurotrophic keratopathy developing within 21 days after diabetic vitrectomy. NK was classified as stage 1 (epithelial changes only without epithelial defect), stage 2 (persistent epithelial defect) or stage 3 (corneal ulcer) according to published criteria.
- decreased corneal sensitivity within the corneal lesion and in at least 1 corneal quadrant outside the lesion.
Who cannot join
- Those patients who needed intraoperative epithelial debridement during vitrectomy, having past history of ocular surgeries other than cataract surgery, or history of herpetic eye disease or limbal stem cell deficiency were excluded.
- active ocular infection or inflammation unrelated to neurotrophic keratopathy, lagophthalmos, and other ocular disease or severe vision loss in the affected eye(s).
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Benha University
Banhā, 13512
Taher Eleiwa, MD PhD, 01069901973, taher.eleiwa@fmed.bu.edu.eg
About this study
Official title: Efficacy and Safety of Topical Insulin in Acute-onset Neurotrophic Keratopathy After Diabetic Vitrectomy
Various treatment options have been proposed in managing NK such as preservative-free lubrication (PF-L), withdrawal of epitheliotoxic medication, prophylactic antibiotics, applying of bandage contact lenses, using hemoderivatives 8, topical insulin, recombinant nerve growth factor (rNGF) or epidermal growth factor (rEGF).11,12, amniotic membrane transplant (AMT), or corneal neurotization.2,4,9,10 Topical insulin has been reported to effectively promote the healing of persistent corneal epithelial defects.
In our retrospective study, we explored the safety and efficacy of topical insulin, as a first-line treatment, in treatment-naïve acute NK after diabetic vitrectomy.
Read the detailed description
Corneal nerves play a vital role in maintaining the homeostasis of the ocular surface. Not only mediating sensory reflexes such as blinking and lacrimation, but also corneal nerves critically maintain the integrity of corneal epithelium and the nerves themselves via producing trophic factors. An insult anywhere from the trigeminal nerve nucleus to the terminal nerve endings of the nasociliary nerve can disrupt this homeostasis and lead to corneal hypoesthesia and neurotrophic keratopathy (NK). The pathogenesis of NK has been associated with infectious, inflammatory, toxic, and iatrogenic etiologies such as ocular herpetic infection, ocular or neurologic surgery, trauma, chemical burn, diabetes, and dry eye disease. 3,4 In diabetic keratopathy, several corneal changes have been reported including abnormal basement membrane structure, poor epithelial adherence, hypothesia and alterations in the corneal stroma, Descemet membrane, and corneal endothelium. Also, NK has been reported as a rare complication of endolaser panretinal photocoagulation (PRP) and transscleral cyclophotocoagulation.7, 8, 9, 10, 11 The suggested mechanism entails the occurrence of thermal injury to the long ciliary nerve branches as they enter the suprachoroidal space at the positions corresponding to 3 and 9 o'clock on the eye. In diabetic patients, NK may present as a persistent epithelial defect refractory to conventional measures, predisposing to microbial keratitis, and/or stromal melting/scarring with subsequent perforation/blindness.3,4 Thus, rapid corneal re-epithelialization is needed to restore the corneal surface integrity.
Various treatment options have been proposed in managing NK such as preservative-free lubrication (PF-L), withdrawal of epitheliotoxic medication, prophylactic antibiotics, applying of bandage contact lenses, using hemoderivatives 8, topical insulin, recombinant nerve growth factor (rNGF) or epidermal growth factor (rEGF).11,12, amniotic membrane transplant (AMT), or corneal neurotization.2,4,9,10 Topical insulin has been reported to effectively promote the healing of persistent corneal epithelial defects.
In our study, we explored the safety and efficacy of topical insulin, as a first-line treatment, in treatment-naïve acute NK after diabetic vitrectomy.
- Conditions
- Corneal Ulcer, Neurotrophic Corneal Ulcer, Diabetes Mellitus
- Being tested
- rapid acting insulin
- Medical subject headings
- Corneal Ulcer, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rapid acting insulinDrug
Topical insulin drops were prepared by diluting 1 unit of fast-acting insulin per 1 mL of an artificial tear with a propylene glycol base. Drops were preserved at low temperature (2°C) and, was provided by the cornea specialist and was self-administered by patients at a dosage of 1 eye drop 4 times daily. Treatment continued until NK healed and then tapered accordingly. Patients would discontinue topical insulin if the condition did not improve or worsen within 4 weeks. Patients were followed up daily and slit-lamp photographs were captured with and without fluorescein corneal staining.
| Study group | Role | What they receive |
|---|---|---|
| Control | Group A was assigned to receive preservative-free lubricants and prophylactic antibiotics. | |
| Study | Group B was assigned to receive topical insulin [1 unit per drop] 4 times per day (QID) in addition to previous treatment. Receives: Drug: rapid acting insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
time to epithelial healing
healed ulcer is defined as <0.5 mm of fluorescein staining in the greatest dimension of the lesion area.
Measured: 4 weeks
Secondary outcomes (1)
any adverse effect of topical insulin or need for amniotic membrane transplantation
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2023
- Study start15 Jul 2023 (estimated)
- Primary completion1 Aug 2023 (estimated)
- Study completion15 Aug 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Corneal UlcerStudies of the same condition, open and under way.
- More trials run by Benha UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Benha University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Taher Eleiwa, Benha University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05940376
- Sponsor's protocol ID
- RC-7-2023
- Status last verified
- Jul 2023
- First submitted
- 2 Jul 2023
- Last updated
- 11 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: study data will be available upon request
Publications
Soares RJDSM, Arede C, Sousa Neves F, da Silva Fernandes J, Cunha Ferreira C, Sequeira J. Topical Insulin-Utility and Results in Refractory Neurotrophic Keratopathy in Stages 2 and 3. Cornea. 2022 Aug 1;41(8):990-994. doi: 10.1097/ICO.0000000000002858. Epub 2021 Sep 3.
PubMed 34483270Galvis V, Nino CA, Tello A, Grice JM, Gomez MA. Topical insulin in neurotrophic keratopathy after resection of acoustic neuroma. Arch Soc Esp Oftalmol (Engl Ed). 2019 Feb;94(2):100-104. doi: 10.1016/j.oftal.2018.06.003. Epub 2018 Jul 17. English, Spanish.
PubMed 30025986
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Topical Insulin in Acute-onset Neurotrophic Keratopathy After Diabetic Vitrectomy
- ClinicalTrials.gov ID
- NCT05940376
- Acronym / sponsor ID
- RC-7-2023
- Conditions
- Corneal Ulcer, Neurotrophic Corneal Ulcer, Diabetes Mellitus
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Benha UniversityUniversity, hospital or other
- Study start
- 15 Jul 2023 (estimated)
- Primary completion
- 1 Aug 2023 (estimated)
- Study completion
- 15 Aug 2023 (estimated)
- First posted
- 11 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Various treatment options have been proposed in managing NK such as preservative-free lubrication (PF-L), withdrawal of epitheliotoxic medication, prophylactic antibiotics, applying of bandage contact lenses, using hemoderivatives 8, topical insulin, recombinant nerve growth factor (rNGF) or epidermal growth factor (rEGF).11,12, amniotic membrane transplant (AMT), or corneal neurotization.2,4,9,10 Topical insulin has been reported to effectively promote the healing of persistent corneal epithelial defects.
In our retrospective study, we explored the safety and efficacy of topical insulin, as a first-line treatment, in treatment-naïve acute NK after diabetic vitrectomy.
Detailed description
Corneal nerves play a vital role in maintaining the homeostasis of the ocular surface. Not only mediating sensory reflexes such as blinking and lacrimation, but also corneal nerves critically maintain the integrity of corneal epithelium and the nerves themselves via producing trophic factors. An insult anywhere from the trigeminal nerve nucleus to the terminal nerve endings of the nasociliary nerve can disrupt this homeostasis and lead to corneal hypoesthesia and neurotrophic keratopathy (NK). The pathogenesis of NK has been associated with infectious, inflammatory, toxic, and iatrogenic etiologies such as ocular herpetic infection, ocular or neurologic surgery, trauma, chemical burn, diabetes, and dry eye disease. 3,4 In diabetic keratopathy, several corneal changes have been reported including abnormal basement membrane structure, poor epithelial adherence, hypothesia and alterations in the corneal stroma, Descemet membrane, and corneal endothelium. Also, NK has been reported as a rare complication of endolaser panretinal photocoagulation (PRP) and transscleral cyclophotocoagulation.7, 8, 9, 10, 11 The suggested mechanism entails the occurrence of thermal injury to the long ciliary nerve branches as they enter the suprachoroidal space at the positions corresponding to 3 and 9 o'clock on the eye. In diabetic patients, NK may present as a persistent epithelial defect refractory to conventional measures, predisposing to microbial keratitis, and/or stromal melting/scarring with subsequent perforation/blindness.3,4 Thus, rapid corneal re-epithelialization is needed to restore the corneal surface integrity.
Various treatment options have been proposed in managing NK such as preservative-free lubrication (PF-L), withdrawal of epitheliotoxic medication, prophylactic antibiotics, applying of bandage contact lenses, using hemoderivatives 8, topical insulin, recombinant nerve growth factor (rNGF) or epidermal growth factor (rEGF).11,12, amniotic membrane transplant (AMT), or corneal neurotization.2,4,9,10 Topical insulin has been reported to effectively promote the healing of persistent corneal epithelial defects.
In our study, we explored the safety and efficacy of topical insulin, as a first-line treatment, in treatment-naïve acute NK after diabetic vitrectomy.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | – | –Group A was assigned to receive preservative-free lubricants and prophylactic antibiotics. |
| Study | – | Drug: rapid acting insulinGroup B was assigned to receive topical insulin [1 unit per drop] 4 times per day (QID) in addition to previous treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult diabetic patients (18 years of age) with neurotrophic keratopathy developing within 21 days after diabetic vitrectomy.
Key inclusion criteria (2 listed)
- Adult diabetic patients (18 years of age) with neurotrophic keratopathy developing within 21 days after diabetic vitrectomy. NK was classified as stage 1 (epithelial changes only without epithelial defect), stage 2 (persistent epithelial defect) or stage 3 (corneal ulcer) according to published criteria.
- decreased corneal sensitivity within the corneal lesion and in at least 1 corneal quadrant outside the lesion.
Key exclusion criteria (2 listed)
- Those patients who needed intraoperative epithelial debridement during vitrectomy, having past history of ocular surgeries other than cataract surgery, or history of herpetic eye disease or limbal stem cell deficiency were excluded.
- active ocular infection or inflammation unrelated to neurotrophic keratopathy, lagophthalmos, and other ocular disease or severe vision loss in the affected eye(s).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rapid acting insulinTopical insulin drops were prepared by diluting 1 unit of fast-acting insulin per 1 mL of an artificial tear with a propylene glycol base. Drops were preserved at low temperature (2°C) and, was provided by the cornea specialist and was self-administered by patients at a dosage of 1 eye drop 4 times daily. Treatment continued until NK healed and then tapered accordingly. Patients would discontinue topical insulin if the condition did not improve or worsen within 4 weeks. Patients were followed up daily and slit-lamp photographs were captured with and without fluorescein corneal staining. | Drug | Study |
Primary outcome
time to epithelial healing
Time frame: 4 weeks
healed ulcer is defined as <0.5 mm of fluorescein staining in the greatest dimension of the lesion area.
1 secondary outcome
any adverse effect of topical insulin or need for amniotic membrane transplantation
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2023.
- Results publication: PubMed 34483270Soares RJDSM, Arede C, Sousa Neves F, da Silva Fernandes J, Cunha Ferreira C, Sequeira J. Topical Insulin-Utility and Results in Refractory Neurotrophic Keratopathy in Stages 2 and 3. Cornea. 2022 Aug 1;41(8):990-994. doi: 10.1097/ICO.0000000000002858. Epub 2021 Sep 3.
- Results publication: PubMed 30025986Galvis V, Nino CA, Tello A, Grice JM, Gomez MA. Topical insulin in neurotrophic keratopathy after resection of acoustic neuroma. Arch Soc Esp Oftalmol (Engl Ed). 2019 Feb;94(2):100-104. doi: 10.1016/j.oftal.2018.06.003. Epub 2018 Jul 17. English, Spanish.
- Individual participant dataSharing planned: Yes. study data will be available upon request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Corneal Ulcer and Neurotrophic Corneal Ulcer, run by Benha University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Taher Kamel Mahmoud Hussein Eleiwa, MD PhD (01069901973, tahereleiwa87@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
time to epithelial healing (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05940376, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2023.