Clinical trial NCT05940376: Topical Insulin in Neurotrophic Keratopathy After Diabetic Vitrectomy
Official title: Efficacy and Safety of Topical Insulin in Acute-onset Neurotrophic Keratopathy After Diabetic Vitrectomy
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Corneal Ulcer
Neurotrophic Corneal Ulcer
Diabetes Mellitus
Lead sponsor: Benha University
Sponsor class: OTHER
First posted: 2023-07-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult diabetic patients (18 years of age) with neurotrophic keratopathy developing within 21 days after diabetic vitrectomy.

Brief 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 (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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: time to epithelial healing
timeFrame: 4 weeks
Secondary outcomes:
measure: any adverse effect of topical insulin or need for amniotic membrane transplantation
timeFrame: 8 weeks
Other outcomes:
Locations:
city: BaNHA
country: Egypt
facility: Benha University
Study officials:
References:
citation: 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.
citation: Galvis 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.