Hydrogel dressings on neurotrophic keratitis in an experimental animal model

AIM:To investigate the therapeutic effects of hydrogel dressings on neurotrophic keratitis in rats.METHODS:Male Wistar rats,aged 42–56d,were randomly divided into control,experimental,and treatment groups,each consisting of five rats.The experimental and treatment groups underwent neurotrophic keratitis modeling in both eyes.After successful modeling,biomedical hydrogels formed with polyvinyl alcohol and polyvinyl pyrrolidone were used in treatment group for 7d.Ocular irritation response and keratitis index scores,Schirmer’s test,tear film break-up time(BUT),sodium fluorescein staining,and hematoxylin and eosin(HE)staining were used to evaluate the effectiveness of the treatment.RESULTS:The neurotrophic keratitis model was successfully established in rats with severe ophthalmic nerve injury,characterized by keratitis,ocular irritation,reduced tear secretion measured by decreased BUT and Schirmer test values,corneal epithelial loss,and disorganized collagen fibers in the stromal layer.Following treatment with hydrogel dressings,significant improvements were observed in keratitis scores and ocular irritation symptoms in model eyes.Although the recovery of tear secretion,as measured by the Schirmer’s test,did not show statistical differences,BUT was significantly prolonged.Fluorescein staining confirmed a reduction in the extent of corneal epithelial loss after treatment.HE staining revealed the restoration of the structural disorder in both the epithelial and stromal layers to a certain extent.CONCLUSION:Hydrogel dressing reduces ocular surface irritation,improves tear film stability,and promotes the repair and restoration of damaged epithelial cells by maintaining a moist and clean environment on the ocular surface in the rat model.

Clinical observation of recombinant human nerve growth factor in the treatment of neurotrophic keratitis

AIM:To characterize changes of corneal nerve morphology and tear indices in patients with neurotrophic keratitis(NK)treated with recombinant human nerve growth factor(rhNGF).METHODS:In a prospective observational study,six patients(nine eyes)were locally treated with rhNGF.Visual acuity,corneal fluorescein staining score,the heights of the tear river,lipid layer thickness(LLT),tear ferning(TF)test,conjunctival impression cytology(CIC)examination,the densities of cornea subbasal nerve fibers were determined before and after treatment.RESULTS:Compared with baseline,there was a significant difference in corneal fluorescence staining scores(P<0.01);all patient corneal epithelial defects recovered completely within 8wk,but there was no significant improvement in the height of the tear river(P=0.202).LLT was significantly increased when compared with baseline(P=0.042);however,the function of conjunctival goblet cells and mucin content did not significantly improve using the TF test and CIC examination(P=0.557,P=0.539).After 8wk of treatment,the average corneal subbasal nerve fiber density increased significantly(P<0.01),as did the number of corneal nerve fiber branches(P=0.001).CONCLUSION:RhNGF can increase the density of corneal subbasal nerve fibers,promote the healing of persistent corneal epithelial defects and corneal ulcers in patients with NK,also improving tear function partially.

Neurotrophic factors and corneal nerve regeneration

The cornea has unique features that make it a useful model for regenerative medicine studies. It is an avascular, transparent, densely innervated tissue and any pathological changes can be easily detected by slit lamp examination. Corneal sensitivity is provided by the ophthalmic branch of the trigeminal nerve that elicits protective reflexes such as blinking and tearing and exerts trophic support by releasing neuromediators and growth factors. Corneal nerves are easily evaluated for both function and morphology using standard instruments such as corneal esthesiometer and in vivo confocal microscope. All local and systemic conditions that are associated with damage of the trigeminal nerve cause the development of neurotrophic keratitis, a rare degenerative disease. Neurotrophic keratitis is characterized by impairment of corneal sensitivity associated with development of persistent epithelial defects that may progress to corneal ulcer, melting and perforation. Current neurotrophic keratitis treatments aim at supporting corneal healing and preventing progression of corneal damage. Novel compounds able to stimulate corneal nerve recovery are in advanced development stage. Among them, nerve growth factor eye drops showed to be safe and effective in stimulating corneal healing and improving corneal sensitivity in patients with neurotrophic keratitis. Neurotrophic keratitis represents an useful model to evaluate in clinical practice novel neuro-regenerative drugs.

Topical delivery of nerve growth factor for treatment of ocular and brain disorders

Neurotrophins are a family of proteins that support neuronal proliferation, survival, and differentiation in the central and peripheral nervous systems, and are regulators of neuronal plasticity. Nerve growth factor is one of the best-described neurotrophins and has advanced to clinical trials for treatment of ocular and brain diseases due to its trophic and regenerative properties. Prior trials over the past few decades have produced conflicting results, which have principally been ascribed to adverse effects of systemic nerve growth factor administration, together with poor penetrance of the blood-brain barrier that impairs drug delivery. Contrastingly, recent studies have revealed that topical ocular and intranasal nerve growth factor administration are safe and effective, suggesting that topical nerve growth factor delivery is a potential alternative to both systemic and invasive intracerebral delivery. The therapeutic effects of local nerve growth factor delivery have been extensively investigated for different ophthalmic diseases, including neurotrophic keratitis, glaucoma, retinitis pigmentosa, and dry eye disease. Further, promising pharmacologic effects were reported in an optic glioma model, which indicated that topically administered nerve growth factor diffused far beyond where it was topically applied. These findings support the therapeutic potential of delivering topical nerve growth factor preparations intranasally for acquired and degenerative brain disorders. Preliminary clinical findings in both traumatic and non-traumatic acquired brain injuries are encouraging, especially in pediatric patients, and clinical trials are ongoing. The present review will focus on the therapeutic effects of both ocular and intranasal nerve growth factor delivery for diseases of the brain and eye.

Umbilical cord blood serum therapy for the management of persistent corneal epithelial defects

AIM:Toevaluatetheroleofumbilical cord blood serum(CBS) therapy in cases with persistent corneal epithelial defects(PED).METHODS:Sixteen eyes of 14 patients with PED who were resistant to conventional treatment were treated with 20% umbilical cord serum eye drops. Patients were followed-up weekly until epithelization was complete.The collected data included the grade of corneal lesion(Grade I: epithelial defect +superficial vascularization,Grade II: epithelial defect +stromal edema, Grade III:corneal ulcer +stromal melting), the size of epithelial defect(pretreatment, 7th, 14 thand 21stdays of treatment),and follow-up time was evaluated retrospectively.RESULTS:The mean size of epithelial defect on two perpendicular axes was 5.2×4.6-mm2(range: 2.5-8 mm×2.2-9 mm2). Mean duration of treatment was 8.3 ±5wk.CBS therapy was effective in 12 eyes(75%) and ineffective in 4 eyes(25%). The epithelial defects in 4ineffective eyes were healed with amniotic membrane transplantation and tarsorrhaphy. The rate of complete healing was 12.5% by 7d, 25% by 14 d, and 75% by 21 d.The healing time was prolonged in Grade III eyes in comparison to eyes in Grade I or Grade II.CONCLUSION:The results of the current study indicated the safety effectiveness of CBS drops in the management of PED. The grade of disease seems have a role on the healing time.