1,721,022 research outputs found
Nerve growth factor therapy for corneal disease
No full textTo review the experimental and clinical data on the effects of nerve growth factor (NGF) in corneal physiopathology and to discuss the future development of NGF therapy for corneal diseases
Diagnosis and management of neurotrophic keratitis
Full text linkMarta Sacchetti,1 Alessandro Lambiase2 1Cornea and Ocular Surface Unit, Ospedale San Raffaele di Milano-IRCCS, Milan, 2Ophthalmology, University La Sapienza of Rome, Italy Abstract: Neurotrophic keratitis (NK) is a degenerative disease characterized by corneal sensitivity reduction, spontaneous epithelium breakdown, and impairment of corneal healing. Several causes of NK, including herpetic keratitis, diabetes, and ophthalmic and neurosurgical procedures, share the common mechanism of trigeminal damage. Diagnosis of NK requires accurate investigation of clinical ocular and systemic history, complete eye examination, and assessment of corneal sensitivity. All diagnostic procedures to achieve correct diagnosis and classification of NK, including additional examinations such as in vivo confocal microscopy, are reviewed. NK can be classified according to severity of corneal damage, ie, epithelial alterations (stage 1), persistent epithelial defect (stage 2), and corneal ulcer (stage 3). Management of NK should be based on clinical severity, and aimed at promoting corneal healing and preventing progression of the disease to stromal melting and perforation. Concomitant ocular diseases, such as exposure keratitis, dry eye, and limbal stem cell deficiency, negatively influence the outcome of NK and should be treated. Currently, no specific medical treatment exists, and surgical approaches, such as amniotic membrane transplantation and conjunctival flap, are effective in preserving eye integrity, without ameliorating corneal sensitivity or visual function. This review describes experimental and clinical reports showing several novel and potential therapies for NK, including growth factors and metalloprotease inhibitors, as well as three ongoing Phase II clinical trials. Keywords: neurotrophic keratitis, cornea sensitivity, cornea innervation, persistent epithelial defec
Neurotrophic factors and corneal nerve regeneration
Full text linkThe 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
A closer look at nerve growth factor: From biology to clinical trials in ophthalmology
No full textIntroduction: Nerve growth factor (NGF) is a pleiotropic neurotrophin that extends its biological activity from the CNS and peripheral nervous system to the immune, endocrine and visual systems. A recombinant human NGF (rhNGF) was developed for systemic administration in diabetic and HIV-related neuropathy but it did not reach the market due to the failure of a Phase III study. More recently, experimental and clinical data showed that NGF eye drop treatment may be effective in several ophthalmic diseases, and clinical trials with a new rhNGF eye drops are currently ongoing.Areas covered: rhNGF produced in Escherichia coli was approved in Europe and in the United States for use in clinical trials in ophthalmic diseases. A Phase I study showed that rhNGF eye drops are safe and well tolerated. rhNGF has recently obtained Orphan Drug Designation for retinitis pigmentosa (RP) and neurotrophic keratopathy and Phase II clinical trials on these conditions are currently ongoing. The authors examine preclinical, pharmacokinetic, safety and efficacy data from the studies using topical ocular NGF.Expert opinion: Results from preclinical, clinical and safety studies have indicated that rhNGF eye drops represent a promising treatment for ophthalmic diseases currently lacking an effective therapy such as neurotrophic keratitis, RP, dry eye and glaucom
Chemokine receptor CCR5 expression in conjunctival epithelium of patients with dry eye syndrome
No full textOBJECTIVE:
To characterize chemokine receptor CCR5 expression on the conjunctival epithelium in dry eye syndromes.
METHODS:
Conjunctival impression cytology samples were obtained from normal subjects (n = 15) and patients with dry eye syndrome (n = 45). Cells were harvested from impression cytology samples, and flow cytometry was performed to quantitatively analyze the cell surface expression of chemokine receptor CCR5. Characterization of CCR5-positive cells was done by 2-color flow cytometry using fluorescein-conjugated anti-CCR5 and phycoerythrin-conjugated anti-CD45 antibodies (where CD45 is a marker for bone marrow-derived cells). To study CCR5 messenger RNA transcripts, real-time polymerase chain reaction was done on RNA isolated from the impression cytology samples of normal subjects (n = 5) and patients with dry eye syndrome (n = 14).
RESULTS:
We found significant up-regulation in cell surface expression of CCR5 in patients with both aqueous tear-deficient and evaporative forms of dry eye syndrome (P<.001). The real-time polymerase chain reaction results (for messenger RNA) corroborated the flow cytometry data (for protein). The majority of the cells expressing CCR5 were non-bone marrow-derived resident epithelial cells of the conjunctiva.
CONCLUSION:
Our findings suggest that CCR5 up-regulation is significantly associated with dry eye syndrome-associated ocular surface disease. Clinical Relevance Chemokine receptor CCR5 or its ligands may serve as useful targets for modulation of tissue immunoinflammatory responses in dry eye syndromes
Autoimmune diseases and the anterior segment of the eye
Full text linkThis special issue focuses on the current approaches for diagnosis, evaluation, and management of autoimmune diseases of the anterior segment of the eye, which range from immune keratoconjunctivitis to anterior uveitis. Immune diseases of the anterior segment of the eye may be caused by several local or systemic conditions and may present in a wide range of diseases including dry eye syndrome, ocular cicatricial pemphigoid (OCP), graft versus host disease (GVHD), and some forms of anterior uveitis often associated with systemic autoimmune diseases such as ankylosing spondylitis. These conditions represent some of the most difficult conditions to diagnose and manage in ophthalmology and often require a multidisciplinary approach
SD-OCT in NIR modality to diagnose retinal microvascular abnormalities in neurofibromatosis type 1
No full textWe identified three different vascular patterns based on their appearance: (i) the simple tortuosity; (ii) the more complex corkscrew; and iii) the moya moya-like configurations. In the “corkscrew” pattern, we identified a spiral attitude of vessels, while the moya moya-like configuration was characterized by tortuous vessels that end in a “puff of smoke” arrangement that resembles the collateral circulation seen in moya moya syndrome.
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