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Mantelli F.,Temple University | Nardella C.,University of Rome La Sapienza | Tiberi E.,Catholic University of the Sacred Heart | Sacchetti M.,Cornea and Ocular Surface Unit | And 2 more authors.
BioMed Research International

Neurotrophic keratitis (NK) is a rare degenerative disease of the cornea caused by an impairment of corneal sensory innervation, characterized by decreased or absent corneal sensitivity resulting in epithelial keratopathy, ulceration, and perforation. The aetiopathogenesis of corneal sensory innervation impairment in children recognizes the same range of causes as adults, although they are much less frequent in the pediatric population. Some extremely rare congenital diseases could be considered in the aetiopathogenesis of NK in children. Congenital corneal anesthesia is an extremely rare condition that carries considerable diagnostic and therapeutic problems. Typically the onset is up to 3 years of age and the cornea may be affected in isolation or the sensory deficit may exist as a component of a congenital syndrome, or it may be associated with systemic somatic anomalies. Accurate diagnosis and recognition of risk factors is important for lessening long-term sequelae of this condition. Treatment should include frequent topical lubrication and bandage corneal or scleral contact lenses. Surgery may be needed in refractory cases. The purpose of this review is to summarize and update data available on congenital causes and treatment of corneal hypo/anesthesia and, in turn, on congenital NK. © 2015 Flavio Mantelli et al. Source

Mantelli F.,IRCCS Fondazione Bietti | Sacchetti M.,Cornea and Ocular Surface Unit | Scuderi G.,University of Rome La Sapienza | Lambiase A.,University of Rome La Sapienza
Expert Opinion on Orphan Drugs

Introduction: 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 glaucoma. © Informa UK, Ltd. Source

Sacchetti M.,Cornea and Ocular Surface Unit | Mantelli F.,Temple University | Merlo D.,Istituto Superiore di Sanita | Lambiase A.,University of Rome La Sapienza
Journal of Ophthalmology

Aims. Several treatments have been proposed to slow down progression of Retinitis pigmentosa (RP), a hereditary retinal degenerative condition leading to severe visual impairment. The aim of this study is to systematically review data from randomized clinical trials (RCTs) evaluating safety and efficacy of medical interventions for the treatment of RP. Methods. Randomized clinical trials on medical treatments for syndromic and nonsyndromic RP published up to December 2014 were included in the review. Visual acuity, visual field, electroretinogram, and adverse events were used as outcome measures. Results. The 19 RCTs included in this systematic review included trials on hyperbaric oxygen delivery, topical brimonidine tartrate, vitamins, docosahexaenoic acid, gangliosides, lutein, oral nilvadipine, ciliary neurotrophic factor, and valproic acid. All treatments proved safe but did not show significant benefit on visual function. Long term supplementation with vitamin A showed a significantly slower decline rate in electroretinogram amplitude. Conclusions. Although all medical treatments for RP appear safe, evidence emerging from RCTs is limited since they do not present comparable results suitable for quantitative statistical analysis. The limited number of RCTs, the poor clinical results, and the heterogeneity among studies negatively influence the strength of recommendations for the long term management of RP patients. © 2015 Marta Sacchetti et al. Source

Sacchetti M.,Cornea and Ocular Surface Unit | Lambiase A.,University of Rome La Sapienza
Clinical Ophthalmology

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. © 2014 Sacchetti and Lambiase. Source

Sacchetti M.,Cornea and Ocular Surface Unit | Mantelli F.,GB Bietti Eye Foudation | Lambiase A.,Biomedical University of Rome | Mastropasqua A.,Biomedical University of Rome | And 2 more authors.
British Journal of Ophthalmology

Aims: Topical ciclosporin A (CsA) is a therapeutic option for dry eye disease (DED) to control ocular surface inflammation and improve tear function. The aim of this study is to systematically review data from randomised clinical trials (RCTs) evaluating efficacy and safety of topical CsA treatment for DED. Methods: Articles published up to December 2012 were identified from Medline, Embase and the Cochrane Controlled Trials Register. A total of 18 RCTs that evaluated the efficacy and safety of different topical CsA formulations for the treatment of DED were selected according to the set criteria. The Jadad score was calculated to assess RCT quality. Results: The mean Jadad score of the included RCTs was 2.8±0.6. All CsA formulations proved safe for the treatment of DED. Symptoms improved in 100% (9/9) RCTs, tear function improved in 72% (13/18) RCTs and ocular surface damage was ameliorated in 53% (9/17) RCTs in patients with DED. No improvements with CsA treatment versus control were observed in DED resulting from surgical procedures, contact lens use and thyroid orbitopathy. Statistical comparison of CsA efficacy through a meta-analysis of data was not possible due to a lack of standardised criteria and comparable outcomes among studies. Conclusions: Although topical CsA appears to be a safe treatment for DED, evidence emerging from RCTs is limited, and this affects the strength of recommendations to healthcare providers and policymakers for optimal management. Standardised diagnostic criteria to assess the efficacy of topical CsA are recommended to improve the design of future RCTs in DED. Source

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