The Experts below are selected from a list of 642 Experts worldwide ranked by ideXlab platform

Teruo Nishida - One of the best experts on this subject based on the ideXlab platform.

  • Role of the Neurokinin-1 Receptor in the Promotion of Corneal Epithelial Wound Healing by the Peptides FGLM-NH2 and SSSR in Neurotrophic Keratopathy.
    Investigative ophthalmology & visual science, 2020
    Co-Authors: Ryoji Yanai, Teruo Nishida, Makoto Hatano, Sho-hei Uchi, Naoyuki Yamada, Kazuhiro Kimura
    Abstract:

    Purpose Neurotrophic Keratopathy is a corneal epitheliopathy induced by trigeminal denervation that can be treated with eyedrops containing the neuropeptide substance P (or the peptide FGLM-NH2 derived therefrom) and insulin-like growth factor 1 (or the peptide SSSR derived therefrom). Here, we examine the mechanism by which substance P (or FGLM-NH2) promotes corneal epithelial wound healing in a mouse model of Neurotrophic Keratopathy. Methods The left eye of mice subjected to trigeminal nerve axotomy in the right eye served as a model of Neurotrophic Keratopathy. Corneal epithelial wound healing was monitored by fluorescein staining and slit-lamp examination. The distribution of substance P, neurokinin-1 receptor (NK-1R), and phosphorylated Akt was examined by immunohistofluorescence analysis. Cytokine and chemokine concentrations in intraocular fluid were measured with a multiplex assay. Results Topical administration of FGLM-NH2 and SSSR promoted corneal epithelial wound healing in the Neurotrophic Keratopathy model in a manner sensitive to the NK-1R antagonist L-733,060. Expression of substance P and NK-1R in the superficial layer of the corneal epithelium decreased and increased, respectively, in model mice compared with healthy mice. FGLM-NH2 and SSSR treatment suppressed the production of interleukin-1α, macrophage inflammatory protein 1α (MIP-1α) and MIP-1β induced by corneal epithelial injury in the model mice. It also increased the amount of phosphorylated Akt in the corneal epithelium during wound healing in a manner sensitive to prior L-733,060 administration. Conclusions The substance P-NK-1R axis promotes corneal epithelial wound healing in a Neurotrophic Keratopathy model in association with upregulation of Akt signaling and attenuation of changes in the cytokine-chemokine network.

  • Potential New Modes of Treatment of Neurotrophic Keratopathy.
    Cornea, 2015
    Co-Authors: Ryoji Yanai, Naoyuki Morishige, Tai-ichiro Chikama, Teruo Nishida, Naoyuki Yamada, Koh-hei Sonoda
    Abstract:

    The cornea focuses external light onto the retina, a function for which it must be transparent and possess a smooth surface. Homeostasis of the corneal epithelium is regulated by various humoral factors present in the tear fluid and by neural factors derived from the trigeminal nerve. Neurotrophic Keratopathy (NK) is characterized by corneal epithelial disorders that result from impairment of trigeminal nerve function and a consequent deficiency of neural factors. The ideal mode of treatment for this condition is the regeneration of damaged trigeminal nerve fibers, but such therapy is not currently available. In this review, we describe established and potential new treatments of NK. Our research demonstrated that a combination of the neurotransmitter substance P and insulin-like growth factor 1 (IGF-1) has a synergistic stimulatory effect on corneal epithelial migration in vitro and on corneal wound closure in vivo. Furthermore, we identified the minimal amino acid sequences of substance P and IGF-1 required for this synergistic action based on the assumption that the clinical application of peptides corresponding to these sequences would have fewer side effects compared with the full-length molecules. Combination of the substance P-derived peptide FGLM-amide and the IGF-1-derived peptide SSSR promoted corneal epithelial wound healing in patients with NK.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01756456.

  • Congenital hypoplastic trigeminal nerve revealed by manifestation of corneal disorders likely caused by neural factor deficiency.
    Case reports in ophthalmology, 2014
    Co-Authors: Naoyuki Morishige, Teruo Nishida, Naoyuki Yamada, Yukiko Morita, Koh-hei Sonoda
    Abstract:

    Purpose: To report a case of hypoplastic trigeminal nerve associated with corneal epithelial disorders that were successfully treated with peptides derived from substance P and insulin-like growth factor-1 (IGF-1). Case Report: A 16-month-old boy was referred for treatment of a persistent corneal epithelial defect on his left eye. Magnetic resonance imaging revealed the apparent absence of the trigeminal nerve on the left side, and the patient was therefore diagnosed with Neurotrophic Keratopathy. Treatment with eye drops containing the tetrapeptides FGLM-NH2 and SSSR derived from the neuropeptide substance P and the growth factor IGF-1, respectively, resulted in resurfacing of the corneal epithelial defect. Discussion: The trigeminal nerve anomaly of the patient likely gave rise to Neurotrophic Keratopathy as a result of a deficiency of neural factors, emphasizing the importance of neural regulation in corneal epithelial homeostasis.

  • advances in treatment for Neurotrophic Keratopathy
    Current Opinion in Ophthalmology, 2009
    Co-Authors: Teruo Nishida, Ryoji Yanai
    Abstract:

    Purpose of reviewTo review the clinical characteristics and possible new mode of treatments for the corneal epithelial disorders associated with Neurotrophic Keratopathy.Recent findingsThe successful clinical applications of eyedrops containing substance P and insulin-like growth factor-1, or peptid

  • open clinical study of eye drops containing tetrapeptides derived from substance p and insulin like growth factor 1 for treatment of persistent corneal epithelial defects associated with Neurotrophic Keratopathy
    British Journal of Ophthalmology, 2008
    Co-Authors: Naoyuki Yamada, Naoyuki Morishige, Tai-ichiro Chikama, Teruo Nishida, Ryoji Yanai, Rie Matsuda, Tadashi Ishimitsu, Akira Kamiya
    Abstract:

    Background/aims: Loss of corneal sensation results in the development of persistent corneal epithelial defects. The combination of a substance P-derived peptide (FGLM-amide) and an insulin-like growth factor-1 (IGF-1)-derived peptide (SSSR) stimulates rabbit corneal epithelial migration in vitro and rabbit corneal epithelial wound closure in vivo. The clinical efficacy of eye-drops containing FGLM-amide and SSSR for the treatment of persistent corneal epithelial defects in individuals with Neurotrophic Keratopathy was examined in a prospective open study. Methods: Twenty-five consecutive patients (26 eyes) with persistent corneal epithelial defects associated with Neurotrophic Keratopathy were treated by administration of eye-drops containing FGLM-amide and SSSR. The course of epithelial healing was monitored by slit-lamp examination. Results: Epithelial defects resurfaced completely in 19 of the 26 eyes (73%) within 4 weeks after treatment initiation. Complete resurfacing of epithelial defects was apparent in 18 of 22 (82%) or in one of four (25%) eyes without or with limbal stem cell deficiency, respectively. No adverse effects of treatment were observed in any subject. Conclusion: Eye-drops containing FGLM-amide and SSSR induced the rapid resurfacing of persistent epithelial defects in stem cell-positive individuals with Neurotrophic Keratopathy.

Asim Ali - One of the best experts on this subject based on the ideXlab platform.

  • treatment of Neurotrophic Keratopathy with minimally invasive corneal neurotisation long term clinical outcomes and evidence of corneal reinnervation
    British Journal of Ophthalmology, 2019
    Co-Authors: Joseph Catapano, Simon Sheung Man Fung, William Halliday, Cecilia Jobst, Douglas Cheyne, Ronald M Zuker, Gregory H Borschel, Asim Ali
    Abstract:

    Aim To report clinical outcomes and evidence of corneal innervation in patients with Neurotrophic Keratopathy (NK) treated with minimally invasive corneal neurotisation (MICN) using a sural nerve graft and donor sensory nerves from the face. Methods Patients undergoing MICN at The Hospital for Sick Children, Toronto, Canada were prospectively recruited. Data on central corneal sensation (CCS, measured with Cochet-Bonnet aesthesiometer), best-corrected visual acuity (BCVA) and corneal epithelial integrity were collected. In four patients who subsequently underwent keratoplasty, immunohistochemical analysis was performed on the corneal explants. One patient underwent magnetoencephalography (MEG) after MICN to characterise the neurophysiological pathways involved. Results Between November 2012 and February 2017, 19 eyes of 16 patients underwent MICN. Mean follow-up was 24.0±16.1 months (range, 6–53). Mean CCS significantly improved from 0.8±2.5 mm to 49.7±15.5 mm at final follow-up (p Conclusions By providing an alternative source of innervation, MICN improves corneal sensation and stabilises the corneal epithelium, permitting optical keratoplasty for patients with NK-related corneal opacity.

  • in vivo confocal microscopy reveals corneal reinnervation after treatment of Neurotrophic Keratopathy with corneal neurotization
    Cornea, 2018
    Co-Authors: Simon S M Fung, Joseph Catapano, Ronald M Zuker, Gregory H Borschel, Uri Elbaz, Asim Ali
    Abstract:

    Purpose To document the presence and location of new sensory nerve fibers after corneal neurotization using in vivo confocal microscopy (IVCM) in 2 patients with Neurotrophic Keratopathy (NK). Methods Two patients with unilateral advanced NK received corneal neurotization to surgically reinnervate the cornea. IVCM was used to identify subbasal nerve fibers and document corneal reinnervation. In 1 patient (case 1), IVCM was performed before and after corneal neurotization; in the second patient (case 2), IVCM was performed after neurotization and corneal transplantation. Results In case 1, who had hand motion visual acuity due to NK-associated corneal perforation that necessitated cyanoacrylate gluing, preoperative IVCM identified no subbasal nerves; however, subbasal nerves were identified 6 months after corneal neurotization, and there were no further episodes of persistent epithelial defects. In case 2, in whom NK with a total absence of corneal sensation was the result of treated basal skull meningioma, corneal sensation, visual acuity, and ocular surface health improved after corneal neurotization. Deep anterior lamellar keratoplasty was performed 2.5 years after corneal sensation was reestablished. IVCM demonstrated corneal reinnervation at the stromal and subbasal level in a pattern different from the normal cornea. Conclusions Corneal neurotization restores corneal sensation by reinnervating the stromal and subbasal layers of the cornea. In doing so, corneal neurotization may halt the process of NK and prevent further visual loss.

Pedram Hamrah - One of the best experts on this subject based on the ideXlab platform.

  • topical recombinant human nerve growth factor cenegermin for Neurotrophic Keratopathy a multicenter randomized vehicle controlled pivotal trial
    Ophthalmology, 2020
    Co-Authors: Stephen C Pflugfelder, Pedram Hamrah, Victor L. Perez, Mina Massarogiordano, Sophie X Deng, Ladan Espandar, Stephen C Foster, John C Affeldt, John A Seedor, Natalie A Afshari
    Abstract:

    Author(s): Pflugfelder, Stephen C; Massaro-Giordano, Mina; Perez, Victor L; Hamrah, Pedram; Deng, Sophie X; Espandar, Ladan; Foster, C Stephen; Affeldt, John; Seedor, John A; Afshari, Natalie A; Chao, Wendy; Allegretti, Marcello; Mantelli, Flavio; Dana, Reza | Abstract: PURPOSE:To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with Neurotrophic Keratopathy. DESIGN:Multicenter, randomized, double-masked, vehicle-controlled trial. PARTICIPANTS:Patients with Neurotrophic persistent epithelial defect with or without stromal thinning. METHODS:The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. MAIN OUTCOME MEASURES:The primary end point was healing of the Neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured Neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (l0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8. RESULTS:Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P l 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient. CONCLUSIONS:Cenegermin treatment showed higher rates of corneal healing than vehicle in Neurotrophic Keratopathy associated with nonhealing corneal defects.

  • topical recombinant human nerve growth factor cenegermin for Neurotrophic Keratopathy a multicenter randomized vehicle controlled pivotal trial
    Ophthalmology, 2020
    Co-Authors: Stephen C Pflugfelder, Pedram Hamrah, Victor L. Perez, Mina Massarogiordano, Sophie X Deng, Ladan Espandar, Stephen C Foster, John C Affeldt, John A Seedor, Natalie A Afshari
    Abstract:

    Purpose To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with Neurotrophic Keratopathy. Design Multicenter, randomized, double-masked, vehicle-controlled trial. Participants Patients with Neurotrophic persistent epithelial defect with or without stromal thinning. Methods The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. Main Outcome Measures The primary end point was healing of the Neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured Neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally ( Results Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%–66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%–73.1%; P Conclusions Cenegermin treatment showed higher rates of corneal healing than vehicle in Neurotrophic Keratopathy associated with nonhealing corneal defects.

  • bilateral nerve alterations in a unilateral experimental Neurotrophic Keratopathy model a lateral conjunctival approach for trigeminal axotomy
    PLOS ONE, 2013
    Co-Authors: Takefumi Yamaguchi, Aslihan Turhan, Deshea L Harris, Harald Pruss, Kai Hu, Ulrich H Von Andrian, Pedram Hamrah
    Abstract:

    To study bilateral nerve changes in a newly developed novel mouse model for Neurotrophic Keratopathy by approaching the trigeminal nerve from the lateral fornix. Surgical axotomy of the ciliary nerve of the trigeminal nerve was performed in adult BALB/c mice at the posterior sclera. Axotomized, contralateral, and sham-treated corneas were excised on post-operative days 1, 3, 5, 7 and 14 and immunofluorescence histochemistry was performed with anti-β-tubulin antibody to evaluate corneal nerve density. Blink reflex was evaluated using a nylon thread. The survival rate was 100% with minimal bleeding during axotomy and a surgical time of 8±0.5 minutes. The blink reflex was diminished at day 1 after axotomy, but remained intact in the contralateral eyes in all mice. The central and peripheral subbasal nerves were not detectable in the axotomized cornea at day 1 (p<0.001), compared to normal eyes (101.3±14.8 and 69.7±12.0 mm/mm2 centrally and peripherally). Interestingly, the subbasal nerve density in the contralateral non-surgical eyes also decreased significantly to 62.4±2.8 mm/mm2 in the center from day 1 (p<0.001), but did not change in the periphery (77.3±11.7 mm/mm2, P = 0.819). Our novel trigeminal axotomy mouse model is highly effective, less invasive, rapid, and has a high survival rate, demonstrating immediate loss of subbasal nerves in axotomized eyes and decreased subbasal nerves in contralateral eyes after unilateral axotomy. This model will allow investigating the effects of corneal nerve damage and serves as a new model for Neurotrophic Keratopathy.

  • Literature review of NTK animal models.
    2013
    Co-Authors: Takefumi Yamaguchi, Aslihan Turhan, Deshea L Harris, Harald Pruss, Ulrich Von Andrian, Pedram Hamrah
    Abstract:

    *Complete subbasal nerve loss was observed in 23 corneas out of 24 (95.8%) In one cornea (4.2%), there was partial residual subbasal nerve observed at Day 7.NTK: Neurotrophic Keratopathy.

Stephen C Pflugfelder - One of the best experts on this subject based on the ideXlab platform.

  • topical recombinant human nerve growth factor cenegermin for Neurotrophic Keratopathy a multicenter randomized vehicle controlled pivotal trial
    Ophthalmology, 2020
    Co-Authors: Stephen C Pflugfelder, Pedram Hamrah, Victor L. Perez, Mina Massarogiordano, Sophie X Deng, Ladan Espandar, Stephen C Foster, John C Affeldt, John A Seedor, Natalie A Afshari
    Abstract:

    Author(s): Pflugfelder, Stephen C; Massaro-Giordano, Mina; Perez, Victor L; Hamrah, Pedram; Deng, Sophie X; Espandar, Ladan; Foster, C Stephen; Affeldt, John; Seedor, John A; Afshari, Natalie A; Chao, Wendy; Allegretti, Marcello; Mantelli, Flavio; Dana, Reza | Abstract: PURPOSE:To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with Neurotrophic Keratopathy. DESIGN:Multicenter, randomized, double-masked, vehicle-controlled trial. PARTICIPANTS:Patients with Neurotrophic persistent epithelial defect with or without stromal thinning. METHODS:The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. MAIN OUTCOME MEASURES:The primary end point was healing of the Neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured Neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (l0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8. RESULTS:Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P l 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient. CONCLUSIONS:Cenegermin treatment showed higher rates of corneal healing than vehicle in Neurotrophic Keratopathy associated with nonhealing corneal defects.

  • topical recombinant human nerve growth factor cenegermin for Neurotrophic Keratopathy a multicenter randomized vehicle controlled pivotal trial
    Ophthalmology, 2020
    Co-Authors: Stephen C Pflugfelder, Pedram Hamrah, Victor L. Perez, Mina Massarogiordano, Sophie X Deng, Ladan Espandar, Stephen C Foster, John C Affeldt, John A Seedor, Natalie A Afshari
    Abstract:

    Purpose To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with Neurotrophic Keratopathy. Design Multicenter, randomized, double-masked, vehicle-controlled trial. Participants Patients with Neurotrophic persistent epithelial defect with or without stromal thinning. Methods The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. Main Outcome Measures The primary end point was healing of the Neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured Neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally ( Results Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%–66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%–73.1%; P Conclusions Cenegermin treatment showed higher rates of corneal healing than vehicle in Neurotrophic Keratopathy associated with nonhealing corneal defects.

  • corneal nerve regeneration in Neurotrophic Keratopathy following autologous plasma therapy
    British Journal of Ophthalmology, 2010
    Co-Authors: Christopher Leveque, Stephen C Pflugfelder
    Abstract:

    Abstract Aims: To evaluate the effect of topical autologous plasma on nerve morphology in patients with Neurotrophic Keratopathy (NK) using the confocal microscope. Methods: Eleven eyes of 6 patients with Neurotrophic Keratopathy (NK), were evaluated for this study. Corneal fluorescein staining was done and corneal sensitivity measurements were done with the Cochet-Bonnet and modified Belmonte gas esthesiometers. The Heidelberg Retina Tomograph 2 Rostock Cornea Module (HRT2-RCM) laser scanning confocal microscope was used to image the corneal surface and subepithelial neural plexus. Four images at the level of the subepithelial nerve plexus in the central cornea were randomly selected for analysis of the corneal nerves. Topical autologous plasma was used 6-8 times per day. Results: BCVA significantly improved after plasma treatment in all patients, (P =0.003). The mean corneal fluorescein staining score significantly decreased after treatment, (P = 0.0003).There was a significant increase in corneal sensitivity measured by Cochet-Bonnet (P < 0.0001) and modified Belmonte (P = 0.01) esthesiometers. The mean number, length, width and density of subepithelial nerves significantly increased after plasma treatment (P=0.0002). Conclusion: In vivo confocal microscopy examination revealed preliminary evidence for improvement of corneal nerve findings suggesting efficacy of autologous plasma treatment in Neurotrophic Keratopathy.

Francisco C Figueiredo - One of the best experts on this subject based on the ideXlab platform.

  • Neurotrophic Keratopathy.
    Progress in retinal and eye research, 2018
    Co-Authors: Harminder S Dua, Elisabeth M. Messmer, Maurizio Rolando, Dalia G Said, Jose M Benitez-del-castillo, Parwez N Hossain, Alex J Shortt, Gerd Geerling, Mario Nubile, Francisco C Figueiredo
    Abstract:

    Neurotrophic Keratopathy (NK) refers to a condition where corneal epitheliopathy leading to frank epithelial defect with or without stromal ulceration (melting) is associated with reduced or absent corneal sensations. Sensory nerves serve nociceptor and trophic functions, which can be affected independently or simultaneously. Loss of trophic function and consequent epithelial breakdown exposes the stroma making it susceptible to enzymatic degradation. Nerve pathology can range from attrition to aberrant re-generation with corresponding symptoms from anaesthesia to hyperaesthesia/allodynia. Many systemic and ocular conditions, including surgery and preserved medications can lead to NK. NK can be mild (epithelium and tear film changes), moderate (non-healing epithelial defect) or severe (stromal melting and perforation). Moderate and severe NK can profoundly affect vision and adversely impact on the quality of life. Medical management with lubricating agents from artificial tears to serum/plasma drops, anti-inflammatory agents, antibiotics and anti-proteases all provide non-specific relief, which may be temporary. Contact lenses, punctal plugs, lid closure with botulinum toxin and surgical interventions like tarsorrhaphy, conjunctival flaps and amniotic membrane provide greater success but often at the cost of obscuring sight. Corneal surgery in a dry ocular surface with reduced sensation is at high risk of failure. The recent advent of biologicals such as biopolymers mimicking heparan sulfate; coenzyme Q10 and antisense oligonucleotide that suppress connexin 43 expression, all offer promise. Recombinant nerve growth factor (cenegermin), recently approved for human use targets the nerve pathology and has the potential of addressing the underlying deficit and becoming a specific therapy for NK.

  • Corneal Neurotization for Neurotrophic Keratopathy: Clinical Outcomes and In Vivo Confocal Microscopic and Histopathological Findings.
    Cornea, 2018
    Co-Authors: Darren S J Ting, Gustavo S. Figueiredo, Christin Henein, Eric A. Barnes, Omar Ahmed, Hardeep Singh Mudhar, Francisco C Figueiredo
    Abstract:

    Purpose:To describe the long-term outcomes and in vivo confocal microscopic (IVCM) and histopathological findings after corneal neurotization surgery.Methods:We included 2 patients who underwent corneal neurotization surgery for severe unilateral Neurotrophic Keratopathy secondary to cerebellopontin