Treatment of Neurotrophic Keratopathy With Nicergoline

Lee, Young-Chun; Kim, Su‐Young

doi:10.1097/ico.0000000000000348

Cited by 27 publications

(31 citation statements)

References 23 publications

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“…In fact, the clinical presentation, the progression and the prognosis are independent from the cause of nerve damage. This is well reflected by the fact that all clinical studies targeting NK are designed to include patients with several different underlying local or systemic conditions and consider them a homogeneous group, as the cause of sensory impairment does not influence the clinical picture, the prognosis, or the therapeutic strategies (Lambiase et al, ; Bonini et al, ; Khokhar et al, ; Aifa et al, ; Hsu and Modi, ; Lee and Kim, ).…”

Section: Role Of Corneal Innervation In the Maintenance Of A Healthy mentioning

confidence: 99%

“…In line with the above, oral nicergoline treatment was recently evaluated in NK in an open, uncontrolled study showing complete corneal healing in 23 out of 27 eyes after 7–30 days of treatment associated with improvement of corneal sensitivity and best corrected visual acuity. The efficacy of this treatment was associated with a significant increase of NGF tear levels (Lee and Kim, ).…”

Section: Role Of Corneal Innervation In the Maintenance Of A Healthy mentioning

confidence: 99%

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Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves

Mastropasqua

Massaro-Giordano

Nubile

et al. 2016

Journal Cellular Physiology

121

111

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Neurotrophic keratitis (NK) is a rare degenerative disease of the cornea caused by trigeminal nerve damage, which leads to loss of corneal sensitivity, corneal epithelium breakdown, and poor healing. Though extremely uncommon, NK is increasingly recognized for its characteristics as a distinct and well-defined clinical entity rather than a rare complication of various diseases that can disrupt trigeminal innervation. Indeed, the defining feature of NK is loss of corneal sensitivity, and its clinical findings do not correlate with the wide range of systemic or ocular conditions that underlie trigeminal nerve damage. Despite increasing awareness of NK as a distinct condition, its management continues to be challenged by the lack of treatments that target nerve regeneration. This review focuses on the role of corneal nerves in maintaining ocular surface homeostasis, the consequences (such as alterations in neuromediators and corneal cell morphology/function) of impaired innervation, and advances in NK diagnosis and management. Novel therapeutic strategies should aim to improve corneal innervation in order support corneal renewal and healing. J. Cell. Physiol. 232: 717-724, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Role Of Corneal Innervation In the Maintenance Of A Healthy mentioning

confidence: 99%

Section: Role Of Corneal Innervation In the Maintenance Of A Healthy mentioning

confidence: 99%

Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves

Mastropasqua

Massaro-Giordano

Nubile

et al. 2016

Journal Cellular Physiology

121

111

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“… 53 A recent study evaluated treatment with oral nicergoline in patients with NK, demonstrating a healing of the epithelial defect in 23 out of 27 eyes, with an improvement of NGF levels and corneal sensitivity. 54 …”

Section: Introductionmentioning

confidence: 99%

Neurotrophic keratitis: current challenges and future prospects

Versura¹,

Giannaccare²,

Pellegrini³

et al. 2018

131

117

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Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The impairment of corneal sensory innervation causes the reduction of both protective reflexes and trophic neuromodulators that are essential for the vitality, metabolism, and wound healing of ocular surface tissues. A wide range of ocular and systemic conditions, including herpetic keratitis, ocular chemical burns, corneal surgery, diabetes, multiple sclerosis, and neurosurgical procedures, can cause NK by damaging trigeminal innervation. Diagnosis of NK requires careful investigation of any ocular and systemic condition associated with the disease, complete ocular surface examination, and quantitative measurement of corneal sensitivity. The clinical stages of NK range from corneal epithelial alterations (stage 1) to persistent epithelial defect (stage 2) and ulcer (stage 3), which may progress to corneal perforation. Management of NK is based on clinical severity, and the aim of the therapy is to halt the progression of corneal damage and promote epithelial healing. Although several medical and surgical treatments have been proposed, no therapies are currently available to restore corneal sensitivity, and thus, NK remains difficult and challenging to treat. The purpose of this review is to summarize available evidence on the pathogenesis, diagnosis, and treatment of NK. Novel medical and surgical therapies including the topical administration of nerve growth factor and corneal neurotization are also described.

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“…Currently, most available treatments for NK promote corneal epithelial healing to prevent the progression of corneal damage. Cenergermin (a recombinant form of human nerve growth factor) 6 and corneal neurotization (surgical transposition of facial nerve branches), 7 therapeutic approaches to NK geared toward the improvement of corneal sensation or visual acuity, are quite expensive, pose surgical risks, and/or are difficult for patients. The ideal therapy for NK would improve corneal trigeminal innervation to restore the trophic supply of the corneal nerves and to stimulate corneal healing.…”

mentioning

confidence: 99%

“…[8][9][10][11] Promising therapeutic approaches include thymosin beta-4, which is under investigation, 12,13 and nicergoline, which may help patients with refractory neurotrophic keratopathy. 6 Among the clinical trials for NK, nerve growth factor has shown the most promise. Two large open-label studies using murine-derived NGF demonstrated a high healing rate associated with improved corneal sensitivity, tear function, and visual acuity.…”

mentioning

confidence: 99%

Topical Pergolide Enhance Corneal Nerve Regrowth Following Induced Corneal Abrasion

Zhang

Muddana

Kumar

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Neurotrophic keratopathy is a degenerative disease that may be improved by nerve growth factor (NGF). Our aim was to investigate the use of pergolide, a dopamine (D1 and D2) receptor agonist known to increase the synthesis and release of NGF for regeneration of damaged corneal nerve fibers. METHODS. Pergolide function was evaluated by measuring axon length and NGF levels by enzyme-linked immunosorbent assay in cultured chicken dorsal root ganglion (DRG) cells with serial doses of pergolide (10, 25, 50, 150, and 300 μg/ml) and with different concentrations of a D1 antagonist. Pergolide function was further evaluated by cornea nerve fiber density and wound healing in a cornea scratch mouse model. RESULTS. Pergolide increased DRG axon length significantly at a dose between 50 and 300 μg/ml. Different concentrations of D1 antagonist (12, 24, 48, and 96 μg/ml) inhibited DRG axon length growth with pergolide (300 μg/ml). Pergolide (50 μg/ml) upregulated NGF expression in DRG cells at both 24 hours and 48 hours. Pergolide improved cornea nerve fiber density at both 1 week and 2 weeks. Pergolide also improved cornea wound healing. CONCLUSIONS. We demonstrated that pergolide can act to promote an increase in NGF which promotes corneal nerve regeneration and would therefore improve corneal sensation and visual acuity in eyes with peripheral neurotrophic keratopathy.

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Treatment of Neurotrophic Keratopathy With Nicergoline

Abstract: Treatment with nicergoline helps patients with neurotrophic keratopathy in whom conventional treatment has failed.

Cited by 27 publications

References 23 publications

Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves

Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves

Neurotrophic keratitis: current challenges and future prospects

Topical Pergolide Enhance Corneal Nerve Regrowth Following Induced Corneal Abrasion

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