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Neurotrophic Keratopathy

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Last updated: February 7th, 2022

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Summary of Evidence

Two techniques of corneal neurotization (direct and indirect) allowed healing of neurotrophic keratopathy and improvement of corneal sensitivity in 26 eyes with neurotrophic keratopathy. {Fogagnolo P, Giannaccare G, Bolognesi F, Digiuni M, Tranchina L, Rossetti L, Dipinto A, Allevi F, Lozza A, Rabbiosi D, Mariani S, Pellegrini M, Cazzola FE, Bagaglia S, Mazzotta C, Gabriele G, Gennaro P, Badiali G, Marchetti C, Campos EC, Biglioli F. Direct Versus Indirect Corneal Neurotization for the Treatment of Neurotrophic Keratopathy: A Multicenter Prospective Comparative Study. Am J Ophthalmol. 2020 Dec;220:203-214.}

 

Corneal neurotisation using processed nerve allografts is a safe and effective procedure for neurotrophic keratopathy in a small sample of patients.(Sweeney et.al., 2020) {Sweeney AR, Wang M, Weller CL, Burkat C, Kossler AL, Lee BW, Yen MT. Outcomes of corneal neurotisation using processed nerve allografts: a multicentre case series. Br J Ophthalmol. 2020 Nov 16:bjophthalmol-2020-317361.}

 

A minimally invasive corneal neurotisation procedure improved corneal sensation and stabilised corneal epithelium in a small sample of patients with neutrophic keratopathy.(Catapano et.al., 2019) {Catapano J, Fung SSM, Halliday W, Jobst C, Cheyne D, Ho ES, Zuker RM, Borschel GH, Ali A. Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation. Br J Ophthalmol. 2019 Dec;103(12):1724-1731.}

 

Review of 54 eyes showed improvement of BCVA (mean of 0.41 logMAR lines) and central corneal sensation (mean filament length change of 38.0mm), with significantly better outcomes in children vs adults. The most common limitation to visual recovery was corneal scarring in 31.5%. {Park JK, Charlson ES, Leyngold I, Kossler AL. Corneal Neurotization: A Review of Pathophysiology and Outcomes. Ophthalmic Plast Reconstr Surg. 2020 Sep/Oct;36(5):431-437.}

Evidence

1. Background

2. Topical Recombinant Human Nerve Growth Factor

Clinical trial

2020 Pflugfelder et.al.

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2020
Clinical trial

Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects. {Pflugfelder SC, Massaro-Giordano M, Perez VL, Hamrah P, Deng SX, Espandar L, Foster CS, Affeldt J, Seedor JA, Afshari NA, Chao W, Allegretti M, Mantelli F, Dana R. Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial. Ophthalmology. 2020 Jan;127(1):14-26.}

  • Randomized clinical trial of cenegermin (20 μg/ml) or vehicle eye drops for 8 weeks in patients with neurotrophic keratopathy (47 patients)
  • Findings (8 weeks):
    • 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.
Vehicle Cenegermin
< 0.5mm lesion staining 29.2% 69.6%
0mm of lesion staining 16.7% 65.2%

Pflugfelder et.al.
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2. Corneal Neurotisation

2.1 Overview

Review

2019 Koaik & Baig

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2019
Review

Current surgical advances and evidence available for corneal nerve regeneration. {Koaik M, Baig K. Corneal neurotization. Curr Opin Ophthalmol. 2019 Jul;30(4):292-298.}

Koaik & Baig
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Review

2019 Wolkow et.al.

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2019
Review

Overview of developments in surgical approaches in corneal neurotization. {Wolkow N, Habib LA, Yoon MK, Freitag SK. Corneal Neurotization: Review of a New Surgical Approach and Its Developments. Semin Ophthalmol. 2019;34(7-8):473-487.}

Wolkow et.al.
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2.2 Techniques

Case series

2020 Fogagnolo et.al.

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2020
Case series

Two techniques of corneal neurotization (direct and indirect) allowed healing of neurotrophic keratopathy and improvement of corneal sensitivity in 26 eyes with neurotrophic keratopathy. {Fogagnolo P, Giannaccare G, Bolognesi F, Digiuni M, Tranchina L, Rossetti L, Dipinto A, Allevi F, Lozza A, Rabbiosi D, Mariani S, Pellegrini M, Cazzola FE, Bagaglia S, Mazzotta C, Gabriele G, Gennaro P, Badiali G, Marchetti C, Campos EC, Biglioli F. Direct Versus Indirect Corneal Neurotization for the Treatment of Neurotrophic Keratopathy: A Multicenter Prospective Comparative Study. Am J Ophthalmol. 2020 Dec;220:203-214.}

Fogagnolo et.al.
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cited by count
Case series

2020 Sweeney et.al.

Article link | Archive link | Metrics cited by count

2020
Case series

Corneal neurotisation using processed nerve allografts is a safe and effective procedure for neurotrophic keratopathy in a small sample of patients. {Sweeney AR, Wang M, Weller CL, Burkat C, Kossler AL, Lee BW, Yen MT. Outcomes of corneal neurotisation using processed nerve allografts: a multicentre case series. Br J Ophthalmol. 2020 Nov 16:bjophthalmol-2020-317361.}

  • Retrospective case series of 17 patients who underwent corneal neurotisation procedure with human cadaveric processed nerve allografts
  • Findings:
    • Following surgery, the time to first gain of corneal sensation occurred at a mean of 3.7 months.The maximal gain of sensation occurred at a mean of 6.6 months.

Sweeney et.al.
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Cohort study

2019 Catapano et.al.

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2019
Cohort study

A minimally invasive corneal neurotisation procedure improved corneal sensation and stabilised corneal epithelium in a small sample of patients with neutrophic keratopathy. {Catapano J, Fung SSM, Halliday W, Jobst C, Cheyne D, Ho ES, Zuker RM, Borschel GH, Ali A. Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation. Br J Ophthalmol. 2019 Dec;103(12):1724-1731.}

  • Prospective cohort study of 19 eyes of 16 patients who underwent a minimally invasive corneal neurotisation was performed using a sural nerve graft and donor sensory nerves from the face
  • Findings
    • The mean central corneal sensation improved from 0.8 to 49.7 at final follow up, and the number of episodes of corneal epithelial defects were significantly reduced.
    • The mean BCVA was stable.

Catapano et.al.
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2.3 Outcomes

Review

2020 Kwan et.al.

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2020
Review

Review of 54 eyes showed improvement of BCVA (mean of 0.41 logMAR lines) and central corneal sensation (mean filament length change of 38.0mm), with significantly better outcomes in children vs adults. The most common limitation to visual recovery was corneal scarring in 31.5%. {Park JK, Charlson ES, Leyngold I, Kossler AL. Corneal Neurotization: A Review of Pathophysiology and Outcomes. Ophthalmic Plast Reconstr Surg. 2020 Sep/Oct;36(5):431-437.}

Kwan et.al.
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cited by count

References

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