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Efficacy of treatments for neurotrophic keratopathy: a systematic review and meta-analysis

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Abstract

Purpose

Management of NK can be difficult, involving a range of treatments with variable efficacy. We conducted a systematic review and meta-analysis to evaluate the efficacy of medical and surgical treatments for neurotrophic keratitis (NK).

Method

PubMed, Cochrane Library, Embase, ClinicalTrial.gov, and ScienceDirect were searched for studies assessing efficacy of NK treatments. We computed random-effect meta-analyses on corneal healing, time to complete healing, and visual acuity changes between baselines and after treatment, stratified on treatment classes. We followed the PRISMA guidelines (registration number CRD42021225721).

Results

We included 20 studies: 571 patients and 5 treatment classes (2 surgical and 3 non-surgical). The percentage of patients with complete corneal healing did not differ between specific treatments (nerve growth factor eyedrops (NGF), 75%, 95CI 46 to 104%; autologous serum (AS), 92%, 86 to 98%; neurotization, 99%, 95 to 103%; amniotic membrane transplantation (AMT), 86%, 78 to 94%). All specific treatments had better percentage of complete healing (p < 0.001) than non-specific treatment groups, i.e., mainly lubricants (23%, 14 to 32). Time to complete healing was 24.2 days (5.4 to 43.1) with NGF, 27.6 days (15.2 to 40.0) with AS, 117 days (28.8 to 205.2) with neurotization, and 16.4 days (11.1 to 21.7) with AMT. Only NGF and AMT improved visual acuity. Efficacy outcomes were not affected by sociodemographic (age, sex) nor severity of disease (Mackie stages).

Conclusion

We confirmed the efficacy of specific treatments in NK. Further comparative trials are needed to investigate the medical and economic benefits of innovative therapies.

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Data Availability

All relevant data are within the paper.

Abbreviations

95CI:

95% Confidence interval

AMT:

Amniotic membrane transplantation

AS:

Autologous serum tears

ES:

Effect sizes

MAR:

Minimal angle of resolution

NGF:

Nerve growth factor

NK:

Neurotrophic keratopathy

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

RCT:

Randomized clinical trials

RoB 2:

Cochrane Risk of Bias 2

SD:

Standard deviation

SIGN:

Scottish intercollegiate guidelines network

SMD:

Standard mean deviation

STROBE:

Strengthening the Reporting of Observational studies in Epidemiology

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Acknowledgements

We thank Nathalie Piñol-Domenech, librarian of the Clermont Auvergne University, and the librarians of University Health Sciences Library of Paris for their support in the elaboration of search strategy in databases and collection of full texts of articles.

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Authors and Affiliations

  1. CHU Clermont-Ferrand, Ophthalmology, University Hospital of Clermont-Ferrand, 63000, Clermont-Ferrand, France

    Sébastien Roumeau, Frédéric Chiambaretta & Valentin Navel

  2. Preventive and Occupational Medicine, CNRS, LaPSCo, Physiological and Psychosocial Stress, CHU Clermont-Ferrand, University Hospital of Clermont-Ferrand, Université Clermont Auvergne, Witty Fit, 63000, Clermont-Ferrand, France

    Frédéric Dutheil

  3. CHU Clermont-Ferrand, Biochemistry and Molecular Genetics, University Hospital of Clermont-Ferrand, 63000, Clermont-Ferrand, France

    Vincent Sapin

  4. CNRS UMR 6293, INSERM U1103, Genetic Reproduction and Development Laboratory (GReD), Translational Approach To Epithelial Injury and Repair Team, Université Clermont Auvergne, 63000, Clermont-Ferrand, France

    Vincent Sapin, Frédéric Chiambaretta & Valentin Navel

  5. Center for Health and Exercise Science Research, Department of Sport, Physical Education and Health, Hong Kong Baptist University, Kowloon Tong, Hong Kong

    Julien S. Baker

  6. Faculty of Medicine and Health, Save Sight Institute, Discipline of Ophthalmology, The University of Sydney, Sydney, NSW, Australia

    Stephanie L. Watson

  7. Sydney Eye Hospital, Sydney, NSW, Australia

    Stephanie L. Watson

  8. CHU Clermont-Ferrand, Clinical Research and Innovation Direction, University Hospital of Clermont-Ferrand, 63000, Clermont-Ferrand, France

    Bruno Pereira

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  1. Sébastien Roumeau
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  2. Frédéric Dutheil
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  3. Vincent Sapin
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  6. Bruno Pereira
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  7. Frédéric Chiambaretta
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  8. Valentin Navel
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Contributions

SR, VN, and FD were responsible for the design and conception of the study. SR, VN, and FD searched and collected studies and data. SR, VN, FC, FD, and BP analyzed and interpreted data. SR, VN, FD, and BP oversaw statistical analyses. SR, VN, FD, VS, JSB, SLW, and FC wrote the manuscript. All authors made critical revisions to the article. All authors gave their final approval of the article.

Corresponding author

Correspondence to Valentin Navel.

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Conflict of interest

No conflicts of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript. FC is a consultant for Aerie, Alcon, Allergan, Horus Pharma, Santen, and Thea.

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Roumeau, S., Dutheil, F., Sapin, V. et al. Efficacy of treatments for neurotrophic keratopathy: a systematic review and meta-analysis. Graefes Arch Clin Exp Ophthalmol 260, 2623–2637 (2022). https://doi.org/10.1007/s00417-022-05602-z

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