Skip to main content

Advertisement

SpringerLink
Log in

How Should Corneal Nerves Be Incorporated Into the Diagnosis and Management of Dry Eye?

  • Cornea (T Yamaguchi, Section Editor)
  • Published:
Current Ophthalmology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Confocal microscopy and aethesiometry have allowed clinicians to assess the structural and functional integrity of corneal nerves in health and disease. This review summarizes literature on nerves in dry eye disease (DED) and discusses how this data can be applied to DED diagnosis and treatment.

Recent Findings

Subjects with DED have a heterogeneous symptom and sign profile along with variability in nerve structure and function. Most studies have reported lower nerve density and sensitivity in aqueous tear deficiency, while findings are more inconsistent for other DED subtypes. Examining nerve status, along with profiling symptoms and signs of disease, can help categorize subjects into disease phenotypes (structural and functional patterns) that exist under the umbrella of DED. This, in turn, can guide therapeutic decision-making.

Summary

Due to the heterogeneity in symptoms and signs of DED, corneal nerve evaluations can be valuable for categorizing individuals into disease sub-types and for guiding clinical decision-making.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Erie JC, McLaren JW, Patel SV. Confocal microscopy in ophthalmology. Am J Ophthalmol. 2009;148(5):639–46.

    Article  PubMed  Google Scholar 

  2. Müller LJ, Marfurt CF, Kruse F, Tervo TMT. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76(5):521–42.

    Article  PubMed  CAS  Google Scholar 

  3. Müller LJ, Pels L, Vrensen GF. Ultrastructural organization of human corneal nerves. Invest Ophthalmol Vis Sci. 1996;37(4):476–88.

    PubMed  Google Scholar 

  4. Liu YC, Lin MT, Mehta JS. Analysis of corneal nerve plexus in corneal confocal microscopy images. Neural Regen Res. 2021;16(4):690–1.

    Article  PubMed  Google Scholar 

  5. Simsek C, Karalezli A, Dogru M, Kojima T. In vivo confocal microscopy evaluation in dry eye and related diseases. Current Ophthalmology Reports. 2019;7(3):187–95.

    Article  Google Scholar 

  6. Jalbert I, Stapleton F, Papas E, Sweeney DF, Coroneo M. In vivo confocal microscopy of the human cornea. Br J Ophthalmol. 2003;87(2):225–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Petroll WM, Robertson DM. In vivo confocal microscopy of the cornea: new developments in image acquisition, reconstruction, and analysis using the HRT-Rostock Corneal Module. The ocular surface. 2015;13(3):187–203.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Shaheen BS, Bakir M, Jain S. Corneal nerves in health and disease. Surv Ophthalmol. 2014;59(3):263–85.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Patel DV, McGhee CNJ. In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review. Br J Ophthalmol. 2009;93(7):853–60.

    Article  CAS  PubMed  Google Scholar 

  10. Mantopoulos D, Cruzat A, Hamrah P. In vivo imaging of corneal inflammation: new tools for clinical practice and research. Semin Ophthalmol. 2010;25(5-6):178–85.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jiao H, Naranjo Golborne C, Dando SJ, McMenamin PG, Downie LE, Chinnery HR. Topographical and morphological differences of corneal dendritic cells during steady state and inflammation. Ocul Immunol Inflamm. 2020;28(6):898–907.

    Article  CAS  PubMed  Google Scholar 

  12. Maruoka S, Inaba M, Ogata N. Activation of dendritic cells in dry eye mouse model. Invest Ophthalmol Vis Sci. 2018;59(8):3269–77.

    Article  CAS  PubMed  Google Scholar 

  13. Schaumburg CS, Siemasko KF, de Paiva CS, Wheeler LA, Niederkorn JY, Pflugfelder SC, et al. Ocular surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis. J Immunol. 2011;187(7):3653–62.

    Article  CAS  PubMed  Google Scholar 

  14. Alhatem A, Cavalcanti B, Hamrah P. In vivo confocal microscopy in dry eye disease and related conditions. Semin Ophthalmol. 2012;27(5-6):138–48.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Al-Aqaba MA, et al. Corneal nerves in health and disease. Prog Retin Eye Res. 2019;73:100762.

    Article  PubMed  Google Scholar 

  16. Yang AY, Chow J, Liu J. Corneal innervation and sensation: the eye and beyond. The Yale journal of biology and medicine. 2018;91(1):13–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Bessou P, Perl ER. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol. 1969;32(6):1025–43.

    Article  CAS  PubMed  Google Scholar 

  18. Golebiowski B, Papas E, Stapleton F. Assessing the sensory function of the ocular surface: implications of use of a non-contact air jet aesthesiometer versus the Cochet–Bonnet aesthesiometer. Exp Eye Res. 2011;92(5):408–13.

    Article  CAS  PubMed  Google Scholar 

  19. Lum E, Murphy PJ. Effects of ambient humidity on the Cochet–Bonnet aesthesiometer. Eye. 2018;32(10):1644–51.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chao C, et al., Ocular surface sensitivity repeatability with Cochet-Bonnet esthesiometer. Optometry and Vision Science, 2015. 92(2).

  21. Stapleton F, Tan ME, Papas EB, Ehrmann K, Golebiowski B, Vega J, et al. Corneal and conjunctival sensitivity to air stimuli. Br J Ophthalmol. 2004;88(12):1547–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Erie, JC, et al., The effect of age on the corneal subbasal nerve plexus. Cornea, 2005. 24(6).

  23. Patel DV, et al., Corneal sensitivity and slit scanning in vivo confocal microscopy of the subbasal nerve plexus of the normal central and peripheral human cornea. Cornea, 2009. 28(7).

  24. Niederer RL, Perumal D, Sherwin T, McGhee CNJ. Age-related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study. Br J Ophthalmol. 2007;91(9):1165–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Parissi M, Karanis G, Randjelovic S, Germundsson J, Poletti E, Ruggeri A, et al. Standardized baseline human corneal subbasal nerve density for clinical investigations with laser-scanning in vivo confocal microscopy. Invest Ophthalmol Vis Sci. 2013;54(10):7091–102.

    Article  PubMed  Google Scholar 

  26. Murphy PJ, Lawrenson JG, Patel S, Marshall J. Reliability of the non-contact corneal aesthesiometer and its comparison with the Cochet–Bonnet aesthesiometer. Ophthalmic Physiol Opt. 1998;18(6):532–9.

    Article  CAS  PubMed  Google Scholar 

  27. Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15(3):276–83.

    Article  PubMed  Google Scholar 

  28. Ganesalingam K, Ismail S, Sherwin T, Craig JP. Molecular evidence for the role of inflammation in dry eye disease. Clin Exp Optom. 2019;102(5):446–54.

    Article  PubMed  Google Scholar 

  29. Patel S, et al. Corneal nerve abnormalities in ocular and systemic diseases. Exp Eye Res. 2020:108284.

  30. Kloosterboer A, Dermer HI, Galor A. Diagnostic tests in dry eye. Expert Review of Ophthalmology. 2019;14(4-5):237–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Labbé A, Alalwani H, van Went C, Brasnu E, Georgescu D, Baudouin C. The relationship between subbasal nerve morphology and corneal sensation in ocular surface disease. Invest Ophthalmol Vis Sci. 2012;53(8):4926–31.

    Article  PubMed  Google Scholar 

  32. Choi EY, et al., Corneal microstructural changes in non-Sjˆgren dry eye using confocal microscopy: clinical correlation. 2015. 56: 680-686.

  33. Labbé A, Liang Q, Wang Z, Zhang Y, Xu L, Baudouin C, et al. Corneal nerve structure and function in patients with non-Sjögren dry eye: clinical correlations. Invest Ophthalmol Vis Sci. 2013;54(8):5144–50.

    Article  PubMed  Google Scholar 

  34. Villani E, et al., In vivo confocal evaluation of the ocular surface morpho-functional unit in dry eye. Optom Vis Sci, 2013. 90(6).

  35. Zhang M, et al., Altered corneal nerves in aqueous tear deficiency viewed by in vivo confocal microscopy. Cornea, 2005. 24(7).

  36. Shetty R, et al. Corneal dendritic cell density is associated with subbasal nerve plexus features, ocular surface disease index, and serum vitamin D in evaporative dry eye disease. Biomed Res Int. 2016;2016:4369750.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Khamar P, Nair AP, Shetty R, Vaidya T, Subramani M, Ponnalagu M, et al. Dysregulated tear fluid nociception-associated factors, corneal dendritic cell density, and vitamin D levels in evaporative dry eye. Invest Ophthalmol Vis Sci. 2019;60(7):2532–42.

    Article  CAS  PubMed  Google Scholar 

  38. Parra A, et al. Tear fluid hyperosmolality increases nerve impulse activity of cold thermoreceptor endings of the cornea. PAIN®. 2014;155(8):1481–91.

    Article  Google Scholar 

  39. Rahman EZ, et al. Corneal sensitivity in tear dysfunction and its correlation with clinical parameters and blink rate. Am J Ophthalmol. 2015;160(5):858–866.e5.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Benítez-del-Castillo JM, et al. Relation between corneal innervation with confocal microscopy and corneal sensitivity with noncontact esthesiometry in patients with dry eye. Invest Ophthalmol Vis Sci. 2007;48(1):173–81.

    Article  PubMed  Google Scholar 

  41. Bourcier T, Acosta MC, Borderie V, Borra´s F, Gallar J, Bury T, et al. Decreased corneal sensitivity in patients with dry eye. Invest Ophthalmol Vis Sci. 2005;46(7):2341–5.

    Article  PubMed  Google Scholar 

  42. Sade De Paiva C, Pflugfelder SC. Corneal epitheliopathy of dry eye induces hyperesthesia to mechanical air jet stimulation. Am J Ophthalmol. 2004;137(1):109–15.

    Article  Google Scholar 

  43. Simsek C, Kojima T, Dogru M, Tsubota K. Alterations of murine subbasal corneal nerves after environmental dry eye stress. Invest Ophthalmol Vis Sci. 2018;59(5):1986–95.

    Article  CAS  PubMed  Google Scholar 

  44. Simsek C, Kojima T, Nagata T, Dogru M, Tsubota K. Changes in murine subbasal corneal nerves after scopolamine-induced dry eye stress exposure. Invest Ophthalmol Vis Sci. 2019;60(2):615–23.

    Article  CAS  PubMed  Google Scholar 

  45. Leonard BC, Stewart KA, Shaw GC, Hoehn AL, Stanley AA, Murphy CJ, et al. Comprehensive clinical, diagnostic, and advanced imaging characterization of the ocular surface in spontaneous aqueous deficient dry eye disease in dogs. Cornea. 2019;38(12):1568–75.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Schiffman RM, et al. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118(5):615–21.

    Article  CAS  PubMed  Google Scholar 

  47. Chalmers RL, Begley CG, Caffery B. Validation of the 5-Item Dry Eye Questionnaire (DEQ-5): discrimination across self-assessed severity and aqueous tear deficient dry eye diagnoses. Cont Lens Anterior Eye. 2010;33(2):55–60.

    Article  PubMed  Google Scholar 

  48. •• Farhangi M, et al. Modification of the Neuropathic Pain Symptom Inventory for use in eye pain (NPSI-Eye). Pain. 2019;160(7):1541–50 This study is very important because it validated a neuropathic pain questionnaire that can be used in individuals with ocular pain, the NPSI-Eye.

    Article  PubMed  PubMed Central  Google Scholar 

  49. •• Qazi, Y., et al., Validity and reliability of a Novel Ocular Pain Assessment Survey (OPAS) in quantifying and monitoring corneal and ocular surface pain. Ophthalmology, 2016. 123(7): p. 1458-1468. This study is very important because it validated a pain questionnaire that can be used in individuals with ocular pain

  50. Tepelus TC, Chiu GB, Huang J, Huang P, Sadda SVR, Irvine J, et al. Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study. Graefes Arch Clin Exp Ophthalmol. 2017;255(9):1771–8.

    Article  PubMed  Google Scholar 

  51. Denoyer A, Landman E, Trinh L, Faure JF, Auclin F, Baudouin C. Dry eye disease after refractive surgery: comparative outcomes of small incision lenticule extraction versus LASIK. Ophthalmology. 2015;122(4):669–76.

    Article  PubMed  Google Scholar 

  52. Spierer O, Felix ER, McClellan AL, Parel JM, Gonzalez A, Feuer WJ, et al. Corneal mechanical thresholds negatively associate with dry eye and ocular pain symptoms. Invest Ophthalmol Vis Sci. 2016;57(2):617–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Liang Q, et al. Ocular surface epithelial thickness evaluation in dry eye patients: clinical correlations. J Ophthalmol. 2016;2016:1628469.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Galor A, et al., Corneal nerve pathway function in individuals with dry eye symptoms. Ophthalmology, 2020.

  55. Tanaka A, et al. In vivo confocal microscopy in patients with dry eye disease demonstrates decreased peripheral corneal nerve density and correlation to clinical signs. Invest Ophthalmol Vis Sci. 2017;58(8):3753.

    Google Scholar 

  56. Bron AJ, Yokoi N, Gaffney E, Tiffany JM. Predicted phenotypes of dry eye: proposed consequences of its natural history. The Ocular Surface. 2009;7(2):78–92.

    Article  PubMed  Google Scholar 

  57. Villani E, Bonsignore F, Cantalamessa E, Serafino M, Nucci P. Imaging biomarkers for dry eye disease. Eye Contact Lens. 2020;46(Suppl 2):S141–s145.

    Article  PubMed  Google Scholar 

  58. IASP Terminology. 2020; Available from: https://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698.

  59. Rosenthal P, Borsook D. The corneal pain system. Part I: the missing piece of the dry eye puzzle∗. The Ocular Surface. 2012;10(1):2–14.

    Article  PubMed  Google Scholar 

  60. Galor A, Moein HR, Lee C, Rodriguez A, Felix ER, Sarantopoulos KD, et al. Neuropathic pain and dry eye. The ocular surface. 2018;16(1):31–44.

    Article  PubMed  Google Scholar 

  61. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clinical ophthalmology (Auckland, NZ). 2014;8:571–9.

    Google Scholar 

  62. Lockwood A, Hope-Ross M, Chell P. Neurotrophic keratopathy and diabetes mellitus. Eye. 2006;20(7):837–9.

    Article  CAS  PubMed  Google Scholar 

  63. Kalangara JP, Galor A, Levitt RC, Covington DB, McManus KT, Sarantopoulos CD, et al. Characteristics of ocular pain complaints in patients with idiopathic dry eye symptoms. Eye Contact Lens. 2017;43(3):192–8.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Galor A, Moein HR, Lee C, Rodriguez A, Felix ER, Sarantopoulos KD, et al. Neuropathic pain and dry eye. Ocul Surf. 2018;16(1):31–44.

    Article  PubMed  Google Scholar 

  65. • Galor, A., et al., Neuropathic ocular pain due to dry eye is associated with multiple comorbid chronic pain syndromes. J Pain, 2016. 17(3): p. 310-318. This study is important because it evaluated dry eye symptoms and signs in individuals chronic pain

  66. • Farhangi M, et al. Individuals with migraine have a different dry eye symptom profile than individuals without migraine. Br J Ophthalmol. 2020;104(2):260–4 This study is important because it evaluated dry eye symptoms and signs in individuals with and without migraine.

    Article  PubMed  Google Scholar 

  67. Crane AM, Feuer W, Felix ER, Levitt RC, McClellan AL, Sarantopoulos KD, et al. Evidence of central sensitisation in those with dry eye symptoms and neuropathic-like ocular pain complaints: incomplete response to topical anaesthesia and generalised heightened sensitivity to evoked pain. Br J Ophthalmol. 2017;101(9):1238–43.

    Article  PubMed  Google Scholar 

  68. Rosenthal P, Borsook D. Ocular neuropathic pain. Br J Ophthalmol. 2016;100(1):128–34.

    Article  PubMed  Google Scholar 

  69. • Dermer H, et al., Corneal sub-basal nerve plexus microneuromas in individuals with and without dry eye. British Journal of Ophthalmology, 2021: p. bjophthalmol-2020-317891. This study is important because it did not find a relationship between a specific anatomic findings (termed microneuroma) and ocular pain.

  70. Rózsa AJ, Guss RB, Beuerman RW. Neural remodeling following experimental surgery of the rabbit cornea. Invest Ophthalmol Vis Sci. 1983;24(8):1033–51.

    PubMed  Google Scholar 

  71. •• Moein H-R, et al. Visualization of microneuromas by using in vivo confocal microscopy: an objective biomarker for the diagnosis of neuropathic corneal pain? The Ocular Surface. 2020;18(4):651–6 This study is very important because it presented an anatomic nerve finding (termed microneuroma) as a potential marker for corneal neuropathic pain.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Chinnery HR, et al., Identification of presumed corneal neuromas and microneuromas using laser-scanning in vivo confocal microscopy: a systematic review. British Journal of Ophthalmology, 2021: p. bjophthalmol-2020-318156.

  73. • Stepp MA, et al., Corneal epithelial “neuromas”: a case of mistaken identity? Cornea, 2020. 39(7). This study is important because it provided an alternative explanation to the anatomic finding termed microneuroma.

  74. Labetoulle M, Baudouin C, Calonge M, Merayo-Lloves J, Boboridis KG, Akova YA, et al. Role of corneal nerves in ocular surface homeostasis and disease. Acta Ophthalmol. 2019;97(2):137–45.

    Article  PubMed  Google Scholar 

  75. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571–9.

    PubMed  PubMed Central  Google Scholar 

  76. Matsumoto Y, et al. Autologous serum application in the treatment of neurotrophic keratopathy. Ophthalmology. 2004;111(6):1115–20.

    Article  PubMed  Google Scholar 

  77. Rao K, Leveque C, Pflugfelder SC. Corneal nerve regeneration in neurotrophic keratopathy following autologous plasma therapy. Br J Ophthalmol. 2010;94(5):584–91.

    Article  PubMed  Google Scholar 

  78. Kruse FE, Rohrschneider K, Völcker HE. Multilayer amniotic membrane transplantation for reconstruction of deep corneal ulcers. Ophthalmology. 1999;106(8):1504–11.

    Article  CAS  PubMed  Google Scholar 

  79. • Bonini S, et al. Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology. 2018;125(9):1332–43 This study is important because it evaluated the efficacy of recombinant NGF in NK.

    Article  PubMed  Google Scholar 

  80. • Pflugfelder SC, et al. Topical recombinant human nerve growth factor (Cenegermin) for neurotrophic keratopathy: a multicenter randomized vehicle-controlled pivotal trial. Ophthalmology. 2020;127(1):14–26 This study is important because it evaluated the efficacy of recombinant NGF in NK.

    Article  PubMed  Google Scholar 

  81. Kim JS, Rafailov L, Leyngold IM, Corneal neurotization for postherpetic neurotrophic keratopathy: initial experience and clinical outcomes. Ophthalmic Plastic & Reconstructive Surgery, 9000. Publish Ahead of Print

  82. Terzis JK, Dryer MM, Bodner BI, Corneal neurotization: a novel solution to neurotrophic keratopathy. Plast Reconstr Surg, 2009. 123(1).

  83. Aggarwal S, Kheirkhah A, Cavalcanti BM, Cruzat A, Colon C, Brown E, et al. Autologous serum tears for treatment of photoallodynia in patients with corneal neuropathy: efficacy and evaluation with in vivo confocal microscopy. The Ocular Surface. 2015;13(3):250–62.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Morkin MI, Hamrah P. Efficacy of self-retained cryopreserved amniotic membrane for treatment of neuropathic corneal pain. The ocular surface. 2018;16(1):132–8.

    Article  PubMed  Google Scholar 

  85. Bates BD, Mitchell K, Keller JM, Chan CC, Swaim WD, Yaskovich R, et al. Prolonged analgesic response of cornea to topical resiniferatoxin, a potent TRPV1 agonist. PAIN. 2010;149(3):522–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Small LR, et al., Oral gabapentinoids and nerve blocks for the treatment of chronic ocular pain. Eye & Contact Lens, 2020. 46(3).

  87. Ozmen MC, et al. Nortriptyline is effective in ameliorating symptoms of neuropathic corneal pain. Invest Ophthalmol Vis Sci. 2019;60(9):4732.

    Google Scholar 

  88. Scholz A, Kuboyama N, Hempelmann G, Vogel W. Complex blockade of TTX-resistant Na+ currents by lidocaine and bupivacaine reduce firing frequency in DRG neurons. J Neurophysiol. 1998;79(4):1746–54.

    Article  CAS  PubMed  Google Scholar 

  89. Diel RJ, Kroeger ZA, Levitt RC, Sarantopoulos C, Sered H, Martinez-Barrizonte J, et al. Botulinum toxin A for the treatment of photophobia and dry eye. Ophthalmology. 2018;125(1):139–40.

    Article  PubMed  Google Scholar 

  90. Johnson M. Transcutaneous electrical nerve stimulation: mechanisms, clinical application and evidence. Reviews in pain. 2007;1(1):7–11.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Diel RJ, Hwang J, Kroeger ZA, Levitt RC, Sarantopoulos CD, Sered H, et al. Photophobia and sensations of dryness in patients with migraine occur independent of baseline tear volume and improve following botulinum toxin A injections. Br J Ophthalmol. 2019;103(8):1024–9.

    Article  PubMed  Google Scholar 

  92. Sivanesan E, Levitt RC, Sarantopoulos CD, Patin D, Galor A. Noninvasive electrical stimulation for the treatment of chronic ocular pain and photophobia. Neuromodulation: Technology at the Neural Interface. 2018;21(8):727–34.

    Article  Google Scholar 

  93. Katz BJ, Digre KB. Diagnosis, pathophysiology, and treatment of photophobia. Surv Ophthalmol. 2016;61(4):466–77.

    Article  PubMed  Google Scholar 

  94. Wilkins AJ, Patel R, Adjamian P, Evans BJW. Tinted spectacles and visually sensitive migraine. Cephalalgia. 2002;22(9):711–9.

    Article  CAS  PubMed  Google Scholar 

  95. Patel S, et al., Dysfunctional coping mechanisms contribute to dry eye symptoms. J Clin Med, 2019. 8(6).

  96. Lamb SE, Hansen Z, Lall R, Castelnuovo E, Withers EJ, Nichols V, et al. Group cognitive behavioural treatment for low-back pain in primary care: a randomised controlled trial and cost-effectiveness analysis. Lancet. 2010;375(9718):916–23.

    Article  PubMed  Google Scholar 

  97. Otis JD, Sanderson K, Hardway C, Pincus M, Tun C, Soumekh S. A randomized controlled pilot study of a cognitive-behavioral therapy approach for painful diabetic peripheral neuropathy. J Pain. 2013;14(5):475–82.

    Article  PubMed  Google Scholar 

  98. Mehra D, Cohen NK, Galor A, Ocular surface pain: a narrative review. Ophthalmology and Therapy, 2020.

Download references

Acknowledgements

This study was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences R&D (CSRD) I01 CX002015 (Dr. Galor) and Biomedical Laboratory R&D (BLRD) Service I01 BX004893 (Dr. Galor), Department of Defense Gulf War Illness Research Program (GWIRP) W81XWH-20-1-0579 (Dr. Galor) and Vision Research Program (VRP) W81XWH-20-1-0820 (Dr. Galor), National Eye Institute R01EY026174 (Dr. Galor) and R61EY032468 (Dr. Galor), NIH Center Core Grant P30EY014801 (institutional) and Research to Prevent Blindness Unrestricted Grant (institutional).

Author information

Authors and Affiliations

  1. Ophthalmology, Miami Veterans Affairs Medical Center, 1201 NW 16th St, Miami, FL, 33125, USA

    Sneh Patel, Divy Mehra & Anat Galor

  2. Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA

    Sneh Patel, Divy Mehra & Anat Galor

  3. Research Services, Miami Veterans Affairs Medical Center, Miami, FL, USA

    Kimberly Cabrera & Anat Galor

Authors
  1. Sneh Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Divy Mehra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kimberly Cabrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anat Galor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anat Galor.

Ethics declarations

Human and Animal Rights

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Cornea

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patel, S., Mehra, D., Cabrera, K. et al. How Should Corneal Nerves Be Incorporated Into the Diagnosis and Management of Dry Eye?. Curr Ophthalmol Rep 9, 65–76 (2021). https://doi.org/10.1007/s40135-021-00268-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40135-021-00268-y

Keywords

Search

Navigation