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Neuropathic Ocular Pain

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Title: Neuropathic Ocular Pain

Authors: Jaxon J. Huang, 4th year medical student, University of Hawaii; Anat Galor, MD MSPH, University of Miami, Bascom Palmer Eye Institute

Date: 8/15/2023

Keywords/Main Subjects: neuropathic ocular pain, eye pain, headache, photophobia, dry eye

Diagnosis: Neuropathic ocular pain

Description of Case:

A 49-year-old female with a history of depression, fibromyalgia, and traumatic brain injury presented to the ophthalmology clinic for dry eye symptoms of irritation and grittiness in both eyes for 2 years. She also reported burning and aching eye pain, frequent headaches, and sensitivity to light and wind. The patient had been using artificial tears 5 times a day for the past 6 months with no relief in symptoms. Her dry eye and ocular pain symptoms were evaluated using questionnaires, including the 5 Item Dry Eye Questionnaire (DEQ5; scale 0-22)1, Ocular Surface Disease Index (OSDI; scale 0-100)2, and the Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye; scale 0-40)3. Her baseline scores were as follows: DEQ5=16 (severe), OSDI=87.5 (severe), NPSI-Eye=27 (severe).

Examination:

Imaging:

Images:

Figure 1. In-vivo confocal microscopy image of corneal nerves showing activated dendritic cells (white dashed circles) and increased nerve tortuosity with decreased nerve density (white arrow).

Figure 1. In-vivo confocal microscopy image of corneal nerves showing activated dendritic cells (white dashed circles) and increased nerve tortuosity with decreased nerve density (white arrow).

Clinical Course:

The patient was diagnosed with neuropathic ocular pain. She was treated with 35 units of Botulinum toxin A (BoNT-A) based on a modified migraine protocol targeting the corrugator, procerus, and the frontalis muscles.11 To target photophobia, the patient was prescribed FL-41 tinted lenses. While she still reported occasional symptoms of ocular irritation, the frequency and severity of her ocular pain and migraines were reduced. Additionally, she endorsed a reduction in photophobia with use of the FL-41 tinted lenses. Her post-treatment questionnaire scores evaluating dry eye and ocular pain symptoms were as follows: DEQ5=10 (mild-moderate), OSDI=79 (severe), NPSI-Eye=17 (moderate).

Discussion:

Ocular pain is frequently incorporated under the term “dry eye disease (DED)”, which encompasses a variety of symptoms such as dryness, irritation, and pain, along with clinical signs of decreased tear production or loss of tear film homeostasis. DED pain symptoms in particular can be driven by nociceptive sources, such as ocular surface inflammation and tear film instability, or by neuropathic sources, such as nerve dysfunction.10, 12, 13 Currently, a diagnosis of a neuropathic contributor to ocular pain is made based on clinical examination findings. Individuals with neuropathic ocular pain (NOP) often describe their pain as “burning” or “shooting” and endorse evoked pain to triggers such as wind and light.14 Additionally, individuals will often present with a discordance between pain symptoms and clinical signs of tear dysfunction, with symptoms that are out of proportion to signs.15 Furthermore, persistent pain after application of a topical anesthetic and abnormal corneal nerve anatomy and function may be observed in NOP.8,16 Individuals with NOP often fail treatments targeted towards improving tear health (e.g. artificial tears and anti-inflammatory drops) and have co-morbid pain conditions, including migraine and fibromyalgia.17, 18
The current treatment of NOP involves targeting underlying nerve dysfunction using topical, oral, or adjuvant therapy. Topical therapies include autologous serum tears and transient receptor potential vanilloid (TRPV1) antagonists19, while oral agents include gabapentin, pregabalin, and nortriptyline, all of which have varying success in treating NOP.20,21 Adjuvant therapies consist of transcutaneous electrical nerve stimulation devices and BoNT-A injections, which have both been shown to decrease symptoms of ocular pain and photophobia.22, 23 In addition, the use of FL-41 tinted lenses has been reported to be helpful in alleviating photophobia and migraine.24 However, despite the wide variety of treatment options available, pain persists in many NOP patients, highlighting the need for new therapeutic approaches.25

Summary of the Case:

NOP is diagnosed clinically based on findings of “burning” pain, pain evoked by wind or light, symptoms that outweigh clinical signs of tear dysfunction, persistent pain after topical anesthetic, and abnormal corneal anatomy and function. While various topical, oral, and adjuvant therapies have been investigated and shown to have varying efficacy, further studies are needed to develop novel approaches for patients who do not respond to current options.

References:

  1. 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.
  2. Schiffman RM, Christianson MD, Jacobsen G, et al. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol 2000;118(5):615-21.
  3. Farhangi M, Feuer W, Galor A, et al. Modification of the Neuropathic Pain Symptom Inventory for use in eye pain (NPSI-Eye). Pain 2019;160(7):1541-50.
  4. Sambursky R, Davitt WF, 3rd, Latkany R, et al. Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye. JAMA Ophthalmol 2013;131(1):24-8.
  5. Ansari Z, Singh R, Alabiad C, Galor A. Prevalence, risk factors, and morbidity of eye lid laxity in a veteran population. Cornea 2015;34(1):32-6.
  6. Foulks GN, Bron AJ. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf 2003;1(3):107-26.
  7. Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5(2):108-52.
  8. Crane AM, Feuer W, Felix ER, 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.
  9. Pult H, Riede-Pult B. Comparison of subjective grading and objective assessment in meibography. Cont Lens Anterior Eye 2013;36(1):22-7.
  10. Belmonte C, Nichols JJ, Cox SM, et al. TFOS DEWS II pain and sensation report. Ocul Surf 2017;15(3):404-37.
  11. Venkateswaran N, Hwang J, Rong AJ, et al. Periorbital botulinum toxin A improves photophobia and sensations of dryness in patients without migraine: Case series of four patients. Am J Ophthalmol Case Rep 2020;19:100809.
  12. Bron AJ, de Paiva CS, Chauhan SK, et al. TFOS DEWS II pathophysiology report. Ocul Surf 2017;15(3):438-510.
  13. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and Classification Report. Ocul Surf 2017;15(3):276-83.
  14. Kalangara JP, Galor A, Levitt RC, et al. Characteristics of Ocular Pain Complaints in Patients With Idiopathic Dry Eye Symptoms. Eye Contact Lens 2017;43(3):192-8.
  15. Ong ES, Felix ER, Levitt RC, et al. Epidemiology of discordance between symptoms and signs of dry eye. Br J Ophthalmol 2018;102(5):674-9.
  16. Galor A, Felix ER, Feuer W, et al. Corneal Nerve Pathway Function in Individuals with Dry Eye Symptoms. Ophthalmology 2021;128(4):619-21.
  17. Galor A, Batawi H, Felix ER, et al. Incomplete response to artificial tears is associated with features of neuropathic ocular pain. Br J Ophthalmol 2016;100(6):745-9.
  18. Lee Y, Kim M, Galor A. Beyond dry eye: how co-morbidities influence disease phenotype in dry eye disease. Clin Exp Optom 2022;105(2):177-85.
  19. Patel S, Mittal R, Sarantopoulos KD, Galor A. Neuropathic ocular surface pain: Emerging drug targets and therapeutic implications. Expert Opin Ther Targets 2022;26(8):681-95.
  20. Small LR, Galor A, Felix ER, et al. Oral Gabapentinoids and Nerve Blocks for the Treatment of Chronic Ocular Pain. Eye Contact Lens 2020;46(3):174-81.
  21. Ozmen MC, Dieckmann G, Cox SM, et al. Efficacy and tolerability of nortriptyline in the management of neuropathic corneal pain. Ocul Surf 2020;18(4):814-20.
  22. Sivanesan E, Levitt RC, Sarantopoulos CD, et al. Noninvasive Electrical Stimulation for the Treatment of Chronic Ocular Pain and Photophobia. Neuromodulation 2018;21(8):727-34.
  23. Reyes N, Huang JJ, Choudhury A, et al. Botulinum toxin A decreases neural activity in pain-related brain regions in individuals with chronic ocular pain and photophobia. Front Neurosci 2023;17:1202341.
  24. Katz BJ, Digre KB. Diagnosis, pathophysiology, and treatment of photophobia. Surv Ophthalmol 2016;61(4):466-77.
  25. Siedlecki AN, Smith SD, Siedlecki AR, et al. Ocular pain response to treatment in dry eye patients. Ocul Surf 2020;18(2):305-11.

Faculty Approval by: Griffin Jardine, MD

Identifier: Moran_CORE_126997

Copyright: Jaxon J. Huang and Anat Galor ©2023. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/