March, 2023

Definition

Corneal neuropathic pain, or corneal neuralgia, may be defined as chronic eye pain lasting more than three months that is not responsive to standard measures, and severe enough to affect daily living. The phenomenon is sometimes described after ocular surgery, including corneal and intraocular, but can occur after any type of eye trauma.

The condition is not well understood and there is no agreement on the diagnostic criteria, causes, incidence, nor treatment.

Pathophysiology

The V1 ophthalmic division of the trigeminal nerve contains nociceptors that respond to a variety to stimuli, including mechanical force and temperature. When stimulated, a signal transduction is transmitted and processed in the pain regions of the cerebral cortex. It is hypothesized that repeated damage to the cornea and its corresponding neuronal pathway results in a hyper‐inflammatory state, which leads to maladaptive sensitization either peripherally at the cornea or centrally at postsynaptic junctions.

Therefore, it may be useful to assess and manage corneal neuropathic pain as either peripheral or central pain sensitization.

Symptoms

Symptoms include, but are not limited to:

• Chronic, unrelenting eye pain
• Dry eye syndrome without signs, which is non‐responsive to standard treatment
• Light sensitivity, burning, foreign body sensation
• Symptom severity has resulted in suicide

Signs

• “Pain without stain”,
• Punctate keratopathy
• No signs may be present

Associated Conditions

• Central somatic sensitivity syndrome
• Fibromyalgia
• Autoimmune disease
• Chronic migraine and headache
• Persistent Post‐operative Pain Disorders (PPP)

Investigations

• Patients’ response to topical anesthetic may be useful in determining if the corneal neuropathic pain is a central or peripheral cause. A response of decreased pain with local anesthetic is suggestive of peripheral etiology.

In vivo Confocal microscopy

The sub‐basal nerve density has been reported to be significantly reduced in corneal neuropathic pain compared with control subjects. Other features described are activated keratocytes and spindle, lateral and stump microneuromas. However, the significance of these findings is unclear, as similar changes can be observed following uncomplicated PRK and LASIK. Therefore, the current role of confocal microscopy in these patients is unclear, and it is available on a limited basis in Canada mostly at academic centers.

Treatment Goals

• Regenerate corneal nerves and reduce inflammation
• Patients with predominantly peripheral sensitization likely have a better outcome than those with central sensitization
• Maximize ocular surface management as with severe dry eye
• Frequent preservative‐free artificial tears, limited use of topical steroids, night‐ time gels, topical cyclosporine
• Most patients will have had this treatment prior to referral with failure to respond

Additional Treatment Options

• Autologous serum drops
• Amniotic membrane
• Neurostimulation
• Corneal growth factors
• Neuromodulation
• Scleral contact lenses
• Systemic treatment may be necessary such as gabapentin, pregabalin, amitriptyline, and low‐dose naltrexone
• Referral to neuro‐ophthalmologist/neurologist/pain specialist. Resources are available in Canada for additional consultation and management

Outcomes

There is a high degree of variability in patient outcomes, with some patients suffering long‐term disability from the symptoms while others show complete resolution after 1 to 2 years. Information in this regard is anecdotal but it is advisable to take all possible measures to manage the disease, as long standing corneal neuralgia tends to be associated with worse patients outcomes.

References

Aggarwal S, Kheirkhah A, Cavalcanti BM, 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):250‐262. doi:10.1016/j.jtos.2015.01.005

Crane AM, Levitt RC, Felix ER, Sarantopoulos KD, McClellan AL, Galor A. Patients with more severe symptoms of neuropathic ocular pain report more frequent and severe chronic overlapping pain conditions and psychiatric disease. British Journal of Ophthalmology. 2017;101(2):227‐231. doi:10.1136/bjophthalmol‐2015‐308214

Galor A, Covington D, Levitt AE, et al. Neuropathic Ocular Pain due to Dry Eye Is Associated With Multiple Comorbid Chronic Pain Syndromes. The Journal of Pain. 2016;17(3):310‐318. doi:10.1016/j.jpain.2015.10.019

Kundu G, Shetty R, D’Souza S, et al. A novel combination of corneal confocal microscopy, clinical features and artificial intelligence for evaluation of ocular surface pain. PLoS One. 2022;17(11):e0277086. doi:10.1371/journal.pone.0277086

Levitt, A.E., Galor, A., Weiss, J.S. et al. Chronic dry eye symptoms after LASIK: parallels and lessons to be learned from other persistent post‐operative pain disorders. Mol Pain 11, 21 (2015). https://doi.org/10.1186/s12990‐015‐0020‐7

Moshirfar M, Benstead EE, Sorrentino PM, Tripathy K. Ocular Neuropathic Pain. In: StatPearls. StatPearls Publishing; 2022. Accessed January 21, 2023. http://www.ncbi.nlm.nih.gov/books/NBK542282/

Neuropathic Corneal Pain ‐ ClinicalKey. 2023.https://www.clinicalkey.com/#!/content/playContent/1‐s2.0‐S0161642017306127

Ocular Neuropathic Pain ‐ EyeWiki. https://eyewiki.aao.org/Ocular_Neuropathic_Pain

Pakravan M, Roshani M, Yazdani S, Faramazi A, Yaseri M. Pregabalin and Gabapentin for Post‐Photorefractive Keratectomy Pain: A Randomized Controlled Trial. European Journal of Ophthalmology. 2012;22(7_suppl):106‐113. doi:10.5301/ejo.5000143

Rosenthal P, Borsook D. Ocular neuropathic pain. Br J Ophthalmol. 2016;100(1):128‐134. doi:10.1136/bjophthalmol‐2014‐306280

The Non-Hospital Surgical Centres (NHSC) Principles is a distilled set of advocacy principles developed by the Canadian Ophthalmological Society. This document is based on feedback from a COS Workshop on NHSC held in September 2021, and from member and stakeholder surveys undertaken during the spring of 2022.

To view the full document please click here:

August 2022

Vision therapy (VT), or behavioural optometry, is a generalized term for behavioural treatments based upon the belief that abnormalities in vision are the underlying cause of learning, neurological and spatial disabilities.

A review of the available literature on these treatments conducted in 2022 by a committee of physicians specializing in pediatric ophthalmology and neuro-ophthalmology found that, with the exception of convergence insufficiency, evidence that these therapies are effective is lacking.

Background

Vision therapy is a term used to refer to a spectrum of in-office supervised exercises that aim to improve visual ability and skill. Vision therapy programs are prescribed for a wide and etiologically diverse group of pathological and non-pathological learning, oculomotor, visual and post-traumatic states. These conditions include strabismus, amblyopia, learning/reading disabilities (dyslexia), myopia, and brain injuries such as stroke, concussion, and trauma with visuospatial neglect. Vision therapy remains an uninsured paramedical service.

Canadian Ophthalmological Society (COS) members have noted a sharp increase in the number of requests to provide an opinion on the effectiveness and validity of prescribed vision therapy programs. These programs can last from several weeks to years and, at times, a lifetime of treatment. The COS Vision Therapy committee feels that additional high-quality evidence-based research must be performed prior to any consideration for public or private insurance coverage.

Read the full position statement here.

September 2018

Context: There is a growing trend among body modification enthusiasts to tattoo their eyeballs (specifically the sclera of the eye) and also implant jewellery under the surface layer (conjunctiva) of the eyeball. This is being done unsafely by untrained artists under questionable conditions and leading to a
variety of unfortunate complications, including loss of vision and loss of the eye in some cases. As eye health care professionals, the Manitoba Association of Optometrists (MAO) and the Eye Physicians and Surgeons of Manitoba (EPSOM) are submitting this joint statement calling for a ban of these dangerous practices leading to unnecessary morbidity and loss of vision in members of the unsuspecting public.

Read the Full Position Statement Here

November 2019

Evidence-Based Recommendations for the Risk of Acute Angle Closure Glaucoma with Routine Use of Hyoscine-n-Butylbromide (Buscopan) for Gastroenterological Procedures.

The Position Stated is based on current evidence and expert medical opinion available at the time and was endorsed by the COS in November 2019.

Background: Hyoscine-n-butylbromide (Buscopan) is a commonly used anticholinergic medication for
gastroenterological endoscopic procedures because of its ability to induce smooth muscle relaxation and decrease spasm. It can also be used for radiologic procedures of the gastrointestinal tract. Buscopan may increase detection of colorectal adenoma by up to 30%, thus this medication should not be withheld needlessly.

July 21, 2022

Advisory Statement: Regarding Light Therapy (Photobiomodulation) for Macular Degeneration

Discussion: Patients with early dry macular degeneration often have relatively normal vision. As the disease progresses to advanced stages, patients can have both a gradual and/or sudden loss of central vision. There are no proven pharmacologic treatments for dry ARMD, however age-related eye disease study (AREDS) vitamin supplementation has been shown in large, randomized trials to decrease the risk of progressing to advanced macular degeneration. Canadian patients have coverage and access to effective, large randomized clinical trial-proven pharmacologic treatments for wet macular degeneration.

Read the full advisory statement here

April 2, 2019

Position Statement by the Canadian Ophthalmological Society (COS) Regarding Diversity and Inclusion

The Canadian Ophthalmological Society (COS) encourages inclusivity and opposes discrimination based on (but not limited to) religion, race, citizenship, country or ethnic origin, language, age, political affiliation or opinion, sex, sexual orientation, gender identity and expression, cognitive or physical ability, and economic status. As the recognized unified voice for ophthalmology in Canada, COS is strengthened by its diversity. COS members come from broad and diverse backgrounds, and this variety of experiences, training, and personal qualities is fundamental to ophthalmologists’ ability to provide the highest quality and culturally competent care for all patients.

July 19th, 2022

Canadian Ophthalmological Society (COS) Position Statement on Biosimilars

Biosimilar biologic drugs (or biosimilars*) were introduced in the Canadian market in 2009, however, the first ophthalmic biosimilar is expected to be launched in Canada in the fall of 2022. With the advent of biosimilar drugs into the Canadian market payors (government and insurers) are developing policies on how these medications are integrated into reimbursement programs for existing “innovator” or reference drugs. The trend currently seems to be toward limiting or restricting physician and patient choice in incorporating biosimilars into the Canadian market.

This seems contrary to the European experience where forced substitution has not been necessary to encourage uptake and realize significant savings.

The physician-patient relationship and a patient’s resulting confidence in their treatment plan is crucial to successful treatment. Limiting choice and mandating changes to existing successful treatment regimens undermines that confidence and could be detrimental to patient care.

In addition, given the unique immunological environment and limited tolerance for inflammation which exists with direct administration of the medication into the eye, the COS cautions against mandating large scale, automatic shifts from the reference to biosimilar medications until sufficient human experience has been accumulated to ensure confidence in safety. Furthermore, as individual patient response to medication varies, physicians must have the opportunity to switch back to the original medication if problems develop in order to prevent harm.

The COS welcomes and supports the potential of biosimilars to expand the choices available for effective treatment of eye disease in a cost-effective manner, however it is vital that payors and payor’s policies do not constrain medical choice or undermine patient confidence in treatment plans.

Created June 2022

*A biosimilar biologic drug, or biosimilar, is a biologic drug that is highly similar to a qualifying biologic drug that was already authorized for sale (known as the reference biologic drug). (Health Canada, Handbook for healthcare professionals on biosimilar biologic drugs, https://www.canada.ca/en/health- canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/biosimilar- biologic-drugs/handbook-healthcare-professionals.html#Biosimilar_Drugs accessed June 27, 2022)

February 16th, 2022

The Canadian Ophthalmological Society (COS) embraces inclusivity and opposes discrimination based on (but not limited to) religion, race, citizenship, country or ethnic origin, language, age, political affiliation, sex, sexual orientation, gender identity and expression, cognitive or physical ability, and economic status. As the recognized unified voice for ophthalmology in Canada, COS is strengthened by its diversity, and the COS is committed to being a leader in equity, diversity and inclusion in ophthalmology. COS members come from broad and diverse backgrounds, and this variety of experiences, training, and personal qualities is fundamental to a physician’s ability to provide the highest quality and culturally competent care for all patients.