Topical Anesthetic Drops for Eye Pain


One of my dear patients sent me this link for Trigeminal Neuralgia Pain.

For years, eyeMDs have been warned to keep tetraine in the office monitored and protected as there have been patients who have take the bottle to use for chronic eye pain. Most eyeMD have seen patients who developed a corneal infection due to secret tetracaine use. While at Harvad, I saw a patient who developed a serious eye infection partly from using daily tetracaine for chronic epithelial erosion. The infection destroyed the patient’s eyeball.

Thus eyeMDs never prescribe anesthetic drops for any reason in general: because the risk that by numbing the eye, the patient will not notice if a bacteria starts to invade the eye.

But this may be changing for patients with severe debilitating eye pain.

The study below shows that amethocaine (Brands: TetraVisc, Tetravisc Forte, Altacaine, and Tetracaine)

Still the FDA has the following warnings for these types of anestetic drops:

Do not use intracamerally since use may damage corneal endothelial cells.
 Prolonged use or abuse may lead to corneal epithelial toxicity and may manifest as epithelial defects which may progress to permanent corneal damage.
 Patients should not touch the eye for at least 10-20 minutes after using anesthetic as accidental injuries can occur due to insensitivity of the eye.

If a patient is under the close watch of an eyeMD, these anestheic drops are an option for debilitating eye pain. It is best if the patient signs a consent form to note the patient understands the risks of using such a drop as the risk of infection and loss of vision and the eye permanetly is a big concern.

I have had 2 patients where tetracaine or any anesthetic eye drop did not help with pain. This response is very rare.

For now, it is important to remember the benefits of this type of drop may outweight the risks depending on the patient. Most eyeMDs know patients who are very close to despair from eye pain. Most know of patients in the media who have taken their lives from dry eye pain. If an anethetic drop would help, most eyeMDs would prescribe. But the risks are real. Thus do not rub the eye aggressively after using this type of drop. Be sure to see your eye doctor at least every couple of weeks while on the drop. See your eye doctor for any redness, tearing, pain outside of the ordinary when on this drop.

Also:

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If a Patient is given a prescription for temporary & well-monitored Anesthetic Drops for Eye Pain (ADEP), the below paper **indicates keeping the drops refrigerated, helps with the burning sensation of these drops

SLC

. 2010; 3: 155–157.
Published online 2010 Dec 12. doi: 10.2147/LRA.S14281
PMCID: PMC3417962
PMID: 22915883

Topical ophthalmic amethocaine alleviates trigeminal neuralgia pain

Correspondence: Silviu Brill, Pain Clinic, Tel-Aviv Medical Center, Weizman 6 St, Tel-Aviv, Israel, Tel +972 36974477, Fax +972 36974583, Email moc.oohay@lirb_s
This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

Introduction

Trigeminal neuralgia (TGN), also called “tic douloureux”, is a neurological condition affecting the sensory division of the fifth cranial (trigeminal) nerve and characterized by recurrent episodes of severe, shock-like pain confined to the distribution of one or more of the nerve’s three major branches: the ophthalmic (V1), maxillary (V2), or mandibular (V3). Typically, excruciating, lancinating facial pain occurs following stimulation of specific trigger zones by movement or touch. The paroxysmal pain may be felt in the lips, gums, cheek, or chin. TGN occurs in about 1 in 25,000 in the general population and is uncommon before the third decade of age.
Pharmacotherapy is at present the first-line treatment for TGN and includes analgesics, anticonvulsants, and antidepressants. Surgical treatment is reserved for refractory and long-lasting pain.
Amethocaine, a 4-(butylamino)benzoic acid 2-(dimethylamino)ethyl ester, is a potent surface local anesthetic that acts by blocking sensory nerve endings near the site of application. In ophthalmology, amethocaine hydrochloride is used to anesthetize the cornea during ophthalmological procedures. When tested before, in a double-blind, placebo-controlled study, Kondziolka et al found that a single application of an eye drop of amethocaine did not cause any statistically significant pain relief in patients with classical TGN.
The aim of the present study was to further test the effectiveness of local instillation of ophthalmic solution of amethocaine 1% in relieving the pain of TGN.

Material and methods

A total of 40 consecutive patients (M-17, F-23) previously diagnosed with TGN and attending our pain clinic from January 1, 2005 to June 1, 2007 were included in this prospective case study. The diagnosis was made according to International Association for the Study of Pain (IASP) criteria.

Instillation method

Two drops of amethocaine 1% were instilled onto the cornea ipsilateral to the painful side. After instillation the eye was closed for 10 minutes and the patient remained for surveillance in the pain clinic for another 20 minutes. For the patients with no significant pain reduction a second eye instillation was performed 15 minutes after the initial instillation. Changes in the severity of pain and frequency of attacks were assessed using the student t-test for paired data.

Results

When attending the pain clinic, all patients suffered from severe typical sharp and lancinating pain in one or more trigeminal nerve branch distributions, facial hyperesthesia, and a visual analog scale (VAS) score >8 (Table 1). The pain attacks occurred despite the fact that patients continued their previous medications, which included nonsteroidal anti-inflammatory agents, opioids, carbamazepine, amitriptyline, duloxetine, citalopram, gabapentin, and pregabalin.

Table 1

Patient demographics and pain reduction (mean ± SD)
Patient (N) Age (years) Pain duration (years) Pain intensity (VAS score)

Pre Post
40 58 ± 15 4.5 ± 2.5 8.48 ± 0.64 4.53 ± 1.77*
Note:
*P < 0.0001.
Abbreviations: SD, standard deviation; VAS, visual analog scale.
The pain was either spontaneous or aggravated by a trigger factor. Sensory branches of the trigeminal nerve that were affected included V1 (23), V2 (26), and V3 (23). Pain distribution in two divisions of the nerve occurred in 16 cases, and in all three divisions in eight cases.
A total of 32 (80%) patients reported a significant reduction in pain 10 minutes after instillation of the drops as compared with pre-treatment pain score. Pre-treatment VAS score was 8.48 ± 0.64 as compared with 4.53 ± 1.77 post-amethocaine treatments (P < 0.0001) (Table 1). The pain reduction was noted regardless of the trigeminal distribution of the symptoms. All the patients also reported a reduction in the frequency of attacks for the following 24 hours (reported by pain diary). There were no adverse events reported in our patients.

Discussion

The first description of TGN was attributed to John Fothergill in 1773 (Fothergill’s disease). However, early descriptions can be found in Avicenna’s writings in the 11th century. The International Association of Pain defines TGN as a recurrent, usually unilateral, brief stabbing pain in the distribution of one or more branches of the fifth cranial nerve.
Amethocaine hydrochloride is a local anesthetic used for minor conjunctival and corneal surgery and is especially useful for the alleviation of pain resulting from removal of foreign bodies from the eye. Our study demonstrated the effectiveness of the application of amethocaine ophthalmic drops in offering a quick relief of the excruciating pain of TGN attacks.
TGN may be idiopathic (classic) or secondary to multiple sclerosis or benign compression of the Gasserian ganglion (the sensory ganglion of the trigeminal nerve). The sensory root of the trigeminal nerve expands into the trigeminal ganglion, which contains the cells of origin of the sensory fibers and from which the three divisions of the nerve arise; it supplies the face, teeth, mouth, and nasal cavity. In 1991, Zavon and Fichte discovered the possibility of using eye anesthetics (proparacaine) for TGN by accident. Zavon, who suffered from TGN, found that his pain vanished for over a year immediately after an eye anesthetic was applied (for corneal ulceration). They then tested the anesthetic on another TGN patient and achieved pain relief for over a month. We should note that repeated use of eye anesthetics may cause toxic keratopathy and may also slow down the healing of eye wounds. Hence, it was recommended that eye anesthetics must be used with great care and that patients should be advised not to rub the eye for at least an hour. However, in our patients, we have not noticed any adverse effects.
Although the pathophysiology and precise etiology of TGN are unknown, both central and peripheral mechanisms have been proposed. Current evidence suggests focal demyelination as a result of vascular compression of the central axons of the trigeminal nerve to be the underlying cause of TGN. It therefore seems that there are several possible theoretical explanations for the beneficial effect of amethocaine ophthalmic drops in relieving TGN pain attacks, eg, 1) peripheral (corneal) suppression of the trigger stimulus might influence the central perception of pain in all three divisions of the trigeminal nerve; 2) migration of local anesthetic from the cornea to the sphenopalatine ganglion; and 3) a central mechanism, with retrograde transport of local anesthetic to the Gasserian ganglion.
According to one suggested theory, the explanation is that peripheral injury or disease of the trigeminal nerve increases afferent firing in the nerve perhaps by ephaptic transmission between afferent unmyelinated axons and partially damaged myelinated axons, and the amethocaine may cease this aberrant activity.
Treatment objectives in the case of TGN are to eliminate pain, reduce the likelihood of recurrence, and prolong the time to recurrence by selectively destroying pain fibers without inducing excessive sensory loss, motor dysfunction, or other complications. Surgical treatment, including micro-vascular decompression; partial trigeminal rhizotomy; stereotactic radiosurgery; radiofrequency denervation; cryotherapy; or chemical denervation targeted to the root (rhizotomy), ganglion (gangliolysis), or branches of the trigeminal nerve, were suggested as potential means of treatment of TGN., However, these involve invasive procedures and substantial risk of complication as well as the need for extra expertise. Peripheral nerve blocks with high concentrations of local anesthetics were previously proved to be safe and useful in the treatment of TGN, leading to pain relief for weeks after an infraorbital block., The treatment of TGN in general is hampered by poor-quality methodological trials.
Our experience presents the potential beneficial effect of topical ophthalmic amethocaine in alleviating TGN pain attacks. Due to the simplicity of this treatment, we suggest that it be considered as a first-line option to use for severe pain attacks in TGN. As the pain in TGN tends to be paroxysmal, treatment with ophthalmic amethocaine may be recommended as a rapid and effective therapeutic measure, especially when the patient cannot attend the pain clinic or is at home. Nevertheless, a prudent approach justifies more extensive randomized placebo-controlled trials with this treatment in order to further explore ideal dosage and possible side effects.

Footnotes

Disclosure
No conflicts of interest were declared in relation to this paper.

References

1. Cole CD, Liu JK, Apfelbaum RI. Historical perspectives on the diagnosis and treatment of trigeminal neuralgia. Neurosurg Focus. 2005;15:18:E4. [PubMed]
2. Kitt CA, Gruber K, Davis M, Woolf CJ, Levine JD. Trigeminal neuralgia: opportunities for research and treatment. Pain. 2000;85:3–7. [PubMed]
3. Kondziolka D, Lemley T, Kestle JR, et al. The effect of single-application topical ophthalmic anesthesia in patients with trigeminal neuralgia. A randomized double-blind placebo-controlled trial. J Neurosurg. 1994;80:993–997. [PubMed]
4. Nurmikko TJ, Eldridge PR. Trigeminal neuralgia: pathophysiology, diagnosis and current treatment. Br J Anaesth. 2001;87:117–132. [PubMed]
5. Zavon MR, Fichte CM. Trigeminal neuralgia relieved by ophthalmic anesthetic. JAMA. 1991;265:2807.[PubMed]
6. Lopez BC, Hamlyn PJ, Zakrzewska JM. Systematic review of ablative neurosurgical techniques for the treatment of trigeminal neuralgia. Neurosurgery. 2004;54:973–982. [PubMed]
7. Mathews ES, Scrivani SJ. Percutaneous stereotactic radiofrequency thermal rhizotomy for the treatment of trigeminal neuralgia. Mt Sinai J Med. 2000;67:288–299. [PubMed]
8. Radwan IA, Saito S, Goto F. High-concentration tetracaine for the management of trigeminal neuralgia: quantitative assessment of sensory function after peripheral nerve block. Clin J Pain. 2001;17:323–326.[PubMed]
9. Goto F, Ishizaki K, Yoshikawa D, Obata H, Arii H, et al. The long lasting effects of peripheral nerve blocks for trigeminal neuralgia using high concentration of tetracaine dissolved in bupivacaine. Pain. 1999;79:101–103. [PubMed]




**
If a Patient is given a prescription for temporary & well-monitored Anesthetic Drops for Eye Pain (ADEP), the below paper indicates keeping the drops refrigerated, helps with the burning sensation of these drops. 

Dear Editor:

Tetracaine is commonly used for topical ophthalmic anesthesia. Unfortunately, it causes discomfort when instilled into the eye.1, 2 Although tetracaine typically is stored at room temperature, storage in cold refrigeration is also acceptable.3, 4 We wondered if tetracaine would cause less discomfort if it is kept cold. We conducted a crossover trial to compare the pain caused by ophthalmic tetracaine stored at room temperature with that caused by the drug refrigerated.
Healthy volunteers were solicited from the emergency department staff by the investigators and included physicians and physician assistants. Informed consent was obtained. The volunteers received 2 drops of tetracaine hydrochloride 0.5% ophthalmic solution (Alcon, Fort Worth, TX) at one temperature in one eye, then were asked to indicate the amount of pain they felt on a 100-mm visual analog scale (VAS).5 After a period of at least 24 hours, volunteers received 2 drops of tetracaine at the alternate temperature in the same eye and were asked to indicate the amount of pain on a second VAS. In our emergency department, room temperature is generally 66° to 68° F and our refrigerator is 39° to 40° F. One investigator instilled warm tetracaine first, one instilled cold tetracaine first, and the third alternated between the two.
The primary outcome of the study was the difference in mean pain scores, as measured by the VAS. Secondary outcomes included the difference in pain scores stratified by the order of tetracaine instillation, and the proportion of volunteers who reported significant differences in pain scores. A difference of 13 mm on the VAS was considered clinically significant.5 We estimated that 22 volunteers were needed. The study was approved by our institutional review board.
Twenty-two volunteers were enrolled; 11 received warm tetracaine first, and 11 received cold tetracaine first. The pain scores reported by the volunteers are shown in Figure 1 (available at http://aaojournal.org). Cold tetracaine was associated with a lower mean pain score (32±24 mm, VAS) compared with warm tetracaine (49±22 mm, VAS). The difference of 17 mm (95% confidence interval [CI], 3–30) was clinically and statistically significant. The intrapersonal differences in pain scores are indicated in Figure 2 (available at http://aaojournal.org). More volunteers favored cold tetracaine than warm tetracaine (59% vs. 9%, respectively; Δ = 50% [95% CI, 26%–74%]). There was little difference in mean pain scores as stratified by the order of tetracaine instillation (38±21 vs. 44±27 mm, VAS; Δ = 6 mm, VAS [95% CI, −9 to 21]).

 Opens large image

Figure 1

Pain scores reported by the volunteers. VAS = visual analog scale.

 Opens large image

Figure 2

Intrapersonal differences in pain scores. VAS = visual analog scale.
We found the pain of ophthalmic tetracaine instillation was lessened by keeping the medication in refrigeration. Although most volunteers reported less pain with cold tetracaine, it was not unanimous. Two volunteers reported significantly more discomfort with cold tetracaine. The highest pain score overall (83 mm, VAS) was accorded to cold tetracaine. Cold tetracaine may be less painful overall, but it may cause more pain in some individuals.
There are several limitations to our study. Assignment of the temperature of the first tetracaine instillation was not random. However, we did not find a difference in pain scores based on the order of the tetracaine instillation. Volunteers were not blinded to the objective of the study (i.e., they knew we were comparing cold and warm tetracaine). We were required by our institutional review board to include this information in our consent document. This may lead to subject bias in the reporting of pain scores. We enrolled healthy volunteers, not patients. Our findings may not be generalizable to the patient population. Finally, we did not assess the duration of discomfort or the efficacy of anesthesia in this study.
In summary, refrigeration of tetracaine diminishes the pain associated with topical ophthalmic anesthesia in most healthy volunteers.
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