By: Paul M. Karpecki, OD, FAAO Clinical Director – PECAA

A new over the counter a-adrenergic receptor (AR) agonist was recently approved by the FDA. It has the ability to reduce redness within 30-60 seconds and last for 8 hours, without rebound hyperemia or tachyphylaxis.

 

 

Delivering Extremely White Eyes

Before

Patients with red eyes feel a social stigma. Many patients have told me it kept them from going out with friends or family, and they were tired of being asked if they were crying, drinking, high or lacking sleep. One patient told me that she had over 35 interviews for a job and felt she was well qualified, but that her chronic red eyes prevented her from being hired (whether it was her confidence that was affected or the response from the interviewee by the red eyes). She was placed on Lumify and reported being offered a job after her very next interview. The social connotations of chronic red eyes are significant. Previous red eye reducers (like Visine or ClearEyes etc.) affect the a-1 or a-1 and 2 receptors leading to rebound hyperemia, and eventual loss of effect or tachyphy-laxis.  Patients then dose more frequently due to the reduced effect, which could lead to corneal toxicity from the preservatives.1

Welcome Low Dose Brimonidine Tartrate

After

Fortunately we’ve had almost 20 years of experience with high doses of brimonidine tartrate when managing glaucoma patients. Brimonidine tartrate is the active ingredient in Alphagan P for example. However the concentration of Alphagan P is 0.1% and generic forms are 0.2%. By reducing the concentration by 4 or 8 fold this drop was able to avoid IOP changes and increase the whitening effect.2   High doses are associated with hyperemia3 and allergic dermatitis4 or ocular allergy5 and low doses with whitening or blanching. LUMIFY is low dose (0.025%) brimonidine tartrate and is a highly selected a-2 adrenergic receptor agonist that was recently FDA approved for the relief of ocular redness due to minor eye irritations. It’s approved to age 5 and older, works within 30-60 seconds and lasts 6-8 hours.  As an aside, there is also an existing non-ocular formulation; 0.33% brimonidine gel is used for the treatment of persistent facial erythema secondary to rosacea.6

MOA

What differentiates this redness reliever is that it is a selective a-2 AR agonist, with minimal action at the a-1-AR site. Previous redness reducers affected AR-1 alone or AR-1 and AR-2 non-selectively.  Examples of selective a-1-AR agonists include tetrahydrozoline (trade name Visine) and mixed AR-1 and AR-2 agonist include naphazoline (Naphcon-A) and oxymetazoline (Clear eyes or Opcon-A). Long-term use of these previous redness reducers is limited due to rebound hyperemia, tachyphylaxis, pupil dilation, corneal toxicity and systemic side effects such as dizziness.7,8  Extended use ocular toxicity has been shown to be so severe as to mimic ocular cicatricial pemphigoid.9 The reason for the rebound hyperemia and tachyphylaxis of these previous redness reducers is due to the fact that a1-ARs are predominantly expressed in arteries.9 This results in constriction of arterial blood flow and oxygen delivery. The bodies response is to initiate down-regulation of a1-ARs and this results in lessening or reduced effect also known as tachyphylaxis. The vasoconstrictor-induced tissue becomes ischemic and the body’s response is vasodilation and hence the rebound redness.10

In contrast, LUMIFY or Brimonidine Tartrate 0.025%, is a very selective a2-AR agonist. This provides preferential venue constriction rather than affecting oxygen flow through the arteries and the resultant ischemia.11 By affecting the veins, which are significant given the concentration of vortex veins and capillary bed volume, constriction at this site results in an increased whitening effect without the risks of tachyphylaxis or rebound hyperemia.11  Furthermore since the drug lasts 8 hours it will typically be dosed once or twice a day further decreasing the risk of toxicity and medicamentosa.12 In FDA phase II and III trials neither tachyphylaxis or rebound hyperemia was noted.13 The ocular adverse events, such as burning on instillation, were minimal and mild as patients reported the drop as ‘very comfortable’ and there were no systemic safety signals detected in the efficacy studies and in the safety study of
pediatric, adult and geriatric subjects.12,13

In-Office or OTC

Doctors will have the option of selling this product in their office or identifying it for patients as an over-the-counter product. I have found in my own personal experience an overwhelming success in helping patients with conjunctival redness due to ocular irritation such as dry eyes, allergies, rosacea, MGD and especially for the chronic hyperemia patient.

Conclusion

In this era of information on demand for patients, we must continue to be educated and aware of new therapeutics such as low dose brimonidine (LUMIFY) which received FDA approval as an OTC redness reducer. Patients will quickly hear about the drop and seek advice and information from the eye care practitioner. Being a first of its kind redness reducer to not show the complication and systemic risks of previous vasoconstrictors, we have a tool at our disposable to provide our patients whiter eyes. This will increase their confidence in your management of their ocular condition and/or increase the patient’s own confidence in social circumstances.

Summary:
1. Spector SL, Raizman MB. Conjunctivitis medicamentosa.  J Allergy Clin Immunol. 1994;94:134-6
2. Pasquali TA, Aufderheide A, Brinton JP et al.  Dilute brimonidine to improve patient comfort and subconjunctival hemorrhage after LASIK.  J Refract Surg. 2013 Jul;29(7):469-75
3. Melamed S, David R.  Ongoing clinical assessment of the safety profile and efficacy of brimoni-dine compared with timolol: year-three results. Brimonidine Study Group II.  Clin Ther 2000;22:103-11
4. Cookson H, McFadden J, White J et al. Allergic contact dermatitis caused by Mirvaso®, brimonidine tartrate gel 0.33%, a new topical treatment for rosaceal erythema. Contact Dermati-tis. 2015 Dec;73(6):366-7
5. Lusthaus JA Goldberg I.  Brimonidine and brinzolamide for treating glaucoma and ocular hyper-tension; a safety evaluation.  Expert Opin Drug Saf. 2017 Sep;16(9):1071-1078.
6. Fowler J Jr, Jackson M, Moore A  et al. Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehicle-controlled pivotal studies.  J Drugs Dermatol. 2013;12:650-6
7. Vaidyanathan S, Williamson P, Clearie K et al.  Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion.  Am J Respir Crti Care Med. 2010;182:19-24
8. Soparkar CN, Wilhelmus KR, Koch DD et al.  Acute and chronic conjunctivitis due to over-the-counter ophthalmic decongestants.  Arch Ophthalmol. 1997;115:34-8
9. Tappeiner C, Sarra GM, Abegg M.  Abuse of vasoconstrictive eyedrops mimicking an ocular pemphigoid.  Eur J Ophthalmol. 2009;19:129-132
10. Corboz MR, Rivelli MA, Mingo GG et al.  Mechanism of decongestant activity of alpha 2-adrenoceptor agonists.  Pulm Pharmacol Ther. 2008;21:449-54
11. Fratelli M, De Blasi A.  Agonist-induced alpha 1-adrenergic receptor changes. Evidence for receptor sequestration FEBS Lett.1987;212(1):149-53.
12.  McLaurin E, Cavet ME, Gomes PJ, et al.  Brimonidine Ophthalmic Solution 0.025% for Reduction of Ocular Redness: A Randomized Clinical Trial.  Optom Vis Sci. 2018 Mar;95(3):264-271
13. Torkildsen GL1, Sanfilippo CM2, DeCory HH et al.  Evaluation of Efficacy and Safety of Brimonidine Tartrate Ophthalmic Solution, 0.025% for Treatment of Ocular Redness.  Curr Eye Res. 2018 Jan;43(1):43-51

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