The shifting landscape of conjunctival hyperemia

A host of environmental factors can contribute to conjunctival hyperemia, characterised by redness, watering and irritation in the eyes. The breadth of topical treatments available is congruent in its scope, but many patients are still searching for the therapeutic that will best suit their unique needs—and failing to find it. José Salgado-Borges, MD, PhD, FEBO, is the clinical director of Clinsborges, in Porto, Portugal, an ambassador of the Tear Film & Ocular Surface Society, and a member of the European Dry Eye Society. Speaking with Ophthalmology Times Europe following the European Dry Eye Society Congress, held this year in Madrid, Spain, Prof Salgado-Borges said changes in the European market are adding new challenges for patients and practitioners.

Patients with conjunctival hyperemia, in particular, are increasingly aware of the treatment options available to them and the ones that remain inaccessible. “Until recently in Portugal and in Europe in general, we only had products available that acted on alpha-1 adrenergic receptors, located in the conjunctival arterioles,” Prof Salgado-Borges said. “However, these drugs, in addition to having a selective alpha-1 effect, which acts preferentially on the conjunctival arterioles producing their constriction, showed an association with tachyphylaxis and rebound effect after their discontinuation.”

For patients suffering from frequent red eyes, Prof Salgado-Borges said, this created a vicious cycle. Patients who used eye drops, and especially those who were long-term users, would experience diminishing returns and intense rebound symptoms, whether they discontinued use by choice or simply due to accessibility or availability issues.

Figure 1 & 2. Clinical photos demonstrate conjunctival hyperemia (1a, 2a) and its resolution (1b, 2b) following an application of brimonidine tartrate 0.025%.

(Image courtesy of Jose Salgado-Borges, MD, PhD, FEBO)

What’s more, he added, is that the phenylephrine hydrochloride eye drop Visadron, which Prof Salgado-Borges called “the most popular vasoconstrictor in Portugal,” was withdrawn from the market, leaving many of his patients unsure of what methods to explore for relief.

Throughout Europe, the United Kingdom and the United States, several ocular products including drops and eye gels have seen recalls and safety notices over the past year, whether due to contamination, potency issues or quality concerns from counterfeit products. Because dry eye disease and other corneal conditions have a significant impact on quality of life, there is a constant patient demand for solutions for conjunctival hyperemia, Prof Salgado-Borges said.

In late 2023, brimonidine tartrate 0.025% (Lumobry, Bausch + Lomb Ireland Limited) received regulatory approval in Europe. The drops, which have been available in the United States under the brand name Lumify for several years, are available in Europe with a mandatory medical prescription. Prof Salgado-Borges explained that he has recommended the drops, which act as an alpha-2 agonist, to certain patients suffering from conjunctival hyperemia. The function of the drug is different from alpha-1 agonists on the market, in that the alpha-2 agonist is selective; brimonidine tartrate 0.025% acts preferentially on the conjunctival venules (Figures 1 and 2).

Clinical trial findings have not demonstrated an association with tachyphylaxis or significant rebound redness from the drops. In one single-centre, double-masked, phase 3 clinical trial, 6o patients were randomly assigned 2:1 to bilateral treatment, with one drop of brimonidine tartrate ophthalmic solution 0.025% or vehicle.¹ Among patients in the brimonidine tartrate group, four experienced mild stinging; this resolved spontaneously and there were no other adverse effects associated with treatment. Further efficacy and safety analyses² demonstrated no tachyphylaxis among patients and limited instances of rebound redness.

The availability of brimonidine tartrate 0.025% comes at a fairly unusual moment for the greater European population of patients with conjunctival hyperemia, Prof Salgado-Borges said. The drug's function is different from that of prior entries to the market, which expands the treatment options for patients who were not candidates for alpha-1 agonists or had developed tachyphylaxis following long-term treatment. Before prescribing brimonidine tartrate 0.025% to patients, Prof Salgado-Borges said, there are specific limitations to which clinicians should give consideration, especially those prescribing in Europe.

“[Brimonidine tartrate 0.025%] is indicated mainly for the treatment of isolated conjunctival hyperemia due to mild to moderate eye irritation in adults.However, in my opinion it shall be used by a medical doctor in complement to the treatment of the aetiology cause of the red eye,” Prof Salgado-Borges said. Because brimonidine tartrate 0.025% is effective for a several pathologies of conjunctival hyperemia, prescribing clinicians should be prepared to carefully monitor and record other ocular and non-ocular symptoms.

Common aetiologies of conjunctival hyperemia include allergies (hay fever), blepharitis, conjunctivitis and dry eye disease, but redness or irritation can be related to non-ocular pathologies. Prof Salgado-Borges warned against ignoring other symptoms if hyperemia were to resolve; further, he emphasised the importance of communicating closely with a patient’s other clinicians when prescribing brimonidine tartrate 0.025%.

For instance, if the patient also sees an immunologist, dermatologist or rheumatologist, those physicians as well as the patient’s general practitioner should be kept in communication. Prof Salgado-Borges named “red flags” that present a need for a comprehensive ocular exam, even if redness and irritation are not present, which include eye pain, photophobia and any reduced visual activity.³

Looking ahead, the main concern for patients with conjunctival hyperemia in Europe will be accessing and affording medications, Prof Salgado-Borges said. This will be of particular concern as new therapeutics enter the market. “Accessing a medical prescription is an inconvenience, and sometimes a significant limitation, for some patients,” he said. “The price is also a concern among patients, at least in Portugal.” Brimonidine tartrate, for one, is available via prescription only, and Prof Salgado-Borges said the price is around 50% higher than other ocular drops on the market. For clinicians, education is key, he added. An ophthalmologist’s role should be to provide data on the eye health landscape to help patients make the decisions that best fit their lifestyles.

References

1. McLaurin E, Cavet ME, Gomes PJ,
Ciolino JB. Brimonidine ophthalmic solution 0.025% for reduction of ocular redness: A randomized clinical trial. Optom Vis Sci. 2018;95(3):264-271. doi:10.1097/OPX.0000000000001182

2. Ackerman SL, Torkildsen GL, McLaurin E, Vittitow JL. Low-dose brimonidine for relief of ocular redness: integrated analysis of four clinical trials. Clin Exp Optom. 2019;102(2):131-139. doi:10.1111/cxo.12846

3. Salgado-Borges J. Red eyes and red flags: The importance of eye examination in diagnosis and guidance. OftalPro. Published February 2024. Accessed July 2024.

José Salgado-Borges, MD, PhD, FEBO | E: salgadoborges@hotmail.com

Prof Salgado-Borges is clinical director of Clinsborges, in Porto, Portugal, and the Tear Film & Ocular Surface
Society Ambassador from Portugal. His website is www.salgadoborges.com.
Salgado-Borges has no financial disclosures related to this article.