New therapeutics, technologies help clinicians fight dry eye

Today's options address surface inflammation, tear production and meibomian gland obstruction.

Optometrists have the opportunity to be “heroes” by using knowledge and technology to combat surface inflammation, loss of homeostasis, decreased tear production and meibomian gland disease.

Ocular surface disease (OSD) therapy choices are increasing, as is awareness of OSD by eye care providers and the general public. More than ever, there is a wider need for improved therapeutic options.

With the continued advancement in the understanding of complexity and nuance within the lacrimal functional unit and OSD, we can now focus therapies and treatments more to the pathophysiology rather than just supplementing the tear film with various lubricants. The complex cycles that underlie OSD can be more effectively targeted with medication, neurostimulation, thermal pulsation and microblepharoexfoliation.

Nicole Harris

It is critical to stay up-to-date on the ever-evolving technologies and medications to best care for these patients.

Surface inflammation

Ocular inflammation is a challenge for the OSD specialist and for dry eye patients. It is critical to “tame the flame” and get ahead of the inflammation. Inadequate inflammation management is a common reason for failure with a provider’s therapy, especially with severe OSD. There has been great improvement and expansion with regard to anti-inflammatory therapies and pharmaceuticals, including stronger steroids such as Durezol (difluprednate, Novartis) and agents with new methods of action such as Xiidra (lifitegrast ophthalmic solution 5%, Shire), which targets ICAM-1.

Kala Pharmaceuticals is developing a mucous penetrating particle that increases penetration of loteprednol etabonate into the ocular tissue. By attaching loteprednol to this nanoparticle, we should see improved penetration and increased tissue concentrations. Phase 3 trials showed improvement in both signs (conjunctival hyperemia) and symptoms (ocular discomfort) at 15 days. Steroid therapy has been a common therapeutic choice, and this potentially safer and smarter drug may be a great step forward for ophthalmic drug delivery.

Cequa (cyclosporine ophthalmic solution 0.09%, Sun Pharmaceutical) was FDA approved in August 2018 and is indicated to increase tear production in patients with dry eye disease. It will provide the highest FDA-approved concentration of cyclosporine A and is the first and only approved CsA product that incorporates a nanomicellar technology to improve its penetration and performance.

Ikervis is a cyclosporine drop (0.1%) from Santen currently approved in Europe for treatment of severe keratitis in adult patients with dry eye disease. By delivering preservative-free cyclosporine in a cationic emulsion, it may reduce the burning sensation associated with current cyclosporine therapies. In a 1-year study, the medication, dosed once daily, was shown to reduce signs/symptoms of inflammation and was well tolerated by patients with severe dry eye. (Baudouin et al.).

Verkazia (Santen) was also recently approved in Europe for the treatment of vernal keratoconjunctivitis (VKC). Much like dry eye, VKC is characterized by chronic inflammation of the conjunctiva and cornea. The current treatment of VKC typically involves a topical ophthalmic antihistamine/mast cell stabilizer and a topical steroid. This new medication contains 0.1% cyclosporine (the same formulation as Ikervis), but is dosed four times daily vs. once daily. In trials, patients reported statistically significant improvement in photophobia, tearing, itching and quality of life throughout a 4-month period (Committee for Medicinal Products for Human Use).

Jacob Lang

Klarity-C (Imprimis) combines cyclosporine 0.1% and chondroitin sulfate to treat inflammation and lubricate the ocular surface at the same time. Chondroitin sulfate acts to protect and rehabilitate the ocular surface as a cell membrane stabilizer and as a lubricant. It has been studied as a lubricant in dry eye patients and has been shown to prolong tear film break-up time as well as improve symptoms (Moon et al.). Chondroitin sulfate has a long history of use in ophthalmic products including the very popular DisCoVisc (1.65% sodium hyaluronate, 4% chondroitin sulfate, Alcon). This, combined with the anti-inflammatory powers of cyclosporine, make this compounded emulsion an excellent option for OSD patients.

The idea of using stronger and smarter formulations of cyclosporine to more aggressively target ocular surface inflammation may have further implications for those suffering from severe keratoconjunctivitis sicca and other ocular surface conditions. These products should give OSD doctors better options when tailoring our anti-inflammatory therapies to our patients.

Tear production

TrueTear (Allergan) is an intranasal device that temporarily increases tear production using neurosensory stimulation. Upon stimulation, the nasolacrimal arc is targeted by activating the trigeminal nerve fibers located in the nasal cavity, specifically the anterior ethmoid nerve. By directly stimulating this pathway, this device can effectively serve as a manual “on” switch for natural tear production. This has benefits over artificial tears because the stimulation helps produce more natural tears that include proteins, lipids and mucin. This drug-free, drop-free therapeutic option adds an instant gratification option for OSD that has been missing in our arsenal for too long.

Oyster Point Pharma is developing new therapeutics currently in phase 2 trials that also target the trigeminal parasympathetic pathway. These innovative compounds are selective nicotinic acetylcholine receptor agonists. Again, these receptors are activating the trigeminal nerve, which can be accessed within the nasal cavity. Stimulating these receptors and the parasympathetic pathway activates the promotion of the lacrimal functional unit. The company is developing two drug candidates – both delivered via a nasal spray – to determine which compound may offer a better safety and efficacy profile and increase the likelihood of regulatory and commercial success.

Lid therapy

The iLux (Alcon) is a new handheld instrument used to help treat MGD. The device works by applying heat and compression onto the lids and meibomian glands in hopes of removing obstruction and increasing meibomian gland flow. During the treatment the provider can visualize the process and the gland orifices directly through a built-in magnifying lens. The heat is produced by LED light to help melt blockages within the glands. According to the manufacturer, there is a temperature sensor in the tip, and the therapeutic heat levels are between 104 degrees F and 108 degrees F. So far, studies have shown non-inferiority to Lipiflow (TearScience) at 1 month. This cost-effective device may have a place in the care for MGD patients and may integrate well into other treatment options addressing obstruction of the meibomian glands, including Lipiflow.

NuLids (NuSight Medical) was released at the last American Optometric Association meeting. It is a doctor-prescribed device for home treatment of dry eye. It looks similar to an electric toothbrush for your eyelids and works by cleaning the lids and lashes while gently stimulating the meibomian glands. In clinical studies, the company reported that nearly 95% of patients reported improvement in symptoms after a 3-day trial of daily use. The company also reported an 81% improvement in meibomian glands yielding liquid secretions and 65% improvement in tear break-up time.

The TearCare System (Sight Science) is an in-office device that targets the meibomian glands by using localized heat therapy. TearCare differs from current in-office treatments by allowing the patient’s eyes to remain open and blinking throughout the test. Localized, external heat in conjunction with natural blink activity helps increase meibum expression. The eyelid devices are single use, flexible bands that stick to the patient’s upper and lower lids, making the treatment comfortable for the patient and easy to perform for the eye care provider and staff.

In the company’s pilot trial (Badawi), a single 12-minute TearCare procedure was compared to the control group that performed 5 minutes of warm compresses daily for 4 weeks. At the 1-month follow-up, TearCare patients were found to have an improvement in tear break-up time of 11.7 ± 2.6 seconds compared to an average worsening of -0.3 ± 1.1 seconds in the control group. Results of the procedure are said to last at least 6 months. A larger, multicenter, randomized trial is currently ongoing.

Editor’s note: This article has been updated to indicate that Oyster Point is developing two drug candidates in a nasal spray with the intent of determining which offers a better safety and efficacy profile and increases the likelihood of regulatory and commercial success.

Disclosures: Harris reports no relevant financial disclosures. Lang reports he is a speaker for Allergan and Takeda and an advisory board member/consultant for Takeda.

Optometrists have the opportunity to be “heroes” by using knowledge and technology to combat surface inflammation, loss of homeostasis, decreased tear production and meibomian gland disease.

Ocular surface disease (OSD) therapy choices are increasing, as is awareness of OSD by eye care providers and the general public. More than ever, there is a wider need for improved therapeutic options.

With the continued advancement in the understanding of complexity and nuance within the lacrimal functional unit and OSD, we can now focus therapies and treatments more to the pathophysiology rather than just supplementing the tear film with various lubricants. The complex cycles that underlie OSD can be more effectively targeted with medication, neurostimulation, thermal pulsation and microblepharoexfoliation.

Nicole Harris

It is critical to stay up-to-date on the ever-evolving technologies and medications to best care for these patients.

Surface inflammation

Ocular inflammation is a challenge for the OSD specialist and for dry eye patients. It is critical to “tame the flame” and get ahead of the inflammation. Inadequate inflammation management is a common reason for failure with a provider’s therapy, especially with severe OSD. There has been great improvement and expansion with regard to anti-inflammatory therapies and pharmaceuticals, including stronger steroids such as Durezol (difluprednate, Novartis) and agents with new methods of action such as Xiidra (lifitegrast ophthalmic solution 5%, Shire), which targets ICAM-1.

Kala Pharmaceuticals is developing a mucous penetrating particle that increases penetration of loteprednol etabonate into the ocular tissue. By attaching loteprednol to this nanoparticle, we should see improved penetration and increased tissue concentrations. Phase 3 trials showed improvement in both signs (conjunctival hyperemia) and symptoms (ocular discomfort) at 15 days. Steroid therapy has been a common therapeutic choice, and this potentially safer and smarter drug may be a great step forward for ophthalmic drug delivery.

Cequa (cyclosporine ophthalmic solution 0.09%, Sun Pharmaceutical) was FDA approved in August 2018 and is indicated to increase tear production in patients with dry eye disease. It will provide the highest FDA-approved concentration of cyclosporine A and is the first and only approved CsA product that incorporates a nanomicellar technology to improve its penetration and performance.

Ikervis is a cyclosporine drop (0.1%) from Santen currently approved in Europe for treatment of severe keratitis in adult patients with dry eye disease. By delivering preservative-free cyclosporine in a cationic emulsion, it may reduce the burning sensation associated with current cyclosporine therapies. In a 1-year study, the medication, dosed once daily, was shown to reduce signs/symptoms of inflammation and was well tolerated by patients with severe dry eye. (Baudouin et al.).

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Verkazia (Santen) was also recently approved in Europe for the treatment of vernal keratoconjunctivitis (VKC). Much like dry eye, VKC is characterized by chronic inflammation of the conjunctiva and cornea. The current treatment of VKC typically involves a topical ophthalmic antihistamine/mast cell stabilizer and a topical steroid. This new medication contains 0.1% cyclosporine (the same formulation as Ikervis), but is dosed four times daily vs. once daily. In trials, patients reported statistically significant improvement in photophobia, tearing, itching and quality of life throughout a 4-month period (Committee for Medicinal Products for Human Use).

Jacob Lang

Klarity-C (Imprimis) combines cyclosporine 0.1% and chondroitin sulfate to treat inflammation and lubricate the ocular surface at the same time. Chondroitin sulfate acts to protect and rehabilitate the ocular surface as a cell membrane stabilizer and as a lubricant. It has been studied as a lubricant in dry eye patients and has been shown to prolong tear film break-up time as well as improve symptoms (Moon et al.). Chondroitin sulfate has a long history of use in ophthalmic products including the very popular DisCoVisc (1.65% sodium hyaluronate, 4% chondroitin sulfate, Alcon). This, combined with the anti-inflammatory powers of cyclosporine, make this compounded emulsion an excellent option for OSD patients.

The idea of using stronger and smarter formulations of cyclosporine to more aggressively target ocular surface inflammation may have further implications for those suffering from severe keratoconjunctivitis sicca and other ocular surface conditions. These products should give OSD doctors better options when tailoring our anti-inflammatory therapies to our patients.

Tear production

TrueTear (Allergan) is an intranasal device that temporarily increases tear production using neurosensory stimulation. Upon stimulation, the nasolacrimal arc is targeted by activating the trigeminal nerve fibers located in the nasal cavity, specifically the anterior ethmoid nerve. By directly stimulating this pathway, this device can effectively serve as a manual “on” switch for natural tear production. This has benefits over artificial tears because the stimulation helps produce more natural tears that include proteins, lipids and mucin. This drug-free, drop-free therapeutic option adds an instant gratification option for OSD that has been missing in our arsenal for too long.

Oyster Point Pharma is developing new therapeutics currently in phase 2 trials that also target the trigeminal parasympathetic pathway. These innovative compounds are selective nicotinic acetylcholine receptor agonists. Again, these receptors are activating the trigeminal nerve, which can be accessed within the nasal cavity. Stimulating these receptors and the parasympathetic pathway activates the promotion of the lacrimal functional unit. The company is developing two drug candidates – both delivered via a nasal spray – to determine which compound may offer a better safety and efficacy profile and increase the likelihood of regulatory and commercial success.

PAGE BREAK

Lid therapy

The iLux (Alcon) is a new handheld instrument used to help treat MGD. The device works by applying heat and compression onto the lids and meibomian glands in hopes of removing obstruction and increasing meibomian gland flow. During the treatment the provider can visualize the process and the gland orifices directly through a built-in magnifying lens. The heat is produced by LED light to help melt blockages within the glands. According to the manufacturer, there is a temperature sensor in the tip, and the therapeutic heat levels are between 104 degrees F and 108 degrees F. So far, studies have shown non-inferiority to Lipiflow (TearScience) at 1 month. This cost-effective device may have a place in the care for MGD patients and may integrate well into other treatment options addressing obstruction of the meibomian glands, including Lipiflow.

NuLids (NuSight Medical) was released at the last American Optometric Association meeting. It is a doctor-prescribed device for home treatment of dry eye. It looks similar to an electric toothbrush for your eyelids and works by cleaning the lids and lashes while gently stimulating the meibomian glands. In clinical studies, the company reported that nearly 95% of patients reported improvement in symptoms after a 3-day trial of daily use. The company also reported an 81% improvement in meibomian glands yielding liquid secretions and 65% improvement in tear break-up time.

The TearCare System (Sight Science) is an in-office device that targets the meibomian glands by using localized heat therapy. TearCare differs from current in-office treatments by allowing the patient’s eyes to remain open and blinking throughout the test. Localized, external heat in conjunction with natural blink activity helps increase meibum expression. The eyelid devices are single use, flexible bands that stick to the patient’s upper and lower lids, making the treatment comfortable for the patient and easy to perform for the eye care provider and staff.

In the company’s pilot trial (Badawi), a single 12-minute TearCare procedure was compared to the control group that performed 5 minutes of warm compresses daily for 4 weeks. At the 1-month follow-up, TearCare patients were found to have an improvement in tear break-up time of 11.7 ± 2.6 seconds compared to an average worsening of -0.3 ± 1.1 seconds in the control group. Results of the procedure are said to last at least 6 months. A larger, multicenter, randomized trial is currently ongoing.

Editor’s note: This article has been updated to indicate that Oyster Point is developing two drug candidates in a nasal spray with the intent of determining which offers a better safety and efficacy profile and increases the likelihood of regulatory and commercial success.

Disclosures: Harris reports no relevant financial disclosures. Lang reports he is a speaker for Allergan and Takeda and an advisory board member/consultant for Takeda.