Cheryl Guttman is a medical writer based in Deerfield, Ill.

Cheryl Guttman Krader, BS, Pharm

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The FDA’s approval of varenicline nasal spray 0.03 mg (Tyrvaya, Oyster Point Pharma) for the treatment of the signs and symptoms of dry eye disease (DED) brings to the management of this common condition a new therapeutic modality that is novel for both its mechanism of action and mode of administration.

The new medication is recommended to be used twice daily, sprayed once into each nostril.

As a highly selective nicotinic acetylcholine receptor agonist, varenicline is designed to bind to cholinergic receptors in the nasal mucosa and activate the trigeminal parasympathetic pathway, resulting in increased production of basal tear film.

Oyster Point Pharma reports FDA approval of TYRVAYA nasal spray for DED treatment

Results from preclinical and clinical studies show that varenicline nasal spray induces goblet cell degranulation and stimulates meibomian gland and lacrimal gland secretion. 

Unlike most prescription topical treatments for DED, varenicline nasal spray 0.03 mg aims to reestablish tear film stability/homeostasis, according to Marian Macsai, MD, chief medical officer of Oyster Point Pharma in Princeton, New Jersey.

“Tyrvaya brings innovation to patients...with DED,” Macsai explained. “It is the first and only nasal spray approved for the treatment of the signs and symptoms of DED, and it is the first and only pharmacological approach to cholinergic neuro-activation via the trigeminal parasympathetic pathway.”

Macsai pointed out that as a new approach to drug delivery for DED, nasal spray administration offers the benefit of avoiding instillation of medication onto an already irritated ocular surface.

“Acting through a novel mechanism of action, Tyrvaya provides a clinically meaningful increase in basal tear film production to provide relief for [patients with DED] as early as 4 weeks after treatment initiation,” Macsai said. “The clinical trial data also showed benefit was achieved in a broad patient population of adults with mild, moderate, or severe DED.”

Researchers pioneer technology that leads successful clinical trial to treat dry eye disease

Jeffrey Nau, PhD, MMS, president and CEO of Oyster Point Pharma, said the approval of Tyrvaya marks a step forward for patients with DED and eye care professionals by providing a new treatment option for the signs and symptoms of DED with a unique route of administration by leveraging nerves that can be accessed in the nose.

“In any therapeutic area, it is always an exciting moment when you follow the science and develop a truly innovative solution for patients that addresses an important medical need. This approval marks that moment for the eye care community as we bring forward a whole new way of treating dry eye disease through a convenient nasal spray that activates the body’s natural tear film production,” he said.

Nau added that the company currently is looking forward to making the treatment option available to eye care professionals and their patients.



The FDA approval of varenicline nasal spray is based on findings from 3 randomized, masked, vehicle-controlled clinical trials—MYSTIC (NCT03873246), ONSET-1 (NCT03636061), and ONSET-2 (NCT04036292)—that included more than 1000 patients with mild, moderate, or severe DED. 

The phase 2 MYSTIC study was a single-site clinical trial study with a 12-week duration. 

Expert insights: Flares of dry eye disease

ONSET-1 was a phase 2b, vehicle-controlled dose-ranging study, and ONSET-2 was a phase 3 pivotal trial comparing 2 concentrations of the varenicline nasal spray against a placebo.

To be eligible for enrollment in these studies, patients had to have a baseline anesthetized Schirmer score of 10 mm/5 min or less with a cotton swab nasal stimulation and corneal fluorescein staining scores of 2 to 14. 

The patients also could have mild, moderate, or severe symptom severity based on having an eye dryness score (EDS) of 0 to 100. Patients in the ONSET studies had to have an Ocular Surface Disease Index score of 23 or higher.

Participants in the premarketing clinical trials were predominantly female (74%) and older adults (mean age 61 years). At baseline, they had a mean anesthetized Schirmer score of 5.1 mm/5 min and mean EDS of 59.3.

MYSTIC had a real-world design as it had no placebo run-in period and patients were allowed to use artificial tears during the study period. 

Data on change in Schirmer score in the MYSTIC trial showed improvement as early as day 7, which was maintained through the 12-week study without evidence of tachyphylaxis.

The primary end point in both ONSET-1 and ONSET-2 was the proportion of eyes achieving a 10 mm or greater increase in Schirmer score from baseline to week 4.

It was met in both trials with statistical superiority of varenicline 0.03 mg compared with placebo (

In ONSET-1, 52% of patients treated with varenicline 0.03 mg met the primary end point compared with 14% of vehicle-treated controls. 

In ONSET-2, 47% of patients treated with varenicline 0.03 mg and 28% of placebo-treated patients achieved a 10 mm or greater increase in Schirmer score from baseline at week 4.

Mean change in Schirmer score from baseline to week 4 also was analyzed and shown to be significantly greater in the varenicline 0.03 mg groups compared with placebo in both ONSET-1 (11.7 vs 3.2 mm) and ONSET-2 (11.3 vs 6.3 mm) (

Patients treated with varenicline 0.03 mg also benefited with greater improvements in EDS compared with controls. 

Changes in EDS were assessed in the controlled adverse environment in ONSET-1 and in the clinic environment in both ONSET trials. 

In addition, a subgroup analysis stratifying patients into those with mild-to-moderate or severe DED based on their EDS showed that the benefit was achieved regardless of disease severity and that the magnitude of improvement was greater in the severe group.

Treatment with varenicline nasal spray 0.03 mg for a period of up to 105 days was safe and well tolerated. 

Sneezing after administration was the most common adverse effect associated with its use, being reported by 82% of patients. With very few exceptions, patients categorized the sneezing as mild. In patients who reported sneezing, 98% rated it as mild. 

No patients treated with Tyrvaya discontinued their participation in the clinical study due to sneezing. 

Other adverse effects in the varenicline treatment groups included cough, throat irritation, and instillation site (nasal) irritation, and they occurred at rates of 5% to 16%.

Articles

Product stimulates basal tear production, restores tear film homeostasis, and relieves symptoms.

Varenicline nasal spray approved as a treatment for dry eye disease

Cynthia Matossian, MD, discussed DED flares, and their detection and management, in an interview for 

Dry eye disease (DED) affects millions of people, and estimated that about 80% of patients with DED experience flares, which are sudden onset, episodic, intermittent exacerbations of symptoms due to increased inflammation.

Timely recognition of DED flares and successful intervention are important because a DED flare can negatively affect health-related quality of life and lead to ocular surface damage, according to Cynthia Matossian, MD.

“A topical corticosteroid can provide rapid and effective treatment for a DED flare,” she said. “Fortunately, there is now a corticosteroid that has been approved by the FDA for the short-term treatment of the signs and symptoms of DED — loteprednol etabonate ophthalmic suspension 0.25% (Eysuvis, Kala Pharmaceuticals)—that is a safe and effective option for treating flares of DED.”

Matossian is the medical director at Matossian Eye Associates, an affiliate of Prism Vision Group, and a multispecialty ophthalmology practice with offices in Doylestown, Pennsylvania; Hopewell, New Jersey; and Hamilton, New Jersey. 

She discussed DED flares, and their detection and management, in an interview for 


Matossian said that a flare of DED occurs when there is disruption of tear film homeostasis. A flare may be what first prompts a patient to seek care for increased ocular discomfort. 

However, flares can also develop in patients with an established diagnosis of DED where their ocular surface inflammation spirals out of control despite prescribed maintenance therapy.

“Dry eye disease has a core inflammatory component, and just like other chronic inflammatory diseases, such as arthritis or asthma, it can be associated with episodic flares,” Matossian said.

There are many situations that can trigger a DED flare. Noncompliance of prescribed medications or at-home dry eye treatments may lead to loss of tear film homeostasis and increased inflammation. 

Flares can also develop after spending prolonged time with visually intensive tasks that promote increased tear film evaporation. This situation describes individuals who have clocked hours of uninterrupted screen time working at their computer, playing video games, or watching television.

Air exhaled onto the ocular surface from the top of a loose-fitting mask worn to cover the nose and mouth during the 

pandemic can also promote tear film evaporation and trigger a DED flare. 

Extended duration of contact lens wear is another trigger, as is exposure to low levels of air humidity, which can be experienced during long plane trips or when spending time in a dry climate. 

During spring and fall, inflammation associated with seasonal allergic conjunctivitis is also a prominent cause of DED flares.


Symptoms of DED flares can present in a variety of ways. Patients may complain of ocular burning, blurred or fluctuating vision, tearing, or they may report their eyes “hurt,” feel tired, or that they just want to close their eyes. 

Patients with contact lenses may describe increased discomfort with their lenses, and patients with allergies may attribute their problem to their allergic disease.

“Depending on their history, patients experiencing a DED flare who have not yet been diagnosed with DED might incorrectly attribute the entirety of their flare symptoms to allergies, think they need a contact lens refitting, or require a stronger prescription for their glasses,” Matossian said. “Even patients with an established diagnosis of DED may not recognize their worsening ocular symptoms to be a classic flare. This is especially true among patients who adhere to their dry eye treatment.”

Matossian noted that eye care providers need to empower technicians to ask appropriate questions in to solicit descriptions from patients to facilitate the diagnosis of a DED flare.

“We also need to educate patients to help them better understand the concept of a DED flare since intermittent exacerbations are likely to recur,” she said.

VIDEO: Seeking out medical care for dry eye flares


According to Matossian, DED flares can impair quality of life in several ways. The symptom-related discomfort and effect of the flare on vision can lead to reduced work productivity. 

Patients using contact lenses for refractive correction may need to stop wearing their lenses, which can impact their self-image and make it difficult to participate in certain recreational activities. 

Symptom bother can also affect mood and therefore interpersonal relations.

Controlling DED and normalizing the ocular surface is also critical for accurate measurements and planning of refractive and cataract surgery. 


Because inflammation is an etiologic factor that perpetuates the pathogenic pathway leading to the progression of dry dye, DED flares can also contribute to cumulative ocular surface damage.

VIDEO: Treatment options for dry eye flares

“The treatment goal is to break the inflammatory cycle; the best way to do that is by diagnosing patients early and by initiating appropriate therapy,” Matossian explained. “We need to keep in mind that patients with a DED flare are suffering and want quick relief when we design their individualized therapeutic plans.”

Among the treatments that are used to control ocular surface inflammation related to DED, topical corticosteroids represent the fastest-acting option. 

There are many topical ophthalmic corticosteroid products, but only loteprednol etabonate ophthalmic suspension 0.25% has an FDA-approved indication for the short-term (up to 2 weeks) treatment of the signs and symptoms of DED, according to Matossian.

“The clinical study investigating loteprednol etabonate ophthalmic suspension 0.25% for short-term treatment of DED showed that it was associated with a rapid onset of benefit and that it was safe,” she said. “Loteprednol etabonate is an ester steroid with an excellent safety profile demonstrated in many clinical studies.”

In addition to the topical corticosteroid, patients with DED may need to be started on immunomodulatory therapy to maintain long-term disease control.

“Topical immunomodulatory therapies [often] take weeks to months to effectively reduce symptoms of DED,” Matossian concluded. “Loteprednol etabonate 0.25% can jump-start the process and make patients feel better quickly. Combining loteprednol with another immunomodulator provides a one-two punch with the steroid bringing immediate relief for the desperate, distraught patient and the immunomodulator helping to control inflammation that can lead to DED progression over the longer term.”


Matossian is a consultant to Kala Pharmaceuticals.

Timely diagnosis and successful intervention are key to successful treatment.

Expert insights:  Flares of dry eye disease

 is a recently formed nonprofit organization created to support ophthalmic education internationally—particularly in low-resource and underserved countries—to improve global eye care, advance scientific ophthalmology, and ultimately preserve and restore vision for people of all nations.

 International Council of Ophthalmology Foundation

 (ICOF), the Ophthalmology Foundation’s programs for advancing and facilitating ophthalmologists’ learning and skills development are moving in a new direction designed to align with contemporary needs and approaches to education, said David E. I. Pyott, MDhc, president of the Ophthalmology Foundation’s Board of Directors.

During the more than 6 months since it was formed, the Ophthalmology Foundation has had many accomplishments and programs under way. 

Considering what has been achieved in such a short time, the enthusiasm of its board members and volunteers, and the expectation that more will be joining the effort, the future looks very bright for the foundation.

“As is the case for any new organization, our aim for creating the Ophthalmology Foundation was to introduce something better,” Pyott said. “It seems we are well on our way to success judging from the passion and interest displayed by our board members.”

Pyott also noted that as the organization moves forward with its mission, it is inviting ophthalmologists who would like to help colleagues in less-developed countries to reach out to learn about becoming volunteers.

The Ophthalmology Foundation was officially established at the end of 2020 and has a board of approximately 35 members, representing an international group of renowned ophthalmologists of all subspecialties from different practice settings as well as leaders in industry.

“The common denominator for the members of our diverse board is their enthusiasm for educating ophthalmologists in lower-income and middle-income countries,” Pyott pointed out.

The organization is being built using the antecedents of the ICOF, but with the clear intention of making it different. 

The Ophthalmology Foundation has 2 major arms: a fellowship program, which is administered by the International Ophthalmological Fellowship Foundation in Germany, and ophthalmic education, which focuses on improving educators’ competencies.

Discussing the fellowship program, Pyott said the Ophthalmology Foundation already has funding to support a greater number of fellowships than were available at any point in the history of the ICOF.

Assuming travel restrictions related to COVID-19 will not interfere, there are now 80 fellowships available including a pair of 12-month fellowships offered by the Retina Research Foundation Helmerich Fellowship, with the remainder being 3-month fellowships. 

The fellowships are in 50 host countries with most in the United States, Germany, and the United Kingdom.

“We will be securing more financing shortly that will be applied to increase the number of fellowships offered, and we hope to be building onto the number of host countries,” according to Pyott.

The ophthalmology education arm targets educating physicians around the world so that they can teach fellows and colleagues. Pyott noted specifically that it does not involve production of ophthalmic educational content.

“There are already great programs that produce educational content, such as the American Academy of Ophthalmology’s Ophthalmic Network of Education,” he explained.

“Our aim is to provide volunteers the teaching skills they need so that they can share their knowledge and expertise.”

The education arm is being led by Karl C. Golnik, MD, Cincinnati, Ohio, and he is being joined by board members Eduardo P. Mayorga, MD, Buenos Aires, Argentina; Ana Gabriela Palis, MD, Buenos Aires, Argentina; and Helena Filipe, MD, Lisbon, Portugal; and a group of another 20 volunteers around the world.

The education programs are being developed and will include online content and in-person learning. In July, online programming was launched with a series called “Teaching Skills for Ophthalmic Educators.” 

It consists of 12 monthly modules, and the content is available on the Ophthalmology Foundation Education Consortium website (

In-person education programs are planned for the Malaysian Ophthalmology Society meeting in August 2021 and the American Academy of Ophthalmology meeting in November 2021.

Future plans include establishing a mentorship program that will pair ophthalmologists who are early in their careers with experienced colleagues who can provide insights on how younger professionals can advance their careers and their educational skills. 

In addition, the Ophthalmology Foundation hopes to hold the 4-day Eyexcel meeting that will have a mix of virtual programming and in-person learning (travel permitting) at an Aravind Eye Hospital in India.

The Ophthalmology Foundation is also publishing a free monthly educators newsletter. It provides resources from around the world that have been reviewed and approved by the Ophthalmic Education Editorial Board and lists upcoming opportunities for fellowships, workshops, and other events of interest to ophthalmic educators. Individuals who are interested in receiving the newsletter can access it on the Ophthalmology Foundation’s website (ophthalmologyfoundation.org), and they can also sign up on the website to receive the monthly newsletter by email.

Individuals interested in learning more about the Foundation’s programs can look to its social media pages on Facebook and LinkedIn.


Ophthalmologists who would like to help their colleagues in lesser developed countries are welcome to become involved with the Ophthalmology Foundation and can do so in various ways. 

If they would like to host a fellow, ophthalmologists working in an academic setting that does not already have a fellowship agreement with the International Ophthalmology Fellows Foundation can reach out to Cordula Gabel-Obermaier, IOFF executive for fellowships, at 

Ophthalmologists who are enthusiastic about educating colleagues are encouraged
to reach out by clicking on the “Contact Us” tab that can be found on the Ophthalmology Foundation’s website to learn about potential educator opportunities.

Pyott also pointed out that the organization would like to hear from anyone who could help its mission by sharing their knowledge and expertise.

“Our current education team includes members with decades of experience as ophthalmic educators,” he said. “However, we hope to build the next generation of volunteers by hearing from younger ophthalmologists who have established themselves in their career and want to devote time to helping colleagues in the rest of the world."

The Ophthalmology Foundation is also grateful to receive donations that will help support the organization’s mission of serving ophthalmic educators around the world.

“The road to building organizations is paved by small donations,” Pyott concluded.

Organization looks to improve global eye care through ophthalmic education.

Ophthalmology Foundation focuses on mission of vision

IOLs introduced into the US market during the last 2 years offer cataract surgeons an almost dizzying array of options for pseudophakic correction, said Priyanka Sood, MD.

Sood described the technologies and offered insights shared with her by colleagues who had experience with the various lenses. At bottom, there are pros and cons to consider for each IOL and achieving patient satisfaction depends on careful selection and thorough preoperative counseling.

“The reality is that none of these lenses is the holy grail able to restore prepresbyopic quality vision,” said Sood, an assistant professor of ophthalmology at Emory University in Atlanta, Georgia.

The monofocal category was expanded recently with 2 novel aspheric hydrophobic acrylic lenses ––the TECNIS Eyhance (ICB00, Johnson + Johnson Vision) and the Clareon (Alcon). The Eyhance IOL has “extended depth of focus (EDoF)-like qualities” through the design of the central 1 mm of its optic. However, the Eyhance was not approved as an EDoF lens and surgeons cannot charge a premium fee for it. Outside the central 1 mm, the Eyhance optic is similar to the monofocal ZCB00 (Tecnis, Johnson + Johnson Surgical Vision), which explains its good contrast sensitivity, Sood said.

Katie Petro, MD, told Sood she has had good results with the Eyhance and that patients who have received implants are happy. Petro noted that the extra range of vision it provides is for fingertip or computer distance. Using a mini-monovision approach targeting approximately –0.5 D in the nondominant eye can give more near vision, she said.

The Clareon is built on the AcrySof IQ IOL platform but features a new precision edge design to decrease photic phenomena. A new biomaterial and manufacturing process aim to decrease the development of nanoparticle glistenings.

Sumitra Khandelwal, MD, told Sood that the long history of good quality vision with the AcrySof platform is an advantage for the Clareon lens. In addition, as a monofocal lens, it avoids the drawbacks of diffractive multifocals. Only time will tell if the design and material innovations achieve their respective goals of decreasing photic phenomena and nanoglistenings.

Uptake of the light adjustable lens (LAL) has been slow but is picking up momentum. Some reasons for its late adoption, according to Neda Shamie, MD, may include the equipment cost and the workflow related to extra visits needed to perform the adjustments. The advantage of the LAL is that it gives clinicians the ability to customize and accurately titrate the refractive power to the target for each patient.

“Dr Shamie believes that the LAL is the ideal IOL for any patient desiring a customizable outcome and most definitely the ideal for any postrefractive surgery patients who would otherwise risk the unpredictability of refractive outcomes with a static IOL,” Sood said.

The new IOL in the EDoF category is the AcrySof IQ Vivity (Alcon). The Vivity uses wavefront-shaping technology on its anterior surface that elongates the depth of focus, giving about a 1.5 D range of vision. Because it is a nondiffractive lens, risks of glare and halos are minimized and quality of vision is better than with a multifocal IOL. However, results from the FDA clinical trial showed some loss of contrast sensitivity with the Vivity lens, and it does not give good reading vision.

Pearls shared from colleagues for improving outcomes include targeting –0.25 D in the dominant eye and –0.5 to –0.65 D in the nondominant eye, taking care intraoperatively to ensure the IOL is centered and giving patients time to neuroadapt.

The 2 newest multifocal IOLs––AcrySof IQ PanOptix (Alcon) and Tecnis Synergy (Johnson + Johnson Vision)––almost guarantee a broader range of vision than EDoF IOLs but not the avoidance of photic phenomena, Sood said.

The PanOptix is a trifocal lens with negative spherical aberration on its anterior surface that has diffractive rings in the central 4.5 mm of its optic. For users’ perspective, Sood turned to several colleagues.

According to Dee Stephenson, MD, her patients are achieving great uncorrected vision at all distances. They are truly glasses-free as long as they have a healthy eye and astigmatism is corrected. Audrey R. Talley Rostov, MD, added that the IOL has to be perfectly centered. The downsides of the PanOptix include the potential for glare, halos, and decreased contrast sensitivity at night. Talley Rostov advised avoiding this IOL for patients younger than age 65 because they tend to dislike the decrease in contrast sensitivity.

The Synergy features a hybrid of trifocal and EDoF optic technologies. Experience with this IOL, which is very new to the market, is limited, although early results seem good. Additionally, colleagues outside the United States who have had access to the lens for a longer period of time say that the reading and intermediate vision it provides are better than that provided by other technologies. Distance vision may not be as good as with the PanOptix, however, according to anecdotal reports.

Sood has no relevant financial interests to disclose.

Physician offers "real talk" on pros and cons that offers surgeons and patients decision-making insights.

GA therapy demonstrates continuous, sustained effects of pegcetacoplan over time

Measures of functional vision, which refers to a person’s ability to use vision to perceive the environment and function in daily life, are needed to establish benefit of novel gene therapies for inherited retinal dystrophies (IRDs). To that end, a novel standardized orientation and mobility (O&M) course, the multiluminance mobility test (MLMT), was developed and validated to assess the response to treatment with AAV2-hRPE65 for patients with vision loss due to biallelic mutations in 

Researchers are now working to develop a virtual reality orientation and mobility (VR-O&M) test that could overcome the practical challenges associated with reliance on a physical course. In a recently published paper, Tomas S. Aleman, MD, and colleagues reported on a study that provided proof-of-concept data supporting the use of a VR-O&M system to evaluate the potential for functional vision improvement using investigational therapies for IRDs.1

“Our initial findings support further investment in time and resources to refine and validate the VR-O&M technique as an alternative to physical mobility courses,” said Aleman, Irene Heinz-Given and John LaPorte Research Associate Professor in the Department of Ophthalmology at the Perelman School of Medicine, University of Pennsylvania in Philadelphia.

“Once basic VR-O&M tests are validated, the limitations of the current designs, such as lack of standardization and the inability of the VR instruments to explore the full range of our visual abilities, will need to be addressed,” he said.

Virtual reality simulator will boost vitreoretinal surgery training

Aleman said plans were being made to evaluate the effects of gene therapy in an ocular disease, such as 

-LCA. It became obvious that a measure of the patient’s real-life behavior was desirable and needed for endorsement of the safety and efficacy of the treatment by regulatory bodies, such as the FDA. The idea of the MLMT obstacle course was pursued as a paradigm that could determine whether the treatment had a positive effect on visual behavior in a real-world simulated environment.

The course requires availability of a large space that is not available in most eye clinics. In addition, assembling the course is time-consuming and not easy.

Limitations for modifying luminance and obstacle size and position in ways that will accommodate testing of the diverse patterns of visual dysfunction and spectrum of severity of vision loss in patients with IRDs is another drawback of a physical course. Furthermore, test performance scoring is done manually by observers who review videos of the testing. The process is time-consuming and the observers must be masked to avoid bias, as patient confidentiality is not maintained in the recording.

A VR-O&M test using a commercially available headset and custom-designed software was pursued as a more flexible alternative.

“A VR testing paradigm requires a much smaller physical space, allows the opportunity for easily introducing virtually unlimited number of environmental modifications, and performance parameters are automatically detected and quantified,” Aleman said. He added that the testing still involves a patient walking through a physical space, but the required area is much smaller than with the MLMT.

In developing the software for the VR-O&M, Aleman and colleagues evaluated several different configurations in cohorts of both normally sighted control subjects and patients with 

-associated Leber congenital amaurosis (LCA). The test itself is similar to the MLMT, as it requires patients to follow arrows through a course while avoiding collisions with randomly placed obstacles. Subjects are fitted with hand trackers and foot trackers to record information. Performance on the VR-O&M course is scored based on the number of collisions and time taken to reach the course exit.

After testing the various configurations, a protocol was selected for further evaluation in 3 patients with 

-LCA, including 2 patients who performed the testing before and after receiving gene therapy. Results from the controls and the patients with LCA from testing done prior to gene therapy showed differences between the 2 groups in the illumination level needed to navigate the obstacle course as well as in the number of collisions that occurred and total time needed for completing the course.

Compared with their pretreatment performance, the patients who were retested after receiving gene therapy demonstrated improvements in required illumination, number of collisions, and total navigation time that corresponded with their improvements in cone- and rod-mediated sensitivities.

Aleman is a coauthor on intellectual property describing the virtual reality mobility test (PCT/US2019/ 029173 pending). He has no other relevant financial interests to disclose.

1. Aleman TS, Miller AJ, Maguire KH, et al. A virtual reality orientation and mobility test for inherited retinal degenerations: testing a proof-of-concept after gene therapy. 

 2021;15:939-952. doi:10.2147/OPTH.S292527

According to investigators, the virtual reality option could overcome hurdles associated with reliance on a physical course. 

Study backs viability of VR paradigm for orientation, mobility testing

Bausch + Lomb and Clearside Biomedical recently announced the FDA granted approval of triamcinolone acetonide injectable suspension (Xipere) for suprachoroidal use for the treatment of macular edema associated with uveitis.

Formerly known as CLS-TA, the novel product represents the first treatment approved by the FDA for injection into the suprachoroidal space. 

The product is a proprietary preservative-free formulation of triamcinolone acetonide (TA), and the injection is performed as an in-office procedure using a proprietary syringe and needle platform (SCS Microinjector).

Study targets use of swept-source OCT to measure macular hole volume

The FDA approval was based on results of PEACHTREE (NCT02595398), a randomized, controlled, masked phase 3 clinical trial comparing treatment with 2 injections of suprachoroidal TA (weeks 0 and 12) or a sham procedure. 

PEACHTREE met its primary end point by showing statistical superiority of suprachoroidal TA vs sham for the percentage of eyes achieving a best-corrected visual acuity (BCVA) gain greater than or equal to 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline to week 24 (47% vs 16%, 

The study also met all secondary end points, including reduction in macular edema and improvement in anterior chamber and vitreous inflammation, and found the investigational corticosteroid was safe and well tolerated. 

Data from MAGNOLIA (NCT02952001), an extension study, showed the treatment benefit of suprachoroidal TA could persist for at least 9 months in many patients.

Steven Yeh, MD, is the first author of the published article reporting the PEACHTREE study and is a professor of ophthalmology at the Truhlsen Eye Institute, University of Nebraska Medical Center in Omaha.

“The approval of Xipere is an exciting advance in the care for patients with intraocular inflammation and macular edema associated with noninfectious uveitis,” he said. “Corticosteroids are a mainstay of treatment for this condition, and Xipere represents a new method of drug delivery that was well tolerated, showed good safety, and had striking benefit for improving visual acuity and other efficacy measures.”

Yeh pointed out that PEACHTREE assessed visual acuity is the primary end point. “This is an important point because of all the measurable clinical features of uveitic macular edema, vision is the one that most affects quality of life for our patients,” he said.

Yeh said the efficacy and safety of suprachoroidal TA may be understood by its pharmacokinetics, which show suprachoroidal delivery results in very compartmentalized distribution of the corticosteroid, targeting the pathology while limiting exposure to tissues that are adversely affected by corticosteroids. 

FDA approves XIPERE for treatment of macular edema associated with uveitis

“Findings from preclinical studies show there is rapid dispersion of TA into the choroid and retina after suprachoroidal injection and persistence of high levels of the corticosteroid for more than 3 months. However, exposure of the anterior segment to the corticosteroid is limited,” he said. “Therefore, suprachoroidal TA offers the potential for rapid and effective control of uveitic macular edema with the potential to limit corticosteroid-related complications of cataract, IOP elevation, and glaucoma exacerbation.”


PEACHTREE randomized 160 patients 3:2 to treatment with triamcinolone 4 mg/0.1 mL or sham procedure. All anatomic subtypes of uveitis were represented in the study population.

Approximately 50% of patients in the suprachoroidal TA arm and two-thirds of controls were phakic. Mean time since uveitis diagnosis was 177 weeks in the suprachoroidal TA arm and 107 weeks in the control arm.

 Mean BCVA at baseline was approximately 55 letters in the suprachoroidal TA arm and 54 letters in the controls. Mean central subfield thickness (CST) in the 2 groups was 481 and 525 μm, respectively.

The secondary end point in PEACHTREE was mean change from baseline in CST measured by spectral domain optical coherence tomography at 24 weeks. 

Additional end points included mean change in BCVA in ETDRS letters by visit, mean change in CST by visit, and changes in signs of inflammation as evaluated by the Standardization of Uveitis Nomenclature scales. 

Mean reduction in CST from baseline to week 24 was significantly greater in the suprachoroidal TA arm than the sham group (153 vs 18 μm, 

Patients treated with suprachoroidal TA gained a mean of 9.6 ETDRS letters from baseline at week 4 and showed further improvement thereafter, reaching a mean gain of 13.8 ETDRS letters at week 24 compared with just 3.0 ETDRS letters in the control group (

Rescue therapy was allowed beginning at week 4 if patients met prespecified criteria or were not improving. It was received by 13.5% of patients in the suprachoroidal TA arm and 72% of control patients.

Tracking macrophages in the macular circulation with commercial OCT


Patients from PEACHTREE were eligible for participation in MAGNOLIA if they completed PEACHTREE without needing any rescue therapy. 

Of 46 patients originally randomized to suprachoroidal TA and 7 originally randomized to sham, 28 in the suprachoroidal TA group and 5 patients in the control group entered the extension study.

During the 24-week follow-up period in MAGNOLIA (48 weeks post randomization and 36 weeks after the second injection), 11 of the 28 patients originally treated with TA received rescue therapy, and 3 were withdrawn because of an adverse event. 

Thus, 14 of the 28 patients (50%) required no rescue therapy. Three of the 7 patients who had been in the PEACHTREE control arm received rescue therapy, and 2 others withdrew.

MAGNOLIA investigated median time to rescue treatment during the extension period as its primary end point and showed it was significantly longer in the triamcinolone group than in the control arm (257 days vs 55.5 days). 

At the end of the study, patients originally treated with suprachoroidal TA had a mean BCVA gain from baseline (PEACHTREE entry) of 12.1 ETDRS letters and a mean CST reduction of 174.5 μm.


No serious adverse events considered by the investigators to be related to treatment with suprachoroidal TA were recorded during PEACHTREE or MAGNOLIA. 

In PEACHTREE, the rate of elevated IOP pertaining to the corticosteroid (this analysis excludes events on the day of the procedure) was higher in the control group than in the triamcinolone arm (15.6% vs 11.5%), and the rate of cataract formation was only slightly higher in the triamcinolone group than among eyes receiving sham injection (7.3% vs 6.3%).

“It is important to note that in PEACHTREE, the suprachoroidal TA injection was well tolerated and associated with a lower rate of elevated IOP than the sham control procedure where rescue therapies could be administered during the trial,” Yeh said.


Yeh said all investigators participating in the premarketing clinical trials received special training for administering the injection. 

“The procedure used for suprachoroidal TA injection is a nuanced technique. However, it is very reproducible, can be learned by any ophthalmologist who is comfortable administering intraocular injections, and is well tolerated by patients,” he said.


Yeh is a consultant to Clearside Biomedical, Bausch + Lomb, Allergan, Regenxbio, Adverum Biotechnologies, and Buoy Health.

1. Khurana RN, Merrill P, Yeh S, et al. Extension study of the safety and efficacy of CLS-TA for treatment of macular oedema associated with non-infectious uveitis (MAGNOLIA). 

 2021;bjophthalmol-2020-317560. doi:10.1136/bjophthalmol-2020-317560

Triamcinolone acetonide injection approved for treatment of macular edema.