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

Cheryl Guttman Krader, BS, Pharm

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Results from a laboratory study measuring oxygen kinetics during corneal crosslinking (CXL) indicate that supplementary oxygen has the potential to substantially increase the efficacy of the procedure, according to Theo G. Seiler Jr, MD.

The laboratory study, which was performed using de-epithelialized porcine eyes, measured local oxygen concentrations at varying corneal depths under atmospheric (21% O2) and hyperoxygenic (100% O2) conditions with different levels of UV irradiation. 

Benefits of topography-guided treatments for irregular corneas

The analyses showed that compared with the atmospheric oxygen environment, supplementary oxygen increased the amount of oxygen available in the stroma during CXL. 

The benefit of the hyperoxygenic environment was particularly seen when using higher UV irradiances that are associated with increased oxygen consumption, noted Seiler, senior physician in the Department of Ophthalmology at the University of Bern in Switzerland.

“The mechanism of action for CXL involves UV-induced activation of riboflavin, the photosensitizer, resulting in the generation of reactive oxygen species that induce formation of covalent bonds within the collagen fibrils and crosslink the proteoglycans between the collagen fibrils,” he said. “Many previous studies have investigated the influence of varying the parameters for riboflavin imbibition and UV irradiation on CXL effectiveness.”

Seiler said the study was motivated by the limited research investigating the role of oxygen that is the third crucial factor for achieving sufficient CXL. 

Corneal crosslinking outcomes look good for pediatric keratoconus

“Our findings show that providing supplementary oxygen is likely to be beneficial by increasing the aerobic reaction and allowing more efficient CXL in deeper corneal layers and at UV irradiance levels less than 3 mW/cm2,” he said.

Measurement of the oxygen concentration at different corneal depths was accomplished by inserting a fiber probe into channels created by a femtosecond laser at depths of 100 μm, 200 μm, and 300 μm. 

Eyes were exposed to 0.1% riboflavin (Vibex Rapid; Avedro/Glaukos) for 10 minutes, and then the oxygen concentration was continuously measured during irradiation at 3, 9, 18, and 30 mW/cm2. 

“In order not to alter the cornea during the measurements, the used fiber probe had a tip that was only around 50 μm in diameter,” Seiler said.

Groups of 8 eyes each were evaluated under each of the testing conditions while the oxygen concentration was continuously measured. 

Under atmospheric oxygen and with irradiation at 3 mW/cm2, representing the conventional Dresden protocol, there was a surplus of oxygen available at all measured depths during the entire CXL procedure. 

However, when the irradiance was increased to 9 mW/cm2, sufficient oxygen for CXL was available only at 100 μm and 200 μm. 

At UV-irradiance above 9 mW/cm2, all oxygen was consumed within the anterior 100 μm, indicating that there was insufficient oxygen for achieving sufficient crosslinking in the profound cornea, Seiler said.

When the testing was done in the hyperoxygenic environment, there was sufficient oxygen available for crosslinking at all measured depths when using the 3 mW/cm2 and 9 mW/cm2 irradiances.

At higher UV irradiances, there was more oxygen available than under atmospheric conditions, although still not enough to provide sufficient oxygen through the entire corneal stroma. 

Corneal transplantation experiences a revolution

Additional analyses determining the consumption of oxygen showed that during the procedure, the half-lives were longer and the depletion rates higher with supplementary oxygen, suggesting a more efficient CXL than under atmospheric oxygen conditions, said Seiler.


This article is based on a presentation given by Seiler at the 2020 ESCRS Virtual Congress. The study was published (Seiler TG et al. Am J Ophthalmol. 2020;223:368-376). Seiler has no relevant financial interests to disclose.

Articles

Ex vivo experiment identifies potential benefit for supplementary oxygen.

Maximizing CXL effectiveness

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

Evaluating safety, efficacy of TP03 for Demodex blepharitis treatment

blepharitis demonstrates that this common condition has important negative functional and psychosocial effects, according to Elizabeth Yeu, MD.

The study, known as ATLAS, analyzed data from questionnaires that were completed by 311 patients who had objective signs of 

mites, collarettes on the lashes, and lid margin erythema. 

The results showed that 80% of patients said that blepharitis negatively affected daily life and that the impacts were felt in multiple ways.

“Many clinicians underestimate the prevalence and impact of 

blepharitis due to symptom overlap with other ocular surface diseases that are often comorbidities, such as dry eye disease,” said Yeu, an assistant professor of ophthalmology at Eastern Virginia Medical School and a partner at Virginia Eye Consultants in Norfolk. “However, it has been estimated that blepharitis affects approximately 20 million Americans, of whom about 45% have an associated infestation with 

Yeu pointed out that ATLAS is a pioneering study investigating the consequences of 

blepharitis, and its results indicate that affected patients may struggle for years with significant clinical, functional, and psychosocial impacts.

“Therefore, it is important that clinicians be proactive about diagnosing 

blepharitis and offering treatment,” she said.

The data for the ATLAS study were derived from participants in SATURN-1, a multicenter, phase 2b/3 clinical trial investigating the efficacy and safety of TP-03 (lotilaner 0.25% ophthalmic solution; Tarsus Pharmaceuticals) for treating 

To be eligible for enrollment in the SATURN-1 study, patients had to have 10 or more collarettes on the upper lashes, 1.5 or more mites per lash, and at least mild lid margin erythema.

The ATLAS participants’ questionnaire responses showed that women were more likely than men to experience a negative impact from their 

blepharitis, but the majority of both men (72%) and women (84%) suffered adverse consequences.

Having difficulty driving at night and feeling or being conscious of their eyes all day were the most common issues, both noted by 47% of patients.

“Notably in terms of emotional impact, about 23% of both males and females said they were constantly worrying about their eyes, and 6% of the participants indicated that their blepharitis affected their mental state, with this impact felt more often by males than females,” Yeu said.

Approximately 30% of both males and females said that blepharitis added time to their daily hygiene routine, 8% reported having discomfort with their contact lenses or having to reduce wear time because of the condition, and 5% noted that they avoided ocular surgery because of the blepharitis.

The cosmetic consequences were also common. Twenty-three percent of respondents (females 27%, males 16%) felt blepharitis had an adverse effect on the appearance of their eyes or eyelids. 

One-third of women indicated the condition interfered with their ability to wear makeup, and 5% of women noted discomfort when wearing artificial lashes.

Tarsus execs discuss origins, treating Demodex blepharitis


Yeu also noted that the identification of collarettes, which are a pathognomonic sign for 

blepharitis, makes the diagnosis easy and straightforward.

blepharitis, and patients who are complaining of itching may be misdiagnosed as having allergic conjunctivitis,” she explained. “Thus, clinical examination to identify collarettes is key for making the diagnosis and helping our patients, and it is easily done when patients look down during the slit-lamp examination.”

Because there is no FDA-approved product for safely and effectively treating 

blepharitis, providing effective treatment is more difficult than making an accurate diagnosis.

“Current management options do not treat the underlying cause of disease, which is the mite infestation,” Yeu said. “In addition, many treatments have low tolerability that makes patient compliance a challenge.”

The study results, Yeu explained, demonstrate that an easy, safe, and effective therapy for 

VA and visual function go the way of ocular inflammation

“Lotilaner solution that is being developed by Tarsus Pharmaceuticals is a specific antiparasitic agent that has been shown to work well for eradicating 

mites and improving signs and symptoms of 

blepharitis, Yeu recommended the use of tea tree oil wipes for patients with no more than 10 collarettes along the lid margin. 

In cases with more marked involvement, she recommends in-office microblepharoexfoliation (BlephEx; Alcon) and topical treatment with an antibiotic-steroid ointment to the lid margins for 7 days, plus tea tree oil wipes for 6 weeks.


Yeu is a consultant for and does research with Tarsus Pharmaceuticals and Alcon.

Symptomatic, psychosocial burdens in participants .

Cheryl Guttman Krader, BS, Pharm

Articles

Expert insights: Flares of dry eye disease

Ophthalmology Foundation focuses on mission of vision

Detailing consequences of Demodex blepharitis

Maximizing CXL effectiveness