Kassi Jackson

home

authors

kassi-jackson

Ora's Caitlin Black, senior director and therapeutic area head of medical devices, discusses exciting new presbyopia IOL technology coming down the pipeline.

Hi, my name is Caitlin Black, senior director and therapeutic area head of medical devices at Ora. We are a full-service clinical development organization overseeing both drug and device clinical trials.

Just returning from ASCRS, I am most excited about the innovation in presbyopia. Presbyopia is the so-called "final frontier" in refractive surgery, and there are many advancements that are providing additional options to presbyopic patients.

We know that worldwide, 1.7 billion people are affected with presbyopia and they currently have limited options. Their quality of life is diminished due to the decreased visual acuity, and many are looking to be free of glasses or obtain spectacle independence.

Since 1949, when IOLs first for implanted we've seen many advancements in IOL technology, including multifocal accommodating IOLs, pinhole IOLs, and extended depth of focus IOLs. Now we're really focused on patient-reported outcomes in our medical trials.

At Ora we work very closely with our sponsors to design study protocols that take into consideration patient's quality of life. We do this through integrating quality of life questionnaires, supplements and being mindful of patient objectives when they enter a clinical trial for a premium IOL.

At Ora we partner with many sites, we have 800 sites that we partner with worldwide and we have individuals on the ground working in 25 countries. This allows us to have really high-quality oversight and monitoring of the clinical trials, which ultimately proceeds with high quality outcomes.

We know that there are many exciting advancements coming in presbyopic IOLs, many IOLs that are currently available outside of the US are entering clinical trial in the United States. I think the next challenge as more lenses become available will be to properly select the technology for the patient for individualized patient outcomes.

Note: This transcript has been lightly edited for clarity.

Videos

Ora's Caitlin Black, senior director and therapeutic area head of medical devices, talks about the next generation of ophthalmic device therapies and diagnostics, clinical trial updates and new innovations that are most exciting for presbyopia treatment.

Advancing IOL technology for treatment of presbyopia

Gloria B. Chiu, FAAO, FSLS, sat down with 

executive editor David Hutton to discuss her poster, "Impact of Delayed Corneal Crosslinking in Keratoconus Patients," presented at ARVO 2022 in Denver, Colorado, United States.

This transcript has been lightly edited for clarity.

Hi, David, thank you so much for this opportunity to be here with you today. Well, it's exciting, first of all, that ARVO was able to bring so many people back in-person to discuss research and all the exciting things we've been learning about and not able to communicate with each other over the last two years.

So my poster, as you mentioned, is titled, "Impact of Delayed Corneal Crosslinking in Keratoconus Patients." Now this poster is really only a sampling and giving us a taste of what we've been seeing in clinic, we would like to in the future share more of a case series including more patients, and the changes we saw on their eyes.

In this particular poster, my colleagues and I from the USC Roski Eye Institute in Los Angeles, discussed data from three patients. So essentially, in summary, the impact of delayed corneal crosslinking in patients who are candidates for this treatment can be very devastating.

And this was seen through these three patients. Due to various reasons, insurance being one of them, lost to follow up, and also the pandemic, we had challenges managing these patients ideally.

So because they were diagnosed with keratoconus, [and] they were young, we wanted to get them this treatment, but many of them had challenges getting insurance approval. Now, as we know, [the] FDA approved corneal crosslinking in the United States in April of 2016. So some of these patients that I was following were referred for crosslinking around that time, around 2017. Insurance coverage wasn't as good as it is now, so back then we really had challenges getting them the coverage they needed.

So we shared three cases on this poster. The first was a 26-year-old female. Essentially, she presented with keratoconus more in her left eye than the right. She had no scars in her right eye but some striae in the left eye. She was referred for crosslinking but because it wasn't covered by her insurance at that time, she couldn't get the treatment. She ended up getting fit with scleral contact lenses in 2017, but as we know the contacts didn't do anything to help the progression of the disease. So unfortunately, even though she could see better, she developed scarring. Then we kind of lost her to follow-up didn't see her back until November of 2020 when we noticed significant progression in her keratoconus. Now she had scars in both eyes, and her glasses were no longer functional. And it's been really challenging and just devastating to see the impact on her eyes and her vision, given that she's a young 20 year old.

Another case, we shared another young Caucasian male. Similarly, he had moderate keratoconus presented in 2017. And he had RGP contacts for many years. But over the years between 2017 to 2019, we followed his corneal tomographies and he looked okay, but then in 2020, when he came back we saw a significant progression. And now we saw central corneal scarring and the right eye. So with keratoconus, we look for changes through the slit lamp, such as corneal thinning, corneal striae corneal scarring. So when we saw this scarring, we referred him immediately for crosslinking. He had it done in March of 2021, in his in his right eye, and then May of 2021, in his left eye. But again, due to the pandemic, which, you know, started in about March of 2020, we weren't able to get him treated as early as we would have liked. And so we did see unfortunately steeping in his corneal topographies.

And with our last patient, he's 44. But, you know, although we generally expect keratoconus to progress in the teens and 20s, it certainly can still progress, especially if there are environmental factors such as eye rubbing. So this patient, 44-year-old, he had significant ocular allergies, floppy eye lid syndrome, and lots of eye rubbing. So he was referred for crosslinking as well, he were RGPs (rigid gas permeable lenses). He had crosslinking in one eye in his in his left eye in August of 2018. Thankfully, however, with his right eye, he had no scars. And he was referred out for improvement in his contact lens fitting, so he got Sclera Lenses, and with changes noted in his right eye later on. So he came back for his routine Scleral Lens care. But then we saw scarring in his right eye when previously we hadn't noted it. And when we sent him out for cross linking for his other eye, we again notice challenges with insurance coverage, even though he had it done in his other eye.

So these are just three instances of keratoconic patients who experienced challenges in getting timely corneal crosslinking that has led to permanent changes in their corneal structure, as well as best-corrected vision. And that's what the poster shows, with some of the images, the tomography that we have. Ultimately, we want to avoid advanced signs, such as corneal scarring, which we know will impact vision. And in our table, we just show essentially the delay these patients experienced and in our case, it wasn't just weeks or months. In some cases, it was years, because they were seen, you know, so soon after the FDA approval, and insurance coverage back then in 2017, wasn't as robust as it is today.

So we noticed changes in their prescription getting higher, decreased best-corrected vision steepening in their K measurements (their keratometry measurements), as well as thinning in their corneas. So with these changes — thinning, also, the development of scarring — these are things that cannot be reversed.

Through this poster — through these three cases — we really want to get the point out that we should initiate crosslinking as soon as possible in good candidates, particularly young individuals, and especially those with ocular allergies or who have history of eye rubbing, because these actions can lead to progression of the disease more rapidly. So particularly with the last couple of years in access to care, delays due to the pandemic, a lot of our patients unfortunately struggled with getting timely treatment; but now, hopefully moving forward once we make the proper diagnosis, and also confirm that they either have progressive keratoconus or ectasia following refractive surgery, we can get them the care they need as soon as possible.

The study evaluates three separate cases, each of which experienced irreversible changes in their corneal structure caused by challenges in getting timely treatment due to various reasons, including insurance, lost to follow up, and the COVID-19 pandemic.

Ill-timed corneal crosslinking led to permanent changes in corneal structure in patients with keratoconus

At Retina World Congress 2022, Prof. Anat Loewenstein presented a talk entitled, “Targeting the Ang/Tie2 Pathway: Efficacy and Outcomes.” In her presentation, she discussed data for the bispecific molecule faricimab and its efficacy at targeting both the VEGF and Ang2 pathways while treating neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DMO).

In my presentation, I showed how targeting both VEGF and Ang2 in a bispecific molecule—faricimab—can help in increasing the durability of the drugs we are using for both diabetic macular oedema and neovascular AMD.

So in my presentation, I showed how in studies for faricimab as compared to a comparator in neovascular macular degeneration. For a duration of two years, a very high percentage of the patients were able to maintain a longer duration interval between doses. And about more than three quarters of the patients were able to maintain a duration of more than three months, and about 45% a duration of four months. And this was maintained while the visual acuity outcomes were non inferior to the comparator.

In addition, a very important point that I emphasize is that there were no signals of significant side effects, no significant intraocular inflammation and no cases of vasculitis or occlusive vasculitis.

For diabetic macular oedema, similarly, about three quarters of the patients in the study, were able to be maintained on a three or four monthly interval. And about 50%—and this percentage increased to 60% in the second year—were able to be maintained on a 16-week interval. And that was when non inferiority of visual acuity and even a better drying of the retina as compared to the comparator again with no significant side effects.

Prof. Anat Loewenstein discusses data regarding the efficacy of faricimab at targeting both the VEGF and Ang2 pathways in patients with neovascular AMD and diabetic macular oedema.

Data reveals efficacy of bispecific targeting of VEGF, Ang2 pathways

The PEARL [phase] 2 study was looking at the compound OC-02 in treating dry eyes. This is a nasal spray that is used twice a day.

Their primary endpoints were to look at increasing Schirmer's, as well as eye discomfort score. By using this nasal spray twice a day, in four randomized groups — so three different concentrations of OC-02 versus placebo — they found that the Schirmer scores were significantly higher in the drug arms, especially the highest drug concentration. And the eye irritation score was also improved most with the highest concentration of the drug.

This molecule is very similar to the OC-01 molecule, which has been FDA approved and marketed. This particular molecule, because of OC-01 being on the market already, is not going to be licensed in the US for marketing.

The take home message is that the use of the cholinergic agonists as a nasal spray to stimulate the trigeminal nerve is a reasonable mechanism to help treat dry eyes. It's novel; it's different than putting eyedrops in your eyes. It may be beneficial for patients who have trouble putting eyedrops in their eyes. A lot of people are used to using nasal sprays for allergies, for example. And so this modality of treatment, as well as a new mechanism, may have extensive benefits for the patients.

The study's primary endpoints were to look at increasing Schirmer's scores, as well as eye discomfort score.

Author | Kassi Jackson

Articles

Ill-timed corneal crosslinking led to permanent changes in corneal structure in patients with keratoconus

Data reveals efficacy of bispecific targeting of VEGF, Ang2 pathways

Investigating efficacy of OC-02 to stimulate the trigeminal nerve for the treatment of dry eyes

Advancing IOL technology for treatment of presbyopia