, sits down with David Bingaman, DVM, PhD, Chief Development Officer of Ora Clinical to discuss the need to accelerate clinical trials and increase investments in retina research. Dr. Bingaman also discusses Ora Clinical’s presence at ARVO 2022.

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Dr David Bingaman of Ora Clinical discusses today’s need to accelerate clinical studies and increase investments in retina and challenging disease states.

Unpacking the need to accelerate clinical studies in retina

Taping the top border of the surgical mask to the clinicians’ skin reduced the potential for ocular surface damage resulting from expirations of air reaching the ocular surface during the COVID-19 pandemic, according to a presentation made by Dr Yuichi Hori at the Association for Research in Vision and Ophthalmology’s 2022 annual meeting in Denver, Colorado, United States.

Dr Hori is a professor and chairman of the Department of Ophthalmology at Toho University Omori Medical Centre, Toho University School of Medicine, Tokyo.

The investigators theorized that dry eye symptoms of dryness, pain, and discomfort associated with mask wear resulted from changes in the ocular surface caused by exposure to breath leakage from the top of the mask.

Sixty volunteers (30 females, 30 males; 27.1 ± 5.2 years) who wore masks for more than 5 hours daily were included in the study, during which the authors measured the ocular surface temperature, fluorescein tear break-up time, and conjunctival blood flow.

Thirteen of the 60 subjects reported dry eye symptoms associated with mask wear. Among the 13 subjects, compared with 47 subjects without mask-associated dry eye symptoms, the ocular surface disease index was significantly elevated and the tear break-up time with and without masks was significantly shorter than in subjects without symptoms of dry eye. The pain sensitivity in the subjects with dry eye symptoms was significantly higher than in those without dry eye symptoms.

The investigators concluded that wearing masks decreased the tear break-up time and increased the ocular surface temperature and blood flow. Taping the top edge of the mask prevented those changes. Fitting masks tightly to the nose or applying tape over the mask may reduce the risk of dry eye symptoms associated with mask wear.

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During a presentation at the Association for Research in Vision and Ophthalmology’s 2022 annual meeting, Dr Yuichi Hori and colleagues found that taping the top border of a surgical mask to a clinicians’ skin reduces the potential for ocular surface damage resulting from expirations of air reaching the ocular surface during the COVID-19 pandemic.

Sealing masks to skin with tape may decrease risk of ocular surface damage during the COVID-19 pandemic

Erica Kahn and colleagues from Ocular Therapeutix Inc. found both that injection of the axitinib intravitreal implant (OTX-TKI) in non-human primates resulted in high levels of the drug in the retinal tissue and was generally well tolerated.

This intravitreal implant is being evaluated to treat wet age-related macular degeneration in a phase 1b clinical trial.

The advantage of this hydrogel-based implant is that it is designed to deliver the tyrosine kinase inhibitor axitinib to the retinal tissue for from 6 to 9 months, in contrast to current AMD injections that are required every 1 to 2 months for these patients.

In this 9-month study in which the implant was administered to Cynomolgus monkeys, the investigators evaluated the effects of different doses and numbers of implants when the animals received either 3 200-µg- (group 1, n=8), one 300-µg- (group 2, n=8), or one 600-µg- (group 3, n=8) OTX-TKI implant in both eyes on Day 0.

The implant was well tolerated in all groups.

The intraocular pressure did not change significantly and no significant inflammatory response was observed.

The researchers measured high levels of axitinib in the retina tissue at 3 and 6 months after injections in all groups. The drug distributions in the retina and choroid/retinal pigment epithelium were higher in group 1 at 3 months but comparable in all groups at 6 months.

At the 6-month time point, the implants in groups 1 and 2 released about 50% of the drug and in group 3 35% of the drug in the vitreous. The investigators pointed out that the daily release rates in group 1 were higher than in the other groups due to the larger surface area with the three implants used in group 1.

The implants degraded at about month 6 and particles of axitinib particles were seen in the vitreous at month 9. There was minimal drug systemically in the animals in all groups based on the plasma samples obtained at month 3.

The axitinib intravitreal implant (OTX-TKI) is being evaluated to treat wet age-related macular degeneration in a phase 1b clinical trial.

Injectable axitinib intravitreal implant delivers high drug levels to retinal tissue

A team of investigators from the New York University Grossman School of Medicine found in a murine model of experimental glaucoma that chronic IOP elevation had a role in the widespread vascular and functional brain changes seen in the animals, according to a presentation

Dr Kevin Chan, an assistant professor at the New York University Grossman School of Medicine, presented the study results at the Association for Research in Vision and Ophthalmology’s 2022 annual meeting in Denver, Colorado, United States, on behalf of Dr Russell Chan, also affiliated with the school.

They hypothesized that the vascular functions of the visual cortex and basal forebrain are involved in glaucoma, because the former has lower choline levels in glaucoma and the latter has cholinergic projections to the visual cortex for modulating the cerebral blood flow and visual processing, they explained.

In a recent experiment, they used resting-state functional magnetic resonance imaging (rsfMRI) to document the relative cerebrovascular reactivity in the brain, specifically, decreased reactivity in the visual cortex and increased reactivity in the basal forebrain in patients in whom the severity of the glaucoma was progressing. The speculation was that a chronic increase in IOP may lead to cerebrovascular reactivity changes in the brains of patients with glaucoma and visual impairment.

The authors conducted the current murine experiment with the goal of elucidating the mechanisms involved. To do so, they administered an intracameral injection of cross-linking hydrogel to the right eye of the mice to obstruct the aqueous outflow and induce a chronically elevated IOP. Untreated mice served as controls. The IOP was measured in both eyes of the mice 2 to 3 times weekly for 3 weeks and measured the optomotor responses of the animals and conducted rsfMRI experiments.

The increase in IOP was induced and sustained in the murine right eyes. The cerebrovascular reactivity decreased in the left untreated eye but not in the right visual cortex and the cerebrovascular reactivity increased in the right basal forebrain in the glaucoma model but not in the control mice.

The authors reported that the IOP in the injected eye was correlated inversely with the relative cerebrovascular reactivity in the left visual cortex and correlated positively with the relative cerebrovascular reactivity in the right basal forebrain. The optomotor responses indicated a decrease in the visual acuity and an increase in the visual contrast threshold in the injected eye, indicating visual impairment. The visual acuity decrease was correlated inversely with the relative cerebrovascular reactivity in the basal forebrain.

The authors concluded that this mapping of the relative cerebrovascular reactivity in the murine brain showed widespread brain changes resulting from the chronic IOP elevation and demonstrates vascular involvement in glaucoma both within and beyond the primary visual pathways.

“Our results showed similar patterns of relative cerebrovascular reactivity changes as those seen in glaucoma patients along with visual impairments, indicating a role of chronic IOP elevation in the widespread vascular and functional brain changes in experimental glaucoma,” the authors concluded.

Investigators from the New York University Grossman School of Medicine presented data at the ARVO 2022 annual meeting that concluded mapping of the relative cerebrovascular reactivity in the murine brain showed widespread brain changes resulting from the chronic IOP elevation and demonstrates vascular involvement in glaucoma both within and beyond the primary visual pathways.

Chronic IOP elevation affects cerebrovascular reactivity in murine visual cortex, linked to widespread brain changes

A team of investigators studied the effects of intensive outdoor activity on the eyes of children and found that the choroidal and central corneal thicknesses increased over a very short period of time following intensive outdoor activity.

Dr Mamoru Ogawa, from the Department of Ophthalmology, and the Laboratory of Photobiology, Keio University School of Medicine, Tokyo, presented the results in a poster at the Association for Research in Vision and Ophthalmology’s 2022 annual meeting in Denver, Colorado, United States.

“This is an important finding considering the rapidly increasing prevalence of myopia that has been recognized worldwide,” investigators noted.

“The increasing myopia prevalence globally is a relatively recent social health problem,” investigators noted, adding that outdoor activity is an evidence-based environmental factor that protects against myopia progression.

According to the presentation, the investigators conducted a study that included 17 children who participated in a program of activity that increased in outdoor duration over a week’s time from more than 2 hours on day 1, 3 hours on day 2, to 6 hours daily on subsequent days for a total of 6 days during the 2021 vacation at a summer camp in Japan.

All children underwent measurement of the refractive error, axial length, corneal and choroidal thicknesses, and tear fluid volume, and the children completed a questionnaire. These parameters were analyzed at the start and end of the program; the data from the left eyes were evaluated.

The children were a mean age of 12 ± 1.0 years and 47.1% were girls. The investigators reported a significant (

 < 0.001) change in the mean choroidal thickness between baseline and the final measurement, i.e., from 359.5 ± 121.7 µm to 397.4 ± 122.1 µm, and a significant (

 < 0.002) change in the central corneal thickness from 579.0 ± 45.6 µm to 584 ± 44.6 µm.

Significant changes were not observed in the refractive error, axial length, or tear fluid volume over the course of the study.

“Our results suggested that intensive outdoor activity even for 1 week increased the choroidal and corneal thicknesses in Japanese schoolchildren,” investigators concluded. “Further studies are needed to assess the effects in more subjects over the long term.”

In a poster presented at the Association for Research in Vision and Ophthalmology’s 2022 annual meeting in Denver, Dr Mamoru Ogawa noted that investigators have found that the choroidal and central corneal thicknesses increased over a very short period of time following intensive outdoor activity.

Bursts of intensive outdoor activity result in increased choroidal, central corneal thickness in paediatric patients

, sits down with Dr Jason S. Slakter to discuss his ARVO 2022 presentation, “Efficacy and Safety of OPT-302 in Combination with Ranibizumab for Polypoidal Choroidal Vasculopathy.” OPT-302 (Opthea Limited) 2 mg combination therapy results indicated a safety profile consistent with the standard of care anti-VEGF-A monotherapy, but also indicated superior improvements in best-corrected visual acuity (BCVA) and anatomic improvements compared to monthly ranibizumab (Lucentis®) monotherapy in patients with polypoidal choroidal vasculopathy (PCV).

At ARVO 2022, Dr Jason S. Slakter presents data on the efficacy and safety of OPT-302 when combined with ranibizumab for polypoidal choroidal vasculopathy. 

BCVA, anatomic improvements found with OPT-302 combination therapy for PCV

Cosmetic iris implants pose serious risks and are strongly discouraged, according to Dr Jorge Alio and Dr Francesco D’Oria, both from Vissum Alicante Miranza Group and the Miguel Hernández University of Elche in Alicante, Spain. However, despite the potential risks, the surgeries are still performed.

The currently available models are the NewColorIris (Kahn Medical Devices) and BrightOcular (Stellar Devices). The NewColorIris, a silicone iris diaphragm with six rounded flaps in the periphery to hold the device in place, has a diameter that ranges from 11 to 13 mm and a pupillary aperture of 3.5 mm and thickness of 0.16 mm. The BrightOcular, which is held in the eye by five triangular flaps in the periphery, comes with diameters ranging from 11.5 to 13.5 mm and thicknesses of 0.16 and 0.18 mm; the authors reported that the posterior face has grooves to facilitate aqueous flow.

Dr Alio and Dr D’Oria conducted a retrospective study of the medical records of five patients (10 eyes; age range, 27–46 years) who had received one of the devices (two with NewColorIris and eight with BrightOcular). The patients had been referred to the Vissum Instituto Oftalmológico de Alicante for complications associated with the latest models of the implants, which had been available for 6 years.

The authors reported that all the devices had been explanted 1–60 months after the surgeries (Figures 1 and 2). The mean endothelial cells density was 848 ± 227.5 cells/mm

. Corneal transplantations had to be performed in 30% of eyes; in other words, two eyes had a Descemet membrane endothelial keratoplasty and one eye had a penetrating keratoplasty.

Three other patients were advised that they would need a corneal transplant. Nine of the 10 eyes developed ocular hypertension and a filtrating surgery was needed in two cases. Early development of cataract was a common complication, with 40% of the patients—who were a mean age of 36 years—requiring cataract surgery.

A representative case was that of a 37-year-old woman who had a cosmetic iris implanted in both eyes and returned 2 years later with problems in her left eye. This patient had a dramatic endothelial cell loss of 1,163 cells/mm

Following referral, iris atrophy was seen superiorly. The investigators said that the endothelial cell density was relatively conserved after explantation, at 1,054 cells/mm

. The cosmetic implant of the other eye also had to be removed for similar reasons.

Figure 3. A NewColorIris implant causes severe edothelial cell loss and chronic uveitis. 

Neither of these commercial devices had been approved by the United States Food and Drug Administration or received a CE mark, but they continued to be implanted. Newer models have not been improved and cause the same complications to develop as the previous models.

“Patients with cosmetic iris implants have a high risk of definitive loss of vision and other serious complications that should be described to patients before implantation,” Dr Alio concluded. “Implantation of cosmetic [iris] implants should be considered today as malpractice in the light of available evidence.”

This article is adapted from Dr Alio and Dr D’Oria’s presentation at the 2021 American Academy of Ophthalmology annual meeting in New Orleans, Louisiana, United States. Dr Alio and Dr D’Oria have no financial interest in this subject matter.

Authors of a retrospective study into complications associated with iris implants advise that the procedure should be considered as malpractice.

Cosmetic iris implants pose high risk of vision loss

The greatest likelihood of a germline mutation in patients with a unilateral retinoblastoma occurred in patients who were 1 year or younger versus those older than 1 year, as well as in a subset of patients 3 months and younger versus those between 3 and 12 months of age. This finding was presented by Dr Carol Shields, chief of the Ocular Oncology Service at Wills Eye Hospital in Philadelphia, Pennsylvania, United States.

Dr Shields and her colleagues conducted a retrospective case series to evaluate the likelihood of germline retinoblastoma in children with solitary unilateral retinoblastoma. She explained that the goal of the study was to determine the risk of patients developing more of these tumours—that is, the risk for a germline mutation.

“It is important to know the germline status because the patients are at risk of developing multiple bilateral retinoblastomas, pinealoblastoma and secondary cancers,” Dr Shields said. “These can lead to blindness and death.”

The investigators retrospectively reviewed 482 consecutive patients who presented with one unilateral retinoblastoma and were later found to have a likely germline tumour. The latter was defined as a family history of retinoblastoma; development of bilateral disease and/or new tumours; and the gold standard: i.e., a documented germline on genetic testing.

A comparative analysis was then completed based on the following patient age groups: 0–1 year; 1–2 years; 2–3 years; and older than 3 years. The results showed that in children aged 0–1 year who presented with one unilateral retinoblastoma, 29% had a germline mutation (odds ratio 2.96). When compared with children older than 3 years, 9% had a germline mutation. This difference reached significance (

Among children who were 12 months or younger with one unilateral retinoblastoma, Dr Shields reported that in the youngest of these children (aged 0–3 months), 61% had a germline mutation. When these children were compared with those aged 9–12 months, the percentage dropped to 22% with a germline mutation. This difference was significant (

“It is clear that the youngest children with a unilateral retinoblastoma are at the greatest risk for a germline mutation,” Dr Shields said. In the other age groups—aged 3–6 months, 6–9 months, 12–24 months, 24–36 months and older than 36 months—the respective percentage of germline mutations was 20%, 24%, 17%, 8% and 9%.

“Of the 482 consecutive patients with a solitary unilateral retinoblastoma who were seen on the Ocular Oncology Service at the Wills Eye Hospital, we found a significant decreasing risk for a germline mutation based on the older patient age at presentation,” Dr Shields concluded.

This article is adapted from Dr Shields’ presentation at the American Academy of Ophthalmology 2021 annual meeting. This presentation received the Best Poster award. Dr Shields has no financial disclosures relevant to this topic.

In one study of children with solitary unilateral retinoblastoma, the youngest children were found to have the greatest risk for a germline mutation.

Study investigates risk of children with unilateral retinoblastoma developing germline mutations

According to a USC news release, ophthalmologists may be able to use electronic technology to directly stimulate retinal neurons by implanting electrode devices inside the eye, a technique that requires expensive and invasive surgery.

Research by the USC Gayle and Edward Roski Eye Institute from several years ago indicates that the number of Americans with visual impairment or blindness is expected to jump to more than 8 million by the year 2050.

With the youngest baby boomers reaching 65 years old by 2029, age-related eye diseases and conditions are expected to swell during what’s being called the “silver tsunami.”

Many cases of visual impairment are likely to be caused by retinal degenerative diseases, the progressive degeneration of the light-sensitive photoreceptors in the retina. As a result, there likely will be a growing need for new technologies that treat vision loss due to diseases of photoreceptor degeneration.

While there are no successful non-invasive therapeutics currently available for the treatment of vision loss, researchers at USC have come up with a new idea to address this growing problem.

The university noted that a research team in the USC Viterbi School of Engineering’s Department of Biomedical Engineering is exploring a non-surgical solution that could restore sight by using another of the five senses.

“This is innovative technology,” Qifa Zhou, professor of biomedical engineering and ophthalmology at USC, said in a statement. “Right now, we are doing animal studies trying to use ultrasound stimulation to replace electric stimulation.”

The university noted that the research group is led by Zhou, and Mark S. Humayun, professor of ophthalmology and biomedical engineering at USC, and one of the inventors of Argus II—the world’s first artificial retina.

“The technology is advantageous since no surgery is required and no device will be implanted inside the body,” Gengxi Lu, a PhD student in Zhou’s lab, said in the news release. “A wearable ultrasound device will generate ultrasound waves to stimulate the retina”.

Similar to how shapes and bright spots appear when you gently push on your eyeball with your eyes closed; researchers realized that applying pressure to the eye can activate neurons and send signals to the brain.

Unlike a normal eye that is activated by light, the blind eyes were stimulated by mechanical pressures generated by ultrasound waves in this study.

“The neurons present in the retina of the eye possess mechanically sensitive channels that respond to mechanical stimulation,” Lu explained. “These neurons are activated when we use ultrasound to generate mechanical pressure.”

To test this ultrasound approach, in pre-clinical studies the team at USC stimulated a blind rat’s eyes using high-frequency ultrasound waves that are inaudible to humans.

The university noted that the technology used in this research is comparable to the ultrasound probe used for baby imaging that sends and receives sound waves through a pregnant patient’s abdomen.

In this case, for retinal stimulation the research group created a small ultrasound device that can be directed at a specific region of the eye to send sound waves to the retina, which is located in the back of the eye.

Using these high-frequency sounds that can be manipulated and focused on a specific area of the eye; the study demonstrated that when the ultrasound waves are projected as a pattern—for example, the letter ‘C’—the rat’s brain was able to pick up a similar pattern.

Unlike in humans, researchers are unable to get direct answers about the rat’s visual experiences during the ultrasound stimulation.

To answer these questions of what exactly the rat was able to visualize from the ultrasound waves, the team measured visual activity directly from the rat’s visual brain area known as the visual cortex by attaching a multi-electrode array.

Based on the visual activities recorded from the brain, researchers found the rat was able to perceive visualizations comparable to the ultrasound stimulation pattern projected to the eye. This work was just published in 

According to the university, the research is currently funded by a four-year, $2.3 million grant from the National Eye Institute (NEI). The team recently applied for another NEI translational grant to take their studies to the next level.

The university also noted that studies are conducted mostly using rodent models. However, the release noted that the team plans to test this approach using non-human primate models prior to conducting human clinical trials.

“Right now, we are using a transducer placed in front of the rat’s eyeball to send the ultrasound signals to the retina, but our final goal is to create a wireless lens transducer” Zhou said.

While the team is currently analysing the capabilities of ultrasound technology for vision study, their future goal is to generate sharper images and install the ultrasound transducer on a wearable contact lens for next generation.

According to the university, there is also a pending patent for this novel ultrasound technology that hopes to change the way visual impairment is treated years down the road.

Xuejun Qian, Gengxi Lu, Biju B. Thomas, Runze Li, Xiaoyang Chen, K. Kirk Shung, Mark Humayun. Noninvasive Ultrasound Retinal Stimulation for Vision Restoration at High Spatiotemporal Resolution; 

, Published Feb. 22, 2022; doi 10.34133/2022/9829316

Researchers at the University of Southern California have stimulated the retinas of blind mice using focused ultrasound technology.

Noninvasive retinal stimulation achieved via ultrasound

“Think of dry eye in everything you do.” This advice was given to new ophthalmologists by Dr Sheri Rowen, the medical director of NVision Eye Centers in Newport Beach, California, United States.

Dry eye sounds simple but is actually a far-reaching, multifactorial disease of the ocular surface that causes loss of homeostasis of the tear film. According to the Tear Film and Ocular Surface Society Dry Eye Workshop II definition, this loss of homeostasis is accompanied by ocular symptoms in which tear film instability, hyperosmolarity, ocular surface inflammation and damage and neurosensory abnormalities all play aetiological roles.

Dr Rowen stated that meibomian gland disease (MGD) is one of the major problems in dry eye disease. Normal glands are symmetrical and are even the same length. They are not dilated. In contrast, with progression of dry eye disease, the glands become truncated and dilated in moderate cases, with subsequent glandular atrophy (dropout) and extreme loss of function in severe cases.

Dr Rowen emphasised the importance of recognising MGD progression to ensure appropriate treatment. Youth and gender are not protective against MGD. Dr Rowen discussed severe cases of gland atrophy in patients in their 20s who presented with complaints of dry eye.

In a 22-year-old man, severe atrophy was already present; in a 26-year-old man who wanted to undergo LASIK surgery for contact lens intolerance, the meibomian glands were almost completely deteriorated.

Gland dropout can start early, often in patients as young as 8–16 years. “Ophthalmologists must be able to recognise this is happening to young patients of both genders to be able to provide appropriate treatment,” Dr Rowen said.

“If these patients are identified when they are young, or optometrists are educated to recognise these cases early [on], ophthalmologists will be able to help them early [on] to avoid the development of atrophy,” Dr Rowen concluded. “Ophthalmologists should always stain the ocular surface with fluorescein and lissamine stains, express the glands and use a questionnaire. This will ensure the identification of 97% of patients with dry eye.”

This article is adapted from Dr Rowen’s presentation at the virtual Real World Ophthalmology Autumn 2021 meeting. Dr Rowen is a consultant to Alcon and Johnson & Johnson.

It is particularly important to identify any signs of meibomian gland disease in patients to prevent gland atrophy and loss of function.

Dry eye pearls for young ophthalmologists

At ARVO 2022, Dr Steven Yeh reviews the results of the Phase 3 PEACHTREE and AZALEA integrated study, revealing significant BCVA gains and low adverse event incidence in the Xipere (triamcinolone acetonide injectable suspension, Bausch + Lomb) arm.

Dr Yeh is a professor of ophthalmology and the Director of Retinal Disease and Uveitis at the Stanley M. Truhlsen Eye Institute at the University of Nebraska Medical Centre.

This integrated analysis looked at patients who received macular oedema for noninfectious uveitis. In PEACHTREE specifically, we treated patients with macular oedema due to noninfectious uveitis. And the AZALEA study looks specifically at safety in this cohort of patients.

And in this study, we looked at the efficacy signals as well as the safety signals, integrating these two cohorts of patients. What we found is that patients who received Xipere showed a significant best corrected visual acuity gain of up to two to three lines of visual acuity improvement at the week 24 time point when we combined the clinical trial data.

This is also reflected in reduction of macular oedema, specifically found that patients who received Xipere showed approximately 150 micron reduction in central subfield thickness, and this was sustained for the duration of the trial.

The other aspect that's very important related to this new technique for the treatment of posterior segment conditions is safety. What we found is that intraocular pressure rates were very favourable. In the Xipere arm specifically, about one in eight individuals showed elevation of intraocular pressure, compared to the slightly higher one and seven of individuals in the patients who were in the sham control arm.

When we broke this down further to the patients in the sham arm who received rescue therapy, we found that 25% of individuals who receive local intravitreal therapies showed an elevation of intraocular pressure, which is really compelling when we think about Xipere as a therapy that's nuanced, and a new technique for the treatment of macular oedema due to noninfectious uveitis.

Other adverse events were very well tolerated, and we're very excited about both the efficacy outcomes, as well as the safety variables as well. Again, visual acuity is very important to all of our patients and again, is related to the quality of life and what patients care about most. This is a new drug delivery technique that we're really looking forward to not only for uveitis, but other posterior segment conditions in the future.

Note: This transcript has been lightly edited for clarity.

The Phase 3 integrated PEACHTREE and AZALEA study data revealed strong safety and efficacy for triamcinolone acetonide via suprachoirodal injection.

Integrated study: Phase 3 PEACHTREE, AZALEA indicate significant BCVA gains, CST reduction

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.

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

 covered the evolution of gene therapy techniques in ophthalmology, use of polarisation-sensitive optical coherence tomography (PS-OCT) to recognize corneal abnormalities, an upcoming pharmaceutical for the treatment of cataracts and the announcement of a partnership between BRIM Biotechnology and Ora Inc. for the late-stage clinical development of lead drug candidate BRM421 for dry eye syndrome (DES).

Making strides in ophthalmology with modern gene therapy techniques

The are several available approaches in gene therapy. We can replace a disease-causing gene with a healthy gene or deactivate a gene that is not functioning properly. In addition, a modified or completely new custom-designed gene can be introduced to treat a disease.

The basic principle is to target missing or faulty genes in monogenic diseases. Usually the “gene therapy drug” is given only once; it carries an instruction to change the sequence of one or more proteins. This change is necessary if those essential proteins are produced in a faulty manner: either they are not produced in sufficient quantities or the catalysis process controlled by the protein is not working correctly.

Major pathobiochemical or pathophysiological pathways have been investigated intensively. Gene therapy products include plasmid DNA and viral or bacterial vectors: in a subset of diseases, cells are extracted, genetically modified and then re-introduced into the body but more commonly a viral vector is used, which entails eliminating the virus gene and using its ability to penetrate the cell to safely deliver the new information.

From an immunological perspective, the eye is the ideal target for gene therapy, which thus makes it likely that, in the future, highly successful gene therapy approaches will lead to cures for certain diseases of the eye.

The missing link in the recognition of corneal abnormalities

Polarisation-sensitive optical coherence tomography (PS-OCT) is a functional extension of the conventional form of OCT and exploits the polarisation properties of light. According to Dr Ritika Mullick, a fellow in Cornea and Refractive Services at Narayana Nethralaya Hospital, Bangalore, India, this imaging modality can aid the early recognition of disease-related changes before they can be seen topographically.

Dr Mullick explained that the human eye is known to have polarisation-altering tissues; using an ultra-high-resolution PS-OCT helps us to study the form birefringence caused by the underlying fibril structures in the corneal stroma. This, in turn, can enable users to detect subnormal distribution of collagen in corneal disorders.

In a clinic setting, this technology can demonstrate both normal corneal biomechanics and clear-cut cases of abnormalities, such as the development of post-SMILE ectasia.

Approaching pharmaceutical treatment for cataracts

A new treatment for cataract has shown extremely positive results in laboratory tests, giving hope that the condition, that currently can only be cured with surgery, could soon be treated with drugs.

A team of international scientists, led by Dr Barbara Pierscionek, deputy dean (Research and Innovation) in the Faculty of Health, Education, Medicine and Social Care at Anglia Ruskin University (ARU), have been carrying out advanced optical tests on an oxysterol compound that had been proposed as an anti-cataract drug.

According to a news release from ARU, in laboratory trials, treatment with the oxysterol compound VP1-001 showed an improvement in refractive index profiles – a key optical parameter that is needed to maintain high focusing capacity – in 61% of lenses. This means that the protein organization of the lens is being restored, resulting in the lens being better able to focus. This was supported by a reduction in lens opacity in 46% of cases.

“This study has shown the positive effects of a compound that had been proposed as an anti-cataract drug but never before tested on the optics of the lens,” Dr Pierscionek, who is also a member of the Medical Technology Research Centre at ARU, said in the release.

Dr Pierscionek added that it is the first research of this kind in the world.

“It has shown that there is a remarkable difference and improvement in optics between eyes with the same type of cataract that were treated with the compound compared to those that were not,” she said.

Strategic alliance combines resources to develop treatment option for dry eye syndrome

BRIM Biotechnology Inc. has entered into a new strategic partnership with Ora Inc. for the late-stage clinical development of lead drug candidate BRM421 for dry eye syndrome (DES).

According to a news release, BRIM intends to initiate Phase 3 clinical studies with Ora’s support later this year.

BRM421 is based on BRIM’s proprietary stem cell regenerative Pigment Epithelium-Derived Factor (PEDF) derived Short Peptide (PDSP) technology platform, which underpins several products in its pipeline and has the potential to be effective in multiple therapy areas and indications. The functional domain of PEDF chosen to generate PDSPs can be used to treat DES by speeding up the cornea repair process through stimulation of corneal stem cell proliferation and differentiation, anti-inflammation and meibomian gland recovery.

Dry Eye Syndrome is a chronic disease that affects the productivity and quality of life of 1.52 billion people worldwide.1 The COVID-19 pandemic has further exacerbated the problem, as prolonged time in front of screens is a risk factor for the disease.

Other risk factors include aging, eye surgeries, dry environments, long-term wearing of contact lenses, and autoimmune diseases. Unlike current treatments, BRM421 is a novel, first-in-class regenerative peptide therapy which, if successful, could offer patients full relief of symptoms plus repair the damage to the cornea.

An end-of-week review of what happened in ophthalmology from 14 May to 20 May.