Reviewed by Zeinab Rozita Ghassabi, MD; and Joel Schuman, MD



A sublayer of the inner plexiform layer (IPL) holds promise as a potential biomarker in efforts to detect early glaucomatous changes, according to Zeinab Rozita Ghassabi, MD, a postdoctoral research fellow, and Joel Schuman, MD, Department of Ophthalmology, New York University Langone Health, New York.

Ghassabi related that animal studies have determined glaucomatous changes start in dendrites and then in the ganglion cells and axons. 

 (vis-OCT) has been especially valuable in this research because the technology facilitates visualization of multiple sublayers of the IPL.

“Vis-OCT has higher axial resolution compared with conventional OCT,” she explained.

Conventional systems are limited to axial resolutions of about 3 to 4 μm in contrast to vis-OCT with an axial resolution in vivo of about 1.8 μm in air and 1.3 μm in eye.

Ghassabi and colleagues tested the potential of the IPL sublayers as glaucoma biomarkers using vis-OCT compared with conventional biomarkers such as the retinal nerve fiber layer and the ganglion cell layer. 

Visualization with en face OCT offers value for ophthalmologists

To do this, they used a prototype instrument, the Aurora X1 vis-OCT system (Opticent Inc) using a 3-D speckle-reduced raster scanning protocol focused on the superior fovea in 9 healthy subjects and 6 patients with glaucoma.




The healthy subjects (average age, 47 years) and 

 patients (average age, 63 years) had respective RNFL thicknesses of 96.43 and 64.6 μm, which differed significantly (

Respective mean deviation values were –1.55 and –19.4 decibels, a difference that also reached significance (

Vis-OCT showed that the IPL has 3 sublayers; in subjects who were healthy and in those with glaucoma, the total IPL values were 39.44 and 35.5 μm (

 = .002, linear regression adjusted for age), respectively. The thickness of sublayer 1 did not differ between the 2 groups. 

Patient-based research powers the revealing of disease mechanisms

The thickness of sublayers 2 and 3 differed significantly: sublayer 2, 17.17 and 14.36 μm (

 = .003, linear regression adjusted for age); sublayer 3, 11.29 and 10.29 μm (

 = .045, linear regression adjusted for age), Ghassabi noted.

Analysis showed a strong correlated with the thickness of sublayer 2 and the mean deviation.

“The IPL is a layer of synapses between the bipolar, amacrine, and retinal ganglion cells and can be divided into on and off sublaminae and 5 strata,” Ghassabi said. “The 5 layers that were visible on vis-OCT images were correlated with 5 morphologic strata, S1 to S5.”

The patients with glaucoma had moderate and advanced disease. The thinning of sublayer 2 that was observed was associated with a decrease in the distance between sublayers 2 and 4 in the patients with glaucoma. 

This thinning was not observed in the healthy subjects.

Taking a step forward in glaucoma patient care

“This finding corroborated the hypothesis that retinal ganglion cells with dendrites stratified in the off sublaminae may be damaged,” she commented.

According to the investigators, the IPL sublayer 2 seems to have high potential as a clinical glaucoma biomarker. Future studies of early-stage 


This article is adapted from Ghassabi’s presentation at the American Glaucoma Society’s virtual annual meeting. She has no financial interest in this subject matter.

Articles

Visible-light optical coherence tomography proves valuable in studies.

IPL offers glaucoma biomarker for early-stage disease


By all accounts, the US is doing pretty well in its battle against COVID-19, with some states boasting more than 70% of its citizens vaccinated.

However, the rest of the world has not achieved that level of success, and because the US is not an island unto itself, the American Medical Association (AMA) is advocating equitable resource distribution of vaccinations to assist low-income countries.

The COVID-19 delta variant is spreading rapidly in the US and elsewhere. This can result in additional surges of infections especially among populations that do not have ready access to vaccinations.

On June 14, the AMA House of Delegates adopted a policy that promotes equitable resource distribution worldwide to combat the virus. 

The association will look to COVID-19 Vaccines Global Access (COVAX) to establish aid for countries that have limited means financially and technologically. 

The COVAX is an initiative that is directed by the World Health Organization, the Global Alliance for Vaccines and Immunizations, and the Coalition for Epidemic Preparedness Innovations.

The AMA explained that its new policy urges “specific steps to bolster production and distribution of therapeutics and vaccines necessary to combat COVID-19.”

“The steps include a temporary waiver of the Trade Related Aspects of Intellectual Property agreement and other relevant property protections; technological transfers relevant for vaccine production; and other support, financial and otherwise, necessary to scale up global vaccine manufacturing,” the association said in a statement.

Other initiatives mentioned in the new policy stipulate that the AMA by working with government and regulatory bodies will encourage prioritization of equity when distributing pandemic-related resources, such as diagnostics, low-cost or free medications, therapeutics, vaccines, raw materials for vaccine production, and personal protective equipment.

Bobby Mukkamala, MD, AMA Board chairman elect, emphasized that doctors and numerous organizations worldwide are combating the virus in countries with meager financial resources, limited supplies and overtaxed hospitals.

“The situation is dire, giving rise to new, more transmissible, more dangerous variants, and global cooperation to ensure equitable distribution of resources is essential to defeating COVID-19,” he said in a statement. “The situation may seem to be getting better here, but in a global pandemic, threats abroad can quickly become threats in the United States and set us all back.”

The American Medical Association is advocating equitable resource distribution of vaccinations to assist low-income countries.









AMA policy: Equitable distribution of resources needed to fight COVID-19

Fasika Woreta, MD, MPH, of the Wilmer Eye Institute, Johns Hopkins University School of Medicine, discusses the determining factors and indicators to consider when treating cataract patients with IOLs.

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In recognition of Cataract Awareness Month, Fasika Woreta, MD, MPH, discusses IOL options for cataract patients. 

Assessing IOL options for cataract patients


Infants may have an edge over adults, with babies demonstrating a stronger immune response to the SARS-CoV-2 virus.

found that young infants have relatively higher antibody levels to the virus compared with adults and these antibodies can protect them against COVID-19, according to Anu Goenka, BSc, MBChB, clinical lecturer, and colleagues from the University of Bristol and Bristol Royal Hospital for Children, Bristol, UK.

Physicians have been observing that children do not seem to become as sick as adults when infected with COVID-19 during the pandemic and, in reality, have had mild cases. 

This has been especially surprising since infants can become severely ill from respiratory syncytial virus and influenza.



Study suggests the eye as a point of SARS-CoV-2 infection

Considering this observation, Goenka and colleagues investigated the antibody and convalescent cellular immune responses to COVID-19 in 4 infants younger than 3 months old with mild disease compared with the parents and adult controls.

The investigators reported that the “infants have high serum levels of IgG and IgA to SARS-CoV-2 spike protein with corresponding functional ability to block SARS-CoV-2 cellular entry” compared with the adults. 

This immune response, the investigators noted, appeared distinct from that of the parents.

The study also found that the infants had robust saliva anti-spike IgG and IgA responses. The spike-specific interferon (IFN)-γproduction by the peripheral blood mononuclear cells in the infants seemed restrained, but the frequency was similar to adults.

Shedding light on ocular findings in COVID-19 patients

The study data suggested that robust functional antibody responses and the restrained IFN-γproduction may be the keys to the protection against severe COVID-19 in these infants.

Goenka said that this information can help in the design of future COVID-19 vaccines.

1. Goenka A, Halliday A, Gregorova M, et al. Young infants exhibit robust functional antibody responses and restrained IFN-γ production to SARS-CoV-2. Cell Reports Medicine Published June 9, 2021; Accedded June 13, 2021; DOI: 

https://doi.org/10.1016/j.xcrm.2021.100327

According to investigators, infants may have an edge over adults, with babies demonstrating a stronger immune response to the SARS-CoV-2 virus. 

Unlocking the keys to mild COVID-19 cases in infants

Although there currently are no options available to treat retinitis pigmentosa (RP), a novel approach has been evaluated in a phase 2 clinical trial that determined the clinical effect of the injection of human retinal progenitor cells to improve vision and visual fields in this patient population by activating and preserving retinal cells to treat RP.

The trial’s findings indicated that this treatment may be able to enhance vision and visual fields in specific patients with RP whose living cells can be rejuvenated, according to David S. Boyer, MD, an adjunct clinical professor of ophthalmology at the Keck School of Medicine of USC in Los Angeles, California.

A heterogeneous group of patients with RP and 20/80 to 20/800 vision were included in the phase 2 trial. The patients were not excluded based on their clinical picture or genetics. 

Optogenetic gene therapy restores vision in 11 RP patients

Three study groups were tested: patients who received an injection of 3 million cells, patients who received an injection of 6 million cells, and a sham control group. 

These were regenerative cells intended to enhance cells that might still be living in the retinas of patients with RP.

The primary end point was the mean change in the best-corrected visual acuity (BCVA) from baseline to month 12. 

The study’s goals were to determine the ideal dose and identify secondary end points and the clinical characteristics of the patients who might benefit most from 1 intravitreal dose in a phase 3 trial. 

Following exclusion as the result of administration of the wrong dose, loss to follow-up, or a preexisting condition, 74 patients were included in study and randomized 1:1:1 in the analysis.

The first steps in gene therapy for achromatopsia

The secondary end points were low light mobility to facilitate navigation through a maze, kinetic visual fields that map the remaining vision, contrast sensitivity, and the results of a visual functioning questionnaire (VFQ-48).

Injection of the 6-million-cell dose showed a moderate improvement in vision of approximately 4.4 letters over the sham treatment. 

The kinetic visual field also showed an improvement, contrast sensitivity, and results of the VFQ-48; however, no improvements were seen in the low luminance test, Boyer reported.

In previous studies, Boyer explained, patients with a visual field of less than 12 degrees had been identified as unable to be reliably measured because of their inability to maintain fixation without central vision. 

Moreover, patients with a 3-line difference in vision between the treated eye and the fellow also had a decrease in vision that could not be improved. 

Expansion study examines safety, efficacy of subretinal gene therapy for X-linked RP

When the investigators evaluated the patients in the phase 2 trial because of these specific parameters, the investigators saw approximately 15 letters of improvement and significant improvements in the kinetic visual fields, contrast sensitivity, VFQ-48, and navigation through the low luminance maze when the patients in the 6-million-cell group and those who received the sham treatment were compared.

At the time of this report, approximately 130 eyes had been treated and the safety profile was excellent. No serious adverse events occurred in the group treated with the higher dose.

“The study found that the 6-million-cell dose was the most effective, all clinical trial end points were useful and supportive of the treatment effect, the treatment had an excellent safety profile, and certain patients from the broad set of [patients with RP] studied can be assessed more reliably,” Boyer said.

However, the question remains as to which patients would benefit the most from this treatment. 

Gene therapy heralds new era for inherited retinal diseases

Heat maps were generated that showed the width and the band of the ellipsoidal zone, and the results indicated that the thickness of the ellipsoidal zone may be predictive of improvements in the end points (BCVA, visual fields, contrast sensitivity, the low luminance level in the maze, and the VFQ-48 results) with treatment with human progenitor cells compared with sham treatment.

Similarly, the mean foveal central thickness also was highly correlated with improvements in the end points in the 6-million-cell group.

“The optical coherence tomography findings indicated structural predictors, ie, the ellipsoidal zone thickness and the mean foveal thickness, for [participants] who received the 6-million-cell dose who were most likely to improve with injection of human progenitor cells,” Boyer concluded. “There was no evidence of structural improvement at 12 months. The potential minimal thickness should be considered as part of the inclusion criteria for future studies. “

The phase 3 trial will begin in the third quarter of 2022. 


This article was adapted from Boyer’s presentation at the Bascom Palmer Eye Institute’s Angiogenesis, Exudation, and Degeneration conference, held virtually in February. Boyer is a consultant to jCyte, which ran the study under discussion and participated in the study.

Investigators find approach improved vision and visual fields in some patients.

Targeting human retinal progenitor cell injections for RP 

According to investigators, the new technology is designed to detect telltale signs of major blinding diseases in retinal blood and tissue that typically go unseen until it is too late.

Investigators believe a non-contact laser imaging system could help doctors diagnose and treat eye diseases that cause blindness much earlier than is now possible.

 developed by engineering investigators at the University of Waterloo in Waterloo, Ontario, Canada, is designed to detect telltale signs of major blinding diseases in retinal blood and tissue that typically go unseen until it is too late.

With current testing methods, diseases such as age-related macular degeneration, diabetic retinopathy and glaucoma, which have no symptoms in their early stages, are usually diagnosed only after vision is irreversibly affected.

“We are optimistic that our technology, by providing functional details of the eye such as oxygen saturation and oxygen metabolism, may be able to play a critical role in early diagnosis and management of these blinding diseases,” said Parsin Haji Reza, director of the PhotoMedicine Labs at Waterloo Univeristy, in a statement.

According to investigators, patented technology at the core of the new system is known as photoacoustic remote sensing (PARS). It uses multicolored lasers to almost instantly image human tissue without touching it.

When used for eyes, the non-invasive, non-contact approach improves both patient comfort and the accuracy of test results, according to the university.

The technology is also being applied by Haji Reza and investigators in his lab to provide microscopic analyses of breast, gastroenterological, skin and other cancerous tissues, and to enable real-time imaging to guide surgeons during the removal of brain tumors.

According to Richard Weinstein, MD, an ophthalmologist and co-founder of the Ocular Health Centre, PARS may move ophthalmology beyond the current gold standard in ophthalmological imaging.

“For the first time, not just in ophthalmology but in the entire medical field, diagnosis and treatment of disease could be made prior to structural change and functional loss,” he said in a statement.

Haji Reza, a professor of systems design engineering and co-founder of startup company illumiSonics, said researchers are working with several ophthalmologists and hope to start clinical trials within two years.

1. Z. Hosseinaee, N. Pellegrino, et. al; Functional and structural ophthalmic imaging using noncontact multimodal photoacoustic remote sensing microscopy and optical coherence tomography; 

According to investigators, the new technology is designed to detect telltale signs of major blinding diseases in retinal blood and tissue that typically go unseen until it is too late. 

Touchless technology could enable early detection, treatment of eye diseases that cause blindness 

The US Supreme Court has once again upheld the constitutionality of the Affordable Care Act (ACA) but did not close the door on future challenges.

In a 7 to 2 ruling, the High Court ruled that Texas lacked standing in its challenge to the individual mandate. In the technical ruling the court failed to address the underlying issues of the suit. 

Justice Stephen Breyer wrote the decision for the majority, while Justices Samuel Alito and Neil Gorsuch dissented.

The opinion brings the latest high-profile challenge to the law to an end.

“Today’s decision by the U.S. Supreme Court is a victory for patients and for the gains in health care coverage achieved through the Affordable Care Act (ACA),” American Medical Association (AMA) President Gerald E. Harmon, MD, said in a statement. “The American Medical Association is pleased that the high court rejected the challenge to the ACA, thereby upholding critical patient protections that are improving the lives and health of millions of Americans, particularly amid a global pandemic.”

The law was challenged by 18 states, led by Texas. Those states the court to rule that Obamacare's requirement for nearly all Americans to obtain health insurance or pay an income tax penalty — known as the individual mandate — is unconstitutional. 

For that reason, they said, the entire law must be scrapped.

The individual mandate was ruled unconstitutional in a 2-1 decision by the U.S. Court of Appeals for the Fifth Circuit in New Orleans, the majority chose to return the case to Judge Reed O’Connor in the Federal District Court in Fort Worth, Texas, to determine whether the mandate can be severed from the rest of the law.

In 2018, O’Connor ruled the ACA was unconstitutional because of how central the mandate was to the law, according to a report from 

O’Connor’s previous ruling was based on Congress’s belief when it enacted the ACA that the individual mandate was a key element to the law that could not be severed from it.

He found the mandate unconstitutional because a 2012 Supreme Court decision upheld the mandate, saying that it fell under Congress’ powers over taxation, according to the 

When the tax penalty was eliminated in 2017, 20 state attorneys general, the plaintiffs in the case, argued that defense of the law was no longer effective and that the rest of the law should be invalidated along with it. 

The Department of Justice refused to defend the law, and later joined the plaintiffs in arguing against the law, according to the 

The Fifth Circuit decision was appealed, which brought the case to the U.S. Supreme Court where the health insurance coverage of about 23 million Americans hung in the balance, according to 

The US Supreme Court ruled Thursday that the Affordable Care Act remains valid, rejecting a claim by several states that a recent change to the law made it unconstitutional. 

Supreme Court upholds Affordable Care Act


Oyster Point Pharma announced today the enrollment of the first participant in its OLYMPIA phase 2 clinical trial of OC-01 (varenicline) nasal spray to treat stage 1 neurotrophic keratopathy (NK). 

The trial — a multicenter, randomized, double-masked, placebo-controlled clinical trial — is expected to enroll an estimated 100 subjects at approximately 18 sites across the U.S., according to a 

OC-01 (varenicline) nasal spray is designed as a multidose, preservative-free nasal spray to treat signs and symptoms of NK and dry eye disease (DED). 

Participants will receive OC-01 (varenicline) nasal spray administered three times a day, as compared to a placebo (vehicle) nasal spray. The trial's pre-specified primary endpoint will be the percentage of subjects who reach complete resolution of fluorescein corneal staining at Day 56, the company reports.

“We believe that OC-01 nasal spray may activate natural tear production through the trigeminal parasympathetic pathway, bypassing the impaired corneal nerves to stimulate the production of natural tear film and potentially improve corneal sensitivity and healing," said Marian Macsai, MD, Oyster Point Pharma's chief medical officer, in a statement. 

After receiving acceptance by the U.S. FDA for its NDA of OC-01 (varenicline) nasal spray earlier this year, the company's target action date for the Prescription Drug User Fee Act (PDUFA) is Oct. 17, 2021.

A U.S. launch of the nasal spray is planned for the fourth quarter, pending FDA approval. 

Oyster Point Pharma announced today the enrollment of the first participant in its OLYMPIA phase 2 clinical trial of OC-01 (varenicline) nasal spray to treat stage 1 neurotrophic keratopathy (NK). 

Oyster Point Pharma enrolls first subject in phase 2 clinical trial of OC-01 nasal spray for neurotrophic keratopathy 

An implantable glaucoma biosensor has received CE mark approval for marketing in the European Union weeks after getting a nod from the FDA.

The sensor (Eyemate-SC, Implandata Ophthalmic Products) is used in conjunction with the company’s Eyemate system for digitally enabled remote glaucoma monitoring and management. 

 patented system is among the first clinically-validated product used for comprehensive remote glaucoma monitoring. US FDA Breakthrough Device Designation (BDD) was obtained in April.

BDD is only assigned for breakthrough technologies that have the potential to provide more effective treatment of life-threatening or irreversibly debilitating diseases in order to provide patients and physicians more timely access to such technologies without compromising safety.

Max G. Ostermeier, CEO and founder of Implandata,moving forward under the

FDA BDD program means the company will benefit from additional FDA input during the premarket development as well during the submission process and through an expedited review once the submission is filed.

“With FDA market authorization, the Eyemate system will now be entitled to Medicare Coverage of Innovative Technology for at least 4 years, offering beneficiaries predictable access to the breakthrough Eyemate system, helping to improve their health outcomes,” he said.

According to the company, the system is an improved version of its predecessor product. Measuring IOP throughout the day, every day, could allow patients and their physicians to tailor glaucoma medications to the patients’ specific needs, Implandata said.

Ostermeier also noted that obtaining CE mark for the less invasive sensor as part of the company’s validated Eyemate system is another important step forward for the company to transform glaucoma care.

“This new version is expanding the addressable glaucoma patient segment and is more readily and safely implanted than the earlier device,” he said in a statement. “With CE mark, we will start to launch the product with various eye centers across Europe.”

The device empowers patients to self-measure their intraocular pressure, and then automatically sends gathered information in real-time to their eye doctor or to cloud-based storage. This information enables eye doctors to obtain close information about therapy effectiveness and to adjust treatment based on a patient’s current condition rather than make therapeutic adjustments based on only a single measurement of IOP acquired during an office visit.

Robert N. Weinreb, MD, chairman and Distinguished Professor of Ophthalmology at University of California, San Diego and Implandata medical advisor, points out that millions of individuals worldwide are at risk of permanent loss of their vision due to glaucoma.

“With the EYEMATE, intraocular pressure now can be monitored more closely to personalize treatment and avoid further vision loss,” he said in a statement.

Kaweh Mansouri, MD, MPH, is a consultant ophthalmologist at Clinique de Montchoisi Lausanne/Switzerland, and adjoint professor at the Department of Ophthalmology, University of Colorado, Denver. He was one of the lead investigators in the clinical study validating the biosensor.

“With CE Mark of the Eyemate-SC biosensor we can now start to introduce the Eyemate system into our clinical routine, which we have eagerly waited for,” he said in a statement. “Our team has been very pleased with the safety and the performance of the product in our clinical study and is very happy by how well the product is accepted by our patients.”

Moreover, Mansouri pointed out that Eyemate will help ophthalmologists to make more informed therapeutic decisions faster.

“This technology empowers patients, resulting in improved adherence with therapy and less worries about undetected IOP peaks and glaucoma progression,” he concluded.

Implandata received FDA Breakthrough Device Designation for its Eyemate-SC in April and now has CE Mark approval in the European Union.  

Biosensor for remote glaucoma care gets new approvals

Habash is the medical director of Technology innovation at the Bascom Palmer EyE Institute. 

Ranya Habash, MD, medical director, Technology Innovation, Bascom Palmer Eye Institute (University of Miami), shares how she approaches the topic of cataract surgery with new cataract patients ahead of undergoing the procedure. 

In recognition of Cataract Awareness Month. 

Oyster Point Pharma enrolls first subject in phase 2 clinical trial of OC-01 nasal spray for neurotrophic keratopathy

Biosensor for remote glaucoma care gets new approvals

Explaining cataract surgery to patients