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

This article was reviewed by Peter A. Campochiaro, MD



Nanoparticles have been used to deliver gene therapy to treat 

, the Johns HopkinsUniversity (JHU) investigators used a uniquely engineered large molecule that facilitated compaction of large bundles of therapeutic DNA to be delivered into the ocular cells.

Regenxbio: Dosing of first patient in Phase 2 AAVIATE trial for wet AMD



This approach does not depend on viral vectors, as many of the gene therapies do, to transport the needed material into the cells. The downside of viral vectors is that an immune response is produced, and dosing cannot be repeated. 

In addition, the one used most often for ocular gene therapy cannot carry large genes, the investigators pointed out.

“Some of the most prevalent inherited retinal degenerations are due to mutations in large genes that simply cannot fit into the most commonly used viral vector,” said Peter A. Campochiaro, MD, the Eccles Professor of Ophthalmology at the JHU School of Medicine in Baltimore, Maryland.

In their research, Campochiaro and Jordan Green, PhD, used a biodegradable polymer that compacts long expanses of DNA to nanoparticles that can enter the cells, which transforms these ocular cells into “mini factories” for creating a therapeutic protein.

Contrast sensitivity shows potential for measuring visual function loss in early AMD

Green is a professor of biomedical engineering, ophthalmology, oncology, neurosurgery, materials science and engineering, and chemical and biomolecular engineering at the JHU School of Medicine.

In the first step of the research, Campochiaro and Green tested the visibility of the nanoparticles once they were in the eye by equipping them with a fluorescent protein gene. 

In this way, they could evaluate the location, amount, and duration of the gene expression that was possible. Remarkably, after 8 months most of the cells were visible, marking their places in the cells.

In the next phase of the experiment, the investigators loaded the nanoparticles with a gene for VEGF. This worked also. 

One month after the injection, abnormal blood vessels developed under and in the retinas of each of the 30 rats in the study, and at the 2- and 5-month evaluations, the blood vessels were more extensive as in untreated chronic AMD, they reported. These results indicate the durability of the genes in the cells.

Characterizing localized retinal layer changes in AMD

The next step was the test of the feasibility of delivery of a therapeutic to the cells to treat the disease in genetically engineered mice in which a form of 

was developed that is similar to the human form.

In the mouse model, Campochiaro and Green reported that there was a 60% reduction in the abnormal blood vessels compared to the control mice, and they reported seeing the same effect again 35 days later.

One potential benefit of this method of treatment is reduction of the number of times patients must return to clinics for reinjections of anti-vascular endothelial growth factor (VEGF) drugs, and a second one is that visual deterioration may be prevented. Jordan described these results as “extremely promising.” 


1. Johns Hopkins Medicine. Scientists use nanoparticle-delivered gene therapy to inhibit blinding eye disease in rodents. 

. July 7, 2020. sciencedaily.com/releases/2020/07/200707113210.htm

Articles

Investigators find that nanoparticles deliver gene therapy successfully in mice, rats.

Exploring novel gene therapy approaches to treat ocular disease


Meibomian gland disease (MGD) is a chronic, progressive condition that benefits from early treatment.

However, it is not always easy to convince early-stage, minimally symptomatic or symptomatic patients that their MGD should be treated.

These patients may not be fully “bought in” to the idea of having MGD, or the disease is affecting them so little that they can’t justify the cost of an in-office treatment like thermal pulsation therapy (LipiFlow, Johnson & Johnson Vision).

Making dry eye manageable for patients working from home

It is not unusual, therefore, for patients to decline or say they will “think about it.”

Our job, as medical professionals, is not to take this personally—and not to accept that it is a final answer, either.

As the disease progresses, such patients may become more symptomatic or more troubled by fluctuating vision, especially if progression is compounded by poor compliance with topical therapies and/or at-home measures such as warm compresses, lid scrubs, and oral omega-3 fatty acid supplementation.

When these patients return for a yearly check-in, they may be ready to hear the message differently.

It is important for eyecare professionals to re-recommend thermal pulsation (or any other out-of-pocket treatment) without judgment. Don’t put patients on the defensive by reminding them that they didn’t follow your previous advice.

I always focus on the objective data and the documented symptomology, presenting specific diagnostic evidence to help patients understand that their disease is advancing.


Caring for dry eye patients through the coronavirus pandemic

For example, I might say, “Last year you were using artificial tears twice a day, and it has increased to about six times a day now. That means your eyes are bothering you more. Is that correct?”

Or I might show them where I see more dropout of the meibomian glands on the dynamic meibomian imaging than I did at their last visit (

We also let patients know that the price for a thermal pulsation procedure has come down in the past 18 months—which is unusual enough in health care that it is always remarked upon.

I explain that the manufacturer reduced the price of the activators and we are happy to pass that savings on to patients. Therefore, if price was a barrier in the past, perhaps it will be less of one now.

I’m careful to reinforce appropriate expectations, by making it clear that while I think the thermal pulsation procedure will be helpful, it is not a miracle cure nor a one-time treatment.It may or may not make an immediate difference in symptoms, and it will need to be repeated in the future.

Being consistent in recommending a treatment that I believe is beneficial for MGD is a good way to recapture patients who might not have been ready for a treatment in the past, but who can still benefit now.


Dr. Matossian is the founder and medical director of Matossian Eye Associates, Pennsylvania and New Jersey; adjunct clinical instructor at Temple University School of Medicine, Philadelphia.

It's not always easy to convince early-stage, minimally symptomatic or symptomatic patients that their MGD should be treated. Cynthia Matossian, MD, FACS, explains why ophthalmologists shouldn't take this personally and how not to accept their denial as a final answer. 

When at first you don’t succeed with MGD patients, keep trying

Reviewed by Richard B. Rosen, MD, DSC (HON)

Medical robots are revolutionizing medicine. Their applications can facilitate superhuman dexterity, enabling the performance of surgical steps otherwise considered impossible and automating repetitive tasks.

The benefits include high positional stability, precision, and accuracy along the x-, y-, and z-axes, removal of time constraints on subretinal and intraretinal drug delivery, and reduction of surgeon fatigue, according to Richard B. Rosen, MD, DSC(HON), of the New York Eye and Ear Infirmary of Mount Sinai in New York, New York.



Robotic technology in surgery: Surgeon's eye of the future

The robotic approaches being developed in ophthalmology include assistive handheld devices, such as the steady-hand stabilizer (Johns Hopkins Group); a comanipulation strategy to stabilize the surgeon’s movement (University of California, Los Angeles); and telemanipulation, which uses a separate robotic manipulator operated by the surgeon (Einhoven Group).

Rosen presented study findings that showed the advantages of robotics over manual procedures during retinal surgery. 

The study was conducted by his associates, Reza Ladha, MD, of the Department of Ophthalmology at the Centre Hospitalier Universitaire (CHU) Saint-Pierre and CHU Brugmann in Brussels, Belgium, and Marc D. de Smet, MD, of Microinvasive Ocular Surgery Center in Lausanne, Switzerland, and an employee of Preceyes in Eindhoven, the Netherlands. 

The investigators used the Preceyes surgical robot with Zeiss Microscopy with integrated optical coherence tomography.

The robot filters tremors to under 10 µm, which is 10 times better than the human performance. The arm of the robot permits intuitive motion with positional stability and memory and allows exchange of instruments, Rosen said.

When the investigators compared the accuracy and precision of the robotic and manual performances, improvement with the robot was markedly greater. Rosen showed that the robot improves precision and accuracy by at least an order of magnitude. 

Improving surgical safety, efficiency, and outcomes for patients


The manual static task performed by an experienced surgeon with minimal tremors of about 100 µm, with additional microjerks reaching 200 µm, became more intense the longer the surgeon remained static.

Other research also supports the use of robotics in ophthalmology. In an Eyesi simulator experiment, retinal injuries were decreased substantially using the robot compared with manual peeling.

In addition, a simulation study looked at manual and robot bleb creation, with the goal of elevating a retinal membrane and avoiding reflux. 



The manual injection created a great deal of reflux and an enlarging bubble of fluid on the membrane’s surface compared with the robotic injection, which formed no bubble.

The investigators also performed subretinal injections in a porcine eye manually and with robotic assistance. 

Rosen reported a 40% success rate of bleb creation with the manual procedure, with leakage in all cases during injection and when the needle was withdrawn; all cases were considered failures. 

3D cataract surgery: Keeping the eye in focus


In contrast, the robotic-assisted technique had a 100% success rate in bleb creation; there was leakage in 20% of cases when the needle was withdrawn, considered an 80% success rate.

“Bleb generation with robotic assistance was more precise and more consistent. Robotic assistance prevented motion and leakage during injection,” Rosen said. “Static manual subretinal positioning showed repeated contact with the underlying retinal pigment epithelium.”

Based on the above results, the investigators noted that robotic assistance removes the time constraints of delivery and allows high-precision positioning for controlled subretinal drug delivery.

“Robotic assistance controls tremor, reduces fatigue, and helps avoid inadvertent injury in tight spaces,” they concluded. “Robotic-assisted ocular surgery shows promise for advancing the surgeon’s ability to perform more complex maneuvers necessary for the next generation of retinal interventions."



Rosen has no financial interest in this subject matter.

Robotic-assisted procedures are proving more precise in every way when compared with manual procedures: automated assistance controls tremor, reduces fatigue, and helps avoid inadvertent injury. 


Robotics: Allowing surgeons to perform the seemingly impossible


The American Medical Association (AMA) this week voiced its support for provisions in proposed Continuing Resolution legislation in Congress that would offer relief to financially strapped physician practices.

According to a statement from the office of House Speaker Nancy Pelosi, the House of Representatives is expected to vote this week on a continuing resolution to keep the government funded through Dec. 11.

“The Continuing Resolution introduced today will avert a catastrophic shutdown in the middle of the ongoing pandemic, wildfires and hurricanes, and keep government open until Dec. 11, when we plan to have bipartisan legislation to fund the government for this fiscal year,” Pelosi said in a statement.

The Continuing Resolution includes provisions that would benefit physician practices feeling the financial pinch amid the pandemic.

According to a statement from the AMA, revisions to the Medicare Accelerated and Advance Payments program (AAP) included in the resolution will help keep doors open during the pandemic and continue to offer patients access at this time.

“Upon passage of the Continuing Resolution, patients should know that their physician is more likely to weather the pandemic’s economic challenges,” AMA President Susan A. Bailey, MD, said in a statement. “Congress recognized the danger, and rightfully modified the program so physicians can keep seeing patients.”

According to the release, Centers for Medicare & Medicaid Services worked quickly in the spring to provide financial assistance to physicians, which proved to be a lifeline for many practices.

The AMA also noted in its release that it also appreciated that the CARES Act postponed the start of recoupment for the AAP until 120 days after initial payment and allows up to 210 days for repayment for physicians.

There have been some concerns from physicians regarding their ability to repay the money during the economic conditions amid the pandemic.

The AMA release noted that earlier this year, surveys showed that from March to May revenues in physician offices were down at least 50 percent. As practices began reopening, some physicians were able to recoup some of the loss but not all due to reduced visits and procedures.

Moreover, the AMA noted in its release that the repayment terms are difficult to achieve. According to those terms, physicians would have all of their Medicare claims withheld to repay the loans on a short timeline. After a few months, any outstanding balances a physician might have would be subjected to a 10.25 percent interest rate.

According to the release, the Continuing Resolution would postpone the recoupment of disbursed funds until 1 year after the advance payment has been issued to a physician practice. The balance would be due by September 2022.

The resolution also would reduce the per claim recoupment amount from 100 percent to 25 percent for the first 11 months and the 50 percent of claims withheld for an additional six months. If not repaid in full, the interest rate kicks in. That interest rate also would be lowered from 10.25 percent to 4 percent.

“Members of Congress and the Administration have settled on a bipartisan response to the economic sword hanging over physician practices. This relief will be felt across the county as physicians will be able to continue providing health care during the pandemic,” Bailey concluded in the statement.

If approved in the House, the proposal would then go to the Senate for a vote. 

The American Medical Association is expressing its support for provisions in proposed Continuing Resolution legislation in Congress that could offer relief to financially strapped physician practices. 

AMA supports House plan to ease Medicare loan repayment terms

In this fourth installment on "2020 vision," pharmaceutical representatives share their outlook on what lies ahead for glaucoma innovations within the ophthalmic space. 

Featured: Chris Adams, Diopter Corp (CEO); Daria Lemann-Blumenthal, BELKIN Laser Ltd (CEO); Victor Chan, MB, MS, director of U.S. Surgical Device Commercial Marketing (Santen, Inc)
Ramin Valian, vice president of International Glaucoma, Reimbursement and Pipeline (Allergan).



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2020 vision: What is the future of ophthalmology?



2020 vision: The future of ophthalmology (Part II)



2020 vision: The future of ophthalmology (Part III) 

Videos

In this fourth installment on "2020 vision," pharmaceutical representatives share their outlook on what lies ahead for glaucoma innovations within the ophthalmic space.  

2020 vision: The future of ophthalmology (Part IV)

Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.


Results of an email survey sent to the Glaucoma Research Foundation (GRF) Ambassadors when most states were poised to ease 

 restrictions showed that only three-fourths of the respondents had a plan in place for reopening their offices after stay-at-home orders were lifted.

Judging from write-in responses, whether or not the glaucoma specialists had developed strategies for returning to practice, they were interested in having colleagues share ideas for establishing safety and for optimizing practice efficiency and patient care delivery. They were also keen to receive post 

 patient education and support materials from GRF.

These topics and more were addressed in a virtual GRF Ambassador Round Table on managing a 

COVID-19 safety challenges accelerating welcome changes

​ 

Held on May 8, the discussion was moderated by Andrew Prince, MD, of Glaucoma Consultants of Greater New York & New Jersey, and Andrew Iwach, MD, of Glaucoma Center of San Francisco, and included input from several GRF Ambassadors that showed the clinicians were meeting the new challenges with different approaches; in part, these reflect variations in practice settings.

Recognizing that the pandemic situation will be evolving and that ideas about best practices are likely to change based on actual experience and changing circumstances, the group looked forward to reconvening to share their practical insights and take away new ideas.


Once stay-at-home orders were issued in California, only patients needing emergency care or a postoperative follow-up visit were being seen at the Glaucoma Center of San Francisco. 

In planning for reopening, staff had to review charts to identify patients who should be given priority for an appointment, according to Iwach.

Patients who have an upcoming visit are being contacted by phone and are being screened for 

 symptoms and informed about new processes in the office. The latter include requirements to wear a mask and enter alone unless they need to be accompanied by someone for language or other reasons.



A screening station has been set up at the entrance to the building where patients are checked for fever and 

 symptoms, asked to clean their hands with a hand sanitizer, and given a mask if they did not bring one. 

Changes were made in the office, including removal of magazines, removal and rearrangement of furniture in the waiting area to create proper social distancing, and installation of plastic shields at the front desks.

Iwach and his associate, Terri-Diann Pickering, MD, identified restaurant supply companies and neighborhood hardware stores as good sources for acquiring protective equipment, including plastic shields, hand sanitizers, gloves, and masks.

Prince mentioned that individuals with an Amazon business account can register as a health care professional; then, they will be put on the top of a queue for getting supplies. 

He also noted that in his practice, a solution containing 70% ethanol with hydrogen peroxide and glycerin that comes in large spray bottles is being used with paper towels for surface disinfection and offers a less expensive alternative to disinfectant wipes.



Transitioning back to ophthalmic care during a pandemic

Practices differed in their use of gloves for staff versus frequent hand washing and sanitizing, but all participants agreed that it was critical for patients to witness attention being given to hygiene.

Minimizing patient time in the office was a universal goal. In general, patients are undergoing necessary testing in the office. Oluwatosin Smith, MD, of Glaucoma Associates of Texas, said her practice is looking at establishing a dedicated center for glaucoma testing that would be separate from the rest of the clinic and might be opened for extended hours to meet the pent-up demand for services.

In-office physician–patient interaction is being limited. Patients are mostly being contacted following their visit once the provider has a chance to review the results from the diagnostic evaluations. 

Depending on the need for follow-up, the results may be discussed over the phone or patients may be offered a telehealth or subsequent in-office visit.



Capabilities of telemedicine for ophthalmologists during a pandemic: Part I


The participants agreed that home monitoring of IOP using a self-tonometer suffers from suboptimal accuracy. 

A few have reduced the use of Goldmann applanation tonometry except when they are not able to get an accurate or reliable measurement with other tonometers that are noncontact or involve minimal time up close with the patient.

Davinder Grover, MD, MPH, of Glaucoma Associates of Texas, said that his group is using a noncontact device to measure corneal-compensated IOP in most patients, but a Tono-Pen is used to check IOP of postsurgical patients during the first month of follow-up.

Visual field testing presents a particular concern, given the special care that needs to be taken to avoid damaging the perimeter bowl. Participants felt that guidance on disinfection from the manufacturer lacked clarity, and many were exploring alternative methods for checking visual fields.

Both Grover and Iwach mentioned that their practices are pursuing other methods of perimetry that can be performed with a low risk to the patient, such as virtual reality goggle-type visual field testing.



Putting to practice retina innovations amid a pandemic

Robert Feldman, MD, of the Robert Cizik Eye Clinic, Houston, Texas, said that visual field testing at his practice has been put on hold while the potential to use an ultraviolet (UV)-C lamp for sanitization is being investigated. He noted, however, that the perimeter manufacturer cautioned that UV-C light could damage the equipment.

Prince said that an air purifier was installed in his practice’s testing room.

“While there is no direct evidence yet that filtration works to reduce transmission of the novel coronavirus, it can be assumed from what we know of similar viruses that air purifiers might help in some situations,” he said.

Prince added that, theoretically, if an air purifier removes or reduces the viral load from the air, the potential for exposure is lessened.

“The novel coronavirus itself is 0.125 microns, but the droplets it travels in when people cough, talk, or breathe are around 1 μm,” he said. “That is a size easily captured by air purifiers with HEPA filters.”



In the GRF Ambassador survey, the majority of respondents indicated that they had been using a telemedicine approach to some extent.

Ambassadors participating in the discussion agreed that telemedicine has limitations for following patients with glaucoma.

Certain patient queries can be handled by phone, and a video visit can be helpful for reviewing medication use or for checking whether a red eye in a surgically treated patient is worrisome. 

Patients gain reassurance knowing that a physician has looked at their red eye, and the interaction itself can be a boost for patients who are socially isolated during the pandemic, Iwach said.



The eyes offer conjunctival clue to COVID-19


Steven Vold, MD, in private practice at Vold Vision in Fayetteville, Arkansas, noted that because of the conducive physical setting of his office building, his practice created a “curbside clinic” where patients could be quickly checked for possible progression of their glaucoma.

“We know that compliance with glaucoma medication is an issue, and the concern when patients are not being seen is that some who have moderate-to-advanced glaucoma could be having asymptomatic worsening,” Vold said.

In Vold’s “clinic,” patients remain in their cars and go from station to station for a “visit” that is completed within 5 to 10 minutes. 

After gathering insurance information and then a history, vision is tested with a device like that used at state motor vehicle departments, IOP is measured with a rebound tonometer, and anterior and posterior segment photographs are taken using a retinal camera through a 3-mm pupil.

Patients are contacted by a physician later in the day.

“I am not saying that it is ideal and I am not advocating this approach as a standard of care,” Vold said. “But I can say we have picked up numerous disc hemorrhages and elevated IOPs, and I think we have actually saved vision for some patients.”



Emerging opportunities — and risks — with telehealth in a pandemic



He added that the service has also been a practice builder. Patients who have seen its availability on the practice’s website have traveled as far as 1000 miles to get access to in-person care.

The encounter is charged as a telehealth visit. Before offering the service, the plan was reviewed with the Arkansas Department of Health and Arkansas State Medical Board.


The GRF Ambassadors’ focus is on patient education, and some of the write-in responses on the GRF Ambassadors survey indicated interest in materials that would give patients confidence about the safety of in-office visits and inform them about new processes.

The physicians continue to do their part.

Vold said that his practice has created some videos with those goals in mind, and Smith noted that she is currently working with the Cure Glaucoma Foundation to develop patient information.

Thomas Brunner, president and CEO of GRF, said that GRF is also collaborating with this effort to inform and educate patients.

“Starting in early April with financial support from Industry, GRF began hosting a number of patient webinars and we recently launched a new video series that includes steps doctors are taking to ensure the safety of their patients.” Brunner added. “GRF can play a unique role in supporting both doctors and patients during this extraordinary time.” 


Vold has no financial disclosures related to this content.

Glaucoma Research Foundation (GRF) Ambassadors webinar provides platform for idea-sharing by ophthalmologists

Pearls for practicing in the COVID-19 era

The most rigorous data in evidence-based medicine is considered to be that generated by prospective, randomized, controlled trials (RCTs). 

RCTs are essential for evaluating the therapeutic impact of a drug or device while eliminating potential confounding factors. 

However, there are many situations in which these gold standard clinical trials are not practical or cost effective.



Clinical trial outcomes for macular edema don’t translate to ‘real-world’ settings

RCTs evaluate outcomes for very tightly defined groups of patients with highly standardized care and optimal adherence and follow-up. 

In the real world, however, patients present with a variety of underlying systemic conditions, prior surgery, and adherence patterns that muddy the picture. This is where retrospective, observational studies can help to fill the knowledge gap with real-world evidence (RWE).

RWE can help to answer key clinical questions, such as how a treatment works in patients who are already on other medications, and whether switching to or adding a new pharmaceutical agent would be more beneficial. 

Real-world studies can demonstrate how a new 

 therapy compares with the prostaglandin analogues (PGAs) that most clinicians rely on for first-line therapy, rather than with timolol, the typical control used in FDA studies. 

In cardiology, a major ongoing RWE study, the ADAPTABLE trial (NCT02697916), is trying to settle the debate over whether patients with coronary artery disease do better on low- or high-dose aspirin.

Developing a new therapy: Where do we go from here?


Increasingly, RWE researchers are looking at big data for answers. Very large data registries permit analysis of records from representative patient populations that are orders of magnitude larger than the number of subjects typically found in a phase 3 clinical trial.

Verana Health, through our partnership with the American Academy of Ophthalmology, is actively engaged in curating and analyzing data from the IRIS Registry (Intelligent Research in Sight) to better inform clinical practice in ophthalmology. 

The IRIS Registry is the largest specialty clinical database in medicine, with 343 million patient visits and billions of data points reported by more than 15,000 ophthalmologists through their electronic health records (EHR) systems. 

Large registries like this offer the opportunity to gather RWE about clinical outcomes. They facilitate research on questions that are critical to patient care but may be less likely to garner industry support such as head-to-head comparisons of new and long-established treatments.



IRIS Registry study: Overall anti-VEGF injection intervals for wet AMD similar at 1, 2 years of treatment


Large registry studies are relatively new but have already led to changes in ophthalmic practice. 

For example, a retrospective analysis of all procedures in the Swedish national cataract registry over a multi-year period revealed that intracameral antibiotics were an important factor in reducing the rate of endophthalmitis.

 

This led to a prospective European study of intracameral antibiotics

 and widespread adoption of this method of infection prophylaxis in Europe. A large health maintenance organization (HMO) in the United States also reached similar conclusion about the value of injected antibiotics in cataract surgery after reviewing a large data set from its own EHR system.

Another national registry helped to establish corneal collagen cross-linking as the standard of care for keratoconus. 





In this case, analysis of healthcare resource utilization in the Netherlands before and after the introduction of crosslinking showed that the procedure was associated with a 25% reduction in corneal transplantation over three years.

We have been able to use the IRIS Registry data to evaluate real-world anti-VEGF injection intervals in 56,672 treatment-naïve patients with 

 

In this study, the authors found that the mean number of injections per eye was approximately five per year.

By the end of year 1, approximately 40% of eyes continually treated with anti-VEGF medications needed injections more frequently than every 8 weeks, including 17%-18% who still needed monthly injections.

In another retrospective review of IRIS Registry data for 12.5 million patients seen by an eye care provider in 2017, researchers evaluated the relationship between smoking and IOP.

 

After adjusting for many factors, including age and glaucoma diagnosis, smokers (both current and those with a history of smoking) had higher mean IOP than those who had never smoked. 

In fact, smoking was the most important predictor of IOP after the glaucoma diagnosis (

IOP homeostasis in glaucoma: Looking below the surface


The ability to access large amounts of information to improve medicine is very exciting. But large data sets can be quite challenging to interpret. Imagine a spreadsheet with billions of rows and columns. 

No human can realistically check it over for errors; sophisticated algorithms are needed to catch and remove errors in a systematic way. The raw data must be cleaned, harmonized, and structured in such a way that it can be used for clinical research.

To better understand this, consider something as simple as visual acuity (VA)—an important outcome measure in ophthalmic studies. 

Data comes into the IRIS Registry every day from thousands of doctors using more than 50 different EHR platforms, each of which collects VA in slightly different fields or formats.



Apps now online to aid patients with visual impairment

VA may have been measured using a Snellen or ETDRS (Early Treatment Diabetic Retinopathy Study) chart, autorefraction, or a pinhole test. The patient may have been tested with or without correction, monocularly or binocularly. 

All of that VA data needs to be harmonized so that “20/20” has the same meaning across millions of records.

At Verana, we are using machine-learning techniques to refine algorithms that characterize important information from “unstructured” data, such as free text and images. 

Imaging is very important in ophthalmology, so the ability to develop algorithms that can mine images for precalculated measurements such as retinal nerve fiber layer thickness, as well as pathological features (eg, drusen) is highly relevant for future research.



In fact, real-world data from large registries opens up many new avenues for clinical research and the advancement of medicine. 

The sheer volume of patients offers a chance to drill down into specific subgroups that are underrepresented in clinical trials and to better understand how a disease process or treatment response might vary by gender, race or ethnicity.

We are also passionate about the opportunity to use RWE from the IRIS Registry and other large registries to develop more personalized patient care. 



Pearls to educate patients about ocular telemedicine options



Currently, a new glaucoma patient is typically treated first with a prostaglandin analog—the best available treatment, based on the literature. 

But what if we had a robust algorithm that could take into account not just the basic diagnosis, but age, ethnicity, gender, and comorbidities, to identify the best treatment paradigm for that individual patient? Ironically, big data has the power to change how we approach small, daily decisions.

And as large as these registries are, there are opportunities to deepen them further through data linking. If we link records from pharmacy prescription databases or serum testing laboratories to the IRIS Registry data, we could get a much clearer picture of diabetic patients’ glycemic control, and potentially be able to evaluate how glycated hemoglobin levels or metformin usage correlate with diabetic retinopathy changes.

We now have the ability to access large volumes of real-world data from very broad patient populations. The possibilities for using that data to improve patient care and drive scientific insights are limitless. 


Roe is chief medical officer of Verana Health. A cardiologist by training, he spent 20 years at Duke University and as an investigator at the Duke Clinical Research Institute in Durham, North Carolina, where he focused on research initiatives leveraging real-world data. He was a principal investigator in the ADAPTABLE trial.


Leng is a practicing retinal specialist, assistant professor of ophthalmology and director of Clinical and Translational Research at Stanford University Medical School in Stanford, California. He has a research background in image analysis, machine learning algorithms, and clinical trial design and execution. He serves as a medical adviser to Verana Health.


Johnston A, Jones WS, Hernandez AF. The ADAPTABLE trial and aspirin dosing in secondary prevention for patients with coronary artery disease. 

. 2016;18(8):81. doi:10.1007/s11886-016-0749-2

Friling E, Lundström M, Stenevi U, Montan P. Six-year incidence of endophthalmitis after cataract surgery: Swedish national study. 

. 2013;39(1):15-21. doi:10.1016/j.jcrs.2012.10.037

Endophthalmitis Study Group, European Society of Cataract and Refractive Surgeons. Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. 

. 2007;33(6):978-988. doi:10.1016/j.jcrs.2007.02.032

Herrington LJ, Shorstein NH, Paschal JR, et al. Comparative effectiveness of antibiotic prophylaxis in cataract surgery. 

. 2016;123(2):287-294. doi:10.1016/j.ophtha.2015.08.039

Godefrooij DA, Gans R, Imhof SM, Wisse RP. Nationwide reduction in the number of corneal transplantations for keratoconus following the implementation of cross-linking. 

. 2016;94(7):675-678. doi:10.1111/aos.13095

MacCumber M, Yu, JS, Sagkriotis A, et al. Injection intervals in treatment-naïve neovascular AMD patients who received anti-VEGF agents: an analysis of the IRIS Registry. Paper presented at: American Academy of Ophthalmology Annual Meeting October 12-15, 2019; San Francisco. 2019: PO471.

Lee CS, Owen JP, Yanagihara RT, et al. Smoking is associated with higher intraocular pressure regardless of glaucoma.

. 2020;3(4)253-261. doi: 10.1016/j.ogla.2020.03.008

Evidence-based medicine can lead to personalized care, better results for patients

Big data drives opportunity for real-world evidence


This article was reviewed by Tracy W. Krick, MD



When the postoperative rates of endophthalmitis between brands and types of topical antibiotics are compared, no single antibiotic has clear superiority over another. 

This finding may lead to an opportunity for patients to cut costs by using less expensive antibiotics after 

Most cataract surgeons prescribe perioperative topical antibiotics to prevent infections after procedures. Numerous options are available, and their costs also vary widely. 

Battling endophthalmitis: New bugs, new technologies, new drugs

Interestingly, there is little information regarding the rates of endophthalmitis infections associated with the various topical antibiotics.

In light of that, Tracy W. Krick, MD, and associates compared the postoperative rates of endophthalmitis among patients who had been treated with different types of antibiotics after 

The investigators also sought to determine prescribing patterns and the costs associated with the topical antibiotics.

This study was a cross-sectional analysis of Medicare patients who had Part D coverage and underwent cataract surgery in 2016. The investigators analyzed the rates of endophthalmitis within 90 days after surgery.

The results showed that endophthalmitis rates were strikingly similar in almost 600,000 patients using different types of topical antibiotics: 0.10% with fluoroquinolones, including ofloxacin, moxifloxacin, and besifloxacin, which accounted for about 35%, 15%, and 10.7%, respectively, of patients; 0.09% with polymyxins; and 0.12% with aminoglycosides, Krick reported.

Endophthalmitis detection by whole genome sequencing and qPCR

“The rates of endophthalmitis were low regardless of the type of topical antibiotics prescribed. Overall, there was no clinically significant difference in the rates of endophthalmitis among patients prescribed different classes of antibiotics,” she said.

A number of options may offer major cost savings, positive results for patients.

Research: Similar endophthalmitis rates for generic, branded topical antibiotics

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