At the American Academy of Ophthalmology annual meeting, Marc Berger, COO of Verana Health, discussed the VeraQ quality measures dashboard for the IRIS registry report. It is anticipated to launch in 2022.

VeraQ is AI-enhanced health data engine that utilizes the Axon, AQUA and IRIS registries to report on unfiltered healthcare data. Additionally, it enable compliance with Merit-based Incetive Payment System (MIPS), meeting care quality measurements required by the Centers for Medicare and Medicaid Services (CMS). It also helps to identify patients who qualify for a clinical trial.

 Very excited to be here with everyone. In terms of the IRIS registry, I think this is the first year where Verana actually has been ingesting and curating data directly from participating practices.

So we are working end-to-end processing of EHR data, where we're partnering with practices and our technology on our platform, the VeraQ platform, brings in the data, and then organizes in a way which which more effectively processes the data and gives us a better sense of for analyzing this information. And in turn, we're able to then provide better insights, more accurate calculations for MIPS specifically, but then they're also use cases that are going to be developed on top of that.

So our use cases are developing particularly around the MIPS calculations and our quality measures. So participating practice will have better and more accurate information, accurate data, be able to run their practices more effectively, and ultimately treat patients with better care.

And that's really the, the keystone of what we're accomplishing over these past two years in our partnership with the AAO. The quality measures database is now being powered by our VeraQ platform. And this platform, like we discussed is more effective from a technological perspective. We've got proprietary algorithms using the data that's provided by participating practices. We're able to provide more accurate and more effective data sets which can then lead to better calculations for MIPS and better quality reporting, just giving doctors and the administrators as part of these practices, better information within their practices.

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Verana Health showcases the VeraQ quality measures dashboard  for the IRIS registry report at AAO 2021.

Verana Health unveils new quality measures dashboard at AAO 2021

Ocular Therapeutix Inc. today announced positive topline results from its Phase 2 clinical trial of OTX-DED (dexamethasone intracanalicular ophthalmic insert) for the short-term treatment of dry eye disease.

The Phase 2 clinical trial is a U.S.-based, randomly assigned, double-masked, vehicle-controlled, multi-center trial evaluating two different formulations of OTX-DED (dexamethasone intracanalicular ophthalmic insert) aimed to enroll approximately 150 subjects with dry eye disease.

According to the company, this trial was designed to assess the safety and efficacy of two formulations of OTX-DED for the short-term treatment of signs and symptoms of dry eye disease by evaluating the primary endpoint of bulbar conjunctival hyperemia and secondary endpoints of eye dryness symptoms using the visual analog scale (VAS), among other methodologies, in each case in comparison with a vehicle hydrogel insert.

The clinical trial was not powered for statistical significance.

The clinical trial enrolled 166 subjects in the modified intent-to-treat (ITT) population which included subjects who were randomized and had the OTX-DED insert placed in the study eye. The clinical trial achieved its pre-specified primary endpoint, demonstrating a statistically significant change of bulbar conjunctival hyperemia from baseline to day 15 compared to vehicle hydrogel using a central reading photographic assessment in the modified ITT population.

Change from baseline using the CCLRU Grading scale (0-4) was -0.51 for the OTX-DED 0.2 mg group (n=55), -0.43 for the OTX-DED 0.3 mg group (n=56), and -0.21 for the vehicle hydrogel insert group (n=55). These differences were statistically significant compared with the vehicle hydrogel for both the OTX-DED 0.2 mg group (p=.004) and the OTX-DED 0.3 mg group (p=.028). Sensitivity analysis using different methods of imputation including last observation carry forward (LOCF), Markov Chain Monte Carlo (MCMC), and fully conditional specification (FCS) were consistent with the primary analysis. Improvements from baseline were noted in the VAS dry eye symptoms for both OTX-DED 0.2 mg and OTX-DED 0.3 mg groups, but there was little separation between OTX-DED and the vehicle hydrogel insert. Other secondary endpoints are being evaluated.

OTX-DED inserts (both formulations) were observed to have a favorable safety profile and were generally well tolerated. There were two non-ocular serious adverse events, both in the vehicle hydrogel insert group, which were evaluated to be not related. There were no ocular serious adverse events. The most common ocular adverse events for subjects treated with OTX-DED were epiphora (lacrimation increase) (8.1%) and elevated intraocular pressure (IOP) (3.6%). All other ocular adverse events occurred in less than 1% of subjects. The most common non-ocular adverse event for subjects treated with OTX-DED was arthralgia (joint pain) which was seen in 1.8% of subjects. All other non-ocular adverse events occurred in less than 1% of subjects.

Michael Goldstein, MD, MBA, president, ophthalmology and chief medical officer of Ocular Therapeutix, pointed out that the company was pleased with the results of the Phase 2 clinical trial.

“Results of the trial showed statistically significant improvement in bulbar conjunctival hyperemia in patients with dry eye disease for OTX-DED compared with the vehicle hydrogel control for both OTX-DED formulations,” he said in a statement. “In my clinical experience, many dry eye patients experience episodic flares of their signs and symptoms related primarily to inflammation.”

Goldstein noted that topical steroids are commonly used for the short-term treatment of dry eye but all steroid eye drops contain preservatives that can lead to ocular surface toxicities such as irritation, burning, and stinging and, when used more chronically, other adverse events such as elevated IOP or cataracts.

“OTX-DED is a new, investigational, physician-administered, preservative-free intracanalicular insert designed to deliver dexamethasone and offering the potential to provide a differentiated treatment,” he added.

Antony Mattessich, president and CEO of Ocular Therapeutix, pointed out that the company hopes to expand its presence beyond the surgical setting and into ophthalmology and optometric offices, which it believes represent an enormous new opportunity to provide customers with its buy-and-bill products.

“The recent approval of Dextenza for the treatment of ocular itching associated with allergic conjunctivitis is our first beachhead to achieving this and the potential to offer a second product like OTX-DED, represents another large, office-based product opportunity,” he concluded. “We look forward to advancing this program in 2022.”

Articles

Study shows statistically significant improvement for primary endpoint of bulbar conjunctival hyperemia for OTX-DED 0.2 mg and 0.3 mg formulations compared with vehicle hydrogel insert. 

Ocular Therapeutix announces topline results for phase 2 clinical trial of OTX-DED for short-term treatment of dry eye disease 

The Juvene modular, shape-changing fluid optic IOL from LensGen Inc. (Image courtesy of LensGen Inc.)

LensGen Inc. has received approval for an Investigational Device Exemption (IDE) from the U.S. Food and Drug Administration (FDA) to initiate a pivotal study of the company's Juvene IOL for patients with cataracts.

The Juvene IOL (LensGen Inc.) is a new modular, shape-changing, fluid optic IOL designed to behave like the natural crystalline lens. It is designed to permanently restore clear and continuous vision at all distances including near and intermediate. The lens is implanted using the same surgical techniques used with traditional intraocular lenses. 

"We are proud to achieve this significant milestone for the company, which allows us to move forward with the IDE pivotal trial with the ultimate goal of seeking premarket approval in the largest eye care market in the world," LensGen CEO Ramgopal Raosaid in a statement. "Achieving IDE approval of a novel device is a tremendous undertaking and enormous accomplishment for the company, and we are grateful to the FDA for their rigorous and insightful guidance throughout the process."

"Based on the Grail Study clinical data and my direct experience with surgery and observations of the patients implanted with Juvene IOL, LensGen technology has the potential to provide a significant new and superior option to our patients," said Eric Donnenfeld, MD, clinical professor in the Department of Ophthalmology at the New York University Grossman School of Medicine and Founding Partner of Ophthalmic Consultants of Long Island.

The Grail investigators, led by Donnenfeld, conducted an exploratory study of the Juvene IOL in which patients underwent small-incision cataract surgery followed by IOL implantation.

The primary outcomes evaluated were the best-corrected distance visual acuity (CDVA), distance-corrected intermediate VA (DCIVA), distance-corrected near (DCNVA), and defocus curves.

LensGen is currently in the processing of raising a Series B Financing expected to close in the first half of 2022.

Grail Study shows refractive stability of Juvene IOL

The approval will allow LensGen to move forward with the IDE pivotal trial with the ultimate goal of seeking premarket approval in the United States. 

LensGen receives IDE approval from FDA to start study of Juvene presbyopia-correcting IOL 

Elevated intraocular pressure (IOP) is the most significant risk factor for developing glaucoma and the only known risk factor that is currently treatable. In patients who already have glaucoma, reducing IOP slows the progression of the disease.1

I am primarily a cataract and refractive surgeon with a high-volume practice in Dothan, Alabama. People travel from far away for cataract surgery and are usually referred by optometrists. When we do the cataract procedures, we also have this 1 chance to improve their IOP.

When patients come in with early to moderate glaucoma, I combine laser with several minimally invasive glaucoma surgeries (MIGS). In over 90% of cases, I perform MicroPulse cyclophotocoagulation (CPC) as well as a canaloplasty and a trabecular meshwork (TM) bypass. In my experience, the effect of the combination is additive.

I use either iStent (Glaukos) or Hydrus (Ivantis) to allow aqueous fluid to bypass the TM and flow out. The canaloplasty, using the Omni Surgical System (Sight Sciences), dilates Schlemm canal and the collector channels to enhance the natural outflow system. The combination of TM bypass stents and canaloplasty with cataract extraction has been shown to be more effective at lowering IOP than the TM bypass alone with cataract extraction.2

I also do CPC procedures, and there are a lot of misconceptions about these treatments. Some think of CPC as an aggressive, end-stage procedure that can cause significant adverse effects and inflammation. A decade ago, CPC was seen as a last resort. Now that you do not have to use as much power, the procedure creates much less inflammation and the effect appears to be quite robust. I have not had issues with hypotony, and inflammation has only been an issue in very limited cases, such as a patient with uveitic glaucoma, and these cases were able to be controlled with topical steroids.

In more advanced glaucoma cases, when I am targeting a bigger reduction in IOP, I use the Cyclo G6 Laser (Iridex) with the continuous wave G-Probe delivery device (Iridex). The continuous wave laser energy is absorbed by melanin in the ciliary processes, and coagulative necrosis of the ciliary body reduces aqueous production. I have found the process to be effective and repeatable, but it involves tissue ablation and there can be more inflammation than with the MicroPulse CPC.

More commonly, for mild to moderate glaucoma, I use the MicroPulse P3 delivery device with the Cyclo G6 Laser to perform transscleral laser therapy (TLT). MicroPulse technology divides the laser beam into microsecond bursts that are interspersed with longer resting intervals. This allows the tissue to cool between pulses and reduces thermal buildup within the tissue targeted by the laser. MicroPulse lasers do not cause thermal necrosis.3,4 Instead, they create a stress response that induces a biological effect.4

In my opinion, MicroPulse TLT is an underutilized nonincisional treatment, although its use is increasing. Iridex reports that 180,000 patients have been treated with MicroPulse TLT in 80 countries. I have started using the procedure more often and earlier in the overall IOP reduction process. MicroPulse TLT is 60% to 80% successful at lowering IOP by at least 20%.5,6

For MicroPulse TLT treatment, I have increased my power setting from 2000 mW to 2500 mW and slowed the speed of the 3 sweeps I do across each hemisphere to deliver more power to the tissues. This is a manufacturer recommendation, and I find it to be more effective.

Using the recommended 31.3% duty cycle, I now treat each hemisphere for 60 to 80 seconds by doing 3 sweeps of 20 to 25 seconds each. I avoid about 30 degrees at the 3 o’clock and 9 o’clock position because there are long ciliary nerves there.

I am now using the revised MicroPulse P3 Probe. It is a little thinner and it is easier to position, especially in patients with deep set eyes. It has 2 plastic pieces—which look a little like bunny ears—that are placed on the limbus and help with alignment. It is very straightforward and quick.

I prefer to operate in an ambulatory surgery center, and I do the CPC laser in the preoperative area, after the patient has received a peribulbar block, while the operating room is being prepared. This has created a very efficient flow for us.

After the cataract extraction and the other MIGS treatments, the postoperative procedure is identical to my usual cataract postoperative regimen, which is generally an intracameral steroid and antibiotic and a nonsteroidal anti-inflammatory drop for 1 month. Slightly fewer than 5% of patients develop cystoid macular edema (CME). This includes all patients, even those with epiretinal membrane and diabetes, so the rate of CME doesn’t seem to be any different than the standard cataract populations in my hands.

There is a less than 10% risk of postoperative hyphema with canaloplasty and trabecular bypass shunts. One tip when doing shunts and stents is to leave the pressure somewhat higher at the end of surgery. It will reduce reflux into the anterior chamber. Now that I do this, targeting a maximum pressure of 25 mm Hg, my hyphema rate is probably between 2% and 4%.

After I perform the procedures, follow-up consultations are carried out by the patient’s referring doctor, which is sometimes hours away from my practice. This makes it especially important for us to use procedures that will not cause pressure spikes or leave the patient’s eyes inflamed.

Along with sending back patients who have quiet, unproblematic eyes, successful comanagement requires communication and education. Before the procedure, the referring doctor should know you do CPC laser and MIGS procedures. They can then begin prepping the patients, both through discussions and by initiating medication for patients with mild to moderate glaucoma, as insurance companies require patients be on medication before they have a trabecular bypass stent procedure.

While patients are having cataract surgery, we are really doing them a service if we also address glaucoma, which is a long-term threat to their vision. I support being proactive and using all 3 procedures together. In my experience, this has been very safe and effective, and over 60% of patients are off drops and at target IOP.

Heersink is an ophthalmologist with Eye Center South in Dothan, Alabama.

1. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. 

. 2002;120(10):1268-1279. doi:10.1001/archopht.120.10.1268

2. Heersink M, Dovich JA. Ab interno canaloplasty combined with trabecular bypass stenting in eyes with primary open-angle glaucoma. 

. 2019;13:1533-1542. doi:10.2147/OPTH.S215667

3. Yu AK, Merrill KD, Truong SN, Forward KM, Morse LS, Telander DG. The comparative histologic effects of subthreshold 532- and 810-nm diode micropulse laser on the retina. 

 2013;54(3):2216-2224. doi:10.1167/iovs.12-11382

4. Inagaki K, Shuo T, Katakura K, Ebihara N, Murakami A, Ohkoshi K. Sublethal photothermal stimulation with a micropulse laser induces heat shock protein expression in ARPE-19 cells. 

. 2015;2015:729792. doi:10.1155/2015/729792

5. Zaarour K, Abdelmassih Y, Arej N, Cherfan G, Tomey KF, Khoueir Z. Outcomes of micropulse transscleral cyclophotocoagulation in uncontrolled glaucoma patients. 

. 2019;28(3):270-275. doi:10.1097/IJG.0000000000001174

6. Subramaniam K, Price MO, Feng MT, Price FW Jr. Micropulse transscleral cyclophotocoagulation in keratoplasty eyes. 

. 2019;38(5):542-545. doi:10.1097/ICO.0000000000001897

According to Sebastian B. Heersink, surgeons can perform several procedures with cataract surgery.

Combining laser with MIGS  to impact intraocular pressure

More than 200 professional medical associations, spearheaded by the Medical Group Management Association, sent a letter to Capitol Hill, urging Congress for a

 3.75% payment adjustment for all services to the Physician Fee Schedule for Medicare for 2022.

According to a press release, the letter was co-signed by more than 200 professional medical associations, including the America Medical Association (AMA), American College of Physicians (ACP), and American Academy of Family Physicians (AAFP).

In the press release, MGMA noted the 3.75% adjustment for 2022 is necessary to provide stability and avoid disruptions to Medicare, especially as the pandemic continues to impact care.

Without the increase, MGMA argues that Medicare patients could lose timely access to essential health care services. A 3.75% adjustment was made for 2021, but it was only temporary, and will soon expire.

“Our organizations would welcome the opportunity to work with Congress to address long-term challenges associated with Medicare payment policy, especially the budget neutrality provision in the MPFS that has precipitated these steep cuts,” the letter stated.

To lend support to the issue, about 250 House members from both sides of the aisle signed a “Dear Colleague” letter (finalized October 2021) — spearheaded by Reps. Ami Bera, MD, D-Calif., and Larry Bucshon, MD, R-Ind., — calling on Congress strike these and other automatic Medicare payment cuts before the end of the year.

After CMS indicated it will allow the 2021 payment adjustment to expire at the end of the year, Bera and Bucshon ultimately introduced H.R. 6020, bipartisan legislation to extend the 3.75% update to the conversion factor for an additional year.

In the letter, the organizations urged Congress to address the cuts by extending the payment adjustment at least through the next year.

“Maintaining this level of funding will provide much-needed stability for physician and non-physician providers, as well as their patients, and provide an opportunity for renewed discussions regarding long-term systemic reforms in the New Year,” the letter added.

AMA President Gerald E. Harmon, MD, pointed out that as doctors continue to risk their health and face financial turbulence amid the pandemic, Congress is slated to allow a 10% Medicare cut to take effect.

“These cuts are unsustainable during normal times, and they are reckless during a public health emergency,” he said in a statement. “The result of congressional inaction is that Medicare patients are certain to experience reduced access to care.”

Harmon added in the statement that there is plenty of blame to go around for this situation.

More than 200 medical associations, including the American Medical Association and the Medical Group Management Association, have co-signed a letter seeking Congressional action on the issue before the end of the year. 

Groups lobby for 3.75% Physician Fee Schedule payment adjustment

Peter J. McDonnell, MD, shares some of many highlights from this year’s annual meeting of the American Academy of Ophthalmology in New Orleans.

Post-AAO 2021 takeaways from Dr. McDonnell

Well, Dr. McDonald, so great to see you again. I hope you've recovered from the Academy meeting this year in New Orleans,

Peter J. McDonald, OD, FAAO: Ms. Stevenson's … always a pleasure to see you. I heard people saw you with the marching band around the convention hall, but I didn't see you do that. But I heard you were really enjoying New Orleans.

: Well, it's great to be back. I just want to take a few minutes and check in with you and see what your impressions were. What the takeaways were that you brought back from this meeting?

 Well, my view: the American Academy of Ophthalmology is a great organization. It should be the model for all the other medical specialties with their professional organizations. They always do a great job with this meeting. They put on the biggest meeting of ophthalmologists in the world. The meetings cover everything.

You learn a lot about whatever is exciting and interesting to you based on your practice. Pandemic or not, the Academy did its usual great job this year to help educate our fellow ophthalmologists. There were medical students there and residents, and everybody by all reports had a great time. My congratulations to the Academy leadership for doing such a good job again this year.

 Absolutely. I know they had a lot of safety precautions in place. You had to be vaccinated to attend the in-person component of it. There was also a virtual component. Masks were required during the actual time they were in the convention center.

A lot of precautions were taken but I feel everybody had a really good time. A lot of good content was presented. Even starting from subspecialty day, I should say that, a lot of the different topics that were focused there and continuing into the main actual conference.

 Yeah. The subspecialty days are so super popular. They have been for decades, and under [CEO] David Parkes’ leadership at the Academy, they've just been growing and growing in interest in popularity. One of the fun features of the subspecialty days is that they reserve parts of the schedule for the breaking exciting news. Not things that were submitted 6 months ago to the Academy, but things that maybe article presentations about what's happened just within the last few weeks.

Despite the pandemic, there's been a lot of innovation this year in ophthalmology and recent FDA approvals of new drugs and new technologies for treating eye disease. There was a lot of good information at the Academy about some of these new products, and that engendered a lot of interest, whether it's front of the eye dry eye or back of the eye for retinal disease.

 Absolutely. I guess in talking to some of your fellow colleagues, what are some of the highlights that you've been hearing from fellow ophthalmologists from this year's meeting?

Well, I was smart enough to become a retina specialist. I'm a cornea person but my retina colleagues tell me there's tremendous interest in the just recently approved port delivery system (PDS) for delivering ranibizumab (Lucentis, Genentech).

During this pandemic, having these people come in every month or 8 weeks to get an intravitreal injection is quite a challenge— both on the patients and the doctors and the clinics. The newly FDA-approved delivery system allows the opportunity to dramatically reduce the number of visits and the frequency of injections for these patients.

I believe the launch of this device is going to be pretty soon and there was tremendous interest in learning about it. I think tremendous eagerness amongst our retina brothers and sisters to be able to begin to look at incorporating this into their practices and to see for which patients it works well and how well it's accepted amongst the patients with (age-related macular degeneration) AMD.

The new, recently approved super choroidal administration of triamcinolone (Bausch + Lomb, Clearside Biomedical) using these micro needles Xipere, is that name apparently of this which will again be launched in the new year. This is an interesting—also new—technology for retinal disease as for macular edema in the setting of uveitis. But instead of intravitreal injections, these are through the sclera into the super choral space.

This is a whole new thing for us ophthalmologists. There is a lot of going to be learning on how to do this. It'll be again interesting to see how this gets adopted. The approval is for macular edema in uveitis patients, but obviously there is the potential for triamcinolone to be helpful for other indications. I think this was an exciting topic in New Orleans. One that will be a very exciting topic coming into the new year in our meetings in 2022.

Then I'm a cornea external disease dry eye person. The newly approved this company called Oyster Point (Pharmaceuticals) and its nasal spray—this is worth learning about. This is the drug that's used to help reduce the craving for smoking and administered intra-nasally.

It improves dry eye in the FDA trials. This will be interesting because it's such a new route of administration, treating an eye problem with a nasal spray. It'll be interesting to see when this launches in the first quarter of next year, how this new way of administering medication for eye disease, [and] how readily it's accepted by both doctors and our dry eye patients.

Some very interesting new technologies. In each case, it's not so much a new drug. They're preexisting drugs but new ways of delivering the drug. Triamcinolone has been around forever. Ranibizumab for a long time. As I mentioned with the nasal spray, the active agent has been available for quite a while now for smoking cessation. It's about new routes of administration for new ophthalmic indication. It's exciting to see all these innovation despite the pandemic.

Peter J. McDonnell, MD, reflects on key takeaways from AAO 2021

As the nation moves into the winter, the Biden administration this week unveiled a six-pronged national strategy it says employs the same science-based approach that was used to successfully combat previous variants of COVID-19 earlier this year.

According to the administration, the plan will ensure the country is using every available tool to combat COVID-19 and save even more lives in the months ahead, while also keeping schools open and safe, and protecting the economy from lockdowns and damage.

The United States has come far in its fight against the virus and is more prepared than ever to deal with the challenges of COVID-19.

“We have the public health tools we need to continue to fight this virus without shutting down our schools and businesses,” the administration said in a statement.

The plan includes boosters for all adults, vaccinations to protect children and keep schools open, expanding free at-home testing for Americans, stronger public health protocols for safe international travel, protections in workplaces to keep the economy open, rapid response teams to battle rising cases, supplying treatment pills to prevent hospitalizations and deaths, a commitment to global vaccination efforts, and steps to ensure the nation is prepared for all scenarios.

“This variant is a cause for concern, not a cause for panic,” President Joe Biden said during a press briefing this week. “We have the best vaccine in the world, the best medicines, the best scientists and we’re learning more every single day — and we’ll fight this variant with scientific and knowledgeable actions and speed, not chaos and confusion.”

The medical community continues to lead the fight against COVID-19, and the head of the American Medical Association was optimistic about the administration’s plan.

Gerald E. Harmon, MD, president of the American Medical Association, said Biden’s plan will make communities—and the world—safer in the face of an evolving pandemic and confirmed cases of the Omicron variant.

“The education and outreach program to seniors will save lives by encouraging widespread acceptance of booster doses of the COVID-19 vaccines,” he said in a statement. “About half of eligible seniors have received a booster dose, and this multipronged approach should help move the needle further.”

Moreover, Harmon noted that the expanded approach for vaccinating children 5 and older will help protect kids and allow schools to stay open.

“This, combined with making at-home testing more widely accessible, will ease the anxiety facing many working families,” he said. “Physicians see a lot to like in this plan. We have rolled up our sleeves and will continue to play a pivotal role in safeguarding our patients and communities.”

Harmon added that the Omicron variant again reminds us that this is a worldwide pandemic.

“It will not end until all nations contribute to the widespread availability of vaccines,” he said. “The U.S. is taking the lead with 1.2 billion donated vaccines and we expect other countries will follow.”

Harmon also lauded the administration for its pledge to deliver 200 million more doses in the next 100 days and the AMA is encouraging the Biden Administration to continue to work on multiple fronts to vaccinate the globe.

According to the White House news release, Biden’s plan encourages people to get their booster shots. To increase these numbers, the administration will team with AARP to provide free rides to the shots for older Americans.

The plan would see Americans with private insurance receive a reimbursement for at-home tests, which can be difficult to find and are costly.

The president also is urging employers to provide paid time off to workers so they can receive their booster vaccine.

To slow the spread of the virus and its variants, the administration will require 

people traveling from other countries to the United States to provide a negative COVID-19 test

 taken within 24 hours before their departure.

AMA President Gerald E. Harmon, MD, said in a statement that President Joe Biden’s pandemic plan will make communities safer amid an evolving pandemic and confirmed cases of the Omicron variant. 

Biden unveils pandemic strategy, which receives AMA support

During the earliest stages of the COVID-19 pandemic, some patients with diabetic macular edema (DME) were reluctant to visit the office for therapy or monitoring. The risks of complications secondary to COVID-19 infection are elevated among patients with comorbidities such as diabetes. Further, the high burden of care associated with DME has led to undertreatment among real-world patients1—a dynamic almost certainly exacerbated by the aforementioned reluctance to visit the clinic. Given these facts, retina specialists should strive to optimize therapy that reduces exposure risk and burden while still providing excellent outcomes.

Patients with DME commonly undergo therapy with anti-VEGF agents, focal laser application, or steroids. Retina specialists need to weigh the benefits of each treatment option in light of the ongoing pandemic.

Patients with DME undergoing therapy with anti-VEGF agents may need to make frequent visits to the clinic to get effective outcomes, increasing the risk of exposure and causing inconvenience for those who are of working age. Data show that regardless of the anti-VEGF agent they choose, real-world patients have visual outcomes that are inferior to those of patients in randomized controlled trials.2 In the LUMINOUS trial (NCT01318941), patients who received at least 5 injections per year gained significantly more letters than those who received 4 or fewer injections per year (6.9 vs 0.5).3 These results were underscored by those of a later study by Pitcher et al, who found that patients with DME who received 7 injections gained 8.0 mean letters, whereas those who received less therapy gained only 3.7 letters (

In a tightly controlled clinical trial, patients return to the clinic for treatment according to the study protocol. However, real-world evidence demonstrates that patients who do not receive frequent treatment struggle to regain vision. Patients and clinicians who wish to avoid frequent office visits might turn to focal laser therapy for DME. Although focal laser is effective in some cases for treating DME, its inability to treat the surrounding tissue creates an environment in which extrafoveal fluid associated with DME resolves while DR remains active in the periphery.

If reducing treatment burden is part of what drives decision-making, then retina specialists may wish to explore steroid therapy. Pivotal trials for both the intravitreal fluocinolone acetonide implant 0.19 mg (Iluvien, Alimera Sciences)5 and the intravitreal dexamethasone implant 0.7 mg (Ozurdex, Allergan)6 showed that sustained-release steroid implants were superior to sham therapy for DME. Ozurdex, which was studied as a 6-month therapy, is approved for the treatment of DME in pseudophakic patients or in those who are scheduled for cataract surgery.7 Iluvien, which is designed to elute fluocinolone acetonide for approximately 36 months, is indicated for patients with DME who have previously been treated with a course of corticosteroids and did not have a clinically significant rise in IOP.8 Often clinicians will administer Iluvien after determining that the patient’s disease responds to corticosteroids, allowing for a longer duration of treatment—and, in the COVID-19 era, reduced risk of transmission in the retina clinic.

Clinicians may wish to consider moving Iluvien further up in their decision tree for the treatment of DME. In a 24-month interim analysis of the prospective, observational, real-world study PALADIN (NCT02424019), investigators found that treatment with Iluvien resulted in a mean visual improvement of 1 to 3 letters, improved central subfield thickness, and fewer DME treatments. Fifty-one percent of patients required no treatment or 1 treatment during the follow-up period and a majority of patients required no rescue treatment at 1 year.9 The case below illustrates how Iluvien therapy may result in no need for further treatment.

Among DME patients who struggle with follow-up appointments, Iluvien therapy may be more effective than anti-VEGF therapy at reducing the risk of vision-threatening complications of proliferative retinopathy. In a time-matched, consecutive series of the aggregated Vestrum database from January 2013 to February 2021, my research team and I found that patients with DME who had at least a 6-month break in follow-up progressed to proliferative diabetic retinopathy at rates of 1% and 10% for those undergoing Iluvien or anti-VEGF therapy, respectively.10 Also, new vitreous hemorrhage was present upon return in more patients undergoing anti-VEGF therapy (6%) compared with Iluvien therapy (< 1%).10

In light of these new data, it is important that clinicians give careful consideration and weigh the high treatment burden of frequent anti-VEGF therapy against the benefits of 36-month sustained treatment with Iluvien. Increasing our field’s use of Iluvien in the treatment of DME may satisfy our patients’ request for fewer office visits while also maximizing patient therapy.

A 73-year-old woman with a history of vitrectomy and membrane peel presented in 2017 with 20/50 VA and DME (

). The patient was lost to follow-up and returned in 6 months with 20/60 VA and worsened edema. I elected to administer Ozurdex, and she returned in 1 month with 20/40 VA and improved edema (

Five months after she received the Ozurdex, her DME had recurred and VA dipped to 20/80 (

). Given her previous positive functional and anatomic response to steroid therapy, I proceeded with Iluvien administration. Her IOP at the time of the Iluvien administration was 18, with a cup to disc ratio of 0.4. She returned in 1 month with 20/40 VA and resolution of the macular edema. At her most recent visit (September 2021), which was 3 years after receiving Iluvien, her VA was 20/25 and her anatomy showed evidence of disease quiescence (

Part of the reason this patient is noteworthy is that she was lost to follow-up for nearly a year during the COVID-19 pandemic, largely due to her discomfort with coming in to the office. Upon her return, her IOP was 15 with a stable cup to disc ratio. During that period, her macular edema was controlled with Iluvien therapy and her VA had actually improved from 20/40 to 20/25.

Luo serves on the advisory board of Alimera Sciences. He has received research grants from Allergan, and is a speaker for Iridex and Regeneron.

1. Kiss S, Malangone-Monaco E, Wilson K, et al. Real-world injection frequency and cost of ranibizumab and aflibercept for the treatment of neovascular age-related macular degeneration and diabetic macular edema. 

. 2020;26(3):253-266. doi:10.18553/jmcp.2020.19245

2. Ciulla TA, Bracha P, Pollack J, Williams DF. Real-world outcomes of anti-vascular endothelial growth factor therapy in diabetic macular edema in the United States. 

a. 2018;2(12):1179-1187. doi:10.1016/j.oret.2018.06.004

3. Mitchell P, Sheidow TG, Farah ME, et al; LUMINOUS Study Investigators. Effectiveness and safety of ranibizumab 0.5 mg in treatment-naïve patients with diabetic macular edema: results from the real-world global LUMINOUS study. 

. 2020;15(6):e0233595. doi:10.1371/journal.pone.0233595

4. Pitcher JD, Moshfeghi AA, Lucas G, Boucher N, Moini H, Saroj N. Evaluation of patients receiving intravitreal antivascular endothelial growth factor for diabetic macular edema in clinical practice in the United States.

. 2021;5(2):108-113. doi:10.1177/2474126420953067

5. Campochiaro PA, Brown DM, Pearson A, et al; FAME Study Group. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. 

. 2012;119(10):2125-2132. doi:10.1016/j.ophtha.2012.04.030

6. Boyer DS, Yoon YH, Belfort R Jr, et al; Ozurdex MEAD Study Group. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. 

. 2014;121(10):1904-1914. doi:10.1016/j.ophtha.2014.04.024

7. Ozurdex. Prescribing information. Allergan, Inc; 2014. Accessed December 6, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022315s009lbl.pdf8.

8. Iluvien. Prescribing information. Alimera Sciences, Inc; 2014. Accessed December 6, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/201923s000lbl.pdf

9. Mansour SE, Kiernan DF, Roth DB, et al. Two-year interim safety results of the 0.2 µg/day fluocinolone acetonide intravitreal implant for the treatment of diabetic macular oedema: the observational PALADIN study. 

 2021;105(3):414-419. doi:10.1136/bjophthalmol-2020-315984

10. Luo C. Diabetic retinopathy progression in anti-VEGF vs. 0.19 mg fluocinolone acetonide implant treated eyes who are lost to follow up. Paper presented at: American Society of Retina Specialists 2020 Virtual Annual Meeting; July 24-26, 2020.

Patients’ reluctance to visit a clinic during the COVID-19 pandemic is pushing retina specialists to optimize therapy. 

Durable therapies for diabetic macular edema amid COVID-19 pandemic

A team of researchers has found evidence that cataract surgery is linked with a lower risk of developing dementia.

The Adult Changes in Thought (ACT) study is a long-standing, Seattle-based observational study at Kaiser Permanente Washington of more than 5000 participants older than 65. Based on the longitudinal data of more than 3000 ACT study participants, researchers have now found that subjects who underwent cataract surgery had nearly 30% lower risk of developing dementia from any cause compared with those who did not.

This decreased risk persisted for at least a decade after surgery. Cataract surgery was also associated with lower risk of Alzheimer disease dementia specifically. The results were reported Dec. 6 in 

Lead researcher Cecilia Lee, MD, MS, associate professor and Klorfine Family Endowed Chair in ophthalmology at the University of Washington School of Medicine, said the observational study adjusted for a number of potential confounders, yet still yielded a strong association.

“This kind of evidence is as good as it gets in epidemiology,” Lee said. “This is really exciting because no other medical intervention has shown such a strong association with lessening dementia risk in older individuals.”

According to the study, the mechanisms by which cataract surgery and lessened dementia risk are associated was not determined in the study. Researchers hypothesize that people may be getting higher quality sensory input after cataract surgery, which might have a beneficial effect in reducing the risk of dementia.

“These results are consistent with the notion that sensory input to the brain is important to brain health,” said co-author Eric B. Larson, MD, MPH, a principal investigator of the ACT study, and senior investigator at Kaiser Permanente Washington Health Research Institute.

According to Lee, another hypothesis is that after cataract surgery, people are getting more blue light.

“Some special cells in the retina are associated with cognition and regulate sleep cycles, and these cells respond well to blue light,” she said. “Cataracts specifically block blue light, and cataract surgery could reactivate those cells.”

Moreover, the study results highlight a case for further research on the eye-brain connection in dementia. Previous studies by Lee’s group at UW have shown a link between other retinal diseases, such as age-related macular degeneration, and the development of Alzheimer’s disease and dementia.

Subjects with macular degeneration or other retinal degenerative diseases are more likely to develop dementia, In the current study, subjects undergoing vision-improving cataract surgery had lower risk of developing dementia. Further understanding the connection between the aging eye and brain may offer insights and potential therapies to slow or prevent age-related dementia.

Researchers tracked participants diagnosed with a cataract or glaucoma but who did not have dementia at the time they volunteered for the study. Participants also did not have cataract surgery at the time of enrollment. Participants are evaluated every two years for cognitive abilities based on the Cognitive Abilities Screening Instrument, which scores in a range from 0-100. Participants with scores less than 85 undergo further neurological tests.

During follow-up of 3038 participants (an average of 7.8 years per person), 853 subjects developed dementia, with 709 cases of Alzheimer disease. Approximately half of the participants (1382 individuals, or 45%) had cataract surgery. Analysis for risk of developing dementia showed that subjects who had undergone cataract surgery in either eye were about 30% less likely to develop any form of dementia for at least 10 years after their surgery.

Analysis was adjusted for an extensive list of factors including health-related confounders. Cataract surgery could appear to have a protective effect due to a healthy patient bias, where participants who underwent cataract surgery might have been healthier and at lower dementia risk. Researchers performed analyses to account for several types of potential bias, but still found strong associations when these factors were accounted for.

Researchers excluded eye surgeries in the two years prior to dementia diagnosis to rule out the possibility that people with cognitive decline prior to dementia diagnosis may have been less conscious of vision issues, and thus less likely to have undergone cataract surgery. Even with this group excluded, the researchers found lower risks of dementia associated with cataract surgery.

As another control, participants were also evaluated for a possible link between eye surgery for glaucoma and dementia. No association was found.

This was a community-based, prospective cohort study with more than 23,000 person-years of follow up. More than 98% of the ACT cohort were seen at least once by eye care clinicians, with an average of 27 encounters. Dementia diagnoses were made by a panel of experts using research criteria. The possibility of healthy patient bias and potential confounders were thoroughly investigated.

Results could be explained by unmeasured or residual confounding factors, like any observational study. There could be coding errors for cataract diagnosis. Only the participant’s first cataract surgery was evaluated so researchers don’t know whether subsequent surgeries impacted dementia risk. The majority of the study population was White, and it is unclear if the effect would be observed in all populations.

“Innovative research like Dr. Lee’s is helping to uncover how age-related changes in our senses contribute to dementia,” said Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF), a nonprofit dedicated solely to accelerate the discovery and development of drugs to treat and prevent Alzheimer’s disease and related dementias.

 research initiative, the ADDF is also supporting Lee’s 

 to develop new diagnostic tools for Alzheimer’s that use non-invasive imaging of the retina and artificial intelligence.

The study was funded by National Institutes of Health (K23EY029246, R01 AG060942, P50 AG05136, U01AG006781, U19 AG066567), an Alzheimer’s Drug Discovery Foundation Diagnostics Accelerator Award, a Latham Vision Innovation Award, and an unrestricted grant from Research to Prevent Blindness.

Lee, C.S., et al. (2021) Association Between Cataract Extraction and Development of Dementia. 

Researchers have now found that subjects who underwent cataract surgery had nearly 30% lower risk of developing dementia from any cause compared with those who did not. 

Study: Cataract surgery linked to decreased risk of dementia 

The LADDER trial was a phase 2 trial that showed overall good safety and efficacy for the port delivery system [PDS] for the treatment of neovascular AMD [age-related macular degeneration]. It looked at varying doses of ranibizumab in the PDS implant. Patients were dosed at 10-mg, 40-mg, and 100-mg concentrations. Interestingly, and this is different than the ARCHWAY study which we’ll talk about shortly, patients were only given a refill of ranibizumab if they met criteria of worsening fluid, vision, or new submacular hemorrhage. The 100-mg concentration, which is what is approved, showed that about 80% of patients were able to go 6 months or longer before needing a refill; the median time for needing the first refill in the 100-mg group was nearly 16 months.

Overall, the port delivery system procedure was very well tolerated. As mentioned before, after the modification of the technique, patients did not have any vitreous hemorrhage within the first month. The refill procedure was also very well tolerated, and was able to be done in an in-office setting.

Coming from very good results from the LADDER trial, ARCHWAY was the phase 3 trial, which was a 2-year study comparing monthly ranibizumab to the PDS implant with 100 mg ranibizumab and refills [every] 6 months. The patients enrolled in this study were patients who had wet AMD, were diagnosed within 9 months of screening, and who were responding to anti-VEGF treatment. The ARCHWAY trial showed that 98% of patients were able to go without any additional treatment in the PDS group. The PORTAL trial is an extension study that will be looking at how patients do beyond 2 years. The safety and tolerability of the procedure were also consistent with the LADDER study, particularly with respect to very low incidence of vitreous hemorrhage, as well as the procedure being very well tolerated.

The patients who were included in the ARCHWAY study were recently diagnosed with neovascular AMD. All the patients had to be diagnosed within 9 months of their screening visit, and they all had to show a good response to anti-VEGF therapy.

The ARCHWAY study so far shows that patients are tolerating the port delivery system very well, even in a long-term manner. We’re also showing that patients have good, consistent visual recovery, as well as good stability of their macular thickness. We also analyzed patients with fluid fluctuations, and showed that patients with the port delivery system have good minimization of fluid fluctuations, similar to having monthly ranibizumab injections. I’m also excited about learning what longer-term data are going to show in the PORTAL study. The PORTAL study is looking at patients well beyond 2 years, as well as multiple refills beyond 2 years.

Chirag Jhaveri, MD, reviews the trial design and results of the LADDER and ARCHWAY studies, which tested the port delivery system in neovascular AMD. 

Durable therapies for diabetic macular edema amid COVID-19 pandemic

Study: Cataract surgery linked to decreased risk of dementia

PDS in Retinal Diseases: Interpreting the LADDER and ARCHWAY Studies