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The prevalence of visual impairment and blindness caused by diabetic retinopathy is increasing worldwide. Early recognition, perhaps via a screening programme, and timely management would be of benefit.

Review of the epidemiology of diabetic retinopathy

AAO 2024, Kelman Lecture, medical education evolution, AI in medicine, robotics, continuous clinician education, "See One, Do One, Teach One" model, healthcare training innovation, Bonnie An Henderson, ophthalmology education

AAO 2024: Bonnie An Henderson, MD, explores future of medical education in Kelman Lecture

Bonnie An Henderson, MD, shares insights for her Kelman Lecture, titled Enhancing the Paradigm of 'See One, Do One, Teach One' with Technology, at the 2024 American Academy of Ophthalmology meeting, October 18 to 21 in Chicago, Illinois. 

Henderson emphasizes the evolution of medical education, reflecting on her own experiences from a time before the internet to the current landscape enriched by digital tools and advancements in artificial intelligence and robotics. She is a clinical professor at the Tufts University School of Medicine in Boston, Massachusetts.

Henderson highlights the transformative journey of medical training. She discusses the shift from traditional learning methods, such as textbooks and lectures, to modern resources like simulators and online platforms. The advent of AI presents an exciting future for education, allowing for the rapid accumulation and dissemination of knowledge.

She offers advice to residents, stressing the importance of diverse educational modalities. She adds that individuals learn differently, and while visual resources like YouTube can be helpful, hands-on experience remains vital. Practicing skills through wet labs, synthetic models, or simulators is crucial for developing the necessary hand-eye coordination and physical dexterity.

Henderson underscores the necessity of continuous learning in a rapidly evolving field. She encourages them to engage with various educational opportunities, whether online or in-person, to stay current with the latest devices, techniques, and medications. With medical advancements accelerating every six months, maintaining up-to-date knowledge is essential for providing optimal patient care and enhancing professional practice. 

Henderson’s presentation touches on the shift in medical education from traditional learning to AI and robotics.

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AAO 2024: Epimacular membranes and metamorphopsia

At this year's American Academy of Ophthalmology (AAO) meeting, Jonathan Brugger, MD, spoke about the changing approach to epimacular membranes and the use of brilliant blue in the procedure.

Editor's note: This transcript has been lightly edited for clarity.

I'm Dr Jonathan Brugger. I'm a vitreoretinal surgeon with Carolina Eye Care in Charleston, South Carolina. And I wanted to shed some light on epimacular membranes. A lot of the teaching that we have been taught in generations was that "we don't want to touch epimacular membranes until they are visually significant." 

However, with safer procedures, better instruments, and now non-toxic, brilliant blue, we should be having earlier intervention on epimacular membranes, to the point that surgeons now are approaching patients that are symptomatic with metamorphopsia to peel even [a] 20/20 vision eye. That's simply because individuals can see that it's the letter T, whether it's perfectly straight or if it's slightly twisted, but the patients now that we are peeling early, have quicker resolution of their metamorphopsia and report that the vision is actually better, that the T is straight, if you will, and we have not caused any harm to the retina. With the non-toxic brilliant blue, we feel confident that we're getting all of the membrane because we're able to re-stain multiple times. 

The adage of "waiting until the membrane gets bad enough," you will be sitting there for a lifetime, because we do know that a majority of these membranes will form and then they do not progress. So you will be watching these patients for years and years and years that are symptomatic but not getting better. And now, I think the time has come that we should start looking at this again for early intervention of peeling symptomatic epimacular membranes.

Diabetic retinopathy has tended to be regarded as a rare occurrence in young patients diagnosed with diabetes, but a recent paper details the growing rates of the disease in young people as a looming “potentially unappreciated public health catastrophe.”

, coauthored by Julie M. Rosenthal, MD, MS, from the University of Michigan Department of Ophthalmology and Visual Sciences and Kellogg Eye Center, pointed to data from 2 recent studies, including the Treatment Options for Type 2 Diabetes in Adolescents and Youth study and the SEARCH for Diabetes in Youth study.

“Diabetic retinopathy in young people is more common than we originally thought,” Rosenthal said in a University of Michigan news release. “So we need to take action by screening for it and intervening when we are able.”

Diabetic retinopathy occurs when high blood sugar damages tiny blood vessels and nerves in the retina, the structure at the back of the eye that acts like the sensor in a digital camera. It can result in vision loss that can be permanent and blinding.

According to the University of Michigan news release, the most effective way to reduce the risk of diabetic retinopathy, according to experts, is to effectively manage the patient’s diabetes.

“In youth-onset Type 1 or Type 2 diabetes, we used to think it was rare to have retinopathy, but we’re finding out more and more that’s just not the case,” Rosenthal explained. “These two major studies found that after just 12 or 13 years of having diabetes, at least 50% of people had some amount of retinopathy, which is unexpectedly and unacceptably high.”

Rosenthal and her co-authors, retina specialist Jennifer K. Sun, MD, MPH, of Harvard, and pediatric endocrinologist Risa M. Wolf, MD, wrote in the paper that among participants in the studies who have Type 2 diabetes, the SEARCH and TODAY studies combined found that 49% to 55% had diabetic retinopathy after having diabetes for only about 12 to 13 years.

In the SEARCH study, 52% of youths with type 1 diabetes had DR. For participants with type 2 diabetes, at a mean 7.5 years after diagnosis, the standardized prevalence of DR was 31%, increasing to 55.7% at a mean 12.4 years after diagnosis.

This was a surprise to investigators, as earlier data from one of the studies at 7 years after diagnosis only showed a rate of 4% to 13%.

Even though much of that retinopathy isn’t immediately threatening to vision, Rosenthal added, “that’s way more than we ever thought before, and given the increasing number of people who have diabetes, and especially with the prevalence of Type 2 diabetes going up, this is something we really need to pay attention to as ophthalmologists and as pediatric endocrinologists.”

Rosenthal acknowledged that it can be a challenge to maintain control of diabetes – especially during the years when diabetic retinopathy can begin taking a toll on the vision of young adult patients.

Moreover, for many patients, life is changing and events such as establishing their own homes, going off to college, starting a new job, or even transitioning from a pediatric endocrinologist to an adult doctor can all get in the way of closely monitoring a dangerous, progressive disease.

Rosenthal pointed out that diabetes is not an easy disease to live with because it impacts every part of a person’s life.

“When your friends aren’t having to deal with this, when you want to be living your life like a normal 18-, 20-, or 22-year-old, it can be really tough to get to your screening exams and keep good control of the disease,” she said.

Rosenethal added that researchers are worried that the disparities that are already present are going to widen if action is not taken.

“We need to make sure people are able to see their doctors and find better ways to get the treatment and the screening that they need,” she said.

That said, it’s important to both control the illness and know whether retinopathy may be progressing.

“While we think that control over blood sugar is a big factor in preventing retinopathy, we know it’s not the only one,” Rosenthal said.

Early screenings and detection can allow ophthalmologists to intervene during the earliest stages of diabetic retinopathy, even before patients have lost vision, suffered a retinal detachment or have had a lot of bleeding in the back of the eye. Rosenthal noted that that early intervention can lead to treatments that may prevent those things from happening and permanently affecting a patient’s vision at such a young age.

Black, Hispanic youths disproportionately affected

While the incidence of both types of diabetes in youths has risen over the past 2 decades, the greatest increase has been among Black and Hispanic youths, a trend that’s projected to continue in coming years.

Diagnoses of Type 1 diabetes are projected to increase 65%, while Type 2 diagnoses may shoot up more than 600%, according to the paper.

Studies also indicate that racial and ethnic minority groups bear a heavier burden of diabetic retinopathy than their white peers.

“We’re very concerned that the disparities that are already present are going to widen if we don’t take action,” Rosenthal said. “We need to make sure people are able to see their doctors and find better ways to get the treatment and the screening that they need.”

Improved screening methods lead to better outcomes

The traditional methods of screening for diabetic retinopathy include examining the retina or taking a picture of the back of the eye to check for changes including bleeding, swelling, tiny aneurisms or patches of the retina that aren’t getting great blood flow.

In recent years, physicians have started to view diabetic retinopathy as more of a problem affecting a “neurovascular unit” of nerves and blood vessels working together.

“We haven’t been looking at the neurologic part of retinopathy,” Rosenthal pointed out, by using tests like contrast sensitivity – for example – trying to see a letter that’s getting closer to the same color as the background.

“Is there something happening in the retina before we’re even seeing the retinopathy that could be affecting these young people?” she asked.

According to the University of Michigan news release, recent studies in adult patients have highlighted changes in how the retina works that ultimately may come before retinopathy is visible on exam or photographs.

Rosenthal further noted she would like to see more and better screening done in ways that make it easier for patients to stay on top of their eye health.

“We need to take screening to where patients already are—at their pediatric endocrinologists’ office or primary care physician, so they don’t have to make an extra trip to the eye doctor,” she explained.

Rosenthal also noted that the young patients and their parents are faced with a number of hurdles to clear when the child is diagnosed with retinopathy, and this could help check one item off their list.

“Many programs such as this are already underway for adults,” she said.

While current treatment options are better today than they were even 10 or 15 years ago, Rosenthal concluded that these treatments remain more reactive than preventative. In the future, Rosenthal said she hopes to have effective treatments that can act at earlier stages of the disease.

Rosenthal JM, Sun JK, Wolf RM. Diabetic Retinopathy in Youths—A Potentially Unappreciated Public Health Catastrophe. 

 Published online October 3, 2024. Accessed October 10, 2024. doi:10.1001/jamaophthalmol.2024.387

Diabetic retinopathy is being diagnosed more in younger patients. Michiganmedicine.org. Published October 9, 2024. Accessed October 10, 2024. https://www.michiganmedicine.org/health-lab/diabetic-retinopathy-being-diagnosed-more-younger-patients?amp

A recent paper reveals increasing rates of diabetic retinopathy in young patients with diabetes, sparking concerns over inadequate screening and management, especially among Black and Hispanic youths. 

Rising diabetic retinopathy rates in youth signal potential public health crisis

Real-world treatment outcomes from a study of patients with retinal vein occlusion

At this year's American Society of Retina Specialists (ASRS) meeting, the Eye Care Network spoke with consultant ophthalmologist Christiana Dinah, BSc, MB BS, MRes. Her presentation focused on real-world outcomes of anti-vascular endothelial growth factor (VEGF) therapies for patients with retinal vein occlusion.

Editor's note: The below transcript has been lightly edited for clarity.

 Hi my name is Christiana Dinah. I'm a consultant ophthalmologist at London North West Trust, in London, United Kingdom. It is my pleasure to present, at ASRS 2024, our work on the real-world outcomes with anti-VEGF therapy in retinal vein occlusion in the United Kingdom. We know the retinal vein occlusion is a significant cause of visual impairment, being the second most common retinal vascular disease, second only to diabetic retinopathy. We are fortunate to have anti-VEGF therapy now, with significantly beneficial results in pivotal randomised controlled trials. 

However, these results have often been difficult to translate in the real world. Additionally, there is sparse data on long-term, real-world outcomes with anti-VEGF therapy in the context of retinal vein occlusion. We extracted data from 16 geographically dispersed eye clinics in the United Kingdom. Our study included approximately 3500 patients in the [branch retinal vein occlusion] BRVO arm and a similar number in the [Central Retinal Vein Occlusion] CRVO arm, so this is quite a large sample size. However, the proportion with follow-up out to 5 years was closer to 500 eyes in each cohort. We included patients that were treatment-naive to any treat previous treatment for retinal vein occlusion, who had had at least 1 anti-VEGF therapy within the timeframe of the study, and had a minimum of 3 month follow-up and up to 60 months follow-up, and that is 5 years. 

Importantly, in the United Kingdom at the moment, the only approved anti-VEGF therapies for retinal vein occlusions are aflibercept, ranibizumab and bevacizumab. So these were the anti-VEGF therapies that we looked at, as under the umbrella of anti-VEGF. To our results, there was significant visual gain, with the average visual acuity gain of approximately 11 to 13 letters in both the branch retinal vein occlusion groups and the central retinal vein occlusion groups. And this was demonstrated quite early, within 3 months, and maintained up to around 12 to 18 months, at which point the visual acuity gains start to reduce slowly, and by the time we get to month 60, that is 5 years, the visual gains at that point is approximately 7 to 8 letters, almost half of the initial gains. We next looked at the number of injections delivered on average in the first year. In both the BRVO cohort and the CRVO cohorts a mean number of 6.4 to 6.5 injections were delivered. And this reduced over the follow-up period to approximately 2.5 injections in both cohorts in the year 5. 

We delved deeper by stratifying the cohorts into low injection receivers, medium injection receivers and high injection receivers. The low cohort received less than 4 injections in within a 12 month period, the medium 4 to 8, and the high greater than 8 injections, and we demonstrated the high cohort reported visual gains similar to what we've seen in the clinical trials that into 15 letter gains, whilst the low cohort reported approximately half of that, and this pattern was evident right out to month 60. Additionally, eyes receiving intravitreal steroids and macular laser increased gradually from year 1 through to year 5, suggesting efforts to achieve or maintain disease control right out to year 5. 

Our study strengths include a large heterogeneous population in a geographically dispersed population across United Kingdom, but limitations include the lack of anatomical data, in addition to a loss to follow-up, whereby the proportion of eyes at the start is approximately 3500 in the BRVO, and in the CRVO, separately whilst at year 5, we have approximately 500 eyes in each arm. The take home message is anti-VEGF therapy does work in retinal vein occlusion and translates into the real-world. However, there are factors limiting our ability to deliver the same volume of injections, as in the randomised control trials. Therefore, there's an unmet need for sustained durable treatments for retinal vein occlusions and long-term monitoring to ensure disease control. Thank you.

Consultant ophthalmologist Christiana Dinah, BSc, MB BS, MRes, presented research findings on retinal vein occlusion in the United Kingdom

ASRS 2024: Real-world treatment outcomes from a study of patients with retinal vein occlusion

ASRS 2024: Intraoperative fluorescein angiography reduces the rate of postoperative vitreous hemorrhage

Alan Franklin, MD, PhD, FASRS, spoke about his presentation, "Intraoperative Fluorescein Angiography Reduces the Rate of Postoperative Vitreous Hemorrhage" at this year's American Society of Retina Specialists (ASRS) meeting in Stockholm, Sweden. 

Hi I'm Alan Franklin, MD, PhD. FASRS, I practice at Diagnostic and Medical Clinic in Mobile, Alabama, [and I] had the opportunity to present intraoperative fluorescein angiography, how that's improving our outcomes in diabetic vitrectomy at this great venue in Stockholm, Sweden. intraoperative fluorescein angiography, was initially described by Steve Charles 20 to 30 years ago, with the advent of digital visualization, it's gotten more traction as our visualization is better. The images and the video on the operating room are quite compelling, but the question begs is even though the video is great, and shows us reproducible biomarkers that we see in clinic, will it help her outcomes.

So we did a study where we looked at our diabetic patients and looked at rate of vitreous hemorrhage after vitrectomy with or without fluorescein angiography guidance intraoperativly of laser and other surgical maneuvers. Indeed, we found that fluorescein angiography reduced our post-op vitreous hemorrhage rate greatly, especially over the first 1 to 2 months with corresponding better vision reported rate with fluorescein guidance during the surgery is on the order of 10%, which is much lower than the standard reported rates after vitrectomy surgery for diabetic retinopathy and we both Dr. Abruro, our colleague and Dominican Republic, and we showed a significant reduction and rates of vitreous hemorrhage after surgery compared to those who did not receive intraoperative fluorescein angiography before surgery, it was highly significant, especially at both the 1- and the 2-month time points And that we had about 90 patients that underwent fluorescein angiography, so it's still a relatively large study. It is limited by the retrospective nature.

Hopefully it'll improve adoption. It's one thing to show pretty pictures and videos, but to show and prove surgical outcomes, hopefully will will get better adoption. We need to work on making this available for both digital visualization platforms and standard optical visualization with a surgical microscope as well.

ASRS 2024: Intraoperative fluorescein angiography improving outcomes in diabetic vitrectomy

ASRS 2024: Ixo-Vec phase 2 interim data presentation

Charles Wykoff, MD, PhD, gives an insight into first-time data from the phase 2, LUNA trial looking at Ixo-Vec at the annual ASRS meeting in Stockholm, Sweden.

Hi I'm Charles Wykoff, retina specialist from Houston, Texas, and it's great to be here ASRS 2024 in Stockholm, Sweden. So at this meeting, we presented first-time data from the LUNA trial looking at Ixo-Vec, previously known as AVDM-022. 

So ixo-Vec is an intravitreal gene therapy that leads to continuous intraocular aflibercept production, and over about 115 patients treated to date. We've seen consistent and strong efficacy at controlling exudative disease activity, and we've also seen notable levels of intraocular inflammation. So into that context, LUNA was designed as a trial, a phase 2 trial, to look at 2 main things: 1 was lower doses of Ixo-Vec, so lower doses of the of the virus that's being given as a gene therapy, and secondly, to look at enhanced steroid prophylactic regimens. 

So 60 patients with wet AMD were randomized to 1 or 4 steroid prophylactic arms, and also a single injection of Ixo-Vec either 6E10 or 2E11, and then followed for what will ultimately be a 1-year primary endpoint, but at this meeting, we're presenting the completed 26 week pre-specified data. So enrolled patients were were heavily pre-treated patients with wet AMD on average 3 years since AMD original diagnosis and 10 mean annualized anti-VEGF injections at baseline vision was about 20/40, CST 350 microns. Let's talk about efficacy, and then safety giving each equal weight. So from an efficacy perspective, after Ixo-Vec dosing, we saw 76% to 83% of patients remaining injection free through week 26. We also saw stability in visual acuity through week 26, and also stability with CST through week 26. And maybe, to me, the most interesting efficacy signal that we saw was looking at the sub-population of patients that had a CST of greater than 300 microns at baseline. In that population of patients, I think, we really saw the anatomic stability achieved here through 26 weeks as those eyes with fluid at baseline actually had a reduction and CST at week 26 of minus 30 microns and CST stability through that 6-month endpoint. 

So from a safety perspective, there were no Ixo-Vec related SAEs and all related adverse events were mild or moderate, the most common being dose-dependent, anterior chamber cellular inflammation as well as anterior pigmentary changes with 91% of patients in the local steroid regimen arms, having no or minimal inflammation at every visit through week 26. You know, again, of the key objectives of the trial was to evaluate these different enhanced steroid prophylactic regimens. 

And so the key learnings from that were twofold. One, the dexamethasone-alone implant did not provide adequate prophylaxis, and therefore early in the trial, there was a protocol amendment that was incorporated to add difluprednate eyedrops to the OZURDEX alone arm. And once we made that change, we saw meaningful reduction in the IOI rates. And the second important finding, I think it's quite relevant to intravitreal gene therapy at large, was that the use of oral steroids, a meaningful relatively-high dose of prednisone over many weeks, did not provide additional benefit beyond local corticosteroid prophylaxis alone. Both of these things were findings that we did not know before the trial. This trial was designed to look at those 2 arms in particular, and both of them now we have much more clarity about what is useful for prophylaxis in this setting. Looking specifically at at the development of anterior chamber cellular activity or anterior chamber pigmentary changes. 

When you look at the data from the patients with the prophylactic regimens that are being considered for future trials, we saw that most patients at most visits did not have cellular activity. There were 4 patients and both the difluprednate-alone, and the difluprednate plus dexamethasone populations that did have cellular inflammation and at least 1 visit, and there was also potential increase in anterior pigmentary cellular activity toward the end of the 26 week period. And then the last point about safety focusing in on the difluprednate-alone population. We saw in that group a dose-dependent dozens of anterior chamber cellular activity and anterior pigmentary changes through week 26. So in particular, in the lower dose, the 6E10 population, there was one patient at 26 weeks that had a very minimal amount of anterior cellular activity, and then 4 patients with anterior pigmentary changes, 3 of them being mild, 1 moderate. 

So that was the summary of LUNA for ASRS 2024 It says 26 week completed data and a pre-specified endpoint and ultimately this will be a 1 year trial. Thank you.

Dr. Michal S. Nowak

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