PIE POST (EURETINA 2021 Edition) - Day 3

Presents… EURETINA 2021

The first-ever Kreissig Award for Excellence in Retinal Research

by Nick Eustice

Ahigh point of this year’s EURETINA conference was the inaugural presentation of the Kreissig Award for Excellence in Retinal Research and the accompanying keynote lecture by its recipient — Dr. Ogugua Okonkwo. Established just last year, the Kreissig Award for Excellence in Retinal Research is given by the Association for Research in Vision and Ophthalmology (ARVO) Foundation, in recognition of “the next generation of curious, enterprising investigators who seek to optimize functional outcomes for patients needing retinal surgery”.

Dr. Okonkwo was introduced by EURETINA President Dr. Frank G. Holz, who highlighted his 19 years of experience at the Eye Foundation Hospital in Lagos, Nigeria. During this time, Dr. Holz described him as instrumental in developing one of the most outstanding surgical centers in all of Africa, devoting a great deal of time and effort to training generations of retinal surgeons.

Exploring various avenues of neuroprotection strategy for NACRAO

Dr. Okonkwo began his lecture, entitled “Exploring Neuroprotective Strategy for NonArteritic Central Retinal Artery Occlusion”, by explaining the condition his research aims to treat. Central retinal artery occlusion, or CRAO, is an ocular variant or analogue of acute ischemic stroke (AIS). These strokes of the retina cause a very sudden loss of vision, which can become permanent without prompt and effective treatment to prevent the death of neurons.

This presentation focused on the non-arteritic (NA) variety of CRAO, whose cause is known to be thromboembolism at the narrowest site of the central retinal artery (CRA), the point of dural penetration. It is the rapid and often complete blockage of blood flow caused by this embolism that makes the condition’s onset so sudden, and which makes the danger to the blocked-off neurons so severe.

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Non-pharmacologic neuroprotective strategies

Dr. Okonkwo’s aim in this study was to explore the potential of various avenues of neuroprotection to improve outcomes in instances of NA-CRAO. He said the treatment outcomes are most likely unsatisfactory, with only 17% of patients regaining functional vision. In 50% of cases, only a small peripheral island of vision remains. Therefore, we have a strong need to develop methods that will produce much more favorable results.

Important principles in treatment methods

The three principles that treatment methods must involve are, first and foremost, acute reperfusion of the CRA, followed by prevention of ocular complications, and vascular review to prevent further end-organ ischemia. While the reperfusion is the natural first step, its timeline is extremely short in terms of the latter two criteria. For even when blood flow is restored to the retina, this does not necessarily lead to a significant recovery of vision.

This, Dr. Okonkwo said, is due to retinal survival time (RST) — the time from the initial ischemic event to the irreversible death of neurons. Retinal survival offers only a relatively short “therapeutic window” for treatment. While previous studies (conducted by Hayreh et. al.) have proposed that this window of RST is only around 240 minutes, Dr. Okonkwo pointed out a series of weaknesses in prior tests. Specifically, these tests involved poorly-controlled use of neuroprotective agents such as anesthesia and hypothermia, and were conducted on Rhesus monkeys.

It seems more likely that RST may vary significantly for different individuals, thereby allowing a therapeutic window that is potentially longer than once supposed. For preclinical stroke, studies have shown that, in other instances of AIS, neurovascular responsiveness was affected by a great many other factors

such as age, sex, and comorbidity. Dr. Okonkwo explained that because of this, it would not be unreasonable to speculate that the window could be nearer to six hours than the previously believed four.

Understanding the penumbra in cranial AIS

Before moving on to discussing treatments, Dr. Okonkwo paused to quickly discuss the concept of the penumbra in cranial AIS, or a more commonly understood stroke. Fundamentally, the blockage of blood flow in AIS occurs in two distinct areas of vascular occlusion: a core area, where the death of neurons leads to irreversible damage, and to the penumbra, an area adjacent to the core where the brain has lost function owing to decreased blood flow, but that loss of function is not irreversible.

This concept applies to NA-CRAO insofar as it introduces the concept of neuroprotection. In treating strokes, neurosurgeons seek to mitigate damage to the penumbra, to allow for maximum recovery. This well-researched field provides many possibilities whose applications may have analogues for NACRAO. These include pharmacologic and non-pharmacologic approaches to slow the progress of pathological damage.

At this point, Dr. Okonkwo cited several pre-clinical studies of possible applications of pharmacological treatments for NA-CRAO. These include angiopoietin, a growth factor that increases blood vessel stabilization and survival; KUS 121, a compound in development at Kyoto University which has shown progress in suppressing retinal cell death; and X-linked inhibitor of apoptosis (XIAP)-mediated gene therapy, which can protect neuronal cells from apoptosis. While future applications for these and other treatments are a possibility, they are still in very early development.

Turning to non-pharmacologic neuroprotective strategies, a number of currently applied treatments from other branches of medicine present possible solutions. Moderate hypothermia, for instance, has developed a rather positive track record in cardiology and is widely used in cardiac resuscitation. Its use has significantly reduced mortality and improved neurological function. In AIS, induced hypothermia has also shown that it can protect from ischemic damage.

When applied to the retina, hypothermia has shown a lot of promise in terms of expanding the RST in practice. Studies have shown that retinal survival time can be prolonged up to 12 hours when induced at a temperature of 20 degrees, and as much as 50 hours when that temperature is reduced to 4 degrees. These results, again, are only based upon lab animals, but could find their way up to patient applications in the future.

The induction of hyperbaric oxygen through a vitrectomy could also provide a helpful neuroprotective measure, providing oxygen to the blood-starved retina through other means until such time that reperfusion can restore normal blood flow, just as with the penumbra in cases of AIS. Studies have shown mixed results, but further study may reveal great potential here as well.

Endless possibilities ahead

Having laid out various possibilities for neuroprotective treatments, Dr. Okonkwo wound down his presentation, suggesting a rubric for what future clinical trials might entail. He closed by stressing that there is an increase both in interest and hope for therapeutic neuroprotection, which combined with reperfusion could assist in saving the vision of NA-CRAO.

Dr. Okonkwo’s lecture shows outstanding research and vision. Congratulations to him on his innovative work and for its recognition with the inaugural Kreissig Award for Excellence in Retinal Research!.

“Overall, with Ozurdex, patients experience less treatment burden, with fewer intravitreal injections compared to anti VEGF. Thus, fewer clinic visits and better adherence.”

Myopia Management

Understanding risk factors and new treatment methods

by Tan Sher Lynn

Myopia has become a serious problem in some parts of Asia, with an increasing prevalence in the US and Europe. On the third day of the EURETINA 2021 Virtual, experts provided updates and shared their knowledge on myopia prevention and treatment.

Genetics, lack of outdoor time, and other risk factors

In her talk “Epidemiology and Risk Factors of Myopia”, Prof. Seang Mei Saw from the National University of Singapore said that myopia and high myopia are very high in young adults in urban Asia — 96.54% in South Korea and 79.2% in Singapore1

“Risk factors for myopia include lack of outdoor time, too much near work, genetics, and height. An exponential rise is observed in individuals who started schooling after the 1980s, jumping to a high prevalence of over 80%,” shared Prof. Saw.

Studies on multivariate models found that time spent outdoors is protective of myopia. “It is the amount of time that a child spends outdoors that protects him/ her from myopia, not so much the type of activity performed or the pattern of light exposure,” she stressed.

A meta-analysis performed by her team in regards to digital screen time and myopia did not find a positive association and further studies are required.

Further, Prof. Saw said that genetics play a role in myopia risk, noting that genetic studies have identified new genes that implicate novel mechanisms, such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology, and angiogenesis.

Latest methods in myopia management

Meanwhile, Prof. Andrzej Grzybowski

from the University of Warmia and Mazury, Poland, presented the conclusions of various recent studies and reviews on myopia control methods.

“Presently, we have two approaches for myopia control. The pharmacology approach is based on different concentrations of atropine, while the optical approach uses orthokeratology and peripheral defocus modifying contact lenses and glasses,” shared Prof. Grzybowski.

The LAMP study pointed out that the efficacy of 0.05% atropine was doubled of that observed with 0.01% atropine in spherical equivalent progression over two years.

A recent paper2 based on 44 unique primary studies contained in 18 eligible reviews and involving 6,400 children confirmed the efficacy of atropine followed by orthokeratology and multifocal soft contact lenses in controlling myopia progression.

Also, a systemic review3 published on the Cochrane Library last year based on 41 studies with 4,772 participants concluded that antimuscarinic topical medication is effective in slowing myopia progression in children; multifocal lenses, either spectacles or contact lenses, may also confer a small benefit; and orthokeratology contact lenses are more effective than SVLs in slowing axial elongation.

“The World Society of Paediatric Ophthalmology and Strabismus Myopia Consensus Statement concluded that atropine 0.01% dose appears to offer an appropriate risk-benefit ratio, with no clinically significant visual side effects

balanced against a reasonable and clinically significant 50% reduction in myopia progression,” Prof. Grzybowski concluded.

More outdoor time and other intervention programs

As to the benefits of outdoor time, Dr. Ian Morgan from the Australian National University noted that disputes remain on whether spending time outdoor slows myopic shifts only before the onset of myopia, or whether it also slows progression in established myopes.

“Epidemiological evidence is limited and contradictory, but there are welldocumented seasonal effects on progression as well as COVID lockdown effects that are consistent with regulation by time outdoors and/or near work,” Dr. Morgan explained.

He recommended increased time outdoors to parents for non-myopic children with siblings who are myopic, or if there is a family history of myopia. He also recommended increased time outdoors to supplement current myopia control procedures, such as low-dose atropine and myopia control contact lenses and spectacle lenses.

References

1. Wong YL, Saw SM. Epidemiology of pathologic myopia in Asia and worldwide. Asia Pac J Ophthalmol (Phila). 2016;5(6):394-402.

2. Prousali E, Haidich AB, Fontalis A, et al. Efficacy and safety of interventions to control myopia progression in children: an overview of systematic reviews and meta-analyses. BMC Ophthalmol. 2019;19(1):106.

3. Walline JJ, Lindsley KB, Vedula SS, et al. Interventions to slow progression of myopia in children. Cochrane Database Syst Rev. 2020;1(1):CD004916.

The Pachychoroid Spectrum

A closer look at the latest diagnosis and therapeutic options

by Tan Sher Lynn

The pachychoroid spectrum is a group of clinical entities that share a common characteristic: a thickened choroid. Experts in this field shared their knowledge in diagnosing and managing this condition on Day 3 of the EURETINA 2021 Virtual Congress.

Different pathologies and characteristics

Dr. Rosa Dolz-Marco from the Oftalvist Clinic, Spain, described the different pathologies that fall under the pachychoroid spectrum.

“Pigmentary changes in pachychoroid spectrum is called pachychoroid pigment epitheliopathy, and it is usually asymptomatic unless it progress-es into another form in the spectrum,” shared Dr. Dolz-Marco. “Pachychoroid pigment epitheliopathy is characterized by the absence of subretinal fluid (acute or

resolved), drusenoid retinal pigment epithelium (RPE) le-sions, and RPE thickening.” It is typical to have the absence of leaking areas and choroidal hyperpermeability.

“In central serous choroidopathy (CSC), the classic form in the pachychoroid spectrum, we may have visual function impairment, neurosensory detachment, and retinal pigment epithelium changes,” she added.

In pachychoroid neovasculopathy (PNV), there is a typical shallow irregular RPE elevation and we can clearly see the tangled network of vessels on the optical coherence tomography angiography (OCTA). “Fluorescein angiography (FA) will show late leakage of an undetermined origin, while the indocyanine green angiography (ICGA) will reveal a late staining plaque,” Dr. Dolz-Marco explained.

She noted that a special type of neovascularization in the pachychoroid spectrum is the aneurysmal type 1 neovascularization (formerly known as polypoidal choroidal vasculopathy, [PCV]), which presents with late leakage in FA, as well as branching vascular network with terminal aneurysmal dilatations in ICGA.

“Last but not least is the peripapillary pachychoroid syndrome (PPS), which unifies all the features of the pachychoroid spectrum and happens especially around the optic nerve. Its maximal thickness is around the optic nerve instead of temporally,” she said.

Photodynamic therapy in CSC and PPS

Photodynamic therapy (PDT) involves the use of light-sensitive medicine and a light source to destroy abnormal

cells. According to Dr. Elon Van Dijk from the Leiden University Medical Center, Netherlands, PDT was originally developed for the treatment of neovascular age-related macular degeneration (nAMD) before being used to induce choroidal remodeling in CSC.

According to Dr. Van Dijk, the SPECTRA trial showed that PDT is more effective than oral eplerenone in the treatment of chronic CSC with regard to anatomical success (a complete resolution of subretinal fluid [SRF]), as well as functional parameters.

“PDT is also helpful in severe cases of CSC, achieving complete resolution of subretinal fluid in 88% of eyes at final follow-up (90 weeks), as well as steroid-associated CSC, with a complete resolution of subretinal fluid in 74% patients at an average of 49 weeks, even when steroid is continued,” he shared.

Meanwhile, in acute CSC, a watchful waiting policy (±2 months) is preferred, unless there is recurrent subretinal fluid, monocular vision, and subretinal fluid in the best-seeing eye, and if the patient heavily depends on optimal vision for professional reasons.

Besides CSC, PDT is also a valuable treatment option in patients with PPS and subfoveal SRF, as presented by Dr. Claudio Lovino from the Università degli Studi della Campania, Italy.

In 2019, he did a multicenter retrospective cohort study involving 25 eyes from 23 patients. The main outcome measure of the study was the proportion of eyes that achieved treatment success at three months after PDT. “Treatment success was achieved in 16 eyes (64%) and a complete resolution of the subretinal fluid was achieved in 10 eyes (40%). Mean best-corrected visual acuity (BCVA) was 20/80 at baseline and 20/63 at three months (p=0.021),” shared Dr. Lovino.

“Today, there is no evidence regarding the optimal clinical management and treatment for these rare and challenging cases. But the analogy in pathogenesis and anatomical features of PPS and CSC built the rationale for us to use PDT in the treatment of PPS,” he said. “Our study demon-strated good anatomical benefits of PDT with significant BCVA improvements at three months,

although we should keep in mind that the functional results in terms of BCVA seem to reduce over time. Nevertheless, additional randomized controlled trials are needed to better clarify the anatomical and functional outcomes after treatment,” Dr. Lovino concluded.

Anti-VEGF therapy in pachychoroid disease

While anti-vascular endothelial growth factor (anti-VEGF) therapy is a common and effective treatment for wet agerelated macular degeneration (AMD), it is also beneficial in treating eyes with macular neovascularization (MNV) complicating pachychoroid disease.

Dr. Enrico Borrelli from the University Vita-Salute San Raffaele, Italy, shared that in the MINERVA study, eyes with MNV secondary to CSC were treated with ranibizumab and experienced a gain of 6.6 letter in visual acuity at a two-month follow-up visit, in contrast with a gain of 1.6 let-ter in the sham group.

He noted that as most patients with pachychoroid disease complicated by MNVs are older than 50 years, it would be

challenging to differentiate pachychoroid disease complicated by exudative MNV from AMD, as these two conditions may have similar characteristics on dye angiographies.

He investigated the relative prevalence of neovascular AMD and exudative MNV secondary to pachychoroid disease in patients older than 50 years with evidence of treatment-naïve exudative MNV over a period of two years, and found that visual prognosis is overall better in MNV complicating pachychoroid disease. “Subjects with pachychoroid disease complicated by MNV have a significantly longer treatment-free interval than subjects with neovascular AMD after a loading dose of anti-VEGF therapy. The latter finding was speculated to be related to lower secretion of VEGF in pachychoroid disease,” shared Dr. Borrelli.

He added that pachychoroid disease is a frequent cause of exudative MNV in aged patients with a high rate of misdiagnosis. It is, therefore, important to perform a correct diagnosis as these two disorders differ in terms of clinical characteristics and prognosis. Anti-VEGF therapy is effective in these cases and PDT may be considered as a combined therapy.

In a following presentation, Dr. Dinah Zur from the Tel Aviv University, Israel, commented that anti-VEGF treatment is effective and requires less frequent injections in pachychoroid aneurysmal type 1 MNV than in nAMD as well, with a mean of 3.5-4.6 annual injections (ranibizumab, aflibercept) and longer treatment-free intervals.

“In cases where anti-VEGF alone does not cause resolution of exudation, the combination therapy of anti-VEGF and PDT is a good option,” Dr. Zur noted .

In central serous choroidopathy, the classic form in the pachychoroid spectrum, we may have visual function impairment, neurosensory detachment, and retinal pigment epithelium changes.”

— Dr. Rosa Dolz-Marco, Spain

Macular Matters

Getting to the root of diseases with subretinal fluid in the macula

by Olawale Salami

Responsible for giving us sharp, clear vision, the macula took the spotlight in the Opthalmologica lecture at the EURETINA 2021 Virtual. Dr. Camiel J.F. Boon, professor of ophthalmology at Amsterdam University Medical Centre and Leiden University, Netherlands, delivered the lecture, sharing valuable insights and new information.

“Due to its unique functional and anatomical characteristics, the macula is especially vulnerable to the accumulation of serous subretinal fluid,” opened Dr. Boon. “Nevertheless, visual acuity can be relatively spared in several of these entities. The differential diagnoses of these clinical entities are broad, but

delineation is possible with thorough clinical history and physical examination, with implications for therapy and prognosis.”

It takes two to tango

The optimal function of the photoreceptors requires efficient nutrient cycling by the retinal pigment epithelium (RPE). However, the key question of what keeps the macula attached has remained unanswered. “The choroid has a higher protein concentration than the retina, leading to the osmotic movement of water,” Dr. Boon explained. “Nutrient and water transport are also mediated by active transport via ion channels. This net

fluid movement keeps the macula dry and attached.”

Dr. Boon added that the retina-choroid interface is highly regulated, and subretinal fluid results from a detachment

“Due to its unique functional and anatomical characteristics, the macula is especially vulnerable to the accumulation of serous subretinal fluid.”

— Dr. Camiel J.F. Boon

of the photoreceptors from the RPE, leading to a visual decline.

Central serous chorioretinopathy (CSC) is essentially a choroid disorder, in which the underlying choroidal tissue degenerates far more severely than the retina. The key etiological factor currently remains unknown.

“In the differential diagnosis, focal or multifocal areas of hyperfluorescent choroidal congestion and leakage are characteristic,” said Dr. Boon. “In CSC, there is a disequilibrium in which increased choroidal permeability and flow affects the barrier function of the RPE, eventually culminating in subretinal fluid accumulation. The treatment is photodynamic therapy.”

Is serous fluid under the macula synonymous with CSC?

There is a broad spectrum of differential diagnoses that can be considered. A variety of neovascular conditions which occur at the interface between the RPE and the Bruch’s membrane may also result in macular fluid accumulation.

The differential diagnosis should consider 12 main pathogenic subgroups: neovascular diseases, vitelliform lesions, inflammatory diseases, ocular tumors, hematological malignancies, paraneoplastic syndromes, genetic disorders, ocular developmental anomalies, medication-related conditions and toxicity-related diseases, rhegmatogenous retinal detachment and

tractional retinal detachment, retinal vascular diseases, and miscellaneous diseases.

In Best’s disease, subretinal fluid formation is linked to mutations in the Best-1 gene that encodes an ion channel in the retinal pigment epithelium. An abnormality in this ion channel results in perturbations in the pumping function of the RPE, especially in the macula. The result of this is fluid accumulation.

Undisturbed visual acuity

According to Dr. Boon, visual acuity can be preserved in many conditions associated with macular subretinal fluid accumulation. “This is because the choroid provides 90% of all the oxygen requirements of macular photoreceptors,” he said.

“Another possible explanation is that the closed compartment may allow a reasonable level of molecular exchange.

Furthermore, cones have fewer oxygen needs than rods, and the fovea may receive oxygen from the perifoveal capillary plexus when detached from the underlying choroid,” he explained. “In addition, cones are more resistant to damage than rods, as seen in the atrophic variant of age-related macular degeneration (AMD), where the rod-rich areas degenerate earlier in the disease process. There is the possibility of an alternative visual cycle in which cones have been shown to recycle visual pigment intra-retinally through the Muller cells.”

Dr. Boon noted that these factors support the observation that visual acuity can be preserved in many macular subretinal fluid accumulation cases.

Looking to the bright future

The exact pathogenesis remains unknown in some of the diseases that are part of the differential diagnosis of serous maculopathy, such as CSC, MEK inhibitor-associated retinopathy (MEKAR), optic pit, tilted disc with inferior staphyloma, serous maculopathy with absence of retinal pigment epithelium (SMARPE), serous maculopathy due to aspecific choroidopathy (SMACH), and serous retinal detachments that occur in Waldenstrom macroglobulinemia.

“A thorough insight into genetic and other risk factors of these diseases is crucial to unraveling their pathogenesis especially in the diseases with high, unmet medical needs,” explained Dr. Boon.

According to him, each of these conditions can be distinguished diagnostically from CSC using the appropriate clinical tools and ophthalmological examinations. Indeed, even a basic ophthalmological work-up using fundoscopy and optical coherence tomography (OCT) can already provide important clues regarding the correct diagnosis. And additional imaging tests such as fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA) can be considered for obtaining a clearer clinical picture.

“In this respect, using a combination of specific imaging and functional tests is essential for guiding the therapeutic decision-making process and can have important clinical and prognostic implications,” concluded Dr. Boon

“Using a combination of specific imaging and functional tests is essential for guiding the therapeutic decisionmaking process and can have important clinical and prognostic implications.”

AI Software

A game-changer in ophthalmic practice

by Nick Eustice

Not too long ago, the idea of artificial intelligence (AI) seemed pretty far-fetched. But today, AI is a very real part of our world, and its applications will only continue to grow as time goes by. Due to its innovative nature, however, we might find ourselves having to think about AI in roles outside what we initially expected, and in contexts that we might find surprising.

That feeling of surprise might show up when you read the title of Prof. Christian Johner’s presentation during Day 3 of the EURETINA 2021 Virtual Conference: “Soft-ware as a Medical Device”.

AI software as a medical device

When we think of a medical device, we might immediately think of a thermometer or an ophthalmoscope in simple terms, or perhaps an optical coherence tomography (OCT) device if we’re thinking of something a bit more complex. But we don’t usually consider software to be a device.

Normally, we consider a device something a bit more tangible, something you can hold in your hand, even if it’s big and heavy. Yet when we consider the world of medical technology, AI software that is used in medical practice is classified by regulating authorities as just that: a device, and a medical one at that.

Speaking during the symposium entitled “From the AI-Lab to Clinical Practice: Clearing the Hurdles”, Prof. Johner, explained the criteria applied by the European Union’s Medical Device Regulations (MDR) when considering whether a piece of AI software is, for legal purposes, a device.

Citing the MDR, Prof. Johner said that a product, whether hardware or software, is a medical device if it is intended by the manufacturer to be used for the diagnosis, treatment, prevention, monitoring, or alleviation of a disease or an injury.

Thus, as we can see, quite a lot of software that is used as a part of one’s practice can be classified as a device,

and consequently held to a very particular standard. Prof. Johner provided a few examples of what might be considered a device.

If software is used in support of clinical decision making, e.g. whether vascular endothelial growth factor (VEGF) therapy would be appropriate in a particular patient’s case, that software is said to be instrumental in making a treatment decision. Therefore, it would be a device. What about software that helps to predict diseases, such as the progression of age-related macular degeneration (AMD)? Here, its classification would be for the purpose of prediction, and this, too, would be a medical device.

Software’s manufacturer intention vs. software’s functionality

The breadth of this definition begs the question: when would software not be considered a device? Prof. Johner provides an example of such a case. Where software is used only for the purposes of training or education, whether of patients or medical professionals, that software would not be considered a medical device. Given the close relationship between education and prevention, however, one can see how this may be a slippery slope.

Here, the greatest degree of importance falls upon the actual intention of the soft-ware’s manufacturer, and not the software’s functionality. Legally, this can be ascertained from instructions, advertising, labeling, and other such literature.

When software is subject to the scrutiny of being a “medical device”, it must undergo the same extensive testing and risk management evaluation as any other physical device. To that end, it is also subject to the same legal liabilities.

Because of the need for safety and concerns for intellectual property, regulations of technology are anything but new, especially in the medical profession. But as technology grows more and more complex and useful, we will probably find ourselves having to look at it in different and surprising ways more and more often.

Soldiers of Sight

The role of aflibercept in treating vision-threatening complications in diabetic macular edema

by Olawale Salami

The efficacy of anti-vascular endothelial growth factor (antiVEGF) in the treatment of diabetic macular edema (DME) is recognized. But can anti-VEGF therapy prevent vision-threatening complications in high-risk eyes? Does prevention of visionthreatening complications result in visual acuity benefit at two or four years?

These questions were addressed by Dr. Neil Bressler, professor of ophthalmology, Johns Hopkins University, Baltimore, USA, and colleagues in the Diabetic Retinopathy Clinical Research Network (DRCR.net).

The DRCR.net Protocol W

The DRCR.net Protocol W is a randomized clinical trial in which eyes with non-proliferative diabetic retinopathy and no macular edema were randomly assigned to receive preventive aflibercept treatment or placebo. The primary outcome was the development of vision-threatening complications.

Dr. Bressler advised physicians on early diagnosis. “Try to identify DME as it develops in the central subfield before vision decreases because visual acuity outcome is not superior if treated before DME develops,” he shared.

Dr. Bressler said that if visual acuity is 20/30 or worse, consider managing DME with anti-VEGF, with a median of 14 injections over two years. “However, suppose DME is identified at a visual acuity of 20/50 or worse. In that case, clinically relevant visual outcomes will likely be superior at one year and over two years when treated with aflibercept compared to bevacizumab or ranibizumab,” he shared.

Dr. Bressler added: “If visual acuity is 20/25 or better, with a median of eight injections over two years, consider starting with aflibercept, or with focal laser treatment followed by aflibercept.”

Taken together, if there’s moderate to severe non-proliferative diabetic retinopathy and no DME, aflibercept prevents vision-threatening complications of proliferative diabetic retinopathy.

Can AI help in the early screening of diabetic retinopathy?

Current data estimates that over 80% of people with diabetes visit their primary care physician at least once a year. However, only about a third of patients undergo screening for diabetic retinopathy. Hence, point of care screening may be a solution to screening these patients and may mitigate

socioeconomic factors, transportation challenges, and referral to specialists.

According to Dr. Jennifer Lim, director of Retina Service University of Illinois, Chicago: “Artificial intelligence (AI) can address the screening burden when applied at the point of care. Autonomous, cloud-based solutions can help rapidly detect more-than-mild diabetic retinopathy (DR) and vision-threatening DR on site.”

Currently, there are two FDA-approved AI systems for detecting DR, namely, the IDxDR and the Eye ART systems. Both methods have high sensitivity and specificity when compared with reading center gradings.

Hand-held portable fundus cameras and smartphones are being paired with AI algorithms to detect referable DR. These lower-cost imaging systems may increase access to early diagnosis globally.

“AI-based DR screening is viable and helps address screening burden in patients with diabetes mellitus,” said Dr. Lim. “The use of autonomous cloud-based solutions that provide real-time diagnosis at the point of care screening is helpful for both the patient and primary care physician. The high sensitivity, specificity, and imageability make it applicable for clinical use today,” she concluded.