
This article was reviewed by Brian Perkins, PhD

Inherited retinal dystrophies (IRDs) are characterized by degeneration of rods and cones; generally, the rods initially degenerate in the peripheral retina, progressing to the central retina, which leads to minimal vision in the fovea and, ultimately, blindness.

The speed of progression varies with the disease. IRDs are not uncommon, and an estimated 1 in 4000 individuals worldwide may be affected, with more gene mutations being identified. Treatments are limited.

Personalizing medicine for patients with IRDs can be challenging.

Investigators find genetic factors may influence diabetic eye disease



“Personalized medicine requires targeting and correcting possibly thousands of unique mutations, considering the wide heterogeneity,” said Brian Perkins, PhD, an associate staff member at the Cleveland Clinic’s Cole Eye Institute in Cleveland, Ohio.

To address this, the National Eye Institute established the Audacious Goals Initiative, which is working toward regeneration of neurons and neural connections in the eye and vision system with the targets being photoreceptors and ganglion cells.

“This goal in humans emerged from the recognition that some species already have the ability to repair damaged photoreceptors,” Perkins said.

Goldfish and zebrafish are noteworthy examples. Fish have similar anatomy and physiology to humans in addition to the ability to regenerate retinal, brain, spinal cord, cardiac, and pancreatic tissues and appendages.

Perkins demonstrated that when a zebrafish’s photoreceptors are damaged, they release molecules that trigger Müller glial cells in the retina to transform into stem cells that divide, mature, and regenerate, restoring the lost rods and cones.

Novel gene therapy/medical device combo sheds light on retina in RP



Much of this knowledge came from examining acute damage to the retina, such as from light damage or mechanical injury, and not from genetic disorders, he explained.

Perkins and his colleagues are investigating zebra-fish that have genetic mutations in genes that are known to cause retinal degenerations in humans.

The 

 gene has been linked to Leber congenital amaurosis and retinitis pigmentosa. Zebrafish with this mutated gene have scoliosis, fertility issues, photoreceptor degeneration, and other pathologies.

Importantly, the few remaining cones in the affected fish are more disorganized and do not regenerate, which raises the question of whether mutant zebra-fish have lost the ability to regenerate.

In siblings of the affected zebrafish and the mutant zebrafish themselves, the investigators damaged the retinas with high-intensity light. 

The photoreceptors were seen to degenerate, and after approximately 2 weeks they began to regenerate. 

Investigators examine anti-VEGF medications in cases with ROP

With cone degeneration, the investigators questioned if the disease environment would limit full regeneration.

Investigation led to the finding that zebrafish with progressive degeneration do not fully regenerate the photoreceptors after damage, Perkins explained.

“This is critical, because it indicates that the disease environment somehow limits the overall capacity for regeneration,” he said.

Many questions remain, including why the retina responds differently to acute damage than to disease, whether full restoration of the cone density is limited by the diseased retina, whether immune cells promote or inhibit regeneration, and whether regeneration can be stimulated without causing additional damage.



Research is unfolding the proteins in retinitis pigmentosa

Future investigation involves translating these findings to mammalian models of blindness to develop better therapies. 

Perkins has no financial interest in this subject matter.

Articles

Studying zebrafish helps unravel mysteries of photoreceptor regeneration .

Regeneration may help restore vision in inherited retinal dystrophies 

The Association for Research in Vision and Ophthalmology (ARVO) will hold its annual meeting for 2021 in a virtual format from Saturday, May 1, to Friday, May 7. 

, ARVO will present its sessions on the Pathable online platform.

Although 3 COVID-19 vaccines have been granted emergency use authorization by the United States Food and Drug Administration, the pandemic continues to affect in-person meetings. 

In December, ARVO announced plans to move its 2021 annual meeting to a fully virtual format. The event had originally been scheduled for early May in San Francisco, California.

According to Julene Joy, CAE, ARVO’s chief marketing and communications officer, the theme of the 2021 ARVO annual meeting is “Revolutionary Eye and Vision Research.”

“Innovation and advanced technologies have fostered significant discoveries in eye and vision research in the last decade rivaling those in any discipline,” Joy said. “The theme of the 2021 ARVO annual meeting is the next revolution of clinically translating these discoveries to restore and preserve vision.”

Joy noted that while virtual conferences can result in long hours, ARVO is alleviating some of that stress with the “Month of ARVO.” 

This will include:

Thursday, May 20 – Friday, May 21, 2021:

According to Joy, all meeting content and materials will be accessible until Wednesday, June 30, 2021.

In a virtual setting, Joy said, attendees can still expect the meeting they know and look forward to every year. 

“Poster and paper presentations, keynote addresses, award lectures, and special events like ARVO’s Got Talent, the ARVO Foundation Gala and the WEAVR Luncheon are adapting to meet the moment,” she said. “Attendees can also expect to still be able to engage with a lively exhibit hall and explore new products and information from our impressive list of exhibitors. Live chat and exhibitor demonstrations will ensure that nothing is missing in the virtual experience.”

The ARVO staff, led by Executive Director Iris M. Rush, CAE, has met the challenges associated with hosting a virtual event amid the pandemic.

“ARVO’s Board of Trustees was quick to prioritize the health and safety of our members, and the decision to go fully virtual was made well in advance, allowing plenty of time for members and staff alike to prepare,” Joy said. “ARVO staff has worked closely with leadership, stakeholders, vendors and our platform provider, Pathable, for months to ensure that we are still providing a premier annual meeting experience with all the features, networking, and learning that our attendees have come to expect.”

Here are some highlights from this year’s program, including keynotes and lectures:


As in years past, ARVO/Alcon Keynote Lectures will bookend the opening and closing days, offering a chance for attendees to focus on key points of the meeting theme and find out how research continues to affect the way they treat patients.


Jonathan Kipnis, PhD, BJC investigator, Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology; professor of neurology, neuroscience and neurosurgery; and director, Center for Brain Immunology and Glia (BIG) at the Washington University School of Medicine in St. Louis, Missouri, will present the opening keynote. 

Kipnis’ research focuses on the interactions between the immune system and the central nervous system. 

As part of its work, his team has detailed how human brain function relies, in large part, on the mechanisms of the immune system and how immune molecules (cytokines) play a key role in neuromodality. The work of the team can have an impact on Alzheimer disease, autism, and multiple sclerosis.

Kipnis is a graduate of the Weizmann Institute of Science in Rehovot, Israel. At the institute, he was a Sir Charles Clore scholar and received a distinguished prize for scientific achievements awarded by the Israeli Parliament, the Knesset.

 In 2018 he received an NIH Director’s Pioneer Award to explore in more depth neuro-immune interactions in healthy and diseased brains.


Delivering the closing keynote address at the ARVO virtual conference is Helen Blau, PhD, the Donald E. and Delia B. Baxter Foundation Professor of Stem Cell Biology, and director of the Baxter Laboratory for Stem Cell Biology at Stanford University School of Medicine.

Blau’s work centers around stem cells, and her focus has been on nuclear reprogramming and the demonstration of the plasticity of cell fate using cell fusion.

During her career, she has served on the Ellison Medical Foundation Scientific Advisory Board and the Harvard Board of Overseers.

Blau is an elected member of the American Academy of Arts and Sciences, the National Academy of Medicine, the National Academy of Sciences, and a fellow of the American Association for the Advancement of Science.



According to ARVO, the 2021 Basic Clinical Lecture will be presented to clinical researchers from a basic perspective. Titled “Transcriptional Dynamics in Eye Development and Disease,” organizers include Elfride De Baere, Carlo Rivolta, and Stephany Hagstrom. 

Speakers include Anand Swaroop, PhD; Sandro Banfi; Janey Wiggs, MD, PhD; Timothy Cherry, PhD; Seth Blackshaw, PhD; and Magdalena Renner. 

The panel will discuss some advances in RNA biology in the eye and transcriptional misregulation as cause of different eye diseases. 

The speakers also will shed light on diagnostic strategies and the role of RNA molecules as biomarkers and as targets for novel therapeutic approaches.


The 2021 ARVO Foundation Gala will be held virtually from 7 PM to 8 PM Sunday, May 2. The event will be open to all ARVO 2021 registrants at no additional fee to attend. ARVO will host its first ARVO’s Got Talent competition during the event. 

The grand prize winner and runner-up videos will be announced and aired during the event. ARVO officials will score the videos and share the highest-scoring entries on the annual meeting virtual platform, Pathable. Votes for the top videos will be accepted from April 15 to May 2.


Speakers for this session include Luk Vandenberghe, PhD; Rupesh Agrawal, MD; Elia Duh, MD; Ashok Kumar, PhD; Timothy Blenkinsop, PhD; and Melanie Ott, MD, PhD. 

Amid the COVID-19 pandemic, there is a great deal of interest in understanding how the coronavirus affects the eye. This symposium will address the issue with a panel of researchers and clinicians focused on ocular and nonocular diseases of coronaviruses.

Epigenomics and Personalized Medicine: “Across the Globe”

Speakers for this symposium include Jayakrishna Ambati, MD; Tara Moore, PhD; Ales Cvekl, PhD; Renu Kowluru, PhD; Michael Dyer, MD; and Louise Porter, PhD. 

This symposium features leading scientists who will share their latest research on the role epigenomics is playing not only during development but also in shaping future personalized medicine for ocular diseases involving tissues from the anterior and posterior segments, including corneal dystrophies, glaucoma, diabetic retinopathy, and macular degeneration.

Epidemiology of Diabetic Retinopathy and Age-Related Macular Degeneration: Past, Present, and Future

Taking the stage for this session is a panel that includes Lloyd Paul Aiello, MD, PhD; Tien Wong, PhD; Barbara Klein, MD; Caroline Klaver, PhD; and Emily Chew, MD. The speakers will discuss past achievements, current challenges, and future research in risk, diagnosis, treatment, and management of DR and AMD.


Focus on the Fovea; What Makes the Fovea Unique?

This session will feature Dennis Dacey, PhD; Constance Cepko, PhD; Raunuk Sinha, PhD; Joseph Carroll, PhD; Cynthia Toth, PhD; and Christine Curcio, PhD. Using a range of techniques, members of the panel have studied the structure, physiology, and pathology of the fovea. The symposium is of interest to basic and clinical researchers.


Childhood Vision Disorders: What is on the Horizon? (EY)


This session will feature Jonathan M. Holmes, MD, Eileen Birch, PhD, Ben Thompson, PhD, Fatema Ghasia, MD, Susan Cotter, OD, MS, FAAO, and Irene Gottlob, MD, PhD. 

The panelists will discuss vision screening using retinal birefringence instrumentation; objective assessment of visual acuity for amblyopia detection; management of amblyopia with binocular treatment and monitored occlusion; impact of fixational eye movement abnormalities on visual function deficits and treatment outcomes in amblyopic children; utility of handheld OCT in children; nonsurgical optical treatments for intermittent exotropia and patient-reported outcome measures and emerging telemedicine approaches for children.


Ocular Tissue Mechanics, Homeostasis, and Diseases (LE)


Scheduled participants include Valerie M. Weaver, PhD, Velia Fowler, PhD, Xiaohua Gong, PhD, P. Vasantha Rao, PhD, David Križaj, PhD and Sara Thomasy, PhD. 

They will highlight advances in the understanding of the mechanobiology of ocular cells and tissues including the cornea, trabecular meshwork, and lens, and the role(s) played by the extracellular matrix, cell adhesion machinery, actomyosin, ion channels, tensile properties, and mechanotranscription in regulation of structural integrity and functional homeostasis and in ocular disease.


Retinal plasticity in disease and regeneration (RC)


This minisymposium is scheduled to feature Daniel Goldman, MD, Stefanie Wohl, PhD, Bryan Jones, PhD, Tom Reh, PhD, Sai Chavala, MD, and Marla Feller, PhD, who will summarize the mechanisms of retinal plasticity, its dynamics, and selectivity during development and in disease models.



Scheduled to share the podium for this session are Darragh Duffy, PhD, Cintia De Paiva, MD, PhD, Dong Feng Chen, MD, PhD, Heping Xu, MD, PhD, Douglas Jabs, MD, and Deborah Ferrington, PhD. 

The panelists will elucidate the implications of aging and its interaction with the immune system on various ocular disorders and their mechanistic underpinnings.



This session will feature Jeffery Holt, MD, Darryl Overby, PhD, Judith West-Mays, PhD, Kate Keller, PhD, Ian Sigal, PhD, and Pedram Hamrah, MD. 

The speakers will focus on recent advances in cellular and biophysical mechanisms involved in different aspects of biomechanics in the eye, with relevance to glaucoma, the cornea, and the lens.


Corneal Wound Healing: Basic Mechanisms and Therapeutic Approaches (CO)


This session will feature Fu-shin Yu, PhD, Krystel Huxlin, PhD, Matilda Chan, MD, Vivien Coulson-Thomas, PhD, Ali Djalilian, MD, and Arkasubhra Ghosh, PHD. 

The panelists will offer an overview on molecular mechanisms and repair processes that govern corneal wound healing and present novel therapeutic strategies for facilitating corneal repair. This program offers information key to other ocular diseases that result from tissue injury.


State of Refraction: Etiology, Comorbidities, and Treatments for the Worldwide Myopia Epidemic (VI)


On the dais for this session is a panel that is scheduled to include Terri Young, MD, MBA, Kathryn Rose, PhD, Machelle Pardue, PhD, Jost Jonas, MD, Christine Wildsoet, OD, PhD, and Maria Liu OD, PhD. 

They will discuss current and potential treatment options, including pharmacological and optical modalities.



Adverse Ocular Outcomes from Emerging Therapies: Mechanisms, Diagnoses, and Management


Speakers for this minisymposium include Stephen H. Tsang, MD, PhD, Tomas Aleman, MD, Alison Skalet, MD, PhD, Bahram Bodhaghi, MD, PhD, and Brian VanderBeek, MD. The panelists will discuss how emerging therapies produce untoward effects in the eye in varied ways.



This session will feature Franklin Caval-Holme, PhD, Richard Lang, PhD, Morven Cameron, PhD, Christophe Ribelayga, Phd, Steven Barnes, PhD, and Erika Eggers, PhD. 

The panelists will discuss recent results on how dopamine levels in the retina are controlled, the importance of dopamine for regulation of neuronal and vascular development. The speakers will detail how dopamine modulates retinal sensitivity in light adaptation and circadian rhythms.


Rho Kinase Inhibitors, a New Class of Treatment for Glaucoma and Corneal Disease (PH)


This panel will feature Casey Kopczynski, PhD, Haiyan Gong, MD, PhD, Arthur Sit, MD, Dan Stamer, PhD, Jeffrey Goldberg, MD, PhD, and Shigeru Kinoshita, MD, PhD. 

Their presentations will include basic science research for understanding the underlying mechanisms and clinical experience with this new drug class.




Speakers will include Yutao Liu, MD, PhD, Markus Preising, MD, PhD, Mary C. Whitman, MD, PhD, Zia Chaudhuri, MS, Joseph L. Demer, MD, Elias Traboulsi, MD, and Mervyn G. Thomas MD. They will discuss genetic determinants for strabismus, which remain elusive.


Longer and Better Vision After Corneal Transplantation for Patients: From Bench to Bedside (CO)


Speakers for this session will include Reza Dana, MD, Jerry Niederkorn, PhD, Pedram Hamrah, MD, Junko Hori, PhD, Shigeru Kinoshita, MD, PhD, Claus Cursiefen, MD, PhD, and Takefumi Yamaguchi, MD, PhD. 

The focus of the speakers is to outline some of the latest knowledge on immunology, neuroimaging, and visual optics in corneal diseases and transplantation.


Novel Biomaterials for Ocular Diseases (CO)


This mini-symposium will feature May Griffith, PhD, Thomas Fuchsluger, MD, Gerd Auffahrt, MD, Uday Kompella, PhD, Jui-Yang Lai, PhD, and Maribel Vazquez, OD. 

The event brings together 6 sections within ARVO, including cornea, lens, pharmacology, glaucoma, and retina. The speakers scheduled for this session will discuss the latest trends involving drug delivery and clinical translation.


Teleophthalmology, the New Normal in a Post-COVID Context (CL)


Scheduled speakers include Anthony Vipin Das, MD, Alex Charter Taleb, MD, PhD, Renata Puertas, MD, Tunde Peto, PhD, Gabriela Saidman, MD, and Sheila John, MD. They will discuss the basics regarding how to start a program and ensuring its quality. 

During the session, the panelists also will report on successful new models of eye care delivery and their impact on preventing blindness by detecting significant eye diseases such as glaucoma, DR, AMD, ROP, and cataracts, as well as the the post-COVID-19 challenges, and where future research lies in regard to emerging technologies available.

Cell Biology of the Homeostasis of the Choroid (RC)


Sharing the stage will be Barbara Braunger, PhD, Patricia D’Amore, PhD, MBA, Bela Anand-Apte, PhD, Robert Mullins, PhD, Gerard A. Lutty PhD, and Wai Wong, MD, PhD. 

The panel for this minisymposium will focus on some of the newly identified mechanisms that contribute to tissue homeostasis and regulate cell-cell interactions in the choroid.



This session will feature Anat Galor, Steven Pﬂugfelder, Pedram Hamrah, MD, Randy Kardon, MD, PhD, Juanita Gallar PhD, and Konstantinos D. Sarantopoulo, MD, PhD. 

During the presentation, this panel will focus on current knowledge and outline current research directions that will lead to improved diagnosis and management of ocular surface pain.

Single Cell RNA-Sequencing Revolution Part II: Applications, Biology, and Clinical Relevance (IM)


This minisymposium will feature Tavé van Zyl, MD, Robert Lavker, PhD, Daniel Saban, PhD, Kapil Bharti, PhD, Thomas Reh, PhD, and Filip Swirski, PhD. During this session, the participants will discuss research approaches using scRNA-seq and cutting edge bioinformatic pipelines. 

Topics to be covered during the session include stem cells, immune cells, primary human cells, iPSCs and organoids of the cornea, trabecular meshwork, retina, and retinal pigment epithelium.


The featured speakers during this symposium include Ruth Ashery-Padan, PhD, Ales Cvekl, PhD, Cheryl Gregory-Evans, PhD, Melinda K. Duncan, PhD, Neil Lagali, PhD, and Christopher Riemann, MD. During this session, the panelists will discuss the roles of PAX6 in tissue development and attempts to relate these functions with the progressive eye diseases experienced by aniridia patients as they age.


For ophthalmologists whose interests cannot be simply defined in a single section, the cross-sectional platform sessions offer a range of options. These will include:

Functional Analysis of Non-Coding Genetic Defects Underlying Inherited Ophthalmic Disease (GEN)


The panel for this section includes Ayellet Segrè, PhD, Elfride de Beare, MD, PhD, Jayshree Advani, PhD, Suzanne de Bruijn, PhD, and Philippe Mourrain, PhD. These researchers are investigating a broad range of inherited eye disorders. They will present their novel and recent functional genomic discoveries.

Technologies for Visual Enhancement in 2021 and Beyond (LV)


This section features Eli Peli, OD, Ava Bittner, OD, PhD, Chris McCarthy, MD, Marie-Celine Lorenzini, PhD, and Ashley Deemer, OD. They will cover topics in robotics, virtual reality, and image enhancement via head-mounted display technology and computer vision algorithms used in implantable technologies.

In Vivo Theranostic Platforms for Monitoring and Activation of Ocular Therapies (MOI)


The panel will include Robert J. Zawadzki, PhD, Artur V. Cideciyan, PhD, Jennifer J. Kang-Mieler, PhD, Karl G. Csaky, MD, PhD, Ursula Schmidt-Erfurth, MD, and M. Valeria Canto-Soler, PhD. During the section, the speakers will bring together both animal and human studies that show promising therapeutic effects of these novel therapies and explore optical tools allowing its monitoring and activation.


The virtual 2021 Women in Eye and Vision Research (WEAVR) Luncheon will be held from 1:15 PM to 3:15 PM Monday, May 3. The event, which will include a keynote address, will be open to all ARVO 2021 registrants. 

‘Revolutionary Eye and Vision Research’ theme of annual meeting.

ARVO sets stage for virtual event

This article was reviewed by Shawn Kavoussi, MD

Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a rapid noninvasive autofluorescence imaging modality that provides additional disease details beyond conventional imaging modalities. 

Using FLIO lifetimes—that is, the rates of autofluorescence decay—different autofluorescence patterns can be appreciated in affected eyes with various retinal diseases.

Ocular gene therapy offers hope for inherited retinal disease

This novel technology casts a new light on fundus imaging by providing different colorful perspectives of retinal diseases that were not available previously, and all in about 2 minutes.

“This novel technology detects the in vivo autofluorescence lifetimes at the back of the eye,” according to Lydia Sauer, MD, from the Department of Ophthalmology and Visual Sciences at the Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah.

Healthy eyes, she explained, exhibit the same characteristic pattern of short FLIO lifetimes in the foveal center and long lifetimes at the optic nerve. 

In contrast, eyes with retinal diseases are characterized by numerous different autofluorescence patterns depending on the diseases present.

Sauer and colleagues studied the phenotypes, genotypes, and longitudinal changes in Stargardt disease in 45 genetically characterized patients (mean age, 39 years), of whom 35 had the 

-associated STGD3, and 7 had PRPH2/RDS-associated macular dystrophy, the last 2 of which are similar to Stargardt disease. Ten patients were followed longitudinally for a mean of 19 months.


Three phenotypes have been identified previously in patients with Stargardt disease 

Type 1 is characterized by only a central lesion, type 2 flecks across the macula, and type 3 large atrophic areas. Imaging technology took a step forward with the advent of FLIO, which also shows these lesions. 

However, FLIO also demonstrates both significantly different lifetimes among the 3 phenotypes and that the lifetimes in the foveal center are correlated significantly with the best-corrected visual acuity, Sauer noted.

Sauer and colleagues reported a particularly important finding,

 that is, FLIO demonstrated that the geographic atrophy secondary to 

has a markedly different appearance from the retinal atrophy associated with Stargardt disease; in contrast, the 2 diseases can appear very similar when using autofluorescence intensity imaging. 



The investigators also reported previously that eyes with AMD were characterized by a ring with prolonged lifetimes that are seen as a shift to blue at the fundus; in contrast, that pattern is not seen in eyes with Stargardt disease.

This pattern difference facilitates easy differentiation of the 2 diseases.


Sauer also is studying the different genotypes in patients with 

“We believe that FLIO imaging can show differences among the many different genetic subtypes,” she said.


Another area of research interest is evaluation of the details in eyes with 

-associated macular dystrophy, which are Stargardt-like dystrophies.

“It is very interesting that all eyes with PRPH2/RDS-associated macular dystrophy showed flecks of short FLIO lifetimes,” she noted.

This is noteworthy because the baseline FLIO image showed some flecks of short FLIO lifetimes that were not visible on the baseline autofluorescence intensity image but only appeared 1 year later on a follow-up image.

“At that time, the FLIO lifetimes are prolonged from short to long and the patient we examined reported a new central scotoma where an area of markedly prolonged FLIO lifetimes was seen on the follow-up image,” she said.

Sauer explained that the relevance of this research is that the short FLIO flecks appear before changes seen on other imaging modalities including OCT.

The researchers believe that when the short FLIO lifetimes are seen, they may be reversible because they precede structural retinal changes. However, by the time the changes appear on other imaging modalities, reversing them may be impossible.



Risk awareness helps identify medication-induced retinal toxicity

These flecks also appear in some patients with Stargardt disease and Sauer noted that they behave the same as in PRPH2/RDS-associated macular dystrophy. 

FLIO lifetimes show a characteristic pattern in Stargardt disease, and different phenotypes can be identified. Different genotypes have characteristic FLIO findings.

“The most important finding is that short flecks initially identified by FLIO imaging prolong over time and these changes seen on FLIO imaging are visible before appearing on OCT images and other imaging modalities,” Sauer concluded. 


Sauer is a medical consultant to Tesseract Health and receives nonfinancial support from Heidelberg Engineering.


1. Sauer L, Gensure RH, Andersen KM, et al. Patterns of fundus autofluorescence lifetimes in eyes of individuals with nonexudative age-related macular degeneration. 

2018;59(4):AMD65-AMD77. doi:10.1167/iovs.17-23764

FLIO provides earlier diagnostic capabilities than other imaging modalities.

Colorful FLIO imaging revelations in Stargardt disease 

This article was reviewed by Daniel F. Martin, MD

The Diabetic Retinopathy Clinical Research (DRCR) Network, established in 2002 by the National Eye Institute, has orchestrated numerous randomly assigned clinical trials over the years that initially focused on improving treatment of 

Over the past 3 years, however, that focus expanded to include studies of all retinal diseases, and in 2019, a new name, the DRCR Retina Network, was adopted to reflect its new mission.

Pilot pregnancy pathway addresses challenges of diabetic retinopathy screening

“Over the past 17 years, this highly collaborative network has conducted more than 30 DR multicenter studies and published more than 100 reports from 160 clinical sites and boasts more than 1800 members,” said Daniel F. Martin, MD, who along with Jennifer Sun, MD, MPH, currently serve as the network chairpersons for the DRCR Retina Network.

Martin is chairman of the Cleveland Clinic Cole Eye Institute, the Barbara and A. Malachi Mixon III Institute Chair in Ophthalmology, and a professor of ophthalmology at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University in Cleveland.

This research group has struck gold over the years with a number of high impact studies that have helped define the standard of care of diabetic retinopathy. 

At a recent Vision Research Symposium sponsored by the Cleveland Eye Bank Foundation, Martin described 5 of the most important findings from DRCR Retina Network studies.

Aflibercept broadly effective for reducing DR severity in post-hoc analysis

 
The seminal finding of this study was that anti-VEGF agents are the most effective treatment for 

. 

In this study, 854 eyes (vision of 20/32-20/320) with DME were randomized to treatment with laser, ranibizumab (Lucentis; Genentech, Inc), ranibizumab with laser, or triamcinolone with laser. 

After 5 years of follow-up, investigators found that when compared with laser, ranibizumab provided significant (

 < .001) increases in vision either as monotherapy or when combined with laser. 

“Anti-VEGF drugs are now standard of care, and Protocol I was the first published large randomly assigned clinical trial that showed just how effective these drugs are for DME,” Martin said.


 
The need for injections decreased dramatically over 5 years. “This was a remarkable finding, and something that we did not expect. In protocol I, patients received a mean of 9 injections in the first year,” Martin said. “Following this intensive treatment, only 2 to 3 injections were required in year 2, and only 0 to 1 injections per year in years 3, 4, and 5. DME can be a relatively self-limited disease, and that may be particularly true with appropriate treatment.”


DME strategies directed by knowledge of mechanisms

 
In this study, the 3 available anti-VEGF treatments, aflibercept (Eylea; Regeneron Pharmaceuticals, Inc), bevacizumab (Avastin; Genentech, Inc), and ranibizumab, were compared over a 2-year period for the treatment of DME. 

The results showed that patients with visual acuity from 20/32 to 20/40 did equally well with any of the 3 drugs. 

But for patients with visual acuity of 20/50 or worse, aflibercept was superior to the other 2 drugs.

As a result of this study, Martin explained, any of the 3 drugs are appropriate choices for patients with DME and vision of 20/40 or better, although bevacizumab is much less expensive than the other 2. 

For those with visual acuity of 20/50 or worse, aflibercept is the most effective drug for reducing DME and improving visual acuity. 

Bevacizumab and ranibizumab are still effective in these eyes, and it may still be reasonable for cost purposes to start with bevacizumab since the absolute difference between drugs in the proportion of patients who gained 10 or more letters was only 10%.

An ongoing DRCR study (Protocol AC) is evaluating whether starting with bevacizumab and then switching to aflibercept if the desired result is not achieved is an effective strategy that does not compromise longer-term visual outcomes.

 
All major clinical trials that have evaluated the efficacy of anti-VEGF drugs for DME have only included eyes 20/32 or worse.

“But what about those eyes that have DME on OCT [optical coherence tomography] but visual acuity of 20/25 or better?” Martin asked. “Do those eyes need to be treated? 

Post hoc analysis: Protocol V provides more practical DME guidance for clinicians



Are long-term visual acuity outcomes compromised if we do not treat? Until Protocol V, we did not know the answer to this question that is commonly encountered in clinical practice.”

In Protocol V, 702 eyes with center-involved DME and vision of 20/25 or better were randomly assigned to initial observation, laser, or treatment with aflibercept. 

The study found that 2-year visual outcomes are excellent whether eyes are initially treated with anti-VEGF versus laser or observation with deferral of anti-VEGF until visual acuity worsens. 

Observation was just as effective as immediate treatment, and over a 2-year period, the long-term outcome was not compromised by delaying treatment until necessary.

Identifying gaps in anti-VEGF treatment among minorities with DME

 
It has been known for years that retinal neovascularization is exquisitely sensitive to anti-VEGF agents. 

However, the question of whether or not repeated anti-VEGF injections could be used effectively for the treatment of proliferative diabetic retinopathy (PDR) had not been answered until Protocol S. 

In Protocol S, patients with PDR were randomly assigned to anti-VEGF treatment with ranibizumab following a defined algorithm versus panretinal photocoagulation (PRP).

At 2 years and at 5 years, anti-VEGF treatment and PRP were found to be equally effective with no difference in long-term visual acuity. 

A major concern that remains in eyes treated with anti-VEGF agents alone, however, is the risk of progression of PDR in these eyes if they are lost to follow-up. 

Probe of IRIS Registry shows anti-VEGF injections leading treatment for PDR

In the first year of Protocol S, patients required a mean of 9 injections to control their proliferative disease, and many needed continued dosing throughout 5 years for the disease to remain quiescent.

Since anti-VEGF treatment does not permanently improve the underlying ischemia that produced the retinal neovascularization, missing injections could lead to recurrence of active disease and the possibility of catastrophic consequences, as have been documented in a few small case series. 

The specific role of anti-VEGF to treat PDR is still evolving, but in selected cases, it can be a reasonable choice that also reduces the risk of DME.

The future of the DRCR Retina Network is bright. Numerous studies will be completed during the next few years, and many new studies are being developed. 

Research suggests course of diabetic eye disease influenced by genetic factors

Planned studies include those that evaluate the use of fenofibrate to reduce diabetic retinopathy, long-term age-related macular degeneration outcomes, prevention of radiation retinopathy, vitreoretinal surgery for epiretinal membranes, and low-dose bevacizumab compared with laser for zone 1 retinopathy of prematurity. 

--

Martin has no financial interest in this subject matter.


1. Diabetic Retinopathy Clinical Research Network; Elman MJ, Aiello LP, Beck RW, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. 

. 2010;117(6):1064-1077. doi:10.1016/j.ophtha.2010.02.031

2. Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. 

 2015;372(13):1193-1203. doi:10.1056/NEJMoa1414264

3. Baker CW, Glassman AR, Beaulieu WT, et al; DRCR Retina Network. Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: a randomized clinical trial. 

. 2019;321(19):1880-1894. doi:10.1001/jama.2019.5790

4. Gross JG, Glassman AR, Liu D, et al; Diabetic Retinopathy Clinical Research Network. Five-year outcomes of panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. 

. 2018;136(10):1138-1148. doi:10.1001/jamaophthalmol.2018.3255

The results from Diabetic Retinopathy Clinical Research Network protocols have become the standard of care for treating DME and proliferative diabetic retinopathy. 

The DRCR Retina Network's top 5 greatest hits

This article was reviewed by Fasika A. Woreta, MD, MPH

When confronted with injuries to the iris, which in many cases can be complex, certain steps help ensure successful outcomes, according to Fasika A. Woreta, MD, MPH, who presented her pearls for managing the iris during open globe repair and reconstruction of the iris following trauma.



In cases of open globe injuries when there is iris prolapse, Woreta advises making a paracentesis opposite to the area of the prolapse; this is followed by injection of a minimal amount of a viscoelastic and gentle repositioning of the iris using an iris sweep. 

Injecting excessive viscoelastic can result in increased pressure and additional iris prolapse.

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“An important point in such cases is to avoid inadvertent incarceration of the iris into the suture as well as to avoid cutting the iris, except in cases in which it is frankly necrotic or epithelialized because the iris tissue can be used for future reconstruction,” said Woreta, an assistant professor of ophthalmology and director of the Eye Trauma Center at Wilmer Eye Institute, Johns Hopkins Medicine in Baltimore, Maryland.

Woreta described a case in which a 30-year-old police officer was hit in the eye by a stray bullet at a shooting range. 

The patient sustained a full-thickness corneal laceration at the limbus with iris prolapse.

The reparative steps in this case followed those mentioned previously: creation of a paracentesis opposite the area of prolapse, injection of minimal viscoelastic, and iris sweep. 

Before any corneal sutures are placed, the iris may prolapse again after the sweep and so placing a few sutures before sweeping may be necessary.

Pearls for ophthalmologists guides for handling damage during open globe repair.

Ophthalmology Times: April 1, 2021

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Options for managing the iris after trauma