October 30, 2020 Conference

AM - Diabetic Retinopathy Update

781st Meeting - Welcome Remarks
Jorge Arroyo

Nauman Chaudhry

Deep transfer learning classification algorithms built on fundus photos generalize with variable accuracy across devices
John Miller, Kun-Hsing Yu, Ashley Kras

Purpose: As deep learning applications to ophthalmology imaging increase in clinical relevance and deployment, there is limited knowledge regarding generalizability of algorithm performance across different platforms. This study set out to examine the accuracy of a fundus photo classifier built on one device dataset can be replicated in a second dataset captured on a different device. Method: 25,000 high quality fundus photos were manually selected from the UK Biobank (UKBB) (Topcon 3D OCT-1000, field angle 45°). A simple deep transfer learning model based on VGG architecture was built to classify images into right vs left eyes. This untouched algorithm was then validated on 2 smaller samples (n=430) of the fundus photos (Optos® California, field angle 200°) from Mass. Eye and Ear Infirmary (MEEI); the first sample was cropped to the posterior pole (MEEI-a) to approximate the region captured by the UKBB sample and the second same (same images) was cropped to the circular fundus edge (MEEI-b). The same process was then repeated in reverse; a model constructed on MEEI images was deployed on UKBB images. Results: The UKBB laterality classification model (LCM) achieved AUROC 0.997. When evaluated on dataset MEEI-a and MEEI-b, the resulting AUROC’s were 0.944 and 0.778 respectively. The LCM subsequently built on MEEI-a achieved AUROC 0.991. When evaluated on MEEI-b and UKBB datasets, performance dropped to AUROC’s of 0.545 and 0.713 respectively. Conclusion: Simple and accurate algorithms generalize variably across devices and scanning protocols. We expect to see similar limitations in other forms of multimodal imaging, including OCT, AF, and OCT-A. This finding highlights the importance of validation studies prior to clinical deployment.

Undiagnosed Retinopathy: Using Big Data to find those at Highest Risk of Blindness
Kristen Nwanyanwu

Importance: Diabetic retinopathy (DR) is a leading cause of preventable blindness. Given both under diagnosis of diabetes and suboptimal DR screening among those with diabetes, there is substantial burden of undiagnosed DR. Objective: To estimate the prevalence and determine the correlates of undiagnosed DR among US adults. Design: Cross-sectional Setting: 2005-2008 National Health and Nutrition Examination Survey Participants: 5,563 participants aged 40+ years who underwent fundus photography. . Main Outcome(s) and Measure(s): Undiagnosed DR, defined as lack of awareness of DR found on fundus photography. Results: Prevalence of undiagnosed DR in adults aged 40+ was 10.6%, representing an estimated 9.8 million individuals. This included nearly one-quarter (23.1%) of those with self-reported diabetes (2.9 million) and 6.8% of those who reported not having diabetes (6.9 million). Notably, among those who reported having diabetes and had photographic evidence of retinopathy, 70.1% had undiagnosed DR. Conclusions and Relevance: A substantial proportion of DR goes undiagnosed. Greater, more targeted efforts are needed to diagnosis and treat DR to decrease the burden of preventable blindness.

Widefield Swept Source OCT Angiography in Diabetic Retinopathy
Nadia Waheed

OCT angiography has been shown to be sensitive to diabetic vascular changes in the eye. Since pathology of diabetic retinopathy may be missed if looking at the posterior pole alone, it is important to be able to do wide field OCT angiography to look for the changes of diabetic retinopathy. In this presentation, I will describe the technological advancements that led to wide field angiography, the techniques of widefield angiography, and how it can assist in the diagnosis, follow up and management of diabetic retinopathy

Introduction of Guest of Honor
Nauman Chaudhry

DRCR Retina Network; Past, Present & Future
Lee M. Jampol, Jennifer K. Sun

Since its founding in 2002 the Network has performed multiple clinical trials that have vastly changed the management of diabetic retinopathy throughout the world. This lecture will review the founding and structure of the DRCR Retina Network. It will also review the major accomplishments, describe the ongoing clinical trials, and describe the future plans for clinical studies. It will cover the management of patients with diabetic macular edema and proliferative diabetic retinopathy based upon the findings of the DRCR studies.

Diabetic Macular Edema: When to Treat and When to Observe
Jorge Arroyo

The treatment strategies for diabetic macular edema include observation, focal argon/micropulse laser, intravitreal injection of anti-VEGF drugs, pneumatic vitreolysis/enzymatic vitreolysis, and pars plana vitrectomy with membrane peeling. Clinicians should be alert for other clinical entities such as vitreomacular traction and retinal arteriolar macroaneurysms which can mimic and/or exacerbate diabetic macular edema.

Severe Nonproliferative Diabetic Retinopathy: What To Do Now?
Brian Y. Kim

Diabetic retinopathy continues to be a leading cause of blindness worldwide. Duration of disease as well as severity of hyperglycemia are among the factors known to be major risks for both the development and progression of diabetic retinopathy. Proliferative diabetic retinopathy has been identified as the most vision threatening form of the disease. Thus, treatment of the nonproliferative stages of the disease remains important. Specifically focusing on severe nonproliferative disease, progression to proliferative disease is very high, with over 50% of patients progressing to proliferative disease within one year. Classic trials such as the Diabetic Retinopathy Study, as well as the Early Treatment Diabetic Retinopathy Study have given guidance for treatment options for these patients. Newer trials such as PANORAMA also specifically look at the use of anti-VEGF therapy for patients with severe nonproliferative diabetic retinopathy. We will review those results in this session.

High Risk PDR: Anti-VEGF or PRP?
Caroline Baumal

Panretinal laser photocoagulation (PRP) has been the main treatment of proliferative diabetic retinopathy (PDR) for over 40 years. However, recent findings from protocol S and other studies demonstrate that anti-VEGF intravitreal injection may be an alternative treatment. The DRCR.net protocol S compared anti-VEGF injection to PRP laser for treatment of PDR. The 5 year study results demonstrated that overall both treatments performed well. Specific retinal factors such as the presence of diabetic macular edema or vitreous hemorrhage may favor anti-VEGF injections, while patients who are not available for frequent office visits may be more suitable for PRP. These issues and cases will be reviewed.

The Future Treatment of Diabetic Retinal Disease
Jeffrey Heier

Anti-VEGF therapy has revolutionized our management of diabetic eye disease, effectively addressing both diabetic macular edema and diabetic retinopathy. However, anti-VEGF therapy has limitations: it requires frequent injections, and only 30-45% of patients with diabetic macular edema achieve meaningful visual gains. Randomized clinical trials have demonstrated we are at the peak of the dose-response curve, with all current anti-VEGF agents achieving similar gains. New treatments focus on increasing efficacy and minimizing treatment burden. New targets beyond the anti-VEGF pathway are being studied. The angiotensin/TIE2 pathway and the plasma kallikrein pathway have been the focus of several studies, and 1 bispecific antibody targeting VEGF and ANG2 is in phase 3 study. Drug delivery, which has been elusive to date, has demonstrated promise, with the port delivery system having achieved efficacy in wet AMD, and currently being studied in diabetic eye disease. Gene therapy has also shown success in wet AMD studies, and is being studied in diabetic eye disease. Both the port delivery system and gene therapy have the potential to alleviate treatment burden and may offer some benefits over the conventional pharmacokinetics of intravitreal injections. The scope and breadth of these therapies highlight the potential of a new “revolution” of management of diabetic eye disease.

A Case for New Classifications of Diabetic Retinopathy.
Lee M. Jampol

The Diabetic Retinopathy Severity Scale (DRSS) is widely used for the classification of both proliferative and nonproliferative diabetic retinopathy. It traces back to the Airlie House classification from the late 1960s. There have been many advances in the diagnosis and management of diabetic retinopathy since then, especially multimodal imaging and anti VEGF medications. This talk will review the advantages, and the disadvantages of the present system. In particular it will describe the shortcomings of the system for classifying patients during the treatment of their retinopathy. Potential considerations for a new classification will be reviewed including especially using modern multimodal imaging.

Panel Discussion
Nauman Chaudhry

PM - Evaluation and Management of Ophthalmic Trauma

Daniel Lefebvre

Eyelid Lacerations
Larissa Habib

When approaching injury to the eyelid a good understanding of anatomy, review of past medical history, knowing the nature of the injury and a thorough examination are essential in completing a successful repair. This presentation will review considerations in approaching these patients as well as varying types of repairs.

Orbital Compartment Syndrome
Jennifer Renz

Orbital compartment syndrome is an ophthalmic emergency that can lead to irreversible vision loss, but may be effectively treated with prompt recognition and expedient lateral canthotomy and cantholysis. It is thus important to thoroughly know the signs and symptoms, understand the details of treatment, and facilitate a good working relationship with our Emergency Medicine colleagues, who are often the first to evaluate and treat these patients.

Intraocular Foreign Bodies
Nicole Siegel

Intraocular foreign bodies (IOFB) can be devastating to the eye. Knowing the material and size of the foreign body and its final location will aid in its retrieval and preoperative planning. An IOFB is an independent risk factor for the development of endophthalmitis. This risk increases with the presence of organic matter and the longer duration that the IOFB is retained in the eye. As a result, the timing of the IOFB removal is very important to mitigate this risk and should be removed, if possible, within 24 hours of the injury to prevent further complications. A variety of techniques will be discussed to aid in the removal of IOFBs from the posterior segment including the use of an intraocular magnet, foreign body forceps, perfluorocarbon liquid and a nitinol basket. Careful surgery and follow up will ensure the best outcomes.

Introduction of Guest of Honor
Daniel Lefebvre

Complex Periocular Trauma
Louise Mawn

This conference will review treatment of patients with complex eyelid and periocular soft tissue trauma. A paradigm for management as well as step-by-step guide to canalicular repair will be presented. Specific discussion will include innovative treatment of blunt and penetrating periocular soft tissue trauma of the eyelids, lacrimal system, and adnexal injury.

Orbital Trauma
Louise Mawn

Orbital trauma can involve challenging triage of globe and adnexal injuries. Clinical cases highlighting psychological and anatomical factors as well as an ophthalmic surgeon’s perspective will be reviewed. The conference will focus on the management of orbital fractures and penetrating trauma of the orbit.

Current Concepts in Open Globe Injury Management
Alice Lorch

Patients who present after trauma should be carefully examined with a high level of suspicion for open globe injury. Attention should be paid to the area and characteristics of injury which will dictate surgical repair. Pre-operative workup should include CT imaging and the literature suggests that best antibiotic prophylaxis is done with IV antibiotics. There are many different surgical considerations for open globe injury repair depending on the extent of injury and subsequent surgeries are often required to treat sequelae of this trauma. Primary enucleation should only be considered in rare situations. Surgeons can counsel patients on prognosis using tools like the Ocular Trauma Score, and recent literature suggests that the presence of orbital fracture is a negative prognostic factor. The consent process for repair is crucial to ensure reasonable patient expectations, but with appropriate technique and followup some patients can regain functional vision.

The Psychological Impact of Ocular Trauma: Observations and Considerations for Care
Ethan Lester, Michelle Jacobo, Ana-Maria Vranceanu

Ocular Traumas (OT) are prevalent and produce drastic effects for both patients and informal caregivers (family and friends providing support) resulting in high levels of functional impairment, increased risk for long-term medical complications, emotional distress, and reduced quality of life (QoL). Ophthalmic clinical researchers interested in visual outcomes rely heavily on patient engagement in their medical care, however survivors of OT and informal caregivers receive very little if any emotional-behavioral support after a traumatic eye injury to aid this engagement. Therefore, to promote optimal recovery outcomes in patients with OT, psychosocial and behavioral factors need similar priority to biomedical care after an OT to produce desired outcomes. Despite an identified need for addressing chronic emotional distress in patients and their informal caregivers (together called dyads), there are no established interventions to date which attempt to address these difficulties in OT dyads early in the course of recovery. Based on our previous dyadic clinical research in acute neurological injuries (Vranceanu et al., in press)1, as well as my embedded clinical psychology clinic at Mass Eye and Ear Infirmary Ocular Trauma Service, our team, the Integrated Brain Health Clinical and Research Program, has commenced a program of clinical work within OT to address relevant clinical issues, including trauma-specific physical (e.g., pain, functional impairment), emotional (e.g., anticipatory worry, hypervigilance, boredom), and behavioral (e.g., medication adherence, follow up rates) sequelae post-OT and have gathered relevant clinical observations to inform future clinical research. In this presentation, I will discuss the psychological impact of ocular trauma as well as the current gaps in clinical research within this population. I will explore relevant considerations for care based on my own clinical observations within OT and consultations with the OT treatment team. Last, I will discuss future directions of adapting evidence-based, brief psychosocial treatment aimed at preventing chronic emotional distress and fostering resilience in dyads of OT.

Panel Discussion: Oculoplastics -- Trauma
Daniel Lefebvre