Highlights from the Cole Eye Institute Retina Summit

The 9th annual Cole Eye Retina Summit prior to the Association for Research in Vision (ARVO) meeting took place on April 26th, 2019 in Vancouver, BC.  The Retina Summit is for retina specialists, comprehensive ophthalmologists, retina fellows and healthcare providers who are interested in applying the most recent advancements in the field.  Covered topics included age related macular degeneration, diabetic retinopathy, retinal vein occlusion, uveitis, pediatric retinal topics, and surgical retina.  Complementing the Cole Eye Retina staff were invited faculty from multiple institutions representing some the best and brightest in our field.  Below is a summary of the major highlights from the meeting.

Geographic Atrophy: What Causes It and Can It Be Treated?

Dr. Daniel Martin, chair of the Cole Eye Institute presented the current hypothesis of the pathogenesis and progression of geographic atrophy (GA).  He reported that we now understand the lesions that proceed geographic atrophy.  For example, large confluent drusen are present in 94% of patient with GA and precedes GA by 6.5 years.  Hyperpigmentation is present in 96% of patients with GA and precedes GA by 4 years and hypopigmentation is present in 81% of patients and precedes GA by 2-3 years.  There also has been significant understanding into the kinetics of GA growth.  We know from natural history studies that GA GA progression toward the periphery grows at 2.34 mm2/year and 0.259 mm2/year toward the fovea (a 2.8 fold faster progression).   Knowing this progression is key to designing clinical trials to investigate therapies to reduce the progression of geographic atrophy.  

Vas Sadda, President and CSO, Doheny Eye Institute, delivered a talk on the promising therapies for dry AMD.  He highlighted the numerous studies underway investigating nutritional supplements, physical therapeutics (rheophoresis, lasers), cell-based therapies (embryonic stem cells), and pharmacotherapeutics (complement inhibitors).  The LEAD study was conducted by Robin Guymer in Australia and investigated nanosecond laser to drusen in an effort to reduce the barrier caused by these deposits in the basement membrane.   While the study showed no apparent benefit in all patients, a post hoc analysis showed benefit in those without reticular pseudodrusen and harm in eyes with reticular pseudodrusen.

David Brown, of Retina Consultants of Houston, presented on promising therapies for exudative age related macular degeneration.  Many of the therapies coming soon build upon the years of clinical efficacy of anti-VEGF agents.  One of the more recent therapies being studies in a phase 3 clinical trial is conbercept (KangHong Pharmaceuticals).  It’s a fusion protein of key extracellular domains from human VEGF receptors 1 and 2, and IgG Fc with pan VEGF inhibition (VEGF A, B, and C).   Interestingly when tested in HUVEC cells, Conbercept outperformed Aflibercept for binding affinity to VEGF and placental like growth factor.  A phase 3 trial of this drug (PANDA study) is ongoing.  

Dr. David Brown, of Retina Consultants of Houston, presented data supporting the use of anti-VEGF for the treatment of diabetic retinopathy.  In particular, Dr. Brown advocated the use of anti-VEGF therapy in patients with severe NPDR (ETDRS grade 43 or worse) when quality of life measures decline significantly.  The PANORAMA study enrolled patients with moderately severe and severe NPDR who received either observation, aflibercept every 8 weeks after a loading dose, or aflibercept every 16 weeks after a loading dose. The 52 week results demonstrated a 65% and 80% improvements in 2 step retinopathy improvements in the 16 week and 8 week groups respectively over 15% in the sham arm treated group.  The number of vision threatening complications from diabetic retinopathy such as tractional detachments and vitreous hemorrhage were 4 fold lower in the treated group than controls.  

Dr. Carl Regillo, Director of the Retina Service at Will’s Eye Hospital, presented his findings regarding treatment failure in diabetic macular edema.  While anti-VEGF treatment is first line therapy for diabetic macular edema and has been supported by numerous clinical trials with regards to its efficacy and safety, even in the these studies there are a significant proportion of patients who do not respond to treatment or manifest persistent fluid on the OCT.  He presented data on findings from Protocol I and T which show that up to a third of patients can demonstrate reduced vision with persistent fluid and up to 60% in some arms show persistent fluid.  This speaks to the need for additional durable anti-VEGF agents with a better drying effect along side either sustained delivery or different mechanisms of action to improve outcomes.  

Nina Berrocal, Professor of Ophthalmology from the Bascom Palmer Eye Institute, presented on tips to operate on adult patients with pediatric retinal disease states like ROP or congential retinopathies.  She illustrated in a few surgical cases how detaching the posterior hyaloid with the Finesse loop is possible and that this was not always detached around the optic nerve initially but was carried to propagate the detachment from the optic nerve outward by using the Finesse loop. In addition, she outlined the clinical findings of adult patients with ROP including the evidence of an old ridge with vascular growth past the glial changes, posterior insertion of the vitreous base, avascularity within a very thin retina, and finally macular dragging.  In addition, querying the patient before surgery about their birth is important in elucidating their history prior to operating on these patients.  

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