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Advances in Management of Choroidal Neovascularization


After participating in this activity, the participant will demonstrate the ability to:
  • Summarize new developments in the identification and treatment of Myopic Choroidal Neovascularization.
  • Describe how early diagnosis and treatment of AMD improves clinical outcomes.
  • Identify patients for appropriate anti-VEGF treatments based on available therapies and the latest data.

Guest Faculty Disclosure
Dr. Colin Tan has disclosed that he has served as a conference speaker for Bayer and Novartis AG, and served on an advisory board for Novartis AG.

Dr. Paul Hahn has disclosed that he has served as a consultant from Second Sight Medical Products, Inc., and served on an advisory board for Genentech, Inc. 

Unlabeled/Unapproved Uses
Dr. Tan and Dr. Hahn have indicated that there will be no references to the unlabeled or unapproved uses of drugs or products in their discussion.







Colin Tan, MBBS, MMed, FRCSEd
Associate Professor of Ophthalmology
National Healthcare Group Eye Institute
Tan Tock Seun Hospital

Paul Hahn, MD, PhD
Associate, NJRetina
Paramus, New Jersey



Release Date: Expiration Date:
October 12, 2017 October 11, 2019



10 Highlights from ASRS 2017

1. Optical Coherence Tomography Features Preceding the Onset of Advanced Age-Related Macular Degeneration
Johanna Seddon, MD, ScM

AMD 1 Symposium: Saturday, Aug 12, 2017; 8:30 AM

eOphthalmology Summary: To identify optical coherence tomography (OCT) biomarkers to predict progression of age-related macular degeneration (AMD), a prospective epidemiologic study followed up 40 eyes of “progressors” (transitioned from the early or intermediate stage to the advanced AMD, i.e., choroidal neovascularization [CNV] or geographic atrophy [GA] involving the center of the macula) and 40 eyes of non-progressors with a mean duration of 5.4 years. Neurosensory retinal thickness abnormalities (odds ratios [ORs]: 19.2 to 72.6; P < .001) and disruption of the ellipsoid zone (ORs: 17.9 and 30.6; P < .001) were found to be significantly associated with higher odds of progression to advanced AMD. Drusenoid detachment of the retinal pigment epithelium (RPE), RPE thickening, pigmentary hyperreflective material and choroidal abnormalities were associated with a 5 to 7 times increased risk of progression. Systematic assessment of OCT features of the early or intermediate stage of AMD showed that abnormalities at the level of photoreceptors, RPE and choroid are associated with progression to both GA and CNV. These findings provide insights into mechanisms of AMD progression, and suggest a potential similar disease mechanism for the 2 subtypes of advanced AMD.

2. RGX-314 Gene Therapy Subretinal Delivery for the Treatment of Neovascular Age-Related Macular Degeneration (nAMD)
Jeffrey Heier, MD

AMD 1 Symposium: Saturday, Aug 12, 2017; 8:50 AM

eOphthalmology Summary: The trial design, challenges and experience of the Phase 1 RGX-314 (an AAV8 vector delivering an anti-VEGF fab protein) trial, a surgical gene therapy to treat neovascular age-related macular degeneration (nAMD), were discussed at the ASRS 2017 Annual Meeting. The investigators developed an automated subretinal delivery process to deliver the gene therapy construct using an animal wet lab procedure. The Phase 1 study will evaluate 3 doses of RGX-314 in a dose escalation with 6 subjects per arm. Subjects who respond to anti-VEGF therapy will receive gene therapy and be followed for 24 months to evaluate safety and evidence of a biologic effect. The procedure includes standardized vitrectomy and an automated injection of 250 microlitres using a MedOne Microdose Injector syringe within the subretinal space outside of the temporal vascular arcades. RGX-314 gene therapy has potential to minimize the treatment burden of frequent intravitreous injections for nAMD.

3. Vision Preference Value Scale and Patient Preferences in Choosing Therapy for Symptomatic Vitreomacular Interface Abnormality
Adrienne Scott, MD B

Macular Pucker Symposium: Saturday, Aug 12, 2017; 11:30 AM

eOphthalmology Summary: To assess a vision preference value scale and patients’ preferences in choosing therapy for symptomatic vitreomacular interface abnormality (VIA) among patients across 3 continents, a cross-sectional questionnaire study was performed among 213 patients (include 100 epiretinal membranes, 100 macular holes and 14 vitreomacular traction) from the U.S., United Kingdom, and Thailand with symptomatic VIA diagnosed within 1 year and visual acuity (VA) less than 20/20. The mean vision preference value (0-1: death to perfect health) was 0.759 (± SD 0.146) without differences identified among the 3 VIA types. Lower vision preference value was associated with lower VA in the better-seeing eye (r=0.11; 95% CI: 0.028, 0.199; P = 0.01), blurry vision (r=-0.07; 95% CI: -0.121, -0.025; P = 0.003), and at UK (P = 0.012) and Thailand (P = 0.022) sites. Patients with higher VA in the affected eye have lower enthusiasm for vitrectomy (OR=0.22; 95% CI: 0.09, 0.52; P = 0.001), versus people have blurry vision (OR=3.14; 95% CI: 1.37, 7.17; P = 0.007). More patients were enthusiastic about vitrectomy (71.1%) compared with intravitreous injection (56.9%) (95% CI: 5.16%, 23.3%; P = 0.002). The data suggest that patients have similar preference values among 3 types of symptomatic VIA, and have slightly more enthusiasm for vitrectomy.

4. Optical Coherence Tomography Angiography in Retinopathy of Prematurity
J. Campbell, MD, MPH

Pediatric Symposium: Saturday, Aug 12, 2017; 1:25 PM

eOphthalmology Summary: To evaluate the role of optical coherence tomography angiography (OCTA) in the clinical diagnosis of retinopathy of prematurity (ROP), Dr. Campbell’s team designed a 100 kHz swept source OCTA system with a novel prototype handheld probe for use in the neonatal intensive care unit. Using this device, they are in the process of acquiring data in patients, focusing on determination of zone 1 disease, rapid structural OCT and OCTA of peripheral stage, and total retinal blood flow (TRBF) in all stages of disease and plus disease. The ultimate hope is that OCT/OCTA can provide objective diagnosis of zone, stage, and plus disease in ROP. So far, OCTA findings have suggested its ability to differentiate active vs regressed extra-retinal neovascularization, while wide-field OCT might provide structural information that is potentially useful in aiding ROP diagnoses.

5. Potential Safety Concerns of Bevacizumab for Retinopathy of Prematurity
Robert Avery, MD

Pediatric Symposium: Saturday, Aug 12, 2017; 2:01 PM

eOphthalmology Summary: To evaluate potential systemic effects of off-label bevacizumab for retinopathy of prematurity (ROP), studies were assessed looking for reports of systemic effects. Two studies of neurodevelopment in ROP babies raise concern that bevacizumab use could contribute to developmental impairment relative to laser use alone. There are reports of bevacizumab injection for ROP causing effects on fellow un-injected eyes, as well as reports of reduced cerebral blood flow after bevacizumab injection for ROP. Pharmacokinetic studies in ROP have shown a maximum serum concentration at 2 weeks almost 10-fold higher than reported in adults. Serum VEGF in babies with ROP is reduced for at least 8 weeks, and other cytokines, some which could affect lung development, are affected as well. Ranibizumab has a much lower systemic exposure that bevacizumab, and may have a slightly shorter duration of effect in ROP than bevacizumab. These reports raised the concerns of potential harm of using bevacizumab in ROP treatment. Randomized clinical trials are indicated to evaluate laser, bevacizumab, and ranibizumab in the treatment of ROP.

6. Adalimumab in Noninfectious Uveitis of Idiopathic Etiology—Efficacy Across Different Anatomical Locations the VISUAL I and VISUAL II Trials
Pauline Merrill, MD

Inflammatory & Infectious Diseases Symposium: Sunday, Aug 13, 2017; 9:00 AM

eOphthalmology Summary: Efficacy of adalimumab, a TNF inhibitor, in patients diagnosed with idiopathic uveitis and stratified by anatomical location of uveitis at study entry in two global phase 3, double-masked trials, VISUAL I (active uveitis) and VISUAL II trials (inactive uveitis), was assessed. Patients received placebo or adalimumab subcutaneously (80 mg week 0, followed by 40 mg every other week from week 1 up to 80 weeks). The primary endpoint was time to treatment failure at or after week 6 for VISUAL I; and at or after week 2 for VISUAL II. The efficacy of adalimumab was significantly greater than placebo in idiopathic uveitis overall in both VISUAL I (81) and VISUAL II (69) trials. Point estimate results favored adalimumab in intermediate (HR 0.83; 0.31-2.18), posterior (HR 0.15; 0.02-1.27) and pan-uveitis (HR 0.50; 0.23-1.08) patients, but the hazard ratio crossed 1.00, precluding definitive confidence of a difference. No new safety concerns were raised, but the presenter noted that patients need to be tested for tuberculosis, be free of demyelinating disease, and be aware of an increased, although low, rate of malignancy associated with this treatment. The data show high efficacy of adalimumab in both active and inactive idiopathic uveitis patients despite the variance of anatomical location of the diseases.

7. The SAKURA Study: Corticosteroid Tapering Success With Every-Other-Month Intravitreal Sirolimus for Noninfectious Uveitis of the Posterior Segment
Alay Banker, MD

Inflammatory & Infectious Diseases Symposium: Sunday, Aug 13, 2017; 9:05 AM

eOphthalmology Summary: The Phase III multinational, randomized, double-masked SAKURA program, was comprised of two studies (one pivotal, included 347 subjects; one supportive, included 245 subjects) assessing the efficacy and safety of every-other-month intravitreal sirolimus (mTOR inhibitor, 440 μg vs 44 μg) injections in subjects with active non-infectious uveitis of the posterior segment. The proportion of subjects achieving systemic corticosteroid tapering success (overall prednisone-equivalent dose ≤5 mg/d at Month 5 without rescue therapy) in conjunction with improvements in vitreous haze was assessed at Month 5. 46 (22.1%) subjects from the 440 µg group and 32 (15.4%) subjects from the 44 µg group formed the Intent-to-Taper population. In the integrated Intent-to-Taper population, 21.2% vs 13.5% of subjects (440 vs 44 µg, respectively) achieved the primary endpoint of no vitreous haze (VH 0) at Month 5 (P = .038), 43.5% (20/46) vs 28.1% (9/32) of subjects (440 vs 44 µg, respectively) achieved vitreous haze reduction (VH 0/0.5+) (P = .168), and 69.6% (32/46) vs 68.8% (22/32) of subjects in the 440 µg vs 44 µg groups achieved tapering success at Month 5 (P = .939). The SAKURA Program show that intravitreal treatment with 440 μg sirolimus led to significant improvements in vitreous haze and more successful tapering of oral corticosteroids in patients with noninfectious uveitis of the posterior segment.

8. Silicone Oil Droplets Are More Common in Fluid From BD Insulin Syringes As Compared To Other Syringes
Geoffrey Emerson, MD, PhD
Presumed Silicone Oil Droplets in the Vitreous Cavity after Intravitreal Bevacizumab Injection With Insulin Syringes
Rahul Khurana, MD

AMD2 Symposium: Monday, Aug 14, 2017; 8:08, 8:13 AM

eOphthalmology Summary: During 2016, the ASRS received numerous reports of silicone oil droplets after intravitreous injection, primarily associated with insulin syringes with a fixed needle. To determine if silicone oil droplets are more common in Becton Dickenson (BD) Insulin Syringes as compared to other syringes, BD insulin syringes, BD tuberculin syringes, Henke Sass Wolf (HSW) insulin syringes, and HSW silicone free syringes (20 of each) were evaluated by loading with 0.06 mL of fluorescein ophthalmic solution (Bausch & Lomb) and incubated at 4 °C for 2-4 weeks. Syringe fluid was ejected onto slides, sampled at the beginning, middle, and end of injection from the syringe and examined microscopically for air and oil droplets. Silicone oil droplets were identified in 5 (25%) (all from the end of injection) of the BD insulin syringes; no oil droplets were found in BD tuberculin syringes, HSW insulin syringes, or HSW silicone-free syringes (ANOVA, P < .05). Air bubbles were visible in the majority of samples from all types of syringes without differences identified (ANOVA, P = 0.2 and 0.36 for BD and HSW, respectively). The results demonstrate that oil droplets are most commonly observed with BD insulin syringes, especially when the plunger is depressed maximally.

9. Ozurdex vs Ranibizumab vs Combination for Central Retinal Vein Occlusion (ORION)
Victor Gonzalez, MD

Retinal Vascular Symposium: Tuesday, Aug 15, 2017; 10:06 AM

eOphthalmology Summary: To compare the effect of dexamethasone intravitreal implant, ranibizumab, and the combination of the two in the treatment of macular edema secondary to central retinal vein occlusion (CRVO), a multicentered randomized masked clinical trial enrolled 34 subjects comparing dexamethasone implant alone (14 subjects) every 16 weeks, ranibizumab alone (11 subjects) every 4 weeks, and the combination of dexamethasone implant every 16 weeks and ranibizumab (9 subjects) according to reinjection parameters assessed monthly through week 20. There was no difference identified in the change in best corrected visual acuity (BCVA) (mean 16.8 vs 18.5 letters, P = .67) nor in the change in central retinal thickness (CRT) (mean -408 vs -486 μm, P = .56) between ranibizumab and combination, nor difference in BCVA (mean 13.2 vs 18.5 letters, P = .36) and in CRT (mean -376 vs -486 μm, P = .50) between dexamethasone implant and combination. The dexamethasone group received a mean injection of 2 vs 3.5 in the combination group and 6 in the ranibizumab group (P < 0.01). The results among a small number of study participants could not identify a difference in structural or functional outcomes between ranibizumab, dexamethasone implant, or the combination of both at 24 weeks in the treatment of macular edema secondary to CRVO while the combination group had fewer injections.

10. Topline Results From Prospective, Double-Masked Phase 2b Clinical Trial Evaluating ALG-1001 (Luminate®) Compared to Bevacizumab in Patients With DME
David Boyer, MD

Proliferative Diabetic Retinopathy: Tuesday, Aug 15, 2017; 3:55 PM

eOphthalmology Summary: The safety and efficacy of a Phase 2b, clinical trial using ALG-1001 (a synthetic RGD-class oligopeptide, integrin receptor inhibitor) to treat patients with centrally-involved diabetic macular edema (DME) was reported. 136 patients with DME involving the fovea, visual acuity of 20/40 to 20/320 (Snellen equivalent), and central 1-mm macular subfield thickness of ≥350 µm on spectral-domain optical coherence tomography (SD-OCT) from 32 U.S. sites were randomly assigned to four groups. Groups received 1.0, 2.0, or 3.0mg of ALG-1001 (3 monthly intravitreal injections at week 0, 4, and 8) or 1.25mg of bevacizumab (6 consecutive monthly injections). At Week 20, the mean (SD) change in BCVA were 5.2 (6.86), 2.7 (7.31), -1.5 (9.97) and 7.0 (8.21) letters gained in 1.0, 2.0 and 3.0mg ALG-1001 versus 1.25mg bevacizumab, respectively. The mean (SD) change in CMT were -77 (141), -16 (110), -1 (152) and -104 (107) μm, respectively. There were no drug related serious adverse events in the ALG-1001 groups. The results suggest that three doses of anti-integrin ALG-1001 monotherapy demonstrate non-inferiority to 6 doses of bevacizumab (≤ 3 letter difference in BCVA and ≤ 30µm difference in CMT) in patients with DME at week 20.







Download the podcast transcript






Neil Bressler, MD
James P. Gills Professor of Ophthalmology Chief of the Retina Division
Wilmer Eye Institute at Johns Hopkins
Baltimore, Maryland

Jun Kong, MD, PhD
Post-Doctoral Clinical Research Fellow
Wilmer Eye Institute Johns Hopkins Hospital
Baltimore, Maryland








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