Controlling hemoglobin A1c levels and reducing blood pressure have a significant impact on modifying diabetic retinopathy (DR) progression, stated Dr. Allen S. Ho, MD, at Retina 2015. Diabetic retinopathy is a leading cause of blindness among working adults worldwide, and diabetic macular edema (DME), is a complication of diabetic retinopathy.
  

The average A1c level among patients with diabetic retinopathy is 9, and each 1% increase in A1c level above 7 increases the chance of the incidence of progression to proliferative diabetic retinopathy by 50% and increases the chance of development of diabetic macular edema by 40%, stated Dr. Ho. “Conversely, if you reduce your A1c by 1% when it’s elevated, you reduce your chance of diabetic macular edema by 40% for each elevated increment of 1%.”
  

This relationship holds true whether the patient has type 1 or type 2 diabetes, whether macular edema is proliferative or non-proliferative, or whether disease is mild, moderate or severe.
  

Blood pressure control and lipid management, too, can impact diabetic retinopathy progression. The American Diabetes Association recommends a target blood pressure of 130/80 mm Hg or less, and each 10 mm Hg reduction in systolic pressure when blood pressure is elevated reduces microvascular complications of diabetic retinopathy by 10%, regardless of severity of hypertension.
  

“We can modify progression of diabetic retinopathy by getting back to basics with glycemic control, blood pressure control and lipid management,” commented Dr. Ho.
  

Source: Healio

Diabetes is the leading cause of blindness among adults aged 20-74. Patients with type 1 or type 2 diabetes are at risk for developing diabetic retinopathy, a debilitating eye disease, which can lead to the more severe condition of diabetic macular edema (DME). The International Diabetes Federation estimates that DME affects 11% of all people living with diabetes worldwide. DME exacts a severe and growing socioeconomic burden on individuals, health systems, and governments, but recent progress in the field may help to alleviate this burden.
  

The development of VEGF-targeted drugs has produced a true paradigm shift in the treatment of DME. Anti-VEGF therapy blocks the expression of “vascular endothelial growth factor” (VEGF) – a key element in the development of DME. Four anti-VEGF agents have been shown to be effective, and two have already been approved in the United States and the European Union. These therapies can help affected patients prevent further vision impairment and, in some cases, even reverse vision loss.
  

Recognizing the clinically transformative nature of these remarkable therapies, the Angiogenesis Foundation convened a Canadian National Multi-stakeholder Expert Summit for Diabetic Macular Edema in Toronto, Ontario on January 16th – 17th. The summit brought together high-level regional representatives including retinal specialists, ophthalmologists, optometrists, diabetologists, diabetes organization leaders, advocates, researchers, and patients.
  

Experts participated in a series of discussions that reviewed the impact of new drugs in the treatment of DME, the challenges to optimized care, and the necessary steps forward to improve patient outcomes. Dialogue particularly highlighted the need for greater preventative and screening measures while continuing to advance treatment options and safety for those afflicted. Despite complex policy differences between the regions in Canada, thought leaders involved in the Summit were optimistic that changes could be made initially through national education and advocacy campaigns. An action plan, as well as other conclusions from the Summit, will be reported in a white paper published by the Foundation in the coming months.
  

The Canadian National Multi-stakeholder Summit is the second DME Expert Summit convened by the Angiogenesis Foundation, yet the first in North America. The previous assembly was held in Paris, France in June 2014, and brought together experts from 12 countries. Key findings and proposed solutions from the Paris summit are available in the white paper report.
  

Visit ScienceofDME.org to learn more about the development and treatment of DME, and connect on Facebook and Twitter to stay updated on the field.
  

The US Food and Drug Administration (FDA) has granted Lucentis (ranibizumab), a vascular endothelial growth factor (VEGF) inhibitor, its Breakthrough Therapy (BT) designation for the treatment of diabetic retinopathy.
  

Diabetic retinopathy is a vision-threatening complication of type 1 and type 2 diabetes. It is the most common diabetic eye disease and a leading cause of vision loss in working adults, affecting over 93 million people worldwide. Diabetic macular edema is a form of diabetic retinopathy.
  

The FDA based the BT designation on results of the RISE and RIDE phase 3 trials. In these trials, meaningful improvements in disease were observed in a clinically significant proportion of diabetic retinopathy patients treated with ranibizumab at 2 years compared with patients treated with sham (control group). Benefits of ranibizumab were maintained during year 3 of treatment, and the safety in the RISE and RIDE phase 3 trials was consistent with previous studies.
  

The BT designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. Drugs qualifying for this designation must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies, or placebo if there is no available therapy. The designation includes all of the FDA’s fast-track program features, as well as more intensive guidance and discussion. The BT designation is distinct from both accelerated approval and priority review, which can also be granted to the same drug if relevant criteria are met.
  

Lucentis is currently indicated for diabetic macular edema, wet age-related macular degeneration, and macular edema following retinal vein occlusion. If approved, Lucentis will be the first ocular medication approved for the treatment of diabetic retinopathy.
  

Source: ASRS

Health Canada recently approved anti-VEGF agent alibercept (Eylea) for the treatment of diabetic macular edema (DME). Eylea is also approved in Canada for the treatment of visual impairment due to macular edema secondary to central retinal vein occlusion (CRVO) and for the treatment of patients with wet age-related macular degeneration (AMD). The drug is also approved in the United States for all three indications.
  

“The additional approvals for Eylea in Canada mean that patients with CRVO and DME will have more treatment options available to help maintain their sight and help them carry out their daily activities,” said Dr. Keith Gordon, CNIB, Vice President Research. “This new treatment option may reduce vision loss due to DME and CRVO, allowing individuals to better maintain their independence.”
  
DME is a significant causes of vision loss in Canada. It is estimated that vision impairment resulting from DME affects approximately 2.5 percent of the nearly 2.4 million Canadians with diabetes, or approximately 60,000 Canadians, making it a major cause of adult onset vision loss.
  

Diabetic Macular Edema (DME) Approval
 
The Health Canada approval of Eylea for the treatment of DME is based on the results of two Phase III clinical studies (VIVIDDME and VISTADME). In both studies, Eylea dosed 2 milligrams monthly (2Q4) and Eylea dosed 2 milligrams every two months (after 5 initial monthly injections) (2Q8), achieved the primary endpoint of significantly greater improvements in best-corrected visual acuity (BCVA) from baseline compared to laser photocoagulation at 52 weeks. Further, in the VISTADME study, patients gained a mean +12.5 (2Q4) and +10.7 (2Q8) letter improvement from baseline and approximately a third of patients gained three lines of vision or more.
  

“The results of two Phase III studies were very positive. Significantly more patients with visual impairment due to diabetic macular edema experience a two- and three-line improvement in visual acuity with Eylea,” said Dr. Michael Kapusta, Ophthalmologist-In-Chief, Jewish General Hospital, and Director of Retina, McGill University, Montreal. “The decision to approve Eylea will offer retina specialists and their patients an excellent option in the management of DME.”
  

Source: BusinessWeek

The U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for EYLEA® (aflibercept) Injection for the treatment of diabetic retinopathy in patients with diabetic macular edema (DME). Under the Prescription Drug User Fee Act (PDUFA), the goal for a priority review is six months, for a target action date of March 30, 2015.
  
In September 2014, the FDA granted EYLEA® (aflibercept) Injection Breakthrough Therapy designation for the treatment of diabetic retinopathy in patients with DME. The FDA created the Breakthrough Therapy designation to expedite the development and review of drugs for serious or life-threatening conditions. A Breakthrough Therapy drug must show preliminary clinical evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy.
  
The Phase 3 VIVID-DME and VISTA-DME trials, which supported the approval of EYLEA in DME, included a pre-specified secondary endpoint evaluating diabetic retinopathy based on an established grading scale in patients with DME. The two-year results from these trials on the primary endpoint of best-corrected visual acuity (BCVA) and overall safety have been previously reported.
  

EYLEA® (aflibercept) Injection is available as a single, 2 milligram (mg) strength intravitreal injection for all approved indications. EYLEA is approved in the U.S. for the treatment of wet age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), and DME.
  

About the VIVID-DME and VISTA-DME Trials
  
The Phase 3 VISTA-DME and VIVID-DME studies of 862 patients compared EYLEA 2 mg given monthly, EYLEA 2 mg given every two months (after five initial monthly injections), or macular laser photocoagulation (at baseline and then as needed). In the DME studies, at one year, the mean changes in Best Corrected Visual Acuity (BCVA), as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart for the monthly and every two month EYLEA groups, were statistically significantly improved compared to the control group and were similar to each other. Across both trials at one year, patients in both EYLEA dosing groups gained, on average, the ability to read approximately two additional lines on an eye chart compared with almost no change in the control group. A secondary endpoint of the trials was the proportion of patients who achieved a 2-step or greater improvement on the ETDRS diabetic retinopathy (DR) severity scale at two years.
  
In these trials, EYLEA had a similar overall incidence of adverse events (AEs), ocular serious AEs, and non-ocular serious AEs across treatment groups and the control group. Arterial thromboembolic events as defined by the Anti-Platelet Trialists’ Collaboration (non-fatal stroke, non-fatal myocardial infarction, and vascular death) also occurred at similar rates across treatment groups and the control group. The most frequent ocular treatment emergent AEs (TEAEs) observed in the VISTA-DME and VIVID-DME trials included conjunctival hemorrhage, eye pain, cataract, and vitreous floaters. The most common nonocular TEAEs included hypertension and nasopharyngitis, which occurred with similar frequency in the treatment groups and the control group.
  

About EYLEA® (aflibercept) Injection for Intravitreal Injection
  
EYLEA is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eye. EYLEA is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis. EYLEA helps prevent VEGF-A and PLGF from interacting with their natural VEGF receptors as shown in preclinical studies.
  
Source: Yahoo

The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved aflibercept (EYLEA®) Injection for diabetic macular edema (DME).
 
EYLEA has already been approved in Japan for the treatment of patients with neovascular age-related macular degeneration (wet AMD), macular edema secondary to central retinal vein occlusion (CRVO), and myopic choroidal neovascularization (myopic CNV). A marketing authorization application has been submitted in Japan for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO).
 
EYLEA is approved in the U.S. for wet AMD, DME and macular edema following retinal vein occlusion (RVO).
 
EYLEA has been approved in almost 80 countries for the treatment of patients with wet AMD and around 60 countries for the treatment of visual impairment due to macular edema secondary to central retinal vein occlusion. EYLEA is also approved for the treatment of DME in over 30 countries. An application has been submitted for marketing authorization in Europe for EYLEA in macular edema following BRVO.
 
About Diabetic Macular Edema (DME) 
Diabetic macular edema (DME) or “swelling of the macula” is a common complication in the eyes of patients with diabetes. It is the most frequent cause of vision loss in patients with diabetes and eventually can lead to blindness. Visual impairment due to DME is estimated to affect around three percent of people with diabetes around the world and is the most frequent cause of blindness in young and mid-aged adults in most developed countries.
 
DME occurs when blood vessels in the retina are damaged by chronic high blood sugar levels caused by diabetes. This allows fluid from blood vessels to leak into the retina, causing macular swelling. Fluid in the macula can cause severe vision loss or blindness. The macula is the part of the retina responsible for central, fine vision.
 
Vascular endothelial growth factor (VEGF), a naturally occurring family of growth factors in the body, appears to play a critical role in the development of DME. Increased VEGF production contributes to the vascular disruptions and leakage that characterize DME.
 
About EYLEA® (aflibercept) Injection for Intravitreal Injection 
EYLEA is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eye. EYLEA is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis. EYLEA helps prevent VEGF-A and PLGF from interacting with their natural VEGF receptors as shown in preclinical studies.
 
EYLEA is for prescription use only. For additional safety information, see the full Prescribing Information for EYLEA.
 
Source: Yahoo

In the National Institutes of Health (NIH) sponsored, Diabetic Retinopathy Clinical Research Network (DRCR.net) comparative effectiveness study in patients with Diabetic Macular Edema (Protocol T), EYLEA® (aflibercept) Injection demonstrated a significantly greater improvement in mean change in best-corrected visual acuity (BCVA) from baseline at 52 weeks compared to both bevacizumab (Avastin® /Genentech) and ranibizumab injection (Lucentis®/Genentech), the primary endpoint of the study. The median number of injections using the protocol-specified retreatment regimen was one fewer in patients treated with EYLEA compared to bevacizumab and ranibizumab. Fewer patients in the EYLEA group received criteria-based macular laser treatments than those treated with bevacizumab and ranibizumab.
 
The rates of most ocular and systemic adverse events (AEs) were similar across the three study groups. The rates of arterial thromboembolic events as defined by the Anti-Platelet Trialists’ Collaboration (non-fatal stroke, non-fatal myocardial infarction, and vascular death) in the trial were 2 percent in the EYLEA group, 4 percent in the bevacizumab group and 5 percent in the ranibizumab group. There were more overall cardiovascular events in the ranibizumab group, compared to the EYLEA group and the bevacizumab group (nominal p less than 0.01); this included more cardiac events and cerebrovascular events in the ranibizumab group.
 
DRCR.net has shared these top-line results with study investigators. DRCR.net is in the process of finalizing and verifiying the data prior to submission for publication.
 
The independent, government-sponsored study was designed to determine if one of three different anti-VEGF therapies is superior to the others for the treatment of diabetic macular edema (DME). In the study, 660 patients were randomized to receive either EYLEA 2 milligrams (mg), bevacizumab 1.25 mg, or ranibizumab 0.3 mg dosed according to a protocol-specified algorithm. Patients were treated with focal/grid laser at or after the 24 week visit if: 1) the OCT central subfield thickness was greater than or equal to 250 microns or there was edema that was threatening the fovea and 2) the eye did not improve on OCT or visual acuity from the last two consecutive injections. Full details of the protocol can be found at www.drcr.net.
 
About EYLEA® (aflibercept) Injection for Intravitreal Injection
 
EYLEA is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eye. EYLEA is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis. EYLEA helps prevent VEGF-A and PLGF from interacting with their natural VEGF receptors as shown in preclinical studies.
 
 

IMPORTANT PRESCRIBING INFORMATION FOR EYLEA® (aflibercept) INJECTION
 
EYLEA® (aflibercept) Injection is a prescription medicine approved for the treatment of patients with:
 
• Wet Age-related Macular Degeneration (AMD): The recommended dose for EYLEA is 2 mg administered by injection in the eye every 2 months (8 weeks) following 3 initial monthly (4 weeks) injections. EYLEA may be dosed once per month, but additional benefit was not seen with this dosing plan.
 
• Macular Edema following Retinal Vein Occlusion (RVO): The recommended dose for EYLEA is 2 mg administered by injection in the eye monthly (every 4 weeks).
 
• Diabetic Macular Edema (DME): The recommended dose for EYLEA is 2 mg administered by injection in the eye every 2 months (8 weeks) following 5 initial monthly (4 weeks) injections. EYLEA may be dosed once per month, but additional benefit was not seen with this dosing plan.
 
 

IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION
 
EYLEA® (aflibercept) Injection is a prescription medication administered by injection into the eye. Patients should not use EYLEA if they have an infection in or around the eye, eye pain or redness, or known allergies to any of the ingredients in EYLEA, including aflibercept. As with all medications, EYLEA can cause side effects.
 
Injection into the eye can result in an infection in the eye and retinal detachment. Inflammation in the eye has been reported with the use of EYLEA.
 
In some patients, injections with EYLEA may trigger a temporary increase in eye pressure within 1 hour of the injection. Sustained increases in eye pressure have been reported with repeated injections, and doctors may monitor this after each injection.
 
There is a potential risk of serious and sometimes fatal side effects related to blood clots, leading to heart attack or stroke in patients receiving EYLEA.
 
Serious side effects related to the injection procedure are rare but can occur including infection inside the eye and retinal detachment.
 
The most common side effects reported in patients receiving EYLEA are increased redness in the eye, eye pain, cataract, moving spots in the field of vision, increased pressure in the eye, and vitreous (gel-like substance) detachment.
 
It is important that patients contact their doctor right away if they think they might be experiencing any side effects.
 
EYLEA is for prescription use only. For additional safety information, please see the full Prescribing Information for EYLEA.
 
Source: Yahoo

The Food and Drug Administration has approved fluocinolone acetonide intravitreal implant (Iluvien) as treatment for diabetic macular edema (DME), an eye condition characterized by swelling in the back of the retina that can lead to vision impairment or even blindness. DME is a complication of diabetes.

 
Iluvien, manufactured by Alimera Sciences Inc. and pSivida Corp., is an injectable implant. The treatment involves positioning a tiny, cylindrical tube containing a drug on the back of the eye – the spot where DME typically forms. Iluvien is expected to launch early next year. The treatment is already approved in 10 European countries, including the UK, France and Germany.
 
Source: Reuters

The European Commission has extended marketing authorization for dexamethasone intravitreal implant (Ozurdex) for the treatment of diabetic macular edema in certain patients.

Under the marketing authorization extension, the dexamethasone 0.7 mg intravitreal implant is indicated for adult patients with visual impairment due to diabetic macular edema who are pseudophakic, or who were unable to undergo noncorticosteroid therapy.

The implant is already indicated for the treatment of macular edema following branch retinal vein occlusion and central retinal vein occlusion, as well as for the treatment of noninfectious uveitis, according to the press release. It was approved by the U.S. Food and Drug Administration on June 30.

Source: Healio

Intravitreal aflibercept for diabetic macular edema (DME) continues to perform better than laser with regard to best corrected visual acuity, according to a presentation showing 2-year subgroup analysis data of the VIVID and VISTA DME studies at the Association for Research in Vision and Ophthalmology meeting.

Four hundred six patients in the VIVID study and 466 patients in the VISTA study were divided into three arms: those who underwent laser photocoagulation plus sham injection, those who received five monthly intravitreal injections of 2 mg Eylea(aflibercept, Regeneron) followed by every 4-week dosing plus sham laser, and those who received five monthly 2 mg intravitreal aflibercept injections followed by every 8-week dosing plus sham laser.

Both laser and aflibercept treatments resulted in slightly better visual outcomes in patients with a baseline BCVA between 39 and 60 letters, compared with those with baseline BCVA between 61 and 73 letters, according to the study.

In the VIVID study, mean increase in BCVA in patients with baseline between 39 and 60 letters was 10.5, 10.7 and 1.2, respectively, in the every 4-week arm, the every 8-week arm and the laser arm. The mean increase in BCVA from baseline was 12.5, 10.7, and 0.2 letters in the VISTA study (P < .0001).   Accordingly, mean BCVA increase in patients with baseline between 61 and 73 letters was 9.1, 8.6 and 0.7 in the VIVID study and 10.5, 9.9, and –0.4 letters in the VISTA study.   “The 2-year results continue to show superiority in intravitreal aflibercept vs. laser consistently at 33% vs. 13% with the laser arm with those who lose 15 letters or less,” David Brown, MD, FACS, told Ocular Surgery News.   Patients in both aflibercept arms combined had a lower rate of serious ocular adverse events (1.6%) in the VIVID study than in the laser arm.   “Safety outcomes need to be watched but were pretty close amongst the arms, and we wait for the sister study, VIVID, for further confirmation,” Brown said.   Source: Healio