Retinal venular calibre may predict visual outcome in diabetic macular edema patients given the anti-vascular endothelial growth factor (VEGF) monoclonal antibody ranibizumab, a pilot study suggests.
  
Factors predictive of the response to ranibizumab in this patient population are currently not known, but previous research indicates that retinal vascular calibre could be one such factor, say Quan Nguyen (University of Nebraska Medical Centre, Omaha, USA) and colleagues.
  
This study used data from individuals with diabetic macular edema who received intravitreal ranibizumab, either alone or together with laser treatment, in the phase II READ-2 trial.
  
Using optic disc-centred fundus photographs, the researchers calculated the baseline central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE), defined as the mean vessel calibre of the six largest arterioles and venules, respectively, in an area one-half to one-disc diameter from the optic disc margin.
  
And best-corrected visual acuity was assessed at baseline and a year after ranibizumab therapy using the Early Treatment of Diabetic Retinopathy Study chart.
  
Following treatment, 10 eyes from the same number of patients showed moderate improvement in vision, defined as a minimum two-line gain. These eyes had a significantly wider baseline CRVE than the 25 eyes from as many individuals whose vision did not improve moderately, at 248.3 µm versus 226.6 µm.
  
By contrast, baseline CRAE did not vary significantly between the participants whose visual acuity did and did not improve.
  
Nguyen et al propose that retinal specialists could use CRVE to predict visual improvement after intravitreal ranibizumab treatment in patients with diabetic macular edema.
  
Source: News Meical

The U.S. Food and Drug Administration today expanded the approved use for ranibizumab injection 0.3 mg (Lucentis) to treat diabetic retinopathy (DR) in patients with diabetic macular edema (DME).
  

Diabetic retinopathy is the most common diabetic eye disease and is a leading cause of blindness in adults in the United States. According to the Centers for Disease Control and Prevention, diabetes (type 1 and type 2) affects more than 29 million people in the United States and is the leading cause of new blindness among people ages 20 to 74 years. In 2008, 33 percent of adults with diabetes aged 40 years or older had some form of DR. In some cases of DR with DME, abnormal new blood vessels grow on the surface of the retina. Severe vision loss or blindness can occur if the new blood vessels break.
  

“Diabetes is a serious public health crisis, affecting more patients every year,” said Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval gives patients with diabetic retinopathy and diabetic macular edema the first significant therapy to treat this vision-impairing complication.”
  

The drug’s safety and efficacy to treat DR with DME were established in two clinical studies involving 759 participants who were treated and followed for three years. In the two studies, participants being treated with ranibizumab showed significant improvement in the severity of their DR at two years compared to patients who did not receive an injection.
  

The FDA granted ranibizumab (Lucentis) for DR with DME breakthrough therapy designation. The FDA can designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may demonstrate a substantial improvement over available therapies for patients with serious or life-threatening conditions.
  

The FDA previously had approved ranibizumab (Lucentis) to treat DME and macular edema secondary to retinal vein occlusions, both of which cause fluid to leak into the macula resulting in blurred vision. Ranibizumab (Lucentis) also is approved to treat wet (neovascular) age-related macular degeneration (AMD), a condition in which abnormal blood vessels grow and leak fluid into the macula.
  

Source: FDA

Vision gains achieved at the conclusion of the RIDE/RISE studies were maintained in patients with diabetic macular edema who were enrolled in a 2-year open-label extension study, Michael S. Ip, MD, told colleagues at Retina 2015. Improvements in retinopathy level were also sustained.
  

After 3 years in RIDE/RISE, 500 participants entered an open-label extension in which ranibizumab 0.5 mg (Lucentis) was given as needed in all three treatment arms according to re-treatment criteria. Mean follow-up time was 14.1 months, less than the anticipated 24 months due to the approval of ranibizumab for DME.
  

One “pitfall” in the analysis is that diabetic retinopathy severity was not a criterion for re-treatment, Ip said.
  

“With respect to visual acuity, it’s well known that we’re paying the price by waiting [to treat],” Ip said. In RIDE/RISE, patients with DME were randomized to one group of sham treatment or to one of two ranibizumab groups for the first 24 months.
  

“The group that was treated with sham for 2 years didn’t quite catch up to the groups that were treated initially with ranibizumab, and this remained the case throughout the open-label with PRN follow-on,” Ip said. “Another way to look at this is, with respect to visual acuity, all three groups in the open-label extension maintained their vision with PRN follow-on. They didn’t lose vision.”
  

Furthermore, fewer injections were given later in the study, with an annualized mean of only 3.8 injections in the extension study.
  

“Many of the injections were up front, in years 1, 2 and 3, and number of injections decreased in subsequent years,” Ip said.
  

Regarding diabetic retinopathy severity, levels were maintained from month 24 to month 36, and then to the end of the extension study.
  

“The two ranibizumab groups had a much higher proportion of patients with a 2- or 3-step or more regression in diabetic retinopathy level. This remained the case to the end of the open-label extension, despite PRN therapy and a mean of 3.8 annualized injections,” Ip said.
  

Ocular and systemic events differed little between the extension period and the end of the RIDE/RISE studies.
  

Source: Healio

Novel pharmacotherapies are in development for the treatment of diabetic macular edema.
  

We hope the combination of the current drugs as well as drugs in the pipeline … will help us to manage our patients with diabetic macular edema,” Quan Dong Nguyen, MD, said at Macula 2015.
  

Among promising pipeline drugs are ALG-1001, AKB-9778 and ASP-8232, he said, all targeting different pathways for treatment.
  

ALG-1001 is a small integrin peptide whose potency relies on anti-angiogenesis and vitreolysis to induce posterior vitreous detachment as well as vitreous liquefaction, according to Nguyen.
  

In a recently completed study combining ranibizumab (Lucentis) with ALG-1001 to treat choroidal neovascularization, the combined therapy reduced the area of neovascularization better than standalone therapy, he said.
  

A phase 2 study of ALG-1001 for treatment of DME is underway.
  

Another pipeline drug under study for treatment of DME, AKB-9778, is a small molecule that targets the enzyme that deactivates the Tie-2 gene. In its normal state, Tie-2 maintains the blood-retinal barrier in normal vasculature. AKB-9778 is administered via subcutaneous injection and is rapidly absorbed and rapidly eliminated.
  

In a phase 1 study of the molecule comparing four different doses given twice daily for 28 days, best corrected visual acuity improved by at least six letters in the three higher doses: 15 mg, 22.5 mg and 30 mg. As well, the study showed good correlation of visual acuity gain and anatomic improvement, he said.
  

“The Tie-2 pathway is critical in the initiation and propagation of diabetic eye disease,” Nguyen said. “AKB-9778, a small molecule activator of Tie-2, has shown promising results in early studies of diabetic eye disease.”
  

The TIME-2 study involving 144 patients randomized to study drug plus ranibizumab, study drug plus sham, or placebo is underway to evaluate the effect of AKB-9778 used in combination with the anti-VEGF.
  

A third promising molecule, ASP-8232, is a VAP-1 inhibitor that has been shown in animal models to improve the ability to reduce ocular hyperpermeability when used in combination with anti-VEGF, according to Nguyen.
  

Source: Healio

Vitrectomized eyes fared as well as non-vitrectomized eyes after treatment with ranibizumab for diabetic macular edema, according to a study presented at Macula 2015.
  

“The efficacy of ranibizumab in the treatment of diabetic retinopathy is well established, but there remain some uncertainties in clinical management with ranibizumab for DME,” Jack Wells, MD, said. “There’s a common clinical impression that the duration of action of anti-VEGF injected in eyes with prior vitrectomy would be shorter than in eyes without prior vitrectomy due to more rapid clearing of the drug, and therefore the treatment would be less effective.”
  

To investigate that theory, Wells and colleagues at the Diabetic Retinopathy Clinical Research Network used 3-year data from the DRCR.net Protocol I to analyze eyes with and without vitrectomy before enrollment assigned to intravitreal ranibizumab (Lucentis) with prompt or deferred laser.
  

“In this small group of eyes with vitrectomy prior to enrollment, the change in vision and OCT [central subfield thickness and volume] from baseline and the number of injections and lasers were fairly similar in eyes with and without prior vitrectomy, after you adjust for baseline imbalances,” he said.
  

Baseline differences in ocular characteristics of vitrectomized eyes included worse visual acuity and thinner maculas, as well as a greater likelihood to have undergone cataract surgery and previous treatment for DME. Non-vitrectomized eyes had milder diabetic severity scores, and vitrectomized eyes had greater tendency for proliferative disease.
  

“There was less rapid improvement in macular edema in vitrectomized eyes, but overall at the end of the 3 years, there were really no differences,” Wells said.
  

Source: Healio