September 1, 2019

Anti-VEGF therapy for exudative macular degeneration places a significant treatment burden both upon patients who must return frequently for intravitreal injections, and upon providers who need to provide a high volume of injections each day.  Additionally, it has been shown that due to a reduced frequency of injections over time, the mean visual gain initially achieved with treatment of this condition gradually erodes.  In an effort to address these issues, Genentech Inc. (South San Francisco, CA) has developed a revolutionary port delivery system to provide continuous treatment with ranibizumab. 

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The core of the system is a refillable reservoir which is surgically implanted into the pars plana.  This reservoir can then be refilled with ranibizumab in the office every few months.  The system was designed to both reduce the treatment burden and to provide continuous release of anti-VEGF in the eye. 

In the LADDER study, patients were randomized to receive either monthly injections of 0.5 mg ranibizumab, or a formulation of 10, 40, or 100 mg/ml ranibizumab via the port delivery system.  The Phase 2 results have just been released and are extremely promising, showing noninferiority to monthly 0.5 mg ranibizumab injections.  As expected, the durability is longest at the highest 100 mg/ml dose.  When approved, this will be the first long-term therapy available for macular degeneration.  We will keep you up to date on the approval and availability of this innovative new system.

November 11, 2017

The MUST trial compared the effectiveness of systemic therapy vs. fluocinolone acetonide implant for severe uveitis.  Intermediate, posterior and panuveitis patients were included.  In a nonprespecified 7-year observational follow-up of 215 participants from the randomized clinical trial, patients who had systemic therapy had significantly better visual acuity compared with those who received the fluocinolone acetonide implant, by a mean of 7 letters.  Previously, the trial had shown no difference at 2 years.  Findings are limited by a 30% loss to follow up, with possible selection bias.

May 4, 2016

5-Year Data from the CATT trial has now become available.  The study showed that vision gains secondary to bevacizumab or ranibizumab during the first 2 years of the trial were not maintained at 5 years.  Still, half of patients could see 20/40 or better.

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"When we first treat wet AMD patients, they typically gain about two lines worth of visual acuity on the eye chart, and what we've seen in this study is that between year 2 and about year 5 of anti-VEGF treatment they lose most of that improvement," said Maureen G. Maguire, PhD, lead author and  professor of ophthalmology at the Perelman School of Medicine at the University of Pennsylvania.

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After 2 years of treatment, participants were free to choose their own course of therapy, although it appears that participants in the 5-year visit following enrollment were seemingly under-treated with anti-VEGF intravitreal injections during years 3, 4 and 5. The mean number of treatments was 15.4.

At 5 years, mean visual acuity was 3 letters worse compared with baseline and 11 letters worse than at 2 years. Between 2 and 5 years, the group originally assigned to ranibizumab lost 4 more letters than the bevacizumab group (P=0.008). Otherwise, there were no significant differences in VA or morphologic outcomes between drug or regimen groups.

The rate of geographic atrophy increased from 20% of participants at 2 years to 41% at 5 years, with the average lesion size increasing by more than 50% during that time period, highlighting  the need for new agents that can prevent or minimize geographic atrophy and expansion of the total neovascular lesion.

Despite the adverse morphologic changes, only 20% had visual acuity of 20/200 or worse. These data are remarkable when considering the VA outcomes in wet AMD before the development of anti-VEGF treatment. Two years after diagnosis, less than 10% of patients retained vision of 20/40 or better with no treatment and less than 15% of patients treated with photodynamic therapy retained 20/40 or better vision.

With most patients changing drugs over time, the ability to identify differential safety effects of the 2 drugs was compromised. But the authors noted no new safety signals after 5 years of treatment. While these results would have been unimaginable before the availability of anti-VEGF therapy, the path for future improvement is clear, the authors write.

"Although anti-VEGF treatment has greatly improved the prognosis for patients overall, we still need to find ways to avoid poor vision in these patients and to decrease the burden of ongoing treatment," said Maguire.

November 13, 2015

Protocol S of the DRCR.net study group is a randomized multi-center clinical trial to evaluate noninferiority of intravitreal ranibizumab vs panretinal photocoagulation (PRP) for the treatment of proliferative diabetic retinopathy, with the primary endpoint as mean visual acuity change letter score over two years.

The trial involved 55 clinical sites across the U.S.  Two hundred three eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits, and 191 eyes received 0.5 mg intravitreous ranibizumab at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol.

At 2 years, visual acuity improved by 2.8 letters from baseline in the ranibizumab group compared with an improvement of 0.2 letters from baseline in the PRP group, with a mean difference of 2.2 letters between treatment groups (P < .001).

There was less peripheral visual field loss, 213 dB in the ranibizumab group vs. 531 dB in the PRP group, and there were less vitrectomies performed in the ranibizumab group, with 4% of eyes requiring vitrectomy compared with 15% of eyes in the PRP group.  When diabetic macular edema was present, ranibizumab was more effective than PRP in preserving central and peripheral visual function, but cost, compliance, nerve function, and patient preference need to be taken into account.

In summary, ranibizumab should be considered a viable treatment option in proliferative diabetic retinopathy, particularly in patients requiring anti-VEGF treatment for diabetic macular edema.  There were no substantial safety concerns in either grou pfor at least 2 years.

March 25, 2015

"Diabetes is a serious public health crisis, affecting more patients every year," Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in a statement. "Today's approval gives patients with diabetic retinopathy and diabetic macular edema another therapy to treat this vision-impairing complication."

In appropriate patients, aflibercept is injected into the eye every month for 5 months and then every 2 months, the FDA said.

The safety and efficacy of aflibercept to treat diabetic retinopathy in patients with DME were demonstrated in two clinical studies involving a total of 679 patients randomly assigned to receive aflibercept or macular laser photocoagulation (control group). At week 100, those treated with aflibercept showed significant improvement in the severity of their diabetic retinopathy compared with control patients, the FDA said.

The most common ocular side effects associated with aflibercept include conjunctival hemorrhage, eye pain, cataracts, vitreous detachment, and increased intraocular pressure. Serious adverse reactions include endophthalmitis and retinal detachment.

Aflibercept had breakthrough therapy designation from the FDA for treatment of diabetic retinopathy with diabetic macular edema.

Aflibercept is already approved in the US to treat wet (neovascular) age-related macular degeneration and diabetic macular edema and macular edema secondary to retinal vein occlusions.

Last month, the FDA approved ranibizumab injection (Lucentis, Genentech) 0.3 mg to treat diabetic retinopathy in patients with diabetic macular edema.

December 15, 2014

Based on the phase 3 RISE/RIDE trials, which show meaningful improvements in diabetic retinopathy in Lucentis-treated patients compared to sham-treated patients over 2 years, the FDA has granted Lucentis breakthrough therapy designation.

February 2014

The Argus II retinal prosthesis is 3 x 5 mm and surgically implanted onto the surface of the retina, where it acts to replace damaged photoreceptor cells in retinitis pigmentosa and other hereditary retinal diseases.  The current generation device has 60 electrodes which stimulate the retina with electrical signals generated from a video camera mounted on a pair of eyeglasses.

January 2014

Five patients with LCA2 had improved visual function within a few months after treatment with a single unilateral injection of adeno-associated virus AAV2-hRPE65v2, and the effect remained stable for 3 years.  Visual function measurements included best-corrected visual acuity, visual field, and reduction in nystagmus frequency compared with baseline.