Volume 12, Number 11
November 2016

WELCOME to Review of Ophthalmology's Retina Online e-newsletter. Each month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with this timely and easily accessible report to keep you up to date on important information affecting the care of patients with vitreoretinal disease.

Zeiss Gets FDA Nod for SS-OCT Posterior Ocular Imaging With PLEX Elite 9000
Having received the first United States FDA clearance for ocular coherence tomography angiography technology in September 2015, Zeiss now has received the first FDA clearance for swept-source OCT imaging technology for posterior ocular structures with Zeiss Plex Elite 9000...

Stealth Initiates Phase I Study of Elamipretide in Dry AMD
Stealth BioTherapeutics announced the initiation of ReCLAIM, a Phase I study evaluating elamipretide in intermediate age-related macular degeneration...

And More...


Dual Antagonism of PDGF and VEGF in nAMD Degeneration

Researchers assessed the safety and efficacy of E10030 (Fovista, Ophthotech), a platelet-derived growth factor antagonist, administered in combination with the anti-vascular endothelial growth factor agent ranibizumab (Lucentis, Roche) compared with ranibizumab monotherapy in individuals with neovascular age-related macular degeneration, as part of a Phase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial.

Four hundred forty-nine individuals with treatment-naïve nAMD were randomized in a 1:1:1 ratio to 1 of the following three intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg; E10030 1.5 mg in combination with ranibizumab 0.5 mg; and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks.

The prespecified primary endpoint was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy letters) from baseline to 24 weeks.

Researchers observed no significant safety issues in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary endpoint of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; p=0.019). A dose-response relationship was evident at each measured time point commencing at four weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size or central subfield thickness on optical coherence tomography. All clinically relevant treatment endpoints of visual benefit (≥15 ETDRS letter gain, final VA ≥20/40 or ≥20/25) and visual loss (≥1 ETDRS line loss, ≥2 ETDRS line loss, final VA ≤20/125 or ≤20/200) favored the E10030 1.5 mg combination group.

In this Phase IIb clinical trial, researchers noted a 62 percent relative benefit from baseline in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant endpoints. Researchers wrote that the study provides strong rationale for a confirmatory Phase III clinical trial.

SOURCE: Jaffe GJ, Ciulla TA, Ciardella AP, et al. Dual antagonism of PDGF and VEGF in neovascular age-related macular degeneration. Ophthalmology 2016; Oct. 28. [Epub ahead of print].


Incidence & Causes of Vision Loss During Aflibercept Treatment for nAMD

Scientists assessed incidence rates, risk factors and final outcomes of individuals with age-related macular degeneration experiencing vision loss despite periodic aflibercept treatment.

The researchers prospectively recruited subjects with treatment-naive AMD and treated the individuals with three monthly injections followed by two monthly injections of aflibercept. They investigated incidence rate and risk factors of more than two lines of vision loss at any visit.

Scientists included 196 eyes of 196 people, and observed vision loss in 16 subjects (8.2 percent). Eleven of 16 people developed vision loss during the first three months (68.8 percent), with vision loss remaining in 11 eyes (68.8 percent) at the final visit. Scientists identified maximum pigment epithelium detachment height (odds ratio=1.46 for a 100 µm increase in PED height) and disruption of the external limiting membrane (odds ratio=4.45) as risk factors for developing vision loss on logistic regression analysis.

Scientists found the incidence rate of vision loss during aflibercept treatment to be relatively low. They wrote that identifying high-risk individuals—those with a high PED height and disruption of the external limiting membrane—would help ensure appropriate informed consent before treatment, and that further studies are needed to establish optimal treatment for this population.

SOURCE: Hata M, Oishi A, Yamashiro K, et al. Incidence and causes of vision loss during aflibercept treatment for neovascular age-related macular degeneration: One-year follow-up. Retina 2016; Oct 26. [Epub ahead of print].

Incidence & Growth of GA: Five Years of AMD Treatment Trials

Researchers estimated the incidence, size and growth rate of geographic atrophy during five years of follow-up among participants in the Comparison of Age-Related Macular Degeneration Treatments Trials, as part of a cohort within a clinical trial involving CATT participants.

They randomly assigned 1,185 CATT participants to ranibizumab or bevacizumab treatment and to three treatment regimens. They released participants from protocol treatment at two years and examined individuals at approximately five years (n=647). Two masked graders assessed the presence and size of GA in digital color photographs (CPs) and fluorescein angiograms (FAs) taken at baseline and at years one, two and five. Researchers used Cox proportional hazard models to identify risk factors for the incidence of GA. Annual change in the square root of the total area of GA served as the measure of growth. Researchers used multivariate linear mixed models, including baseline demographic, treatment and ocular characteristics on CP/FA, and optical coherence tomography as candidate risk factors to estimate adjusted growth rates, standard errors (SEs) and 95 percent confidence intervals. The main outcome measures were geographic atrophy incidence and growth rate.

Among the 1,011 participants who didn’t have GA at baseline and who had follow-up images gradable for GA, the cumulative incidence was 12 percent at one year, 17 percent at two years and 38 percent at five years. At baseline, factors including older age, hypercholesterolemia, worse visual acuity, larger choroidal neovascularization area, retinal angiomatous proliferation (RAP) lesion, GA in the fellow eye and intraretinal fluid were associated with a higher risk of incident GA. Thicker subretinal tissue complex and presence of subretinal fluid were associated with less GA development. The overall GA growth rate was 0.33 mm/year (SE, 0.02 mm/year). Eyes treated with ranibizumab in the first two years of the clinical trial had a higher growth rate than eyes treated with bevacizumab (adjusted growth rate, 0.38 vs. 0.28 mm/year; p=0.009). Researchers noted that GA in the fellow eye, hemorrhage and absence of subretinal pigment epithelium fluid at baseline were associated with a higher growth rate.

Researchers wrote that development of GA is common five years after initiating therapy and that several risk factors identified at two years of follow-up persisted at five years of follow-up.

SOURCE: Grunwald JE, Pistilli M, Daniel E, et al. Incidence and growth of geographic atrophy during 5 years of comparison of age-related macular degeneration treatments trials. Ophthalmology 2016; Sept 13. [Epub ahead of print].

OCT-reflective Drusen Substructure Prediction of Progression to AMD

Researchers sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography-reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration-related features and progression, as part of a retrospective analysis of a prospective study.

Participants included individuals with intermediate AMD (n=349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral-domain optical coherence tomography study.

Researchers analyzed baseline SD-OCT scans for the presence of ODS (one eye per individual). They evaluated cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD-OCT and color photographs, including drusen volume, geographic atrophy and pre-atrophic features, for the entire macular region. They made similar local associations within a 0.5-mm-diameter region around individual ODS and corresponding control regions without ODS in the same eye. Main outcome measures included pre-atrophy SD-OCT changes; and GA, central GA and choroidal neovascularization from color photographs.

Researchers defined four phenotypic subtypes of ODS: low-reflective cores; high-reflective cores; conical debris; and split drusen. Among the 307 eligible eyes, 74 (24 percent) had at least one ODS. The ODS at baseline were associated with: greater macular drusen volume at baseline (p<0.001); development of pre-atrophic changes at year two (p=0.001 to 0.01); and development of macular GA (p=0.005) and pre-atrophic changes at year three (p=0.002 to 0.008), but not development of CNV. The ODS at baseline in a local region were associated with presence of pre-atrophy changes at baseline (p=0.02 to 0.03) and development of pre-atrophy changes at years two and three within the region (p=0.008 to 0.05). Researchers concluded that OCT-reflective drusen substructures are biomarkers of progression to GA, but not CNV, in eyes with intermediate AMD. They added that OCT-reflective drusen substructures may be clinically helpful in monitoring AMD progression and informing mechanisms in GA pathogenesis.

SOURCE: Veerappan M, Abdul-Karim M, El-Hage-Sleiman A-KM, et al. Optical coherence tomography reflective drusen substructures predict progression to geographic atrophy in age-related macular degeneration. Ophthalmology 2016; Oct 25. [Epub ahead of print].

Intravitreal Ranibizumab & Oral DHA Supplementation Plus Antioxidants for DME

Investigators assessed the two-year effectiveness of intravitreal ranibizumab combined with a dietary supplement rich in docosahexaenoic acid along with antioxidants in 62 individuals with diabetic macular edema. Brudy Technology (Barcelona), a maker of DHA nutritional products, was a collaborator on the study.

In a randomized, single-blind, controlled study, 33 subjects (42 eyes) received intravitreal ranibizumab alone and 29 (34 eyes) combined with DHA (1,050 mg/day). Monthly ranibizumab (0.5 mg) for the first four months was followed by as-needed treatment.

At 24 months, the difference in the reduction of central subfield macular thickness between groups significantly favored the DHA supplementation group (CI, 7.20 to 97.656; p=0.024), although improvement in best-corrected visual acuity measured in the Early Treatment Diabetic Retinopathy Study letters did not reach statistical significance (CI, 5.4 to 11.2, p<0.66). At 24 months, gains of >5 and >10 letters were significantly higher in the DHA supplementation group compared with controls when investigators considered worse-seeing and better-seeing eyes, but they did not find other differences at 12 months and 24 months.

Investigators found that intravitreal ranibizumab combined with DHA supplementation reduced central subfield macular thickness after two years of follow-up compared with ranibizumab alone in individuals with DME.

SOURCE: Lafuente M, Ortín L, Argente M, et al. Combined intravitreal ranibizumab and oral supplementation with docosahexaenoic acid and antioxidants for diabetic macular edema: Two-year randomized single-blind controlled trial results. Retina 2016; Oct 26. [Epub ahead of print].

Total Retinectomy in Cases With Advanced Proliferative Vitreoretinopathy

Researchers evaluated the long-term results of total retinectomy in individuals with rhegmatogenous retinal detachment and severe proliferative vitreoretinopathy.

Seven eyes of seven cases had pars plana vitrectomy, with or without pars plana lensectomy, and total retinectomy, with or without silicone oil tamponade, for the management of rhegmatogenous retinal detachment and proliferative vitreoretinopathy (Grade D1-3) after previous complex vitreoretinal surgery procedures. Researchers retrospectively evaluated visual acuity, intraocular pressure, details of previous operations and development of complications.

Five eyes had a history of penetrating eye trauma, one had persistent fetal vasculature and one had Coats’ disease. Individuals were all male, with a mean age of 15 ±11 years (range, 2 to 31). The mean follow-up was 49.7 ±50.2 months (range, 12 to 132). In three eyes (42 percent), enucleation and evisceration were avoided over a mean 100 ±30.2 month follow-up. All seven eyes had corneal opacity and band keratopathy after a mean 4.4 ±3.2 months. Four eyes had phthisis bulbi after a mean 7 ±4.2 months. No individuals developed rubeosis iridis related to the total retinectomy.

Researchers determined that total retinectomy may be a last option to preserve the eyeball in cases with massive fibrosis and rhegmatogenous retinal detachment, despite previous complex surgical treatments.

SOURCE: Karacorlu M, Sayman MI, Hocaoglu M, et al. Long-term results of total retinectomy in cases with advanced proliferative vitreoretinopathy. Retina 2016; Nov 8. [Epub ahead of print].

Topical Apraclonidine for Pain Reduction After Intravitreal Injections

Investigators assessed the efficacy of topical apraclonidine in reducing pain and subconjunctival hemorrhage after intravitreal injections, as part of a prospective, randomized, double-blinded study.

They examined 39 individuals twice, at each monthly IViT of 1.25 mg/0.05 mL bevacizumab, and randomly assigned subjects to receive either topical apraclonidine 0.5% or placebo to the treated eye, 30 minutes before the first IViT. At the second IViT, they switched the intervention. Thirty minutes after the injection, investigators measured SCH size by a slit lamp, and assessed pain by the numerical rating scale (NRS-11).

The mean pain score was 1.69 (SD ±1.44) in the apraclonidine group and 3.28 (SD ±2.27) in the control group (p<0.001). Phakic subjects had a greater pain reduction after topical apraclonidine (p<0.001). Subconjunctival hemorrhage incidence was 41 percent in the apraclonidine group and 51.3 percent in the control group (p=0.503). Mean SCH size was 1.71 mm2 (SD ±5.83) in the apraclonidine group and 3.25 mm2 (SD ±6.41) in the control group (p=0.253). After topical apraclonidine, researchers found a smaller reduction in SCH size in individuals with choroidal neovascularization or hypertension (p=0.003 and 0.044, respectively), and a greater reduction in phakic individuals (p=0.048).

Investigators concluded that topical apraclonidine 0.5% administered 30 minutes before IViT significantly decreased pain by a factor of 1.94; it did not decrease the incidence or size of SCH in the entire cohort, although it did so in several subpopulations.

SOURCE: Lagstein O, Ben-Artzi N, Achiron A, et al. Topical apraclonidine reduces pain after intravitreal injections: A double-blind randomized controlled trial. Retina 2016; Nov. 10. [Epub ahead of print].

Correlation of Microvascular Structures on OCTA With VA in RVO

Scientists analyzed the correlation of superficial and deep capillary plexuses using optical coherence tomography angiography with visual acuity in eyes with retinal vein occlusion. They retrospectively reviewed the medical records of 33 individuals with RVO (branch RVO in 21 cases, central RVO in 11 cases) and included 33 healthy subjects as a control group, evaluated by OCTA.

OCTA was performed on a 3-mm x 3-mm region centered on the fovea and parafoveal area. The foveal avascular zone, and foveal and parafoveal vascular density in superficial and deep vascular plexuses were analyzed using OCTA.

The area of superficial and deep FAZ in eyes with RVO was larger than that in fellow eyes and control eyes (p=0.034, p=0.018). The number of superficial and deep parafoveal VDs in eyes with RVO was significantly lower than that in fellow eyes and control eyes (p=0.001, p<0.001). The area of superficial FAZ was negatively correlated with best-corrected visual acuity, and the superficial and deep parafoveal VDs were positively correlated with best-corrected visual acuity. Eighteen of 21 eyes with BRVO (85.7 percent) showed a high concordance rate with respect to the location of BRVO and the lowest parafoveal VD area. Multivariate analysis showed that the deep parafoveal VD was associated with BCVA.

Scientists suggested that OCTA enabled detection of FAZ enlargement, increased parafoveal capillary nonperfusion and decreased parafoveal VD in eyes with RVO. The area of superficial FAZ and parafoveal VD were correlated with BCVA in eyes with RVO, they added.

SOURCE: Kang J-W, Yoo R, Jo YH, et al. Correlation of microvascular structures on optical coherence tomography angiography with visual acuity in retinal vein occlusion. Retina 2016; Nov. 8. [Epub ahead of print].

Nondamaging Retinal Laser Therapy for Treatment of CSC

Researchers summarized the literature addressing subthreshold or nondamaging retinal laser therapy for central serous chorioretinopathy, and discussed results and trends that warrant further investigation by analysis of literature evaluating NRT with micropulse or continuous wave lasers for CSCR.

They included 16 studies of 398 subjects (e.g., retrospective case series, prospective nonrandomized interventional case series and prospective randomized clinical trials). All studies but one evaluated chronic CSCR, and laser parameters varied greatly between studies. Mean central macular thickness decreased on average by ~80 µm at three months. Mean best-corrected visual acuity increased on average by about nine letters at three months, and no study reported a decrease in acuity below presentation. No retinal complications were observed with the various forms of NRT used, but six subjects in two studies with micropulse laser experienced pigmentary changes in the retinal pigment epithelium attributed to excessive laser settings.

Researchers wrote that NRT demonstrated efficacy and safety in 12-month follow-up in subjects with chronic and possibly acute CSCR. They added that NRT would benefit from better standardization of the laser settings and understanding of mechanisms of action, as well as further prospective randomized clinical trials.

SOURCE: Wood EH, Karth PA, Sanislo SR, et al. Nondamaging retinal laser therapy for treatment of central serous chorioretinopathy: What is the evidence? Retina 2016; Nov. 10. [Epub ahead of print].

OCT of Retinal Lesions in Infants With Congenital Zika Syndrome

Researchers evaluated the affected retinal layers in infants with congenital Zika syndrome and associated retinal abnormalities using optical coherence tomography, as part of a cross-sectional, consecutive case series including eight infants (age range: 3 to 5.1 months) with CZS.

Researchers obtained OCT images in the affected eyes of seven infants with CZS who had undergone previous ophthalmologic examinations on March 17, 2016, and in one infant on January 1, 2016. They performed an IgM antibody-capture enzyme-linked immunosorbent assay for ZIKV on the cerebrospinal fluid samples of seven of the eight infants (88 percent), and other congenital infections were ruled out.

Among the eight infants (three male, five female, mean [SD] age at exam, 4.1 [0.7] months), seven who underwent cerebrospinal fluid analysis for ZIKV had positive findings for IgM antibodies. Eleven of the 16 eyes (69 percent) of the eight infants had retinal alterations, and researchers performed OCT imaging in nine (82 percent) of them, along with OCT in one unaffected eye. The main OCT findings in the affected eyes included discontinuation of the ellipsoid zone and hyperreflectivity underlying the retinal pigment epithelium in nine eyes (100 percent), retinal thinning in eight eyes (89 percent), choroidal thinning in seven eyes (78 percent); and colobomatous-like excavation involving the neurosensory retina, retinal pigment epithelium and choroid in four eyes (44 percent).

Researchers wrote that Zika virus can cause severe damage to the retina, including the internal and external layers, and the choroid. They added that the colobomatous-like finding seen in OCT images related to the excavated chorioretinal scar observed clinically.

SOURCE: Ventura CV, Ventura LO, Bravo-Filho V, et al. Optical coherence tomography of retinal lesions in infants with congenital Zika syndrome. JAMA Ophthalmology 2016; Nov. 10. [Epub ahead of print].

Relationship Between Macular Thickness Measurement and Signal Strength on OCT

Investigators examined the relationship between signal strength and macular thickness as measured by Stratus optical coherence tomography’s fast macular thickness protocol in healthy subjects, as part of a prospective cross-sectional study.

Seventy-nine eyes of 42 healthy subjects were enrolled. Investigators recorded the age, gender and eye (right vs. left) of each subject. They used the Stratus OCT fast macular thickness scan protocol and the retinal thickness map analysis to measure macular thickness. Each eye was imaged at least six times to acquire images with signal strengths of 4 through 9 out of 10 via adjustment of the focusing knob. The OCT parameters included in the analysis were thickness in the central 1 mm and in the different quadrants in the 3-mm area.

Overall, 79 eyes of 42 cases with a mean age of 38.4 ±12.4 were included. Investigators found no significant difference between signal strength measurements obtained with different signal strengths in the central thickness (p=0.20). In the superior, nasal, inferior and temporal quadrants, a signal strength of 8 demonstrated up to 3 µm thicker measurements than a signal strength of 5 (p<0.05). In general linear regression analysis, after accounting for age and gender, signal strength didn’t remain a significant predictor of thickness in any quadrant.

Investigators determined that, when using fast map macular measurements, a signal strength of 5 is clinically as efficient as a signal strength of 8 in measuring macular thickness in all quadrants; as such, insisting on higher signal strength may not be necessary.

SOURCE: Segal O, Shapira Y, Gershoni A, et al. Relationship between macular thickness measurement and signal strength using Stratus optical coherence tomography. Clin Ophthalmol 2016;10:2259-64.


Zeiss Gets FDA Nod for SS-OCT Posterior Ocular Imaging With PLEX Elite 9000

Having received the first United States FDA clearance for ocular coherence tomography angiography technology in September 2015, Zeiss now has received the first FDA clearance for swept-source OCT imaging technology for posterior ocular structures with Zeiss Plex Elite 9000. The SS-OCT and OCTA platform was designed for advanced retina research and is at the core of the Advanced Retina Imaging Network, led by Philip J. Rosenfeld, MD, PhD. The network is a global consortium of clinicians and scientists from around the world working at the forefront of retinal disease research focused on exploring new clinical applications for the diagnosis and treatment of eye disease, and advancing OCT innovation. The FDA clearance will help U.S. members of the network more easily enroll individuals and may facilitate faster Institutional Review Board review for protocol approval of research. The wide-field high-resolution visualization provided by the SS-OCT and OCTA imaging of the platform expands clinicians’ ability to examine the critical microstructures and microvasculature of the posterior segment at any depth of interest from vitreous to sclera. Read more.

Stealth Initiates Phase I Study of Elamipretide in Dry AMD

Stealth BioTherapeutics announced the initiation of ReCLAIM, a Phase I study evaluating elamipretide in intermediate age-related macular degeneration. Top-line data are expected mid-year 2017. ReCLAIM is an open-label study to evaluate the safety and tolerability of 12 weeks of treatment with daily subcutaneous injections of elamipretide in individuals age 55 and above who have at least one eye with intermediate AMD, and have either drusen on the retina without any geographic atrophy or noncentral GA. The study's primary endpoints are safety and tolerability, and the secondary endpoints are changes from baseline in physical/ophthalmic exams and feasibility of subcutaneous injections in this population. Read more.

Source: Stealth BioTherapeutics, November 2016

Actemra Found Superior to Steroids Alone for Steroid-free Remission of Giant Cell Arteritis

Genentech, a member of the Roche Group, announced positive results from the Phase III GiACTA study that evaluated Actemra (tocilizumab) in people with GCA. GiACTA met its primary and key secondary endpoint, demonstrating that Actemra, initially in combination with a six-month steroid (glucocorticoid) taper, enabled significantly more individuals to achieve sustained disease remission while also significantly reducing steroid exposure compared with steroids alone. The primary endpoint was met, with Actemra significantly increasing the proportion of individuals achieving sustained remission at one year (56 percent [QW; p<0.0001] and 53.1 percent [Q2W; p<0.0001]) vs. 14 percent with a six-month steroid taper regimen given alone. The study also met its key secondary endpoint, demonstrating that Actemra significantly increased the proportion of people achieving sustained remission at one year (56 percent [QW; p<0.0001] and 53.1 percent [Q2W; p=0.0002]) compared to 17.6 percent with a 12-month steroid taper regimen given alone. Read more.

Source: Genentech, November 2016


Ocular Therapeutix announced positive topline results from its Phase III clinical trial of Dextenza (dexamethasone insert) 0.4 mg for the treatment of post-surgical ocular inflammation and pain. Dextenza is a product candidate administered by a physician as a bioresorbable intracanalicular insert and designed for drug release to the ocular surface for up to 30 days. The trial successfully met its two primary efficacy endpoints for inflammation and pain, achieving statistically significant differences between the treatment group and the placebo group for the absence of inflammatory cells on day 14 and the absence of pain on day eight, respectively. A total of 52.3 percent of individuals treated with Dextenza showed an absence of inflammatory cells in the anterior chamber of the study eye on day 14 compared with 31.1 percent of those receiving the placebo vehicle control punctum plug (p<0.0001). Read more.

Source: Ocular Therapeutix, November 2016

RP May Be Treated by Reprogramming Sugar Metabolism

Columbia University Medical Center researchers have demonstrated that vision loss associated with a form of retinitis pigmentosa can be slowed dramatically by reprogramming the metabolism of photoreceptors in the retina. The study, conducted in mice, represents a novel approach to RP treatment in which the therapy aims to correct downstream metabolic aberrations of the disease rather than the underlying genetic defect. The findings were published online in the Journal of Clinical Investigation. In an earlier paper, researchers theorized that rods deteriorate in RP in part because of an inability to use glucose to rebuild the rods’ outer segment. “We hypothesized that diseased rods could be rescued by reprogramming sugar metabolism,” said Stephen H. Tsang, MD, PhD, László Z. Bitó associate professor of ophthalmology, Pathology & Cell Biology, Columbia University. Dr. Tsang tested this hypothesis in mice with a mutation in the Pde6 gene that disrupts rod metabolism, leading to an RP-like disorder. The mice were treated so that their rods could not express Sirt6, a gene that inhibits sugar metabolism. Examination of photoreceptors with electroretinography showed the mice had significantly greater measures of rod and cone health than untreated controls. Overall, the metabolomes of the treated mice had accumulated the molecules needed to build the outer segment and rods and cones survived longer in the treated mice than in the controls. While the treatment significantly prolonged survival of the diseased rods and cones, it didn’t prevent their eventual death. Dr. Tsang said the team’s next challenge is to figure out how to extend the therapeutic effect of Sirt6 inhibition. Read more.

Source: Columbia University Medical Center, November 2016

New Protein Offers Link Between Aging & Macular Degeneration

The discovery of a novel protein that links aging and age-dependent retinal diseases could lead to potential new treatments for conditions that cause sight loss in later life. In a study in mice, to be published in the eLife, researchers from the University of Wisconsin-Madison reveal that Transmembrane 135 regulates retinal aging and that mutations in the protein result in age-dependent disease. Tmem135 has previously been associated with fat storage and long life in the roundworm Caenorhabditis elegans, but its molecular function has never been characterized clearly. The new study shows that irregular levels of the protein lead to symptoms of macular degeneration. The team of researchers studied mouse models that exhibit retinal abnormalities similar to those seen in normal-aged mice, but with earlier onset and faster development. Genetic mapping revealed that the mutation in Tmem135 caused these symptoms. The team also discovered that the protein regulated the size of the mitochondria, an energy-producing organelle essential for various metabolic functions of cells. The team aims to determine the exact biochemical and molecular functions of Tmem135 in mitochondria and to examine its roles in the aging process of other tissues and various age-dependent diseases. Read more.

Source: eLife Sciences Publications, November 2016

Upstate Discovery Advances Understanding of Retinal Cell Formation

SUNY Upstate Medical University researchers Andrea S. Viczian, PhD, and Michael E. Zuber, PhD, and colleagues, have advanced understanding of how retinal cells are formed by identifying two genes—Tbx3 and Pax6—that start the process of eye development. Their discovery could play a role in how retinal diseases such as age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa might be treated. The findings were recently published in Development. Eye field transcription factors are a group of seven genes that work together and are required for the formation of a normal eye. Prior to the researchers’ discovery, it was assumed that all seven EFTFs were required to start eye formation. In their study, the team used frog embryos, whose retinas develop in a similar manner and contain the same retinal cell types as those of the human retina. They found that only two of the seven EFTFs, Tbx3 and Pax6, were necessary to start the process of eye formation and the retina. With further study, the discovery may also be translated into generating retinal cells in culture for therapeutic use. Read more.

Source: SUNY Upstate Medical University, October 2016


Care Trend Report, Volume II, supported by Allergan, is a 40-page report that examines and compares the perspectives of managed care organizations, ophthalmologists and optometrists on current eye-care issues. Findings from three surveys are analyzed along with commentary from an independent Editorial Advisory Panel of 10 managed-care and eye-care experts. A total of 83 MCOs, 65 ophthalmologists and 127 optometrists completed the three surveys. Findings include: MCOs name the rising cost of care as the leading challenge in eye care, while ophthalmologists and optometrists cite decreasing reimbursements as the top challenge; and approximately three-quarters of ophthalmologists (n=64) and optometrists (n=127) agree that a patient’s health plan formulary has a great or moderate influence on prescribing decisions. Read more.

Source: Allergan, November 2016

Researchers Initiate Phase II Gene Therapy Trial for Choroideremia

Following a successful Phase I gene therapy trial for choroideremia, Robert MacLaren, professor of Ophthalmology at University of Oxford, and his team initiated a Phase II trial enrolling 30 subjects in which Professor MacLaren is using an operating microscope with integrated optical coherence tomography that will refine the surgery integral to gene replacement therapy. The OPMI Lumera 700 Rescan purchase is the result of a number of donors, including: Fight for Sight; Tommy Salisbury Choroideremia Fund at Fight for Sight; National Eye Research Centre; Choroideremia Research Foundation USA; Saturday Hospital Fund; and benefactors of the MacLaren Group. The intraoperative OCT microscope enables surgeons to track changes in the retinal anatomy in real time, and enable safe and precise delivery of the gene therapy with the goal of improved vision for patients. Read more.

Source: Oxford Clinical Trials Research Unit, November 2016


Second Sight Medical Products announced that the Centers for Medicare & Medicaid Services finalized its Medicare hospital outpatient payment rate of $150,000.50 for 2017, which includes the cost of the Argus II Retinal Prosthesis System. In addition, the company announced that the American Medical Association Current Procedural Terminology Editorial Panel approved two new Category III CPT codes for initial programming and subsequent reprogramming of the Argus II. The codes will be published on January 1, 2017, and can be reported by clinicians beginning on July 1, 2017. Read more.

Source: Second Sight, November 2016


Applied Genetic Technologies Corp. filed an Investigational New Drug application with the U.S. Food and Drug Administration to conduct a Phase I/II clinical trial of the company's gene therapy product candidate for the treatment of achromatopsia caused by mutations in the CNGA3 gene. The Company previously initiated a Phase I/II clinical trial of its gene therapy product for the treatment of achromatopsia caused by mutations in the CNGB3 gene, and plans to initiate a clinical study evaluating the safety and efficacy of the therapy product for CNGA3-related achromatopsia in the United States in upcoming months. Read more.

Source: AGTC, October 2016


Spark Therapeutics announced a multiyear research agreement with Guangping Gao, PhD, the Penelope Booth Rockwell Chair in Biomedical Research, director of the Horae Gene Therapy Center, and professor of microbiology and physiological systems at the University of Massachusetts Medical School. Dr. Gao will collaborate with Spark Therapeutics to identify adeno-associated virus vectors from a proprietary library of AAV capsids and evaluate their efficacy, with the goal of enhancing the efficiency of gene delivery to cells in the retina, liver and central nervous system. Read more.

Source: Spark Therapeutics, October 2016


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