Review of Ophthalmology's Retina Online

Volume 14, Number 5
May 2018

WELCOME to Review of Ophthalmology's Retina Online 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.

Genentech announced that the U.S. Food and Drug Administration approved the Lucentis (ranibizumab injection) 0.3 mg prefilled syringe as a new method of administering the medicine to treat all forms of diabetic retinopathy...

MeiraGTx announced that the U.S. Food and Drug Administration granted Fast Track designation for AAV-RPGR for the treatment of X-linked retinitis pigmentosa due to defects in the retinitis pigmentosa GTPase regulator gene...

And More...

Estimating Medicare & Patient Savings from Use of Bevacizumab for Exudative AMD Treatment

Researchers estimated Medicare cost savings from the use of bevacizumab in the United States for the treatment of exudative age-related macular degeneration by replacing the use of bevacizumab with ranibizumab and aflibercept, as part of a retrospective trend study.

Main outcome measures were spending by Medicare as tracked by Current Procedural Terminology codes for intravitreal injections (67028) and treatment-specific J-codes (J0178, J2778, J9035, J3490 and J3590) for inhibitors of vascular endothelial growth factor. These claims were identified from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services among fee-for-service Medicare beneficiaries from 2012 to 2015. The 2008 claims were acquired from the 100-percent FFS Part B Medicare Claims File.

The use of bevacizumab from 2008 to 2015 resulted in an estimated savings of $17.3 billion, which corresponded to a $13.8 billion savings to Medicare and a $3.5 billion savings to individuals receiving treatments. This amount underestimated the actual cost savings to Medicare providers since approximately 30 percent of Medicare-eligible recipients received care within Medicare Advantage plans and were not included in this analysis.

Researchers estimated the cost savings from the use of bevacizumab from 2008 to 2015 for Medicare FFS beneficiaries undergoing treatment for exudative AMD at $17.3 billion. They added that additional savings over the $17.3 billion would have accrued from the use of bevacizumab if diagnostic categories such as diabetic macular edema and retinal vein occlusion were included in this study.

Rosenfeld PJ, Windsor MA, Feuer WJ, et al. Estimating Medicare and patient savings from the use of bevacizumab for the treatment of exudative age-related macular degeneration. Am J Ophthalmol 2018; Apr 12. [Epub ahead of print].



Emixustat Hydrochloride for GA Secondary to AMD

Researchers determined whether emixustat hydrochloride reduced the rate of geographic atrophy enlargement compared with placebos in subjects with age-related macular degeneration, and evaluated the safety and tolerability of emixustat over 24 months of treatment.

The multicenter, randomized, double-masked, placebo-controlled, Phase IIb/III clinical trial included individuals with GA secondary to AMD, a visual acuity score of at least 35 letters, and GA with a total area of 1.25 to 18 mm2. Subjects were randomized (1:1:1:1) to emixustat 2.5 mg, 5 mg, 10 mg or placebo, administered orally once daily for 24 months. Visits included screening, baseline, and months one, two, three, six, nine, 12, 15, 18, 21, 24 and 25.

The primary efficacy end point was the mean annual growth rate of total GA area in the study eye, as measured by a central reading center using fundus autofluorescence images. The change from baseline in normal luminance best-corrected visual acuity was a secondary efficacy end point.

Of 508 randomized subjects, 320 completed the study. Demographics and baseline characteristics were comparable between treatment groups. On average, GA lesions in the study eye grew at a similar rate in each group (emixustat: 1.69 to 1.84 mm2/year; placebo: 1.69 mm2/year; p≥0.81). Changes in NL-BCVA were also comparable between groups. Subjects with a larger low-luminance deficit at baseline (≥20 letters) demonstrated a more rapid growth of GA over 24 months. No relationship was observed between the risk-allele status of the AMD-associated single-nucleotide polymorphisms tested and the growth rate of GA. The most common adverse events in emixustat-treated subjects were delayed dark adaptation (55 percent), chromatopsia (18 percent), visual impairment (15 percent) and erythropsia (15 percent).

Researchers wrote that emixustat didn’t reduce the growth rate of GA in AMD. They noted that the most common adverse events were ocular in nature and likely related to the drug’s mechanism of action. Researchers added that data gained from this study over a two-year period added to the understanding of the natural history of GA and the baseline characteristics affecting the growth rate of GA.

SOURCE: Rosenfeld PJ, Dugel PU, Holz FG, et al. Emixustat hydrochloride for geographic atrophy secondary to age-related macular degeneration. Ophthalmology 2018; April 28. [Epub ahead of print].



Efficacy of Anti-amyloid β Monoclonal Antibody in GA Secondary to AMD

Investigators assessed the efficacy of intravenous GSK933776—a humanized monoclonal antibody directed against the N-terminal amino acids of amyloid β—for the treatment of geographic atrophy in age-related macular degeneration. The prospective, randomized, placebo-controlled, double-masked, multicenter Phase II clinical trial included individuals with GA secondary to AMD, a visual acuity score of at least 35 letters and GA with a total area of 1.9 to 17 mm2.

Participants were monitored monthly for four months during an observation period to determine the rate of GA enlargement in the study eye, after which subjects were randomized into one of four treatment arms (GSK933776 at three and six months, 15 mg/kg/month or placebo). At each monthly visit beyond 18 months, participants underwent visual acuity testing under normal- and low-luminance conditions. Ocular imaging included color fundus photography, fundus autofluorescence, fluorescein angiography and spectral-domain OCT. The main outcome measure was enlargement in GA area measured from color fundus photographs, with reference to fundus autofluorescence images.

A total of 191 participants were randomized into the study, with 139 (73 percent) fulfilling the efficacy population criteria. Over 18 months, GSK933776 didn’t reduce the rate of GA enlargement compared to the placebo. Overall, investigators recorded no consistent meaningful differences relative to the placebo in any of the visual function measures. They did find a correlation between a low-luminance VA deficit at baseline and the rate of GA enlargement, although genetic variations in the complement factor I gene didn’t correlate with GA progression. Investigators identified no serious ocular adverse events related to the GSK933776 treatment, and reported a similar number of serious non-ocular adverse events across all treatment groups.

Investigators wrote that intravenous amyloid β inhibition with GSK933776 didn’t slow the rate of GA enlargement compared to placebo, and that no clinically meaningful differences relative to the placebo were observed in visual function testing over 18 months. They added that a low-luminance VA deficit was associated with faster GA enlargement; however, no correlation was shown between genetic variations in the CFI gene and the rate of GA enlargement.

SOURCE: Rosenfeld PJ, Berger B, Reichel E, et al. A randomized phase II study of an anti-amyloid β monoclonal antibody in geographic atrophy secondary to age-related macular degeneration. Ophthalmology Retina 2018; Apr 17. [Epub ahead of print].

Bioengineered RPE Monolayer for Advanced Dry AMD

Researchers wrote that retinal pigment epithelium dysfunction and loss are hallmarks of non-neovascular age-related macular degeneration. Without proper RPE function and structure, a majority of overlying photoreceptors degenerate, leading to severe, progressive vision loss. Clinical and histological studies suggest that RPE replacement strategies might delay disease progression or restore vision.

As such, a prospective, interventional, FDA-cleared, Phase I/IIa study is being conducted to assess the safety and efficacy of a composite subretinal implant in subjects with advanced NNAMD. The implant, known as the California Project to Cure Blindness-Retinal Pigment Epithelium 1, consists of a polarized monolayer of human embryonic stem cell-derived RPE on an ultra-thin, synthetic parylene substrate designed to mimic Bruch's membrane.

Researchers reported an interim analysis of the Phase I cohort consisting of five subjects. Four of five individuals enrolled in the study successfully received the composite implant. In all implanted subjects, optical coherence tomography imaging showed changes consistent with hESC-RPE and host photoreceptor integration. None of the implanted eyes showed progression of vision loss, one eye improved by 17 letters and two eyes demonstrated improved fixation.

Researchers concluded that the concurrent structural and functional findings suggested that CPCB-RPE1 might improve visual function, at least in the short term, in some individuals with severe vision loss from advanced NNAMD.

SOURCE: Kashani AH, Lebkowski JS, Rahhal FM, et al. A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration. Sci Transl Med 2018 Apr 4;10:435.

Baseline SD-OCT Characteristics of AMD: Amish Eye Study

Investigators described spectral-domain optical coherence tomography findings in an Amish cohort to assess markers for early age-related macular degeneration.

They performed a family-based, prospective cohort study of 1,146 elderly Amish subjects (2,292 eyes) (ages, 50 to 99 years) with a family history of at least one individual with AMD. All subjects underwent complete ophthalmic exams, SD-OCT using Cirrus and Spectralis instruments (20 × 20-degree scan area), fundus autofluorescence, infrared imaging and color fundus photography. Investigators analyzed SD-OCT characteristics in subjects with AMD (with and without subretinal drusenoid deposits) and normal healthy cohorts.

Participants' mean age was 65.2 years (SD ±11). Color fundus photographic findings in 596 subjects (53 percent) were consistent with AMD; the remaining 478 subjects (43 percent) showed no signs of AMD. The choroid was significantly thinner on OCT in those with AMD (242 ±76 µm, p< 0.001) compared with those without AMD (263 ±63 µm). Subretinal drusenoid deposits were found in 143 eyes (7 percent), and 11 of 143 eyes (8 percent) had no other manifestations of AMD. Drusen volume (p<0.001) and area of geographic atrophy were significantly greater (p<0.001), and choroid was significantly thinner (p<0.001) in subjects with subretinal drusenoid deposits than those without deposits.

Investigators reported that subretinal drusenoid deposits, though relatively uncommon in this population, could be found in the absence of other AMD features, and that eyes with these deposits had thinner choroids.

SOURCE: Nittala MG, Song YE, Sardell R, et al. Amish eye study: Baseline spectral domain optical coherence tomography characteristics of age-related macular degeneration. Retina 2018; May 9. [Epub ahead of print].

Topographic Correspondence of Macular Atrophy with CNV in Ranibizumab-treated Eyes

Researchers quantified the extent of topographic correspondence between baseline choroidal neovascularization and macular atrophy at follow-up in eyes with NVAMD, as part of a post hoc analysis of randomized, controlled clinical trial (TREX-AMD) data.

They followed 60 treatment-naïve neovascular age-related macular degeneration subjects from the TREX-AMD trial for 18 months. At month 18, they graded regions of macular atrophy on fundus autofluorescence aided by spectral-domain optical coherence tomography. They manually graded CNV lesions on fluorescein angiography, with lesion components (including classic and occult CNV) delineated. FAF and FA images were registered to quantify the area and location of overlap between CNV and MA. Findings included the following:
• Twenty-six eyes had MA at month 18 and CNV at baseline.
• A total of 84.6 percent of eyes showed evidence of MA and CNV overlap.
• By month 18, MA appeared in regions corresponding with: baseline classic CNV in 36.4 percent of eyes, occult CNV in 40.9 percent and both regions in 22.7 percent, with more MA area in regions of occult rather than classic CNV.
• Baseline MA position corresponded with: baseline classic CNV in 76.9 percent of eyes, occult CNV in 61.5 percent of eyes and both regions in 15.4 percent, with more MA area in regions of occult rather than classic CNV.
• Among eyes with MA and CNV at baseline but no overlap, 50 percent progressed to involve regions with baseline CNV. Six eyes had no baseline MA but developed MA at month 18 within regions of baseline CNV.

Researchers determined that more MA lesions developed within the region of baseline CNV (type I, CNV-based MA) than outside (type II, CNV-independent MA) in ranibizumab-treated eyes with NVAMD. They found that baseline MA also tended to be located within regions of CNV in the pre-treatment phase.

SOURCE: Abdelfattah NS, Hariri A, Al-Sheikh M, et al. Topographic correspondence of macular atrophy with choroidal neovascularization in ranibizumab treated eyes of the TREX-AMD Trial. Am J Ophthalmol 2018; May 12. [Epub ahead of print].

Association of Single-Nucleotide Polymorphisms with Pseudodrusen in AMD

Investigators evaluated the association of SNPs in complement factor H, age-related maculopathy susceptibility 2, HtrA serine peptidase 1, complement C2, complement C3, lipase C and complement factor B genes, with the presence of pseudodrusen and pseudodrusen subtypes (i.e., dot, reticular and confluent).

In this post hoc analysis of cross-sectional data from U.S. participants in the Comparison of AMD Treatments Trials, genotyping was performed in 835 participants with TaqMan assays for the SNPs:
• rs1061170 (Y402H variant in CFH);
• rs800292 (I62V variant in CFH);
• rs10490924 (A69S variant in ARMS2);
• rs11200638 (HTRA1);
• rs547154 (C2);
• rs2230199 (R102G variant in C3);
• rs10468017 (LIPC); and
• rs4151667 (L9H variant in CFB).

The main outcomes included presence and subtype of baseline pseudodrusen in either eye, determined using color fundus photography, red-free images and fluorescein angiograms.

Among 835 participants enrolled for genotyping, 755 (90.4 percent) were evaluated for pseudodrusen. Of these:
• 471 (62.4 percent) were female and 750 (99.3 percent) were white; the mean (SD) age was 78.3 (7.5) years;
• 213 of 755 participants (28.2 percent) had pseudodrusen, 107 (14.2 percent) had dot pseudodrusen, 180 (23.8 percent) had reticular pseudodrusen, and 102 (13.5 percent) had confluent pseudodrusen. After adjusting for age, sex and smoking status:
• ARMS2 risk allele T was associated with higher risk of pseudodrusen (OR, 1.93; CI, 1.19 to 3.12) for TT vs. GG (p=0.04), with a similar association found with HTRA1 (OR, 2.04; CI, 1.26 to 3.31) for AA vs. GG (p=0.03);
• CFH Y402H risk allele C was associated with lower risk of pseudodrusen (OR, 0.61; CI, 0.38 to 0.97) for CC vs. TT but was not statistically significant after correcting for multiple comparison (p=0.20); and
• CFH Y402H, ARMS2, HTRA1 and C3 were significantly associated with reticular pseudodrusen.

Investigators wrote that, among individuals with neovascular AMD, risk alleles ARMS2 and HTRA1 were associated with an increased risk of pseudodrusen, and risk allele CFH Y402H was associated with a lower risk of pseudodrusen, supporting findings from previous studies. They added that understanding the role of these SNPs in the development of pseudodrusen might improve the field’s understanding of the pathogenesis of AMD and help develop future therapies.

SOURCE: Lin LY, Zhou Q; Hagstrom S, et al, et al. Association of single-nucleotide polymorphisms in age-related macular degeneration with pseudodrusen. JAMA Ophthalmol 2018; May 3. [Epub ahead of print].

Ranibizumab in Eyes with DME & Macular Nonperfusion in RIDE and RISE

Researchers looked for characteristics that distinguish individuals with diabetic macular edema with coexisting macular nonperfusion (MNP) at baseline, and assessed the potential of individuals with DME to achieve favorable visual acuity, anatomic and diabetic retinopathy outcomes over 24 months, as part of a post hoc analysis of the RIDE/RISE Phase III, randomized, double-masked trials.

Participants included study eyes with best-corrected VA/fluorescein angiogram data at baseline. To measure MNP, researchers overlaid the Early Treatment Diabetic Retinopathy Study grid on FAs of the macula. They calculated the MNP area by estimating the percentage of capillary loss in the central, inner and outer subfields, and converting the data into disc areas using a software algorithm.

Main outcome measures included:
• baseline characteristics, MNP area, BCVA and central subfield thickness at months 12 and 24; and
• incidence of study eyes with ≥2-step DR improvement at months three, six, 12, 18 and 24.

Baseline MNP was detected in 28.2 percent in the ranibizumab 0.3-mg group (n=213), 25.8 percent in the ranibizumab 0.5-mg group (n=225) and 26.3 percent in the sham arm (n=228). Findings included:
• at baseline, individuals with MNP were younger and had shorter diabetes duration, worse vision, increased CST and worse DR severity than those without MNP (p<0.01);
• in the ranibizumab 0.3-mg group, eyes with baseline MNP had lower mean baseline BCVA (53.4 ETDRS letters) than those without baseline MNP (57.2 ETDRS letters)(p=0.05), but comparable mean BCVA gain at month 24 (+15.6 ETDRS letters) than those without baseline MNP (13.4 ETDRS letters)(p=0.2);
• eyes with baseline MNP had increased CST at baseline, but a greater decrease in CST by month 24; and
• the proportion of eyes with ≥2-step DR improvements was greater for eyes with MNP than without baseline MNP in each ranibizumab arm.

Researchers found that eyes with concurrent DME and baseline MNP entering RIDE/RISE studies experienced robust VA and anatomic improvement with ranibizumab, despite having worse vision and increased CST compared with eyes without baseline MNP. As such, they recommended that these cases should not be excluded from therapy consideration.

SOURCE: Reddy RK, Pieramici DJ, Gune S, et al. Efficacy of ranibizumab in eyes with diabetic macular edema and macular nonperfusion in RIDE and RISE. Ophthalmology 2018; May 8. [Epub ahead of print].

Dex Implant for DME in Naive vs. Refractory Eyes: IRGREL-DEX Study

Researchers investigated the efficacy and safety of repeated dexamethasone implants over 24 months in treatment-naive diabetic macular edema eyes compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment. This multicenter, retrospective study assessed best-corrected visual acuity and central subfield thickness (CST). Safety data (intraocular pressure rise and need for cataract surgery) were recorded.

A total of 130 eyes from 125 individuals were included. Baseline best-corrected visual acuity and CST were similar for naive (n=71) and refractory eyes (n=59). Vision in both groups improved significantly after 24 months (p<0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (11.3 ±10 vs. 7.3 ±2.7 letters, p=0.01) and were more likely to gain ≥10 letters (OR 3.31, CI 1.19 to 9.24, p=0.02). At six, 12 and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was greater in refractory eyes than in naive eyes (313 ±125 vs. 279 ±61 μm, p=0.10).

Over a follow-up period of 24 months, vision improved in DME eyes after treatment with dexamethasone implants—in treatment-naive eyes as well as in eyes refractory to anti-VEGF treatment. Improvement was greater in naive eyes, however.

SOURCE: Iglicki Matias, Busch C, Zur D, et al. Dexamethasone implant for diabetic macular edema in naive compared with refractory eyes: The International Retina Group real-life 24-month multicenter study. The IRGREL-DEX Study. Retina 2018; April 24. [Epub ahead of print].

Somatotype, Risk of Hydroxychloroquine Retinopathy and Safe Daily Dosing Guidelines

The aim of this study was to determine whether somatotype influenced the risk of hydroxychloroquine retinopathy, and if dosing by real body weight, ideal body weight or the lesser of these better predicted risk of HCR.

Investigators enrolled 565 people taking HC, and recorded height and weight, and used sensitive ancillary testing, which included:
• 10-2 visual fields;
• spectral-domain optical coherence tomography;
• fundus autofluorescence imaging; and
• multifocal electroretinography.
Investigators compared body mass index for individuals without and with HCR, along with logistic regression models of:
• age;
• cumulative dose; and
• daily dosing based on RBW, IBW or the lesser of these.
Area under the curve of receiver operating characteristic plots aided researchers in evaluating the diagnostic accuracy of RBW, IBW and the lesser of these guidelines for safe dosing. Researchers compared probability plots for the risk of retinopathy and BMI for the different recommended guidelines on safe dosing.

A total of 41 individuals had HCR. The median BMI was 27.6 (interquartile range (IQR 24.3, 32.6) for those without HCR and 24 (IQR 21, 31.6) for those with HCR (p=0.0102). AUC for univariate ROC plots of retinopathy vs. dosing by RBW was 0.71, by IBW was 0.72 and by lesser of these was 0.76. AUC for multivariate ROC plots of retinopathy vs. models incorporating gender, age, cumulative dose and BMI, and customizing dosing by RBW was 0.82, by IBW was 0.82 and by lesser of these was 0.83. For all of the multivariate logistic models, the risk of retinopathy was higher for lower BMIs.

Investigators concluded that short, asthenic women were at higher risk for HCR. They wrote that the 2011 American Academy of Ophthalmology guidelines were safer for short, obese women, but that 2016 AAO guidelines were safer for short, asthenic individuals. They suggested that selecting daily dosing based on the lesser of the RBW and IBW guidelines would be safest for all individuals.

SOURCE: Browning DJ, Lee C. Somatotype, the risk of hydroxychloroquine retinopathy, and safe daily dosing guidelines. Clin Ophthalmol 2018;12:811-18.

Systemic & Ocular Determinants of Peripapillary RNFL Thickness

Scientists analyzed systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in a European population, as part of a cross-sectional meta-analysis.

They included 16,084 European adults from eight cohort studies (mean age range, 56.9 ±12.3 to 82.1±4.2 years) of the European Eye Epidemiology consortium. Scientists examined associations with pRNFLT measured by spectral-domain OCT using multivariable linear regression and pooled results from random effects meta-analyses. Main outcome measures included determinants of pRNFLT.

Mean pRNFLT ranged from 86.8 ±21.4 μm in the Rotterdam Study I to 104.7 ±12.5 μm in the Rotterdam Study III. Scientists found the following factors to be associated with reduced pRNFLT:
• older age (β=-0.38 μm/year; CI, -0.57 to -0.18);
• higher intraocular pressure (β=-0.36 μm/mmHg; CI, -0.56 to -0.15);
• visual impairment (β=-5.50 μm; CI, -9.37 to -1.64);
• history of systemic hypertension (β=-0.54 μm; CI, -1.01 to -0.07); and stroke (β=-1.94 μm; CI, -3.17 to -0.72).
• A suggestive, non-significant association was observed for dementia (β=-3.11 μm; CI, -6.22 to 0.01).
• Higher pRNFLT was associated with more hyperopic spherical equivalent (β=1.39 μm/diopter; CI, 1.19 to 1.59) and smoking (β=1.53 μm; CI, 1 to 2.06) for current smokers compared with never-smokers.

In addition to previously described determinants such as age and refraction, researchers found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. They wrote that these factors might be of clinical relevance, especially in monitoring glaucoma with newly occurring vascular comorbidities.

SOURCE: Mauschitz MM, Bonnemaijer PWM, Diers K, et al. Systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness measurements in the European Eye Epidemiology (E3) population. Ophthalmology 2018; Apr 28. [Epub ahead of print].



Genentech announced that the U.S. Food and Drug Administration approved the Lucentis (ranibizumab injection) 0.3 mg prefilled syringe as a new method of administering the medicine to treat all forms of diabetic retinopathy. In April 2017, Lucentis 0.3 mg became the first and only FDA-approved medicine to treat all forms of diabetic retinopathy in people with or without diabetic macular edema. The Lucentis 0.3 mg PFS is the first syringe prefilled with an anti-vascular endothelial growth factor agent FDA-approved to treat both DR and DME. Read more.

Source: Genentech, April 2018


MeiraGTx announced that the U.S. Food and Drug Administration granted Fast Track designation for AAV-RPGR for the treatment of X-linked retinitis pigmentosa due to defects in the retinitis pigmentosa GTPase regulator gene. The company is conducting an open-label, Phase I/II dose-escalation clinical trial of AAV-RPGR in adult and pediatric subjects diagnosed with XLRP caused by mutations in the eye-specific form of the RPGR gene, called RPGR open reading frame 15. AAV-RPGR has also received Orphan Drug designation from the FDA. In addition to the study, MeiraGTx is also continuing to enroll and conduct an ongoing natural history study of individuals with X-linked retinitis pigmentosa. Read more.

Source: MeiraGTx, April 2018


Novartis presented new data from the HAWK and HARRIER Phase III trials at the Association for Research in Vision and Ophthalmology 2018 Annual Meeting (April 29 to May 3) in Honolulu. HAWK and HARRIER are 96-week, prospective, double-masked, multicenter, Phase III studies randomizing subjects 1:1:1 to brolucizumab (RTH258) 3 mg (n=358), brolucizumab 6 mg (n=360) or aflibercept 2 mg (n=360) (HAWK), or 1:1 with either brolucizumab 6 mg (n=370) or aflibercept 2 mg (n=369) (HARRIER). Data on a secondary endpoint examining the predictability of 12-week dosing for individuals with neovascular age-related macular degeneration treated with brolucizumab were presented for the first time at the meeting. The majority of individuals with a need for q8 were identified during the first q12 interval (80 percent of the brolucizumab 6-mg group in HAWK and 78 percent of the brolucizumab 6-mg group in HARRIER). Individuals receiving brolucizumab 6 mg who successfully completed the first q12w interval had an 87.4 percent and 82.5 percent probability of remaining on q12w treatment until week 48 in HAWK and HARRIER, respectively (82.6 percent probability for the 3-mg brolucizumab arm of HAWK). Brolucizumab subjects who were successfully identified as being suitable for the q12w interval dosing in the first q12w interval immediately after loading were likely to remain on q12w treatment for the remainder of the study.

Source: Novartis, March 2018

Regeneron Provides Update on Reports of Inflammation Following Eylea Injection

Regeneron released an update regarding post-marketing reports of intraocular inflammation following administration of Eylea (aflibercept) injection. The open letter to health-care providers explains that Regeneron initiated an extensive review of manufacturing processes and didn’t identify an association between inflammation rates and Eylea. However, the analysis did identify an association with certain batches of syringes co-packaged in certain lots of final Eylea cartons that were distributed in the United States. While no causative factor could be identified, Regeneron sent a communication to the ASRS, FDA and health-care providers recommending that practitioners not use the identified syringes and offering to exchange the Eylea kits containing these syringes. Regeneron also stopped distribution of Eylea kits with the identified syringes. As of April 2018, the overall rate of reported intraocular inflammation has returned to historical levels of one to four reports per 10,000 vials. Read more.

Source: Regeneron Pharmaceuticals, May 2018


Iconic Therapeutics announced enrollment of the first patient in its second Phase II study of Icon-1 administered intravitreally in combination with, and as treatment after, anti-VEGF therapy with aflibercept (Eylea). The Dose Exploration and Continuation Option multicenter study is recruiting subjects with choroidal neovascularization secondary to age-related macular degeneration to generate additional clinical data with a higher dose of ICON-1 than previously evaluated. Read more.

Source: Iconic Therapeutics, May 2018

Massachusetts Eye and Ear Doctor Honored for Retina Research

Joan W. Miller, MD, the David Glendenning Cogan Professor and Chair of Ophthalmology at Harvard Medical School and the chief of ophthalmology at Massachusetts Eye and Ear and Massachusetts General Hospital, will receive two awards recognizing her contributions to the field of retina and ophthalmology: the 2018 Charles L. Schepens, MD /American Academy of Ophthalmology Award and the Gertrude D. Pyron Award of the Retina Research Foundation. Dr. Miller and her colleagues pioneered the development of photodynamic therapy using verteporfin (Visudyne), the first approved pharmacological therapy able to reduce and slow vision loss in patients with age-related macular degeneration. The group also identified the key role of vascular endothelial growth factor in ocular neovascularization, leading to the development of anti-VEGF therapies. Read more.

Source: Massachusetts Eye and Ear, May 2018


Researchers affiliated with Japan's Kawasaki Innovation Gateway at Skyfront have developed new mouse models of retinal degeneration to enable transplantation of retinal sheets derived from human embryonic stem cells. Results of the research, reported in Stem Cell Reports, show promise for the approach to aid in treating retinal degeneration, the researchers say. Read more.

Source: King Skyfront, May 2018


Optos, part of Nikon Corp., announced that it launched Monaco, the first ultra-widefield imaging device combined with OCT, in the United States. Monaco, a new compact desktop UWF retinal imaging device, provides greater imaging functionality and represents the company’s first imaging device with ultra-widefield color imaging, three-in-one color depth imaging and autofluorescence modalities combined with OCT. The device is designed to enhance pathology detection and disease management, and improve clinical flow. Read more.

Source: Optos, May 2018


Bausch + Lomb announced the results from the ninth consecutive year of the Antibiotic Resistance Monitoring in Ocular Microorganisms surveillance study, presented at the 2018 Association for Research in Vision and Ophthalmology Meeting in Honolulu. Researchers also presented preliminary 2017 surveillance data on antibiotic resistance levels. The nine-year trend analysis confirmed the previously noted decrease in methicillin resistance among Staphylococcus aureus (from 39 percent to 14 percent; p<0.001) but not among coagulase-negative staphylococci (p=0.455), with more than half of CoNS demonstrating continued persistence in MR. Further analysis showed decreased resistance among S. aureus to azithromycin (62 percent to 52 percent), ciprofloxacin (39 percent to 16 percent), tobramycin (24 percent to 6 percent), and chloramphenicol (6.6 percent to 4.4 percent), and among CoNS to ciprofloxacin (46 percent to 22 percent) (p≤0.005 for all) Read more.
In addition, the company introduced Lumify (brimonidine tartrate ophthalmic solution 0.025%), the first over-the-counter eye drop developed with low-dose brimonidine tartrate for the treatment of eye redness. In clinical trials, Lumify eye drops demonstrated a strong safety and efficacy profile with low risk for rebound redness and 95 percent symptom improvement seen at one minute and lasting up to eight hours. The ophthalmic solution is an alpha-2-adrenergic receptor agonist with a unique method of action that selectively constricts venules while maintaining the availability of oxygen to surrounding tissue, the company says. Six clinical studies were conducted in more than 600 individuals to evaluate the safety and efficacy of Lumify, including studies with pediatric and geriatric subjects. Read more.
Lastly, the company announced that it initiated a clinical trial evaluating the safety and efficacy of a new ophthalmic viscosurgical device with a novel formulation. The company aims to file for pre-market approval with the FDA at the conclusion of the clinical trial, and bring the OVD to the U.S. market in 2019. Read more.

Source: Bausch + Lomb, May 2018


4D Molecular Therapeutics expanded its 2016 research agreement with F. Hoffmann-La Roche Ltd. and Hoffmann-La Roche Inc. to develop and commercialize several ophthalmology products, including 4DMT’s intravitreally delivered choroideremia clinical candidate, 4D-110. 4DMT will be responsible for vector discovery and optimization, product design and engineering, preclinical and early-stage clinical development, and manufacturing, while Roche will conduct clinical trials and globally commercialize the new therapeutics. Read more.

Source: 4D Molecular Therapeutics, April 2018


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