Volume 12, Number 5
May 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 Receives CE Mark Approval for PLEX Elite 9000
A new swept-source OCT technology platform from Zeiss empowers clinical experts to expand discovery in clinical research for retina, after the company received the CE mark approval for Plex Elite 90001...

BrightFocus Honors Macular Degeneration Researchers
BrightFocus Foundation recognized five scientists in the fields of macular degeneration and glaucoma research, awarding them grants named in honor of leaders in vision research and advocacy...

And More...

Five-Year Outcomes with Anti-VEGF Treatment of nAMD

Researchers described outcomes five years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration, as part of a cohort study using people enrolled in the Comparison of AMD Treatments Trials.

Individuals were assigned randomly to ranibizumab or bevacizumab, and to one of three dosing regimens. After two years, they were released from the clinical trial protocol, and at five years, they were were recalled for exam. Main outcome measures included visual acuity and morphologic retinal features.

VA was obtained for 647 of 914 (71 percent) living individuals with average follow-up of 5.5 years. The mean number of exams for AMD care after the clinical trial ended was 25.3, and the mean number of treatments was 15.4. Most individuals (60 percent) were treated one time or more with a drug other than their assigned drug. At the five-year visit, 50 percent of eyes had VA of 20/40 or better, and 20 percent had VA of 20/200 or worse. Mean change in VA was -3 letters from baseline, and -11 letters from two years. Among 467 eyes with fluorescein angiography, mean total lesion area was 12.9 mm2—a mean of 4.8 mm2 larger than at two years. Geographic atrophy was present in 213 of 515 (41 percent) gradable eyes and was subfoveal in 85 eyes (17 percent). Among 555 eyes with spectral-domain optical coherence tomography, 83 percent had fluid (61 percent intraretinal; 38 percent subretinal; and 36 percent subretinal pigment epithelium). Mean foveal total thickness was 278 μm—a decrease of 182 μm from baseline, and 20 μm from two years. The retina was abnormally thin (<120 μm) in 36 percent of eyes. Between two and five years, the group originally assigned to ranibizumab for two years lost more VA than the bevacizumab group (-4 letters; p=0.008). Otherwise, no statistically significant differences were found in VA or morphologic outcomes between drug or regimen groups.

Vision gains during the first two years were not maintained at five years. However, 50 percent of eyes had VA of 20/40 or better, which researchers said confirmed anti-VEGF therapy as a major, long-term therapeutic advance for neovascular AMD.

SOURCE: Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Maguire MG, Martin DF, Ying GS, et al. Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2016 Apr 20.

Variation in Intravitreal Injection Rates and Medicare Anti-VEGF FFS Payments

Investigators estimated geographic variation of intravitreal injection rates and Medicare anti-vascular endothelial growth factor drug costs per injection in aging Americans, as part of an observational cohort study using 2013 Medicare claims database.

Participants included U.S. fee-for-service (FFS) Part B Medicare beneficiaries and their providers via Medicare Provider Utilization and Payment Data furnished by the Centers for Medicare & Medicaid Services. Data was used to identify all intravitreal injection claims and anti-VEGF drug claims among FFS Medicare beneficiaries in all 50 states and the District of Columbia in 2013. The rate of FFS Medicare beneficiaries receiving intravitreal injections and the mean Medicare-allowed drug payment per anti-VEGF injection was calculated nationally and for each state. Geographic variations were evaluated by using extremal quotient; coefficient of variation; and systematic component of variance (SCV).

Main outcome measures included: the rate of FFS Medicare Part B beneficiaries receiving intravitreal injections (CPT code 67028) nationally and by state; and mean Medicare-allowed drug payment per anti-VEGF injection (CPT code 67028; and treatment-specific J-codes J0178, J2778, J9035, J3490 and J3590) nationally and by state.

In 2013, the rate of FFS Medicare beneficiaries receiving intravitreal injections varied widely by sevenfold across states (range by state: four per 1,000 [Wyoming]-28 per 1,000 [Utah]), averaging 19 per 1000 beneficiaries. The mean SCV was 8.5, confirming high non-random geographic variation. More than 2.1 million anti-VEGF drug claims were found, totaling more than $2.3 billion in Medicare payments for anti-VEGF agents in 2013. The mean national Medicare drug payment per anti-VEGF injection varied widely by 6.2-fold across states (range by state: $242 [South Carolina]-$1509 [Maine]), averaging $1,078 per injection. Nationally, 94 percent of injections were office-based, and 6 percent were facility-based.

High variation was observed in intravitreal injection rates and in Medicare drug payments per anti-VEGF injection across the United States in 2013. Investigators suggested that identifying factors that contribute to high variation may help the ophthalmology community to optimize further the delivery and use of anti-VEGF agents.

SOURCE: Erie JC, Barkmeier AJ, Hodge DO, et al. High variation of intravitreal injection rates and medicare anti-vascular endothelial growth factor payments per injection in the united states. Ophthalmology. 2016 Mar 12. pii: S0161-6420(16)00179-2.

Subretinal Drusenoid Deposit Prevalence in Older Persons with, without AMD

Scientists analyzed the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration using multimodal imaging, as part of a cross-sectional study.

A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary-care ophthalmology clinics were included. Subjects were imaged using spectral-domain optical coherence tomography of the macula and optic nerve head (ONH); infrared reflectance; fundus autofluorescence; and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) nine-step scale. Criteria for SDD presence were: identification on ≥one en face modality plus SD-OCT, or on ≥two en face modalities if absent on SD-OCT. Subretinal drusenoid deposits were considered present at the person level if present in one or both eyes.

Overall prevalence of SDD was 32 percent (197/611), with 62 percent (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, p=0.0002). Prevalence of SDD was 23 percent in subjects without AMD and 52 percent in subjects with AMD (p<0.0001). Among those with early and intermediate AMD, SDD prevalence was 49 percent and 79 percent, respectively. After age adjustment, those with SDD were 3.4 times more likely to have AMD than those without SDD (95 percent confidence interval, 2.3-4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2 percent (12/610). Of persons with SDD detected by SD-OCT and confirmed by at least one en face modality, 47 percent (89/190) were detected exclusively on the ONH SD OCT volume.

Scientists concluded that subretinal drusenoid deposits were present in approximately one-quarter of older adults with healthy maculae, and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD was strongly associated with AMD presence and severity, and increased with age; retinal topography, including peripapillary involvement, resembled that of rod photoreceptors. Scientists recommended the need for consensus on SDD detection methods to advance the collective knowledge base about this lesion type and its clinical and biologic significance.

Zarubina AV, Neely DC, Clark ME, et al. Prevalence of subretinal drusenoid deposits in older persons with and without age-related macular degeneration, by multimodal imaging. Ophthalmology. 2016 May;123(5):1090-100.

Pseudodrusen & Incidence of Late AMD in Fellow Eyes

Investigators assessed the association between pseudodrusen and incidence of late age-related macular degeneration in fellow eyes of individuals with unilateral neovascular AMD, as part of a cohort study within the Comparison of AMD Treatments Trials.

Individuals with neither nAMD nor geographic atrophy in the fellow eye at baseline were included. Presence and type (dot, reticular or confluent) of baseline pseudodrusen were assessed using digital color fundus photography (CFP) viewed under full-color; green channel; and blue channel; red-free images; and fluorescein angiography. Incidence of nAMD was based on monthly clinical exam and reading center evaluation of images at years one and two. Incidence of GA was based on reading center evaluation of CFP and FA images at years one and two. Associations of baseline pseudodrusen with incident nAMD and GA were summarized with adjusted risk ratios (aRRs) and their 95 percent confidence intervals from multivariate Cox models, with adjustment of covariates identified through backward stepwise selection.

Among 620 fellow eyes, 176 (28.4 percent) had baseline pseudodrusen (55 percent dot, 82 percent reticular, 35 percent confluent). Within two years, nAMD occurred in 54 eyes (30.7 percent) with pseudodrusen and in 72 eyes (16.2 percent) without pseudodrusen (aRR, 2.05; 95 percent CI, 1.43-2.93); GA occurred in 27 eyes (15.3 percent) with pseudodrusen and in 37 eyes (8.3 percent) without pseudodrusen (aRR, 1.89; 95 percent CI, 1.13-3.17); late AMD occurred in 73 eyes (41.5 percent) with pseudodrusen and in 101 eyes (22.8 percent) without pseudodrusen (aRR, 2.07; 95 percent CI, 1.51-2.83). Dot pseudodrusen were associated independently with nAMD (aRR, 2.53; 95 percent CI, 1.60-4.00), whereas confluent pseudodrusen were associated independently with GA (aRR, 4.35; 95 percent CI, 1.69-11.2). Eyes with pseudodrusen had increased incidence of late AMD regardless of whether the Age-Related Eye Diseases Study (AREDS) severity score was two (28.7 percent vs. 10.3 percent); three (34.9 percent vs. 13.7percent); or four (50.5 percent vs. 32.0 percent).

Scientists observed that pseudodrusen were associated independently with a higher incidence of both nAMD and GA in fellow eyes of CATT participants. As well, dot pseudodrusen were associated with nAMD, whereas confluent pseudodrusen were associated with GA. Scientists advised that pseudodrusen should be considered along with the AREDS severity score for predicting late AMD.

SOURCE: Zhou Q, Daniel E, Maguire MG, et al. Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology. 2016; Apr 1. [Epub ahead of print].

Circulating Vitamin D Concentration and AMD

Vitamin D may be involved in ocular function in older adults, but no consensus exists on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration. Investigators systematically reviewed and quantitatively assessed the association of circulating 25OHD concentration with AMD.

A Medline search was conducted in November 2015, with no date limit. Fixed and random-effects meta-analyses were performed to compute: standard mean difference in 25OHD concentration between individuals with AMD and without AMD; and AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies, 10 cross-sectional studies and one cohort study met the selection criteria. The number of participants ranged from 65 to 17,045 (52 percent to 100 percent women), and the number with AMD ranged from 31 to 1,440.

Circulating 25OHD concentration was 15 percent lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio=0.83 [95 percent CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95 percent CI:0.28-0.79]). Circulating 25OHD <50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95 percent CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95 percent CI:0.90-1.76]).

Investigators concluded that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L were associated with late AMD.

SOURCE: Annweiler C, Drouet M, Duval GT, et al. Circulating vitamin D concentration and age-related macular degeneration: Systematic review and meta-analysis. Maturitas. 2016;Apr 2 [Epub ahead of print].

Diabetic Retinopathy Features on SS-OCT Compared With FA & Normal Eyes

Investigators evaluated the potential clinical utility of OCTA using a prototype swept-source OCT device compared with fluorescein angiography for analysis of the retinal microvasculature in diabetic retinopathy.

In a prospective, observational, cross-sectional study conducted at a tertiary care academic retina practice from November 2013 through November 2014, a cohort of diabetic and control eyes were imaged with a prototype SS-OCT system. The stage of DR was determined by clinical exam. Imaging was performed using angiographic 3-mm × 3-mm and 6-mm × 6-mm SS-OCT scans to generate three-dimensional en-face OCT angiograms for each eye. Two trained Boston Image Reading Center readers reviewed and graded FA and OCTA images independently.

Main outcomes and measures included measuring the size of the foveal nonflow zone and the perifoveal intercapillary area on OCTA in normal and diabetic eyes using Boston Image Reading Center image analysis software.

The study included 30 people with diabetes (mean [SD] age, 55.7 [10] years) and six controls (mean [SD] age, 55.1 [6.4] years). A total of 43 diabetic and 11 normal control eyes were evaluated with OCTA. FA was performed in 17 of 43 diabetic eyes within eight weeks of the OCTA. OCTA was able to identify a mean (SD) of 6.4 (4.0) microaneurysms (95 percent CI, 4.4-8.5), while FA identified a mean (SD) of 10 (6.9) microaneurysms (95 percent CI, 6.4-13.5). The exact intraretinal depth of microaneurysms on OCTA was localized in all cases (100 percent). The sensitivity of OCTA in detecting microaneuryms when compared with FA was 85 percent (95 percent CI, 53-97), while the specificity was 75 percent (95 percent CI, 21-98). The positive predictive value was 95 percent CI, 59-99; and the negative predictive value was 91 percent 60 percent (95 percent CI, 17-92).

Investigators offered that OCTA enabled noninvasive visualization of macular microvascular pathology in eyes with DR. It identified fewer microaneurysms than FA, but located their exact intraretinal depth. It also allowed precise and reproducible delineation of the foveal nonflow zone and perifoveal intercapillary area. As such, investigators found that OCTA evaluation may be of clinical utility in evaluating and grading diabetic eye disease.

SOURCE: Salz DA, de Carlo TE, Adhi M, et al. Select Features of Diabetic Retinopathy on Swept-Source Optical Coherence Tomographic Angiography Compared With Fluorescein Angiography and Normal Eyes. JAMA Ophthalmol. 2016 Apr 7.

Using EDI SD-OCT for In Vivo Assessment of Choroid in Diabetic Retinopathy

Scientists measured the largest hyporeflective (LHR) lumen in the choroid and subfoveal choroidal thickness in individuals with diabetic retinopathy and in controls using enhanced-depth imaging spectral domain optical coherence tomography, as part of a prospective, cross-sectional study.

A total of 240 eyes (n=120) and control subjects (n=120) were matched for age, sex and refractive error. The LHR lumens of the choroidal vessels and SFCT were measured by EDI SD-OCT. Further intergroup classification into nonproliferative and proliferative DR, with or without macular edema, was performed.

The mean diameter of the LHR lumen in individuals with DR (139.24 ±35.53 µm) was significantly smaller (p<0.01) than in controls (186.37 ±26.43 µm). The mean SFCT was also significantly less (p<0.01) in individuals with diabetes (277.15 ±32.24 [µm) as compared with controls (313.68 ±25.13 µm). No significant intergroup variation was detected.

Scientists concluded that individuals with DR showed smaller LHR lumen and SFCT compared with control eyes, and that in vivo assessment of the choroid in DR was possible using EDI SD-OCT.

SOURCE: Verma A, Nagpal M, Mehrotra N, et al. In vivo assessment of choroid in diabetic retinopathy by enhanced depth imaging in spectral domain optical coherence tomography. Asia Pac J Ophthalmol (Phila). 2016 Mar 23. [Epub ahead of print].

Choroidal Thickness Changes in PDR Treated With PRP vs. PRP With Intravitreal Bevacizumab

Scientists compared choroidal thickness and retinal thickness between eyes with proliferative diabetic retinopathy treated with panretinal photocoagulation (PRP) or PRP with intravitreal bevacizumab (PRP + IVB).

Thirty-three people with PDR were randomized to have one eye treated with PRP and the other with PRP + IVB. Change in CT was compared with baseline using enhanced-depth imaging optical coherence tomography at baseline, and months one; three; six; and 10 after treatment. Change in RT was similarly assessed using spectral-domain optical coherence tomography. Changes in CT and RT were assessed in all nine macular areas as defined by Early Treatment Diabetic Retinopathy Study subfields.

The PRP + IVB group had a significant decrease in subfoveal CT at three and 10 months (323.9 ±62 μm at baseline vs. 320.7 ±64.8 μm at month three [p=0.024] and 304.7 ±65.6 μm at month 10 [p=0.003]). Subfoveal CT significantly decreased at 10 months compared with baseline in the PRP group (320.8 ±57.7 at baseline to 297 ±66.3 [mu]m at 10 months, p=0.01). Subfoveal CT was not significantly different between the two groups at 10 months. The best-corrected visual acuity did not change after treatment in the two groups, and there was no correlation between BCVA and CT changes (r=0.222, p=0.37 in the PRP group and r=0.387, p=0.12 in the PRP + IVB group). Significant increases in RT were seen in the PRP + IVB group at six months, and in the PRP group at months one; three; six; and 10. A correlation between changes in CT and RT was only seen in the PRP group at 10 months after treatment.

Scientists noted that eyes with PDR treated with PRP + IVB, and PRP had significant reduction in CT at 10 months; however, eyes also treated with IVB underwent an earlier, but transient, reduction at three months and less RT increase.

SOURCE: Roohipoor R, Sharifian E, Ghassemi F, et al. Choroidal thickness changes in proliferative diabetic retinopathy treated with panretinal photocoagulation versus panretinal photocoagulation with intravitreal bevacizumab. Retina. 2016 Apr 4. [Epub ahead of print].

FAF & SD-OCT Findings for Diabetic Retinal Pigment Epitheliopathy

To describe the characteristics of diabetic retinal pigment epitheliopathy using fundus autofluorescence and spectral-domain optical coherence tomography, researchers engaged in a retrospective study including: 17 eyes from 10 individuals with proliferative diabetic retinopathy with granular hypo-autofluorescence and/or variable hyper-autofluorescence on FAF (DRPE group); and 17 eyes from 10 age- and sex-matched individuals with PDR without abnormal autofluorescence (PDR group).

Eyes with diabetic macular edema were excluded. Visual acuity; retinal thickness; and choroidal thickness were compared between the groups.

Eyes in the DRPE group had worse logMAR VA than eyes in the PDR group (0.369 ±0.266 vs. 0.185 ±0.119; p 0.026). The thickness of the retinal pigment epithelium plus the inner segment/outer segment of the photoreceptors was reduced to a greater degree in the DRPE group than the PDR group (p<0.001). Moreover, the thickness of the outer nuclear layer plus the outer plexiform layer was thinner in the DRPE group than in the PDR (p=0.013). However, the thickness of the inner retina showed no differences between the two groups. CT was significantly thicker in the DRPE group than in the PDR group (329.00 ±33.76 vs. 225.62 ±37.47 μm; p<0.001).

Researchers observed that eyes with DRPE showed reduced VA; a thinner outer retina; and thicker choroid than eyes with PDR. They determined that alterations of autofluorescence on FAF, and changes in the outer retinal thickness and CT on SD-OCT were helpful in differentiating DRPE in individuals with PDR.

SOURCE: Kang EC, Seo Y, Byeon SH, et al. Diabetic retinal pigment epitheliopathy: fundus autofluorescence and spectral-domain optical coherence tomography findings. Graefes Arch Clin Exp Ophthalmol. 2016 Apr 6. [Epub ahead of print].

Mortality in Older Demographic with Retinopathy & Concomitant Conditions

Researchers looked at the impact of retinopathy on mortality in older persons with concomitant health conditions in a population-based prospective cohort study. A total of 4,966 individuals ages 67 to 96 years (43.2 percent were male) from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS) were included.

Retinopathy was evaluated from digital fundus images (between 2002 and 2006) using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Mortality was assessed through September 2013 (cause of death assigned through 2009). Cox proportional hazards regression models, with age as the time scale, estimated the association between retinopathy and death while controlling for risk factors and the presence of concomitant health conditions.

The main outcome measures were mortality from all causes and cardiovascular disease (CVD).

Among the 4,966 participants, 503 (10.1 percent) had diabetes and 614 (12.4 percent) had retinopathy at baseline. A subset of these (136 [2.7 percent]) had both diabetes and retinopathy. After a median follow-up of 8.6 years, 1,763 persons died; 276 (45.0 percent) with retinopathy (76 with diabetes) and 1,487 (34.2 percent) without retinopathy (162 with diabetes). Some 366 deaths resulted from CVD through 2009, 72 (11.7 percent) in those with retinopathy and 294 (6.8 percent) without retinopathy. In multivariable analyses, retinopathy was significantly associated with all-cause mortality (hazard ratio [HR], 1.26; 95 percent CI, 1.10-1.43; p<0.01) and CVD-related mortality (HR, 1.57; 95 percent CI, 1.20-2.06; p<0.01). Findings were more striking in men: all-cause HR, 1.33 (95 percent CI, 1.11-1.60) and CVD HR, 1.81 (95 percent CI, 1.25-2.63). Risk of mortality was further increased among those with retinopathy concomitant with microalbuminuria (all-cause HR, 1.70; 95 percent CI, 1.03-2.23, and CVD HR, 2.04; 95 percent CI, 1.27-3.28); and those with retinopathy, microalbuminuria and diabetes (all-cause HR, 2.01; 95 percent CI, 1.22-3.31, and CVD HR, 5.24; 95 percent CI, 1.91-14.42). A history of clinical stroke increased the risk of CVD-related mortality among persons with retinopathy (HR, 3.30; 95 percent CI, 2.05-5.32), particularly those with retinopathy and diabetes (HR, 5.38; 95 percent CI, 1.80-16.06).

Even minimal retinopathy was a significant predictor of increased mortality in older individuals, particularly men, irrespective of diabetes status, according to researchers. They added that individuals with retinopathy may warrant closer clinical management of general health.

SOURCE: Fisher DE, Jonasson F, Klein R, et al. Mortality in Older Persons with Retinopathy and Concomitant Health Conditions. Ophthalmology. 2016; Apr 7. [Epub ahead of print].

Postvitrectomy Intravitreal Triamcinolone Therapy for DME

Researchers conducted a study to evaluate the functional and anatomical effect of intravitreal triamcinolone acetonide therapy (IVTA) in previously vitrectomized eyes with diabetic macular edema.

In the retrospective, multicenter case series study including vitrectomized individuals with DME who underwent IVTA injections, central macular thickness measured with spectral-domain optical coherence tomography and best-corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters were evaluated after each procedure. All relevant medical data were collected, including previous ophthalmologic treatments and comorbidities.

Twenty vitrectomized eyes of 20 individuals, mean age 58.1 years (range 40 to 72 years of age), were enrolled. All individuals presented with DME and received at least one IVTA injection. Mean time between pars plana vitrectomy and IVTA was 12.9 ±8.7 months. Mean pretreatment was 438.8 ±90.8 μm, and posttreatment CMT was 301.2 ±76.2 μm, a statistically significant difference (p<0.001). Mean gain in BCVA letter score was 7.83 ±14.9 letters after treatment (p=0.039). Mean intraocular pressure was significantly increased after IVTA (17.2 ±1.9 mmHg at baseline vs. 21.2 ±4.59 mmHg after IVTA, p=0.002).

Researchers observed a positive anatomical and functional effect in their cohort with results suggesting that, despite prior vitrectomy, triamcinolone was a valid therapeutic approach for eyes with persistent DME. They advised that further prospective randomized studies with larger patient samples were needed to validate this conclusion.

SOURCE: Costa JF, Sousa K, Marques JP, et al. Efficacy and safety of postvitrectomy intravitreal triamcinolone therapy for diabetic macular edema. Eur J Ophthalmol. 2016. Mar 7 [Epub ahead of print].

Post-Ranibizumab Functional Parameters, Aqueous Flare & Cytokines in ME With BRVO

Investigators analyzed correlations between functional-morphological parameters; the aqueous flare value (an indicator of inflammation); and aqueous humour levels of cytokines/inflammatory factors in individuals with branch retinal vein occlusion and macular edema who received intravitreal ranibizumab injection and were followed for six months.

Aqueous humour levels of 11 cytokines or growth inflammatory/factors were measured in 45 individuals with BRVO and macular edema who received IRI. Those with recurrent macular edema were given further IRI as needed. Aqueous humour levels of vascular endothelial growth factor; soluble VEGF receptor (sVEGFR); and other cytokines/inflammatory factors were measured by the suspension array method. Aqueous flare values were measured with a laser flare meter, and macular edema was examined by optical coherence tomography.

Significant correlations were observed between the aqueous flare and the aqueous levels of sVEGFR-1; placental growth factor; monocyte chemoattractant protein 1; soluble intercellular adhesion molecule-1; interleukin (IL)-6; and IL-8. Significant correlations were also detected between the change of the aqueous flare and improvement of central macular thickness after one month and six months, and at the first recurrence. A significant correlation was noted between the change of the aqueous flare and BCVA improvement at six months after IRI, but not at one month or at the first recurrence.

Investigators said their findings point to an association between aqueous flare and inflammatory factors/cytokines, and suggested that aqueous flare value change may influence the long-term prognosis in individuals with BRVO receiving IRI therapy for ME.

SOURCE: Noma H, Mimura T, Yasuda K, et al. Functional–morphological parameters, aqueous flare and cytokines in macular oedema with branch retinal vein occlusion after ranibizumab. Br J Ophthalmol. 2016; Apr 12. [Epub ahead of print].

Changes in Course of Retinopathy of Prematurity from 1986 to 2013

To compare infant and retinopathy of prematurity characteristics from three clinical studies conducted over a 27-year period in the United States, researchers conducted a secondary analysis of results of three clinical studies including infants with birth weight (BW)<1,251 g.

They analyzed data from the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) and Early Treatment for Retinopathy of Prematurity (ETROP) trials, and primary data from the Telemedicine Approaches for the Evaluation of Acute-Phase Retinopathy of Prematurity (e-ROP) study. Infant characteristics and onset, severity and time course of ROP were the main outcome measures.

Across the three studies, mean (SD) BW and mean gestational age (GA) decreased over time from CRYO-ROP (954 g [185 g], 27.9 weeks [2.2 weeks]); to ETROP (907 g [205 g], 27.4 weeks [2.2 weeks]); to e-ROP (864 g [212 g], 27.0 weeks [2.2 weeks]), with an increase in the percentage of infants enrolled weighing <750 g (15.8 percent CRYO; 24.9 percent ETROP, 33.4 percent e-ROP; p<0.0001). The percentage of infants who developed ROP varied only minimally (65.8 percent CRYO; 68.0 percent ETROP; 63.7 percent e-ROP; p=0.003). Moderately severe ROP (defined as prethreshold or referral warranted) varied (17.8 percent CRYO; 12.3 percent ETROP; 19.4 percent e-ROP; p<0.0001), whereas the time of onset of any ROP did not vary (34.3 weeks CRYO; 34.1 weeks ETROP; 34.8 weeks e-ROP).

Researchers reported that the BW and GA of infants enrolled in ROP studies in the United States have decreased over the past 27 years, whereas ROP prevalence and onset of disease are stable.

SOURCE: Quinn GE, Barr C, Bremer D, et al. Changes in Course of Retinopathy of Prematurity from 1986 to 2013. Ophthalmology. 2016; April 12.

OCT Analysis of VMA Prevalence in the Retina Clinic

Researchers determined the prevalence of vitreomacular adhesion (VMA) in a random sample of people at three U.S. retina clinics and assessed comorbid retinal conditions; ocular diseases; prior treatment history; and other medical histories.

The observational, retrospective cohort study was based on individuals at the Doheny Eye Centers, Duke Eye Center and Tufts Medical Center who received a bilateral spectral-domain optical coherence tomography scan (one scan/eye) for clinical evaluation with available medical records. The study had three phases: collection of retrospective patient data; review of OCT scans at a reading center to assess VMA and associated conditions; and analyses and reporting of data on the prevalence of VMA, patient demographics and comorbid conditions. Data were obtained from electronic health records and OCT grading forms. Outcome measures from bilateral SD-OCT scans and medical records included OCT evaluation of VMA and retinal comorbid conditions.

In 719 people with 1,483 reviewable OCT scans, the prevalence of VMA was estimated at 14.74 percent (90 percent CI, 12.58 percent-16.92 percent). The prevalence of unilateral VMA was estimated at 12.39 percent, while bilateral VMA was 2.36 percent. In individuals with VMA, 34 out of 123 eyes with VMA (27.64 percent) also had fovea deformed by vitreomacular traction. Macular hole (MH) was significantly more prevalent in VMA-diagnosed eyes vs. non-VMA-diagnosed eyes (6.5 percent vs. 1.9 percent; p=0.02). A significantly higher incidence of full-thickness MH (p=0.008); operculum/flaps (p<0.0001); and lamellar or pseudo-holes (p=0.048) was seen in VMA-diagnosed vs. non-VMA-diagnosed eyes. Age; MH as a comorbid condition; full-thickness MH; lamellar or pseudo-holes; and operculum were predictive of a VMA diagnosis.

The prevalence of VMA was estimated at 14.74 percent in a random sample of people from three retina clinics. Researchers reported that VMA diagnosis was predicted by factors including: age; MH as a comorbid condition; and lamellar or pseudo-holes.

SOURCE: Reichel E, Jaffe GJ, Sadda SR, et al. Prevalence of vitreomacular adhesion: an optical coherence tomography analysis in the retina clinic setting. Clin Ophthalmol. 2016;10:627-33.


Zeiss Receives CE Mark Approval for PLEX Elite 9000

A new swept-source OCT technology platform from Zeiss empowers clinical experts to expand discovery in clinical research for retina, after the company received the CE mark approval for Plex Elite 90001. The device broadens researchers' ability to examine the critical retinal microstructures and microvasculature of the eye at any depth of interest (e.g., vitreous, retina and choroid) by providing OCT and OCT angiography imaging that is fast, dense, wide and deep, with visualization improving upon other technologies. Read more.

Source: Carl Zeiss Meditec, April 2016

BrightFocus Honors Macular Degeneration Researchers

BrightFocus Foundation recognized five scientists in the fields of macular degeneration and glaucoma research, awarding them grants named in honor of leaders in vision research and advocacy. The five recognized today are among a group of 32 scientists who will collectively receive nearly $5 million in vision research grants this year from BrightFocus, a record level of financial support. The awards were presented at a Seattle breakfast event coinciding with the annual meeting of the Association for Research in Vision and Ophthalmology. Read more.

Source: BrightFocus Foundation, May 2016

Acucela Initiates Phase II Clinical Trial Addressing PDR

Acucela initiated a Phase II clinical trial with enrollment of the first patient to assess the benefits of emixustat hydrochloride for treatment of proliferative diabetic retinopathy. Acucela submitted a clinical study protocol to the U.S. Food and Drug Administration and received Institutional Review Board approval to initiate a randomized, placebo-controlled, Phase II clinical trial evaluating emixustat in individuals with PDR. In this three-month study, 20 individuals will be dosed once daily with oral emixustat. Read more.

Source: Acucela, April 2016

Ohr Enrolls First Patient in Phase III Wet AMD Clinical Program

Ohr Pharmaceutical enrolled the first individual in its first Phase III clinical trial of drug candidate squalamine lactate ophthalmic solution, 0.2% for treatment of neovascular age-related macular degeneration. The first of two randomized, double-masked, placebo-controlled trials will include approximately 165 centers in the United States and Canada with a target enrollment of 650 treatment-naïve subjects with wet AMDs. Read more.

Source: Ohr Pharmaceutical, April 2016

Clearside Releases Positive Preliminary Results in ME Associated with RVO

Clearside Biomedical announced that its Phase II clinical trial evaluating concomitant administration of suprachoroidal Zuprata, the company’s proprietary form of triamcinolone acetonide, together with intravitreal aflibercept (Eylea) for the treatment of macular edema associated with retinal vein occlusion achieved its primary endpoint. In preliminary results from the trial, subjects in the active arm (those receiving concomitant administration) qualified for approximately 60 percent fewer intravitreal Eylea treatments than those in the control arm who initially received Eylea alone, during the three-month observation period following initial treatment (p=0.013). The trial, known as Tanzanite, is the first controlled, masked, randomized clinical trial conducted in individuals with RVO in which the drug was administered through the suprachoroidal space. Read more.

Source: Clearside Biomedical, April 2016

Salutaris Wet AMD Distance of Choroid Study Presented at ARVO 2016

Results from the Salutaris Medical Devices wet age-related Macular Degeneration Distance of Choroid Study (DOCS) were featured in two presentations at the Association for Research in Vision and Ophthalmology annual meeting. The first poster, by Dr. Kamaljit Balaggan, presented clinical results informing an upcoming interventional study employing the SalutarisMD novel episcleral brachytherapy device for treatment of wet AMD. Dr. Balaggan’s presentation evaluated variations in expected dwell times and doses to determine if a mean target depth is appropriate for people receiving episcleral brachytherapy for treating wet AMD. A second poster presented an analysis of a subset of DOCS data by Dr. Daren Hanumunthadu, Honorary Research Fellow at Moorfields Eye Hospital. Dr. Hanumunthadu's presentation utilized data acquired through a SalutarisMD-sponsored study and described the repeatability of choroidal thickness measurements in wet AMD using the SS-OCT device. Read more.

Source: SalutarisMD, May 2016

International Thought Leaders Gather for First Retina World Congress

With less than a year until the inaugural Retina World Congress, scheduled for February 23 to 26, 2017, at the Fort Lauderdale Marriott, Fla., Congress organizers and representatives of participating international retina societies gathered at an informational event during the Association for Research and Vision in Ophthalmology annual meeting to discuss the evolution of global educational exchange in retina. A nonprofit-designated international conference, RWC will feature presentations from international thought leaders in retina on the most current clinical and scientific research, as well as accredited professional education courses, expert panel discussions on cases and controversies, and industry exhibits. Proceedings will be published in the International Journal of Retina and Vitreous. Read more.

Source: Retina World Congress, April 2016

Icare Unveils Updated ic100 Handheld Tonometer

Icare released the ic100 tonometer featuring added ergonomic benefits and EasyNav interface with large color screen for ease of use, along with the rebound technology of successor TA01i. The device requires no calibration, drops, air or specialized skills, and is suitable for all patient types in most settings. A built-in intelligent position assistant facilitates operation, and red and green lights help operators guide the tonometer into the correct position for testing. The examiner simply loads, aligns and measures. The ic100 also incorporates an automated measuring sequence capable of taking a series of six measurements in one touch. The new design is intended to ensure intraocular pressure measurements that are precise, reliable and reproducible. Read more.

Source: Icare, April 2016

PhotoPharmics Discovery May Mean Parkinson’s Can Be Treated Through Eyes

Researchers are looking outside the brain for clues to the cause of Parkinson’s. Since retinal tissue is similar to brain tissue, and the two are directly connected, scientists found that when the motor center in animals’ brains was damaged, corresponding damage happened in the animals’ eyes within only a few weeks. In a series of experiments, researchers placed several toxins known to cause Parkinson’s into animals’ eyes, in amounts that were too small to diffuse into the brain. In each case, the animals developed Parkinson’s. Using the eyes as a treatment pathway, scientists delivered minute amounts of dopamine and other medications to the eye, resulting in rapid symptom recovery in the animals. Subsequent studies delivering drugs that block dopamine made symptoms worse. Because dopamine in the eye is activated by light, researchers experimented by administering light to the animals’ eyes and found a twofold improvement over medication. These discoveries led to research in humans with specialized phototherapy. Preliminary studies have shown dramatic symptomatic improvements. Read more.

Source: PhotoPharmics, April 2016

Academy Honors Congressmen for Efforts to Ensure Eye Care

The American Academy of Ophthalmology is honoring five Members of Congress with 2016 Visionary Awards for their outstanding legislative efforts to advance the quality of eye care available in the United States. Sen. Bill Cassidy, MD (R-La) introduced legislation to help ensure that certified health information technology systems meet expectations. His bill, the Transparent Ratings on Usability and Security to Transform Information Technology (TRUST IT) Act of 2015, would improve care by enabling providers and patients to get the information they need when they need it. It would also require the Office of the National Coordinator for Healthcare Information Technology and the Office for Civil Rights to update its website to ensure patients better understand the rights they have to access their personal health information. Reps. Phil Roe, MD (R-Tenn); Paul Tonko (D-NY); Raul Ruiz, MD (D-Calif) are spearheading an effort to help ensure access to Avastin for ophthalmic applications. Rep. Ami Bera, MD (D-Calif) led a successful initiative in the U.S. House urging leaders to reverse a decision by the Centers for Medicare & Medicaid Services to rescind a new Medicare rule to end global payments for surgical procedures starting in 2017. Ophthalmologists are among many medical specialists who contend that such a policy will confuse beneficiaries, and create an administrative burden for surgeons by unbundling the services covered for all necessary services before, during and after a surgical procedure. Read more.

Source: American Academy of Ophthalmology, April 2016

Medidur for Posterior Uveitis Granted Orphan Drug Designation in Europe

pSivida announced that the European Commission granted orphan medicinal product designation to Medidur for the treatment of chronic non-infectious uveitis of the posterior of the eye. Orphan drug designation provides up to 10 years of market exclusivity in Europe following marketing approval, access to the centralized marketing authorization procedure and other regulatory and financial incentives. Read more.

Source: pSivida Corp, May 2016


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