Review of Ophthalmology Online

Volume 14, Number 10
Monday, March 5, 2018


In this issue: (click heading to view article)
######### Comparison of Retinal Microvascular Changes in HTG or NTG Using OCTA
######### Characteristics of Foveal Cystoid Spaces & Response to Ranibizumab for DME
######### Development & Course of Scars in AMD Treatments Trials
######### ARMS2 A69S & CFH Y402H Risk in Wet AMD


Comparison of Retinal Microvascular Changes in HTG or NTG Using OCTA

Investigators compared changes in the retinal vasculature of eyes with high-tension or normal-tension glaucoma. The right eyes of 43 HTG subjects, 33 NTG subjects and 51 age- and sex-matched normal subjects were included in this cross-sectional study.

Signals were projected from the internal limiting membrane to the retinal pigment epithelium. Investigators automatically measured the retinal perfused vessel densities in the peripapillary and parafoveal regions with optic coherence tomography angiography and the split-spectrum amplitude-decorrelation angiography algorithm.

Compared with normal eyes, glaucomatous eyes had a smaller retinal nerve fiber layer thickness, smaller full parafoveal retinal thickness and lower retinal perfused vessel density in the peripapillary and parafoveal regions (all p<0.01). The visual fields, RNFL and retinal thicknesses, and PVD in the parafoveal region in HTG eyes were similar to those in NTG eyes. However, NTG eyes had a significantly lower mean PVD in the peripapillary region than HTG eyes. When different sectors of the peripapillary region were studied, the difference was still significant in most sectors (all p<0.05), except the inferotemporal sector (p=0.676).

Investigators concluded that the retinal perfused vessel density was significantly reduced in HTG and NTG eyes—more prominently so in the peripapillary region in NTG eyes.

SOURCE Xu H, Zhai R, Zong Y et al. Comparison of retinal SOURCE Xu H, Zhai R, Zong Y et al. Comparison of retinal microvascular changes in eyes with high-tension glaucoma or normal-tension glaucoma: A quantitative optic coherence tomography angiographic study. Graefes Arch Clin Exp Ophthalmol 2018; Feb 15. [Epub ahead of print].

Characteristics of Foveal Cystoid Spaces & Response to Ranibizumab With DME

Scientists assessed the association between the characteristics of foveal cystoid spaces and short-term responsiveness to ranibizumab treatment for diabetic macular edema at three months from the initial injection.

They retrospectively reviewed 66 eyes of 61 individuals with center-involved DME who received three consecutive ranibizumab injections and follow-up, as-needed administrations. They evaluated the relationship between visual improvement at three months and preoperative optical coherence tomography parameters including hyperreflective foci, heterogeneous OCT reflectivity, mean levels of OCT reflectivity and height of foveal cystoid spaces.

Twenty-three eyes without preoperative hyperreflective foci in the foveal cystoid spaces had significantly greater improvement in logMAR visual acuity at three months than 43 eyes with foci (p=0.006). That was similar to the greater reduction in CSF thickness in eyes without lesions after treatment at the same time point (p<0.001). VA improvement at three months wasn’t associated with the height (R=0.215, p=0.083) or reflectivity levels (R=-0.079, p=0.538) of foveal cystoid spaces. There were no differences in VA changes between eyes with and without heterogeneous reflectivity in foveal cystoid spaces (p=0.297). Multivariate analyses showed that the logMAR VA and absence of hyperreflective foci in foveal cystoid spaces were associated with VA improvement at three months.

Scientists determined that hyperreflective foci in foveal cystoid spaces at baseline predicted poorer short-term responsiveness to ranibizumab injections for DME.


SOURCE: Murakami T, Suzuma K, Uji A, et al. Association between characteristics of foveal cystoid spaces and short-term responsiveness to ranibizumab for diabetic macular edema. Jpn J Ophthalmol 2018; Feb. 19. [Epub ahead of print].

Development and Course of Scars in AMD Treatments Trials

Researchers described risk factors for scar formation and changes to fibrotic scar through five years in the Comparison of Age-related Macular Degeneration Treatments Trials, as part of a multicenter, prospective cohort study.

A total of 1,061 subjects participated in CATT. Researchers evaluated color photographic and fluorescein angiographic images from baseline and one, two and five years. They estimated the incidence of scar formation with Kaplan-Meier curves and assessed risk factors with Cox regression models. Main outcome measures included scar formation, fibrotic scar area and macular atrophy associated with fibrotic scars.

The cumulative proportion of eyes with scars was 32 percent at one year, 46 percent at two years and 56 percent at five years. Baseline factors associated with increased risk (adjusted hazards ratio and 95% CI) were:
• classic choroidal neovascularization (aHR, 4.49; CI, 3.34 to 6.04) vs. occult;
• hemorrhage >1 disc area (aHR, 2.28; CI, 1.49 to 3.47) vs. no hemorrhage;
• retinal thickness >212 μm (aHR, 2.58; CI, 1.69 to 3.94) vs. <120 μm;
• subretinal tissue complex thickness >275 μm (aHR, 2.64; CI, 1.81 to 3.84) vs. ≤75 μm;
• subretinal fluid thickness >25 μm (aHR, 1.31; CI, 0.97 to 1.75) vs. no fluid;
• visual acuity in fellow eye 20/20 (aHR, 1.72; CI, 1.25 to 2.36) vs. 20/50 or worse;
• retinal pigment epithelium elevation absence (aHR, 1.71; CI, 1.21 to 2.41); and
• subretinal hyperreflective material (aHR, 1.72; CI, 1.25 to 2.36).

Among 68 eyes that developed fibrotic scars at one year, VA decreased by a mean of an additional 13 letters between years one and five. Mean scar area was 1.2 disc area at one year, 1.2 disc area at two years and 1.9 disc area at five years. Atrophy was present in 18 percent at one year, 24 percent at two years and 54 percent at five years. Mean areas were 1.6, 2 and 3.1 disc areas. Atrophy replaced fibrotic scars in eight eyes at five years. Researchers found no significant correlation between scar and atrophy growth; the rate of growth for both was similar between the clinical trial and observation periods.

Researchers found that several morphologic features, including classic CNV and large hemorrhages, were associated with scar formation. In addition, they wrote, rates of new scar formation declined after two years, and most fibrotic scars and accompanying macular atrophy expanded over time, reducing VA.

Source: Daniel E, Pan W, Ying GS, et al. Development and course of scars in the comparison of age-related macular degeneration treatments trials. Ophthalmology 2018; Feb 14. [Epub ahead of print].

ARMS2 A69S & CFH Y402H Risk in Wet AMD

Investigators designed a meta-analysis to pool studies that analyzed CFH (Y402H or I62V) and ARMS2 A69S in the same samples to compare the effect of CFH and ARMS2 in neovascular AMD.

Included studies had genotype data of studied groups for ARMS2 A69S and CFH. To modify the heterogeneity in the variables, investigators used a random-effects model. They performed meta-analyses using STATA, in addition to funnel plots and Egger’s regression tests for evaluation of possible publication bias.

Overall, researchers included 6,676 neovascular AMD cases and 7,668 controls. Pooled overall odds ratios (95%, CI) for neovascular AMD/control were:
• ARMS2 A69S: OR=2.35 (2.01 to 2.75) for GT vs. GG; OR=8.57 (6.91 to 10.64) for TT vs. GG;
• CFH Y402H: OR=1.94 (1.73 to 2.18) for CT vs. TT; OR=4.89 (3.96 to 6.05) for CC vs. TT;
• ARMS2 A69S genotype OR/CFH Y402H genotype OR (homogeneous genotypes): Asia=2.14; Europe: 1.87; America: 1.82; Middle East: 3.56; pooled: 1.75; and
• ARMS2 A69S genotype OR/CFH Y402H genotype OR (heterogeneous genotypes): Asia=0.93; Europe: 1.39; America: 2.06; Middle East: 1.20; pooled: 1.21.
The studies revealed that ARMS2 A69S risk genotypes had stronger predisposing effects on neovascular AMD compared with CFH Y402H risk genotypes.

Investigators wrote that the inclusion criteria to select studies that analyzed the effect of these two loci in the same case-control samples showed a much stronger effect with ARMS2 A69S for neovascular AMD compared with CFH Y402H.

SOURCE: Bonyadi MHJ, Yaseri M, et al. Comparison of ARMS2/LOC387715 A69S and CFH Y402H risk effect in wet-type age-related macular degeneration: A meta-analysis. Int Ophthalmol 2018; Feb 8. [Epub ahead of print].

  • Apellis Provides Update on Phase II Study (FILLY) of APL-2 in GA
    Apellis Pharmaceuticals provided an update with 18-month data on its Phase II trial (FILLY) of complement C3 inhibitor APL-2 in individuals with geographic atrophy associated with age-related macular degeneration. The company previously reported that APL-2 met its primary endpoint of reducing the growth rate of GA lesions (measured as the square root transformation of GA lesion area) compared with sham after 12 months of treatment. APL-2 administered monthly via intravitreal injection showed a 29-percent reduction in the growth rate compared with sham after 12 months (p=0.008). Read more.

  • IDx-DR Meets Endpoints in Trial of AI-Based DR Diagnostic Solution
    IDx announced that IDx-DR, an artificial intelligence-based system for the autonomous detection of diabetic retinopathy, met its endpoints in a U.S. Food & Drug Administration trial involving 900 people with diabetes. IDx-DR was developed to assess for DR during routine office visits with primary care providers, with results available in minutes. IDx-DR has been under review by the FDA since January. The submission, which included data from the clinical trial, was granted expedited review under the FDA's Breakthrough Device program. The trial evaluated the diagnostic accuracy of IDx-DR in detecting moderate to severe diabetic retinopathy, including macular edema. Read more.

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