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Microvascular Changes Using OCTA in Diabetic Eyes Without Signs of Retinopathy

Investigators compared quantitative optical coherence tomography angiography parameters of macular ischemia in diabetic eyes without retinopathy with those in healthy non-diabetic controls, as part of a cross-sectional study from August 2014 through June 2017. Thirty-nine eyes of 39 diabetic individuals without clinical evidence of diabetic retinopathy, and 40 eyes of 40 healthy, non-diabetic subjects were included. (By way of disclosure, several of the authors are consultants to, reimbursed speakers for, or have a financial interest in Optovue, the maker of the device studied.)

Subjects underwent OCTA imaging using prototype AngioVue software (RTVue XR Avanti). Analyses of the foveal avascular zone and vasculature surrounding the FAZ were performed on the automatically generated en face OCTA images of the superficial and deep retinal vasculatures using vessel-based and FAZ-based metrics. Main outcome measures included the comparison of measurements made in the superficial and deep retinal capillary plexuses of diabetic and normal eyes.

FAZ-based analyses revealed statistically significant differences between diabetic and normal eyes in the FAZ area (superficial and deep layers), perimeter (superficial layer), major axis length (superficial layer) and minor axis layer (superficial and deep layers). Vessel-based analysis revealed statistically significant differences in the binarized flow index (superficial and deep layers), including and excluding the FAZ area.

Quantitative OCTA parameters revealed subclinical macular ischemia at the superficial and deep retinal capillary plexuses in diabetic eyes that didn’t manifest clinical retinopathy. Investigators wrote that vessel- and FAZ-based metrics applied to OCTA images might serve as effective tools for screening and disease monitoring in individuals with diabetes without clinical evidence of retinopathy.

SOURCE: Alibhai AY, Moult EM, Shahzad R, et al. Quantifying microvascular changes using OCT angiography in diabetic eyes without clinical evidence of retinopathy. Ophthalmology Retina 2017; Nov. 7. [Epub ahead of print].

Early Response to Intravitreal Dexamethasone Implants for DME to Predict Visual Outcomes

Researchers studied whether early visual acuity response to intravitreal dexamethasone implant therapy in diabetic macular edema was associated with long-term outcomes, as part of a retrospective case series

The multicenter, retrospective, medical-records review of DME eyes treated with 0.7 mg intravitreal dexamethasone implants and 18-month follow-up included 102 eyes. Eyes with vitreoretinal interface abnormalities or those that had undergone vitrectomy were excluded. Eyes were categorized into three groups based on change in best-corrected VA at three months (logMAR equivalence of <5-, 5- to 9- or ≥10-letter gain). VA outcomes were determined for each early response group. Researchers assessed the relationship between early (three months) and overall change in BCVA, using regression analysis.

In the study population, <5-, 5-to-9- and ≥10-letter BCVA improvements were seen at three months in 44.1 percent, 18.6 percent and 37.3 percent of eyes, respectively. Among suboptimal (<5-letter) responders at three months, 6.7 percent showed ≥10-letter gains at the study’s conclusion compared with 29 percent in the robust (≥10-letter) early-response group (p=0.009). Changes in BCVA at three months showed significant positive correlation with overall change in BCVA (coefficient=0.44, p=0.002).

A similar proportion of eyes demonstrated suboptimal (<5-letter) and robust (≥10-letter) early response to treatment at three months. Eyes with a robust early response demonstrated ≥10-letter, long-term gain in BCVA at a significantly higher rate compared with those with poor early response. Researchers found that early treatment response directly correlated with overall BCVA change.

SOURCE: Al-Khersan H, Hariprasad SM, Chhablani J, et al. Early response to intravitreal dexamethasone implant therapy in diabetic macular edema may predict visual outcome. Am J Ophthalmol 2017; Oct 12. [Epub ahead of print].

Aflibercept in DME Refractory to Bevacizumab: Outcomes & Predictors of Success

Investigators evaluated functional and anatomical outcomes after aflibercept in individuals with diabetic macular edema with poor response to bevacizumab. They retrospectively reviewed individuals with DME recalcitrant to bevacizumab who were switched to aflibercept between January and December 2015.

All individuals had a minimal follow-up of three months before the conversion and underwent at least three injections of bevacizumab. Functional outcome measures consisted of best-corrected visual acuity, while anatomical outcomes were demonstrated through central macular thickness measured by optical coherence tomography.

Investigators reviewed 49 eyes of 34 subjects. Mean VA improved from 0.55 ±0.32 to 0.46 ±0.33 logMAR (p=0.038). Mean CMT decreased from 473 ±146 μm to 349 ±85 μm (p<0.001). Twelve eyes (24 percent) demonstrated absence of ME after aflibercept. Previous bevacizumab exposure didn’t correlate with different outcomes. The variation of VA in response to aflibercept was significantly superior in the group with poorer VA before the switch (mean variation: -0.097 ±0.21 logMAR) when compared to eyes with VA <0.4 logMAR (mean variation: +0.019 ±0.090 logMAR; p=0.036). The same scenario was verified for anatomical outcomes, as eyes with poor vision before the switch (≥0.4 logMAR) achieved superior reduction in CMT in response to aflibercept (mean CMT variation: -157 ±171 μm vs. -49.5 ±39.9 μm; p<0.01). CMT before switching was a predictor of CMT reduction after the switch (B=-0.945; CI, -1.1; -0.76; p<0.001).

Investigators found that conversion to aflibercept for persistent DME resulted in functional and anatomical improvements; these outcomes were not influenced by previous bevacizumab exposure. They added that CMT before switching was a predictor of anatomical changes after aflibercept.

SOURCE: Laiginhas R, Silva MI, Rosas V, et al. Aflibercept in diabetic macular edema refractory to previous bevacizumab: Outcomes and predictors of success. Graefes Arch Clin Exp Ophthalmol 2017; Oct. 29. [Epub ahead of print].

Reduced Light Sensitivity Due to Impaired Retinal Perfusion in BRVO

This study looked at light sensitivity reduction in areas of eyes where impaired retinal perfusion was established by fluorescein angiogram, as part of a retrospective, observational case series. Participants had branch retinal vein occlusion that recovered from retinal edema and hemorrhage.

Using the total deviation display of the Humphrey perimetry program, the study demonstrated 30-2 in 43 eyes from 42 individuals with BRVO whose perfusion status was assessed by FA images taken at least six months after disease onset. Investigators classified each of 15 retinal squares in the affected vertical hemisphere as perfused, partially perfused or non-perfused. Three evaluators assessed the correlation between light sensitivity and perfusion in 645 squares—15 squares from each of the subject eyes.

Light sensitivity was significantly different among 459 perfused (median: -4 dB, n=258), partially perfused (median: -8 dB, n=41) and non-perfused (median: -16 dB, n=160) (p<0.000001, Kruskal-Wallis test) retinal squares (71.2 percent) having complete evaluator agreement on perfusion status. The lead investigator wrote that light sensitivity decreased in retinal areas exhibiting impaired perfusion, likely due to neuronal loss in the inner retinal layer in eyes with chronic BRVO.

SOURCE: Iijima H. Reduced light sensitivity due to impaired retinal perfusion in branch retinal vein occlusion. Jpn J Ophthalmol 2017; Nov 1. [Epub ahead of print].

Phenotype Associations With Genetic Variants in AMD

Age-related macular degeneration was recently associated with 52 single-nucleotide polymorphisms at 34 loci in a genome-wide association study. These genetic variants could modulate different biological pathways involved in AMD, contributing to phenotypic variability, researchers wrote. To better understand the effects of these SNPs, the researchers performed a deep phenotype association study (DeePAS) in the Age-Related Eye Disease Study 2, followed by replication using AREDS participants, to identify genotype associations with AMD and non-AMD ocular and systemic phenotypes. 



The cohort study involved AREDS and AREDS2 participants. AREDS2 participants (discovery cohort) underwent phenotyping for AMD, other eye conditions; as well as cardiovascular, neurologic, gastrointestinal and endocrine disease; cognitive function and serum nutrient levels (139 AMD and non-AMD phenotypes). Researchers obtained genotypes of 52 GWAS SNPs. They performed DeePAS by correlating the SNPs with all phenotypes, using logistic and linear regression models. They replicated associations that reached Bonferroni-corrected statistical significance in AREDS. 



A total of 1,776 AREDS2 participants had five years of follow-up; 1,435 AREDS participants had 10 years. The DeePAS revealed a significant association between the rs3750846 SNP at the ARMS2/HTRA1 locus with subretinal/subretinal pigment epithelial hemorrhage related to neovascular AMD (OR 1.55 [CI, 1.31 to 1.84], p=2.67 × 10^-7). This novel association remained significant after conditioning on participants with neovascular AMD (p=2.42 × 10^-4). Carriers of rs3750846 had poorer visual acuity during follow-up (p=6.82 × 10^-7) and were more likely to have a first-degree relative with AMD (p=5.38 × 10^-6). Two SNPs at the CFH locus—rs10922109 and rs570618—were associated with the drusen area in the Early Treatment Diabetic Retinopathy Study Report grid (p=2.29 × 10^-11; and p=3.20 × 10^-9, respectively) and the center subfield (p=1.24 × 10^-9 and p=6.68 × 10^-8, respectively). SNP rs570618 was additionally associated with the presence of calcified drusen (p=5.38 × 10^-6). All genotype-phenotype associations, except for a positive family history of AMD with rs3750846, were significantly replicated in AREDS. Researchers identified no pleiotropic associations.

Researchers suggested that the associations between SNPs at the ARMS2/HTRA1 locus, subretinal/sub-RPE hemorrhage and poorer visual acuity, and SNPs at the area of CFH locus and drusen might provide new insights in the pathophysiological pathways underlying different stages of AMD.

Source: van Asten F, Simmons M, Singhal A, et al. A deep phenotype association study reveals specific phenotype associations with genetic variants in age-related macular degeneration. Ophthalmol 2017; Oct. 30. [Epub ahead of print].

Aflibercept for nAMD Beyond the First Year: Consensus Recommendations

An expert panel of U.K. retina specialists developed recommendations for continued administration of aflibercept solution for injection after the first year of treatment for neovascular age-related macular degeneration, based on experience and treatment outcomes seen in year two. The 2017 update reiterates that the treatment goal is to maintain or improve the macular structural and functional gains achieved in year one while attempting to reduce or minimize the treatment burden.

The panel recommended that, at the end of year one, two treatment options should be considered: Do not extend the treatment interval and maintain fixed, eight-weekly dosing; or extend the treatment interval using a treat-and-extend regimen up to a maximum of 12 weeks. Criteria for not extending the treatment interval are: persistent macular fluid with stable vision; recurrent fluid; decrease in vision in the presence of fluid; macular hemorrhage; new choroidal neovascularization; or any other sign of exudative disease activity considered vision threatening in the opinion of the treating clinician.

Treatment extension is recommended for eyes with a dry macula and stable vision. Under both options, the treatment interval may be shortened if visual and/or anatomic outcomes deteriorate, the recommendations suggest. Monitoring without treatment may be considered for eyes with a fluid-free macula for a minimum duration of 48 weeks. Also, a patient completing one full year of monitoring without requiring injections may be considered for discharge from the clinic. The treatment algorithm incorporates return-to-fixed-eight-weekly dosing for disease reactivation during treatment extension, and reinstatement of treatment for disease recurrence following discontinuation or discharge. For bilateral nAMD, the recommendations also prescribed that either the eye requiring the more intensive treatment or the eye with better vision should determine the retreatment schedule overall.

SOURCE: Patel PJ, Devonport H, Sivaprasad S, et al. Aflibercept treatment for neovascular AMD beyond the first year: Consensus recommendations by a UK expert roundtable panel, 2017 update. Clin Ophthalmol 2017;11:1957-66.

Residual Choroidal Vessels in Atrophy Can Appear as CNV on OCTA

Scientists aimed to present a post-processing approach in optical coherence tomography angiography to facilitate the visualization and interpretation of lesions in age-related macular degeneration with coexisting atrophy and choroidal neovascularization.

The retrospective study included 32 eyes with atrophy and treated CNV, and eight eyes with treatment-naive geographic atrophy. Scientists pseudocolored en face OCT slabs highlighting atrophy and merged them with the corresponding OCTA. They analyzed cross-sectional OCT and post-processed OCTA to identify CNV and normal choroidal vessels related to the atrophy. Using electronic microscopy, they then correlated the OCTA findings with those in donor eyes with treatment-naive GA.

Medium-sized choroidal vessels were displaced anteriorly in atrophy areas in all 40 eyes, as visualized in the choriocapillaris slab, and in the outer retinal slab in 30 of 40 eyes (75 percent). Scientists used cross-sectional OCTA to confirm CNV presence. Post-processing successfully highlighted CNV and distinguished it from choroidal vessels in atrophy. Electronic microscopy of donor eyes confirmed the anterior displacement of medium-sized choroidal vessels in GA.

Scientists suggested that the anterior displacement of larger choroidal vessels in atrophy requires clinician vigilance to avoid misinterpreting these vessels as CNV on en face OCTA. They proposed a post-processing approach to help interpret en face OCTA in those cases. In the absence of other tools, they encouraged clinicians to rely on flow location relative to Bruch’s membrane on cross-sectional OCTA images.

SOURCE: Nesper PL, Lutty GA, Fawzi AA, et al. Residual choroidal vessels in atrophy can masquerade as choroidal neovascularization on optical coherence tomography angiography: Introducing a clinical and software approach. Retina 2017; Oct. 20. [Epub ahead of print].

Use of a Neural Net to Model the Impact of OCT Abnormalities on Vision in AMD

Researchers developed a neural network for estimating visual acuity from the optical coherence tomography images of individuals with neovascular age-related macular degeneration, and demonstrated its ability to model the impact of specific, controlled OCT changes on vision, as part of an artificial intelligence study.

They assessed 1,400 OCT scans of individuals with nAMD. And they used 15 physical features for each eligible OCT and age as input data and corresponding VAs to validate and test the network. They used the network to model the acuity impact of defined OCT changes in subretinal fluid, subretinal hyperreflective material and loss of external limiting membrane integrity.

Researchers analyzed 1,210 OCT scans resulting in 1,210 data points. A 10-layer, feed-forward neural network with one hidden layer of 10 neurons helped predict acuity and demonstrated a root mean square error of 8.2 letters for predicted vs. actual VA, with a mean regression coefficient of 0.85. A virtual model using this network demonstrated the relationship between VA and programmed changes in OCT characteristics. When the external limiting membrane was intact, researchers found a shallow decline in acuity with increasing subretinal fluid but a steeper decline with equivalent increasing subretinal hyperreflective material. When ELM was not intact, all VAs were reduced. Increasing subretinal hyperreflective material or subretinal fluid reduced vision further still, but with a smaller gradient than when ELM was intact.

The neural network generated an estimated VA value from OCT images in individuals with AMD. Researchers suggested that these findings should have clinical and research interest for assessing macular degeneration, in particular in estimating visual prognosis or highlighting the need for developing treatments targeting visually destructive pathologies.

SOURCE: Aslam TM, Zaki HR, Mahmood S, et al. Use of a neural net to model the impact of optical coherence tomography abnormalities on vision in age-related macular degeneration. Am J Ophthalmol 2017; Oct 31. [Epub ahead of print].

Long-acting Intravitreal Dexamethasone Implants for Refractory Uveitic ME

Researchers aimed to report the functional and anatomical outcomes of a prospective study looking at repeated dexamethasone intravitreal implants in individuals with uveitic refractory macular edema.

Researchers regularly reviewed 12 eyes of nine individuals with intermediate and posterior noninfectious inflammatory uveitis complicated with refractory macular edema after a dexamethasone intravitreal implant. Individuals were examined at baseline, 30, 90, 135 and 180 days using best-corrected visual acuity, slit lamp exam, intraocular pressure, optical coherence tomography and fluorescein angiography. After six months of follow-up, eyes were reassessed to receive a second implant.

BCVA significantly improved when comparing baseline values after the first (16.2 letters) and second implant (25.8 letters), with a 9.6-letter improvement (p<0.05). BCVA was better after the second implant compared with the first throughout follow-up but without statistical significance. Mean central macular thickness was 446.3 ±129.9 µm at baseline and was significantly reduced until day 135 (p<0.05). CMT reductions after the second injection showed a similar pattern, although differences weren’t statistically significant. Cataract progression was observed in four of eight phakic eyes (50 percent) after the first implant and in two of three phakic eyes following the second implant, with one eye requiring cataract surgery. One eye developed an IOP >30 mmHg 30 days after the second implant, and was treated topically.

Researchers concluded that repeated dexamethasone intravitreal implants in uveitic individuals with refractory macular edema could be used effectively in a clinical setting and exhibited an acceptable safety profile.

Source: Zola M, Briamonte C, Lorenzi U, et al. Treatment of refractory uveitic macular edema: Results of a first and second implant of long-acting intravitreal dexamethasone. Clin Ophthalmol 2017;11:1949-56.