DATA FROM OPREGEN TRIAL WILL BE PRESENTED AT ARVO BioTime announced that a poster presentation based on data from its Phase I/IIa clinical trial of OpRegen in the advanced form of dry age-related macular degeneration will be presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology on May 8, in Baltimore... ALLEGRO NAMES SARAYBA VP OF CLINICAL AFFAIRS Allegro Ophthalmics announced that Melvin Sarayba, MD, joined the company as vice president of clinical affairs... And More...

Intravitreal Ziv-Aflibercept vs. Bevacizumab in Treatment of DME

Researchers compared the efficacy of two doses of intravitreal ziv-aflibercept with intravitreal bevacizumab in the treatment of center-involved diabetic macular edema at 12 weeks in a three-armed, double-blind, randomized clinical trial.

Cases included eyes with center-involved DME; 123 eyes with DME were randomly assigned to three injections of 1.25 mg of IVZ, 2.5 mg of IVZ and 1.25 mg of IVB every four weeks. A complete ophthalmologic exam and central macular thickness measurement by optical coherence tomography were performed every four weeks up to 12 weeks. The main outcome measure included change in best-corrected visual acuity at 12 weeks.

Although no significant difference was evident between the two IVZ groups at 12 weeks, the BCVA change was significantly better in the IVZ 1.25 mg group than in the IVB group at the 12-week visit (p=0.021). With regard to CMT changes, there was no significant difference between the two IVZ groups; however, a significantly greater reduction in CMT was observed in the IVZ 2.5 mg group compared with the IVB group at 12 weeks (p=0.037). Subgroup analysis disclosed no difference in BCVA outcomes at 12 weeks among the groups in the eyes with baseline BCVA ≥20/50. In the eyes with baseline BCVA <20/50, the improvement was significantly better at 12 weeks in the IVZ 1.25 mg group compared with the IVB group (p=0.011).

The 12-week results revealed that both the 1.25-mg and 2.5-mg doses of IVZ and IVB demonstrated BCVA improvement over baseline in the treatment of center-involved DME. However, researchers detected a stronger effect of IVZ compared with IVB for visual acuity improvement and macular thickness reduction in the eyes with initial BCVA <20/50. Researchers suggested that longer-term efficacy and safety data would be needed to determine the role of IVZ in clinical use.

SOURCE: Baghi A, Bonyadi MHJ, Ramezani A, et al. Two doses of intravitreal ziv-aflibercept versus bevacizumab in treatment of diabetic macular edema: A three-armed, double-blind randomized trial. Ophthalmology Retina 2017;1:2:103-110.

Assessing Type 2 Diabetes & DR With OCTA

Researchers wrote that optical coherence tomographic angiography is able to visualize retinal microvasculature without the need for injection of fluorescein contrast dye; however, it’s only able to capture a limited view of the macula and doesn’t show leakage. As such, researchers evaluated the retinal microvasculature in cases of type 2 diabetes using OCTA and assessed the association of OCTA characteristics with diabetic retinopathy and systemic risk factors.

The prospective, observational study ran from Jan. 1, 2016, to June 30, 2016, at medical retina clinics at the Singapore National Eye Center in 50 individuals with type 2 diabetes with and without DR (n=100 eyes). Researchers examined the retinal microvasculature with swept-source OCTA and semi-automated software to measure the capillary density index and fractal dimension at the superficial vascular plexus and deep retinal vascular plexus. They collected data on histories of individuals’ glycated hemoglobin A1c, hypertension, hyperlipidemia, smoking and renal impairment.

Main outcomes and measures included the CDI and FD at the SVP, DVP for each severity level of DR, and the association of systemic risk factors in relation to the CDI and FD.

The mean (SD) glycated hemoglobin A1c of the 50 individuals (26 men and 24 women; mean age, 59.5 [8.9] years) was 7.9 percent (1.7 percent). The mean CDI at the SVP decreased from 0.358 (0.017) in individuals with no DR to 0.338 (0.012) in people with proliferative DR (p<0.001), and the DVP decreased in individuals with no DR from 0.361 (0.019) to 0.345 (0.020) in those with proliferative DR (p=0.04). The mean FD at the SVP increased from 1.53 (0.05) in individuals with no DR to 1.60 (0.05) in individuals with proliferative DR (p<0.01), and the DVP increased from 1.55 (0.06) in individuals with no DR to 1.61 (0.05) in those with proliferative DR (p=0.02). Relating to systemic risk factors, hyperlipidemia (OR, 9.82; CI, 6.92 to 11.23; p< 0.001) smoking (OR, 10.90; CI, 8.23 to 12.34; p<0.001) and renal impairment (OR, 3.72; CI, 1.80 to 4.81; p=0.05) were associated with reduced CDI, while increased glycated hemoglobin A1c (≥8 percent) (OR, 8.77; CI, 5.23 to 10.81; p<0.01) and renal impairment (OR, 10.30; CI, 8.21 to 11.91; p<0.001) were associated with increased FD.

Researchers wrote that OCTA is a novel imaging modality to quantify the retinal capillary microvasculature in individuals with diabetes that could be potentially used in interventional trials to study the effect of systemic risk factors on the microvasculature previously not accessible in a noninvasive manner. They added that the relevance of these findings to visual acuity remains largely unknown at this time.

SOURCE: Ting DS, Tan GS, Agrawal R, et al. Optical coherence tomographic angiography in type 2 diabetes and diabetic retinopathy. JAMA Ophthalmol 2017; Feb 16. [Epub ahead of print].

Choroidal Thickness in Diabetic Cases Without DR

Investigators compared choroidal thickness between diabetic individuals without diabetic retinopathy and a nondiabetic group to explore how CT relates to disease duration, mean arterial pressure, glycemia, glycosylated hemoglobin, intraocular pressure and ocular pulse amplitude.

They assessed CT using a spectral-domain optical coherence tomography and enhanced depth mode at 13 locations (subfoveal and three measurements 500 μm apart in four directions: nasal; temporal; superior; and inferior). They also used linear regression models.

A total of 175 people were recruited (125 diabetic individuals without DR and 50 non-diabetic individuals). In diabetic individuals, CT tended to be thicker in all locations (6.16 to 24.27 μm), without statistical significance. CT was negatively associated with age (p<0.001) in both groups, but was positively associated in the diabetic group with ocular pulse amplitude (with a mean increase between 8.5 and 11.6 μm for each millimeter of mercury increase in ocular pulse amplitude). Diabetic individuals’ CT appeared to stabilize after 150 months of diabetes with no fluctuation in glycosylated hemoglobin and mean arterial pressure, although with higher glycemia levels (>160 mg/dL).

Investigators wrote that diabetic individuals without DR appeared to experience a thickening of the choroid. They suggested that the tissue may be functionally different in diabetes since patterns seemed to differ between diabetic individuals without DR and non-diabetic individuals.

SOURCE: Tavares Ferreira J, Vicente A, Proença R, et al. Choroidal thickness in diabetic patients without diabetic retinopathy. Retina 2017; Mar 3. [Epub ahead of print].

Retinal Vascular Anatomy by Projection-resolved OCTA

With optical coherence tomography angiography—a noninvasive method of 3D imaging of the retinal and choroidal circulations— vascular depth discrimination is limited by superficial vessels projecting flow signal artifact onto deeper layers, researchers wrote. The projection-resolved OCTA algorithm improves depth resolution by removing projection artifact while retaining in-situ flow signal from real blood vessels in deeper layers, they added.

This novel technology enabled the researchers to study the normal retinal vasculature in vivo with better depth resolution than previously possible. Their investigation in normal human volunteers revealed the presence of two to four distinct vascular plexuses in the retina, depending on location relative to the optic disc and fovea. The vascular pattern in these retinal plexuses and interconnecting layers were consistent with previous histologic studies.

Based on these findings, researchers proposed an improved system of nomenclature and segmentation boundaries for detailed three-dimensional retinal vascular anatomy by OCTA that could serve as a basis for future investigation of both normal retinal anatomy, as well as vascular malformations, nonperfusion and neovascularization.

SOURCE: Campbell JP, Zhang M, Hwang TS, et al. Detailed vascular anatomy of the human retina by projection-resolved optical coherence tomography angiography. Sci Rep 2017;10;7:42201.

Projection Artifact Removal for Visualization of Macular Neovascularization Via OCTA

In a study partially funded by Carl Zeiss Meditec, clinicians and Zeiss researchers aimed to visualize and quantify the size and vessel density of macular neovascularization using optical coherence tomography angiography with a projection artifact removal algorithm, as part of a multicenter, observational study.

Participants included subjects with MNV in ≥one eye. Individuals were imaged using a swept-source OCTA prototype system or a spectral-domain OCTA prototype system. An optical microangiography algorithm helped generate the OCTA images, and a novel algorithm removed overlying retinal circulation projection artifacts from the images. Investigators assessed the size and vascularity of the MNV, using concurrent fluorescein angiography and indocyanine green angiography images to validate the artifact-free OMAG images whenever available.

Thirty subjects (40 eyes) diagnosed with MNV were imaged. Five individuals were imaged before and after intravitreal injections of vascular endothelial growth factor inhibitors. After using the projection artifact removal algorithm, investigators found improved visualization of the MNV. Lesion sizes and vascular densities were more easily measured on all the artifact-free OMAG images. In the five eyes treated with vascular endothelial growth factor inhibitors, vascular density was reduced in all five after treatment and, in four eyes, the size of the MNV decreased. One of five individuals showed a slight increase in lesion size, but a decrease in vascular density.

Investigators determined that, using the OMAG algorithm, OCTA imaging of MNV combined with removal of projection artifacts resulted in improved visualization and measurement of the neovascular lesions. Thus, they determined that OMAG with projection artifact removal could be useful for assessing the response of MNV to treatment using OCTA imaging.

SOURCE: Zhang Q, Zhang A, Lee CS, et al. Projection artifact removal improves visualization and quantitation of macular neovascularization imaged by optical coherence tomography angiography. Ophthalmology Retina 2017;1:2:124-136.

Comparison Between SD-OCTA and SS-OCTA of Choroidal Neovascularization

In a study partially sponsored by Carl Zeiss Meditec, employees of the company and other researchers compared the images of choroidal neovascularization using swept-source and spectral-domain optical coherence tomography angiography.

Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec). Both 3 × 3- and 6 × 6-mm² scans were obtained on both instruments. The 3 × 3-mm² SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm² SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm² scans and twice in the 6 × 6-mm² scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm² scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. Investigators analyzed 27 consecutive eyes from 23 individuals. For the 3 × 3-mm² scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm², respectively (p=0.047). For the 6 × 6-mm² scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm², respectively (p=0.003).

Investigators determined that the areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm² scans.

Miller AR, Roisman L, Zhang Q, et al. comparison between spectral-domain and swept-source optical coherence tomography angiographic imaging of choroidal neovascularization. Invest Ophthalmol Vis Sci 2017;1:58:3:1499-1505.

Automated Quantitation of CNV: Comparing SD-OCTA and SS-OCTA

In a study partially sponsored by Carl Zeiss Meditec, a group composed of employees of the company and other investigators compared the lesion sizes of choroidal neovascularization imaged with spectral-domain and swept-source optical coherence tomography angiography, and measured using an automated detection algorithm.

Individuals diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography algorithm helped generate OCTA images. Researchers derived OCTA datasets for imaging CNV by segmenting from the outer retina to 8 μm below Bruch's membrane. An artifact removal algorithm helped to generate angiograms free of retinal vessel projection artifacts. Researchers developed an automated detection algorithm to quantify the size of the CNV. They compared automated measurements with manual measurements, along with measurements from SD-OCTA and SS-OCTA instruments.

Researchers analyzed 27 eyes from 23 subjects diagnosed with CNV. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (p=0.61, paired t-test) and 6 × 6-mm (p=0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (p=0.41, paired t-test) and 6 × 6-mm (p=0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (p=0.011, paired sample t-test) and the 6 × 6-mm scans (p=0.021, paired t-test).

Researchers found that the automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.

Zhang Q, Chen CL, Chu Z, et al. Automated quantitation of choroidal neovascularization: a comparison study between spectral-domain and swept-source oct angiograms. Invest Ophthalmol Vis Sci 2017;1;58:3:1506-13.

OCTA of Flat Irregular PED in Chronic CSC

Scientists assessed the rate of choroidal neovascularization detected by optical coherence tomography angiography in flat, irregular pigment epithelium detachments in chronic central serous chorioretinopathy.

They reviewed data on all consecutive individuals with chronic CSC who underwent OCTA over a one-year period. They assessed the presence of flat, irregular PED, defined as an irregular elevation of the retinal pigment epithelium enabling the visualization of a distinct Bruch's membrane on high-resolution OCT B-scans. Two graders reviewed clinical multimodal imaging and OCTA data for the detection of CNV.

Eighty-eight eyes of 61 individuals with chronic CSC were included. Mean age (±SD) was 54.5 ±12.2 years; 78.7 percent were males. Mean subfoveal choroidal thickness (±SD) was 452.6 ±145.6 μm. Flat, irregular PEDs were detected in 59 eyes of 51 people. OCTA detected the presence of CNV in flat, irregular PEDs in 35.6 percent of cases. Conversely, using the combination of spectral-domain OCTA fluorescein and indocyanine green angiography, CNV was detected in only 25 percent of flat, irregular PEDs. All hyporeflective, flat, irregular PEDs on OCT were avascular on OCTA, although they were at least partially hyperreflective when associated with CNV.

One-third of flat, irregular PEDs in chronic CSC contained CNV, and OCTA detected CNV more frequently than other imaging modalities. Scientists suggested that further longitudinal studies were needed to assess the indication of anti-vascular endothelial growth factor treatments in such cases.

SOURCE: Bousquet E, Bonnin S, Mrejen S, et al. Optical coherence tomography angiography of flat irregular pigment epithelium detachment in chronic central serous chorioretinopathy. Retina 2017; Mar 3. [Epub ahead of print].

Using OCTA to Evaluate Macular Ischemia in BRVO Eyes

Investigators quantitatively assessed macular morphology and perfusion status in eyes with branch retinal vein occlusion after resolution of macular edema using optical coherence tomography and optical coherence tomography angiography. They also evaluated the impact on visual function.

Investigators included 30 consecutive eyes with BRVO macular edema that resolved after treatment with intravitreal ranibizumab injections. They measured macular sensitivity by microperimetry, defect length of foveal ellipsoid zone band by OCT, and foveal avascular zone and parafoveal nonperfusion areas (NPAs) by OCTA.

LogMAR visual acuity was significantly associated with the defect length of the foveal ellipsoid zone band (p=0.005), the parafoveal NPA in the superficial capillary plexus (p=0.007) and the parafoveal NPA in the deep capillary plexus (p=0.006). Macular sensitivity correlated with parafoveal thickness on the affected side (p=0.034), the defect length of the foveal ellipsoid zone band (p=0.048), parafoveal NPA in the superficial capillary plexus (p=0.008) and parafoveal NPA in the deep capillary plexus (p=0.012). Multivariate analysis showed that parafoveal NPA was most significantly associated with the logMAR visual acuity (β=0.500, p=0.005) and macular sensitivity (β=-0.480, p=0.007).

Investigators determined that, in eyes with BRVO-associated macular edema resolved by intravitreal ranibizumab treatments, visual function was strongly associated with parafoveal NPA size.

SOURCE: Kadomoto S, Muraoka Y, Ooto S, et al. Evaluation of macular ischemia in eyes with branch retinal vein occlusion: An optical coherence tomography angiography study. Retina 2017; Feb 17. [Epub ahead of print].

Macular Thickness Center Point Shift on SD-OCT

Investigators evaluated the effect of spectral domain-optical coherence tomography measurement center shift on macular thickness, as part of a prospective, observational case series including 60 normal eyes of 60 subjects.

Experienced examiners performed SD-OCT macular scanning (macular cube 512 × 128 scan) twice. They recorded average retinal thicknesses of the nine macular sectors as defined by the Early Treatment Diabetic Retinopathy Study. Each coefficient of repeatability was calculated for macular thickness measurements of ETDRS subfields. Thereafter, the measurement center was manually decentered to a seven scan point, from the central fovea in steps of 58.7 μm horizontally and 47.2 μm vertically. At each shift point, investigators compared the change in macular thickness.

When the displacement distance between the measurement center point and the foveal center was within 117.4 μm horizontally and 141.6 μm vertically, the macular thickness measurements didn’t show significant differences. However, if the offset of the EDTRS grid center from the anatomic fovea exceeded these measurements, investigators noted that the thickness at the fovea increased, and the opposite region at the inner circle was significantly thinner than the displaced point.

Investigators concluded that the effect of measurement center shift must be considered when analyzing macular thickness measurements in various ophthalmologic diseases.

SOURCE: Kim KN, Shin IH, Sung JY, et al. The effect of center point shift on the measurement of macular thickness: A spectral domain-optical coherence tomography study. Graefes Arch Clin Exp Ophthalmol 2017; Mar 6. [Epub ahead of print].

Dexamethasone Intravitreal Implant vs. Ranibizumab in Treatment of ME Secondary to Brachytherapy for Choroidal Melanoma

Researchers evaluated the efficacy of an intravitreal dexamethasone implant 0.7 mg compared with intravitreal ranibizumab for the treatment of radiation maculopathy with macular edema secondary to plaque brachytherapy in choroidal melanoma.

Eight individuals were treated with intravitreal ranibizumab, and eight others received the intravitreal dexamethasone implant. Researchers evaluated visual acuity and foveal thickness using spectral-domain optical coherence tomography.

The mean calculated irradiation to the fovea and mean times from brachytherapy to maculopathy development did not differ significantly between groups. In the ranibizumab group, a mean 7.8 ±3.9 injections were given, and the mean follow-up was 33 ±15 months (range: 7 to 52 months). In the dexamethasone group, a mean 2.1 ±0.8 injections were given and the mean follow-up was 22 ±seven months (range:11 to 31 months). The mean VA improved significantly from the baseline to the last follow-up visit in both groups. Foveal thickness decreased significantly in both groups—from 459 ±81 μm to 243 ±58 μm in the ranibizumab group, and from 437 ±71 μm to 254 ±44 μm in the dexamethasone group—from the baseline to the last follow-up visit. No individuals developed significant cataracts or ocular hypertension in either group.

Researchers concluded that intravitreal ranibizumab and intravitreal dexamethasone were effective treatments for macular edema secondary to plaque brachytherapy for uveal melanoma. They added that individuals treated with intravitreal dexamethasone required fewer injections to achieve anatomical and functional improvement.

SOURCE: Russo A, Reibaldi M, Avitabile T, et al. Dexamethasone intravitreal implant vs ranibizumab in the treatment of macular edema secondary to brachytherapy for choroidal melanoma. Retina. 2017; Mar 7. [Epub ahead of print].

Vitrectomy for Macular Disorders Associated with Lamellar Macular Hole Epiretinal Proliferation

Scientists compared the surgical outcomes of lamellar macular holes, based on lamellar hole-associated epiretinal proliferation and full-thickness macular hole, as part of a retrospective chart review.

Thirty-three individuals were enrolled for this study and divided into three groups depending on the type of macular hole and presence of LHEP. Group 1 had epiretinal membranes with LMH without LHEP; group 2 had LMH with LHEP; and group 3 had full-thickness macular hole with LHEP. Scientists recorded the best-corrected visual acuity and obtained optical coherence tomography scans.

Preoperative BCVA showed no significant difference between groups (p=0.968). Final VA of group 1 was better than that of group 2 (p=0.009). Group 1 showed less postoperative ellipsoid zone disruption compared with group 2 (p=0.010), and the duration of LHEP to surgery had no significant correlation with postoperative VA (p=0.629).

Lamellar macular holes with LHEP showed poorer visual outcomes compared with those with highly reflective epiretinal membranes. Lamellar macular holes with LHEP showed a greater chance of ellipsoid zone disruption. These findings may explain the wide variability of visual outcomes previously reported after vitrectomy for LMH.

Source: Choi WS, Merlau DJ, Chang S. Vitrectomy for macular disorders associated with lamellar macular hole epiretinal proliferation. Retina 2017; Mar 15. [Epub ahead of print].

Genotypic & Phenotypic Characteristics of CRB1-associated Retinal Dystrophies

Researchers described the phenotype, long-term clinical course, clinical variability and genotype of individuals with CRB1-associated retinal dystrophies, as part of a retrospective, cohort study.

They included 55 individuals with CRB1-associated retinal dystrophies from 16 families. They conducted a medical record review for age at onset, medical history, initial symptoms, best-corrected visual acuity, ophthalmoscopy, fundus photography, full-field electroretinography, Goldmann visual fields and spectral-domain optical coherence tomography.

Main outcome measures included age at onset, VA survival time and decline rate, and electroretinography and imaging findings.

A retinitis pigmentosa phenotype was present in 50 individuals, 34 of whom were from a Dutch genetic isolate; five individuals had a Leber’s congenital amaurosis phenotype. The mean follow-up time was 15.4 years (range, 0 to 55.5 years). For RP individuals, the median age at symptom onset was four years. In the RP group, these median ages were reached for these symptoms: low vision, 18; severe visual impairment, 32; and blindness, 44, with a VA decline rate of 0.03 logMAR per year. The presence of a truncating mutation did not alter the annual decline rate significantly (p=0.75). Asymmetry in VA was found in 31 percent of individuals. The annual VF decline rate was 5 percent in individuals from the genetic isolate, which was significantly faster than in non-GI cases (p<0.05). Full-field electroretinography responses were extinguished in 50 percent of individuals; were pathologically attenuated without a documented rod or cone predominance in 30 percent; and showed a rod-cone dysfunction pattern in 20 percent of RP patients. Researchers found cystoid fluid collections in the macula in half of the RP cases.

Researchers determined that CRB1 mutations were associated with a spectrum of progressive retinal degeneration. They added that VA survival analyses indicated that the optimal intervention window for subretinal gene therapy was within the first two to three decades of life.

SOURCE: Talib M, van Schooneveld MJ, van Genderen MM, et al. Genotypic and phenotypic characteristics of CRB1-associated retinal dystrophies. Ophthalmology 2017; Mar 20. [Epub ahead of print].