Effect of Aflibercept on macular retinal layers and peripheral non perfusion in subjects with Proliferative Diabetic retinopathy

Background: The relation between UWF fluorescein angiography (FA) and retinal non-perfusion were studied previously. The relationship between retinal thickness and retinal non-perfusion in subjects with diabetic retinopathy has not been studied using SD-OCT and UWF. Thus, in this current study we used SD-OCT to visualize the individual layers of retina and to evaluate whether the extent of non-perfusion is correlated with macular retinal layer thickness in subjects with PDR with no diabetic macular edema. Methods: In this prospective longitudinal multicenter, randomized study a total of 36 eyes of thirty six subjects were included in final analysis. Subjects with any history of anti-VEGF therapy, steroid therapy, pan-retinal photocoagulation or vitreoretinal surgery, macular edema, or SD-OCT determined central retinal thickness (CRT) of more than 320 μm in the study eye were excluded. All subjects underwent ETDRS BCVA testing, slit lamp and indirect ophthalmoscopy examination and diagnostic testing at all visits using Optos 200Tx (Optos plc, Dunfermline, United Kingdom), Heidelberg Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) with 9X image averaging. UWFA images were obtained and then transformed to stereographic projection images using proprietary manufacturer software. Regions of non-perfusion were identified and manually graded using Image J. Results: The mean age of the subjects was 57 ± 13 years and 19 were female. The mean total retinal thickness was significantly lower at month 12 when compared to baseline 258.47 ± 23.52 µm vs. 285.19 ± 23.62 µm (p0.05). For both the treatment arms, the mean total NPA at month 12 (280 ± 143 mm2) increased, but not significantly (p=0.12) differ, when compared with baseline (242 ± 169 mm2). Ischemic index (ISI, %), however, was significantly (p=0.009) increased at month 12 (34 ± 17) when compared with baseline (27 ± 16). Conclusion: The total NPA was significant and independently correlated with GCL and thinning of inner retinal layers continues even after treatment. The thickness of multiple retinal sublayers appears to decrease over time in eyes receiving intravitreal aflibercept for proliferative diabetic retinopathy despite an absence of a change in peripheral non-perfusion. The underlying pathophysiology for these reductions over time warrants further investigation

Post hoc analysis of ellipsoid zone changes beyond the central subfield in symptomatic vitreomacular adhesion patients from the OASIS trial

Background/aims OASIS is a Phase IIIb trial (NCT01429441) assessing long-term outcomes in subjects with symptomatic vitreomacular adhesion (VMA). The purpose of this study is to report on the frequency, severity, location and time course of ellipsoid zone (EZ) alterations in ocriplasmin-treated and sham control eyes in the OASIS study.Methods 220 patients (146 ocriplasmin, 74 sham) subjects with VMA were enrolled in this masked post hoc analysis phase IIIb, randomised, sham-controlled double-masked multicentre clinical trial. A masked post hoc analysis of OCT images was performed at the Doheny Image Reading Center from subjects enrolled in the OASIS trial. The status of the EZ band was assessed in three different macular regions: the central subfield (CS) (≤1 mm diameter), the parafoveal area (PAA) (>1 to ≤3 mm) and the perifoveal area (PEA) (>3 to ≤6 mm). The EZ band was rated as normal/intact, full thickness macular hole (FTMH), abnormal but continuous, discontinuous/disrupted or absent at visits from baseline (pretreatment) to week 1 (day 7), month 1 (day 28), month 3, month 6, month 12 and the final follow-up at month 24. EZ band status was compared in both study and control eyes.Results A total of 208 patients (138 ocriplasmin, 70 sham) were included in this analysis. At baseline, FTMH was present in 48.6%, 8.0%, 0% and 52.8%, 2.9%, 0% in the CS, PAA and PEA of the ocriplasmin and sham groups, respectively. The EZ was graded to be abnormal but continuous, discontinuous/disrupted or absent at Baseline in 21.0%, 4.3%, 2.8% in the CS, PAA and PEA, respectively, of the ocriplasmin group; and 12.9%, 10.0%, 4.3% in the CS, PAA and PEA of the sham group. For the ocriplasmin group in the PAA, this frequency increased to 6.6% at week 1, was 9.8% at month 1, but improved to 3.8% at month 3, and remained stable to 1.6% at month 24. These differences, however, were not statistically significant.Conclusions Ocriplasmin treatment for symptomatic VMA was associated with EZ abnormalities in a small percentage of patients that was best assessed in regions (PEA) relatively unaffected by the VM interface disease at baseline. The EZ abnormalities were apparent by week 1, persisted at month 1, and appeared to resolve in the majority of cases by month 3.Trial registration number NCT0142944

Choroidal thickness in non-ocular Behçet's disease – A spectral-domain OCT study

Purpose: To evaluate choroidal thickness in patients with non-ocular Behçet's disease (BD) using spectral domain optical coherence tomography (SD-OCT) and to compare the results to normal eyes. Methods: In this retrospective observational comparative study, we collected OCT and clinical data from the charts of 4 patients (7 eyes) with BD who had been referred for a screening eye exam and had a normal ocular examination. Data from 9 healthy volunteers (17 eyes) were collected as age-matched controls. The choroid was manually segmented from volume OCT scans using custom Doheny Image Reading Center OCT grading software (3D-OCTOR). Main outcome measures were choroidal thickness and intensity were compared between eyes of patients with BD and those of healthy controls. Results: Eyes of patients with non-ocular BD had significantly thinner mean central subfield choroidal thickness (227.5 ± 56.93 versus 306.85 ± 17.85, P = 0.04) and central subfield choroidal volume (0.18 ± 0.04 vs 0.24 ± 0.02, P = 0.005). There was no significant difference in mean choroidal thickness in the whole ETDRS grid or in mean choroidal intensity in the central subfield and the whole ETDRS grid between eyes of patients with non-ocular BD and those of controls. Conclusion: This study demonstrates that BD may have subclinical manifestations in the choroid, resulting in thinning of the choroid relative to normal eyes, even without overt signs of ocular involvement. Keywords: Choroidal thickness, Behçet's disease, Spectral domain optical coherence tomography, Choroidal intensity, Choroidal reflectivit

Effect of OCT B-Scan Density on Sensitivity for Detection of Intraretinal Hyperreflective Foci in Eyes with Age-Related Macular Degeneration

To evaluate the impact of reducing the density of B-scans in an optical coherence tomography (OCT) volume on the sensitivity for detecting intraretinal hyperreflective foci (IHRF) in eyes with intermediate age-related macular degeneration (AMD) A total of 165 eyes with intermediate AMD and IHRF were evaluated in this retrospective analysis. For each case, Cirrus HD-OCT volumes were imported into the reading center 3 D-OCTOR software. The number of IHRF cases was assessed based on all 128 B-scans (spaced 47 μm apart), using a categorical scale (graded as 1-4, 5-9, 10-14, 15-19, and >20). Additionally, the B-scan densities in the volume were lowered to 64 B-scans (spaced 94 μm apart), 43 B-scans (spaced 140 μm apart), and 32 B-scans (spaced 188 μm apart). The number of eyes with any IHRF and the numerical category of IHRF in the eye were used to compare the sensitivity at each reduced B-scan density against the reference 128 B-scan volume. In the primary analysis for the qualitative presence or absence of any IHRF, the sensitivity decreased to 98.2% (p = .32) with 64 B-scans, 92.7% (p = .001) with 43 B-scans, and 75.2% (p = .001) with 32 B-scans, compared with the 128 B-scan reference. With regard to the number of IHRF per eye, there was a significant difference (with a lower level chosen on the scale) when the B-scan density was reduced to 43 or 32 B-scans (p = .002 and p < .001, respectively). Increasing the inter-B-scan spacing from 47 to 188 microns significantly reduced the ability to accurately determine whether IHRF were present in an eye. An increase in inter-B-scan spacing to 140 microns was associated with a significant misclassification of the IHRF quantity. These findings may be relevant in the design of OCT scanning protocols for studies utilizing these biomarkers for AMD progression

Changes in Retinal Layer Thickness in the Contralateral Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration

Purpose: To evaluate the thickness of the outer retinal layers and its relationship with visual function in fellow eyes of participants with unilateral neovascular age-related macular degeneration (AMD). Design: Longitudinal study. Participants: We enrolled 105 subjects with unilateral neovascular AMD from 3 clinical centers in Europe. Methods: The fellow eye, without advanced AMD, was selected for the study. Subjects were followed up with visits occurring every 6 months for 2 years. Spectral domain optical coherence tomography volume scans were collected at 3 clinical sites, in Belfast, Northern Ireland; Coimbra, Portugal; and Milan, Italy. Detailed manual segmentation of outer retinal layers was performed using the custom-designed and validated grading software 3D OCTOR. Thickness measurements for neurosensory retina, photoreceptor layer (PRL) outer segments, retinal pigment epithelium plus drusen (RPE+drusen) complex, and choroidal layers from each sector of the standard macular grid were obtained. Measures of vison were distance visual acuity, near visual acuity, Smith-Kettlewell Institute low-luminance acuity score, and reading speed. Subjects were grouped based on the presence or absence of subretinal drusenoid deposits (SDDs) for further analysis. Main Outcome Measures: Change in thickness of retinal layers and change in measures of vision. Results: In all, 85 eyes were included in the analysis. The average duration of follow-up was 20.5 \ub1 5.8 months. By the final visit, the RPE+drusen complex was significantly thinner when compared with baseline (29.7 \u3bcm vs. 34.09 \u3bcm; P = 0.03). Low-luminance deficit was significantly worse at the final visit (P &lt; 0.001) and correlated with PRL outer segment thickness (r = 0.33; P =0.02). The RPE+drusen complex was significantly thicker in eyes with SDDs compared with that in those without SDDs (30.67 \u3bcm vs. 28.64 \u3bcm; P = 0.02). PRL outer segments became significantly thinner over time in eyes with SDDs compared with those in eyes without SDDs. Conclusions: The RPE+drusen complex layer becomes thinner over time in fellow eyes of subjects with unilateral neovascular AMD. The rate of PRL outer segment thinning was higher in eyes with SDDs than in eyes without SDDs. These findings are preliminary steps in the identification of early biomarkers for detecting and monitoring the progression of AMD

Comparison of Spectralis and Cirrus optical coherence tomography for the detection of incomplete and complete retinal pigment epithelium and outer retinal atrophy

To evaluate and compare the detection of incomplete and complete retinal pigment epithelial and outer retinal atrophy (iRORA and cRORA) using Spectralis and Cirrus optical coherence tomography (OCT) devices. Subjects with late age-related macular degeneration (AMD) were imaged on the same day with Spectralis and Cirrus OCT. Two masked, independent and experienced retina specialist graders evaluated each case for the presence of cRORA and iRORA lesions. A significantly higher number of lesions were observed using Spectralis compared with Cirrus (239 vs 226 and 223 vs 209). Higher number of iRORA lesions were identified with Spectralis (105 vs 90 and 96 vs 82) and no significant difference was observed between devices for cRORA lesions (134 vs 136 and 128 vs 126). When considering the presence or absence of iRORA or cRORA, the agreement between devices for both graders was excellent for cRORA and good for iRORA. Spectralis and Cirrus OCT identified a similar number of cRORA lesions, though more iRORA lesions could be detected with Spectralis OCT. These findings may have implications for developing acquisition protocols for trials based on the intended atrophy targets and highlight the importance of using a consistent OCT instrument across a study

Alterations of the Ganglion Cell Complex in Age-Related Macular Degeneration: an AMISH Eye Study Analysis

To compare the Ganglion Cell Complex (GCC) thickness in eyes with age-related macular degeneration (AMD) versus healthy controls in an elderly Amish population DESIGN: Cross-sectional study METHODS: This is a post hoc analysis of the family-based prospective study of Amish subjects. Study subjects were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc, Dublin, CA) using a macular cube protocol of 512 × 128 scans (128 horizontal B-scans, each compromising 512 A-scans) over a 6 mm x 6 mm region centered on the fovea. The ganglion cell analysis algorithm calculated the GCC thickness by segmenting the outer boundaries of the retinal nerve fiber layer (RNFL) and inner plexiform layer (IPL) in all B-scans of the volume, with the region between these boundaries representing the combined thickness of the GCL and the IPL layer. A number of parameters were used to evaluate the GCC thickness: the average GCC thickness, minimum (lowest GCC thickness at a single meridian crossing the elliptical annulus), and sectoral (within each of six sectoral areas: superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal). The stage of AMD was graded on color fundus photographs in accordance with the Beckman Initiative for Macular Research classification system. Of 1339 subjects enrolled in the Amish eye study, a total of 1294 eyes of twelve hundred and ninety-four subjects had all required imaging studies of sufficient quality and were included in the final analysis, and of these 798 (62%) were female. Following age adjustment, the average GCC thickness was significantly (p<0.001) thinner in AMD subjects (73.71 ± SD; 13.77 µm) compared to normals (77.97 ± 10.42 µm). Independent t test showed that, early (75.03 ± 12.45 µm), and late AMD (61.64 ± 21.18 µm) groups (among which GA eyes had the lowest thickness of 58.10 ± 20.27 microns) had a statistically significant lower GCC thickness compared to eyes without AMD. There was no significant difference in average GCC thickness between early AMD and intermediate AMD (76.36 ± 9.25 µm) eyes. The GCC thickness in AMD eyes is reduced compared to normal eyes, but the relationship is complex with the greatest reduction in late AMD eyes (particularly GA eyes) but no difference between early and intermediate AMD eyes

Association of Pegcetacoplan With Progression of Incomplete Retinal Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular Degeneration: A Post Hoc Analysis of the FILLY Randomized Clinical Trial

IMPORTANCE: Change in areas of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) within eyes with geographic atrophy (GA) might reflect similar changes among eyes with drusen but no GA. OBJECTIVE: To evaluate the potential association of pegcetacoplan with progression of iRORA in eyes with GA secondary to AMD. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the phase 2 multicenter, randomized, single-masked, sham-controlled FILLY trial of intravitreal pegcetacoplan for 12 months took place from February 2 to July 7, 2020. Participants comprised 167 patients with GA secondary to AMD who received pegcetacoplan monthly (n = 41) or every other month (n = 56) or a sham injection (n = 70) in the FILLY trial, completed the month 12 study visit, and did not develop exudative AMD. INTERVENTIONS: Intravitreal pegcetacoplan, 15 mg, or sham injection, monthly or every other month for 12 months. MAIN OUTCOMES AND MEASURES: Masked readers analyzed spectral-domain optical coherence tomography scans in regions beyond a perimeter of 500 μm from the GA border according to the Classification of Atrophy Meetings criteria. Primary outcome measures were progression from iRORA to complete RPE and outer retina atrophy (cRORA) from baseline to 6 and 12 months. RESULTS: Among the 167 patients in the study, at baseline, iRORA was present in 45.0% of study eyes (18 of 40) in the pegcetacoplan monthly group, 61.8% of study eyes (34 of 55) in the pegcetacoplan every other month group, and 50.7% of study eyes (34 of 67) in the sham group. At 12 months, progression from iRORA to cRORA occurred in 50.0% of study eyes (9 of 18) in the pegcetacoplan monthly group (P = .02 vs sham), 60.6% of study eyes (20 of 33) in the pegcetacoplan every other month group (P = .06 vs sham), and 81.8% of study eyes (27 of 33) in the sham group. Compared with sham treatment, the relative risk of progression at 12 months from iRORA to cRORA was 0.61 (95% CI, 0.37-1.00) for eyes in the pegcetacoplan monthly group and 0.74 (95% CI, 0.54-1.02) for eyes in the pegcetacoplan every other month group. CONCLUSIONS AND RELEVANCE: Eyes receiving intravitreal pegcetacoplan had lower rates of progression from iRORA to cRORA compared with controls, suggesting a potential role for pegcetacoplan therapy earlier in the progression of AMD prior to the development of GA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0250333