Comparison of SD-Optical Coherence Tomography Angiography and Indocyanine Green Angiography in Type 1 and 2 Neovascular Age-related Macular Degeneration.

Purpose: The purpose of this study is to compare the ability of spectral domain optical coherence tomography angiography (SD-OCTA) and indocyanine green angiography (ICGA) to detect and measure lesion area in patients with type 1 and 2 choroidal neovascularization (CNV). Methods: Types 1 and 2 neovascular AMD (nAMD) were included in this prospective and observational case series. ETDRS best-corrected visual acuity (BCVA), ophthalmic examination with funduscopy, OCTA (AngioVue), fluorescein angiography (FA), ICGA, and OCT (Spectralis) were performed. CNV measurements were done manually by two experienced graders using the systems' innate region selection tools. Results: Forty eyes of 39 consecutive patients with nAMD were included. Mean age was 77 ± 6.4 years, ETDRS BCVA was 67 ± 13 letters, and 11 eyes were treatment naïve. Nineteen CNV lesions were classified as type 1 and 21 as type 2. ICGA was able to identify CNV in all eyes. By contrast, OCTA detected CNV in 95% of type 1 and 86% of type 2 nAMD eyes. Mean overall CNV area (CNV-A) was 2.8 ± 2.7 mm2 in ICGA and 2.1 ± 2.7 mm2 in OCTA. Both lesion types CNV-A appeared significantly smaller in OCTA compared with ICGA (P < 0.01). Bland-Altman plot revealed a mean difference (bias) between OCTA and ICGA CNV-A of 0.76 ± 1.74 mm2. Intraclass correlation coefficient (ICC) for CNV-A was 0.91 and 0.93 for ICGA and OCTA, respectively. ICGA CNV-A in the four OCTA-negative eyes (median 4.7 mm2) was not significantly different from the 36 OCTA-positive eyes (median 1.7 mm2). Conclusions: Type 1 and 2 CNV-A were significantly smaller in OCTA than in ICGA. OCTA was generally less successful in detecting CNV than ICGA in patients who were included into this study based on FA and OCT. However, OCTA detected all type 1 lesions except for one, indicating that the SD-OCTA signal is limited by detection limits of blood flow velocity rather than lesion type. Further efforts are needed pushing the limits of lowest detectable and fastest distinguishable flow until OCTA can deliver realistic qualitative and quantitative imaging of type 1 and 2 CNV for diagnosis and monitoring.

Geographic Atrophy and Foveal-Sparing Changes Related to Visual Acuity in Patients With Dry Age-Related Macular Degeneration Over Time.

PURPOSE: To correlate the area of geographic atrophy (GA) and residual foveal sparing (FS), and to identify the minimum FS and maximum GA area allowing sufficient visual acuity (VA) for daily tasks. DESIGN: Prospective cohort study. METHODS: Thirty-six eyes of 25 patients with GA and FS were followed for 18 months using spectral-domain optical coherence tomography and VA tests. Volume scans were imported into software enabling grading of areas in B-scans and computing of planimetric measurements in complete volume scans. Correlation of areas 1 (complete atrophy), 2 (FS in the central millimeter), and 3 (FS in the central 3 mm) with each other and with best-corrected VA (BCVA) were evaluated. RESULTS: Baseline means of areas 1, 2, and 3 were 6.15 mm2, 0.49 mm2, and 3.08 mm2, respectively. At 1 year, area 1 increased by a mean of 1.33 mm2, while areas 2 and 3 were decreased by 0.12 mm2 and 0.65 mm2, respectively. From baseline to 18 months and from visit to visit, all areas and BCVA changed progressively (P < .001). Significant thresholds in GA size and FS for achieving a BCVA ≥ 70 ETDRS letters were detected (area 1: ≤6 mm2; area 2: ≥0.48 mm2; and area 3: ≥3.28 mm2). CONCLUSION: GA and FS changed inversely over time. In general, FS highly correlated with BCVA, while GA progression correlated with the central 3-mm FS regression, but not with BCVA. A threshold in GA and FS area could be determined for BCVA necessary for daily activity.

Effect of intravitreal dexamethasone implant on intra-ocular cytokines and chemokines in eyes with retinal vein occlusion.

PURPOSE: To investigate the influence of intravitreal dexamethasone implant on inflammatory and angiogenic cytokine levels in the aqueous of patients with retinal vein occlusion (RVO). METHODS: Forty eyes of 40 consecutive patients with macular oedema (ME) due to branch and central retinal vein occlusion (BRVO/CRVO) were treated with an intravitreal dexamethasone implant (Ozurdex® ) at baseline and evaluated until month 6. Retreatment was performed in case of recurrent ME earliest 4 months after the baseline treatment. Aqueous humour samples were taken at baseline, months 1, 3, 6 and at the time of each retreatment. Concentrations of 29 different cytokines were measured by Luminex® bead assays. The control group comprised healthy patients undergoing cataract surgery. RESULTS: At baseline concentrations of interleukin (IL)-8, angiopoietin (ANG)-2 and intercellular adhesion molecule (ICAM)-1 were highly elevated in patients with CRVO compared with controls (p = 0.006; p = 0.02; p = 0.03). Vascular endothelial growth factor (VEGF) concentrations were upregulated in patients with BRVO and CRVO (p = 0.003; p = 0.001). Retreatment with a dexamethasone implant was necessary after 4 months in 14/8 (BRVO/CRVO) patients, 5 months in 5/3 patients and 6 months in one patient (BRVO). After the initial treatment, macrophage chemo-attractant protein (MCP)-1 and IL17-E concentrations decreased in BRVO (p < 0.001; p = 0.01) and MCP-1 and IL1-α in CRVO (p = 0.01; p = 0.003). Vascular endothelial growth factor (VEGF) concentrations did not change during treatment in either group (p = 0.3). A mixed-effect model showed that cytokine concentrations positively correlated with central retinal thickness changes. CONCLUSIONS: Intravitreal dexamethasone treatment resulted in alterations in the concentrations of pro-inflammatory cytokines MCP-1 and IL17-E in patients with BRVO and MCP-1 and IL1-α in patients with CRVO. These data highlight the important role of inflammatory mediators involved in ME due to RVO.

Relationship of retinal morphology and retinal sensitivity in the treatment of neovascular age-related macular degeneration using aflibercept.

PURPOSE: To relate the functional response to distinct morphological features of the retina during aflibercept treatment for neovascular AMD (nAMD). METHODS: A total of 726 retinal locations in 22 consecutive eyes presenting with treatment-naive nAMD underwent a standardized examination with spectral-domain optical coherence tomography (SD-OCT) and topographic microperimetry (MP) at baseline, after 3 and 12 months of continuous intravitreal aflibercept therapy. The retinal sensitivity at each stimulus location was registered to the corresponding location on SD-OCT morphology. Subsequently, the microperimetric responses were evaluated with respect to the following underlying SD-OCT features: neovascular complex (NVC), subretinal fluid (SRF), intraretinal fluid (IRF), intraretinal cystoid space (IRC), serous pigment epithelium detachment (sPED), and fibrovascular pigment epithelium detachment (fPED). RESULTS: Baseline sensitivity was reduced to mean values of 1.8 dB in NVC, 2.2 dB in IRC, 2.8 dB in IRF, 2.6 dB in sPED, 3.6 dB in SRF, and 4.6 dB in fPED. Improvements in retinal sensitivity were most pronounced during the initial 3-month interval, when significant recovery was documented for SRF and sPED with +4.0/5.5 dB (P < 0.0001) and to a lesser extent for IRF, IRC, fPED, with +1.1, 1.7, 2.3 dB, respectively. From month 3 to 12, the additional benefit ranged from 0.3 to 1.0 dB (P > 0.05 for each category). CONCLUSIONS: Significant functional benefits following intravitreal aflibercept treatment could be detected over all defined morphological pathologies. The level of improvement varied dependent on the associated feature with the best prognosis for visual improvement in SRF and sPED and least with intraretinal fluid and particularly intraretinal cysts.

Visual acuity and microperimetric mapping of lesion area in eyes with inflammatory cystoid macular oedema.

PURPOSE: To evaluate the effect of fluid accumulation on local visual function in inflammatory cystoid-macular-edema (ICME). METHODS: This cross-sectional study applied optical-coherence-tomography over a 12×12 fovea-centered field in 50 patients with ICME and mapped the extent of fluid-filled spaces in various retinal layers, of subretinal-fluid and of diffuse-edema. Regression analysis examined effect of planimetric fluid-distribution on best-corrected-visual-acuity (BCVA) and mean microperimetric-sensitivity. RESULTS: BCVA decreased with increasing central-neuroretinal-thickness (r= 0.52, p= 0.001), total central-retinal-thickness, including subneuroretinal-fluid (r= 0.41, p= 0.006), total cystoid-and-diffuse edema-area (r= 0.35, p= 0.036) and cystoid inner-nuclear-layer area (r= 0.39, p= 0.02). Mean retinal-sensitivity decreased with increasing diffuse edema-area (r= -0.86, p<0.0001), total cystoid-and-diffuse edema-area (r= -0.54, p= 0.001), cystoid inner-nuclear-layer area (r= -0.46, p= 0.008) and cystoid ganglion-cell-layer area (r= -0.6, p=0.049), central-neuroretinal-thickness (r= -0.42, p= 0.028) and total central-retinal-thickness (r= -0.34, p= 0.039). In multivariate-analyses BCVA was best described by central-neuroretinal-thickness, duration of edema, total cystoid-and-diffuse edema-area and cystoid inner-nuclear-layer area (R(2) = 0.5, p= 0.002). Mean retinal-sensitivity was best described by diffuse edema-area, total cystoid-and-diffuse edema-area and central-neuroretinal-thickness (R(2) = 0.75, p< 0.0001). Subretinal-fluid area and cystoid outer-nuclear/Henle's layer area had no effect on either BCVA or microperimetry. CONCLUSIONS: Thickening of the neurosensory-fovea, not subfoveal-fluid, had major impact on both BCVA and retinal-sensitivity. The extent of edema in inner retinal layers also had major impact on both of these two functional parameters. Visual-impairment seems to differ depending on the layers involved, thus different types of fluid accumulation may potentially be given varying treatment priorities.

Systematic correlation of morphologic alterations and retinal function in eyes with uveitis-associated cystoid macular oedema during development, resolution and relapse.

PURPOSE: To evaluate morphological changes due to uveitis-associated cystoid macular oedema (uvCME) and their impact on central retinal sensitivity (CRS) before and after intravitreal triamcinolone-acetonide (IVTA). METHODS: 28 eyes with uvCME were examined with microperimetry and spectral-domain optical-coherence-tomography (SD-OCT) before and after IVTA. Microperimetry-maps were superimposed on SD-OCT and morphological-alterations were correlated point to point with CRS and followed-up for 3 months. The effects of morphological-alterations on CRS over time were evaluated with a linear mixed-model. RESULTS: Mean-CRS increased significantly after IVTA (p=0.009). Proportion of cysts correlated negatively with corresponding CRS (estimate/95% CI -3.8 dB/-6.6 to -0.9, p=0.011). Proportion of diffuse macular-oedema (DifME) had no significant effect on mean-CRS (-0.76 dB/-4.9 to 3.3, p=0.71). The proportion of serous retinal detachment (SRD) had a borderline significant effect on mean-CRS (-9.5 dB/-19.1 to 0.1, p=0.052), however the initial presence of SRD at baseline had no significant negative effect on mean-CRS (-1.3 dB/-4.9 to 2.3, p=0.46). Patients with epiretinal-membrane showed lower mean-CRS than patients without (-3.3 dB/-6.5 to -0.008, p=0.05). The lowest percentage of morphological-alterations was achieved 30 days post IVTA concordant to best visual-acuity (logMAR 0.16 ± 0.26), while best mean-CRS was achieved 90 days post IVTA (16.9 ± 1.8 dB). Fixation-stability showed no significant improvement. CONCLUSIONS: UvCME Morphological-alterations were associated with specific CRS-decreases. DifME showed no significant- and SRD only a borderline effect on mean-CRS, which implicates that their presence should be considered when interpreting SD-OCT and making treatment-decisions.

Correlation of OCT characteristics and retinal sensitivity in neovascular age-related macular degeneration in the course of monthly ranibizumab treatment.

PURPOSE: To evaluate the functional treatment response 3 months and 12 months after monthly ranibizumab in neovascular age-related macular degeneration (NAMD). METHODS: Twenty-six eyes showing treatment-naïve NAMD were examined with the Heidelberg Spectralis OCT (SD-OCT) and the Nidek MP-1 microperimeter (MP) at baseline, after 3 months, and after 12 months of monthly ranibizumab therapy. Each test point of light sensitivity was transferred to the corresponding location on SD-OCT, and subsequently the microperimetric results were evaluated with respect to the following oct findings: neovascular complex (NVC), subretinal fluid (SRF), intraretinal fluid (IRF), intraretinal cystoid space (IRCS), serous pigment epithelium detachment (SPED), and fibrovascular pigment epithelium detachment (FPED). RESULTS: Loci of an initial NVC improved significantly from a mean retinal sensitivity value of 2.6 dB ± 0.8 dB at baseline to 7.4 dB ± 0.9 dB (P < 0.0001) at month 12. Initial SRF, IRF, and IRCS improved significantly from a mean value of 5.1 dB ± 0.9 dB to 12.4 dB ± 0.9 dB (P < 0.0001), 4.0 dB ±1.0 dB to 9.3 dB ± 0.9 dB (P < 0.0001), and 3.4 dB ± 0.9 dB to 8.2 dB ± 0.9 dB (P < 0.0001), respectively. An initial SPED improved significantly from a mean retinal sensitivity value of 1.9 dB ± 1.1 dB at baseline to 9.4 dB ± 1.1 dB (P < 0.0001) at month 12; a FPED improved significantly from 5.2 dB ± 0.9 dB at baseline to 7.6 dB ± 0.9 dB (P < 0.0001) at month 12. CONCLUSIONS: Functional benefit could be detected at all locations of macular pathology, with a lower benefit in the case of FPED and in the case of additional IRCS, and a marked benefit for all types of macular edema. (https://eudract.ema.europa.eu/, number 2006-005684-26.).