Francisco A. Folgar

Progression of Intermediate Age-related Macular Degeneration with Proliferation and Inner Retinal Migration of Hyperreflective Foci

PURPOSE Drusen and migrating retinal pigment epithelium have been associated with hyperreflective foci (HF) detected by spectral-domain optical coherence tomography (SD-OCT). This study sought to quantify the change in intraretinal HF distribution and its correlation with age-related macular degeneration (AMD) disease progression. DESIGN Prospective observational study from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study. PARTICIPANTS Patients (n=299) with 1 enrolled eye with intermediate AMD and baseline SD-OCT, followed by SD-OCT imaging at 1-year and 2-year visits. METHODS The number and location of HF were scored in SD-OCT scans of all 299 eyes. The change in transverse (horizontal) and axial (vertical) distribution of HF in the macula were evaluated with pairwise signed-rank tests. Two-year inner retinal HF migration was determined by the change in HF-weighted axial distribution (AxD) score calculated for each eye. The correlation of HF with SD-OCT features of AMD progression was evaluated with logistic regression analysis. MAIN OUTCOME MEASURES The mean change in number of HF, transverse and axial distribution of HF in the macula, and AxD per eye. RESULTS In 299 study eyes, the 2-year increase in the number of HF (P<0.001) and the AxD (P<0.001) per eye represented longitudinal proliferation and shift to inner retinal layers, respectively. Eyes with geographic atrophy (GA) at 2 years were correlated with the presence of baseline HF (P<0.001; odds ratio [OR], 4.72; 95% confidence interval [CI], 2.43-9.80), greater number of baseline HF (P<0.001; OR, 1.61 per HF; 95% CI, 1.32-2.00), and greater baseline AxD (P<0.001; OR, 1.58 per AxD point; 95% CI, 1.29-1.95). CONCLUSIONS Proliferation and inner retinal migration of SD-OCT HF occurred during follow-up in eyes with intermediate AMD. These characteristics were associated with greater incidence of GA at year 2; therefore, SD-OCT HF proliferation and migration may serve as biomarkers for AMD progression. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Spatial correlation between hyperpigmentary changes on color fundus photography and hyperreflective foci on SDOCT in intermediate AMD.

PURPOSE Macular hyperpigmentation is associated with progression from intermediate to advanced age-related macular degeneration (AMD). The purpose of this study was to accurately correlate hyperpigmentary changes with spectral domain optical coherence tomography (SDOCT) hyperreflective foci in eyes with non-advanced AMD. METHODS A prospective cross-sectional analysis of 314 eyes (314 subjects) with intermediate AMD was performed in the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study to correlate hyperpigmentary changes on color fundus photographs (CFP) with abnormal morphology on SDOCT. Spatial coregistration was performed with an automated algorithm in two nonoverlapping subsets of 20 study eyes, which permitted double-masked CFP and SDOCT grading by certified investigators. RESULTS Macular CFP hyperpigmentation was significantly associated with SDOCT intraretinal hyperreflective foci in the 314 study eyes (P < 0.001). In a substudy of 40 eyes, automated intermodality spatial coregistration was successfully achieved in all 136 (100%) retinal regions selected for CFP and SDOCT grading. In one subset of 20 study eyes, 28 of 39 (71.8%) retinal CFP regions with hyperpigmentation were correlated with focal hyperreflectivity on SDOCT, versus seven of 39 (17.9%) control regions (P < 0.001). In another subset of 20 eyes, 21 of 29 (72.4%) SDOCT regions with hyperreflective foci were correlated with hyperpigmentary changes on CFP, versus two of 29 (6.9%) control regions (P < 0.001). CONCLUSIONS A novel algorithm achieves automated intermodality spatial coregistration for masked grading of regions selected on CFP and SDOCT. In intermediate AMD, macular hyperpigmentation has high spatial correlation to SDOCT hyperreflective foci and often represents the same anatomical lesion. (ClinicalTrials.gov number, NCT00734487.).

Outer retinal tubulation in the comparison of age-related macular degeneration treatments trials (CATT)

PURPOSE To determine the prevalence of, risk factors for, and visual acuity (VA) correlations with outer retinal tubulation (ORT) seen on spectral-domain optical coherence tomography (SD OCT) in eyes with neovascular age-related macular degeneration (AMD) after anti-vascular endothelial growth factor (VEGF) therapy. DESIGN Prospective cohort study within a randomized clinical trial. PARTICIPANTS Patients with SD OCT images at weeks 56 and 104 in the Comparison of AMD Treatments Trials (CATT). METHODS Participants in the CATT were assigned randomly to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a monthly or pro re nata (PRN) injection-dosing regimen. A subset of eyes was imaged with SD OCT beginning at week 56. Cirrus 512×128 or Spectralis 20°×20° volume cube scan protocols were used to acquire SD OCT images. Two independent readers at the CATT OCT reading center graded scans, and a senior reader arbitrated discrepant grades. The prevalence of ORT, identified as tubular structures seen on at least 3 consecutive Cirrus B scans or 2 consecutive Spectralis B scans, was determined. The associations of patient-specific and ocular features at baseline and follow-up with ORT were evaluated by univariate and multivariate analyses. MAIN OUTCOME MEASURES Outer retinal tubulations. RESULTS Seven of 69 eyes (10.1%) at 56 weeks and 64 of 368 eyes (17.4%) at week 104 had ORTs. Absence of diabetes, poor VA, blocked fluorescence, geographic atrophy, greater lesion size, and presence of subretinal hyperreflective material at baseline were associated independently with greater risk of ORT at 104 weeks (P < 0.05). Neither drug nor dosing regimen were associated significantly with ORT. The mean VA of eyes with ORT at week 104 (58.5 Early Treatment Diabetic Retinopathy Study letters) was worse than the mean VA of eyes without ORT (68.8 letters; P < 0.0001). CONCLUSION At 2 years after initiation of anti-VEGF therapy for neovascular AMD, ORTs are present in a substantial proportion of eyes. We identified baseline features that independently predict ORTs. It is important to identify ORTs because eyes with ORTs have worse VA outcomes than those without this finding.

Catheter-mediated subselective intracoronary gene delivery to the rabbit heart: introduction of a novel method.

Recent studies suggest that gene therapy using replication‐deficient adenoviruses will benefit treatment of cardiovascular diseases including heart failure. A persistent hurdle is the effective and reproducible delivery of a transgene to the myocardium with minimal iatrogenic morbidity. In this study, we sought to design a relatively non‐invasive percutaneous gene delivery system that would maximize cardiac transgene expression and minimize mortality after intracoronary adenovirus injection.

Spectral domain optical coherence tomography characterization of pediatric epiretinal membranes.

Purpose: To compare the macular morphology of pediatric versus adult eyes with epiretinal membrane (ERM) using spectral domain optical coherence tomography and identify characteristics associated with postoperative visual acuity. Methods: This retrospective study analyzed spectral domain optical coherence tomography from pediatric subjects and a randomly selected cohort of adult subjects with ERM. Morphologic retinal and ERM features were graded by two masked spectral domain optical coherence tomography readers and compared with a postoperative change in visual acuity. Results: Pediatric ERMs (age, 0.3–16.5 years) were more confluently attached to the retina than adult ERMs (age, 40–88 years; P = 0.009) and had less fibrillary appearance of the inner retina when separation was present (P = 0.044). Pediatric ERMs were associated with more vessel dragging (P = 0.019) and less external limiting membrane (P = 0.001) and inner segment band visibility (P = 0.010), with a trend toward foveal sparing by ERM (P = 0.051) and “taco” retinal folds (P = 0.052) compared with adult eyes. Visual acuity improvement was associated with intact (P = 0.048) and smooth (P = 0.055, trend) inner segment band in children and with smooth inner segment band (P = 0.083, trend) and visible external limiting membrane (P = 0.098, trend) in adults. Conclusion: We identified morphologic differences between pediatric and adult ERM on spectral domain optical coherence tomography. Similar to adults, photoreceptor integrity with pediatric ERM seems to predict better visual acuity changes after surgical ERM removal.

Comparison of Optical Coherence Tomography Assessments in the Comparison of Age-Related Macular Degeneration Treatments Trials

OBJECTIVE To determine agreement between spectral-domain (SD) and time-domain (TD) optical coherence tomography (OCT) image assessments by certified readers in eyes treated for neovascular age-related macular degeneration (AMD). DESIGN Cross-sectional study within the Comparison of AMD Treatments Trials (CATT). PARTICIPANTS During year 2 of CATT, 1213 pairs of SD OCT and TD OCT scans were compared from a subset of 384 eyes. METHODS Masked readers independently graded OCT scans for presence of intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (RPE) fluid and performed manual measurements of retinal, SRF, and subretinal tissue complex thicknesses at the foveal center. MAIN OUTCOME MEASURES Presence of fluid was evaluated with percent agreement, κ coefficients with 95% confidence intervals (CIs), and McNemar tests. Thickness measurements were evaluated with mean difference (Δ) ±95% limits of agreement and intraclass correlation coefficients (ICCs) with 95% CIs. RESULTS Between SD OCT and TD OCT, agreement on presence of any fluid was 82% (κ = 0.46; 95% CI, 0.40-0.52), with 5% more SD OCT scans demonstrating fluid (P<0.001). Agreement on presence of SRF was 87% and sub-RPE fluid was 80%, with more SD OCT scans demonstrating fluid (both P < 0.001). Agreement on IRF was 73% (κ = 0.47; 95% CI, 0.42-0.52), with 6% more TD OCT scans demonstrating fluid (P < 0.001). Between SD OCT and TD OCT, mean thickness of the retina was Δ = 5±67 μm, SRF was Δ = 1.5±35 μm, and subretinal tissue complex was Δ = 5±86 μm. Thickness measurements were reproducible for retina (ICC = 0.84; 95% CI, 0.83-0.86), SRF (ICC = 0.88; 95% CI, 0.86-0.89), and subretinal tissue complex (ICC = 0.91; 95% CI, 0.89-0.92), with ≤25-μm difference in these measurements in 71%, 94%, and 61% of paired scans, respectively. CONCLUSIONS Agreement on fluid presence and manual thickness measurements between paired scans from each OCT modality was moderate, providing a reasonable basis to compare CATT results with future SD OCT-based trials. Fluid was detected 5% more frequently with SD OCT, which may increase frequency of fluid-based treatment. Lower-resolution and artifactual interpretation of dark areas as cystoid edema may explain the greater frequency of IRF detected with TD OCT.

A Comparative Study of Rebound Tonometry With Tonopen and Goldmann Applanation Tonometry Following Vitreoretinal Surgery.

PURPOSE To investigate agreement in intraocular pressure (IOP) measurements among Icare rebound tonometry, Tonopen tonometry, and Goldmann applanation tonometry following vitreoretinal surgery. DESIGN Reliability analysis of tonometers. METHODS Fifty-eyes of 50 adults undergoing vitreoretinal surgery were enrolled. IOP was measured on first postoperative day using Icare (Tiolat, Helsinki, Finland), followed by Tonopen (Reichert, Depew, New York, USA) and Goldmann (Haag-Streit USA, Mason, Ohio, USA) in randomized order. Intraclass correlation coefficients (ICC) and Bland-Altman plots were calculated for all subcategories. RESULTS Icare successfully measured IOP in all eyes, while Goldmann was unmeasurable in 6 eyes (12%) and Tonopen in 1 eye (2%). Mean IOP by Icare, Tonopen, and Goldmann was 15.9 ± 8.9, 16.9 ± 6.2, and 16.0 ± 7.3 mm Hg, respectively (P = .76). Type of intraocular tamponade, status of lens, status of cornea, gauge of instrumentation, and history of prior vitrectomy did not result in significant differences among the 3 tonometers. ICC was excellent (>0.75) in all subgroups, except at IOP <10 and ≥ 23 mm Hg (based on Icare). In eyes with IOP <10 mm Hg, Icare underestimated IOP (mm Hg; P = .01) compared to Goldmann (2.0 ± 2.1) and Tonopen (3.5 ± 2.4), whereas at IOP ≥ 23 mm Hg Icare was overestimated (P = .01) compared to Goldmann (3.77 ± 3.49) and Tonopen (4.97 ± 3.33). Overall, differences in IOP were ≤ 3 mm Hg in 58% of eyes for Icare-Tonopen, 72% for Tonopen-Goldmann, and 62% for Icare-Goldmann. CONCLUSION IOP measurements using Icare rebound tonometry, Tonopen, and Goldmann tonometry are in excellent agreement following vitreoretinal surgery. However, Icare overestimates at IOP ≥ 23 and underestimates at IOP <10 mm Hg.