Ramzi Sayegh

A Systematic Comparison of Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence in Patients with Geographic Atrophy

PURPOSE To evaluate spectral-domain optical coherence tomography (SD-OCT) in providing reliable and reproducible parameters for grading geographic atrophy (GA) compared with fundus autofluorescence (FAF) images acquired by confocal scanning laser ophthalmoscopy (cSLO). DESIGN Prospective observational study. PARTICIPANTS A total of 81 eyes of 42 patients with GA. METHODS Patients with atrophic age-related macular degeneration (AMD) were enrolled on the basis of total GA lesion size ranging from 0.5 to 7 disc areas and best-corrected visual acuity of at least 20/200. A novel combined cSLO-SD-OCT system (Spectralis HRA-OCT, Heidelberg Engineering, Heidelberg, Germany) was used to grade foveal involvement and to manually measure disease extent at the level of the outer neurosensory layers and retinal pigment epithelium (RPE) at the site of GA lesions. Two readers of the Vienna Reading Center graded all obtained volume stacks (20×20 degrees), and the results were correlated to FAF. MAIN OUTCOME MEASURES Choroidal signal enhancements and alterations of the RPE, external limiting membrane (ELM), and outer plexiform layer by SD-OCT. These parameters were compared with the lesion measured with severely decreased FAF. RESULTS Foveal involvement or sparing was definitely identified in 75 of 81 eyes based on SD-OCT by both graders (inter-grader agreement: κ=0.6, P < 0.01). In FAF, inter-grader agreement regarding foveal involvement was lower (48/81 eyes, inter-grader agreement: κ=0.3, P < 0.01). Severely decreased FAF was measured over a mean area of 8.97 mm(2) for grader 1 (G1) and 9.54 mm(2) for grader 2 (G2), consistent with the mean SD-OCT quantification of the sub-RPE choroidal signal enhancement (8.9 mm(2) [G1] -9.4 mm(2) [G2]) and ELM loss with 8.7 mm(2) (G1) -10.2 mm(2) (G2). In contrast, complete morphologic absence of the RPE layer by SD-OCT was significantly smaller than the GA size in FAF (R(2)=0.400). Inter-reader agreement was highest regarding complete choroidal signal enhancement (0.98) and ELM loss (0.98). CONCLUSIONS Absence of FAF in GA lesions is consistent with morphologic RPE loss or advanced RPE disruption and is associated with alterations of the outer retinal layers as identified by SD-OCT. Lesion size is precisely determinable by SD-OCT, and foveal involvement is more accurate by SD-OCT than by FAF.

High-Resolution Optical Coherence Tomography after Surgery for Vitreomacular Traction: A 2-Year Follow-up

PURPOSE To characterize the morphologic changes in vitreomacular traction (VMT) before and after surgery using spectral-domain optical coherence tomography (SD OCT) and to identify patterns relevant to visual function. DESIGN Prospective, interventional case series. PARTICIPANTS Thirty eyes of 30 consecutive patients with visual acuity of less than 20/32 resulting from idiopathic VMT. METHODS A conventional 20-gauge 3-port vitrectomy was performed, including removal of the epiretinal membrane (ERM) and internal limiting membrane. Examinations were performed 1 day before surgery and 1 and 3 days as well as 1, 3, 6, 12, and 24 months after surgery. The SD OCT scan sets were analyzed with regard to central retinal thickness (CRT), retinal volume (RV), graded parameters of inner/outer retinal layer integrity (ILI/OLI), presence of retinal surface folds (RSF), and foveal contour. MAIN OUTCOME MEASURES Visual acuity and morphologic characteristics of the inner and outer retinal layers revealed by SD OCT. RESULTS Spectral-domain OCT revealed a complete absence of the ERM and early release of traction forces in each eye. Best-corrected visual acuity increased progressively over 24 months. Morphologically, RSF resolved within 1 month after surgery, followed by a marked decrease in CRT and RV over the next 3 months. There was no significantly correlation between RSF, CRT, or RV with functional improvement, and CRT and RV did not return to physiologic values. Recovery of ILI and OLI proceeded slowly, reaching significance at 12 months, and correlated strongly with visual function. CONCLUSIONS Spectral-domain OCT seems to be a valuable method for evaluating retinal changes after surgery for VMT. Reconstitution of neurosensory layers was identified as the most relevant parameter for visual improvement.

In vivo identification of alteration of inner neurosensory layers in branch retinal artery occlusion

Background/aims To characterise the extension and progression of alteration of neurosensory layers following acute and chronic branch retinal artery occlusion (BRAO) in vivo using spectral-domain optical coherence tomography. Methods In this observational case series, eight eyes with acute BRAO and nine eyes with chronic BRAO were analysed using a Spectralis Heidelberg Retina Angiograph (HRA)+optical coherence tomography system including eye tracking. Patients with acute BRAO were examined within 36±5 h after primary event and at weekly/monthly intervals thereafter. Segmentation measurements of all individual neurosensory layers were performed on single A-scans at six locations in affected and corresponding non-affected areas. The thickness values of the retinal nerve fibre layer together with the ganglion cell layer (NFL/GCL), inner plexiform layer (IPL), inner nuclear layer together with outer plexiform layer (INL/OPL), outer nuclear layer (ONL), and photoreceptor layers together with the retinal pigment epithelium (PR/RPE) were measured and analysed. Results Segmentation evaluation revealed a distinct increase in thickness of inner neurosensory layers including the NFL/GCL (35%), IPL (80%), INL/OPL (48%) and mildly the ONL by 21% in acute ischaemia compared with corresponding layers in non-ischaemic areas. Regression of intraretinal oedema was followed by persistent retinal atrophy with loss of differentiation between IPL and INL/OPL at month 2. In contrast, the ONL and subjacent PR/RPE retained their physiological thickness in patients with chronic BRAO. Conclusion In vivo assessment of retinal layer morphology allows a precise identification of the pathophysiology in retinal ischaemia.

Intraretinal cysts are the most relevant prognostic biomarker in neovascular age-related macular degeneration independent of the therapeutic strategy

Background/aims To investigate the impact of antiangiogenic monotherapy and photodynamic therapy (PDT) as add-on strategy on retinal morphology, and to analyse prognostic biomarkers for visual outcome and retreatment frequency in neovascular age-related macular degeneration (nAMD). Methods 255 patients participating in the MONT BLANC study were evaluated. Patients were randomised to receive as-needed ranibizumab monotherapy or combination therapy (verteporfin PDT and ranibizumab). Outcome measures included visual acuity (VA), retinal morphology assessed by optical coherence tomography and retreatment frequency. Results The proportion of scans showing intraretinal cysts (IRC) or subretinal fluid (SRF) decreased more intensively in the combination than in the monotherapy group. Pigment epithelial detachments (PED) decreased significantly only in the combination group. Patients with IRC presented the lowest initial VA, and IRC had the strongest negative predictive value for functional improvement in both groups. SRF showed a predictive value for a higher number of ranibizumab injections (combination, +0.9; monotherapy, +0.8) and a higher number of PDT treatments in the combination group (+0.3). PED was associated with a higher number of ranibizumab injections only in the monotherapy group (+1.2). Conclusions Combination and monotherapy showed a distinct response pattern for morphological parameters in nAMD. IRC was the only relevant prognostic parameter for functional outcome. Trial registration number NCT00433017.

Lesion Size Detection in Geographic Atrophy by Polarization-Sensitive Optical Coherence Tomography and Correlation to Conventional Imaging Techniques

PURPOSE To investigate the reproducibility of automated lesion size detection in patients with geographic atrophy (GA) using polarization-sensitive spectral-domain optical coherence tomography (PS-OCT) and to compare findings with scanning laser ophthalmoscopy (SLO), fundus autofluorescence (FAF), and intensity-based spectral-domain OCT (SD-OCT). METHODS Twenty-nine eyes of 22 patients with GA were examined by PS-OCT, selectively identifying the retinal pigment epithelium (RPE). A novel segmentation algorithm was applied, automatically detecting and quantifying areas of RPE atrophy. The reproducibility of the algorithm was assessed, and lesion sizes were correlated with manually delineated SLO, FAF, and intensity-based SD-OCT images to validate the clinical applicability of PS-OCT in GA evaluation. RESULTS Mean GA lesion size of all patients was 5.28 mm(2) (SD: 4.92) in PS-OCT. Mean variability of individual repeatability measurements was 0.83 mm(2) (minimum: 0.05; maximum: 3.65). Mean coefficient of variation was 0.07 (min: 0.01; max: 0.19). Mean GA area in SLO (Spectralis OCT) was 5.15 mm(2) (SD: 4.72) and 2.5% smaller than in PS-OCT (P = 0.9, Pearson correlation coefficient = 0.98, P < 0.01). Mean GA area in intensity-based SD-OCT pseudo-SLO images (Cirrus OCT) was 5.14 mm(2) (SD: 4.67) and 2.7% smaller than in PS-OCT (P = 0.9, Pearson correlation coefficient = 0.98, P < 0.01). Mean GA area of all eyes measured 5.41 mm(2) (SD: 4.75) in FAF, deviating by 2.4% from PS-OCT results (P = 0.89, Pearson correlation coefficient = 0.99, P < 0.01). CONCLUSIONS PS-OCT demonstrated high reproducibility of GA lesion size determination. Results correlated well with SLO, FAF, and intensity-based SD-OCT fundus imaging. PS-OCT may therefore be a valuable and specific imaging modality for automated GA lesion size determination in scientific studies and clinical practice.

Performance of OCT segmentation procedures to assess morphology and extension in geographic atrophy

Purpose:  Investigating segmentation procedures and morphological findings in time domain (TD) and current spectral domain (SD) optical coherence tomography (OCT) devices in patients with geographic atrophy (GA).

A systematic correlation of morphology and function using spectral domain optical coherence tomography and microperimetry in patients with geographic atrophy

Aims This study has been designed to describe the functional impact of distinct pathologies within the retinal layers in patients with geographic atrophy (GA) by means of a point-to-point correlation between optical coherence tomography (OCT) and microperimetry. Methods Retinal morphology and function of 23 patients suffering from GA of the retinal pigment epithelium (RPE) have been investigated using the Spectralis OCT (Heidelberg Engineering) and the MP1 microperimeter (Nidek Technologies). The point-to-point overlay of morphology and function has been done using proprietary software, allowing OCT image grading to define distinct alterations of the neurosensory retina, the RPE and the choroid. By overlaying the retinal sensitivity map on the OCT data set, retinal layer alterations could be evaluated regarding their impact on visual function. Results A total of 1005 stimulation points in the lesion area in 2107 spectral domain OCT B-scans were graded in 43 eyes of 23 patients (mean best corrected visual acuity=20/70). Retinal sensitivity decreases with an increasing number of morphological alterations graded (p<10−13). Alterations of the RPE and the external limiting membrane (p<0.02) were associated with absolute scotomas. Furthermore, the loss of the external limiting membrane as the largest area of morphological alteration among our patients with GA (mean area=5.65 mm2), had a significant impact (p<10−4) on sensitivity (−1.3 dB). Conclusions Mapping retinal sensitivity to distinct retinal pathologies revealed outer retinal layers, in addition to the RPE, as significant for sensitivity loss. Therefore in GA the RPE loss and the alteration of outer retinal layers should be analysed, which could also provide insight into lesion progression.

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.).

Polarization-Sensitive Optical Coherence Tomography and Conventional Retinal Imaging Strategies in Assessing Foveal Integrity in Geographic Atrophy

PURPOSE To compare current imaging methods with respect to their ability to detect the condition of the fovea in patients with geographic atrophy (GA). METHODS The retinas of 176 eyes with GA were imaged using two spectral-domain optical coherence tomography (SD-OCT) systems, Cirrus HD-OCT and Spectralis HRA+OCT, and fundus autofluorescence (FAF) and infrared imaging (IR) was used in the scanning laser ophthalmoscope (SLO) mode. Polarization-sensitive OCT (PS-OCT), which selectively visualizes the RPE in addition to SD-OCT features, was used to image 95 eyes. Geographic atrophy lesions were categorized as fovea spared, involved, or not quantifiable (grades 0, 1, and 2). Morphologic gradings were subsequently correlated with best-corrected visual acuity (BCVA) measurements to independently identify the corresponding functional condition of the fovea. Cohens κ statistics with a bootstrap method was applied to compare retinal imaging methods. RESULTS In PS-OCT, 84% of eyes with BCVA greater than or equal to 20/40 were detected, whereas in conventional retinal imaging the rate ranged from 27% in FAF to 45% in the SD-OCT segment. Cohens κ statistics revealed significant differences between the gradings of PS-OCT and conventional imaging with κ = 0.488 and a global Hotellings T2 statistic of 17.9 with a P value of P = 0.003. Statistical tests revealed no statistically significant differences between the conventional retinal imaging modalities. CONCLUSIONS Polarization-sensitive OCT can better allow correct grading of the fovea in relation to BCVA and identify foveal sparing than other imaging modalities. The differences in imaging precision should be considered in diagnostic and therapeutic evaluations.

Therapeutic Interventions For Macular Diseases Show Characteristic Effects On Near And Distance Visual Function

Purpose: To compare therapy-induced reading and distance visual acuity (dVA) increases in neovascular age-related macular degeneration (nAMD) and uveitis-associated cystoid macular edema. Methods: This longitudinal study included 68 treatment-naive eyes: 39 subfoveal nAMD eyes with disrupted photoreceptor layers treated with monthly ranibizumab and 29 uveitis-associated cystoid macular edema eyes with intact photoreceptor layer treated with 1 triamcinolone injection. Patients were examined with high-definition optical coherence tomography, Early Treatment Diabetic Retinopathy Study dVA (logarithm of the minimum angle of resolution), reading acuity (logRADscore), and maximum reading speed (words per minute) over 3 months of therapy. Results: In uveitis-associated cystoid macular edema, logarithm of the minimum angle of resolution and logRADscore improved 1 day post treatment, from 0.49 ± 0.28 to 0.39 ± 0.3 (P = 0.018) and 0.71 ± 0.53 to 0.56 ± 0.49 (P = 0.012), respectively. In nAMD, logarithm of the minimum angle of resolution improved 1 week after anti–vascular endothelial growth factor therapy from 0.59 ± 0.29 to 0.49 ± 0.24 (P = 0.002), with no change in logRADscore. One month after treatment, logRADscore improved from 1.09 ± 0.65 to 0.90 ± 0.60 (P = 0.002). In uveitis-associated cystoid macular edema, the recovery course of reading and dVA was comparable, and in nAMD, reading acuity recovery was delayed. Irrespective of disease, a small reduction in dVA resulted in a larger reading acuity decrease. Conclusion: Cystoid macular edema resolution was associated with rapid synchronous reading and dVA improvement, whereas nAMD was followed by faster recovery of distance than reading acuity. In both conditions, reading acuity expressed by critical angular resolution was more suppressed by active disease and recovered relatively more than distance acuity. These discrepancies indicate that reading acuity might be a more sensitive measure for vision decrease in macular diseases than dVA. Reading acuity seems to be an important adjunct assessing intravitreal therapy efficacy.