Florian Sulzbacher

Diagnostic Evaluation of Type 2 (Classic) Choroidal Neovascularization: Optical Coherence Tomography, Indocyanine Green Angiography, and Fluorescein Angiography

PURPOSE To evaluate the diagnostic characteristics of type 2 (classic) choroidal neovascularizations secondary to age-related macular degeneration using spectral domain-optical coherence tomography (SD OCT), indocyanine green angiography (ICGA), and fluorescein angiography (FA). DESIGN Observational case series. METHODS SETTING Institutional. STUDY POPULATION Thirteen treatment-naïve eyes with type 2 choroidal neovascularization without an occult component. MAIN OUTCOME MEASURES Greatest horizontal dimension, based on the anatomic features of the neovascular complex by SD OCT (Spectralis; Heidelberg Engineering), ICGA, and FA; retinal leakage area in late-phase FA and ICGA; and the area of retinal edema in SD OCT. OBSERVATION PROCEDURES For direct comparison, ICGA and FA images were overlaid manually on infrared plus SD OCT images using VirtualDub and Paint.NET software. Greatest horizontal dimension was measured using Image J software (National Institutes of Health). RESULTS The mean greatest horizontal dimension of the neovascular complex and the retinal leakage area consistently were smaller on ICGA compared with the area of retinal edema on SD OCT. According to FA, the greatest horizontal dimension of early, well-demarcated hyperfluorescence was significantly smaller than the neovascular complex on SD OCT. In addition, the greatest horizontal dimension of the retinal leakage area in late-phase FA consistently was smaller than the area of retinal edema on SD OCT. CONCLUSIONS In classic choroidal neovascularization, ICGA and FA seem to underestimate the extension of the neovascular complex and the associated retinal pathologic features compared with SD OCT imaging.

Morphologic and functional evaluations during development, resolution, and relapse of uveitis-associated cystoid macular edema.

Objectives: To describe progression and resolution of uveitis-associated cystoid macular edema (uvCME) using spectral-domain optical coherence tomography and find predictive factors for successful intravitreal triamcinolone acetonide (IVTA) therapy. Methods: Twenty-nine eyes with treatment-naive uvCME were examined before and at 5 scheduled visits within 3 months after intravitreal triamcinolone acetonide administration. Distribution, resolution, relapse, and development of uvCME were evaluated using spectral-domain optical coherence tomography to describe morphology, progression, and relapse according to a standardized reading protocol. Applying repeated measures analysis of variance, morphologic findings were evaluated as predictive factors of the treatment outcome. Results: At baseline, 89.3% presented with focal CME; 65.6% had outer nuclear/Henley’s layer and inner nuclear layer cysts. Following intravitreal triamcinolone acetonide administration, cysts of outer nuclear/Henley’s layer diminished before those of inner nuclear layer (P = 0.0004). Small-pointed subretinal detachment (SRD) resolution synchronized with inner nuclear layer cyst extinction, whereas dome-shaped SRD resolution lagged behind (P = 0.014). Relapses of CME appeared in 71.4% of eyes with parafoveal inner nuclear layer cysts. Cysts of outer nuclear/Henley’s layer were present in an additional 28.6%. None of the eyes developed SRD during CME relapse. The main effect variables “SRD” and “absence of epiretinal membrane” were associated with greater best-corrected visual acuity improvement (P = 0.05 and P = 0.047), whereas the side effect variables “CME duration”, “age,” and “uveitis location” had no additional effect on best-corrected visual acuity. Baseline SRD predicted a relapse-free clinical course within the observational period (P = 0.025). Conclusion: Different morphologic patterns in uvCME may represent different stages in uvCME progression, and initial morphologic appearance can be linked to the clinical prognosis after the treatment.

One Year Follow-up of Functional Recovery in Neovascular AMD During Monthly Anti-VEGF Treatment

PURPOSE To identify neurosensory recovery, testing different functional variables during monthly intravitreal standard anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (AMD). DESIGN Prospective interventional cohort study. METHODS Sixty-four treatment-naïve neovascular AMD patients with subfoveal lesions were treated and examined monthly for distance visual acuity, reading acuity, maximum reading speed, and contrast sensitivity and with microperimetry evaluating the percentage of absolute and relative scotoma and mean central retinal sensitivity weighted by area. Improvements in reading acuity, distance acuity, reading speed, contrast sensitivity, mean central retinal sensitivity, and scotoma area in dependence of age, lesion type, lesion size, and mean central retinal sensitivity were evaluated by a random-slope and random-intercept model. Recovery pattern of parameters was compared by correlating the individual slopes of each variable. RESULTS Initially, a rapid short-term effect of anti-VEGF treatment was documented throughout all functional variables. Progressive functional gain over 1 year was observed for distance visual acuity (P = .011), contrast sensitivity (P ≤ .0001), and mean central retinal sensitivity (P ≤ .0001), but not for reading acuity (P = .31) and maximum reading speed (P = .94). Decrease of absolute scotoma area missed statistical significance over time (P = .053) and also fixation stability did not improve (P = .08). However, lesion size influenced the course of absolute scotoma area (P = .0015), while lesion type had no effect on any visual function variable evaluated. The individual slopes of reading acuity and distance visual acuity showed a moderate correlation; however, all other variables showed only a weak or no significant correlation among each other. CONCLUSION Visual recovery in anti-VEGF therapy is reflected in a characteristic pattern of functional changes over time, whereas distance visual acuity does not seem to comprehensively reflect overall visual function gain.

Identification and clinical role of choroidal neovascularization characteristics based on optical coherence tomography angiography

To suggest a novel classification of neovascular age‐related macular degeneration (AMD) based on optical coherence tomography angiography (OCTA) and to correlate morphological characteristics based on optical coherence tomography (OCT)/OCTA with clinical criteria of disease activity.

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.).

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).

Differential diagnosis of macular edema of different pathophysiologic origins by spectral domain optical coherence tomography.

Purpose: To develop a classification approach based solely on spectral domain optical coherence tomography to differentiate macular edema (ME) of different disease entities and to determine underlying pathology. Methods: A cross-sectional study including 153 participants: 27 with Irvine–Gass, 31 with uveitic ME, 24 with ME after branch retinal vein occlusion, 13 with central retinal vein occlusion, 44 with diabetic ME, and 14 controls. Spectral domain optical coherence tomography was graded according to a standardized reading protocol. Grading characteristics were: ME pattern in the central line (horizontal/vertical) and in volume scans, distribution of cysts in Early Treatment Diabetic Retinopathy Study grid, morphologic features, and quantitative parameters such as individual layer thickness. The parameters in a best-fitting multivariate model were evaluated for reliability to predict the underlying pathology using a leave-one-out crossover-validation analysis. To evaluate clinical reliability, two masked clinicians graded spectral domain optical coherence tomography images according to the assessed parameters. Results: The best-fitting multivariate model revealed that microfoci, ME pattern in vertical line scan, and foveal retinal nerve fiber layer thickness are the best indicators of the underlying pathology of ME. Classification accuracy of this model was 96%, mean cross-validated test classification accuracy was 84% (r² = 0.95, P < 0.0001). Clinical relevance was examined with 2 independent readers, yielding classification accuracies of 86% in both cases. Conclusion: Macular edema demonstrates characteristic patterns, morphologic features, and layer thicknesses dependent on the underlying disease process. Diagnostic recognition of these features may allow clinical and automated disease identification based primarily on spectral domain optical coherence tomography analysis.

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 −3.8dB/−6.6 to −0.9, p=0.011). Proportion of diffuse macular-oedema (DifME) had no significant effect on mean-CRS (−0.76dB/−4.9 to 3.3, p=0.71). The proportion of serous retinal detachment (SRD) had a borderline significant effect on mean-CRS (−9.5dB/−19.1 to 0.1, p=0.052), however the initial presence of SRD at baseline had no significant negative effect on mean-CRS (−1.3dB/−4.9 to 2.3, p=0.46). Patients with epiretinal-membrane showed lower mean-CRS than patients without (−3.3dB/−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±1.8dB). 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.

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.