Katharina Eibenberger

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.

Anti-VEGF treatment in branch retinal vein occlusion: a real-world experience over 4 years.

To determine long‐term outcome of intraocular antagonism of vascular endothelial growth factor (VEGF) in macular oedema (ME) secondary to branch retinal vein occlusion (BRVO).

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

To investigate the influence of intravitreal dexamethasone implant on inflammatory and angiogenic cytokine levels in the aqueous of patients with retinal vein occlusion (RVO).

RETREATMENT WITH ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY BASED ON CHANGES IN VISUAL ACUITY AFTER INITIAL STABILIZATION OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 3-Year Follow-up Results.

Purpose: To evaluate the 3-year therapeutic benefit of intravitreal bevacizumab in neovascular related macular degeneration (nAMD) in a standard clinical setting involving 3 initial injections and a pro re nata regimen as recommended in the PRONTO study. Methods: In this interventional clinical study, 181 eyes of 160 consecutive patients with active neovascular related macular degeneration meeting recommended criteria for inclusion and protocol criteria for anti–vascular endothelial growth factor therapy undergoing intravitreal bevacizumab monotherapy were observed. Data of treatment-naive eyes (Group 1, n = 114) were analyzed separately from eyes that had undergone previous photodynamic therapy plus intravitreal triamcinolone (Group 2, n = 67). Re-treatment criteria were based on clinical outcome following the official European label regimen. After 1 year of continuous service at an academic referral center, follow-up was performed in private practices in collaboration with the referral center. Main outcome parameters were best-corrected visual acuity and central retinal thickness. Results: After 3 years, best-corrected visual acuity decreased in the overall population (0.23 ± 0.16 to 0.16 ± 0.21. P = 0.002) and in both groups compared with baseline (0.24 ± 0.21 to 0.17 ± 0.21, Group 1, P = 0.03; 0.22 ± 0.19 to 0.16 ± 0.21, Group 2, P > 0.05), whereas central retinal thickness increased in the overall population (291 ± 92 to 319 ± 110 &mgr;m, P = 0.01) and in both groups (291 ± 96 to 325 ± 117 &mgr;m, Group 1, P > 0.05; 290 ± 83 to 308 ± 96 &mgr;m, Group 2, P > 0.05) because of chronic cystic degeneration changes of the macula. Mean treatment rate was 5.1 ± 3.9 (Group 1) versus 3.7 ± 2.7 (Group 2, P = 0.01). Five cases of severe intraocular inflammation after intravitreal bevacizumab were documented. Discussion: While the functional and morphological benefits persisted for the first year after intravitreal bevacizumab treatment, after this time both functional and morphologic results were disappointing during long-term follow-up with visual acuity loss as the main retreatment criterion. After stabilization of the disease, a monthly follow-up of optical coherence tomography and re-treatment based on morphologic, clinical, and vision outcomes may increase the efficacy in patients with neovascular related macular degeneration under anti–vascular endothelial growth factor treatment.

Extent of Detached Retina and Lens Status Influence Intravitreal Protein Expression in Rhegmatogenous Retinal Detachment

PURPOSE The aim of the study was to compare intravitreal cytokines and chemokines to clinical parameters in patients with rhegmatogenous retinal detachment (RRD). METHODS In this prospective study vitreous samples were taken undiluted from 60 patients with RRD and 20 age-matched controls with idiopathic epiretinal membranes at the beginning of primary vitrectomy. The following clinical parameters were assessed from RRD patients prior to surgery: number of quadrants detached, RD height, lens status, symptom duration, and refractive power. Concentrations of 40 different proteins in the vitreous of RRD eyes were measured by multiplex protein array, compared with controls and correlated to clinical parameters. RESULTS Ten cytokines and chemokines were significantly upregulated in the vitreous of RRD eyes compared with controls (tissue inhibitors of metalloproteinases [TIMP]-1 and -2, macrophage inflammatory protein [MIP]-1α, monocyte chemoattractant protein [MCP]-1, IL-6, and -8, inducible protein (IP)-10, brain-derived neurotrophic factor [BDNF], TGFβ-3, and platelet-derived growth factor [PDGF]-AB/BB). Linear regression analysis revealed that IL-8 and TGFβ-3 increased with the number of retinal quadrants detached, while TIMP-1 rose in eyes with greater RD heights. Concentrations of IP-10 and myeloperoxidase (MPO) peaked in eyes with two or more quadrants detached, while TIMP-2 was highest expressed in the vitreous of eyes with great RD height. In pseudophakic eyes with higher detachment height levels of vascular cell adhesion molecule (VCAM)-1 were significantly increased, while neural cell adhesion molecule (NCAM) was decreased in pseudophakic patients with shallow RD height. CONCLUSIONS Extent of RRD and lens status significantly influence intravitreal proinflammatory, profibrotic, and proapoptotic protein expression. These data contribute to the fundamental understanding of pathophysiological mechanisms in RRD and may serve as a basis for development of adjunct therapeutics to facilitate functional restoration.

ROLE OF ADDITIONAL DEXAMETHASONE FOR THE MANAGEMENT OF PERSISTENT OR RECURRENT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION UNDER RANIBIZUMAB TREATMENT.

Purpose: To assess the efficacy of a combination therapy of intravitreal ranibizumab together with a dexamethasone implant in comparison with ranibizumab monotherapy in neovascular age-related macular degeneration. Methods: Forty eyes of recurrent or persistent neovascular age-related macular degeneration were included in this prospective study. Patients were randomly assigned to two groups. Based on a pro re nata treatment regimen, the first group received intravitreal ranibizumab monotherapy (IVM). The second group received a combination of intravitreal dexamethasone implant and ranibizumab (intravitreal combination [IVC]) at baseline and was retreated with ranibizumab as needed. A second dexamethasone implant was allowed for retreatment after at least 6 months. Retreatment criteria included evidence of subretinal fluid, cystoid macular edema or new hemorrhage, and/or a visual acuity decrease of 5 Early Treatment Diabetic Retinopathy Study letters. Results: During 12 months, a mean of 7.95/5.5 (IVM/IVC; P = 0.042) retreatments were given. The median time until first retreatment differed significantly between the groups (P = 0.004). Functional variables could be maintained in both groups with no differences between them. Visual acuity changed from 62 letters at baseline to 67 at Month 12 in the IVM and remained stable at 68 letters in the IVC group (P = 0.68); macular sensitivity changed from 6.95 dB to 7.01 dB in IVM and from 7.24 dB to 7.12 dB in IVC (P = 0.4). Central retinal thickness decreased, however, with no difference between the groups (P = 0.38). In the IVM/IVC group, 11/12 (55/60%) patients were phakic at the time of study entry. One (9%) patient from the IVM and 4 (33%) from the IVC group were referred to cataract surgery after study completion (P = 0.4). Conclusion: This pilot study indicates combined therapy to delay retreatment in patients with persistent/recurrent neovascular age-related macular degeneration and an overall reduction in required ranibizumab retreatments compared with ranibizumab monotherapy with consistent functional outcomes.

Macula-On Versus Macula-Off Pseudophakic Rhegmatogenous Retinal Detachment Following Primary 23-Gauge Vitrectomy Plus Endotamponade

Abstract Aim: To evaluate anatomical and functional outcomes of macula-on and macula-off rhegmatogenous retinal detachment (RRD) after 23-gauge vitrectomy and gas endotamponade, in eyes after successful cataract surgery. Methods: Forty-six pseudophakic eyes of 46 consecutive patients who underwent surgery for RRD repair were included. Based on the severity degree and extension of the RRD, diluted C3F8, SF6 or C2F6 gases were used for endotamponade. Patients were followed 1 month, 3 months, 6 months and 12 months after surgery. Main outcome variables were functional and anatomic outcomes till 12 months after surgery. Results: Proliferative vitreoretinopathy of grade B or C was observed in 43%. C3F8 was used in 59%, SF6 in 28% and C2F6 in 13%. Reattachment after the first intervention was achieved in 89%. Preoperatively, 63% of patients presented with fovea-off retinal detachment. No intraoperative complications were registered. Preoperatively, eyes with macula-on RRD had a logMar BCVA of 0.3 ± 0.6 compared with 1.2 ± 0.7 in the macula-off group (p = 0.01). The mean visual acuity significantly improved to 0.06 ± 0.1 logMar in macula-on eyes and to 0.2 ± 0.3 logMar in macula-off eyes at 12 months (p = 0.01 compared to baseline and p = 0.04 between both the groups). The mean final postoperative CRT was 318 ± 48 µm in the macula-on group compared with 305 ± 71 µm in the macula-off group (p = 0.5). Conclusions: Even morphological improvement after 23-gauge vitrectomy and gas endotamponade was comparable between macula-on and macula-off eyes, macula-off RRDs showed delayed visual rehabilitation. Both groups showed significant visual acuity improvement until 12 months, however, macula-on RRDs showed significantly more improvement than macula-off RRDs.

Development of Surgical Management in Primary Rhegmatogenous Retinal Detachment Treatment from 2009 to 2015

ABSTRACT Purpose: To evaluate the evolution of surgical methods over a 7-year period in patients with primary rhegmatogenous retinal detachment (RRD) and its relation to functional outcome and intra- and postoperative complications. Methods: This prospective observational study included 628 patients with primary RRD who underwent surgical repair between January 2009 and December 2015. The main outcome measures were the type of surgical procedure ((scleral buckle (SB), pars plana vitrectomy (PPV), combination of SB and PPV or cryocoagulation (CC)) and intraocular tamponades. In addition, functional outcome and intra/postoperative complications were assessed over the observational period. Results: During the 7-year observation, the percent of SB procedures decreased from 40.5% in 2009 to 2.7% in 2014, while PPV increased from 38% in 2009 to above 90% in 2014. In 2015, the SB procedure was performed in 10.3% and PPV in 85.6% of patients with RRD (p < 0.001). No consistent trend was observed for the use of intraocular gas tamponade. The functional outcome within the 7-year observation ranged from 0.25 ± 0.31logmar in 2012 to 0.42 ± 0.40logmar in 2009 and showed no statistically significant trend (p = 0.28). Intraoperative complications did not change between 2009 and 2015. The rate of cataract surgery and epiretinal membrane development did not change (p = 0.27; p = 0.09). The percent of re-detachment ranged from 6.2 to 16.5% within the observational period (p = 0.14). Conclusion: A shift toward PPV alone for primary RRD repair was observed during the 7-year observation. No decrease in functional outcome or increase of intra- and postoperative complications or decrease of primary and final anatomic success rate was observed following the change in surgical procedure.

Monitoring retinoschisis and non-acute retinal detachment by optical coherence tomography: morphologic aspects and clinical impact

To differentiate retinoschisis (RS) from non‐acute retinal detachment (naRD) in clinical routine using optical coherence tomography (OCT), describe unique morphological OCT characteristics and monitor disease progression.

SPECTRAL DOMAIN-OPTICAL COHERENCE TOMOGRAPHY IMAGE CONTRAST AND BACKGROUND COLOR SETTINGS INFLUENCE IDENTIFICATION OF RETINAL STRUCTURES.

Purpose: To evaluate image contrast and color setting on assessment of retinal structures and morphology in spectral-domain optical coherence tomography. Methods: Two hundred and forty-eight Spectralis spectral-domain optical coherence tomography B-scans of 62 patients were analyzed by 4 readers. B-scans were extracted in 4 settings: W + N = white background with black image at normal contrast 9; W + H = white background with black image at maximum contrast 16; B + N = black background with white image at normal contrast 12; B + H = black background with white image at maximum contrast 16. Readers analyzed the images to identify morphologic features. Interreader correlation was calculated. Differences between Fleiss-kappa correlation coefficients were examined using bootstrap method. Any setting with significantly higher correlation coefficient was deemed superior for evaluating specific features. Results: Correlation coefficients differed among settings. No single setting was superior for all respective spectral-domain optical coherence tomography parameters (P = 0.3773). Some variables showed no differences among settings. Hard exudates and subretinal fluid were best seen with B + H (&kgr; = 0.46, P = 0.0237 and &kgr; = 0.78, P = 0.002). Microaneurysms were best seen with W + N (&kgr; = 0.56, P = 0.025). Vitreomacular interface, enhanced transmission signal, and epiretinal membrane were best identified using all color/contrast settings together (&kgr; = 0.44, P = 0.042, &kgr; = 0.57, P = 0.01, and &kgr; = 0.62, P ⩽ 0.0001). Conclusion: Contrast and background affect the evaluation of retinal structures on spectral-domain optical coherence tomography images. No single setting was superior for all features, though certain changes were best seen with specific settings.