Christian Pruente

Management of neovascular age-related macular degeneration.

Neovascular age-related macular degeneration (AMD) is becoming an increasing socio-medical problem as the proportion of the aged population is continuously increasing. However, new insights in the pathogenesis of the disease offer the opportunity to develop targeted therapies that attack the disease process more successfully than ever. This review article will focus on summarizing the actual options in the management of neovascular AMD and provide a short overview about recent therapeutic options in clinical and preclinical evaluation. The recent development of anti-VEGF substances for use in clinical routine has markedly improved the prognosis of patients with neovascular AMD. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF), for the first time in the history of AMD treatments, results in a significant increase in visual acuity in patients with neovascular AMD. Overall, anti-angiogenic approaches provide vision maintenance in over 90% and substantial improvement in 25-40% of patients. The combination with occlusive therapies like photodynamic therapy (PDT) potentially offers a reduction of re-treatment frequency and long-term maintenance of the treatment benefit. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. Nevertheless, the growing number of novel therapeutic options will have to provide proof of concept in randomized controlled clinical trials, a major challenge in view of the rapidly evolving field. For those therapies, which are already in clinical use, reasonable diagnostic tools for follow-up need to be developed, as the burden of continuous clinical monitoring of all patients and all indications is significant for patients and doctors. Ultimately, economic issues will be the limiting factor for the clinical availability of different treatment options.

Response of Retinal Vessels and Retrobulbar Hemodynamics to Intravitreal Anti-VEGF Treatment in Eyes with Branch Retinal Vein Occlusion

PURPOSE To investigate whether intravitreal ranibizumab (0.05 mL) treatment affects retinal vessel diameters and retrobulbar blood velocities in patients with acute branch retinal vein occlusion (BRVO). METHODS Thirty patients with clinically significant macular edema secondary to BRVO were included. The duration of the study was three months. Patients were studied before and one week, one month, two months, and three months after the first ranibizumab injection. Depending on the clinical requirements, up to three ranibizumab injections were administered. Retinal vessel diameters were measured using a retinal vessel analyzer. Flow velocities in the retrobulbar central retinal artery were measured using color doppler imaging. Best-corrected visual acuity was assessed using ETDRS charts. Measurements were done in the affected as well as in the contralateral eye. RESULTS Three patients were lost for follow up. In the remaining 27 patients, significant vasoconstriction was observed in retinal veins (P < 0.001 versus baseline) and in retinal arteries (P = 0.001 versus baseline) of the affected eyes. In addition, a significant reduction in flow velocities was observed in the BRVO eyes over time (peak systolic velocity: P = 0.003, end diastolic velocity: P = 0.003). The reduction in retinal vessel diameters and flow velocities did not correlate with changes in visual acuity or number of re-treatments. In the contralateral eyes no change in retinal blood flow parameters was seen. CONCLUSIONS BRVO is an ischemic retinal disease. Given that ranibizumab treatment reduces retinal perfusion in these eyes the potential long-term effects of this vasoconstriction need to be considered.

Time course of morphologic effects on different retinal compartments after ranibizumab therapy in age-related macular degeneration

PURPOSE To analyze the effect of ranibizumab therapy on retinal and subretinal compartments in age-related macular degeneration and to compare the time course of compartment specific effects to visual function. DESIGN Prospective noncomparative case series. PARTICIPANTS Fourteen patients with changes in 3 major compartments owing to neovascular age-related macular degeneration. METHODS Standard treatment with 3 monthly doses of intravitreal ranibizumab was performed. Eyes were examined at baseline and weeks 1, 4, and 12 using a standardized protocol. Manual segmentation was applied to all 128 B-scans contained in a macular raster scan (MRS). MAIN OUTCOME MEASURES Morphology and time course of different retinal and subretinal compartments. RESULTS High-definition optical coherence tomography and manual segmentation allowed for precise identification of volumes within individual compartments. All morphologic parameters responded positively to therapy, but demonstrated a specific time course. Subretinal fluid was identified as the most relevant factor for visual function, whereas changes in retinal and subpigment epithelial volumes did not correlate with the time course of functional rehabilitation. CONCLUSION Analysis of MRS identified a characteristic impact of therapy on retinal and subretinal morphology.

Randomised clinical trial of intravitreal Avastin vs photodynamic therapy and intravitreal triamcinolone: long-term results

PurposeTo compare 1-year functional and anatomic outcomes of intravitreal bevacizumab (IVB) and photodynamic therapy plus intravitreal triamcinolone (PDT+IVTA) combination in patients with neovascular age-related macular degeneration (AMD).MethodsIn this prospective, randomised, controlled clinical trial, 28 patients were included. All patients were randomised 1 : 1 to 0.04 ml/1 mg of IVB or PDT plus same day 0.1 ml/4 mg IVTA (PDT+IVTA). Follow-up examinations were performed in monthly intervals in IVB group and every 3 months in PDT+IVTA group. Main outcomes were change in mean visual acuity (VA), mean central retinal thickness (CRT) and the mean number of treatments.ResultsAt month 12, mean VA improved to a 1.5-line gain in IVB group, and lost three letters in PDT+IVTA group (P=0.02). Mean CRT was reduced from 357 μm at baseline to 244 μm at month 12 in IVB group and from 326 μm to 254 μm, respectively, in PDT+IVTA group (P=0.8). The mean number of treatments was 6.8 in the IVB group vs1.9 in the PDT+IVTA group. No significant local or systemic safety concerns were detected during follow-up time.ConclusionsPatients treated with IVB showed a significant better VA outcome compared with the PDT+IVTA group despite the fact that both modalities showed equal potency in reducing CRT during a 12-month period.

Identification of Optical Density Ratios in Subretinal Fluid as a Clinically Relevant Biomarker in Exudative Macular Disease

PURPOSE To investigate the potential role of optical density ratios (ODRs) obtained from subretinal fluid analysis in exudative macular disease and to identify the predictive role of ODRs under therapy in comparison to conventional morphometric measurements (CMMs). METHODS Fifteen patients with neovascular age-related macular degeneration (nAMD) and 15 with acute central serous chorioretinopathy (CSC) were included in this prospective comparative and interventional case series. High-definition optical coherence tomography (SD-OCT) was performed according to a standardized protocol. nAMD patients received a standard treatment consisting of three monthly doses of intravitreous ranibizumab. Best corrected visual acuity (BCVA) was assessed at baseline (BSL) and weeks 2, 4, and 12. SD-OCT parameters were compared between CSC and nAMD at baseline. Predictive factors for functional recovery under ranibizumab treatment were identified in patients with nAMD. RESULTS ODR showed highly significant differences between CSC and nAMD, whereas it was not possible to differentiate between these diseases on the basis of CMM. During follow-up, CMM correlated with BCVA at BSL only, whereas ODR showed a significant correlation with BCVA at week 4 and 12 during antiangiogenic therapy. CONCLUSIONS Results suggest that CMM may correlate with BCVA at BSL, but has limited predictive value regarding recovery of visual function. Most interesting, ODR correlated with BCVA under therapy and was the only parameter that was pathognomic for nAMD in contrast to CSC in this study. ODR may reflect the status of the blood-retina barrier and may be used for pathophysiologic differentiation and prognostic purposes in exudative macular disease.

Linguatula serrata Tongue Worm in Human Eye,Austria

Linguatula serrata, the so-called tongue worm, is a worm-like, bloodsucking parasite belonging to the Pentastomida group. Infections with L. serrata tongue worms are rare in Europe. We describe a case of ocular linguatulosis in central Europe and provide molecular data on L. serrata tongue worms.

Correlation of High-Definition Optical Coherence Tomography and Fluorescein Angiography Imaging in Neovascular Macular Degeneration

PURPOSE To correlate the morphologic characteristics of choroidal neovascular lesions (CNV) in age-related macular degeneration (AMD) using raster scanning high-definition optical coherence tomography (HD-OCT) and conventional fluorescein angiography (FA). METHODS In this comparative clinical study, 37 consecutive patients with classic, minimally classic, or occult CNV; 13 patients with early AMD; and 10 age-matched healthy individuals were included. HD-OCT imaging (Topcon, Tokyo, Japan) and FA (scanning retinal ophthalmoscope; HRA2; Heidelberg Engineering, Dossenheim, Germany) were performed after a complete standardized ophthalmic examination. Only one eye of each patient was included in the study. A point-to-point correlation between HD-OCT and FA images was performed. Early and late FA images at defined locations were correlated with OCT measurements, including 3D maps, 2D single scans, a thickness linear graph, and the 3D retinal pigment epithelium (RPE) segmentation. RESULTS With HD-OCT imaging used to delineate the lesion morphology, early AMD was detected as having a normal foveal contour and minimal alteration in the macular area; classic CNV as a well-defined lesion with steep margins and a craterlike configuration, occult CNV as an ill-defined, flat lesion with a convex surface; and minimally classic CNV as having classic and occult components. FA-OCT overlay images provided a significant correlation between FA patterns and OCT features such as retinal thickness (RT). CONCLUSIONS 3D-OCT provided realistic anatomic maps of the retina, RPE, and RT in patients with AMD. Discrimination between the predominant CNV lesion types was achieved, and their precise shape was identified, together with information about the lesions localization and leakage activity.

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.

Topographic angiography and optical coherence tomography: a correlation of imaging characteristics.

Purpose Topographic angiography (TAG) using confocal scanning laser angiography and optical coherence tomography (OCT) are new imaging modalities that have been introduced during recent years. OCT and TAG imaging were compared to specify the characteristics of each imaging modality. Methods TAG using fluorescein angiography (FA) provides a three-dimensional profile of the vascular structures based on the analysis of a set of 32 confocal images over a depth of 4 mm. OCT provides cross-sectional images of the neurosensory retina and the retinal pigment epithelium-choriocapillary complex (RPE-CC). The authors compared and evaluated both modalities in 10 patients with predominantly classic choroidal neovascularization (CNV), 10 patients with serous pigment epithelial detachment (PED), and 10 patients with geographic RPE atrophy, all secondary to age-related macular degeneration (ARMD). Results In patients with classic CNV, TAG detected neovascular structures and delineated their configuration. In PEDs pooling of extravascular fluid is demonstrated, and in geographic RPE atrophy TAG showed reduced choroidal perfusion. Classic CNV was demonstrated by OCT as a hyperreflective band at the level of the RPE-CC, and PED showed a dome-shaped RPE detachment. In geographic RPE atrophy, OCT imaged loss of the RPE band and had an increased depth resolution. Conclusions TAG and OCT are useful imaging modalities in the evaluation of ARMD cases. TAG visualizes the vascular configuration and dynamic perfusion and leakage changes. OCT is able to document intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV. Both modalities may provide further valuable insight into ARMD pathogenesis, enhance diagnostic quality, and improve the assessment of therapeutic effects.

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.