Magdalena A. Wirth

Optical Coherence Tomography Angiography of the Foveal Avascular Zone in Retinal Vein Occlusion

Purpose: The aim of the study was to visualize and to quantify pathological foveal avascular zone (FAZ) alterations through optical coherence tomography angiography (OCT-A) in eyes with retinal vein occlusion (RVO) in comparison to the unaffected fellow eyes. Procedures: OCT-A was conducted with the Avanti® RTVue 100 XR system (Optovue Inc., Fremont, Calif., USA). The borders of the superficial vascular layer (SVL) were defined as 3 μm below the internal limiting membrane and 15 μm below the inner plexiform layer, and for the deep vascular layer (DVL) as 15 and 70 μm below the inner plexiform layer, respectively. The length of the horizontal, vertical and maximum FAZ was manually measured for the SVL and DVL in each eye. Additionally, the angle between the maximum FAZ diameter and the papillomacular plane was measured. Results: OCT-A depicted defects within the perifoveal vasculature in eyes with branch retinal vein occlusion (BRVO; n = 11) and central retinal vein occlusion (CRVO; n = 8). These resulted in an enlargement of the maximum FAZ diameter in eyes with RVO (n = 19) in comparison to the healthy fellow eyes (n = 19; 921 ± 213 vs. 724 ± 145 µm; p = 0.008). Furthermore, a significant correlation was found between best-corrected visual acuity (BCVA) and the maximum FAZ diameter in the DVL (Spearmans ρ = -0.423, p < 0.01). Lastly, in the eyes with RVO, the angle between the papillomacular plane and the maximum FAZ diameter was only in 21.05% (SVL) and 15.79% (DVL) of the cases at 0 ± 15 or 90 ± 15°, respectively. In healthy eyes, these angles (which putatively represent a regular FAZ configuration) were more prevalent (SVL 68.42 vs. 21.05%, p = 0.003; DVL 73.68 vs. 15.79%, p < 0.001). Conclusion: OCT-A shows morphological alterations of the FAZ in eyes with CRVO and BRVO. The correlation of the maximum FAZ diameter with BCVA suggests that these alterations are functionally relevant.

LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM: A Retrospective Multicenter Study.

Purpose: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. Methods: A retrospective multicenter study between 2003 and 2016 at three European sites, City Hospital Triemli Zurich, Switzerland (CHT), Zealand University Hospital Roskilde, Denmark (ZUH) and University Clinic Bern, Switzerland (UCB). Intravitreal injection (IVI) database of each department was reviewed. All anti-vascular endothelial growth factor injections were performed using a standardized sterile technique in an operation room. Injection protocols were similar between the three sites. No preinjection antibiotics were given. Postoperative antibiotics varied among sites. Results: A total of 134,701 intravitreal injections were performed at the 3 sites between 2003 and 2016. Ten cases of presumed endophthalmitis were documented: 4 in 50,721 at CHT (95% CI: 0.0071–0.0087%), 2 in 44,666 at ZUH (95% CI: 0.0039–0.0051%), and 4 in 39,314 at UCB (95% CI: 0.0092–0.011%). This results in one case in 13,470 intravitreal injections and a combined incidence of 0.0074% per injection (95% CI: 0.0070–0.0078%). Positive cultures were found in 4 out of 10 presumed endophthalmitis cases. Conclusion: The standardized sterile technique in an operation room with laminar airflow showed very low rates of endophthalmitis at three European sites.

Comparison of Progression Rate of Retinal Pigment Epithelium Loss in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab and Aflibercept

Purpose. Retinal pigment epithelium (RPE) loss in neovascular age-related macular degeneration (nAMD) seem to have a linear progression but might be influenced by the treatment. The purpose of the study is the comparison of RPE loss over three years in patients treated with intravitreal ranibizumab to patients who were switched to aflibercept. Methods. A retrospective analysis with 96 eyes switched to aflibercept was conducted. The progression rate of RPE loss was evaluated in patients who showed atrophy one year prior to switch (n = 17) or on switch date (n = 19). The RPE loss was evaluated by spectral domain optical coherence tomography (SD-OCT). Further, 22 eyes from patients treated with ranibizumab were compared. Results. The median yearly progression of RPE loss after square root transformation showed no significant difference in the year prior to switch compared to the year after switch (p = 0.854). In patients who received only ranibizumab, the median yearly progression of RPE loss was 0.15 mm/y, for aflibercept patients, 0.13 mm/y. This difference was not statistically significant (p = 0.172). Conclusions. There seems to be a linear progression rate of RPE loss in patients treated with ranibizumab as well as in patients with aflibercept. No significant increase of progression rate was found after switch to aflibercept.

Optical coherence tomography angiography in age-related macular degeneration: persistence of vascular network in quiescent choroidal neovascularization

T his retrospective study was designed to evaluate the characteristics of quiescent type 2 choroidal neovascular (CNV) lesions, as well as differences between active CNV [under current anti-vascular endothelial growth factor (anti-VEGF) treatment] and inactive CNV. Therefore, we analysed split-spectrum amplitude-decorrelation angiography (SSDA)-based optical coherence tomography (OCT) (Optovue RTVue XR Avanti) images of 12 eyes (n = 12, 6 versus 6) with age-related macular degeneration (AMD). Quiescent CNVs were defined by the absence of any activity sign, such as subretinal or intraretinal fluid, choroidal or retinal haemorrhage or an increasing size of pigment epithelial detachments after anti-VEGF treatment cessation in formerly treated CNV. Eyes with currently quiescentCNVhad receiveda totalmean of 14.4 (SD 8.56) anti-VEGF injections (ranibizumab or aflibercept) according to a treat and extend dosing regimen (Freund et al. 2015). No injections for at least 15 months prior study enrolment were administered. Agematched control eyes were chosen randomly from our database of patients under anti-VEGF therapy for AMD. The persistence of a pathologic vascular network was seen in all quiescent CNV lesions (Figs. 1,2). Inactive lesions were characterized by a main vessel trunk (mean diameter 20.4 1.8 lm) and an intralesional rarefication of capillaries.Nouniformpattern of persistent lesions was seen. The average dimensions of inactive lesions amounted to 262.5 9 246.1 lm ( 48.5 9 51.6) as measured in two perpendicular orientations. Active lesions measured 178.6 9 139.3 lm ( 65.3 9 60.6). Five of six active lesions were characterized by a peripheral halo (mean gap to normally vascularized tissue 14.3 5.3 lm) (Fig. 3). The majority of active lesions (five of six) were localized in the choroidal capillary layer [defined as 30 lm and 60 lm below the retinal pigment epithelium (RPE)] and the outer retina (defined as 70 lm below the inner plexiform layer (IPL) and 30 lmbelow theRPE) (Fig. 4), whereas inactive lesions were found only in choroidal capillary layers. In contrast to the frequent misperception that neovascular lesions regress after long-term anti-VEGF treatment (Do et al. 2012; Wang et al. 2016), our findings appear to imply the persistence of neovascular lesions in quiescent CNV. This observation may indicate that inactivity of CNV lesions, as observed by structural SD-OCT, is not necessarily accompanied by a regression and reduction in size of former active CNV. Regular anti-VEGF treatment over a certain period of time may lead to a higher level of vascular maturity resulting in quiescent, non-leaking lesions. Mature vessels are adequately covered by pericytes, less fenestrated and consequently not dependent on external VEGF. Mature pericytes supply their ‘own’ neighbouring vascular endothelial cells with VEGF (Furuya et al. 2005). The regression of mature vessels due to VEGF blockage is therefore no expectable corollary. This raises the question, whether exudative AMD requires a lifelong treatment? As a potential counterargument, it may be mentioned that an increasing atrophic area and/or the formation of a subretinal scar (occurring in advanced stages of all AMD forms) is accompanied by less VEGFproducing tissue. This may result in a natural cessation of leakage. Recently, R. Spaide described an abnormalization of vessels after long-term exposure to anti-VEGF agents. This abnormalization was characterized by larger vessel diameters and a reduced number of ‘fresh’ capillaries. Iatrogenic ‘pruning’ of sprouting vessels by anti-VEGF agents resulted in higher blood flow levels in the remaining vascular network, in turn giving rise to a higher risk of arteriogenesis (Spaide 2015). In

Branch Retinal Vein Occlusion – Update on Treatment Options

The advent of new pharmacotherapeutic options and diagnostic methods have led to a revolution in the management of branch retinal vein occlusion over the past few years. Despite the variety of treatment options, we are confronted with several questions: which drug should we use? Is switching between or combining treatment options beneficial? What is the recommended treatment regimen? When should we start treatment and for how long should we continue it? Should we still use retinal laser therapy? The wide range of possibilities and emerging treatment choices not only aids, but also challenges clinicians striving for evidence-based management.

Angio-OCT de la zona avascular foveal en ojos con oclusión venosa de la retina

Objetivo: El objetivo del estudio comprendía visualizar y cuantificar las alteraciones patológicas de la zona avascular foveal (ZAF) mediante angio-OCT en ojos con oclusión venosa de la retina (OVR) en comparación con el ojo contralateral sano. Procedimientos: La angio-OCT se llevó a cabo mediante el sistema Avanti® RTVue 100 XR (Optovue Inc., Fremont, Calif., EE. UU.). Los bordes de la capa vascular superficial (CVS) se definieron como 3 μm por debajo de la membrana limitante interna y 15 μm por debajo de la capa plexiforme interna y, para la capa vascular profunda (CVP), como 15 y 70 μm por debajo de la membrana limitante interna y de la capa plexiforme interna, respectivamente. La longitud de la ZAF horizontal, vertical y máxima de la CVS y la CVP en cada ojo se midió de forma manual. Además, se midió el ángulo entre el diámetro máximo de la ZAF y el plano papilomacular. Resultados: La angio-OCT representó los defectos dentro de la vasculatura en el área perifoveal en ojos con oclusión de rama venosa de la retina (ORVR; n = 11) y con oclusión de la vena central de la retina (OVCR; n = 8). Esto resultó en un crecimiento del diámetro máximo de la ZAF en ojos con OVR (n = 19) en comparación con el ojo contralateral (n = 19; 921 ± 213 frente a 724 ± 145 µm; p = 0,008). Además, se observó una correlación significativa entre la mejor agudeza visual corregida (MAVC) y el diámetro máximo de la ZAF en la CVP (ρ de Spearman = -0,423, p < 0,01). Por último, en los ojos con OVR, el ángulo entre el plano papilomacular y el diámetro máximo de la ZAF se dio tan solo en el 21,05% (CVS) y en el 15,79% (CVP) de los casos a 0 ± 15 ó 90 ± 15°, respectivamente. En ojos sanos, estos ángulos (que supuestamente representan una configuración de la ZAF regular) fueron más prevalentes (CVS 68,42 frente a 21,05%, p = 0,003; CVP 73,68 frente a 15,79%, p < 0,001). Conclusiones: La angio-OCT muestra alteraciones morfológicas de la ZAF en ojos con OVCR y ORVR. La correlación del diámetro máximo de la ZAF con la MAVC indica que estas alteraciones resultan funcionalmente relevantes.