Effects of three intravitreal injections of aflibercept on the ocular circulation in eyes with age-related maculopathy

Aims: To investigate changes in ocular perfusion following three consecutive intravitreal injections with aflibercept for treatment of neovascular age-related macular degeneration (nAMD). Methods The study included 20 eyes from 20 Caucasian patients with unilateral nAMD and 20 fellow eyes. All nAMD eyes were treated with standard intravitreal injection of aflibercept (IVA;2 mg). Measurements of ocular perfusion at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). Measurements were conducted at baseline, 1 week after the first injection, at the time point of the second and third injection as well as 1 month after the third injection. Results In treated eyes, mean blur rate (the main output parameter of LSFG) in the ONH microvasculature and in the choroid was significantly reduced 1 week after the first IVA treatment. The effect persisted throughout the entire follow-up period (p<0.001). No change in ocular perfusion was observed in fellow eyes. Conclusions: IVA for treatment of nAMD leads to a reduction in perfusion of the ONH and the choroid in the treated eye with no apparent effect on the fellow eye

Semiautomated SD-OCT Measurements of Corneal Sublayer Thickness in Normal and Post-SMILE Eyes

Purpose:To test the reliability of a novel algorithm for measuring corneal epithelial thickness (ET) and stromal thickness of normal eyes and post-small incision lenticule extraction (SMILE) corneas with spectral-domain optical coherence tomography.Methods:In this prospective observational study, a customized semiautomated software algorithm was developed and applied to measure corneal ET and stromal thickness along the horizontal corneal meridian. Measurements were performed by 2 examiners in a randomized fashion on a sample of 40 eyes with previous SMILE for treatment of myopia and a control group composed of 40 normal eyes. The intrauser repeatability and interuser reproducibility were analyzed by calculating typical indices including the coefficient of variation and intraclass correlation coefficient. Corneal sublayer thickness profiles were compared between normal and post-SMILE eyes.Results:In both groups, coefficients of variation were 3.2% or lower and intraclass correlation coefficients were 0.929 or higher indicating excellent reliability of the measurement method. Central ET was on an average 6 m greater in post-SMILE corneas (58.8 5.4 m) compared with normal eyes (52.8 +/- 4.0 m), with P < 0.01. Also, there was greater interindividual variability in ET in post-SMILE corneas and their horizontal epithelial profile seemed to show a lenticular appearance.Conclusions:Highly favorable indices of measurement reliability were achieved for this novel method of measuring corneal sublayer pachymetry not only in normal eyes but also in eyes with previous SMILE. The corneal ET profile was significantly altered in post-SMILE eyes compared with normal corneas

Effectiveness of Selective Laser Trabeculoplasty and analysis of factors with possible influence on it

Aktuell liegt der einzige evidente Therapieansatz beim Offenwinkelglaukom in der Senkung des Augeninnendrucks. Neben der medikamentösen und chirurgischen Therapie gilt die Selektive Lasertrabekuloplastik (SLT) als komplikationsarme Option, um dies zu erreichen. In dieser retrospektiven Studie wurde die Effektivität der SLT überprüft und prognostisch relevante Faktoren darauf untersucht. Es wurden 130 Augen (90 Patienten) analysiert. Der Augeninnendruck war bis zu ein Jahr nach der Behandlung signifikant gesenkt. Folgende Variablen zeigten einen signifikant positiven Einfluss auf das Ausmaß der Drucksenkung: hohes Ausgangsdruck-Niveau, geringe Hornhautdicke und hohe Gesamtenergie. Der Augeninnendruck war nur bei Augen mit Pigmentierungsgrad 1 und 2 signifikant gesenkt. Bei der medikamentösen Vorbehandlung zeigten nur Augen, die mit Nicht-Prostaglandin-Augentropfen behandelt worden waren, und Augen, die mit einer Kombinationstherapie aus Prostaglandinanaloga und anderen Wirkstoffen behandelt worden waren, eine signifikante Drucksenkung.Reduction of intraocular pressure (IOP) is still the only evidence-based treatment option in glaucoma therapy. Besides pharmacological and surgical approaches, Selective Lasertrabeculoplasty (SLT) is a safe option to achieve this objective. The aim of this retrospective study was to validate SLT’s effectiveness and identify potential influencing factors. A total of 130 eyes (90 patients) with primary open angle glaucoma were analysed IOP was significantly reduced until one year post-procedure. The following parameters showed significant positive influence on pressure reduction: high baseline IOP, low CCT and high energy dosage. IOP was lowered significantly only in eyes with low to moderate pigmentation degree. Regarding the medical pre- treatment, only eyes pre-treated with non-prostaglandin analogues and eyes pre-treated with a combination of prostaglandin analogues (PGA) and non- prostaglandin analogues showed a significant pressure reduction

Vascular Aspects in Glaucoma: From Pathogenesis to Therapeutic Approaches

Glaucomatous optic neuropathies have been regarded as diseases caused by high intraocular pressure for a long time, despite the concept of vascular glaucoma dating back to von Graefe in 1854. Since then, a tremendous amount of knowledge about the ocular vasculature has been gained; cohort studies have established new vascular risk factors for glaucoma as well as identifying protective measures acting on blood vessels. The knowledge about the physiology and pathophysiology of the choroidal, retinal, as well as ciliary and episcleral circulation has also advanced. Only recently have novel drugs based on that knowledge been approved for clinical use, with more to follow. This review provides an overview of the current vascular concepts in glaucoma, ranging from novel pathogenesis insights to promising therapeutic approaches, covering the supply of the optic nerve head as well as the aqueous humor production and drainage system

Laser speckle flowgraphy derived characteristics of optic nerve head perfusion in normal tension glaucoma and healthy individuals : a Pilot study

The purpose of this prospective, case control study was to investigate the differences in optic nerve head blood flow measured with Laser Speckle Flowgraphy (LSFG) between Caucasian patients with normal tension glaucoma and healthy subjects. It included 20 eyes from 20 Caucasian patients with diagnosis of normal tension glaucoma and 20 eyes from age- and sex-matched healthy individuals. In the glaucoma group the antiglaucomatous therapy was paused 3 weeks prior to the investigations. Measurement of optic nerve head blood flow was performed with LSFG. The mean blur rate was obtained for different vascular compartments of the optic nerve head. Parameters for the characterization of pulse-waveform of the mean blur rate were calculated. It was shown that the mean blur rate was significantly lower in the glaucoma group compared to the control group (P < 0.001). The significant differences in the pulse-waveform parameters blow out time (P=0.028) and flow acceleration time index (P < 0.001) indicate a flatter curve in NTG patients. In conclusion, LSFG can detect differences in optic nerve head blood flow between eyes with normal tension glaucoma and healthy eyes.Published versio

Differences in optic nerve head blood flow regulation in normal tension glaucoma patients and healthy controls as assessed with laser speckle flowgraphy during the water drinking test

Précis: Optic nerve head (ONH) perfusion was not significantly altered in subjects with normal tension glaucoma (NTG) nor in healthy individuals after performing the water drinking test (WDT), because of its limited effect on ocular perfusion pressure (OPP). Purpose: ONH blood flow can be maintained stable in healthy individuals because of a physiological phenomenon called autoregulation. Impairment of autoregulation has been shown especially under condition of NTG. The purpose of this study was to investigate the ONH blood flow autoregulation in patients with NTG by influencing the OPP with the WDT. Methods: The study included 9 eyes from 9 white patients with a diagnosis of NTG and 9 eyes from age-matched and sex-matched healthy individuals. In the glaucoma group, the antiglaucomatous therapy was paused 3 weeks before the investigations. Measurements of ONH blood flow were performed with laser speckle flowgraphy. After baseline measurements, individuals ingested 800 mL of water in <5 minutes. Measurements were repeated after 15, 30, and 45 minutes. Results: The water ingestion led to a significant rise in intraocular pressure (P<0.001) but also mean arterial pressure (P<0.001) in both groups. This resulted in stable OPP (P=0.051) with no significant difference between the groups (P=0.43). ONH blood flow remained stable over time in both groups (P=0.719). No significant interaction of time and group was shown for all parameters. Conclusions: Our findings show that the WDT does not significantly influence the OPP and therefore has to be considered inferior to other methods used to assess blood flow autoregulation

Shortterm effect on the ocular circulation induced by unilateral intravitreal injection of aflibercept in agerelated maculopathy

Purpose: Intravitreal injection of antivascular endothelial growth factor (antiVEGF) is the standard treatment for neovascular agerelated macular degeneration (AMD). As VEGF is a physiological key player for regulating retinal vascular tone, questions have been raised whether the application of antiVEGF could induce alterations in ocular perfusion. Methods: The study included 20 eyes from 20 Caucasian patients with unilateral neovascular AMD and 20 fellow eyes. All eyes were treated with standard intravitreal injection of aflibercept (IVA). Measurements of blood flow at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). The intraocular pressure (IOP), systolic and diastolic blood pressure, heart rate, mean arterial pressure (MAP) and ocular perfusion pressure (OPP) were analysed. Measurements were performed at baseline and repeated immediately after the injection and 30 and 45 min later. Results: Mean time between injection of aflibercept and first followup was 8:56 4:25 min. The injection led to significant rise in IOP. In the injected eyes, mean blur rate (MBR, i.e. a relative measure of perfusion and the main outcome parameter of LSFG) within the major vessels of the ONH as well as at the entire ONH region decreased significantly (p < 0.001). No change in MBR was observed in the fellow eye. Choroidal blood flow was maintained stable in both eyes. Conclusion: Intravitreal injection of aflibercept (IVA) led to a shortterm reduction in perfusion only in the treated eye. This was independent from IOP, indicating a direct pharmacological effect. No changes in choroidal perfusion were observed during the first 45 min after the injection.(VLID)360086

Comparison of deep sclerokeratodissection, a new variant of nonpenetrating glaucoma surgery, with deep sclerectomy

Purpose: The aim of this study was to evaluate the safety and efficacy of deep sclerokeratodissection (DSKD), a new nonpenetrating technique in glaucoma surgery. Materials and Methods: Retrospective comparison between patients treated with DSKS or deep sclerectomy (DS) between 2013 and 2014. In DSKD, the first and only flap is dissected directly into clear cornea with unroofing Schlemm's canal. Beside routine clinical follow-up (visual acuity, intraocular pressure [IOP] readings, slit lamp and fundus examination), postoperative ultrasound biomicroscopy (UBM) investigation and quality of life (QoL) assessment were performed. Statistically significant differences were determined by parametric or nonparametric tests, depending on normality. Results: Twelve (38.7%) DSKDs and 19 (61.3%) conventional DS' were included in this analysis. IOP decreased significantly from 21.5 ± 9.2 mmHg to 6.2 ± 5.4 mmHg on day 1, 13.4 ± 7.7 at 1 month, 12.0 ± 4.1 at 3 months, 12.5 ± 3.1 mmHg at 6 months, and 13.4 ± 4.3 mmHg at 12 months (P 0.1). There was no significant difference in intra- and post-operative complications, the morphology of the surgical site in the UBM as well as in the QoL assessment. Conclusion: The results indicate that DSKD is a safe and efficient new variant of nonpenetrating glaucoma surgery. IOP can be lowered as effectively compared to conventional DS, with a similarly low rate of complications. Further reports are necessary to confirm these results

Early alterations in retinal microvasculature on swept-source optical coherence tomography angiography in acute central serous chorioretinopathy

Abstract The purpose of the study was to evaluate the retinal blood flow in patients with acute central serous chorioretinopathy (CSC) over an observational period of 1 month using swept-source optical coherence tomography (SS-OCTA), focusing especially on changes in the area of subretinal fluid (A-SRF). We correlated these findings with conventional indocyanine green angiography (ICGA). ICGA and SS-OCTA images were collected and analyzed of 12 eyes of 12 patients. The A-SRF was annotated and a qualitative analysis of choriocapillaris, the vessel density (VD) and perfusion density (PD) of the retinal superficial capillary plexus (SCP) and the deep capillary plexus (DCP) was performed in A-SRF and the unaffected remaining area (RA). The VD and PD in the DCP were statistically significantly lower in A-SRF than in the RA at baseline. (VD: p = 0.014; PD: p = 0.036). After 1 month, there was a statistically significant difference in the VD and PD of the DCP (VD: p = 0.015; PD: p = 0.014), and for the PD of the SCP between the A-SRF and the RA (p = 0.015), with lower values in the A-SRF. We found low perfused areas in choriocapillaris corresponding to hypofluorescent areas on ICGA. In conclusion there is a difference in VD and VD of the DCP in the area of SRF in acute CSC. These alterations may lead to a chronic change in the microvasculature and potentially to morphological changes

Assessment of choroidal neovascularization perfusion: a pilot study with laser speckle flowgraphy

Purpose: The purpose of this study was to quantify perfusion in the area of choroidal neovascularization (CNV) using laser speckle flowgraphy (LSFG) before and after intravitreal anti-vascular endothelial growth factor (VEGF) injection. Methods: Retrospective case series. Fifteen eyes of 15 patients with treatment-naïve CNV due to age-related macular degeneration (AMD) and with available LSFG images were included. The main outcomewas themean blur rate (MBR) quantified as ameasure of perfusion within the CNV area observed on indocyanine green angiography. Twelve patients had available longitudinal data until one month after the injection, used to evaluate changes in perfusion, central macular thickness (CMT), visual acuity, and ocular perfusion pressure. Reproducibility of LSFG measurements was investigated at each time point from two images taken within five minutes. Results: Intraclass correlation coefficients for LSFG measurements were higher than 0.8 indicating excellent reproducibility. There was a significant decrease in perfusion after oneweek (-26.4±14.4%; P=0.027),whereas, after onemonth, perfusion was no longer significantly different from baseline (P = 0.121). CMT showed a progressive decrease over the follow-up period. Changes in perfusion were strongly correlated with changes in CMT after one week, but not thereafter. Conclusions: This pilot study suggests a method to select a region in the CNV area to quantify perfusion using LSFG. MBR could represent a parameter possibly related to regrowth of the CNV after anti-VEGF treatment. Large-scale studies are needed to assess the usefulness of LSFG in defining re-treatment criteria for neovascular AMD