Efficacy of a Disease Management Program of a Tertiary Center and Ophthalmologic Practitioners for the Treatment of Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of the study was to examine real-world data of patients with neovascular age-related macular degeneration (nAMD) within a disease management program (DMP) treated with anti-VEGF. METHODS: A monocentric, retrospective chart review of 379 eyes of a local DMP was conducted at the Department of Ophthalmology, Kepler University Clinic Linz. Eyes were treated either with bevacizumab or aflibercept using a pro re nata scheme, consisting of 3 injections every 4 weeks in case of presence of disease activity. The observational period was up to 24 months. Disease activity was monitored by visual acuity (VA), clinical examination, and optical coherence tomography (OCT). For (re-)treatments, ophthalmologic practitioners referred patients directly to the intravitreal injection, avoiding redundant examinations. RESULTS: VA improved significantly for all patients after 2 months (logMAR 0.47 ± 0.36; p = 0.000) compared to baseline (0.55 ± 0.37), and for the aflibercept group for up to 6 months (0.36 ± 0.27; p = 0.018). After 12 months, VA remained stable without further significant improvement and decreased by 24 months compared to baseline. The median number of injections was 6 over the first 12 months and 4 in the second year. CONCLUSION: Data revealed the efficacy of a DMP for nAMD involving both ophthalmologic practitioners and a tertiary center. Avoiding redundant examinations increased the efficacy of a clinical setting.

Measuring optic nerve head perfusion to monitor glaucoma: a study on structure-function relationships using laser speckle flowgraphy.

PURPOSE: We aimed to describe the global and localized correlations among visual field (VF) sensitivity, optic nerve head (ONH) perfusion measured by laser speckle flowgraphy (LSFG) and neural structure measured by optical coherence tomography (OCT) in open-angle glaucoma (OAG) and to compare the floor effect for LSFG and OCT. METHODS: Cross-sectional, multicenter study including one eye each from fifty OAG patients (mean age 69.3 years; average VF mean deviation, MD, -8.5 dB, range -25.17 to 0.85 dB) and fifty-one controls. Patients underwent SITA standard 24-2 automated perimetry and measurement of ONH perfusion, peripapillary retinal nerve fibre layer thickness (RNFLT) and macular ganglion cell-inner plexiform layer thickness (GCIPLT). We tested the presence of a significant change (breakpoint) in the correlation slope with VF sensitivity to assess floor effect. RESULTS: The correlation between the LSFG parameter Mean All (MA) of the global disc area and MD (r = 0.56, p < 0.001) did not show a breakpoint, in contrast to the correlations between MD and OCT global parameters, which showed breakpoints at -8.53 and -4.05 dB for RNFLT and GCIPLT, respectively. Global and localized correlations with VF sensitivity were stronger for LSFG compared to OCT. In particular, LSFG outperformed OCT in the correlation with the central VF sector (r = 0.50, p < 0.001 and r = 0.06, p = 0.67 for MA and RNFLT, respectively). CONCLUSION: The global and sectoral correlations with VF sensitivity and the favourable floor effect compared to OCT indicate LSFG as a promising tool to monitor progression particularly in late-stage glaucoma. Further longitudinal studies are warranted.

A comparative study of various prism adaptation forms in the surgical management of esophoria.

PURPOSE: To evaluate the outcome in participants who underwent surgery for esophoria following one of three different methods of preoperative prism adaptation test (PAT). METHODS: This prospective, multicentre study was carried out at five eye departments from 2012 to 2019. 116 participants were included and allocated to three groups as per investigator choice: Group 1 (n = 55) had a short prism adaptation period ranging from 1 to 5 hours during their visit at the clinic. Group 2 (n = 36) underwent partial prism correction for at least 4 weeks before surgery. Group 3 (n = 25) underwent full prism correction for at least 4 weeks before surgery. Motoric success was determined by postoperative angle of deviation (AOD), and sensoric success was evaluated with Lang and Bagolini striated lens test. RESULTS: A significant increase (p < 0.001) in AOD after PAT was observed in all groups, with no significant difference between groups (distance: p = 0.22; near: p = 0.31). Motoric and sensoric success was comparable between groups 3 months (p = 0.52; p = 0.55) and 1 year (p = 0.53; p = 0.29) after surgery. Prolonged prism adaptation (n = 24) for more than 365 days was not associated with better results. CONCLUSION: Our study indicates that the postoperative result is independent from the duration and amount (partial or full correction) of prism adaptation before surgery at least up to one year of follow-up. Prolonged prism adaptation (>365 days) before surgery does not improve the results.

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.

A Swept source optical coherence tomography angiography study: Imaging artifacts and comparison of non-perfusion areas with fluorescein angiography in diabetic macular edema.

PURPOSE: Swept Source Optical coherence tomography angiography (SS-OCTA) is a novel technique to visualize perfusion and vascular changes like ischemia in patients with diabetic retinopathy. The aim of this study was to compare non-perfusion areas on conventional fluorescein angiography (FA) with those on SS-OCTA using detailed manual annotation in patients with diabetic macular edema (DME) and to evaluate possible artifacts caused by DME on SS-OCTA. METHODS: 27 eyes of 21 patients with DME were analyzed in this prospective, cross-sectional study; on all, standard ophthalmological examination, SS-OCTA and FA imaging were performed. Early-phase FA and SS-OCTA images were analyzed for capillary dropout and foveal avascular zone (FAZ) was measured on both modalities. Artifacts in SS-OCTA imaging caused by DME were marked and analyzed. RESULTS: The mean age of the patients was 62.6 ± 11.5 years. On FA the mean size of the annotated non-perfusion areas was 0.14 ± 0.31 mm2 whereas the mean size in SS-OCTA was 0.04 ± 0.13 mm2; areas marked on FA were statistically significantly larger than on SS-OCTA (p<0.01). Mean size of FAZs was similar between FA and OCTA images. (p = 0.91). Seven eyes (25.9 percent) showed imaging artifacts due to DME in SS-OCTA. CONCLUSION: SS-OCTA is a valid tool to analyze capillary perfusion status of patients with DME, although areas of non-perfusion were measured smaller than in conventional FA. More non-perfusion areas were found on SS-OCTA images. FAZ measurements were similar using the two modalities. However, SS-OCTA is prone to artifacts and therefore requires reviewing of imaging results: up to 25 percent of the analyzed eyes showed artifacts on OCTA, which occurred in the areas of diabetic macular edema and did not correspond to capillary drop out.

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

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.

Prospective comparison of apex-centered vs standard pupil-centered femtosecond laser-assisted capsulotomy in cataract surgery.

PURPOSE: To compare the lens tilt after apex-centered capsulotomy with standard pupil-centered capsulotomy. SETTING: Clinical practice. DESIGN: Prospective, randomized, investigator-masked trial. METHODS: This prospective, randomized, investigator masked study included 40 patients with age-related cataract scheduled for femtosecond laser-assisted cataract surgery (FLACS) in both eyes. The main outcome was the tilt of the intraocular lens (IOL), measured with the IOLMaster 700. RESULTS: The study enrolled 80 eyes of 40 patients. The mean distance from the center of the apex-centered capsulotomy to the pupil-centered capsulotomy was 175.8 ± 97.2 µm. The amount of IOL tilt was not significantly reduced with the new technique (P > .05). Tilt orientation was more stable in eyes treated with apex-centered capsulotomy. CONCLUSIONS: Centration of the capsulotomy on the lens apex in FLACS does not influence the amount of IOL tilt but the orientation stability. The clinical importance of this finding has to be further elucidated.

Differences in swept-source OCT angiography of the macular capillary network in high tension and normal tension glaucoma.

AIM OF THE STUDY: The purpose of the present study was to determine if swept-source optical coherence tomography angiography (OCTA) of the superficial plexus in the macular region can detect differences between high-tension open-angle glaucoma (HTG) and normal-tension glaucoma (NTG). MATERIALS AND METHODS: In this prospective study 60 eyes from 60 patients (40 HTG; 20 NTG) underwent fovea centred 3 × 3 mm cube macula OCTA imaging by a swept-source OCTA device (Plex Elite, Zeiss, Jena, Germany). Quantitative analysis of the vasculature at the superficial plexus was performed by assessing the Perfusion Density (PD), defined as the total area of perfused vasculature per unit area in a region of measurement, for each group, respectively. Besides, macular ganglion cell layer thickness and mean deviation from visual field testing was assessed and correlated with PD. RESULTS: Average superficial PD of the measured 3 × 3 mm field was comparable between HTG and NTG (P = .567). In both groups a significant relation of PD and age (HTG: r = -0.48, p = .002; NTG: r = -0.615; p = .004) was shown, indicating reduced PD with increasing age. For both groups a positive correlation between PD and mean deviation (MD) (HTG: r = 0.492, p = .003; NTG: r = 0.530, p = .029) as well as PD and GCL thickness was shown (r = 0.486, p = .002 vs. r = 0.389; p = .09). However, the latter did not reach statistical significance in the NTG group. CONCLUSION: PD at the central 3 mm around the fovea is comparable between HTG and NTG. Significant correlation with age and MD was shown in both groups.

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.

Patterns of morphologic alteration correlate with vision in diabetic macular oedema: a cross-sectional evaluation of patients using the SAVE II protocol.

PURPOSE: We sought to describe and evaluate patients with clinically significant diabetic macular oedema (CSME) according to the improved SAVE II protocol and correlate findings with visual acuity and systemic parameters in the outpatient clinic for DR (diabetic retinopathy) management. METHODS: This was a cross-sectional case series study of patients with CSME, regardless of prior treatment. Visual acuity testing was performed according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol. Optical coherence tomography (OCT) and fluorescence angiography (FA) were performed. All imaging data were evaluated according to an improved version of the SAVE grading protocol for CSME (SAVE II). The main outcome measures were SAVE II oedema types and best-corrected visual acuity. Additional parameters of a blood sample (fasting glucose, haemoglobin A1c, serum creatinine, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins) were taken. RESULTS: In total, 66 eyes of 66 patients were included. The mean age of the patients was 64.9 ± 8.2 years. Two eyes were classified as SAVE oedema type 1, 19 eyes as SAVE oedema type 2, 28 eyes as SAVE oedema type 3, and 28 eyes as SAVE oedema type 4, respectively. Central retinal thickness and laboratory parameters were not significantly different between the groups. There was a statistically significant difference in ETDRS visual acuity between the SAVE groups 2 and 4 (p < 0.001) with lower vision in group 4. There was no statistically significant difference between oedema types 2 and 3 (p = 0.065) and oedema types 3 and 4 (p = 0.13). CONCLUSION: There was a significant correlation between the four defined oedema types and visual acuity. Morphologic findings did not correlate with any of the evaluated blood parameters.

Aqueous humour cytokine changes during a loading phase of intravitreal ranibizumab or dexamethasone implant in diabetic macular oedema.

PURPOSE: To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes. METHODS: In a prospective, randomized, controlled, double-blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm-Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20. RESULTS: The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM-1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM-1) (weeks 2 and 8) and monocyte chemo-attractant protein 1 (MCP-1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time-points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 µm) compared with baseline (440 ± 144 µm) in the Lucentis group. CONCLUSION: The dexamethasone implant affected the aqueous cytokines and proteins MCP-1, sICAM-1, sVCAM-1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections.

Short-term effect on the ocular circulation induced by unilateral intravitreal injection of aflibercept in age-related maculopathy.

PURPOSE: Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the standard treatment for neovascular age-related macular degeneration (AMD). As VEGF is a physiological key player for regulating retinal vascular tone, questions have been raised whether the application of anti-VEGF 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 follow-up 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 short-term 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.

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.

[Testing and approach when non-organic visual loss is suspected]. / Prüfung und Vorgehen bei Verdacht auf nichtorganische Sehstörung.

Approximately 5% of the patients in the ophthalmological practice suffer from non-organic vision loss. In children non-organic vision loss has been observed from the age of 6 years. In order to be able to make a rapid diagnosis knowledge of the relevant clinical tests is decisive. If a patient shows signs of non-organic visual loss, diagnostic externalization of the visual function is crucial. Depending on the symptoms there are various tests, which can be used to differentiate between organic and non-organic disorders. For therapeutic and economic reasons an early diagnosis of a non-organic visual loss is crucial. Ophthalmologists need to differentiate between malingering and augmentation, where the patient is aware of the fraud and tries to gain personal benefit from it, and somatoform disorders. In the latter, a more sensitive approach is recommended.

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 < 0.01). No significant difference in the IOP was observed between the two groups at any follow-up (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.