FACE-Q Patient Report-Assisted Subjective and Objective Evaluation of Blepharoplasty Outcomes Using Two Different Suturing Techniques: A Randomized and Patient-Blinded Pilot Study.

BACKGROUND: /Objectives To compare two suturing techniques in patients undergoing upper eyelid blepharoplasty by using the FACE-Q™ Eye Module questionnaire to assess patient-reported outcomes and by blinded Likert-scale gradings of two experienced surgeons. METHODS: 90 patients undergoing bilateral blepharoplasty were randomly assigned to a suturing technique (running cutaneous or subcuticular closure) using Prolene 6.0. Patients completed the FACE-Q eye module questionnaire before surgery and 7 days and 3 months after surgery. Further, two trained oculoplastic surgeons assessed the outcome. FACE-Q ratings were RASCH-transformed, and linear models were fitted for appraisal and satisfaction results. Intraclass correlation coefficient (ICC) was calculated to assess the surgeons' rating agreement. RESULTS: There was no statistically significantly difference in patients' FACE-Q self-assessments regarding satisfaction with eyes and appraisal of upper eyelids between the two suturing techniques investigated, both 7 days and 3 months after blepharoplasty. The more content the patient at baseline, the less the increase in satisfaction after 3 months. There was good agreement between blinded graders in outcome assessment expressed by an ICC of 0.86. Dry-eye symptoms increased after surgery, independent of the suturing technique, patient age or sex. CONCLUSION: In conclusion, this study shows that post operative patient satisfaction is independent of suturing technique, but depends on baseline FACE-Q reports. These findings are valuable in patient communication and selection and are in line with observer-based assessments. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

LONGITUDINAL CHANGES IN QUANTITATIVE AUTOFLUORESCENCE DURING PROGRESSION FROM INTERMEDIATE TO LATE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To prospectively investigate the development of quantitative autofluorescence (qAF) during progression from intermediate to late age-related macular degeneration (AMD). METHODS: Quantitative autofluorescence images from patients with intermediate AMD were acquired every three months with a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) using a built-in autofluorescence reference. The association between changes in longitudinal qAF and progression toward late AMD was assessed using Cox regression models with time-dependent covariates. RESULTS: One hundred and twenty-one eyes of 71 patients were included, and 653 qAF images were acquired. Twenty-one eyes of 17 patients converted to late AMD (median follow-up: 21 months; 12 eyes: atrophic AMD; nine eyes: neovascular AMD). The converting patients' mean age was 74.6 ± 4.4 years. Eleven eyes in the converting group (52.4%) were pseudophakic. The presence of an intraocular lens did not affect the qAF regression slopes (P > 0.05). The median change for atrophic AMD was -2.34 qAF units/3 months and 0.78 qAF units/3 months for neovascular AMD. A stronger decline in qAF was significantly associated with an increased risk of developing atrophic AMD (hazard ratio = 1.022, P < 0.001). This association, however, was not present in the group progressing toward neovascular AMD (hazard ratio = 1.001, P = 0.875). CONCLUSION: The qAF signal declines with progression to atrophy, contrary to developing neovascularization. Quantitative autofluorescence may allow identification of patients at risk of progressing to late AMD and benefits individualized patient care in intermediate AMD.

Three-dimensional assessment of para- and perifoveal photoreceptor densities and the impact of meridians and age in healthy eyes with adaptive-optics optical coherence tomography (AO-OCT).

An adaptive optics optical coherence tomography (AO-OCT) system is used to assess sixty healthy eyes of thirty subjects (age 22 to 75) to evaluate how the outer retinal layers, foveal eccentricity and age effect the mean cone density. The cone mosaics of different retinal planes (the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST), and the full en-face plane (FEF)) at four main meridians (superior, nasal, inferior, temporal) and para- and perifoveal eccentricities (ecc 2.5° and 6.5°) were analyzed quantitatively. The mean overall cone density was 19,892/mm2 at ecc 2.5° and 13,323/mm2 at ecc 6.5°. A significant impact on cone density was found for eccentricity (up to 6,700/mm2 between ecc 2.5° and 6.5°), meridian (up to 3,700/mm2 between nasal and superior meridian) and layer (up to 1,400/mm2 between FEF and IS/OS). Age showed only a weak negative effect. These factors as well as inter-individual variability have to be taken into account when comparing cone density measurements between healthy and pathologically changed eyes, as their combined effect on density can easily exceed several thousand cones per mm2 even in parafoveal regions.

INVESTIGATING A GROWTH PREDICTION MODEL IN ADVANCED AGE-RELATED MACULAR DEGENERATION WITH SOLITARY GEOGRAPHIC ATROPHY USING QUANTITATIVE AUTOFLUORESCENCE.

PURPOSE: To investigate geographic atrophy (GA) progression using quantitative autofluorescence (qAF) in eyes with solitary GA. METHODS: Forty-three eyes of 26 patients (age 79.7 ± 7.2 years; 28 women; 16 pseudophakic) underwent spectral-domain optical coherence tomography and qAF imaging at baseline and after 12 months. The junctional zone (AJZ) and a nonaffected 300-µm-wide control area (AC) were delineated on spectral-domain optical coherence tomography scans and transferred to the qAF image. Linear mixed models were calculated to investigate the association between GA progression and qAF, age, and baseline GA area. Mixed model analyses of variance were used to investigate differences in qAF between areas. RESULTS: Quantitative autofluorescence of the three inferior sections of both the AJZ (P = 0.028; P = 0.014 and P = 0.032) and the AC (P = 0.043; P = 0.02 and P = 0.028) were significantly associated with GA progression after 12 months. However, qAF measurements were not associated with GA progression in the overall model (P > 0.05). Mean qAF was significantly lower in the AJZ and growth area (AG12) than in the AC (both P ≤ 0.001). CONCLUSION: The authors report a statistically significant association between GA growth area and qAF measurements at specific retinal locations and a significant difference in qAF between the GA border and unaffected areas outside the lesion. Quantitative autofluorescence measurements may be limitedly useful for predicting GA progression.

SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY, FLUORESCEIN ANGIOGRAPHY, AND INDOCYANINE GREEN ANGIOGRAPHY COMPARISONS REVISITED: Using a Novel Deep-Learning-Assisted Approach for Image Registration.

PURPOSE: To compare area measurements between swept source optical coherence tomography angiography (SSOCTA), fluorescein angiography (FA), and indocyanine green angiography (ICGA) after applying a novel deep-learning-assisted algorithm for accurate image registration. METHODS: We applied an algorithm for the segmentation of blood vessels in FA, ICGA, and SSOCTA images of 24 eyes with treatment-naive neovascular age-related macular degeneration. We trained a model based on U-Net and Mask R-CNN for each imaging modality using vessel annotations and junctions to estimate scaling, translation, and rotation. For fine-tuning of the registration, vessels and the elastix framework were used. Area, perimeter, and circularity measurements were performed manually using ImageJ. RESULTS: Choroidal neovascularization lesion size, perimeter, and circularity delineations showed no significant difference between SSOCTA and ICGA (all P > 0.05). Choroidal neovascularization area showed excellent correlation between SSOCTA and ICGA (r = 0.992) and a Bland-Altman bias of -0.10 ± 0.24 mm. There was no significant difference in foveal avascular zone size between SSOCTA and FA (P = 0.96) and an extremely small bias of 0.0004 ± 0.04 mm and excellent correlation (r = 0.933). Foveal avascular zone perimeter was not significantly different, but foveal avascular zone circularity was significantly different (P = 0.047), indicating that some small cavities or gaps may be missed leading to higher circularity values representing a more round-shaped foveal avascular zone in FA. CONCLUSION: We found no statistically significant differences between SSOCTA and FA and ICGA area measurements in patients with treatment-naive neovascular age-related macular degeneration after applying a deep-learning-assisted approach for image registration. These findings encourage a paradigm shift to using SSOCTA as a first-line diagnostic tool in neovascular age-related macular degeneration.

2018 Update on Intravitreal Injections: Euretina Expert Consensus Recommendations.

Intravitreal injections (IVI) have become the most common intraocular procedure worldwide with increasing numbers every year. The article presents the most up-to-date review on IVI epidemiology and techniques. Unfortunately, important issues related to pre-, peri- and postinjection management lack randomized clinical trials for a final conclusion. Also, a great diversity of approaches exists worldwide. Therefore, expert consensus recommendations on IVI techniques are provided.

Regulation of retinal oxygen metabolism in humans during graded hypoxia.

Animal experiments indicate that the inner retina keeps its oxygen extraction constant despite systemic hypoxia. For the human retina no such data exist. In the present study we hypothesized that systemic hypoxia does not alter inner retinal oxygen extraction. To test this hypothesis we included 30 healthy male and female subjects aged between 18 and 35 years. All subjects were studied at baseline and during breathing 12% O2 in 88% N2 as well as breathing 15% O2 in 85% N2. Oxygen saturation in a retinal artery (SO2art) and an adjacent retinal vein (SO2vein) were measured using spectroscopic fundus reflectometry. Measurements of retinal venous blood velocity using bidirectional laser Doppler velocimetry and retinal venous diameters using a Retinal Vessel Analyzer (RVA) were combined to calculate retinal blood flow. Oxygen and carbon dioxide partial pressure were measured from earlobe arterialized capillary blood. Retinal blood flow was increased by 43.0 ± 23.2% (P < 0.001) and 30.0 ± 20.9% (P < 0.001) during 12% and 15% O2 breathing, respectively. SO2art as well as SO2vein decreased during both 12% O2 breathing (SO2art: -11.2 ± 4.3%, P < 0.001; SO2vein: -3.9 ± 8.5%, P = 0.012) and 15% O2 breathing (SO2art: -7.9 ± 3.6%, P < 0.001; SO2vein: -4.0 ± 7.0%, P = 0.010). The arteriovenous oxygen difference decreased during both breathing periods (12% O2: -28.9 ± 18.7%; 15% O2: -19.1 ± 16.7%, P < 0.001 each). Calculated oxygen extraction did, however, not change during our experiments (12% O2: -2.8 ± 18.9%, P = 0.65; 15% O2: 2.4 ± 15.8%, P = 0.26). Our results indicate that in healthy humans, oxygen extraction of the inner retina remains constant during systemic hypoxia.

Interaction between leukocytes and erythrocytes in the human retina: effects of pentoxifylline on hyperoxia-induced vasoconstriction during increased neutrophil counts.

PURPOSE: Pentoxifylline, a nonselective phosphodiesterase inhibitor, shows vasodilator effects in certain vascular beds and reduces blood viscosity. We have previously shown that under states of vasoconstriction an interaction between circulating erythrocytes and leukocytes may play a role in the control of blood flow. The reason for this observation is not entirely clear but may be related to a mechanical interaction between red and white blood cells. In the present study we hypothesized that pentoxifylline may alter this interaction during oxygen-induced vasoconstriction. METHODS: 24 healthy male subjects participated in this double masked, randomized, placebo-controlled 2 way cross over trial. In order to increase white blood cell count (WBC) count, 300 µg of G-CSF was administered intravenously. Vasoconstriction of retinal vessels was induced by oxygen inhalation. 400mg of pentoxifylline or placebo was infused at two different study days. White blood cell flux was assessed with the blue-field entoptic technique. Vessel calibers were measured with a dynamic vessel analyzer (DVA) and red blood cell velocity (RBCV) was determined with laser Doppler velocimetry (LDV). Retinal blood flow was calculated based on retinal vessel diameters and RBCV. RESULTS: Administration of G-CSF induced a significant increase in WBC, both in the placebo and the pentoxifylline group (p<0.01 for both groups). Retinal vessel diameter, RBCV, calculated retinal blood flow and white blood cell flow were not altered by administration of pentoxifylline. Hyperoxia induced a pronounced decrease in retinal blood flow parameters. No difference was observed between groups during oxygen breathing in vessel diameters (p=0.54), RBCV (p=0.34), calculated retinal blood flow (p=0.3) and white blood cell flow (p=0.26). CONCLUSION: Our data indicate that short time administration of pentoxifylline does not alter the oxygen-induced effect on ocular blood flow parameters during leukocytosis. Whether long-term treatment could improve retinal blood flow under states of vasoconstriction remains to be investigated.

Long-term results after surgical basal cell carcinoma excision in the eyelid region: revisited.

The aim of the study was to readdress basal cell carcinoma (BCC) in the periocular region to prove the efficacy of histologically controlled surgical treatment and to identify high-risk characteristics.Retrospective analysis of 451 microscopically controlled BCC excisions in the periocular region. Tumor location, tumor size, AJCC 7 classification, and histological results were recorded. The same procedure was followed for recurrences.A recurrence rate of 5.0% was observed after the first microscopically controlled excision. Recurrent BCCs show a shift from nodular to sclerosing BCC as the primary histological type as well as a change in primary location from lower eyelid to medial canthus. The frequency of BCC with deep extension increased from 7.3% to 24.7%, and 57.1% after the second and third operations, respectively. The recurrence rate increased to 9.5% and 42.9%, after the second and third operations, respectively.In conclusion, we are facing the same challenges in surgical BCC treatment as 30 years ago. The distribution of periocular BCC location, histologic subtype and recurrence rates mirror the literature und the general consensus. The recurrence rate increases with every operation needed. Sclerosing BCCs with deep extension at the medial canthus bear the greatest risk for recurrence. In such cases, centers of expertise should be consulted and additional treatment options should be considered.

Role of endothelin-A receptors in optic nerve head red cell flux regulation during isometric exercise in healthy humans.

Endothelin-1 (ET-1) is an important regulator of vascular tone in the eye. It appears to play a role in ocular disease because of its strong vasoconstrictor action, its role in intraocular pressure homeostasis, and its neurotoxic potential. We have previously shown that ET-1 is involved in choroidal red cell flux (RCF) regulation during isometric exercise in healthy humans. In the present study we hypothesized that ET-1 also plays a role in optic nerve head (ONH) RCF regulation during isometric exercise. To test this hypothesis, we performed a randomized, double-masked, placebo-controlled, two-way crossover study in 15 healthy volunteers. Subjects were randomized to receive intravenous infusions of the specific endothelin type A receptor antagonist BQ-123 and placebo on two different study days. During these infusion periods, subjects performed squatting for 6 min to increase ocular perfusion pressure (OPP). ONH RCF was assessed with laser-Doppler flowmetry, and OPP was calculated from mean arterial pressure and intraocular pressure. BQ-123 did not change OPP or ONH RCF at baseline. The relative increase in OPP during isometric exercise was comparable between both groups (between 84 and 88%, P = 0.76 between groups; P < 0.001 vs. baseline). Isometric exercise increased ONH RCF during placebo and BQ-123, but the increase was more pronounced when the endothelin type-A receptor antagonist was administered (placebo, 27.3 ± 5.4%; and BQ-123, 39.2 ± 4.4%; P = 0.007 between groups). The present data indicate that ET-1 regulates red cell flux in the ONH beyond the autoregulatory range.

Role of nitric oxide in optic nerve head blood flow regulation during an experimental increase in intraocular pressure in healthy humans.

The present study set out to investigate whether nitric oxide, a potent vasodilator, is involved in the regulatory processes in optic nerve head blood flow during an experimental increase in intraocular pressure (IOP). The study was conducted in a randomized, double-masked, placebo-controlled, three way cross-over design. 12 healthy subjects were scheduled to receive either L-NMMA (an unspecific nitric oxide synthase inhibitor), phenylephrine (an α-adrenoceptor agonist) or placebo on three different study days. Optic nerve head blood flow was measured using laser Doppler flowmetry and IOP was increased stepwise with a suction cup. Mean arterial pressure (MAP) and IOP were measured non-invasively and ocular perfusion pressure (OPP) was calculated as OPP = 2/3 MAP-IOP. Administration of L-NMMA and phenylephrine significantly increased MAP and therefore OPP at rest (p < 0.01). L-NMMA significantly reduced baseline blood flow in the optic nerve head (p < 0.01). Application of the suction cup induced a significant increase in IOP and a decrease in OPP (p < 0.01). During the stepwise increase in IOP, some autoregulatory potential was observed until OPP decreased approximately -30% below baseline. None of the administered substances had an effect on this autoregulatory behavior (p = 0.49). The results of the present study confirm that the human optic nerve head shows some regulatory capacity during a decrease in OPP. Nitric oxide is involved in the regulation of basal vascular tone in the optic nerve head but does not seem to be involved in the regulatory mechanisms during an acute increase in IOP in young healthy subjects.

Impact of Choroidal Melanoma Characteristics on Progression-Free Survival in Patients Undergoing Hypofractionated Stereotactic Photon Radiotherapy.

INTRODUCTION: In an effort to replace ultrasonography-based thickness measurements, we investigated whether choroidal melanoma characteristics are related to progression-free survival (PFS) in patients monitored after linear accelerator (LINAC)-based hypofractionated stereotactic photon radiotherapy. METHODS: In a retrospective dataset, we used a linear mixed model to assess the associations between PFS and tumor characteristics; in particular, thickness, largest basal diameter (LBD), base area and volume. RESULTS: Thickness and LBD are statistically significantly associated with PFS. In a subgroup of 16 patients undergoing enucleation due to melanoma recurrence or progression, there were statistically significant changes in mean thickness and LBD before surgery. Mean PFS was 42 ± 30 months. CONCLUSION: Ultrasonography-based thickness measurements may not be necessary for treated choroidal melanoma monitoring; instead, we propose sequential LBD assessments, which should preferably be performed using fundus photography in future.

Correlation of vascular and fluid-related parameters in neovascular age-related macular degeneration using deep learning.

PURPOSE: To identify correlations between the vascular characteristics of macular neovascularization (MNV) obtained by optical coherence tomography angiography (OCTA) and distinct retinal fluid volumes in neovascular age-related macular degeneration (nAMD). METHODS: In this prospective interventional study, 54 patients with treatment-naïve type 1 or 2 nAMD were included and treated with intravitreal aflibercept. At baseline and month 1, each patient underwent a SD-OCT volume scan and volumetric flow scan using a swept-source OCTA. A deep learning algorithm was used to automatically detect and quantify fluid in OCT scans. Angio Tool, a National Cancer Institute algorithm, was used to skeletonize MNV properties and quantify lesion size (LS), vessel area (VA), vessel density (VD), total number of endpoints (TNE), total number of junctions (TNJ), junction density (JD), total vessel length (TVL), average vessel length (AVL) and mean-e-lacunarity (MEL). Subsequently, linear regression models were used to investigate a correlation between OCTA parameters and fluid quantifications. RESULTS: The median amount of fluid within the central 6-mm EDTRS ring was 173.7 nl at baseline, consisting of 156.6 nl of subretinal fluid (SRF) and 2.3 nl of intraretinal fluid (IRF). Fluid decreased significantly in all compartments to 1.76 nl (SRF) and 0.64 nl (IRF). The investigated MNV parameters did not change significantly after the first treatment. There was no significant correlation between MNV parameters and relative fluid decrease after anti-VEGF treatment. Baseline fluid correlated statistically significant but weakly with TNE (p = 0.002, R2  = 0.17), SRF with TVL (p = 0.04, R2  = 0.08), VD (p = 0.046, R2  = 0.08), TNE (p = 0.001, R2  = 0.20) and LS (p = 0.033, R2  = 0.09). IRF correlated with VA (p = 0.042, R2  = 0.08).The amount of IRF at month 1 correlated significantly but weakly with VD (p = 0.036, R2  = 0.08), JD (p = 0.019, R2  = 0.10) and MEL (p = 0.005, R2  = 0.14). CONCLUSION: Macular neovascularization parameters at baseline and month 1 played only a minor role in the exudation process in nAMD. None of the MNV parameters were correlated with the treatment response.

OCTA Biomarker Search in Patients with nAMD: Influence of Retinal Fluid on Time-Dependent Biomarker Response.

PURPOSE: Previous studies have identified a link between optical coherence tomography (OCT)-derived and OCT angiography (OCTA)-based parameters in patients with neovascular AMD (nAMD); the latter may serve as direct biomarkers for macular neovascularization (MNV) activity. The aim of this study was to assess the individual influence of retinal thickness (RT) as well as intra- and sub-retinal fluid (IRF, SRF) presence on the treatment response over time as assessed by previously identified OCTA-derived MNV vascular parameters. METHODS: During the first 3 months of anti-VEGF therapy patients were prospectively followed. RT, SRF and IRF were determined from SSOCT/A (PlexElite, Zeiss) images and using the semi-automated AngioTool software, vessel area (VA), total vessel length (TVL), total number of junctions (TNJ), junction density (JD), vessel density (VD) as well as MNV area were exported. IRF and SRF were identified manually on OCT volume scans .The associations between RT, IRF, and SRF and SSOCTA vascular parameters were analyzed using linear mixed models. RESULTS: 31 eyes of 31 patients with treatment-naïve and OCTA-positive nAMD MNV were included in this analysis. VA, TVL, TNJ, and MNV area show a statistically significant change over time in response to anti-VEGF treatment, even after correcting for the presence of SRF, IRF, or RT (all p < 0.05). This is not the case for JD and VD (both p > 0.05). CONCLUSIONS: OCTA-based parameters VA, TVL, TNJ, and MNVarea show a strong response to anti-VEGF therapy over time, independent of the presence of IRF, SRF or RT. We conclude that the above listed OCTA parameters could contribute to our understanding of MNV biology and to guide individualized treatment in the future. TRIAL REGISTRY: The authors confirm that all ongoing and related trials are registered. ClinicalTrials.gov Number: NCT02521142.

Effects of increased white blood cell count on endothelin-induced vasoconstriction in healthy subjects.

It is known that administration of granulocyte-colony stimulating factor is followed by an increase of white blood cell count. There is evidence from other vascular beds that an increase in white blood cell count impairs blood flow regulation especially in the microcirculation. Whether this also holds true for the ocular circulation is unknown. In the following study we investigated whether an increase in white blood cell count alters the endothelin-1 induced vasoconstriction in humans. Neither granulocyte-colony stimulating factor nor endothelin-1 had any consistent effect on blood pressure, pulse rate or intraocular pressure. Administration of granulocyte-colony stimulating factor induced a pronounced increase in retinal white blood cell density (p < 0.01). Administration of endothelin-1 decreased choroidal (p < 0.01) and retinal blood flow (p < 0.01). The change in choroidal blood flow in response to endothelin-1 was not altered by pre-treatment with granulocyte-colony stimulating factor. By contrast, the decrease in retinal blood flow was more pronounced during an increase in white blood cell count (p = 0.02) when compared to placebo. Our data indicates that during pronounced vasoconstriction, as induced by administration of endothelin-1, vascular regulation can be altered by the number of circulating white blood cells. Whether this effect is caused by an interaction of red and white blood cells in the microcirculation or a yet unknown mechanism needs further investigation.

Microvascular Retinal Changes in Patients with Marfan Syndrome.

PURPOSE: To determine microvascular changes in patients with genetically proven Marfan syndrome. METHODS: In a cross-sectional study, 32 eyes of 16 patients with genetically proven Marfan syndrome were evaluated using swept-source optical coherence tomography angiography (SS-OCTA). Patients were analyzed regarding lens status and systemic vascular disease. The foveal avascular zone (FAZ) and vessel density (VD) of the superficial and deep vascular plexus and central retinal thickness (CRT) were evaluated on SS-OCTA. RESULTS: 44/56% patients presented without/with subluxation of the lens. 69% of patients had presence of mitral valve insufficiency, aortic dilatation or aneurysm of the aortic root. In patients with Marfan syndrome the mean area of the FAZ was 0.2 ± 0.1 mm and the average VD of the superficial/deep vascular plexus was 36 ± 5%/22 ± 7%. In patients with subluxation of the lens FAZ area and perimeter were larger when compared to patients without subluxation of the lens (0.18 ± 0.08/0.28 ± 0.10 mm and 1.7 ± 0.4/2.3 ± 0.8; p = 0.02). VD of the superficial vascular plexus was reduced in patients with subluxation of the lens (on average 39 ± 3/33 ± 8; p = 0.01) together with an increased CRT in the inner segments of the ETDRS grid when compared to patients without subluxation of the lens. In patients with systemic vascular disease a larger FAZ area (0.19 ± 0.06/0.25 ± 0.1 mm; p = 0.04) and reduced VD of the superficial vascular plexus in the central ETDRS grid (28 ± 7/21 ± 6; p = 0.02) was observed in comparison to patients without systemic vascular changes. CONCLUSIONS: In patients with Marfan syndrome SS-OCTA imaging revealed microvascular differences in patients with lens subluxation and/or systemic vascular disease.

Impact of large choroidal vessels on choriocapillaris flow deficit analyses in optical coherence tomography angiography.

PURPOSE: To investigate the impact of large choroidal vessels (LCV) on Choriocapillaris (CC) flow deficit (FD) analyses with swept-source optical coherence tomography angiography (SS-OCTA). DESIGN: Prospective, cross-sectional study. METHODS: Macular 6x6mm SS-OCTA scans were obtained from intermediate age-related macular degeneration (iAMD) and healthy eyes. Images were captured and processed according to most common standards and analyzed for percentage of flow-deficits (FD%) within four 1x1mm squares at the corners of each image. Choroidal thickness (CT), iris color and refraction error were considered as potential influential factors for LCV visibility. A linear mixed model and logistic regression models were calculated for statistical evaluation. RESULTS: Sixty-nine iAMD and 49 age-matched healthy eyes were enrolled. LCV were visible in at least one sector in 52% of iAMD and 47% of healthy eyes. Within the iAMD group FD% were significantly lower in areas containing LCV (p = 0.0029). Increasing CT resulted in an odds ratio decrease of LCV (OR: 0.94, p<0.0001). Below a CT value of ≤118µm LCV could be expected with a sensitivity of 86% and a specificity of 85%. CONCLUSIONS: LCV can significantly affect CC FD analyses of SS-OCTA images. Their visibility is negatively associated with CT. The impact of LCV should be taken into account when performing CC FD assessments, especially in patients where reduced CT is to be expected and inclusion of affected areas should be considered carefully.

Retinal vessel diameters, flicker-induced retinal vasodilation and retinal oxygen saturation in high- and low-risk pregnancy.

PURPOSE: To compare retinal vascular parameters between high-risk and low-risk pregnant women over time during pregnancy. METHODS: In a longitudinal study, we included pregnant women with normal blood pressure and normal body mass index (BMI, group 1), pregnant women with systemic hypertension and/or overweight (group 2) and age-matched nonpregnant healthy women (group 3). Using the dynamic vessel analyser (DVA) we investigated flicker-induced vasodilation in retinal arteries (FLA) and veins (FLV), central retinal arterial and vein equivalent (CRAE, CRVE), arterio-venous ratio (AVR) and retinal arterial and venous oxygen saturation (SartO2 , SveinO2 ). Study visits were scheduled 2nd trimester (TP 2), 3rd trimester (TP 3) and postpartum (PP). RESULTS: Data from 29 women in group 1, 25 women in group 2 and 33 women in group 3 were included for analysis. FLA, FLV, CRAE, CRVE, AVR and SveinO2 were altered in group 2 (p-values between < 0.001 and 0.009). At TP 3 the differences between groups were most pronounced. In contrast, there were only minor differences between group 1 and 3. Changes in retinal parameters were independently associated with systemic blood pressure and BMI. CONCLUSIONS: The present analysis indicates that flicker-induced retinal vasodilation, retinal vessel diameters and retinal oxygen saturation are altered in high-risk pregnant women. Hence, these parameters are candidate biomarkers for pregnancy complications, a hypothesis that deserves further study.

Retinal vessel architecture in retinopathy of prematurity and healthy controls using swept-source optical coherence tomography angiography.

PURPOSE: To determine microvascular changes in children with a history of retinopathy of prematurity (ROP) and in a control group of full-term children. METHODS: In a cross-sectional study, 30 eyes of 15 children aged 6-8 years with a history of ROP were evaluated with swept-source optical coherence tomography angiography (SS-OCTA). Twenty-eight eyes of 22 age-matched full-term children served as a healthy control group. The foveal avascular zone (FAZ), vessel density (VD) and choroidal vascular flow area (VFA) were evaluated on OCTA and correlated with central retinal thickness (CRT), visual acuity (VA), birth weight (BW), gestational age (GA) and ROP stages. RESULTS: Twenty-two eyes of 14 children with a history of ROP (stage 1-3) and 25 eyes of 19 full-term children were available for evaluation. In the ROP group, the gestational age was 27 ± 2 weeks and birth weight was 781 ± 164 g. In the ROP group, CRT was higher in the central ETDRS segment (mean difference [95% CI]: 32.8 µm [18.7; 47.0], p = 0.0002) compared to the controls. Smaller mean FAZ area (-0.12 [-0.19; -0.04], p = 0.004) and perimeter (-662 [-1228; -96], p = 0.03) was found in comparison to the control group. An oval shape of the FAZ was observed among patients with a history of ROP. The mean central VD of the superficial plexus was 28 ± 8/23 ± 8% and of the deep plexus 7 ± 7/3 ± 5% (ROP group/control group; p > 0.05). No statistically significant difference was found regarding the choroidal VFA. Only weak correlation of FAZ and VD with function was observed. CONCLUSIONS: Swept-source optical coherence tomography angiography imaging revealed significant microvascular anomalies in children with a history of ROP indicating disturbance of early morphological development of the central retina.

Profiling neovascular age-related macular degeneration choroidal neovascularization lesion response to anti-vascular endothelial growth factor therapy using SSOCTA.

PURPOSE: To identify the changes in distinct vascular parameters of choroidal neovascularization (CNV) in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD) during the primary response to anti-VEGF therapy using aflibercept. METHODS: Patients were prospectively followed during the first 3 months according to a standardized protocol with mandatory visits at days 7 and 14 after each anti-VEGF treatment up to day 90. Fourteen eyes were seen in addition at days 1 and 3 post-initial injection. Aflibercept was administered at baseline (BL), day 30 and 60. 6 × 6mm SSOCTA (PlexElite, Zeiss) images were acquired. Using the semi-automated AngioTool, CNV area, vessel area, vessel density (VD), the number of junctions, junctions density, total vessel length, average vessel length, total number of endpoints and lacunarity were assessed. RESULTS: Thirty-two consecutive patients presenting with treatment-naïve, SSOCTA-positive CNV lesions were included. Close follow-up showed a characteristic neovascular response curve with a dynamic decrease in lesion size within days and a reactive increase following 2 weeks after initial treatment. An undulating pattern was seen for all neovascular parameters except for vascular density, with variable statistical significance. Due to a flattening of the therapeutic response as early as after the second treatment, CNV lesion size and most of the related parameters had an increase in activity above baseline values at the end of the loading phase. Lesion size was the leading feature of reactivation by a mean increase of 19.3% after three monthly aflibercept injections. Subgroup analysis based on lesion size revealed a significant correlation between best-corrected visual acuity and quantitative change in lesion size over time, but not baseline size. CONCLUSIONS: Using SSOCTA, a morphologic neovascular response pattern can be identified in anti-VEGF treatment of CNV. A synchronized early decrease and consecutive reactivation in a large spectrum of neovascular biomarkers including size and internal structure are visualized in a qualitative and quantitative manner. SSOCTA analyses allow new insights in CNV morphology changes and therapeutic response.