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Background The aim of this study was to describe features of disease activity in patients with treated stable macular neovascularisation (MNV) in neovascular age related macular degeneration (nAMD) using optical coherence tomography angiography (OCTA). Methods Thirty-two eyes of 32 patients with nAMD were included in this prospective, observational study. These patients were undergoing treatment with aflibercept on a treat-and-extend regimen attending an extension to a 12-week treatment interval. Results All subjects had no macular haemorrhage and no structural OCT markers of active MNV activity at the index 12-week treatment extension visit. 31/32 OCTA images were gradeable without significant imaging artefact. The mean MNV size was 3.6mm2 ± 4.6mm2 and 27 (87.1%) had detectable MNV blood flow. 29/31 (93.5%) subjects had MNV with mature phenotypes including 10 non-specific, 10 tangle and 3 deadtree phenotypes. MNV halo and MNV central feeder vessel were noted in 18 (58.1%) and 19 (61.3%) of subjects respectively; only 1 (3.2%) subject was noted to have a MNV capillary fringe. Conclusions MNV blood flow is still detectable using OCTA in the majority of subjects in this study with treated stable MNV. OCTA features associated included MNV mature phenotype, MNV feeder vessel, MNV halo and absence of capillary fringe.

Optical Coherence Tomography (OCT) is an intravascular imaging modality enabling detailed evaluation of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). However, its clinical application remains hampered by time-consuming manual quantitative analysis. We aimed to validate a semi-automated quantitative OCT analysis software (Iowa Coronary Wall Analyzer, ICWA-OCT) to improve OCT-analysis in HTx patients. 23 patients underwent OCT evaluation of all three major coronary arteries at 3 months (3M) and 12 months (12M) after HTx. We analyzed OCT recordings using the semiautomatic software and compared results with measurements from a validated manual software. For semi-automated analysis, 31,228 frames from 114 vessels were available. The validation was based on a subset of 4287 matched frames. We applied mixed model statistics to accommodate the multilevel data structure with method as a fixed effect. Lumen (minimum, mean, maximum) and media (mean, maximum) metrics showed no significant differences. Mean and maximum intima area were underestimated by the semi-automated method (β-method mean = − 0.289 mm 2, p < 0.01; β-method max = − 0.695 mm 2, p < 0.01). Bland–Altman analyses showed increasing semi-automatic underestimation of intima measurements with increasing intimal extent. Comparing 3M to 12M progression between methods, mean intimal area showed minor underestimation (β-method mean = − 1.03 mm 2, p = 0.04). Lumen and media metrics showed excellent agreement between the manual and semi-automated method. Intima metrics and progressions from 3M to 12M were slightly underestimated by the semi-automated OCT software with unknown clinical relevance. The semi-automated software has the future potential to provide robust and time-saving evaluation of CAV progression.

PURPOSE: To determine the prevalence of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in a population-based child cohort and to study their association with other optic nerve head features and myopia.DESIGN: Observational, population-based cohort study of 1407 children aged 11-12 years.METHODS: Optical coherence tomography scans of optic nerve heads were graded for PHOMS, disc tilt, prelaminar hyperreflective lines, and scleral canal diameter and investigated for associated prenatal and ocular parameters. Children with optic disc drusen or optic disc edema were excluded.RESULTS: PHOMS were found in 8.9% of children. The location of PHOMS was predominantly in the superonasal section of the optic disc. Myopia and optic nerve head tilt were more common in children with PHOMS than in children without PHOMS (P < .001 and P < .001, respectively). Prelaminar hyperreflective lines were found in 17.9% of children with PHOMS compared to 7.3% of children without PHOMS (P < .001). Prelaminar hyperreflective lines with and without PHOMS were associated with a shorter axial length of the eye (P < .001). There were no prenatal factors associated with PHOMS. Prelaminar hyperreflective lines were associated with higher birth weight and continued maternal smoking during pregnancy (P = .01 and P = .02, respectively).CONCLUSIONS: PHOMS had a prevalence of 8.9% in healthy children without optic disc drusen or optic disc edema and was associated with increasing myopic refraction and the presence of a tilted optic nerve head and prelaminar hyperreflective lines. Given the high prevalence of PHOMS, they should not unreservedly be taken as evidence of optic neuropathy.

Age-related macular degeneration (AMD) is a progressive retinal disease, causing vision loss. A more detailed characterization of its atrophic form became possible thanks to the introduction of Optical Coherence Tomography (OCT). However, manual atrophy quantification in 3D retinal scans is a tedious task and prevents taking full advantage of the accurate retina depiction. In this study we developed a fully automated algorithm segmenting Retinal Pigment Epithelial and Outer Retinal Atrophy (RORA) in dry AMD on macular OCT. 62 SD-OCT scans from eyes with atrophic AMD (57 patients) were collected and split into train and test sets. The training set was used to develop a Convolutional Neural Network (CNN). The performance of the algorithm was established by cross validation and comparison to the test set with ground-truth annotated by two graders. Additionally, the effect of using retinal layer segmentation during training was investigated. The algorithm achieved mean Dice scores of 0.881 and 0.844, sensitivity of 0.850 and 0.915 and precision of 0.928 and 0.799 in comparison with Expert 1 and Expert 2, respectively. Using retinal layer segmentation improved the model performance. The proposed model identified RORA with performance matching human experts. It has a potential to rapidly identify atrophy with high consistency.

PURPOSE: To determine whether combinations of devices with different measuring principles, supported by artificial intelligence (AI), can improve the diagnosis of keratoconus (KC). METHODS: Scheimpflug tomography, spectral-domain optical coherence tomography (SD-OCT), and air-puff tonometry were performed in all eyes. The most relevant machine-derived parameters to diagnose KC were determined using feature selection. The normal and forme fruste KC (FFKC) eyes were divided into training and validation datasets. The selected features from a single device or different combinations of devices were used to develop models based on random forest (RF) or neural networks (NN) trained to distinguish FFKC from normal eyes. The accuracy was determined using receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity. RESULTS: 271 normal eyes, 84 FFKC eyes, 85 early KC eyes, and 159 advanced KC eyes were included. A total of 14 models were built. Air-puff tonometry had the highest AUC for detecting FFKC using a single device (AUC = 0.801). Among all two-device combinations, the highest AUC was accomplished using RF applied to selected features from SD-OCT and air-puff tonometry (AUC = 0.902), followed by the three-device combination with RF (AUC = 0.871) with the best accuracy. CONCLUSION: Existing parameters can precisely diagnose early and advanced KC, but their diagnostic ability for FFKC could be optimized. Applying an AI algorithm to a combination of air-puff tonometry with Scheimpflug tomography or SD-OCT could improve FFKC diagnostic ability. The improvement in diagnostic ability by combining three devices is modest.

Funding: Supported by the Macula Foundation, Inc. (New York, NY, USA) and by Fundação para a Ciência e Tecnologia (FCT)–Portugal, cofunded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020). ACF was funded by a FCT PhD studentship (PD/BD/135503/2018). DC was supported in part by a studentship from Fundação Luso-Americana para o Desenvolvimento (FLAD, USA R&D@PhD–Proj 2020/0140). Purpose: To characterize macular blood flow connectivity in vivo using high-resolution optical coherence tomography (HighRes OCT). Methods: Cross-sectional, observational study. Dense (6-µm interscan distance) perifoveal HighRes OCT raster scans were performed on healthy participants. To mitigate the limitations of projection-resolved OCT-angiography, flow and structural data were used to observe the vascular structures of the superficial vascular complex (SVC) and the deep vascular complex. Vascular segmentation and rendering were performed using Imaris 9.5 software. Inflow and outflow patterns were classified according to vascular diameter and branching order from superficial arteries and veins, respectively. Results: Eight eyes from eight participants were included in this analysis, from which 422 inflow and 459 outflow connections were characterized. Arteries had direct arteriolar connections to the SVC (78%) and to the intermediate capillary plexus (ICP, 22%). Deep capillary plexus (DCP) inflow derived from small-diameter vessels succeeding ICP arterioles. The most prevalent outflow pathways coursed through superficial draining venules (74%). DCP draining venules ordinarily merged with ICP draining venules and drained independently of superficial venules in 21% of cases. The morphology of DCP draining venules in structural HighRes OCT is distinct from other vessels crossing the inner nuclear layer and can be used to identify superficial veins. Conclusions: Vascular connectivity analysis supports a hybrid circuitry of blood flow within the human parafoveal macula. Translational Relevance: Characterization of parafoveal macular blood flow connectivity in vivo using a precise segmentation of HighRes OCT is consistent with ground-truth microscopy studies and shows a hybrid circuitry. publishersversion published

OBJECTIVE: To evaluate the difference in early vascular healing between the ultrathin-strut biodegradable-polymer sirolimus-eluting Orsiro stent (O-SES) and the polymer-free biolimus-A9-eluting BioFreedom stent (BF-BES), assessed with optical coherence tomography (OCT) after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarctions (STEMIs).METHODS: Eighty patients with STEMI who underwent primary PCI were randomly allocated 1:1 to treatment with BF-BES or O-SES. OCT was acquired after PCI and at 1-month follow-up. The primary endpoint was 1-month OCT-assessed vascular healing index based on the presence of uncovered and malapposed stent struts and intraluminal filling defects where low vascular healing index indicated favorable vascular healing.RESULTS: At 1-month, the vascular healing index was similar in O-SES 11.5 [interquartile range (IQR) 9.5-17.5], compared to BF-BES 11.5 (IQR 7.1-12.5; P = 0.14). Percentage of uncovered struts [O-SES 31.5% (IQR 20.7-41.9), P = 0.43] vs. BF-BES 27.8% (IQR 19.4-41.9; P = 0.44), and median volume of neointimal hyperplasia [O-SES 4.9 mm3 (IQR 1.4-13.1) vs. BF-BES 7.1 mm3 (IQR 2.8-17.0), P = 0.18] did not differ significantly between the two stent groups. Complete coverage was not observed in any of the stents. The percentages of stents with malapposition did not differ significantly (O-SES 87.1% vs. BF-BES 71.4%, P = 0.14) whereas percentage of malapposed struts [O-SES 3.5% (IQR 0.8-5.5) vs. BF-BES 0.8% (IQR 0.0-1.8), P = 0.003] was lower in the BF-BES group.CONCLUSION: In patients with STEMI, the drug-coated BF-BES and the thin strut O-SES had similar vascular healing index at 1-month. However, the thin O-SES struts were more often malapposed.

Purpose Retinal vein cannulation is an experimental procedure during which a clot-dissolving drug is injected into an obstructed retinal vein. However, due to the fragility and minute size of retinal veins, such procedure is considered too risky to perform manually. With the aid of surgical robots, key limiting factors such as: unwanted eye rotations, hand tremor and instrument immobilization can be tackled. However, local instrument anatomy distance and force estimation remain unresolved issues. A reliable, real-time local interaction estimation between instrument tip and the retina could be a solution. This paper reports on the development of a combined force and distance sensing cannulation needle, and its experimental validation during in vivo animal trials. Methods Two prototypes are reported, relying on force and distance measurements based on FBG and OCT A-scan fibres, respectively. Both instruments provide an 80 μm needle tip and have outer shaft diameters of 0.6 and 2.3 mm, respectively. Results Both prototypes were characterized and experimentally validated ex vivo. Then, paired with a previously developed surgical robot, in vivo experimental validation was performed. The first prototype successfully demonstrated the feasibility of using a combined force and distance sensing instrument in an in vivo setting. Conclusion The results demonstrate the feasibility of deploying a combined sensing instrument in an in vivo setting. The performed study provides a foundation for further work on real-time local modelling of the surgical scene. This paper provides initial insights; however, additional processing remains necessary. ispartof: International Journal Of Computer Assisted Radiology And Surgery vol:14 issue:2 pages:301-309 ispartof: location:Germany status: published

The aim of the study presented here was to evaluate retinal and optic nerve head (ONH) perfusion in patients with severe asymptomatic carotid artery stenosis (CAS) compared with healthy controls and to analyze the impact of carotid endarterectomy using optical coherence tomography angiography (OCT-A). 25 eyes of 25 patients with CAS (study group) and 25 eyes of 25 healthy controls (control group) were prospectively included in this study. OCT-A was performed using RTVue XR Avanti (Optovue, Inc, Fremont, California, USA). The flow density data in the superficial and deep retinal OCT-angiogram of the macula and in the radial peripapillary capillary network (RPC) of the ONH were extracted and analyzed. The flow density in the superficial retinal OCT angiogram of the macula and in the ONH were significantly lower in the study group compared with the control group (macula: p = 0.003) (ONH: p = 0.013). The flow density in the ONH improved significantly after carotid endarterectomy (p = 0.004). A reduced flow density was observed in patients with CAS when compared with healthy controls. The flow density also improved after carotid endarterectomy. Quantitative changes in the microvascular density, as measured using OCT-A, could well be useful in the diagnosis of CAS and the evaluation of therapy success.

Aims To evaluate the timing and spectral-domain optical coherence tomography (SD-OCT) features of diabetic macular oedema (DME) recurrence according to baseline OCT patterns in patients treated with dexamethasone implant (DEX-I). Methods This is a retrospective observational study (72 eyes/65 patients). Best-corrected visual acuity, timing of DME recurrence, and SD-OCT pattern [intraretinal cysts (IRC), IRC plus subretinal fluid (mixed), external limiting membrane (ELM), ellipsoid (IS/OS) layer integrity] were assessed at baseline and monthly until first DME recurrence. Results Forty-two (58.3%) and 30 (41.6%) DME eyes had an IRC and mixed DME pattern at baseline, respectively. Twenty-four out of thirty mixed eyes (80%) relapsed without subretinal fluid. At baseline, mixed eyes showed similar changes in ELM and IS/OS (60 and 76.6% of eyes, respectively) versus IRC eyes (42.8 and 80.9% of eyes). After DME recurrence, more mixed eyes at baseline showed ELM and IS/OS changes (63.3 and 86.6%) than IRC eyes (50 and 76.2%). 33.3% of mixed eyes had DME recurrence at ≥ 6 months from first DEX-I implant versus 19% of IRC eyes. Conclusions Mixed DME eyes were treated with DEX-I relapse later and more frequently without subretinal fluid than IRC eyes. SD-OCT characteristics of different DME patterns at baseline can predict morphological features and timing of DME recurrence.

Purpose: RPE65-associated retinal dystrophy (RPE65-RD) is an early onset, progressive, severe retinal dystrophy. We sought to characterize the natural history of retinal degeneration in affected individuals.Methods: We performed cross-sectional and longitudinal quantitative and qualitative assessments of retinal architecture in RPE65-RD using spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging. Twenty-six subjects (mean age, 14.8 years, range, 5-24 years) with RPE65-RD underwent SD-OCT and FAF imaging, of whom 14 subjects were followed up over time. Foveal thickness (FT), outer nuclear layer thickness (ONLT), ellipsoid zone width (EZW), and ellipsoid zone area (EZA) were calculated where possible. These were correlated with age, best corrected visual acuity (BCVA), and central 30° retinal sensitivity (V30). Intra-observer agreement, test-retest repeatability, and interocular symmetry were also investigated.Results: We identified structural interocular symmetry, the presence of autofluorescence in 46% (12/26) of subjects, and the presence of foveal hypoplasia (associated with significantly worse BCVA) in 50% of subjects. EZW and EZA were measurable in 67% (35/52) and 37% (19/52) of eyes, respectively, with both demonstrating good agreement on repeated measurement. The annual rate of progression using EZW was -300.63 µm/year, and -1.17 mm2/year in EZA. EZW was found to have a statistically significant correlation with BCVA and V30.Conclusions: We identified the presence of autofluorescence in half of our subjects, with foveal hypoplasia also noted in half of our cohort. EZW, and to a lesser extent EZA, were robust measures of retinal degeneration and represent valuable metrics to determine the impact of intervention. (ClinicalTrials.gov number NCT02714816.).

Purpose: To introduce the concept of using a Bowman layer (BL) onlay graft to manage superficial herpetic corneal scarring and to describe the clinical outcomes of the first 2 cases undergoing this procedure. Methods: Two patients with a quiescent superficial corneal scar after herpes (varicella zoster virus [n = 1] and herpes simplex virus [n = 1]) keratitis underwent BL onlay transplantation. After the removal of the host epithelium and limited superficial keratectomy, an isolated BL graft was placed onto the host corneal surface. The cornea was then covered with an amniotic membrane and a bandage contact lens. Best spectacle-corrected visual acuity (VA) and/or best contact lens-corrected VA (BCLVA), biomicroscopy, corneal tomography, and anterior segment optical coherence tomography were recorded at 1 week, 1 month, and 3, 6, 9, 12, and 18 months postoperatively. Results: In both cases, the surgical and postoperative courses were uneventful. An improvement of the corneal clarity was observed at biomicroscopy, and no varicella zoster virus/herpes simplex virus reactivation occurred throughout the follow-up period. Biomicroscopy, Scheimpflug imaging, and anterior segment optical coherence tomography showed a completely epithelialized and well-integrated graft postoperatively. In case 1, BCLVA with a scleral lens improved from 20/100 (0.1) preoperatively to 20/32 (0.6) postoperatively. For case 2, no preoperative BCLVA was available, but a BCLVA of 20/36 (0.55) was achieved after the procedure. Conclusions: A BL onlay graft may be a feasible surgical procedure, which may have the potential to reduce superficial corneal scarring and/or anterior corneal irregularities without resorting to deeper keratoplasty in these complex cases.

Purpose To compare the characteristics of eyes that had manual vs. automated segmentation of choroidal neovascular membrane (CNVM) using optical coherence tomography angiography (OCTA). Methods All patients with CNVM underwent OCTA using the Zeiss Angioplex Cirrus 5000. Slabs of the avascular outer retina, outer retina to choriocapillaris (ORCC) region and choriocapillaris were generated. Manual segmentation was done when there were significant segmentation artifacts. Presence of activity of CNVM was adjudged by the presence of subretinal fluid (SRF) on structural OCT and was compared to activity detected on en face OCTA slabs based on well-defined criteria. Results Eighty-one eyes of 81 patients were recruited of which manual segmentation was required in 46 (57%). Eyes with automated segmentation had significantly more CNVM in the ORCC (75%) whereas those with manual segmentation had deeper CNVM (sub-RPE = 22%, intra-PED = 22%) (p Conclusions Manual segmentation of OCTA is required in more than 50% eyes with CNVM and this progressively increases with increasing depth of CNVM location from the ORCC to below the RPE. There is moderate concordance between OCTA and structural OCT in determining CNVM activity.

PURPOSE: To evaluate the relationship between subjective and objective measurements of lens density and the energy of phacoemulsification.SETTING: University Eye Clinic, Maastricht University Medical Centre, Maastricht, the Netherlands.DESIGN: Cross-sectional study.METHODS: The study population included 69 patients. Nuclear opalescence (NO) was graded with the Lens Opacities Classification System III (LOCS III). Thereafter, lens density was measured objectively with Scheimpflug imaging, anterior segment optical coherent tomography and spectral fundus reflectometry (SFR). Cumulative dissipative energy (CDE) and total ultrasound time (US t.t.) of the phacoemulsification were noted. The relationship between the different measurement techniques and energy of phacoemulsification was assessed using Spearman's correlation coefficients.RESULTS: We found moderate to strong correlations between LOCS III and objective measurements of the lens density (rho's from 0.53 to 0.78, p < 0.05) and a moderate correlation between three objective measurement techniques (rho's between 0.29 and 0.57, p < 0.05). There was a moderate correlation between CDE, US t.t. and lens density measurements (rho's from 0.29 to 0.55, p < 0.05), and the highest correlation was found between CDE and NO scores. Exclusion of patients with advanced cortical and posterior subcapsular opacities improved the correlation between SFR and lens density measurements but not the correlation with the energy of phacoemulsification.CONCLUSION: Lens Opacities Classification System III has shown the highest correlation with phacoemulsification energy and may be a preferred technique for prediction of use of phacoemulsification energy. Advanced cortical and posterior opacities may interfere with the quality of objective measurements but do not affect the correlation between lens density measurements and phacoemulsification energy.

Central serous chorioretinopathy (CSCR), one of the most common diseases in retina clinics, needs a special attention by retina specialists. Considering the challenges in diagnosis, classification, and management of this enigmatic disease and lack of level 1 evidence, there is a need for consensus with regard to establishing management protocols.

Supplemental Digital Content is Available in the Text. In this interventional case series, 8 patients presenting macular telangiectasia Type 1 with macular edema were treated by intravitreal aflibercept. The favorable clinical response observed with this treatment is consistent with the profile of angiogenic factors analyzed in their aqueous humors., Purpose: To evaluate intravitreal aflibercept in macular telangiectasia Type 1 (MacTel 1) patients and measure their ocular angiogenic profile. Methods: Eight subjects with MacTel 1 refractory to bevacizumab, ranibizumab, or laser therapy and switched to aflibercept were included. Best-corrected visual acuity, central macular thickness, and cystic areas quantified on optical coherence tomography B-scans were assessed during 12 months. Perifoveal capillary densities were measured on optical coherence tomography angiography. Aqueous humor was sampled from six patients and eight control subjects undergoing cataract extraction. Growth factors were quantified using a multiarray immunoassay. Results: Over 12 months, patients received 6.6 ± 1.4 (range, 5–8) intravitreal aflibercept injections. Twelve months after switching to aflibercept, best-corrected visual acuity increased by ≥5 letters in 5 of 8 patients, compared with preaflibercept levels. Mean best-corrected visual acuity improved from 79.6 (∼20/50) to 88.0 (∼20/35) Early Treatment Diabetic Retinopathy Study letters (P = 0.042), and central macular thickness decreased from 434 ± 98 μm to 293 ± 59 μm (P = 0.014). Compared with control subjects, the profile of angiogenic factors in MacTel 1 eyes revealed no difference in vascular endothelial growth factor-A levels but significantly higher levels of placental growth factor (P = 0.029), soluble vascular endothelial growth factor receptor-1 (sFlt-1; P = 0.013), vascular endothelial growth factor-D (P = 0.050), and Tie-2 (P = 0.019). Placental growth factor levels inversely correlated with both superficial and deep capillary plexus densities on optical coherence tomography angiography (P = 0.03). Conclusion: The clinical response to aflibercept coupled to the angiogenic profile of MacTel 1 eyes support the implication of the placental growth factor/Flt-1 pathway in MacTel 1.

PURPOSE: We aimed to investigate changes in retinal vascular geometry over time after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR).METHODS: Thirty-seven eyes with PDR were included. Wide-field fluorescein angiography (Optomap, Optos PLC., Dunfermline, Scotland, UK) was used to diagnose PDR at baseline and to assess activity at follow-up month three and six. At each time-point, a trained grader measured retinal vessel geometry on optic disc (OD) centred images using semiautomated software (SIVA, Singapore I Vessel Assessment, National University of Singapore, Singapore) according to a standardized protocol.RESULTS: At baseline, the mean age and duration of diabetes were 52.8 and 22.3 years, and 65% were male. Mean HbA1c was 69.9 mmol/mol, and blood pressure was 155/84 mmHg. Of the 37 eyes with PDR, eight (22%) eyes had progression at month three and 13 (35%) progressed over six months. Baseline characteristics, including age, sex, duration of diabetes, HbA1c, blood pressure, vessel geometric variables and total amount of laser energy delivered did not differ by progression status. However, compared to patients with progression of PDR, patients with favourable treatment outcome had alterations in the retinal arteriolar structures from baseline to month six (calibre, 154.3 μm versus 159.5 μm, p = 0.04, tortuosity 1.12 versus 1.10, p = 0.04) and in venular structures from baseline to month three (fractal dimension 1.490 versus 1.499, p = 0.04, branching coefficient (BC) 1.32 versus 1.37, p = 0.01).CONCLUSION: In patients with PDR, successful PRP leads to alterations in the retinal vascular structure. However, baseline retinal vascular geometry characteristics did not predict treatment outcome.

Purpose To follow choroidal thickness (ChT) over time in birdshot retinochoroiditis (BRC) using enhanced depth imaging optical coherence tomography (EDI-OCT) and study the effect of early and sustained treatment on ChT. Patients and methods Eighteen patients were included and EDI-OCT measurements of ChT were analyzed retrospectively in five groups of patients with follow-up times ranging from 1 year to ≥15 years. The OCT images were evaluated and ChT was calculated under the foveola and 1500 μm temporal, nasal, superior, and inferior to the foveola. To assess the effect of treatment, 13 patients with a disease duration ≥10 years were divided into two groups depending on their treatment status: early and sustained therapy vs insufficient, late, or no treatment. ChT was compared in these two groups along with the number of typical fundus BRC lesions. Results The ChT decreased (r=–0.41, P=0.0018) over the disease duration, which ranged from

PURPOSE: To determine the diurnal variations in peripapillary and macular flow density (FD), as measured using optical coherence tomography angiography (OCTA) and to elaborate on the relationship between diurnal FD, circulatory parameters and intraocular pressure (IOP) variations in primary open-angle glaucoma (POAG). METHODS: Forty eyes of 40 POAG patients were drawn into this cross-sectional study. The retinal microvasculature of the macula (superficial and deep layers) and optic nerve [radial peripapillary capillary (RPC)] was examined by OCTA (AngioVue® , Optovue). Optical coherence tomography angiography (OCTA) measurements were conducted at 08:00, 11:00, 15:00 and 20:00 over the course of two consecutive days. Intraocular pressure (IOP) and circulatory parameters were assessed accordingly. Diurnal variations in FD were analysed using linear mixed models. RESULTS: While superficial macular FD and RPC FD revealed not to be affected by diurnal variations (p = 0.492, p = 0.319), FD in the deep layer of the macula increased throughout the day (p < 0.001). Superficial macular FD was influenced significantly by mean arterial pressure (MAP) (p = 0.006) and heart rate (HR) (p = 0.033), whereas FD in the RPC layer was significantly affected by HR (p = 0.010). No statistically significant effect of IOP fluctuations on FD was observed. CONCLUSION: This study shows diurnal fluctuations of deep macular FD measured by OCTA and outlines the relationship between FD and hemodynamic parameters (MAP/HR) in POAG patients.

PURPOSE: We aimed to compare the thickness of anterior sclera, corneal layers, and pre-ocular tear film between patients with primary Sjögren's syndrome and healthy individuals. METHODS: Fifty-one patients with primary Sjögren's syndrome and 41 healthy control participants were recruited in this cross-sectional and comparative study. The thickness of the pre-ocular tear film, corneal epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium were measured on the corneal apex. Anterior scleral thickness was measured at distances of 1 mm and 3 mm from the limbus. The anterior segment module of spectral-domain optical coherence tomography was used to measure thicknesses of pre-ocular tear film, corneal layers, and anterior sclera. RESULTS: Tear film thickness, Schirmer's test, and tear break up time values were significantly lower in the Sjögren's disease group than in the healthy controls (p

Purpose: To investigate ophthalmic features in a large group of patients with primary hyperoxaluria type 1 (PH1) and to determine the relation between ocular involvement and systemic disease severity. Design: Retrospective, cross-sectional, multicenter study of the OxalEurope Registry Network. Methods: Sixty-eight patients with PH1 were included. Infantile PH1 was diagnosed in 12 patients, and non-infantile PH1 was diagnosed in 56 patients (17 with end-stage renal disease). Ophthalmic examination included best corrected visual acuity (BCVA) testing and multimodal retinal imaging, including fundus photography and optical coherence tomography (OCT). In selected cases, fundus autofluorescence imaging was performed. Results: All eyes (n = 24) of infantile PH1 patients revealed severe retinal alterations and oxalate deposits, including macular crystals and hyperpigmentations (n = 9, 38%), and subretinal fibrosis (n = 15, 63%) with (n = 7, 47%) or without (n = 8; 53%) associated chronic retinal edema. In 9 eyes (38%, all with subretinal fibrosis), BCVA was significantly reduced (

PURPOSE: To calculate the prevalence of all vitreomacular interface (VMI) disorders and stratify according to age, sex and (pre)diabetes status.METHODS: The presence of VMI disorders was assessed in 2660 participants aged between 40 and 75 years from The Maastricht Study who had a gradable macular spectral-domain optical coherence tomography (SD-OCT) volume scan in at least one eye [mean 59.7 ± 8.2 years, 50.2% men, 1531 normal glucose metabolism (NGM), 401 prediabetes, 728 type 2 diabetes (DM2, oversampled)]. A stratified and multivariable logistic regression analysis was used.RESULTS: The prevalence of the different VMI disorders for individuals with NGM, prediabetes and DM2 was, respectively, 5.7%, 6% and 6.7% for epiretinal membranes; 6%, 9.6% and 6.8% for vitreomacular traction; 1.1%, 0.7% and 0.3% for lamellar macular holes; 0.1%, 0% and 0% for pseudoholes; 1.1%, 1.9% and 5.5% for macular cysts. None of the participants was diagnosed with a macular hole. The prevalence of epiretinal membranes, vitreomacular traction and macular cysts was higher with age (p < 0.001). Vitreomacular traction and lamellar macular holes were more frequent in women (p < 0.01). DM2 is positively associated [OR = 3.9 (95% CI 2.11-7.22, p < 0.001)] with macular cysts and negatively associated with lamellar macular holes [OR = 0.2 (95% CI 0.04-0.9, p = 0.036)] after adjustment for age and sex. The calculated prevalence of VMI disorders was 15.9%.CONCLUSIONS: The calculated prevalence of VMI disorders in individuals aged between 40 and 75 years is 15.9%. The prevalence depends on age, sex and glucose metabolism status for several types of VMI disorders.

Purpose: To investigate the frequency of toxic retinopathy in patients with lupus erythematosus and rheumatoid arthritis with long-term use of chloroquine diphosphate or hydroxychloroquine through spectral domain optical coherence tomography and the outcomes of ophthalmological exams (visual acuity - Snellen’s table, color vision test - Ishihara’s table, fundoscopy, and retinography - red-free). Methods: A cross-sectional study was carried out involving the ophthalmologic evaluation of patients using regular chloroquine diphosphate or hydroxychloroquine for a period of 1 year or longer. The patients completed a questionnaire on their opinions and treatment regularity. The same patients underwent ophthalmologic examination and spectral domain optical coherence tomography. Results: The prevalence of toxic retinopathy caused by antimalarials was 4.15% (9 of 217 patients), 7.4% (4 of 54 patients) following chloroquine diphosphate usage, and 0.82% (1 of 121 patients) following hydroxychloroquine usage. Only patients with advanced stage maculopathy presented abnormalities during the ophthalmologic exam: the color vision test was altered in 11.1%, and visual acuity and fundoscopy were altered in 33.3%. Identification of early toxic retinopathy, detected in six patients, was possible using spectral domain optical coherence tomography. The mean duration of antimalarial drug usage among patients with toxic retinopathy was 10.4 years. Only 31% of the patients reported some symptoms during treatment, and although 24% were afraid to use the medication, they did so as prescribed. Conclusion: Use of spectral domain optical coherence tomography was essential for the diagnosis of early-stage antimalarial toxic retinopathy in patients with the following characteristics: asymptomatic, antimalarial use 7 days a week for a period of more than 5 years, and normal clinical ophthalmologic examination. RESUMO Objetivo: Investigar a frequência da retinopatia tóxica em pacientes com lúpus eritematoso e artrite reumatóide com uso crônico de difosfato de cloroquina ou hidroxicloroquina, através de tomografia de coerência óptica de domínio espectral e os resultados dos exames oftalmológicos (acuidade visual - tabela de Snellen, teste de visão de cor - tabela de Ishihara, fundoscopia e retinografia - red free). Métodos: Foi realizado um estudo transversal envolvendo a avaliação oftalmológica de pacientes em uso regular de difosfato de cloroquina ou hidroxicloroquina por um período de um ano ou mais. Os pacientes responderam a um questionário sobre a sua opinião e regularidade do tratamento. Os mesmos pacientes realizaram exame oftalmológico clínico e tomografia de coerência óptica de domínio espectral. Resultados: A prevalência de retinopatia tóxica por antimaláricos foi de 4,15% (9 dos 217 pacientes), 7,4% (4 de 54 pacientes) após uso de difosfato de cloroquina e 0,82% (1 de 121 pacientes) após uso de hidroxicloroquina. Apenas os pacientes com maculopatia em fase avançada apresentaram alterações durante os exames clínicos: teste de visão de cores alterado em 11,1%, e a acuidade visual e fundoscopia foram alteradas em 33,3%. A identificação de retinopatia tóxica precoce, detectada em seis pacientes, foi possível por meio da tomografia de coerência óptica de domínio espectral. A duração média do tempo de uso de drogas antimaláricas entre os pacientes com retinopatia tóxica foi de 10,4 anos. Apenas 31% dos pacientes relataram algum sintoma durante o tratamento e apesar de 24% terem medo de usar a medicação, eles o fizeram conforme prescrito. Conclusão: O uso da tomografia de coerência óptica de domínio espectral foi essencial para o diagnóstico de retinopatia tóxica antimalárica em estágio inicial em pacientes com as seguintes características: uso assintomático, antimalárico 7 dias por semana por um período maior que cinco anos e exame oftalmológico clínico normal.

Aims: To show non-inferiority of the 67- or 87 µm thick, sirolimus-eluting Orsiro drug eluting stent (DES) to the 122 µm thick, biolimus-eluting Nobori DES regarding size of vessel lumen outside the stent at 13-month follow-up.Methods and results: This study was a substudy to the SORT-OUT VII trial, a prospective, 1:1-randomized, comparison of the two stents in patients with stable coronary artery disease or acute coronary syndrome. Optical coherence tomography was acquired after percutaneous coronary intervention and at 13-month follow-up. The substudy was powered to access non-inferiority (Δ = 0.60 mm2) of the Orsiro DES to the Nobori DES for the primary endpoint of mean extra stent lumen (ESL) i.e. vessel lumen outside the stent at 13-month follow-up. We randomized 124 patients to Orsiro (n = 60) or Nobori (n = 64). Due to a difference in the one-sided 95%-confidence interval of 0.26 mm2, but increased to 0.82 mm2 after appropriate log-transformation, it could not be rejected that Orsiro exceeded the non-inferiority limit. Testing for superiority, Orsiro had a significantly larger mean ESL at follow-up (Orsiro: 0.11 mm2 [0.02;0.30] mm2, Nobori: 0.03 mm2 [0.00;0.17] mm2, P = 0.04). Stent strut coverage was, Orsiro: 97.6 % [93.8;99.4]%, and Nobori: 96.3 % [90.5;98,6]% (P = 0.13).Conclusion: Orsiro DES had a significantly larger mean ESL at follow-up and it could not be excluded that Orsiro exceeded the limit for non-inferiority. Nobori DES had a more heterogeneous distribution of neointima but stent strut coverage did not differ significantly between the two stents.

To use optical coherence tomography angiography (OCTA) to evaluate foveal microvascular changes in diabetes by comparing the area of foveal avascular zone (FAZ) in healthy controls and patients with diabetes with no diabetic retinopathy (NDR) as well as different stages of diabetic retinopathy (DR). A systematic literature search was performed based on the population, intervention, comparison and outcome (PICO) strategy by two independent reviewers. The search was performed in PubMed, Embase and Cochrane Library, including keywords 'diabetes mellitus', 'DR' and 'OCTA'. Of 358 studies initially identified, 215 studies were screened after duplicate removal. Of these, we included 12 (nine cross-sectional and three retrospective) studies in this review. With the data at hand, it was not possible to perform a meta-analysis. The selected studies included patients with NDR (n = 8), non-proliferative diabetic retinopathy (NPDR, n = 8) and proliferative diabetic retinopathy (PDR, n = 6). Several of the studies provided information for more than one diabetic group. In general, there was a trend towards a larger area of FAZ in patients with diabetes. As compared to healthy controls, this was reported in patients with NDR (five of eight studies), NPDR (seven of eight studies) and PDR (six of six studies). Optical coherence tomography angiography (OCTA) is non-invasively able to identify foveal capillary non-perfusion as an early event in DR. In some studies, this has even been identified in patients without clinically identifiable microvascular lesions. Longitudinal studies would be needed to examine if OCTA-findings are able to predict long-term structural and functional outcome.

Purpose: To (a) determine the normative values for optical coherence tomography (OCT) parameters such as central macular thickness, retinal nerve fiber layer thickness, and choroidal thickness in healthy children; (b) investigate the relationships of these parameters with axial length, central corneal thickness, refractive errors, and intraocular pressure; and (c) determine interexaminer agreement for choroidal thickness measurements. Methods: In this cross-sectional study, 120 healthy children aged 8-15 years underwent detailed ophthalmological examination and OCT measurements. Choroidal thickness was measured at three separate locations by two independent examiners. Results: The mean global retinal nerve fiber layer thickness was 98.75 ± 9.45 μm (79.0-121.0). The mean central macular thickness was 232.29 ± 29.37 μm (190.0-376.0). The mean subfoveal choroidal thickness obtained by examiner 1 was 344.38 ± 68.83 μm and that obtained by examiner 2 was 344.04 ± 68.92 μm. Interexaminer agreement was between 99.6%-99.8% for choroidal thickness at three separate locations. Central macular thickness increased with axial length (r=0.245, p=0.007). Choroidal thickness increased with age (r=0.291, p=0.001) and decreased with axial length (r=-0.191, p=0.037). Global retinal nerve fiber layer thickness decreased with axial length (r=-0.247, p=0.007) and increased with central corneal thickness (r=0.208, p=0.022). Global retinal nerve fiber layer thickness positively correlated with choroidal thickness (r=0.354, p

Purpose: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population.Design: Cross-sectional meta-analysis.Participants: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9 +/- 12.3-82.1 +/- 4.2 years) of the European Eye Epidemiology (E3) consortium.Methods: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis.Main Outcome Measures: Determinants of pRNFLT.Results: Mean pRNFLT ranged from 86.8 +/- 21.4 mu m in the Rotterdam Study I to 104.7 +/- 12.5 mu m in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (beta = -0.38 mu m/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (10P) (beta = -0.36 mu m/mmHg; 95% CI, -0.56 to -0.15), visual impairment (beta = -5.50 mu m; 95% CI, -9.37 to -1.64), and history of systemic hypertension (beta = -0.54 mu m; 95% CI, -1.01 to -0.07) and stroke (beta = -1.94 mu m; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (beta = -3.11 mu m; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (beta = 1.39 mu m/diopter; 95% CI, 1.19-1.59) and smoking (beta = 1.53 mu m; 95% CI, 1.00-2.06 for current smokers compared with never-smokers).Conclusions: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities. (C) 2018 by the American Academy of Ophthalmology

BackgroundSmall hard macular drusen can be observed in the retina of adults as young as 18 years of age. Here, we seek to describe the in vivo topography and geometry of these drusen.MethodsRetinal images were acquired in young, healthy adults using colour fundus photography, spectral domain optic coherence tomography (SD-OCT), reflectance flood-illuminated adaptive optic ophthalmoscopy (AO flood) and reflectance adaptive optic scanning light ophthalmoscopy (AOSLO) in both confocal and non-confocal split-detection modalities. Small bright yellow hard drusen within a 10 degree radius from the foveal centre were characterised.ResultsSmall hard drusen were seen on colour photographs in 21 out of 97 participants and 26 drusen in 12 eyes in 11 participants were imaged using the full protocol. Drusen were easily identifiable in all modalities, except a few very small ones, which were not visible on SD-OCT. On AOSLO images, these drusen appeared as round, oval or lobular areas (up to three lobules) of diameter 22–61 µm where cone photoreceptor reflectivity and density was decreased (p=0.049). This was usually associated with discrete thickening of the retinal pigment epithelium (RPE) complex.ConclusionHigh lateral resolution imaging of small lobular hard retinal drusen suggests formation through the confluence of two or more smaller round lesions. The outline and size of these smaller lesions corresponds to 1–4 RPE cells. Prospective longitudinal studies are needed to determine the ultimate fate of small hard drusen and their potential relation to age-related macular degeneration.