...investigators have attempted over the decades to identify early changes in the retinal vessels in diabetes and determine whether they could inform about the development of retinopathy and other ...complications. ...the incremental value of a novel biomarker over standard available biomarkers should be assessed not only with standard statistical measures such as the area under the curve (AUC) of the receiver operating characteristic curve or C-statistic, but also with more recently developed measures such as weighted net reclassification index (wNRl) and net benefit (NB) (5).
OBJECTIVE:Reduction in capillary density or rarefaction is a hallmark of essential hypertension. We measured the retinal capillary density using noninvasive optical coherence tomographic angiography ...(OCT-A) in adults with treated systemic hypertension and determined possible correlations with ambulatory blood pressure (BP) and renal parameters.
METHODS:This observational cross-sectional study consisted of 153 normal eyes from 77 nondiabetic hypertensive adults mean (SD) age, 58 (9) years; 49% women; 23% poorly controlled BP. Data on 24-h ambulatory BP monitoring, serum creatinine, and urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. Retinal capillary density measured with the OCT-A (AngioVue) at superficial (SVP) and deep vascular plexuses (DVP). Linear regression was used to investigate the association of risk factors with capillary density.
RESULTS:Retinal capillary density (percentage) at DVP was reduced in patients with poorly controlled BP (SBP = 148 ± 8 mmHg; 27.2 ± 13.0) compared with those with well controlled BP (SBP = 125 ± 9 mmHg; 34.7 ± 11.3). In the multivariable analysis, poorly controlled BP β = −6.49, 95% confidence interval (CI), −12.39 to −0.59, higher SBP (β = −0.23, 95% CI −0.44 to −0.02) and lower eGFR (β = 6.42, 95% CI 1.25–11.60) were associated with sparser retinal capillary density. Systemic factors were not associated with capillary density at SVP (all P > 0.05).
CONCLUSION:In adults with treated systemic hypertension, retinal capillary density reduced with higher BP and poorer eGFR. These findings highlight the potential role of OCT-A to study early microvascular changes because of systemic hypertension.
To investigate the association of lens parameters-specifically, lens vault (LV), lens thickness (LT), and lens position (LP)-with angle closure.
Prospective, comparative study.
One hundred two ...Chinese subjects with angle closure (consisting of primary angle closure, primary angle-closure glaucoma, and previous acute primary angle closure) attending a glaucoma clinic and 176 normal Chinese subjects with open angles and no evidence of glaucoma recruited from an ongoing population-based cross-sectional study.
All participants underwent gonioscopy and anterior-segment optical coherence tomography (AS OCT; Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure LV, defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the 2 scleral spurs, on horizontal AS OCT scans. A-scan biometry (US-800; Nidek Co, Ltd, Tokyo, Japan) was used to measures LT and to calculate LP (defined as anterior chamber depth ACD +1/2 LT) and relative LP (RLP; defined as LP/axial length AL).
Lens parameters and angle closure.
Significant differences between angle-closure and normal eyes were found for LV (901±265 vs. 316±272 μm; P<0.001), LT (4.20±0.92 vs. 3.90±0.73 mm; P = 0.01), LT-to-AL ratio (0.18±0.04 vs. 0.16±0.03; P<0.001), ACD (2.66±0.37 vs. 2.95±0.37 mm; P<0.001), and AL (22.86±0.93 vs. 23.92±1.37 mm; P<0.001), but no significant differences were found for LP (4.76±0.51 vs. 4.90±0.54 mm; P = 0.34) or RLP (0.21±0.02 vs. 0.20±0.02; P = 0.14). After adjusting for age, gender, ACD, LT, and RLP, increased LV was associated significantly with angle closure (odds ratio OR, 48.1; 95% confidence interval CI, 12.8-181.3, comparing lowest to highest quartile), but no association was found for LT (OR, 1.78; 95% CI, 0.76-4.16), LP (OR, 1.94; 95% CI, 0.59-6.31), or RLP (OR, 2.08; 95% CI, 0.66-6.57). There was low correlation between LV and LT (Pearson's correlation coefficient PCC, 0.17), between LV and RLP (PCC, 0.08), or between LV and LP (PCC, 0.2).
Eyes with angle closure have thicker lenses with greater LV compared with normal eyes. The LV, which represents the anterior portion of the lens, is a novel parameter independently associated with angle closure after adjusting for age, gender, ACD, and LT.
To describe the natural history of branch retinal vein occlusion (BRVO) based on the best available evidence from the literature.
Branch retinal vein occlusion is the second most frequent major ...retinal vascular disease. Although several new treatments for BRVO are currently being introduced, data on its natural history are sparse.
English language articles were retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008, supplemented by manually searching the references of review articles published within the last 5 years. All relevant observational studies evaluating the natural history of BRVO and all clinical trials evaluating BRVO interventions with an untreated control arm were independently identified by 2 investigators.
Of a total of 5965 citations retrieved, 24 eligible studies were identified and reviewed, providing 1608 eyes with BRVO with data on natural history. Visual acuity (VA) was moderately poor at baseline (<20/40). Although VA generally improved, with mean improvement ranging from 1 letter at 6 weeks to 28 letters up to 24 months, few studies reported improvement beyond 20/40. Over a 1-year period, 5% to 15% of eyes developed macular edema (ME), but of those with ME at baseline, 18% to 41% resolved. At baseline, 5% to 6% of eyes had bilateral BRVO, with 10% developing fellow eye involvement over time. There were few high-quality studies on other outcomes, including development of new vessels.
Visual acuity generally improved in eyes with BRVO without intervention, although clinically significant improvement beyond 20/40 was uncommon.
IMPORTANCE: Optical coherence tomographic angiography (OCT-A) is able to visualize retinal microvasculature without the need for injection of fluorescein contrast dye. Nevertheless, it is only able ...to capture a limited view of macula and does not show leakage. OBJECTIVES: To evaluate the retinal microvasculature using OCT-A in patients with type 2 diabetes as well as the association of OCT-A characteristics with diabetic retinopathy (DR) and systemic risk factors. DESIGN, SETTING, AND PARTICIPANTS: A prospective, observational study was conducted from January 1 to June 30, 2016, at medical retina clinics at the Singapore National Eye Center among 50 patients with type 2 diabetes with and without DR (n = 100 eyes). We examined the retinal microvasculature with swept-source OCT-A and a semiautomated software to measure the capillary density index (CDI) and fractal dimension (FD) at the superficial vascular plexus (SVP) and deep retinal vascular plexus (DVP). We collected data on histories of patients’ glycated hemoglobin A1c, hypertension, hyperlipidemia, smoking, and renal impairment. MAIN OUTCOMES AND MEASURES: The CDI and FD at the SVP and DVP for each severity level of DR and the association of systemic risk factors vs the CDI and FD. RESULTS: The mean (SD) glycated hemoglobin A1c of the 50 patients (26 men and 24 women; 35 Chinese; mean SD age, 59.5 8.9 years) was 7.9% (1.7%). The mean (SD) CDI at the SVP decreased from 0.358 (0.017) in patients with no DR to 0.338 (0.012) in patients with proliferative DR (P < .001) and at the DVP decreased in patients with no DR from 0.361 (0.019) to 0.345 (0.020) in patients with proliferative DR (P = .04). The mean (SD) FD at the SVP increased from 1.53 (0.05) in patients with no DR to 1.60 (0.05) in patients with proliferative DR (P < .01) and at the DVP increased from 1.55 (0.06) in patients with no DR to 1.61 (0.05) in patients with proliferative DR (P = .02). For systemic risk factors, hyperlipidemia (odds ratio OR, 9.82; 95% CI, 6.92-11.23; P < .001), smoking (OR, 10.90; 95% CI, 8.23-12.34; P < .001), and renal impairment (OR, 3.72; 95% CI, 1.80-4.81; P = .05) were associated with reduced CDI, while increased glycated hemoglobin A1c (≥8%) (OR, 8.77; 95% CI, 5.23-10.81; P < .01) and renal impairment (OR, 10.30; 95% CI, 8.21-11.91; P < .001) were associated with increased FD. CONCLUSIONS AND RELEVANCE: Optical coherence tomographic angiography is a novel imaging modality to quantify the retinal capillary microvasculature in patients with diabetes. It can be potentially used in interventional trials to study the effect of systemic risk factors on the microvasculature that was previously not accessible in a noninvasive manner. The relevance of these findings relative to visual acuity, however, remains largely unknown at this time.
IMPORTANCE: A deep learning system (DLS) that could automatically detect glaucomatous optic neuropathy (GON) with high sensitivity and specificity could expedite screening for GON. OBJECTIVE: To ...establish a DLS for detection of GON using retinal fundus images and glaucoma diagnosis with convoluted neural networks (GD-CNN) that has the ability to be generalized across populations. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, a DLS for the classification of GON was developed for automated classification of GON using retinal fundus images obtained from the Chinese Glaucoma Study Alliance, the Handan Eye Study, and online databases. The researchers selected 241 032 images were selected as the training data set. The images were entered into the databases on June 9, 2009, obtained on July 11, 2018, and analyses were performed on December 15, 2018. The generalization of the DLS was tested in several validation data sets, which allowed assessment of the DLS in a clinical setting without exclusions, testing against variable image quality based on fundus photographs obtained from websites, evaluation in a population-based study that reflects a natural distribution of patients with glaucoma within the cohort and an additive data set that has a diverse ethnic distribution. An online learning system was established to transfer the trained and validated DLS to generalize the results with fundus images from new sources. To better understand the DLS decision-making process, a prediction visualization test was performed that identified regions of the fundus images utilized by the DLS for diagnosis. EXPOSURES: Use of a deep learning system. MAIN OUTCOMES AND MEASURES: Area under the receiver operating characteristics curve (AUC), sensitivity and specificity for DLS with reference to professional graders. RESULTS: From a total of 274 413 fundus images initially obtained from CGSA, 269 601 images passed initial image quality review and were graded for GON. A total of 241 032 images (definite GON 29 865 12.4%, probable GON 11 046 4.6%, unlikely GON 200 121 83%) from 68 013 patients were selected using random sampling to train the GD-CNN model. Validation and evaluation of the GD-CNN model was assessed using the remaining 28 569 images from CGSA. The AUC of the GD-CNN model in primary local validation data sets was 0.996 (95% CI, 0.995-0.998), with sensitivity of 96.2% and specificity of 97.7%. The most common reason for both false-negative and false-positive grading by GD-CNN (51 of 119 46.3% and 191 of 588 32.3%) and manual grading (50 of 113 44.2% and 183 of 538 34.0%) was pathologic or high myopia. CONCLUSIONS AND RELEVANCE: Application of GD-CNN to fundus images from different settings and varying image quality demonstrated a high sensitivity, specificity, and generalizability for detecting GON. These findings suggest that automated DLS could enhance current screening programs in a cost-effective and time-efficient manner.
Statistical learning methods are widely used in medical literature for the purpose of diagnosis or prediction. Conventional accuracy assessment via sensitivity, specificity, and ROC curves does not ...fully account for clinical utility of a specific model. Decision curve analysis (DCA) becomes a novel complement as it incorporates a clinical judgment of the relative value of benefits (treating a true positive case) and harms (treating a false positive case) associated with prediction models. The preference of a patient or a policy‐maker is formulated statistically as the underlying threshold probability, above which the patient would choose to be treated. Net benefit is then calculated for possible threshold probability, which places benefits and harms on the same scale. We consider the inference problems for DCA in this paper. Interval estimation procedure and inference methodology are provided after we derive the relevant asymptotic properties. Our formulation can accommodate the classification problems with multiple categories. We carry out numerical studies to assess the performance of the proposed methods. An eye disease dataset is analyzed to illustrate our proposals.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Overweight and obesity are thought to significantly influence a person's risk of cardiovascular disease, possibly via its effect on the microvasculature. Retinal vascular caliber is a surrogate ...marker of microvascular disease and a predictor of cardiovascular events. The aim of this systematic review and meta-analysis was to determine the association between body mass index (BMI) and retinal vascular caliber.
Relevant studies were identified by searches of the MEDLINE and EMBASE databases from 1966 to August 2011. Standardized forms were used for data extraction. Among over 44,000 individuals, obese subjects had narrower arteriolar and wider venular calibers when compared with normal weight subjects, independent of conventional cardiovascular risk factors. In adults, a 1 kg/m(2) increase in BMI was associated with a difference of 0.07 μm 95% CI: -0.08; -0.06 in arteriolar caliber and 0.22 μm 95% CI: 0.21; 0.23 in venular caliber. Similar results were found for children.
Higher BMI is associated with narrower retinal arteriolar and wider venular calibers. Further prospective studies are needed to examine whether a causative relationship between BMI and retinal microcirculation exists.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The relative contribution of mechanical and vascular factors to the pathogenesis of myopic macular degeneration (MMD) is unclear. To address this gap, we examined the association of choroidal ...thickness (CT) and scleral thickness (ST) with MMD.
Prospective, clinic-based case series of 62 eyes of 41 patients with high myopia (≤-6 diopters or axial length ≥26.5 mm). Swept-source optical coherence tomography (SSOCT) was performed to measure subfoveal CT and ST. Myopic macular degeneration was graded from fundus photographs according to the International Meta-Analysis for Pathologic Myopia (META-PM) classification. Presence of MMD was defined as META-PM category ≥ 2 and severe MMD was defined as category ≥ 3.
The distribution of MMD severity was 15 (24.2%) in category 1, 28 (45.2%) in category 2, 10 (16.1%) in category 3, and 9 (14.5%) in category 4. Correlation of MMD severity was strong for subfoveal CT (r = -0.70, P < 0.001) but weak for subfoveal ST (r = -0.31, P = 0.01). Subfoveal CT, but not ST, was independently associated with presence of MMD (age and gender adjusted odds ratio OR per 10 μm decrease in CT 1.41, P = 0.002), and subfoveal CT, but not subfoveal ST, was significantly thinner in eyes with severe MMD (≥ category 3) than in eyes with mild MMD (CT: 31.5 ± 40.5 μm versus 82.0 ± 57.1 μm, P < 0.001; ST: 261.6 ± 78.5 μm versus 297.0 ± 73.8 μm, P = 0.09).
We demonstrated significant thinning of the choroid with increasing MMD severity. In contrast, ST was weakly correlated with MMD. These data suggest progressive loss of choroid may be important in the pathogenesis of MMD.
To characterize and compare morphologic and vascular features of the choroid in patients with typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) and to ...determine if PCV subtypes can be identified based on these choroidal features.
Choroidal features of patients with AMD and PCV recruited from the prospectively planned Asian AMD Phenotyping Study were analyzed. Patients underwent choroidal imaging using spectral-domain optical coherence tomography with enhanced depth imaging. Raw optical coherence tomographic images were loaded on a custom-written application on MATLAB that enabled delineation for detailed morphologic and vascular analyses, including the curvature of the choroid-sclera interface, number of inflection points, choroidal thickness and choroidal vascular area within the macular (6 mm centered on fovea) and foveal (1.5 mm centered on fovea) regions. An inflection point represents the contour of the choroid-sclera interface, with >1 point signaling irregular shape.
A total of 156 eyes of 156 patients (78 affected eyes of 78 patients with typical AMD and 78 affected eyes of 78 patients with PCV) were analyzed. Eyes with PCV had thicker baseline choroidal thickness and greater choroidal vascular area compared with those with typical AMD (P < 0.05); these differences were no longer significant after adjusting for age and hypertension (P > 0.05). Typical PCV subtype with choroidal thickness of ≥257 μm had significantly greater choroidal vascular area at macular (mean difference = 0.054 mm; P < 0.001) and foveal (mean difference = 0.199 mm; P < 0.001) regions compared with eyes with typical AMD. However, eyes with PCV without thick choroid had similar choroidal vascular area as eyes with typical AMD.
Based on the choroidal vascular features, two subtypes of PCV can be classified: typical PCV with increased choroid vascularity and polypoidal choroidal neovascularization with low choroidal vascularity. These data provide further understanding of different AMD and PCV subtypes.
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