Areas Of Dropout Research Articles

Occult retinal neovascularization following intravitreal bevacizumab and laser treatment for retinopathy of prematurity

BackgroundWe present a patient with retinopathy of prematurity (ROP) who developed worsening plus disease after complete regression of stage 3 ROP. The use of fundus fluorescein angiography (FFA) aided the visualization of occult neovascularization that caused the disease progression.Case presentationThe patient was at high risk for ROP due to low birth weight of 690 g and gestational age of 25 weeks. After the diagnosis of stage 3 ROP in zone I without plus disease, she was treated initially with bilateral intravitreal bevacizumab (IVB) and followed by laser photocoagulation 5 weeks later. Despite the resolution of ROP stage, the plus disease worsened. Neither systemic risk factors nor skip laser areas were observed. Hence, FFA was performed and subsequently identified occult neovascularization with active leakage. Additional IVB and laser treatment in the capillary dropout area inside vascularized retina were added. The plus disease improved but mild arteriolar tortuosity persisted.ConclusionsWorsening of plus disease after completion of laser ablation and IVB with complete regression of stage 3 ROP is rare. Systemic risk factors such as continuous oxygen therapy and cardiovascular disease should be ruled out. FFA aided in identifying occult neovascularization and prompted further treatment.

Parapapillary choroidal microvasculature dropout in eyes with primary open-angle glaucoma

The purpose of this study was to evaluate how various parameters are related to microvasculature dropout (MvD) area measured using optical coherence tomography angiography (OCTA). We measured the area of MvD in 55 patients with primary open-angle glaucoma (POAG). Using OCTA, MvD area and peripapillary choroidal atrophy (PPA) area were assessed in a 4.5 mm × 4.5 mm region. The following were examined: circumpapillary nerve fiber layer (cpRNFL) thickness, optic disc area, optic disc cupping area, optic disc rim area, Humphrey Field Analyzer (HFA) 24/10–2 mean deviation (MD), and pattern standard deviation (PSD). The relationship between MvD area and each parameter was evaluated using Spearman’s rank correlation coefficient analysis. Mean MvD area and PPA area were 0.18 ± 0.17 mm2 and 1.13 ± 0.72 mm2, respectively. MvD area was significantly correlated with optic disc rim area (p = 0.0017), cpRNFL (p = 0.0027), HFA 24/10–2 MD, and PSD (p < 0.001). In eyes with POAG, MvD area indicates the severity of glaucoma, which might be associated with structural changes in the peripapillary vasculature around the optic disc.

Visual acuity changes associated with foveal ischemia detected by optical coherence tomography angiography in type II diabetic patients without diabetic retinopathy

Purpose Diabetic macular ischemia is a vision-threatening complication of diabetes mellitus. Early detection of ischemic changes can preserve the vision. The aim of the study was to detect the early macular ischemic changes in patients with no diabetic retinopathy (NDR), using optical coherence tomography angiography, and to correlate these changes with the best-corrected distance visual acuity (BCDVA). Patients and methods A case–control study was conducted to compare 30 diabetic eyes with NDR with 30 healthy control eyes. The glycemic control was determined by glycosylated hemoglobin level less than 6.5%. The diabetic group was further subdivided into those with normal BCDVA and those with decreased BCDVA. The outcome measures included BCDVA and optical coherence tomography angiography features. Results Compared with controls, the diabetics with decreased BCDVA were found to have significantly thinner central macular thickness (P<0.001), larger foveal avascular zone (FAZ) area (P<0.001) in the superficial and deep capillary plexuses (sFAZ and dFAZ), and lower vascular density (VD) (P<0.05) regarding the central density and the superior, inferior, and temporal quadrants. In addition, they showed significantly larger associated capillary dropout areas in the superficial and deep capillary plexuses and significantly lower foveal and parafoveal VD compared with diabetics with normal BCDVA (P<0.001 and 0.05, respectively). Diabetics with normal BCDVA showed no significant difference from the controls regarding the dFAZ and VD but showed significantly lower sFAZ area (P<0.05). Conclusion Diabetic ischemic microvascular changes including decreased VD and enlarged FAZ areas precede clinically visible retinopathy and might be correlated with decreased visual acuity in patients with NDR.

Novel optical coherence tomography angiography biomarkers in the diagnosis and assessment of diabetic macular edema and diabetic macular ischemia in patients with non-proliferative diabetic retinopathy.

The present study aims to determine the macular and choroidal optical coherence tomography angiography (OCTA) biomarkers in the assessment and monitoring of diabetic macular edema (DME) and diabetic macular ischemia (DMI) in patients with non-proliferative diabetic retinopathy (NPDR). In this cohort study, a total of 176 eyes of 110 patients with NPDR were investigated at our institute over a period of 10 months. Eyes were divided into four groups based on the severity of NPDR. Each eye was subjected to OCTA (Topcon 3D OCT-1 Maestro2) macula 6 × 6 mm2 en face. It features IMAGEnet 6 software for dynamic viewing of OCTA and imaging data. Four OCTA biomarkers for the macula were identified: foveal avascular zone area (FAZ area), foveal avascular zone contour irregularity (FAZ-CI), capillary dropout areas (CDA), and perifoveal intercapillary areas (PICA). The choroidal OCTA biomarker was the number of choroidal circulation flow voids (CCFV). For all analyses, P < 0.05 was considered statistically significant. Increase in FAZ area and number of CDA were statistically significant (p < 0.0001) with an increase in central foveal thickness, suggesting a correlation of ischemic changes with an increase in DME. FAZ-CI, enlarged PICA, and CCFV were significantly associated with more severe NPDR patients. A correlation between DME and DMI in a patient of NPDR and its progression can be evaluated in a single visit. A unique feature of our study is it revealed novel diagnostic biomarkers of OCTA for DMI and DME.

Relationship between meibomian gland loss in infrared meibography and meibum quality in dry eye patients

BackgroundIn the present study, we evaluated the correlation between meibomian gland dropout and meibum quality in the same central 8 meibomian glands of the eyelid.MethodsNinety-nine eyes of 91 patients with dry eye were included in the study. Dropout of the 8 central meibomian glands of the eyelids was graded as 0, 1, 2, or 3, according to the dropout area. The meibum quality was graded as follows: grade 0, no secretion; 1, inspissated/toothpaste consistency; 2, cloudy liquid secretion; and 3, clear liquid secretion. For 68 eyes of 68 patients, correlation analysis between dropout and meibum quality was performed. To precisely analyze the direct correlation between meibomian gland dropout in meibography and meibum quality, we evaluated 31 eyes of 23 patients with focal dropout in meibography.ResultsThe median (interquartile range) meiboscore was 1.0 (2.0) in the upper eyelids and 0.0 (1.0) in the lower eyelids. The median (interquartile range) meibum quality grade was 3.0 (1.0) in the upper eyelids and 1.0 (1.0) in the lower eyelids. No significant correlation between the meiboscore and meibum quality grade was detected in the upper (p =0.746) or lower (p =0.551) eyelids. Analysis of the direct correlation between meibomian gland dropout in meibography and meibum quality in patients with focal dropout (loss of 1 or 2 adjacent meibomian glands), however, indicated that meibomian glands with dropout secreted little to no meibum.ConclusionsOverall analysis revealed no relationship between meibomian gland dropout and meibum quality, but more detailed investigation of each meibomian gland alone revealed that meibomian glands with dropout secrete little to no meibum.

2D Short-Time Fourier Transform for local morphological analysis of meibomian gland images.

Meibography is becoming an integral part of dry eye diagnosis. Being objective and repeatable this imaging technique is used to guide treatment decisions and determine the disease status. Especially desirable is the possibility of automatic (or semi-automatic) analysis of a meibomian image for quantification of a particular gland's feature. Recent reports suggest that in addition to the measure of gland atrophy (quantified by the well-established "drop-out area" parameter), the gland's morphological changes may carry equally clinically useful information. Here we demonstrate the novel image analysis method providing detailed information on local deformation of meibomian gland pattern. The developed approach extracts from every Meibomian image a set of six morphometric color-coded maps, each visualizing spatial behavior of different morphometric parameter. A more detailed analysis of those maps was used to perform automatic classification of Meibomian glands images. The method for isolating individual morphometric components from the original meibomian image can be helpful in the diagnostic process. It may help clinicians to see in which part of the eyelid the disturbance is taking place and also to quantify it with a numerical value providing essential insight into Meibomian gland dysfunction pathophysiology.

Meibomian Gland Dysfunction Associated with Bortezomib in a Multiple Myeloma Patient

Purpose: This study reports a case of meibomian gland dysfunction associated with bortezomib, which is a treatment of choice for multiple myeloma.Case summary: A 59‐year‐old female patient presented to our hospital with a complaint of dryness that had worsened for 2 months and eye discharges that were difficult to remove even after washing her face. The patient had been diagnosed with multiple myeloma 5 months prior and had undergone four cycles of bortezomib therapy. Slit‐lamp microscopy revealed a number of pouting of the meibomian gland (MG) orifices in both eyes. Meibography revealed that more than one‐third and less than twothirds of the total MG area of both upper lids were lost and more than two‐thirds of the total MG area of both lower lids were lost. No clinically significant improvements were noted at 8 months despite thorough eyelid hygiene therapy, including warm compresses, topical antibiotics, steroids, and artificial tears. However, when the patient revisited our clinic 2 months after completing bortezomib treatment, the subjective symptoms had improved and all of the pouting of MG orifices had disappeared. There was no significant difference in the MG dropout area for either eye compared with the observations from a previous visit during bortezomib treatment.Conclusions: Clinicians should be aware that MG dysfunction may occur or worsen in patients receiving bortezomib treatment and should consider this when establishing a treatment plan for meibomian dysfunction or when educating patients.

Evaluation of the Ocular Surface, Conjunctival Impression Cytology and Meibomian Gland Dropout in Patients with Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an idiopathic disease with chronic inflammation. We aimed to determine the changes caused by the chronic inflammatory nature of FMF on the ocular surface, meibomian glands (MG), and conjunctiva via conjunctival impression cytology (CIC). Forty-two FMF patients with a mean age of 11.93±3.92 years and 36 control patients with a mean age of 11.83±3.38 years were included in the study. Ocular surface anomalies of the patients were evaluated using Schirmer II, TBUT and OSDI. MG function (meibum quality), morphology (meiboography), and CIC were evaluated. Although there was a significant difference between the groups in terms of Schirmer II and TBUT, OSDI scores did not significantly differ (P=0.022, 0.010, and 0.099 respectively), and no significant dry eye sign was observed in either group. There was significant difference between the groups in terms of the percent area of MG dropout, MG density, meiboscore (P=0.020, 0.023, and 0.031 respectively), but no significant difference was observed in relation to MG quality (P=0.650). Although conjunctival impression cytology was of a higher grade in the patients with FMF according to Nelson's classification, no significant difference was observed between the groups (P=0.109). Although there was a decrease in the number of MGs in FMF patients, no significant deterioration was observed in conjunctival cytology. In these patients, tear film stability may deteriorate in particular. Clinicians should be aware of the possibility of ocular surface disease secondary to MG dropout in patients with FMF.

Morphological variants of meibomian glands: correlation of meibography features with histopathology findings

PurposeThis study describes the histopathological features of different morphological variants of human meibomian glands (MGs) seen on infrared imaging.MethodsTarsal plates dissected from seven cadaveric upper eyelids were imaged using infrared...

Improving the Breath-Holding CVR Measurement Using the Multiband Multi-Echo EPI Sequence.

Blood oxygen level-dependent (BOLD) functional MRI (fMRI) is commonly used to measure cerebrovascular reactivity (CVR), which can convey insightful information about neurovascular health. Breath-holding (BH) has been shown to be a practical vasodilatory stimulus for measuring CVR in clinical settings. The conventional BOLD fMRI approach has some limitations, however, such as susceptibility-induced signal dropout at air tissue interfaces and low BOLD sensitivity especially in areas of low . These drawbacks can potentially be mitigated with multi-echo sequences, which acquire several images at different echo times in one shot. When combined with multiband techniques, high temporal resolution images can be acquired. This study compared an advanced multiband multi-echo (MBME) echo planar imaging (EPI) sequence with an existing multiband single-echo (MB) sequence to evaluate the repeatability and sensitivity of BH activation and CVR mapping. Images were acquired from 28 healthy volunteers, of which 18 returned for repeat imaging. Both MBME and MB data were pre-processed using both standard and advanced denoising techniques. The MBME data was further processed by combining echoes using a -weighted approach and denoising using multi-echo independent component analysis. BH activation was calculated using a general linear model and the respiration response function. CVR was computed as the percent change related to the activation. To account for differences in CVR related to TE, relative CVR (rCVR) was computed and normalized to the mean gray matter CVR. Test–retest metrics were assessed with the Dice coefficient, rCVR difference, within subject coefficient of variation, and the intraclass correlation coefficient. Our findings demonstrate that rCVR for MBME scans were significantly higher than for MB scans across most of the gray matter. In areas of high susceptibility-induced signal dropout, however, MBME rCVR was significantly less than MB rCVR due to artifactually high rCVR for MB scans in these regions. MBME rCVR showed improved test–retest metrics compared with MB. Overall, the MBME sequence displayed superior BOLD sensitivity, improved specificity in areas of signal dropout on MBME scans, enhanced reliability, and reduced variability across subjects compared with MB acquisitions. Our results suggest that the MBME EPI sequence is a promising tool for imaging CVR.

Image based analysis of meibomian gland dysfunction using conditional generative adversarial neural network

ObjectiveMeibomian gland dysfunction (MGD) is a primary cause of dry eye disease. Analysis of MGD, its severity, shapes and variation in the acini of the meibomian glands (MGs) is receiving...

Footprints of Nanoscale DNA-Silver Cluster Chromophores via Activated-Electron Photodetachment Mass Spectrometry.

DNA-templated silver clusters (AgC) are fluorescent probes and biosensors whose electronic spectra can be tuned by their DNA hosts. However, the underlying rules that relate DNA sequence and structure to DNA-AgC fluorescence and photophysics are largely empirical. Here, we employ 193 nm activated electron photodetachment (a-EPD) mass spectrometry as a hybrid MS3 approach to gain structural insight into these nanoscale chromophores. Two DNA-AgC systems are investigated with a 20 nt single-stranded DNA (ssDNA) and a 28 nt hybrid hairpin/single-stranded DNA (hpDNA). Both oligonucleotides template Ag10 clusters, but the two complexes are distinct chromophores: the former has a violet absorption at 400 nm with no observable emission, while the latter has a blue-green absorption at 490 nm with strong green emission at 550 nm. Via identification of both apo and holo (AgC-containing) sequence ions generated upon a-EPD and mapping areas of sequence dropout, specific DNA regions that encapsulate the AgC are assigned and attributed to the coordination with the DNA nucleobases. These a-EPD footprints are distinct for the two complexes. The ssDNA contacts the cluster via four nucleobases (CCTT) in the central region of the strand, whereas the hpDNA coordinates the cluster via 13 nucleobases (TTCCCGCCTTTTG) in the double-stranded region of the hairpin. This difference is consistent with prior X-ray scattering spectra and suggests that the clusters can adapt to different DNA hosts. More importantly, the a-EPD footprints directly identify the nucleobases that are in direct contact with the AgC. As these contacting nucleobases can tune the electronic structures of the Ag core and protect the AgC from collisional quenching in solution, understanding the DNA-silver contacts within these complexes will facilitate future biosensor designs.

Meibomian Gland Morphology: The Influence of Structural Variations on Gland Function and Ocular Surface Parameters

To objectively and quantitatively characterize meibomian gland morphology and to investigate the influence of morphological variations on gland function and ocular surface and tear film parameters. One hundred fifty subjects were enrolled. The examinations included tear osmolarity, tear meniscus height, bulbar conjunctival hyperemia, noninvasive tear film breakup time, lid margin thickness, foam secretion, meibomian gland expressibility, count of functioning glands, corneal and conjunctival staining, fluorescein breakup time, lid wiper epitheliopathy, and Schirmer test. Patient symptoms were assessed using the Ocular Surface Disease Index questionnaire. Images from noncontact meibography were analyzed using an automated method that objectively estimates dropout area, number of glands, gland length and width, and gland irregularity. Gland irregularity highly correlated with dropout area (r = -0.4, P < 0.001) and showed significant partial correlations with fluorescein breakup time (r = 0.162, P = 0.049) and the Ocular Surface Disease Index questionnaire (r = -0.250, P = 0.002) Subjects with dropout area <32% were divided into 2 groups: high and low irregularity. Gland expressibility was statistically significantly different between the 2 groups (U = 319.5, P = 0.006). In the high irregularity group, gland irregularity correlated with the Schirmer test (r = 0.530, P = 0.001) and corneal fluorescein staining (r = -0.377, P = 0.021). Automated morphological analysis of meibomian gland structure provides additional quantitative and objective information regarding gland morphology. The link between dropout area and gland function is not clear. Assessment of gland irregularity might better predict gland function and its effects on ocular surface and tear film parameters.

Microperimetry and OCT angiography evaluation of patients with ischemic diabetic macular edema treated with monthly intravitreal bevacizumab: a pilot study

BackgroundFunctional and anatomical evaluation of patients with ischemic diabetic macular edema after monthly injections of Bevacizumab.MethodsFive eyes from five patients with diabetic macular edema associated with macular ischemia in fluorescein angiography (FA), received 6 monthly intravitreal injections of Bevacizumab. All subjects underwent SD-OCT, FA, OCT angiography (OCTA) and microperimetry at baseline and after 6 months follow-up. Primary outcome measures were improvement of best corrected visual acuity (BCVA), microperimetry and assessment of macular perfusion (foveal avascular zone size and capillary loss).ResultsFive patients completed the follow-up. BCVA improved from 20/180 to 20/74 (p = 0.01) and macular sensitivity improved from 11.66 to 16.26 dB (p < 0.007). We also observed that areas of ischemia on OCTA represented areas of lower macular sensitivity on microperimetry. No changes in macular perfusion status were noted.ConclusionsMonthly intravitreal Bevacizumab in patients with ischemic diabetic macular edema improved BCVA and macular sensitivity without compromise of perfusion in the macula. Capillary dropout areas in OCTA correlated with lower retinal sensitivity on microperimetry.

A Novel Automated Approach for Infrared-Based Assessment of Meibomian Gland Morphology

PurposeWe present and validate a new methodology for analyzing, in an automated and objective fashion, infrared images of the meibomian glands (MG).MethodsThe developed algorithm consists of three main steps: selection of the region of interest, detection of MG, and analysis of MG morphometric parameters and dropout area (DOA). Additionally, a new approach to quantify the irregularity of MG is introduced. We recruited 149 adults from a general population. Infrared meibography, using Keratograph 5M, was performed. Images were assessed and graded subjectively (Meiboscore) by two experienced clinicians and objectively with the proposed automated method.ResultsThe correlation of subjective DOA assessment between the two clinicians was poor and the average percentage of DOA estimated objectively for each Meiboscore group did not lie within their limits. The objective assessment showed lower variability of meibography grading than that obtained subjectively. Additionally, a new grading scale of MG DOA that reduces intraclass variation is proposed. Reported values of MG length and width were inversely proportional to the DOA. Gland irregularity was objectively quantified.ConclusionsThe proposed automatic and objective method provides accurate estimates of the DOA as well as additional morphologic parameters that could add valuable information in MG dysfunction understanding and diagnosis.Translational RelevanceThis approach highlights the shortcomings of currently used subjective methods, and provides the clinicians with an objective, quantitative and less variable alternative for assessing MG in a noninvasive and automated fashion. It provides a viable alternative to more time-consuming subjective methods.

Noncontact Meibography in Patients with Keratoconus.

Purpose To examine the morphological changes in the meibomian glands of patients with keratoconus as well as to study the relationship between these changes in the morphology and several tear film parameters. Methods Examination of the meibomian gland (MG) of 300 keratoconus patients presenting to the center using infrared noncontact meibography system (Sirius, CSO, Italy) between January 2017—January 2019. 100 eyes of healthy individuals were also enrolled as a control group. Tear breakup time (TBUT) test and Schirmer test II were evaluated. Subjective symptoms were also assessed using Ocular Surface Disease Index (OSDI). Results Mean age of keratoconus patients was 19 ± 12 years and 21 ± 14 years in control group. Average TBUT was 4.9 ± 2.1 sec. and average Schirmer test was 5.3 ± 2.2 mm which was significantly lower than control group (p=0.05). Meibomian gland dropout in the lower eyelid of the keratoconus group was as follows: grade 0 (no loss of meibomian glands): 100 eyes; grade 1 (gland dropout area <1/3 of the total meibomian glands): 85 eyes; grade 2 (gland dropout area 1/3 to 2/3): 68 eyes; and grade 3 (gland dropout >2/3): 47 eyes. Conclusion Keratoconus shows significant meibomian gland dropout and distortion that can be recorded by noncontact meibography. Sirius meibography is a simple, cost-effective method of evaluating meibomian gland dropout as a part of the routine refractive examination.

Grading and baseline characteristics of meibomian glands in meibography images and their clinical associations in the Dry Eye Assessment and Management (DREAM) study

PurposeTo describe and evaluate a comprehensive grading system for meibomian gland (MG) digital infrared images developed for the Dry Eye Assessment and Management (DREAM) Study. MethodsCross-sectional study. Reading Center (RC) certified readers independently evaluated MG features of both lids from meibography images of dry eye disease subjects. Dropout areas were measured using planimetry software. Inter-reader and grade-regrade agreement and comparison of meiboscale scores (Meiboscale©; Pult) from clinical centers to RC percent dropout and of MG features with clinical parameters were evaluated. ResultsAmong 551 eyes of 277 patients at baseline, 62 (11%) upper lid and 5 (1%) lower lid images were missing. Lid eversion was poor in 63 (13%) of upper lids compared to 15 (3%) of lower lids. Intraclass correlation for inter-reader and grade-regrade agreement was moderate to substantial for most MG features. MG features were more frequent in the upper lid (p < 0.001), except for dropout glands, gaps, fluffy gland areas and dropout areas. Clinic meiboscale score was associated with RC percent dropout (p < 0.001), a clinic score of 0% having a mean RC score of 19%, and a clinic score of >75% having a mean RC score of 66%. MG plugging was associated with ghost glands (p = 0.009), dropout glands (p < 0.001) and a composite severity score (p = 0.02); turbid and absent secretions were associated with ghost glands (p = 0.046). ConclusionRC readers identified MG features with good reproducibility. Upper lids had more MG features. RC dropout areas correlated well with clinic meiboscale scores. Ghost glands were associated with paste like and absent meibomian secretions.

Reconstruction of 3D Pavement Texture on Handling Dropouts and Spikes Using Multiple Data Processing Methods.

Tire–pavement interactions, like friction and rolling resistance, are significantly influenced by pavement macro-texture and micro-texture. Accurate texture measurement at the micro-texture level is vital to achieve the desired level of safety, comfort, and sustainability of the pavement. However, the existence of dropouts and spikes in the collected data is still inevitable based on current laser devices, which leads to erroneous texture characterization. This study utilized an advanced laser sensor to measure three-dimensional (3D) pavement texture at the micro-level at a given speed. Using a proposed interpolation method, the dropout areas in the raw measurements were filled up. Butterworth’s high-pass and low-pass filters were applied to separate two texture components from the profile. Based on a statistical analysis for the micro-texture amplitude, an appropriate threshold was determined in order to identify the spikes. A three-step-spike-removal method was proposed and found to be effective in clearing the spikes. The 3D pavement profiles were finally reconstructed without dropouts and spikes. Mean profile depth (MPD) was calculated with different baselines. It was found that the presence of spikes leads to a greater MPD value and the MPD is sensitive to the baseline length. A shorter baseline is recommended to mitigate the impact of spikes on the accuracy of the MPD.

SnapshotDx Quiz: December 2018

SnapshotDx Quiz: December 2018

Are psychotherapies with more dropouts less effective?

Psychotherapy dropout is often regarded as an indicator of treatment failure; however, evidence of a relationship between dropout and outcome has not been well established. The current research consisted of three meta-analytic studies, the results of which found (a) individuals who dropped out began treatment more distressed than those who completed therapy, (b) individuals who dropped out of therapy were more distressed at posttreatment than individuals who completed therapy, and (c) treatments with higher rates of dropout were also less effective for the treatment completers. Dropout may particularly signal poor outcomes for shorter treatments. The continued ambiguity in the meaning of dropout is discussed as well as the promising potential for future research in the area of dropout as it relates to outcome.