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Correlation of retinal layer changes with vision gain in diabetic macular edema during conbercept treatment.
Xu, Y, Qu, Y, Suo, Y, Gao, J, Chen, X, Liu, K, Xu, X
BMC ophthalmology. 2019;(1):123
Abstract
BACKGROUNDS To assess the changes in individual retinal layer thickness and visual function associated with gains in visual acuity after an intravitreal conbercept injection in the diabetic macular edema (DME) on spectral domain optical coherence tomography (SD-OCT) and microperimetry during 1-year follow-up. METHODS Retrospective observational study. Twenty patients with clinically significant DME in the study eye were imaged by SD-OCT every 3 months and MP1 microperimeter in the third month while receiving anti-vascular endothelial growth factor (VEGF) (conbercept) treatment. In each patient, seven retinal layers were segmented in 98 scans covering a 6 mm × 6 mm area of the macula at baseline and during 1 year of treatment. An automatic, full-threshold microperimetry of the central field (10° × 10°, 40 stimulated points) with the MP1 microperimeter. Thickness and microperimetry changes were quantitatively measured and evaluated for their correlation with increases in visual acuity. RESULTS Although thicknesses of the inner nuclear layer (INL) and the outer nuclear layer (ONL) were reduced the most after treatment (p < 0.05), decreases of the ganglion cell layer (GCL) (r = 0.591, p = 0.006) and inner plexiform layer (IPL) (r = 0.663, p = 0.001) in central subfield area was associated with best-corrected visual acuity (BCVA) gain, and had the best estimation of BCVA gain (adjust R2 = 0.544). Mean macular sensitivity in the central subfield was also well correlated with BCVA gain (r = 0.531, p = 0.016). CONCLUSIONS Neural recovery occurred after the resolution of edema during conbercept treatment, due to the decreases in GCL and IPL associating with gains in vision and improved microperimetry.
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2.
Imaging and Biomarkers in Diabetic Macular Edema and Diabetic Retinopathy.
Kwan, CC, Fawzi, AA
Current diabetes reports. 2019;(10):95
Abstract
PURPOSE OF REVIEW Diabetic retinopathy (DR) is the leading cause of acquired vision loss in adults across the globe. Early identification and treatment of patients with DR is paramount for vision preservation. The aim of this review paper is to outline current and new imaging techniques and biomarkers that are valuable for clinical diagnosis and management of DR. RECENT FINDINGS Ultrawide field imaging and automated deep learning algorithms are recent advancements on traditional fundus photography and fluorescein angiography. Optical coherence tomography (OCT) and OCT angiography are techniques that image retinal anatomy and vasculature and OCT is routinely used to monitor response to treatment. Many circulating, vitreous, and genetic biomarkers have been studied to facilitate disease detection and development of new treatments. Recent advancements in retinal imaging and identification of promising new biomarkers for DR have the potential to increase detection, risk stratification, and treatment for patients with DR.
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The Diabetic Retinopathy Clinical Research Network (DRCR.net) and Its Contributions to the Treatment of Diabetic Retinopathy.
Sun, JK, Jampol, LM
Ophthalmic research. 2019;(4):225-230
Abstract
Over the past two decades, the Diabetic Retinopathy Clinical Research Network (now known as the DRCR Retina Network) has contributed to multiple and substantial advances in the clinical care of diabetic eye disease. Network studies helped establish anti-vascular endothelial growth factor (VEGF) agents as an effective alternative to panretinal photocoagulation for eyes with proliferative diabetic retinopathy (PDR) and as first-line therapy for eyes with visual impairment for diabetic macular edema (DME), defined treatment algorithms for the use of intravitreal medications in these conditions, and provided critical data to understand how to better evaluate the diabetic eye using optical coherence tomography and other imaging modalities. Ongoing DRCR.net studies will address whether anti-VEGF therapy is effective at preventing vision-threatening complications in eyes with severe non-proliferative diabetic retinopathy, if photobiomodulation has a beneficial effect in eyes with DME, and whether initiation of DME treatment with bevacizumab and rescue with aflibercept can provide visual outcomes as good as those achieved with aflibercept alone. Future plans for the Network also include the expansion into non-diabetic eye disease in areas such as age-related macular degeneration.
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Variability in the ocular phenotype in mucopolysaccharidosis.
Sornalingam, K, Javed, A, Aslam, T, Sergouniotis, P, Jones, S, Ghosh, A, Ashworth, J
The British journal of ophthalmology. 2019;(4):504-510
Abstract
PURPOSE Mucopolysaccharidoses (MPSs) are a heterogeneous group of lysosomal storage disorders. Ocular complications (such as corneal clouding, retinopathy and optic neuropathy) are common. Notably, there is a paucity of data on the effect of genotype and systemic treatments (enzyme replacement therapy or haematopoietic stem cell transplantation) on the ocular phenotype in MPS. We prospectively studied the ocular features of patients with MPSI (Hurler/Hurler-Scheie/Scheie), MPSIV (Morquio) and MPSVI (Maroteaux-Lamy), to evaluate the effect of different therapeutic interventions and to correlate the findings with genetic and biomarker data. METHODS Prospective observational cohort study. Study participants underwent detailed ocular examination including visual acuity; assessment of corneal clouding (Iris camera Corneal Opacification Measure score and Pentacam densitometry) and retinal and optic nerve imaging (optical coherence tomography and wide-field fundus imaging). Data on genotype, biomarkers and delivered therapies (type and length of treatment) were also collected for each patient where available. RESULTS Overall, 21 patients with MPSI, 4 patients with MPSIV and 3 patients with MPSVI were recruited. Corneal clouding scores were higher in MPSI compared with MPSIV and MPSVI. Retinopathy was evident in patients with MPSI only. Association was observed between corneal clouding and biomarkers in MPSI, MPSIV and MPSVI. However, no clear association was seen between genotype or treatment type and ocular phenotype. CONCLUSIONS The ocular phenotype in MPS is variable, with corneal clouding occurring in MPSI, MPSIV and MPSVI, and retinopathy in MPSI only. There was an association between corneal clouding and efficacy of systemic treatment as measured by biomarkers.
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Isolation of Retinal Exosome Biomarkers from Blood by Targeted Immunocapture.
Klingeborn, M, Skiba, NP, Stamer, WD, Bowes Rickman, C
Advances in experimental medicine and biology. 2019;:21-25
Abstract
The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier, provides nutrients, recycles visual pigment, and removes spent discs from the photoreceptors, among many other functions. Because of these critical roles in visual homeostasis, the RPE is a principal location of disease-associated changes in age-related macular degeneration (AMD), emphasizing its importance for study in both visual health and disease. Unfortunately, there are no early indicators of AMD or disease progression, a void that could be filled by the development of early AMD biomarkers. Exosomes are lipid bilayer membrane vesicles of nanoscale sizes that are released in a controlled fashion by cells and carry out a number of extra- and intercellular activities. In the RPE they are released from both the apical and basal sides, and each source has a unique signature/content. Exosomes released from the basolateral side of RPE cells enter the systemic circulation via the choroid and thus represent a potential source of retinal disease biomarkers in blood. Here we discuss the potential of targeted immunocapture of eye-derived exosomes and other small extracellular vesicles from blood for eye disease biomarker discovery.
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Single session of pattern scanning laser versus multiple sessions of conventional laser for panretinal photocoagulation in diabetic retinopathy: Efficacy, safety and painfulness.
Nemcansky, J, Stepanov, A, Nemcanska, S, Masek, P, Langrova, H, Studnicka, J
PloS one. 2019;(7):e0219282
Abstract
PURPOSE To evaluate the clinical efficiency, safety and painfulness of retinal laser photocoagulation employing a pattern scanning laser system Pascal given in a single-session versus conventional laser multiple-session treatment of the same patient with diabetic retinopathy during 12-month follow-up. METHODS The cohort included 60 eyes in 30 patients treated at the Ophthalmology Clinic, Faculty Hospital Ostrava, from 2008 to 2013. Panretinal laser coagulation was performed on one eye using the multispot panretinal photocoagulation given in a single-session system Pascal (OptiMedica, Santa Clara, California). On the other eye laser treatment was carried out by the classic conventional multiple-session method. RESULTS The performance of Pascal panretinal laser coagulation was evaluated as significantly less painful (visual scale of pain was 3.28 ± 1.9) than the performance of conventional photocoagulation (visual scale of pain was 3.93 ± 1.88) with similar efficiency. Distribution of progression of diabetic retinopathy in individual patients was very similar in both groups under comparison, and was strictly paired in 24 of the 30 patients at the end of 1-year follow-up. CONCLUSION Laser photocoagulation of the retina with the use of short impulse durations and patterns in patients with diabetic retinopathy given in one session possesses similar efficiency to that of conventional retinal photocoagulation in multiple sessions. The single session treatment is also better tolerated by patients and in addition to this, it shortens the performance of the whole therapy, which potentially saves considerable funds of all subjects participating in the process of treatment. TRIAL REGISTRATION ClinicalTrials.gov NCT03672656.
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Comparative ophthalmic assessment of patients receiving tafenoquine or chloroquine/primaquine in a randomized clinical trial for Plasmodium vivax malaria radical cure.
Warrasak, S, Euswas, A, Fukuda, MM, Ittiverakul, M, Miller, RS, Krudsood, S, Ohrt, C
International ophthalmology. 2019;(8):1767-1782
Abstract
PURPOSE Ophthalmic safety observations are reported from a clinical trial comparing tafenoquine (TQ) efficacy and safety versus sequential chloroquine (CQ)/primaquine (PQ) for acute Plasmodium vivax malaria. METHODS In an active-control, double-blind study, 70 adult subjects with microscopically confirmed P. vivax malaria were randomized (2:1) to receive 400 mg TQ × 3 days or 1500 mg CQ × 3 days then 15 mg PQ × 14 days. MAIN OUTCOME MEASURES clinically relevant changes at Day 28 and Day 90 versus baseline in the ocular examination, color vision evaluation, and corneal and retinal digital photography. RESULTS Post-baseline keratopathy occurred in 14/44 (31.8%) patients with TQ and 0/24 with CQ/PQ (P = 0.002). Mild post-baseline retinal findings were reported in 10/44 (22.7%) patients receiving TQ and 2/24 (8.3%) receiving CQ/PQ (P = 0.15; treatment difference 14.4%, 95% CI - 5.7, 30.8). Masked evaluation of retinal photographs identified a retinal hemorrhage in one TQ patient (Day 90) and a slight increase in atrophy from baseline in one TQ and one CQ/PQ patient. Visual field sensitivity (Humphrey™ 10-2 test) was decreased in 7/44 (15.9%) patients receiving TQ and 3/24 (12.5%) receiving CQ/PQ; all cases were < 5 dB. There were no clinically relevant changes in visual acuity or macular function tests. CONCLUSIONS There was no evidence of clinically relevant ocular toxicity with either treatment. Mild keratopathy was observed with TQ, without conclusive evidence of early retinal changes. Eye safety monitoring continues in therapeutic studies of low-dose tafenoquine (300 mg single dose). CLINICAL TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01290601.
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8.
Mechanisms enhancing the protective functions of macular xanthophylls in the retina during oxidative stress.
Widomska, J, Subczynski, WK
Experimental eye research. 2019;:238-246
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Abstract
Macular xanthophylls (MXs) are distinguished from other dietary carotenoids by their high membrane solubility and preferential transmembrane orientation. Additionally, these properties enhance the chemical and physical stability of MXs in the eye retina, and maximize their protective activities. The effectiveness of MXs' protection is also enhanced by their selective accumulation in the most vulnerable domains of retinal membranes. The retina is protected by MXs mainly through blue-light filtration, quenching of the excited triplet states of potent photosensitizers, and physical quenching of singlet oxygen. To perform these physical, photo-related actions, the structure of MXs should remain intact. However, the conjugated double-bond structure of MXs makes them highly chemically reactive and susceptible to oxidation. Chemical quenching of singlet oxygen and scavenging of free radicals destroy their intact structure and consume MXs. Consequently, their physical actions, which are critical to the protection of retina, are diminished. Thus, it is timely and important to identify mechanisms whereby the chemical destruction (bleaching) of MXs in retinal membranes can be reduced. It was shown that nitroxide free radicals (spin labels) located in membranes protect MXs against destruction, and their effect is especially pronounced during the light-induced formation of singlet oxygen. That should extend and enhance their positive action in the retina through physical processes. In this review, we will discuss possible applications of this new strategy during ophthalmological procedures, which can cause acute bleaching of MXs and damage the retina through oxidative processes.
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Automated retinal lesion detection via image saliency analysis.
Yan, Q, Zhao, Y, Zheng, Y, Liu, Y, Zhou, K, Frangi, A, Liu, J
Medical physics. 2019;(10):4531-4544
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Abstract
BACKGROUND AND OBJECTIVE The detection of abnormalities such as lesions or leakage from retinal images is an important health informatics task for automated early diagnosis of diabetic and malarial retinopathy or other eye diseases, in order to prevent blindness and common systematic conditions. In this work, we propose a novel retinal lesion detection method by adapting the concepts of saliency. METHODS Retinal images are first segmented as superpixels, two new saliency feature representations: uniqueness and compactness, are then derived to represent the superpixels. The pixel level saliency is then estimated from these superpixel saliency values via a bilateral filter. These extracted saliency features form a matrix for low-rank analysis to achieve saliency detection. The precise contour of a lesion is finally extracted from the generated saliency map after removing confounding structures such as blood vessels, the optic disk, and the fovea. The main novelty of this method is that it is an effective tool for detecting different abnormalities at the pixel level from different modalities of retinal images, without the need to tune parameters. RESULTS To evaluate its effectiveness, we have applied our method to seven public datasets of diabetic and malarial retinopathy with four different types of lesions: exudate, hemorrhage, microaneurysms, and leakage. The evaluation was undertaken at the pixel level, lesion level, or image level according to ground truth availability in these datasets. CONCLUSIONS The experimental results show that the proposed method outperforms existing state-of-the-art ones in applicability, effectiveness, and accuracy.
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OCT angiography-based monitoring of neovascular regression on fibrovascular membrane after preoperative intravitreal conbercept injection.
Hu, Z, Su, Y, Xie, P, Chen, L, Ji, J, Feng, T, Wu, S, Liang, K, Liu, Q
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2019;(8):1611-1619
Abstract
PURPOSE To quantify the preoperative neovascular change pattern on the fibrovascular membrane (FVM) within 7 days after intravitreal injection of conbercept (IVC) using optical coherence tomography angiography (OCTA) in proliferative diabetic retinopathy (PDR). METHODS Prospective, observational study of PDR patients with visible FVM receiving or not receiving IVC. Neovascular changes were assessed by OCTA pre-IVC and 1, 3, 5, and 7 days post-IVC. Vessel skeleton density (SD) and vessel density (VD) were quantified by an intensity-based optical microangiography algorithm. The interclass correlation coefficient (ICC) was calculated to assess the agreement between measurements. The SD and VD were compared between follow-ups using repeated-measures analysis in the IVC group. RESULTS The ICC was 0.992 (95% confidence interval [CI]: 0.982-0.996) for SD and 0.926 (95% CI: 0.838-0.912) for VD of neovascularization. The neovascularization on FVM significantly regressed in the IVC group (n = 16) compared with no IVC (n = 8) (p = 0.001 for SD and p < 0.001 for VD). The comparisons between consecutive follow-ups showed a statistically significant reduction in SD and VD at 1 and 3 days post-IVC. However, from day 3 onward, the SD and VD remained unchanged. There was no development or progression of tractional retinal detachment within the 7-day period after IVC. CONCLUSION OCTA-based quantification of the neovascularization on FVM in PDR is feasible, with high inter-reader agreement. The regression of neovascularization reaches a plateau 3 days after IVC. CLINICAL TRIAL REGISTRATION This trial is registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , registration number ChiCTR-IPR-17014160).