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The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis.
Ulhaq, ZS, Soraya, GV, Budu, , Wulandari, LR
Scientific reports. 2020;(1):17453
Abstract
Interleukin-6 (IL-6) is one of the key regulators behind the inflammatory and pathological process associated with ophthalmic diseases. The role of IL-6-174 G/C polymorphism as well as intraocular IL-6 levels among various eye disease patients differ across studies and has not been systematically reviewed. Thus, this study aims to provide a summary to understand the relationship between IL-6 and ophthalmic disease. In total, 8,252 and 11,014 subjects for IL-6-174 G/C and intraocular levels of IL-6, respectively, were retrieved from PubMed, Scopus and Web of Science. No association was found between IL-6-174 G/C polymorphisms with ocular diseases. Subgroup analyses revealed a suggestive association between the GC genotype of IL-6-174 G/C with proliferative diabetic retinopathy (PDR). Further, the level of intraocular IL-6 among ocular disease patients in general was found to be higher than the control group [standardized mean difference (SMD) = 1.41, 95% confidence interval (CI) 1.24-1.58, P < 0.00001]. Closer examination through subgroup analyses yielded similar results in several ocular diseases. This study thus indicates that the IL-6-174 G/C polymorphism does not predispose patients to ocular disease, although the GC genotype is likely to be a genetic biomarker for PDR. Moreover, intraocular IL-6 concentrations are related to the specific manifestations of the ophthalmic diseases. Further studies with larger sample sizes are warranted to confirm this conclusion.
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ACUTE MACULAR AND PERIPAPILLARY ANGIOGRAPHIC CHANGES WITH INTRAVITREAL INJECTIONS.
Barash, A, Chui, TYP, Garcia, P, Rosen, RB
Retina (Philadelphia, Pa.). 2020;(4):648-656
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Abstract
PURPOSE Intravitreal injections acutely and temporarily increase intraocular pressure (IOP), and this may have cumulative long-term effects including an increased risk for glaucoma surgery. This study was designed to measure retinal perfusion density changes on optical coherence tomography (OCT) angiography and OCT thickness alterations associated with acutely increased IOP after intravitreal injections. METHODS Retrospective observational clinical study of 40 eyes (39 patients) with various retinopathies from October 2016 to June 2017 at a tertiary care retina clinic in NYC. Patients were older than 18 years, with vision >20/100, able to fixate and without media opacities precluding OCT angiography, receiving intravitreal bevacizumab or aflibercept for diabetic retinopathy, retinal vein occlusion, macular degeneration, retinal neovascularization, or radiation retinopathy. The 3-mm × 3-mm macular and 4.5-mm × 4.5-mm peripapillary OCT angiography perfusion density, macular OCT thickness, and IOP were measured before and immediately after intravitreal injections. Paired t-test was used to compare preinjection and postinjection values for perfusion density and OCT thickness. Regression analysis was performed for potential effects of baseline IOP, IOP change, and age. RESULTS Statistically significant decreases in angiographic perfusion density (P < 0.05) were found in most areas of the superficial and deep layer macular OCT angiography, and the overall optic nerve head and the radial peripapillary capillary layer, preferentially temporal. Macular OCT thickness was significantly decreased in the temporal region and increased in the nasal region. Regression analysis showed relationships between age and decreased superficial macular perfusion. Preinjection IOP was only related to OCT thickness in the fovea. Intraocular pressure change was related only to decreased superficial macular perfusion density. CONCLUSION Intravitreal injections produce acute IOP changes that are associated with reduced macular and peripapillary perfusion density. Therefore, it is possible that patients receiving regular intravitreal injections may be sustaining perfusion-related injury to ocular structures that may produce glaucomatous damage to the macula and optic nerve.
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Vessel Density around Foveal Avascular Zone as a Potential Imaging Biomarker for Detecting Preclinical Diabetic Retinopathy: An Optical Coherence Tomography Angiography Study.
Ragkousis, A, Kozobolis, V, Kabanarou, S, Bontzos, G, Mangouritsas, G, Heliopoulos, I, Chatziralli, I
Seminars in ophthalmology. 2020;(5-6):316-323
Abstract
Purpose: The purpose of this study was to investigate the changes of optical coherence tomography angiography (OCTA) parameters in diabetic retinopathy (DR) using an updated software with 3D projection artifact removal. Methods: In this cross-sectional observational study, 192 eyes of 111 patients with diabetes mellitus (DM) and 55 eyes of 34 age-matched healthy subjects were included. Diabetic patients were divided into three subgroups: without DR, with mild non-proliferative DR, and with moderate-to-severe non-proliferative DR. All eyes underwent dilated fundoscopy along with 3x3mm and 6x6mm OCTA image acquisition. Vessel density (VD), retinal thickness and foveal avascular zone (FAZ) parameters were analyzed. Correlation analyses between OCTA parameters and DR severity were also performed. Results: There was a statistically significant difference in all OCTA parameters among groups, except for superficial foveal VD in 6x6mm scan and whole image retinal thickness in both 3x3mm and 6x6mm scans, while 3x3mm scan parameters were found to be diagnostically superior to the corresponding ones of 6x6mm scan. As the DR stage progressed, the mean VD values decreased. FD-300, which is the VD of a 300-μm width annulus surrounding FAZ, demonstrated the strongest inverse correlation with DR severity (r = -0.590/rs = -0.562, p < .001) and showed the highest area under the ROC curve (AUROC = 0.833 ± 0.030, p < .001) in scan 3 × 3. Conclusion: OCTA shows progressive decrease of VD parameters with increasing DR severity. Foveal VD, FAZ area, and perimeter are not very useful indexes due to the high interindividual variability of FAZ size. OCTA and specifically FD-300 may serve as a promising DR screening tool for detecting preclinical microvascular alterations.
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Longitudinal Panretinal Leakage and Ischemic Indices in Retinal Vascular Disease after Aflibercept Therapy: The PERMEATE Study.
Figueiredo, N, Srivastava, SK, Singh, RP, Babiuch, A, Sharma, S, Rachitskaya, A, Talcott, K, Reese, J, Hu, M, Ehlers, JP
Ophthalmology. Retina. 2020;(2):154-163
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Abstract
PURPOSE To characterize the longitudinal panretinal retinal vascular dynamics in diabetic macular edema (DME) and retinal vein occlusion (RVO) over a 12-month period while being treated with intravitreal aflibercept injections (IAIs). DESIGN Prospective open-label study (clinicaltrials.gov identifier, NCT02503540). PARTICIPANTS Thirty-one treatment-naive eyes with foveal-involving retinal edema secondary to DME and RVO. METHODS Participants received 2 mg IAI every 4 weeks for the first 6 months, followed by 2 mg every 8 weeks. Ultra-widefield fluorescein angiography (UWFA; California Optos [Optos, Dunfermline, United Kingdom]) and spectral-domain OCT (Cirrus; Zeiss, Oberkochen, Germany) scans were obtained and analyzed using a novel quantitative assessment platform. Visual acuity, central subfield thickness, and adverse events also were collected. MAIN OUTCOME MEASURES The primary end point was the mean change in panretinal leakage index at month 12 from baseline as measured by UWFA. RESULTS Mean age was 67.1 years. At month 12, visual acuity significantly improved by a mean of 18.4±21.4 letters (P < 0.0001), and central subfield thickness also improved significantly, with a mean reduction of 301.3±250.3 μm (P < 0.0001). Mean panretinal leakage index improved significantly, decreasing from 3.4% at baseline to 0.5% at month 6 (P <0.0001) and 0.4% at month 12 (P < 0.0001). Panretinal ischemic index did not demonstrate any significant change but showed a nonsignificant increase from 5.5% at baseline to 6.1% at month 6 (P = 0.315) and 8.7% at month 12 (P = 0.193). Eyes with DME showed a decrease in leakage index from 3.5±2.7% at baseline to 1.6±0.8% at month 12 (P = 0.018) and overall stability in ischemic index from 5.0±4.1% at baseline to 4.7±3.5% at month 12 (P = 0.689). Participants with RVO showed a decrease in leakage index from 3.3±1.1% at baseline to 0.02±0.03% at 12 months (P < 0.0001) and a nonsignificant increase in ischemic index from 5.9±4.5% at baseline to 12.6±9.8% at month 12 (P = 0.172). CONCLUSIONS Intravitreal aflibercept injections resulted in a dramatic reduction in panretinal leakage index. Panretinal ischemic index did not improve and trended toward worsening.
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PHOTORECEPTOR DAMAGE IN DIABETIC CHOROIDOPATHY.
Borrelli, E, Palmieri, M, Viggiano, P, Ferro, G, Mastropasqua, R
Retina (Philadelphia, Pa.). 2020;(6):1062-1069
Abstract
PURPOSE To investigate the relationship between choriocapillaris (CC) hypoperfusion and photoreceptor alterations in eyes with nonproliferative diabetic retinopathy (NPDR). METHODS In this prospective, observational, case-control study, 30 eyes (30 patients) with NPDR and 30 healthy eyes from 30 controls were enrolled at the University G. d'Annunzio, Chieti-Pescara, Italy. This study cohort underwent an ophthalmologic examination, including optical coherence tomography and optical coherence tomography angiography. The main outcome measures were as follows: 1) "normalized" reflectivity of en face image segmented at the ellipsoid zone level, which was calculated to quantify the photoreceptor damage, and 2) CC perfusion density. Secondary outcome measures were as follows: 1) superficial retinal capillary plexus (SCP), intermediate retinal capillary plexus (ICP), and deep retinal capillary plexus (DCP) perfusion density (based on the area of vessels); 2) SCP, ICP, and DCP vessel length density (based on a map with vessels of 1-pixel width); and 3) SCP, ICP, and DCP vessel diameter. RESULTS Mean ± SD age was 58.9 ± 11.1 years (range 38-79 years) in the NPDR group and 61.7 ± 11.3 years (range 39-87 years) in the control group (P > 0.05 for all the comparisons). Compared with controls, NPDR eyes displayed a lower "normalized" reflectivity (0.96 ± 0.25 in controls and 0.73 ± 0.19 in the NPDR group, P < 0.0001). Moreover, the NPDR group was characterized by an impaired perfusion in both the retinal and choroidal vasculature. In multiple regression analysis, ellipsoid zone "normalized" reflectivity displayed a significant direct association with CC perfusion density in patients with NPDR (P = 0.025 and P = 0.476, in NPDR and controls, respectively). CONCLUSION Eyes with NPDR are affected by macular hypoperfusion and photoreceptor damage, the latter investigated as ellipsoid zone "normalized" reflectivity. The diabetic choroidopathy seems to be strongly associated with photoreceptor damage.
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SEVERITY OF DIABETIC MACULAR EDEMA CORRELATES WITH RETINAL VASCULAR BED AREA ON ULTRA-WIDE FIELD FLUORESCEIN ANGIOGRAPHY: DAVE Study.
Fan, W, Uji, A, Wang, K, Falavarjani, KG, Wykoff, CC, Brown, DM, Van Hemert, J, Sagong, M, Sadda, SR, Ip, M
Retina (Philadelphia, Pa.). 2020;(6):1029-1037
Abstract
PURPOSE To quantify retinal nonperfusion area and retinal vascular bed area (RVBA) in mm on ultra-widefield fluorescein angiography in eyes with diabetic macular edema (DME) and explore their relationship with the severity of DME. METHODS Prospective, observational case series. Baseline ultra-widefield fluorescein angiography images of 40 eyes from 29 patients with treatment-naive DME who participated in the DAVE study (NCT01552408) were stereographically projected at Doheny Image Reading Center. The retinal vasculature was automatically extracted to calculate RVBA. Nonperfusion area was manually delineated by two masked certified graders. Retinal vascular bed area and nonperfusion area were computed in mm automatically by adjusting for peripheral distortion and then correlated with the severity of DME. RESULTS The global RVBA for the entire retina in eyes with DME was increased compared with healthy controls (54.7 ± 16.6 mm vs. 37.2 ± 9.9 mm, P < 0.001) and correlated with the severity of DME (P < 0.05). Retinal ischemia (nonperfusion area) was nonuniformly distributed and not related to DME extent (P > 0.05). CONCLUSION Eyes with DME have an increased RVBA compared with healthy controls. The severity of DME appears to be related to global RVBA, but not to retinal ischemia.
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Influence of Metabolic Parameters and Treatment Method on OCT Angiography Results in Children with Type 1 Diabetes.
Wysocka-Mincewicz, M, Baszyńska-Wilk, M, Gołębiewska, J, Olechowski, A, Byczyńska, A, Hautz, W, Szalecki, M
Journal of diabetes research. 2020;:4742952
Abstract
AIM: To evaluate the influence of metabolic parameters and the treatment method in children with type 1 diabetes (T1D) on the optical coherence tomography angiography (OCTA) results as early markers of diabetic retinopathy (DR). Material and Methods. This prospective study enrolled 175 consecutive children with T1D. OCTA was performed using AngioVue (Avanti, Optovue). Whole superficial capillary vessel density (wsVD), fovea superficial vessel density (fsVD), parafovea superficial vessel density (psVD), whole deep vessel density (wdVD), fovea deep vessel density (fdVD), parafovea deep vessel density (pdVD), foveal thickness (FT), parafoveal thickness (PFT), and foveal avascular zone (FAZ) in superficial plexus were evaluated and analyzed in relation to individual characteristics, i.e., sex, weight, height, body mass index (BMI), and metabolic factors: current and mean value of glycated hemoglobin A1c (HbA1c). Furthermore, the analysis concerned the diabetes duration, age at the T1D onset, and type of treatment-multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII). RESULTS In the study group, we did not identify any patient with DR in fundus ophthalmoscopy. Age at the onset of diabetes correlated negatively with FAZ (r = -0.17, p < 0.05). The higher level of HbA1c corresponded to a decrease of wsVD (r = -0.13, p < 0.05). We found significantly lower fsVD (32.25 ± .1 vs. 33.98 ± .1, p < 0.01), wdVD (57.87 ± .1 vs. 58.64 ± .9, p < 0.01), and pdVD (60.60 ± .2 vs. 61.49 ± .1, p < 0.01) and larger FAZ area (0.25 ± .1 vs. 0.23 ± .1, p < 0.05) in the CSII vs. MDI group. CONCLUSION The metabolic parameters, age of the onset of diabetes, and treatment method affected the OCTA results in children with T1D. Further studies and observation of these young patients are needed to determine if these findings are important for early detection of DR or predictive of future DR severity.
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Relationship Between Retinal Fractal Dimension and Nonperfusion in Diabetic Retinopathy on Ultrawide-Field Fluorescein Angiography.
Fan, W, Nittala, MG, Fleming, A, Robertson, G, Uji, A, Wykoff, CC, Brown, DM, van Hemert, J, Ip, M, Wang, K, et al
American journal of ophthalmology. 2020;:99-106
Abstract
PURPOSE To correlate fractal dimension (FD) of the retinal vasculature with the extent of retinal nonperfusion area in diabetic retinopathy (DR) on ultrawide-field fluorescein angiography (FA). DESIGN Cross-sectional study. METHODS Baseline Optos 200Tx ultrawide-field FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center. The retinal vasculature was extracted from an early-phase FA frame by exploiting the elongated nature of the vessels and then skeletonized for calculation of FD using a box-counting method. The nonperfusion area was delineated by 2 independent, reading center-certified graders who were masked to the study groups and who were using a standardized protocol and then computed in millimeters squared. RESULTS While no difference in FD was observed for the entire retina in DR compared with normal control subjects, a significantly smaller FD was found in the far-periphery of the DR eyes (P < .001). FD for the entire retina was negatively associated with global nonperfusion area (R = -0.44; P < .001), and this relationship was also present within the 3 concentric retinal zones (posterior: R = -0.31, P = .016; midperiphery: R = -0.35, P = .007; and far periphery: R = -0.31, P = .015). CONCLUSIONS Peripheral FD on ultrawide-field FA is reduced in DR eyes compared with normal eyes and is correlated with severity of retinal nonperfusion. FD can be calculated automatically without the need for correction of peripheral distortion, and therefore it may prove to be a useful surrogate biomarker when precise quantification of nonperfusion is not feasible.
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Changes in choroidal vascular parameters following pan-retinal photocoagulation using swept-source optical coherence tomography.
Kim, JT, Park, N
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2020;(1):39-47
Abstract
BACKGROUND To assess the effect of pan-retinal photocoagulation (PRP) on choroidal vascular parameters in eyes with advanced diabetic retinopathy (DR). METHODS Forty patients (65 eyes) with severe nonproliferative DR or proliferative DR who underwent PRP were included. Changes in choroidal vascular parameters were assessed at 3, 6, and 12 months after PRP by using swept-source optical coherence tomography (OCT) and OCT angiography and were compared with baseline values. RESULTS Choroidal vascularity index (CVI) significantly decreased from 66.27% ± 1.55% at baseline to 65.85% ± 1.61%, 65.77% ± 1.29%, and 65.74% ± 1.60% at 3, 6, and 12 months after PRP, respectively. The ratio of luminal area to stromal area (L/S ratio) also significantly decreased from 1.98 ± 0.15 at baseline to 1.94 ± 0.14, 1.95 ± 0.13, and 1.93 ± 0.14 at 3, 6, and 12 months after PRP, respectively. The subfoveal choroidal thickness (SFCT) similarly showed a significant decrease from 319.50 ± 56.64 μm at baseline to 299. 07 ± 51.14 μm, 294.70 ± 58.96 μm, and 280.93 ± 53.57 μm at 3, 6, and 12 months after PRP, respectively. However, the choriocapillaris vessel density in both the fovea and parafovea showed no significant differences following PRP. CONCLUSION Eyes with advanced DR showed a significant reduction in CVI, L/S ratio, and SFCT over 12 months after PRP treatment.
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Objective Evaluation of Proliferative Diabetic Retinopathy Using OCT.
Schwartz, R, Khalid, H, Sivaprasad, S, Nicholson, L, Anikina, E, Sullivan, P, Patel, PJ, Balaskas, K, Keane, PA
Ophthalmology. Retina. 2020;(2):164-174
Abstract
PURPOSE To present the routine use of OCT and OCT angiography (OCTA) for the objective diagnosis and monitoring of proliferative diabetic retinopathy (PDR). DESIGN Retrospective, observational case series. PARTICIPANTS Patients with diabetic retinopathy imaged using a standardized PDR protocol. METHODS Patients routinely imaged with a standardized PDR protocol between March 2017 and January 2019 were included. This included a 12×9-mm structural OCT volume centered on the macula and a 6×6-mm OCTA scan centered on the optic nerve head obtained using a Topcon swept-source system (DRI OCT-1 Triton, Topcon, Tokyo, Japan). Ultra-widefield fluorescein angiography (FA) was also performed when clinically indicated. The ground truth for each case was determined by merging the findings from biomicroscopy and imaging modalities to generate the maximum level of detection for each finding. MAIN OUTCOME MEASURES Detection rates of new-onset, regression, and reactivation of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) using different modalities (biomicroscopy/color photography, structural OCT, B-scan OCTA, en face OCTA). Detection of progression of tractional retinal detachment (TRD). RESULTS A total of 383 eyes of 204 patients were evaluated. After excluding patients without PDR or with insufficient image quality, 47 eyes of 35 patients were included. For the detection of new-onset NVD and NVE, structural OCT had the highest detection rate (100%) of all modalities. However, for the detection of regression or reactivation of neovascularization (NV), B-scan OCTA had the highest detection rate (100%). Structural OCT detected regression only in 45.5% of cases, resulting in a low detection rate of reactivation (12.5%). Among 10 eyes with TRD, OCT detected fovea-threatening TRD during follow-up in 7 eyes, resulting in vitrectomy. CONCLUSIONS This study demonstrates the utility of novel multimodal imaging in the daily management of patients with PDR. Posterior pole structural OCT had the best detection rate for NV, and B-scan OCTA showed the most potential for objective monitoring of disease after treatment.