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- Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy: Cross-sectional Analyses of Baseline Data of the EUROCONDOR ProjectPublication . B M Santos, Ana Rita; Ribeiro, Luísa; Bandello, Francesco; Lattanzio, Rosangela; Egan, Catherine; Frydkjaer-Olsen, Ulrik; García-Arumí, José; Gibson, Jonathan; Grauslund, Jakob; Harding, Simon P.; Lang, Gabriele E.; Massin, Pascale; Midena, Edoardo; Scanlon, Peter; Aldington, Stephen J.; Simão, Sílvia; Schwartz, Christian; Ponsati, Berta; Porta, Massimo; Costa, Miguel Ângelo; Hernández, Cristina; Cunha-Vaz, José; Simó, RafaelThis cross-sectional study evaluated the relationship between 1) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 (P = 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes.
- Diabetic Choroidopathy: Choroidal Vascular Density and Volume in Diabetic Retinopathy With Swept-Source Optical Coherence TomographyPublication . Wang, Jay C.; Laíns, Inês; Providência, Joana; Armstrong, Grayson W.; B M Santos, Ana Rita; Gil, Pedro; Gil, João; Talcott, Katherine E.; Marques, João H.; Figueira, João; Vavvas, Demetrios G.; Kim, Ivana K.; Miller, Joan W.; Husain, Deeba; Silva, Rufino; Miller, John B.Purpose To compare choroidal vascular density (CVD) and volume (CVV) in diabetic eyes and controls, using en face swept-source optical coherence tomography (SS-OCT). Design Prospective cross-sectional study. Methods Setting: Multicenter. Patient Population: Total of 143 diabetic eyes—27 with no diabetic retinopathy (DR), 47 with nonproliferative DR (NPDR), 51 with NPDR and diabetic macular edema (DME), and 18 with proliferative DR (PDR)—and 64 age-matched nondiabetic control eyes. Observation Procedures: Complete ophthalmologic examination and SS-OCT imaging. En face SS-OCT images of the choroidal vasculature were binarized. Main Outcome Measures: CVD, calculated as the percent area occupied by choroidal vessels in the central macular region (6-mm-diameter circle centered on the fovea), and throughout the posterior pole (12 × 9 mm). The central macular CVV was calculated by multiplying the average CVD by macular area and choroidal thickness (obtained with SS-OCT automated software). Multilevel mixed linear models were performed for analyses. Results Compared to controls (0.31 ± 0.07), central macular CVD was significantly decreased by 9% in eyes with NPDR + DME (0.28 ± 0.06; ß = −0.03, P = .02) and by 15% in PDR (0.26 ± 0.05; ß = −0.04, P = .01). The central macular CVV was significantly decreased by 19% in eyes with PDR (0.020 ± 0.005 mm3, ß = −0.01, P = .01) compared to controls (0.025 ± 0.01 mm3). Conclusions Choroidal vascular density and volume are significantly reduced in more advanced stages of diabetic retinopathy. New imaging modalities should allow further exploration of the contributions of choroidal vessel disease to diabetic eye disease pathogenesis, prognosis, and treatment response.
- Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edemaPublication . Busch, Catharina; Zur, Dinah; Fraser-Bell, Samantha; Laíns, Inês; Santos, Ana Rita; Lupidi, Marco; Cagini, Carlo; Gabrielle, Pierre-Henry; Couturier, Aude; Mané-Tauty, Valérie; Giancipoli, Ermete; Ricci, Giuseppe D'Amico; Cebeci, Zafer; Rodríguez-Valdés, Patricio J.; Chaikitmongkol, Voraporn; Amphornphruet, Atchara; Hindi, Isaac; Agrawal, Kushal; Chhablani, Jay; Loewenstein, Anat; Iglicki, Matias; Rehak, MatusIn a real-world setting, eyes with DME considered refractory to anti-VEGF therapy after three monthly injections which were switched to DEX implant and had better visual and anatomical outcomes at 12 months than those that continued treatment with anti-VEGF therapy.
- Sensitivity of psychophysical, electrophysiological and structural tests for detection and progression monitoring in ocular hypertension and glaucomaPublication . Raimundo, Miguel; Mateus, Catarina; Faria, Pedro; Oliveiros, Bárbara; Cardoso, João; Silva, João Filipe; Pereira, José Moura; Castelo-Branco, MiguelTo characterize early visual impairment of patients in the glaucoma spectrum, using psychophysical, electrophysiological and structural methods. Cohort of 52 patients, 18 patients with ocular hypertension (HT), 15 glaucoma suspects (GS) and 19 with primary open-angle glaucoma (G), and 20 age-matched controls. Quantitative psychophysical methods were used to assess magno (FDT, Frequency Doubling Technology), parvo and koniocellular pathways (Cambridge Color Test), and RGC function was assessed by Pattern Electroretinogram. RGC axonal thickness was obtained using OCT. Reduced mean achromatic contrast sensitivity (p=0.0298) was found in patients with HT, as well as a reduced PERG N-95 wave amplitude (p=0.0499). Chromatic thresholds were significantly increased for protan, deutan and tritan axes (p<0.03) in these patients when compared to controls. At approximately 80% specificity, FDT showed only moderate sensitivity to detect early functional damage (superior nasal, 66% sensitivity). The pattern of disease progression decline is approximately linear for all tests, but more severe in OCT, RNFL thickness ( = 0.47). We found relative damage of magno, parvo and koniocellular retinocortical pathways beginning in ocular hypertension. FDT and CCT Protan performed well in detecting early damage in ocular hypertension, whereas longitudinal analysis using OCT for RFNL appeared to be the best to monitor the progression. The sensitivity of currently available tests is lower comparing with our previously reported novel psychophysical tools (sensitivity above 90% for 80% specificity). We believe early diagnosis in glaucoma is possible by exploiting visual pathways with a small degree of redundancy through high sensitivity functional tests.
- Optical coherence tomography baseline predictors for initial best-corrected visual acuity response to intravitreal anti-vascular endothelial growth factor treatment in eyes with diabetic macular edema: the chartres studyPublication . B M Santos, Ana Rita; Costa, Miguel Â; Schwartz, Christian; Alves, Dalila; Figueira, João; Silva, Rufino; Cunha-Vaz, Jose GPurpose: To identify baseline optical coherence tomography morphologic characteristics predicting the visual response to anti-vascular endothelial growth factor therapy in diabetic macular edema. Methods: Sixty-seven patients with diabetic macular edema completed a prospective, observational study (NCT01947881-CHARTRES). All patients received monthly intravitreal injections of Lucentis for 3 months followed by PRN treatment and underwent best-corrected visual acuity measurements and spectral domain optical coherence tomography at Baseline, Months 1, 2, 3, and 6. Visual treatment response was characterized as good (≥10 letters), moderate (5–10 letters), and poor (<5 or letters loss). Spectral domain optical coherence tomography images were graded before and after treatment by a certified Reading Center. Results: One month after loading dose, 26 patients (38.80%) were identified as good responders, 19 (28.35%) as Moderate and 22 (32.83%) as poor responders. There were no significant best-corrected visual acuity and central retinal thickness differences at baseline (P = 0.176; P = 0.573, respectively). Ellipsoid zone disruption and disorganization of retinal inner layers were good predictors for treatment response, representing a significant risk for poor visual recovery to anti-vascular endothelial growth factor therapy (odds ratio = 10.96; P < 0.001 for ellipsoid zone disruption and odds ratio = 7.05; P = 0.034 for disorganization of retinal inner layers). Conclusion: Damage of ellipsoid zone, higher values of disorganization of retinal inner layers, and central retinal thickness decrease are good predictors of best-corrected visual acuity response to anti-vascular endothelial growth factor therapy.
- Measurements of retinal fluid by oct leakage in diabetic macular edema: A biomarker of visual acuity response to treatmentPublication . Santos, Ana Rita; Alves, Dalila; Santos, Torcato; Figueira, João; Rufino, Silva; Cunha-Vaz, José G.Optical coherence tomography leakage changes after anti-vascular endothelial growth factor treatment of diabetic macular edema, identifying the degree of decrease in retinal fluid in the outer layers of the retina is a more robust biomarker of BCVA recovery than central retinal thickness, disorganization of the inner retinal layer, or ellipsoid zone disruption changes.
- Real-world outcomes of observation and treatment in diabetic macular edema with very good visual acuity: the OBTAIN studyPublication . Busch, Catharina; Fraser-Bell, Samantha; Zur, Dinah; Rodríguez-Valdés, Patricio J.; Cebeci, Zafer; Lupidi, Marco; Fung, Adrian T.; Gabrielle, Pierre-Henry; Giancipoli, Ermete; Chaikitmongkol, Voraporn; Okada, Mali; Laíns, Inês; Santos, Ana Rita; kunavisarut, Paradee; Sala-Puigdollers, Anna; Chhablani, Jay; Ozimek, Malgorzata; Hilely, Assaf; Unterlauft, Jan Darius; Loewenstein, Anat; Iglicki, Matias; Rehak, MatusIn a real-world setting, the majority of DME patients with very good VA maintained vision at 12 months, regard- less of whether the DME was treated or not. This study supports close observation of eyes with DME and very good VA with consideration of treatment when a one line drop in vision is observed.
- Real-world outcomes of non-responding diabetic macular edema treated with continued anti-VEGF therapy versus early switch to dexamethasone implant: 2-year resultsPublication . Busch, Catharina; Fraser-Bell, Samantha; Iglicki, Matias; Lupidi, Marco; Couturier, Aude; Chaikitmongkol, Voraporn; Giancipoli, Ermete; Rodríguez-Valdés, Patricio J.; Gabrielle, Pierre-Henri; Laíns, Inês; Santos, Ana Rita; Cebeci, Zafer; Amphornphruet, Atchara; Degenhardt, Valentin; Unterlauft, Jan-Darius; Cagini, Carlo; Mané-Tauty, Valérie; Ricci, D'Amico Giuseppe; Hindi, Isaac; Agrawal, Kushal; Chhablani, Jay; Loewenstein, Anat; Zur, Dinah; Regak, MatusThe beneficial effect of an early switch to DEX implant in DME non-responders seen at month 12 was main- tained during the second year. A later switch from anti-VEGF to steroids still provided significant improvement. Eyes continued on anti-VEGF over a period of 24 months maintained vision. A quarter of eyes, which had not improved vision at 12 months, exhibited a delayed response to treatment.
- Characterization of initial stages of diabetic macular edemaPublication . Santos, Ana Rita; Santos, Torcato; Alves, Dalila; Marques, Inês P.; Lobo, Conceição; Cunha-Vaz, JoséThis study is aimed at characterizing the type of retinal edema in the initial stages of retinopathy in type 2 diabetes. In this retrospective cross-sectional study, spectral domain optical coherence tomography (OCT) layer by layer analysis of the retina in association with OCT-Leakage, an algorithm to detect sites of low optical reflectivity, were used to examine eyes with minimal, mild, and moderate diabetic retinopathy (DR). A total of 142 eyes from 142 patients (28% women) aged 52–88 years were imaged. Macular edema, either subclinical (SCME) or central-involved macular edema (CIME), was present in 43% of eyes in group 10–20, 41% of eyes in group 35, and 38% of eyes in group 43–47. The inner nuclear layer (INL) was the layer showing higher and most frequent increases in retinal thickness (79%). The edema was predominantly intracellular in group 10–20 (65%) and extracellular in groups 35 (77%) and 43–47 (69%). Eyes from diabetic patients in the initial stages of DR with different Early Treatment Diabetic Retinopathy Study gradings show similar prevalence of SCME and CIME, independent of the severity of the retinopathy. Retinal edema is located mainly in the INL and appears to be mostly extracellular except in the earliest stages of diabetic retinal disease where intracellular edema predominates.
- Optical coherence tomography leakage in neovascular age-related macular degeneration: Identification of choroidal neovascularization activity by location and quantification of abnormal fluid under anti-vascular endothelial growth factor therapyPublication . Farinha, Cláudia; Santos, Torcato; Santos, Ana Rita; Lopes, Marta; Alves, Dalila; Silva, Rufino; Cunha-Vaz, JoséOptical coherence tomography leakage identified and quantified the fluid related to choroidal neovascularization activity. Low optical reflectivity change in the outer segment layer correlates with functional outcome and increasing LOR in the external layers may be a marker of early recurrence. Combining optical coherence tomography angiography and optical coherence tomography leakage allows both for choroidal neovascularization morphology and activity analysis.