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Photoreceptor degeneration in ABCA4-associated retinopathy and its genetic correlates.
Pfau, M, Cukras, CA, Huryn, LA, Zein, WM, Ullah, E, Boyle, MP, Turriff, A, Chen, MA, Hinduja, AS, Siebel, HE, et al
JCI insight. 2022;(2)
Abstract
BACKGROUNDOutcome measures sensitive to disease progression are needed for ATP-binding cassette, sub-family A, member 4-associated (ABCA4-associated) retinopathy. We aimed to quantify ellipsoid zone (EZ) loss and photoreceptor degeneration beyond EZ-loss in ABCA4-associated retinopathy and investigate associations between photoreceptor degeneration, genotype, and age.METHODSWe analyzed 132 eyes from 66 patients (of 67 enrolled) with molecularly confirmed ABCA4-associated retinopathy from a prospective natural history study with a median [IQR] follow-up of 4.2 years [3.1, 5.1]. Longitudinal spectral-domain optical coherence tomography volume scans (37 B-scans, 30° × 15°) were segmented using a deep learning (DL) approach. For genotype-phenotype analysis, a model of ABCA4 variants was applied with the age of criterion EZ-loss (6.25 mm2) as the dependent variable.RESULTSPatients exhibited an average (square-root-transformed) EZ-loss progression rate of [95% CI] 0.09 mm/y [0.06, 0.11]. Outer nuclear layer (ONL) thinning extended beyond the area of EZ-loss. The average distance from the EZ-loss boundary to normalization of ONL thickness (to ±2 z score units) was 3.20° [2.53, 3.87]. Inner segment (IS) and outer segment (OS) thinning was less pronounced, with an average distance from the EZ-loss boundary to layer thickness normalization of 1.20° [0.91, 1.48] for the IS and 0.60° [0.49, 0.72] for the OS. An additive model of allele severity explained 52.7% of variability in the age of criterion EZ-loss.CONCLUSIONPatients with ABCA4-associated retinopathy exhibited significant alterations of photoreceptors outside of EZ-loss. DL-based analysis of photoreceptor laminae may help monitor disease progression and estimate the severity of ABCA4 variants.TRIAL REGISTRATIONClinicalTrials.gov identifier: NCT01736293.FUNDINGNational Eye Institute Intramural Research Program and German Research Foundation grant PF950/1-1.
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WIDE-FIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF DIABETIC TRACTIONAL RETINAL DETACHMENTS BEFORE AND AFTER SURGICAL REPAIR.
Russell, JF, Scott, NL, Townsend, JH, Shi, Y, Gregori, G, Crane, AM, Flynn, HW, Sridhar, J, Rosenfeld, PJ
Retina (Philadelphia, Pa.). 2021;(8):1587-1596
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Abstract
PURPOSE Wide-field (WF) swept-source (SS) optical coherence tomography angiography (SS-OCTA) was used to image diabetic tractional retinal detachments (TRDs) before and after pars plana vitrectomy. The clinical utility of SS-OCTA was assessed. METHODS Patients with diabetic TRDs were imaged prospectively with SS-OCTA. Ultrawide-field imaging was obtained when possible. Postoperative WF SS-OCTA imaging was performed. RESULTS From January 2018 through December 2019, 31 eyes of 21 patients with diabetic TRDs were imaged. Wide-field SS-OCTA en-face images captured all areas of TRD and fibrovascular proliferation within the posterior pole that were visualized on ultrawide-field imaging. Optical coherence tomography angiography B-scans revealed the vascularity of preretinal membranes and identified areas of vitreoretinal traction and posterior vitreous detachment. Ten eyes underwent pars plana vitrectomy. Postoperative SS-OCTA imaging demonstrated removal of fibrovascular membranes, relief of traction, and resolution of TRDs. Retinal ischemia before and after surgical repair appeared similar. CONCLUSION All clinically relevant features of diabetic TRDs were identified at baseline and assessed longitudinally after pars plana vitrectomy using WF SS-OCTA, which showed resolution of vitreoretinal traction and no apparent change in the status of retinal perfusion after surgery. If the media are clear and fixation is adequate, WF SS-OCTA is likely the only imaging modality needed for the diagnosis and longitudinal evaluation of diabetic TRDs.
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THE EFFECT OF ELECTIVE CATARACT EXTRACTION BY PHACOEMULSIFICATION IN EYES WITH VITREOMACULAR TRACTION SYNDROME.
Mantopoulos, D, Prenner, JL, Patel, VK, Roth, DB, Shah, SP, Tsavaris, O, Fine, HF, Wheatley, HM
Retina (Philadelphia, Pa.). 2021;(1):75-81
Abstract
PURPOSE To evaluate the effect of cataract extraction (CE) by phacoemulsification on the vitreomacular interface (VMI) of eyes with preexisting vitreomacular traction (VMT). METHODS Retrospective, observational case series. Patients with VMT who elected to proceed with CE, before any vitreoretinal intervention, were studied. Eyes with at least a 12-month follow-up period were included. The status of the vitreomacular adhesion at different time points was assessed using spectral-domain optical coherence tomography. The best-corrected visual acuity was recorded at different time points. Other macular and systemic comorbidities were documented. RESULTS Fifteen eyes from 15 phakic patients with symptomatic VMT were included. Six of them were male subjects. Seven patients had diabetes mellitus and two of them also had nonproliferative diabetic retinopathy. The preoperative macular comorbidities included macular hole in six eyes (Stage 1 in 3 eyes and Stage 2 or 3 in another 3 eyes), epiretinal membrane in five eyes, and cystoid macular edema in four eyes. After uncomplicated CE, the VMT was released in 5 eyes, whereas in 10 eyes, CE did not significantly change the status of the vitreomacular adhesion. Three of 3 eyes with preexisting full-thickness macular hole (Stage 2 or 3 macular hole) were found to have Stage 4 macular hole shortly after CE. In seven of seven patients with diabetes mellitus, the status of the vitreomacular interface did not change after CE. Eventually, 7 of 15 patients underwent additional pars plana vitrectomy. Compared with the baseline vision, and vision before other interventions, the visual acuity after CE improved in 5 patients, remained unchanged in 7 patients, and decreased in the 3 patients with Stage 2 or 3 macular hole. The mean preoperative and early postoperative visual acuity was 20/59 and 20/68, respectively (P > 0.05). CONCLUSION The effect of CE in phakic eyes with known VMT varies significantly. In the current case series, every eye with VMT and Stage 2 or 3 macular hole ended up with Stage 4 macular hole, although the VMT did not change significantly in the eyes of diabetic patients. Studies with larger sample size are needed to further elucidate the impact of elective CE on VMT.
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NONCONFOCAL ULTRA-WIDEFIELD SCANNING LASER OPHTHALMOSCOPY: Polarization Artifacts and Diabetic Macular Edema.
Ajlan, RS, Barnard, LR, Mainster, MA
Retina (Philadelphia, Pa.). 2020;(7):1374-1378
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PURPOSE Bowtie-shaped polarization artifacts are often present in nonconfocal ultra-widefield scanning laser ophthalmoscope (SLO) images. We studied these artifacts and evaluated their potential value as clinical biomarkers in screening for center-involving diabetic macular edema (DME). METHODS We performed a retrospective, observational, cohort study on 78 diabetic adult patients (143 eyes) who had spectral domain optical coherence tomography and nonmydriatic nonconfocal ultra-widefield SLO testing on the same day. Scanning laser ophthalmoscope green-only (532 nm), red-only (635 nm), and composite pseudocolor (532 plus 635 nm) images were examined for the presence of a foveal bowtie polarization artifact. RESULTS Polarization artifacts were absent in all but one eye with center-involving DME (32 of 33 eyes). Polarization artifacts were also absent in many eyes without center-involving DME (49 of 110 eyes in pseudocolor images). As clinical biomarkers of center-involving DME, artifact absence has high specificity (99, 100, and 98% for green, red, and pseudocolor images, respectively) but poor sensitivity (49, 31, and 40% for green, red, and pseudocolor images, respectively). CONCLUSION Foveal bowtie-shaped polarization artifacts occur routinely in nonconfocal ultra-widefield SLO images. Their presence indicates preserved foveal Henle fiber layer structure. Contemporary nonconfocal ultra-widefield SLO images lack the sensitivity for their bowtie artifacts to serve as reliable biomarkers in screening for center-involving DME.
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Early visual field changes in patients with type 1 diabetes mellitus.
Ozates, S, Simsek, M, Elgin, U, Keskin, M, Aycan, Z
European journal of ophthalmology. 2020;(6):1467-1472
Abstract
PURPOSE To assess the visual field sensitivity changes and investigate the association between visual field sensitivity and retinal nerve fiber layer thickness in patients with type 1 diabetes mellitus. MATERIALS AND METHODS In this cross-sectional and observational study, 46 patients (22 males, 24 females) with type 1 diabetes mellitus and no diabetic retinopathy formed the diabetes mellitus group and 50 age-matched healthy subjects (32 males, 18 females) formed the control group. Retinal nerve fiber layer thickness, full-threshold standard automated perimetry, and short-wavelength automated perimetry were performed. Main outcomes were retinal nerve fiber layer thickness, mean deviation, pattern standard deviation, and short fluctuation. RESULTS Average retinal nerve fiber layer thickness was significantly thinner in the diabetes mellitus group (p < 0.001). The mean values of mean deviation and pattern standard deviation of the full-threshold standard automated perimetry did not differ between the groups (p = 0.179, p = 0.139, respectively). Mean short fluctuation was significantly greater in the diabetes mellitus group (p < 0.001). Both mean deviation and pattern standard deviation of the short-wavelength automated perimetry were significantly greater in the diabetes mellitus group (p < 0.001, p < 0.001, respectively). Pattern standard deviation of short-wavelength automated perimetry equal or higher than 1.57 dB had 91% sensitivity and 90% specificity (area under the curve = 0.969, p < 0.001) and short fluctuations of full-threshold standard automated perimetry equal or higher than 0.80 dB had 80% sensitivity and 76% specificity over detecting early retinal nerve fiber layer loss in patients with type 1 diabetes mellitus (area under the curve = 0.855, p < 0.001). CONCLUSION This study showed that thinner retinal nerve fiber layer in patients with type 1 diabetes mellitus may be associated with abnormal retinal sensitivity to short-wavelength stimulations in short-wavelength automated perimetry; however, retinal sensitivity to white stimulus was similar to that in healthy subjects in full-threshold standard automated perimetry.
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Distribution of peripheral lesions identified by mydriatic ultra-wide field fundus imaging in diabetic retinopathy.
Verma, A, Alagorie, AR, Ramasamy, K, van Hemert, J, Yadav, NK, Pappuru, RR, Tufail, A, Nittala, MG, Sadda, SR, Raman, R, et al
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2020;(4):725-733
Abstract
PURPOSE To analyze the distribution of diabetic retinopathy (DR) lesions in an Indian population using ultra-wide field (UWF) fundus imaging. METHODS Seven hundred fifteen subjects (1406 eyes) with diabetic retinopathy in India were enrolled in this multicenter, prospective, observational study using UWF pseudocolor imaging with Optos Daytona Plus (Optos plc, Dunfermline, Scotland, UK). Images were transmitted to Doheny Image Reading Center, Los Angeles, CA, for grading. The ETDRS grid was overlaid on stereographic projections of UWF images, and images were graded independently by 2 masked graders. Lesion distribution was graded as predominantly central (PCL) or predominantly peripheral (PPL) according to previous criteria, considering both lesion number and area. An image was graded as PPL if > 50% of the lesion area was seen in at least one peripheral field as compared with the corresponding ETDRS field. Diabetic retinopathy severity was also assessed based on the International Classification of Diabetic Retinopathy (ICDR) grading scale. The main outcome measures were lesion distribution (PPL versus PCL): overall and within specific fields in eyes with various grades of DR. RESULTS Lesion distribution was rated to be PPL in 37% of eyes and PCL in 63% of eyes (P < 0.003). The frequency of a PPL distribution varied significantly across all ICDR severity levels, with frequencies of mild non-proliferative DR (NPDR) (30.9%), moderate NPDR (40.3%), severe NPDR (38.5%) and PDR (34.9%), P = 0.005. When assessing which individual fields were rated to show a PPL distribution, the frequency was greatest in field 4 and least in field 7. For any grade of DR, temporal fields showed the greatest PPL frequency, followed in order by the superior, inferior, and nasal fields (P < 0.001). Only 3.5% of eyes showed PPL distribution in all five peripheral fields. CONCLUSIONS One-third of the UWF images showed a PPL distribution in this cohort with the temporal quadrant having the widest distribution of PPL. As the PPL distribution varied significantly between various grades of DR, UWF imaging may prove to be important for screening of referral warranted retinopathy.
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Ganglion Cell - Inner Plexiform Layer Damage in Diabetic Patients: 3-Year Prospective, Longitudinal, Observational Study.
Lim, HB, Shin, YI, Lee, MW, Koo, H, Lee, WH, Kim, JY
Scientific reports. 2020;(1):1470
Abstract
Diabetes is expected to accelerate age-related ganglion cell-inner plexiform layer (GC-IPL) loss, but there is limited information on the rate of reduction in GC-IPL thicknesses. We aimed to evaluate the reduction rate of GC-IPL thickness in diabetic patients, and to compare the rates between patients without and with diabetic retinopathy (DR). We included 112 eyes of 112 patients with diabetes [49 eyes without DR (no-DR group) and 63 eyes with mild to moderate non-proliferative DR (NPDR group)] and 63 eyes of 63 normal controls (control group) in this study. Macular GC-IPL thickness in all participants was measured for 3 years at 1-year intervals. The reduction rates of GC-IPL thickness were determined by linear mixed models and compared among the three groups. The estimated reduction rates of the average GC-IPL thickness in the no-DR (-0.627 μm/year) and NPDR (-0.987 μm/year) groups were 2.26-fold (p = 0.010) and 3.56-fold (p = 0.001) faster, respectively, than the control group (-0.277 μm/year). Age, duration of diabetes, and baseline average GC-IPL thickness were associated with longitudinal changes in average GC-IPL thickness. The GC-IPL reduction rate was significantly faster in diabetic patients, with and without DR. Physicians should therefore be aware that GC-IPL damage continues even if there is no DR.
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Longitudinal Angiographic Evidence That Intraretinal Microvascular Abnormalities Can Evolve into Neovascularization.
Russell, JF, Shi, Y, Scott, NL, Gregori, G, Rosenfeld, PJ
Ophthalmology. Retina. 2020;(12):1146-1150
Abstract
PURPOSE The hallmark of proliferative diabetic retinopathy (PDR) is retinal neovascularization. Tortuous intraretinal vascular segments known as intraretinal microvascular abnormalities (IRMAs) are a known risk factor for neovascularization (NV), but whether IRMA represents a biomarker or a vascular precursor lesion to NV has not been demonstrated. The purpose of this study was to determine whether IRMA may evolve directly into NV. DESIGN Retrospective analysis of prospective, observational case series. PARTICIPANTS Patients with treatment-naïve PDR. METHODS Patients were imaged longitudinally with fluorescein angiography (FA) and swept-source (SS) OCT angiography (OCTA) before and after panretinal photocoagulation (PRP). MAIN OUTCOME MEASURES Presence and colocalization of IRMA and NV on serial FA and SS OCTA. RESULTS Two PDR patients showed multiple NV and IRMA lesions at baseline examination. Three months after PRP, FA demonstrated profuse leakage from 3 new NV lesions in one patient and 1 new NV lesion in another patient. Multimodal imaging showed that these 4 lesions were IRMAs at baseline. Swept-source OCTA performed before PRP and 1 week, 1 month, and 3 months after PRP confirmed that the precursor IRMA lesions were intraretinal tortuous vascular lesions at baseline and that they developed into preretinal NV with contiguous intraretinal components. NV was found to develop and adhere to the posterior hyaloid even in areas of pre-existing hyaloidal detachment. CONCLUSIONS Diabetic retinal NV can develop from IRMA. Early identification of IRMAs may be an accurate means of predicting progression to PDR, and frequent monitoring of IRMAs with SS OCTA may facilitate early diagnosis of PDR.
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Reproducibility of Fixed-luminance and Multi-luminance Flicker Electroretinography in Patients With Diabetic Retinopathy Using an Office-based Testing Paradigm.
Wroblewski, JJ, McChancy, C, Pickel, K, Buterbaugh, H, Wieland, T, Gonzalez, A
Journal of diabetes science and technology. 2020;(6):1095-1103
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BACKGROUND We evaluated the reproducibility of office-based flicker electroretinography (ERG) in patients with nonproliferative diabetic retinopathy (NPDR). METHODS An observational study was conducted in which ultra-widefield fluorescein angiography (UWF-FA) was performed on 20 patients with mild-to-moderate NPDR; images were graded by the Fundus Photography Reading Center (Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA). Fixed- and multi-luminance flicker ERG was repeated four times (greater than or equal to seven days apart). Recording consistency was assessed using intra-class correlation coefficients (ICCs), coefficients of variation, and Pearson correlations. RESULTS 82.5% and 17.5% of eyes had mild and moderate NPDR using UWF-FA; 90% of the angiograms were given a high confidence grade. Fixed-luminance phase values were highly reproducible (ICC: 0.949; P < .001). There was a significant negative correlation between fixed-luminance phase and log-corrected ischemic index values (-0.426; P = .015). CONCLUSIONS Office-based, fixed-luminance phase values are highly reproducible and negatively correlate with retinal ischemia in NPDR, suggesting that global retinal dysfunction may be reliably quantified early in patients with diabetes.
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Relationship between diabetic macular edema and choroidal layer thickness.
Endo, H, Kase, S, Takahashi, M, Saito, M, Yokoi, M, Sugawara, C, Katsuta, S, Ishida, S, Kase, M
PloS one. 2020;(1):e0226630
Abstract
PURPOSE To investigate the relationship between diabetic macular edema (DME) and the choroidal layer thickness in diabetic patients. METHODS This is a retrospective observation study. Three hundred eighteen eyes of 159 diabetes mellitus (DM) patients and age-matched 100 eyes of 79 healthy controls were enrolled. DME was defined as over 300 μm in the central retinal subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector. The central choroidal thickness (CCT), as well as inner and outer layers were determined based on enhanced depth imaging (EDI)-OCT. Diabetic patients with/without systemic diabetic treatments (DT) at the start of this study was defined as DT+ and DT-, respectively. The number of eyes examined was 62 and 256 eyes in DME+and DME-groups, respectively. DM patients were further subdivided into 4 groups with/without DME and DT; DME+DT+(35 eyes), DME-DT+(159 eyes), DME+DT-(27 eyes), and DME-DT-group (97 eyes). Multiple comparisons on CCT layers including control and each DM group were statistically examined. RESULTS The total CCT layer was 254±83, 283±88, and 251±70 μm in the control, DME+, and DME-group, respectively. A total CCT layer in DME+was significantly thicker than the DME-group (P < 0.05). The outer CCT layer was 195±75, 222±83, and 193±63 μm in the control, DME+, and DME-group, respectively. The outer CCT layer in DME+ was significantly thicker than the DME-group (P < 0.05). In the subdivided groups, the total CCT layers in the control, DME+DT+, DME-DT+, DME+DT-and DME-DT-groups were 254±83, 274±88, 247±66, 290±84 and 258±75 μm, respectively. The outer CCT layers in each group were 195±75, 214±83, 189±58, 228±77, and 201±70 μm, respectively. Total CCT and the outer layer in DME+DT-was significantly thicker than the DME-DT+group (each P < 0.05). In contrast, there was no significant difference in inner layer between the groups. CONCLUSIONS The total and outer CCT layers of diabetic eyes were significantly thickened in the DME+DT-as compared with the DME-DT+group, suggesting that CCT may be related to the pathology of DME.