Ischemic Index Research Articles

Model-based analysis of the sensitivities and diagnostic implications of FFR and CFR under various pathological conditions.

Although fractional flow reserve (FFR) and coronary flow reserve (CFR) are both frequently used to assess the functional severity of coronary artery stenosis, discordant results of diagnosis between FFR and CFR in some patient cohorts have been reported. In the present study, a computational model was employed to quantify the impacts of various pathophysiological factors on FFR and CFR. In addition, a hyperemic myocardial ischemic index (HMIx) was proposed as a reference for comparing the diagnostic performances of FFR and CFR. Obtained results showed that CFR was more susceptible than FFR to the influence of many pathophysiological factors unrelated to coronary artery stenosis. In particular, the numerical study proved that increasing hyperemic coronary microvascular resistance significantly elevated FFR while reducing CFR despite fixed severity of coronary artery stenosis, whereas introducing aortic valve disease only caused a significant decrease in CFR with little influence on FFR. These results provided theoretical evidence for explaining some clinical observations, such as the increased risk of discordant diagnostic results between FFR and CFR in patients with increased hyperemic microvascular resistance, and significant increase in CFR after surgical relief of severe aortic valve disease. When evaluated with respect to the predictive value for hyperemic myocardial ischemia, the performance of FFR was found to be considerably compromised in the presence of severe coronary vasodilation dysfunction or aortic valve disease, whereas the relationship between CFR and HMIx remained relatively stable, suggesting that CFR may be a more reliable indicator of myocardial ischemia under complex pathophysiological conditions.

Longitudinal Panretinal Leakage and Ischemic Indices in Retinal Vascular Disease after Aflibercept Therapy: The PERMEATE Study

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). Prospective open-label study (clinicaltrials.gov identifier, NCT02503540). Thirty-one treatment-naive eyes with foveal-involving retinal edema secondary to DME and RVO. 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. The primary end point was the mean change in panretinal leakage index at month 12 from baseline as measured by UWFA. 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). Intravitreal aflibercept injections resulted in a dramatic reduction in panretinal leakage index. Panretinal ischemic index did not improve and trended toward worsening.

Quantitative Ultra-Widefield Angiographic Features and Associations with Diabetic Macular Edema

To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and microaneurysms. Retrospective image analysis study. Eyes with diabetic retinopathy that had undergone spectral-domain OCT, UWFA, and ultra-widefield fundus photography. OCT images were analyzed to determine the presence or absence of DME, central subfield thickness (CST), and subretinal fluid. Using a semiautomated analysis platform, UWFA images were segmented for ischemia, leakage, and microaneurysms with manual correction as needed. Clinical variables, including age, gender, race, hemoglobin A1C levels, blood pressure, cholesterol levels, use of blood thinners, smoking status, and lens status also were evaluated. Factors associated with the presence and severity of DME. A total of 304 eyes (156 right eyes, 148 left eyes) from 178 diabetic patients were analyzed in the study. Panretinal leakage index, microaneurysm count, and ischemic index were not significantly different between eyes with and without DME in univariate assessment. Zonal assessments of macular microaneurysms and macular leakage index values revealed that eyes with DME showed a significantly higher microaneurysm count (P= 0.001) and leakage index (P < 0.0001) in the posterior pole compared with eyes without DME. Severity of macular thickening (i.e., CST) was associated significantly with macular leakage index and posterior pole microaneurysm count (P= 0.0002 and P= 0.03, respectively). In addition to posterior pole leakage index and microaneurysm count, DME was associated with older age (P < 0.01), higher systolic blood pressure (P < 0.001), and white race (P= 0.03). Multivariate assessment confirmed the independent association of presence of DME with macular leakage index and macular microaneurysm count (P < 0.01). Quantitative measures of leakage index and microaneurysm count in the posterior pole on UWFA images were associated with the presence and severity of DME. Panretinal analyses were not linked to DME as strongly. Additional research is needed to determine the role of quantitative UWFA in predicting DME development and characterizing patient prognosis.

Intravitreal Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy: Outcomes from the Randomized RECOVERY Trial

Evaluate the impact of intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY) on retinal nonperfusion (RNP) in eyes with proliferative diabetic retinopathy (PDR). Prospective, randomized clinical trial. Eyes with treatment-naïve PDR and extensive RNP without diabetic macular edema. Patients were randomized 1:1 to intravitreal 2 mg aflibercept every 4 weeks (monthly) or every 12 weeks (quarterly). The primary outcome measure was change in total RNP area (in square millimeters) from baseline to year 1. Secondary outcomes included ischemic index (ISI), diabetic retinopathy severity scale (DRSS) scores, visual acuity, central retinal thickness, and adverse events. The mean and 95% confidence interval were calculated for each outcome. Through 1 year, the monthly (n= 20) and quarterly (n= 20) cohorts received 11.0 and 3.95 mean aflibercept injections, and DRSS scores improved 2 steps or more in 74% and 67% of patients, respectively. Among all patients through 1 year, mean total area of RNP increased from 235 mm2 to 266 mm2 (P= 0.18) and ISI increased from 25.8% to 31.9% (P= 0.004). Retinal nonperfusion outcomes favored monthly dosing. Mean total RNP increased from 207 mm2 at baseline to 268 mm2 (P= 0.01) at 1 year in the quarterly cohort and remained stable at 264 mm2 at baseline and 1 year (P= 0.70) in the monthly cohort (P= 0.05, monthly vs. quarterly cohorts). Although many eyes demonstrated increased areas of RNP longitudinally (n= 24 [66.7%]), this was more common with quarterly dosing (n= 14 [77.8%]), and a proportion of eyes (n= 12 [33.3%]) demonstrated localized areas of apparent reperfusion of nonperfused retina, more commonly in the monthly cohort (n= 8 [44.4%]). Widespread evidence of retinal reperfusion with aflibercept dosing of PDR eyes with extensive RNP was not identified, and therefore the primary outcome of the current study was not met. Nevertheless, zones of apparent reperfusion were detected in some patients, and a dose response was identified with a reduction of RNP progression with monthly compared to quarterly dosing.

Multiple Effects of Intravitreal Aflibercept on Microvascular Regression in Eyes with Diabetic Macular Edema

To evaluate the effects of intravitreal aflibercept (IVA) on the number of microaneurysms and sizes of nonperfused areas (NPAs) in eyes with diabetic macular edema (DME). Interventional, prospective study. Twenty-five eyes of 25 DME patients (average age, 64.0±8.8 years) were treated with 3 consecutive monthly IVA injections. Fluorescein angiography (FA) and OCT were performed before the IVA injections (baseline) and at 1 week after the IVA treatment. The number of microaneurysms and the ischemic index (ISI), a measure of NPA, were determined. The correlations between central retinal thickness (CRT) and number of microaneurysms and the ISI were also determined. The mean number of microaneurysms and NPA evaluated as the ISI. At baseline, the mean CRT was 485.7±90.6 μm. After treatment, the mean CRT was reduced significantly to 376.9±81.6 μm (P= 0.1× 10-5, repeated analysis of variance). The mean number of microaneurysms was decreased significantly from 49.6±33.2 at baseline to 24.8±18.1 at 3 months after the initial treatment. This was a 50.4±21.2% reduction (P= 0.3× 10-5, paired t test). The mean ISI was also decreased significantly from 55.5±20.4% at baseline to 28.8±16.8% after treatment (P= 0.3× 10-5, paired t test). This was a reduction of 43.3±28.5%. A significant correlation was found between the CRT and number of microaneurysms at both baseline (r= 0.56; P= 0.004) and after treatment (r= 0.53; P= 0.006). A significant correlation was found between CRT and ISI at baseline (r= -0.39; P= 0.03) but not after treatment (r= -0.06; P= 0.79). The reduction in the number of microaneurysms was correlated with reduction in CRT.

Quantitative Ultra-Widefield Angiography and Diabetic Retinopathy Severity: An Assessment of Panretinal Leakage Index, Ischemic Index and Microaneurysm Count

To investigate the relationship between the diabetic retinopathy (DR) severity and quantitative ultra-widefield angiographic metrics, including leakage index, ischemic index, and microaneurysm count. Retrospective image analysis study. Eyes with DR that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color photography were identified. All eyes were laser-naive and had not received any intravitreal pharmacotherapy within 6 months of UWFA. Each eye was graded for DR severity. Quantitative angiographic parameters were evaluated with a semiautomated analysis platform with expert reader correction, as needed. Angiographic parameters included panretinal leakage index, ischemic index, and microaneurysm count. Clinical characteristics analyzed included age, gender, race, hemoglobin A1C level, hypertension, systolic blood pressure, diastolic blood pressure, and smoking history. Association of DR severity with panretinal leakage index, ischemic index, and microaneurysm count. Three hundred thirty-nine eyes were included with mean age of 62±13 years. Forty-two percent of eyes were from women and 57.5% were from men. Distribution of DR severity was as follows: mild NPDR in 11.2%, moderate NPDR in 23.9%, severe NPDR in 40.1%, and PDR with 24.8%. Panretinal leakage index [mild NPDR (mean = 0.51%), moderate NPDR mean = 1.20%, severe NPDR (mean = 2.75%), and PDR (mean = 5.84%); P<2×10-16], panretinal ischemic index [mild NPDR (mean = 0.95%, moderate NPDR (mean = 1.37%), severe NPDR (mean = 2.80%), and PDR (mean = 9.53%); P<2×10-16], and panretinal microaneurysm count [mild NPDR (mean = 36), moderate NPDR (mean = 129), severe NPDR (mean = 203), and PDR (mean = 254); P<5×10-7] were strongly associated with DR severity. Multivariate analysis demonstrated that ischemic index and leakage index were the parameters associated most strongly with level of DR severity. Panretinal leakage index, panretinal ischemic index, and panretinal microaneurysm countareassociated with DR severity. Additional research is needed to understand the clinical implications of these parameters related to progression risk, prognosis, and implications for therapeutic response.

USE OF THE ISCHEMIC INDEX ON WIDEFIELD FLUORESCEIN ANGIOGRAPHY TO CHARACTERIZE A CENTRAL RETINAL VEIN OCCLUSION AS ISCHEMIC OR NONISCHEMIC.

To understand the relationship between baseline ischemic index (IsI) values on ultra-widefield fluorescein angiography and classification as ischemic central retinal vein occlusion (CRVO). Single-center retrospective cohort study of CRVO patients imaged using ultra-widefield fluorescein angiography from which IsI values were calculated. An ischemic CRVO was defined as those eyes with an afferent pupillary defect and counting fingers acuity or worse or neovascularization during the first year of follow-up. Logistic regression was performed to characterize the relation between the IsI and clinical outcomes. Sixty eyes of 60 treatment-naive CRVO patients with baseline ultra-widefield fluorescein angiography and ≥1 year of follow-up were identified. Those with an IsI ≥35% were significantly more likely to have an ischemic CRVO during the first year of follow-up than those with an IsI <35% (83.3 vs. 13.9%, odds ratio 111, P < 0.0001). Baseline and final logarithm of the minimum angle of resolution acuity were worse in eyes with an IsI ≥35% (1.18 vs. 0.46, P < 0.001 and 1.26 vs. 0.45, P < 0.001, respectively) despite similar baseline and final central subfield thickness (P = 0.1-0.23). A baseline IsI of ≥35% on ultra-widefield fluorescein angiography in eyes with treatment-naive CRVO was sensitive (90%) and specific (92.5%) for classification as an ischemic CRVO during the first year of follow-up.

Association of Retinal Inner Layer Disorganization With Ultra-Widefield Fluorescein Angiographic Features and Visual Acuity in Branch Retinal Vein Occlusion.

To assess the impact of the disorganization of retinal inner layers (DRIL) on visual acuity (VA) and its correlation with ischemic index (IsI) on ultra-widefield fluorescein angiography (UWFFA) in eyes with acute, treatment-naïve branch retinal vein occlusion (BRVO). Retrospective, longitudinal study of BRVO eyes with 1 year of follow-up or more. Area of intraretinal cysts, DRIL length, extent of disruption of external limiting membrane (ELM), and ellipsoid zone (EZ) were graded on the central 1,000 μm of foveal optical coherence tomography (OCT) scan. Baseline IsI was calculated on UWFFA. Thirty eyes of 30 patients with a mean follow-up of 25.4 months ± 11.0 months were evaluated. At baseline, 50% had DRIL (mean 443.1 μm ± 460.4 μm). DRIL length at baseline was predictive of worse VA at 12 months (P = .029), and DRIL length at 12 months was predictive of worse final VA(P = .011). In multivariate analyses, DRIL length was associated with final VA (P = .008) after controlling for other OCT parameters. There was no association between baseline IsI on UWFFA and DRIL. DRIL served as an independent OCT biomarker predictive of worse VA during a period of 2 years in acute, treatment-naïve BRVO. Development of DRIL was influenced by presence of CME, intraretinal cyst area, and extent of ELM and EZ disruption, but not by severity of baseline IsI. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:354-364.].

Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response

Cardioprotection by salvage of the infarct-affected myocardium is an unmet yet highly desired therapeutic goal. To develop new dedicated therapies, experimental myocardial ischemia/reperfusion (I/R) injury would require methods to simultaneously characterize extent and localization of the damage and the ensuing inflammatory responses in whole hearts over time. Here we present a three-dimensional (3D), simultaneous quantitative investigation of key I/R injury-components by combining bleaching-augmented solvent-based non-toxic clearing (BALANCE) using ethyl cinnamate (ECi) with light sheet fluorescence microscopy. This allows structural analyses of fluorescence-labeled I/R hearts with exceptional detail. We discover and 3D-quantify distinguishable acute and late vascular I/R damage zones. These contain highly localized and spatially structured neutrophil infiltrates that are modulated upon cardiac healing. Our model demonstrates that these characteristic I/R injury patterns can detect the extent of damage even days after the ischemic index event hence allowing the investigation of long-term recovery and remodeling processes.

Distribution of Nonperfusion and Neovascularization on Ultrawide-Field Fluorescein Angiography in Proliferative Diabetic Retinopathy (RECOVERY Study): Report 1

To explore the distribution of nonperfusion area (NPA) on ultrawide-field fluorescein angiography (UWF FA) in proliferative diabetic retinopathy (PDR) and its relationship with the presence of neovascularization of the optic disc (NVD) and distribution of neovascularization elsewhere (NVE). Prospective, observational case series. Baseline Optos 200Tx UWF FA images of 38 eyes with treatment-naïve early-stage PDR from the RECOVERY (NCT02863354) study were stereographically projected at the Doheny Image Reading Center. Two independent/masked certified graders manually delineated the NPA and the total visible retinal area (TRA). NPA and TRA were then computed in square millimeters using the manufacturer software. Ischemic index (ISI) was calculated by dividing NPA by TRA. NPA and ISI were correlated with the presence and distribution of neovascularization in the corresponding zones. Eyes with NVD appeared to have more severe global NPA than those without (P= .026). Although the ISI appeared to increase with increasing distance from the foveal center (P < .001), NVE was more likely to be located in the posterior pole than the midperiphery or far-periphery (P < .001). Presence of NVE in the posterior polar retina appeared to demonstrate more severe ischemia in the posterior pole and midperiphery than those without (P < .05), but interestingly, was not correlated with the severity of overall global ischemia or of ischemia in the far-periphery alone (P > .05). Whereas the presence of NVD was associated with the severity of global ischemia, the distribution of NVE did not appear to be influenced by the distribution of ischemia.

Combined Multimodal Analysis of Peripheral Retinal and Macular Circulation in Diabetic Retinopathy (COPRA Study)

To systematically examine the relationships between the microvascular indices that are measured on OCT angiography (OCTA) and the presence and extent of peripheral nonperfusion in persons with diabetic retinopathy. A retrospective cross-sectional study of patients who had varying degrees of diabetic retinopathy. The study sample was recruited from 2 large tertiary referral retina clinics. In total, 82 eyes of 45 patients with varying degrees of diabetic retinopathy were enrolled and analyzed. Relationships between peripheral ischemia measured on fluorescein angiography (FA) and OCTA metrics, including foveal avascular zone (FAZ) and vessel density measurements. A significant decrease in mean signal index in both the superficial and deep plexus and binarized flow index in the superficial plexus were found with increasing duration of diabetes mellitus. OCT and OCTA grading showed increasing central macular thickness and prevalence of microvascular abnormalities in the superficial and deep capillary bed with worse retinopathy as measured on the Diabetic Retinopathy Severity Scale. FAZ area and major axis and minor axis length were strongly associated with diabetic retinopathy severity. On classifying eyes into tertiles of peripheral ischemia measured on FA, significant increases in various FAZ metrics, including FAZ area and minor axis length, were noted. Statistically worsening of FAZ OCTA metrics was only seen between tertiles 2 and 3, indicating a non-linear relationship. The presence of neovascularization of the disc, neovascularization elsewhere, or intraretinal microvascular abnormality was associated with a significant increase in FAZ major axis length in the superficial plexus and a significant decrease in binarized flow index in the deep plexus. OCTA metrics are indicators of the severity of peripheral retinal nonperfusion. However, the central ischemic index did not exhibit a linear relationship with peripheral capillary nonperfusion. Our findings suggest that a rise in intraocular vascular endothelial growth factor as a consequence of mild peripheral capillary nonperfusion may play a compensatory role in maintaining the central macular microcirculation. Further investigations with studies employing longitudinal design will improve our understanding of the relationship between macular microcirculation and peripheral ischemia.

Analysis of quantitative correlations between microaneurysm, ischaemic index and new vessels in ultrawide-field fluorescein angiography images using automated software

Background/AimTo analyse ultrawide-field fluorescein angiography (UWF-FA) images of diabetic retinopathy using a novel software that automatically calculates microaneurysm (MA) and non-perfusion area.MethodsTwo hundred UWF-FA images of treatment-naïve diabetic retinopathy (38...

The association between physical activity and cardiac performance is dependent on age: the Copenhagen City Heart Study

This study aimed to test the hypothesis that regular physical activity is associated with improved cardiac function measured by tissue Doppler imaging (TDI) in the general population. Within a large prospective community-based population study, cardiac function was assessed in 2221 persons by TDI. Longitudinal displacement (LD), early diastolic velocity (e’), and myocardial performance index (MPI) was obtained by TDI. Linear univariable and multivariable regression analyses were performed in relation to age groups (< 50 years, 50–65 years, > 65 years) and self-reported level of physical activity: I (inactivity), II (light activity), III (moderate activity), and IV (high-level activity). Participants < 50 years in the most active group had significantly better cardiac performance when compared to all other activity levels (higher levels of e’, LD, and lower levels of MPI). The findings remained with statistical significance after adjustment for sex, ischemic heart disease, diabetes, hypertension, and body mass index (e’ = 11.0, 95% CI (10.4–11.6), p < 0.001; LD = 12.8 (12.3–13.4), p < 0.003; MPI: 0.40 (0.38–0.42), p = 0.02). In age > 65 years, there was a tendency of impaired cardiac function in higher levels of exercise. Interaction analysis revealed that age significantly modified the association between physical activity and cardiac function (p < 0.001). We found a positive association between higher level of physical activity and improved cardiac function in younger persons (< 50 years). In the general population, however, the association interacted with age and amongst persons above 65 years there was a negative association between higher level of physical activity and cardiac function.

Differences in the Incidence of Major Risk Factors in Patients with Ischemic or Hemorrhagic Stroke in the Siberian Population

Background. The study of the incidence of risk factors (RF) of stroke for primary and secondary prevention of this disease remains relevant. There are modifiable and non-modifiable RF.Aim. To study the frequency of the main RF in patients with ischemic and hemorrhagic stroke in the urban population of Krasnoyarsk (Eastern Siberia).Material and methods. Examination of 124 patients with an ischemic stroke and 28 with hemorrhagic was performed. Patients received treatment in neurologic center of Krasnoyarsk in 2014 year. The main criterion of inclusion was the confirmed diagnosis of an ischemic or hemorrhagic stroke. All patient had the clinic-tool and neurovisualizing examination and collecting the individual and family anamnesis with examination of modifiable and non-modifiable RF. The research of the neurologic status at patients both with ischemic, and with a hemorrhagic stroke was conducted by the standard technique. Based on results of computer or magnetic resonance imaging of a brain the diagnosis of an ischemic or hemorrhagic stroke was established.Results. A distinctive feature of patients with hemorrhagic stroke was the occurrence of a vascular accident in younger age (6 years earlier) in comparison with ischemic stroke. Among patients with ischemic stroke elevated body mass index (BMI) was in 87 (70.2%) patients, burdened heredity was in 8.1% of cases, and 43.5% of patients were smokers. Among patients with hemorrhagic stroke 16 (57.1%) patients had elevated BMI. People with burdened heredity were not identified among them. Smoking was found in 22 (78.6%) patients in this group.Conclusion. Improvement of treatment and prevention of an ischemic stroke are in many respects connected with clarification of RF and pathogenic mechanisms of its development. The rational pharmacotherapy directed to pointed impact on individual RF can reduce the risk of development of stroke not only at individual, but also at the population level.

Peripheral Ischemia in Diabetic Retinopathy and Retinal Vein Occlusion: New Insights with Ultra-Wide-Angle Fundus Imaging and Wide-Angle Fluorescein Angiography

In several diseases such as diabetic retinopathy and retinal vein occlusion, relevant pathophysiological changes take place in the retinal periphery. These changes may determine the prognosis and outcomes of therapy. Recent ultra-wide-angle camera systems promise improved and simplified visualisation of the outer periphery of the retina. This could potentially lead to novel clinical applications of these methods, with potential impact on therapy decisions. Literature and database research on ultra-wide imaging for diabetic retinopathy and retinal vein occlusion. With ultra-wide-angle angiography, it is possible to visualise up to 3.2-fold more retinal surface than conventional 7SF images (7SF: 7 standard field). Initial studies imply that diabetic changes can be found outside of the boundaries of the 7SF images. Patients with central vein occlusion have more extended and severe macular oedema and poorer visual acuity if ischemia of the periphery is more pronounced (measured by the ischemic index [ISI]). The amount of ischemia influences the size of the macular oedema, its resolution under therapy and the number of anti-VEGF injections needed to treat it. Ultra-wide-angle camera systems allow visualisation of the peripheral retina outside the boundaries of standard methods. Initial studies have detected potentially relevant changes in the outer periphery, which would have been missed by 7SF. Nevertheless, there have been no systematic studies on the relevance of these changes with regards to prognosis and therapeutic decisions.

Ultra-Wide-Field Fluorescein Angiography–Guided Normalization of Ischemic Index Calculation in Eyes With Retinal Vein Occlusion

The purpose of this study was to compare the use of central and montaged ultra-wide-field fluorescein angiography (UWFFA) images for calculating the area of nonperfusion (NP) and ischemic index (ISI) in patients with retinal vein occlusion (RVO) and macular edema (ME) and to correlate these measurements with best-corrected visual acuity (BCVA) and central macular thickness (CMT). Thirty eyes of 30 RVO patients with recurrent ME were enrolled. Baseline UWFA images were sent to the Doheny Image Reading Center for quantitative analysis by certified graders. The association between ISI from the various zones and BCVA and CMT was examined by Spearman rank correlation and compared. Generalized linear models (GLMs) were used to analyze associations between BCVA and disease status. The NP area and ISI for central and montaged images were not significantly different for any retinal zone. A modest but statistically significant negative linear correlation was observed between BCVA and ISI, ranging from r = -0.3825 in the perimacular area (PMA) to r = -0.584 in the far peripheral area (FPA). On GLM analysis, both PMA (β = -1.059; 95% confidence interval: -1.74 to -0.378) and FPA (β = -0.505; 95% confidence interval: -0.988 to -0.021) were significant independent predictors of BCVA. We found no correlation between ISI from the various zones and CMT in this cohort. Montaging of UWFFA images may not be required to adequately quantify and represent areas of NP in eyes with RVO. NP in both the PMA and peripheral retina appear relevant to visual function, highlighting the importance of evaluating the retinal periphery in these individuals.

Quantification of radiation retinopathy after beam proton irradiation in centrally located choroidal melanoma

To localize and quantify ischemic changes induced by proton beam irradiation of central choroidal melanoma and to identify baseline predictors correlated with the extent of ischemic changes. Retrospective chart review of patients with central choroidal melanoma treated by proton beam irradiation and conducted widefield fluorescein angiography (≥ 20months after radiation therapy). Quantification and location of ischemic areas and correlation to baseline predictors. Multiple linear regression model was performed for analyses. Twenty-five eyes from 25 patients were included in final analysis. Mean largest basal tumor area was 56.6 ± 40.0mm2 and mean maximal tumor prominence 2.5 ± 1.4mm. Mean total radiated area was 339.1 ± 68.3mm2. All patients showed ischemic changes. Mean ischemic area was 387.6 ± 123.3mm2 and mean ischemic index (ischemic area/total visible area) was 0.53 ± 0.23. Twenty-two patients (88%) presented ischemic changes outside of the irradiation field, which comprised of 23% of total ischemic area. Mean angular distance between lateral border of irradiation field and ischemic area outside of the radiated area was 44.8 ± 36.5°. Multivariable analysis revealed a positive correlation of total ischemic area with total radiated area (p = 0.02) and initial sonographic tumor prominence (p = 0.02). Ischemic changes induced by proton beam irradiation of central choroidal melanoma were localized and quantified. Ischemic changes exceed the tumor area distinctly and are found also outside of the irradiation field in the majority of patients. Size of irradiation area and tumor prominence are positively correlated with extent of ischemic area.

Association of Disorganization of Retinal Inner Layers with Ischemic Index and Visual Acuity in Central Retinal Vein Occlusion

To determine whether disorganization of retinal inner layers (DRIL) on optical coherence tomography (OCT) is associated with ischemia on ultra-widefield fluorescein angiography (UWFFA) and with visual outcomes in eyes with acute, treatment-naïve central retinal vein occlusion (CRVO). Retrospective, single-institution, longitudinal cohort study. Twenty-five consecutive patients with treatment-naïve CRVO and ≥ 1 year follow-up. Two independent masked graders evaluated the extent of DRIL, ellipsoid zone disruption, external limiting membrane disruption, and other OCT parameters at the baseline, 6- month, 12-month, and final visits. Baseline UWFFA images were assessed for ischemic index values and foveal avascular zone (FAZ) enlargement. Associations of DRIL with UWFFA findings and clinical outcomes including corrected visual acuity (VA). The median time to final follow-up was 24 months (range 12.1 - 43.9 months). Median DRIL extent at baseline was 765 µm (range 0 - 1000 µm). Eighteen of 25 eyes (72%) had some degree of DRIL at baseline, and 20 of 25 eyes (80%) had cystoid macular edema (CME). Neither the presence nor extent of DRIL at baseline was associated with presenting VA. In a cross-sectional analysis of each visit, extent of DRIL correlated with worse VA at both the 6-month (ρ = 0.656; p = 0.001) and final (ρ = 0.509; p = 0.016) visits. At final follow-up, DRIL extent was the OCT parameter most strongly correlated with baseline ischemic index (ρ = 0.418; p = 0.047) and baseline enlarged FAZ (p = 0.057) on UWFFA. On multivariate regression analysis, DRIL extent at final follow-up was the only OCT parameter associated with worse VA (p = 0.013) and remained significant when accounting for CME as a potential confounder. Extent of DRIL was not associated with presenting VA in treatment-naïve eyes with acute CRVO. Following six months of follow-up however, DRIL extent correlated with worse VA and was predictive of worse VA throughout more than 2 years of follow-up. Ischemic features on UWFFA at baseline are predictive of the extent of DRIL development at final follow-up.

Changes in retinal ischaemic index correlate with recalcitrant macular oedema in retinal vein occlusion: WAVE study

AimTo evaluate changes in the ischaemic index (ISI) after targeted retinal photocoagulation (TRP) and to investigate the correlation between these changes and macular oedema (ME).MethodTwenty-four eyes of 24 patients with...

Extension of peripheral nonperfusion in eyes with retinal vein occlusion during intravitreal dexamethasone treatment.

To evaluate the change in peripheral perfusion status in patients with retinal vein occlusion (RVO) during dexamethasone treatment. Thirty-five eyes of patients with macular oedema due to either branch or central retinal vein occlusion were included. At baseline, patients were treated with an intravitreal dexamethasone implant (Ozurdex® ) and followed until month 6. Wide-field angiographies were classified as ischaemic and nonischaemic. Peripheral nonperfusion (PNP) was determined manually by calculating the percentage of nonperfusion area in relation to the total visible retina (ischaemic index). Thirteen eyes showed evidence of >10 disc area of PNP at baseline and were graded as ischaemic RVO. In nonischaemic eyes, the mean area of PNP was 0.3% at baseline, 0.6% after 1month, 0.6% after 3months and 0.6% after 6months, respectively (p>0.05). In ischaemic RVO, the ischaemic index was calculated to be 18% at baseline. One month after treatment, mean area of PNP was 16% and after 3months was 19% (p=0.8; p=0.6). After retreatment, total PNP area was 18% (month 6; p=0.9). During treatment, best-corrected visual acuity (BCVA) increased and central retinal thickness (CRT) decreased from baseline to final follow-up with no differences between nonischaemic/ischaemic RVO. A significant negative correlation between the total area of PNP and visual acuity was identified (r=-0.6; p=0.04). Using 200° wide-field fluorescein angiography, the ischaemic index was shown to remain stable during dexamethasone treatment. This finding was consistent in ischaemic as well as in nonischaemic conditions.