The ophthalmic artery resistive index as a predictor of choriocapillaris ischemia in multivariate logistic models

ABSTRACT Objective Vascular findings in preeclampsia are usually attributed to increased vascular tone. Recently, however, important studies have improved the understanding of the main pathophysiological events in this condition, especially vascular brain remodeling, impaired autoregulation, and damage of the blood-brain barrier, which are well recognized features of cerebral overperfusion. Methods In this study, the association between choriocapillaris ischemia with ophthalmic artery blood flow parameters on orbital Doppler ultrasound is reported for the first time using multivariate logistic models. Multivariate logistic models with ophthalmic artery blood flow parameters, as well as major clinical and laboratory predictive variables were established for choriocapillaris ischemia and choriocapillaris ischemia with retinal detachment. Results In a series of 165 patients, 46 (28%) presented choriocapillaris ischemia; among them, 20 (12%) presented associated retinal detachment. The ophthalmic artery resistive index was the main predictor for choriocapillaris ischemia and choriocapillaris ischemia with retinal detachment in multivariate logistic models. Ophthalmic artery resistance lower than 0.56 was associated with a significantly high incidence of both outcomes. Conclusion This study supports that the branching pattern of choroidal arterioles and the lobular organization of choriocapillaris are the major morphological aspects underlying endothelial damage and lobular ischemia in the context of choroidal overperfusion. Overperfused lobules bordering areas of choriocapillaris ischemia produce a perfusion pressure gradient, with lobular reperfusion, leakage from reperfused choriocapillaris, and retinal detachment. Ophthalmic artery-resistive index lower than 0.56 is proposed as a major predictor of the overperfusion-related choriocapillaris ischemia and choriocapillaris ischemia with retinal detachment in preeclampsia.


INTRODUCTION
Preeclampsia is a multisystem progressive condition characterized by endothelial damage, coagulation cascade activation, shifting of blood volume from peripheral to central territories, and end-organ damage.Clinically, preeclampsia is suggested in presence of significant increase in blood pressure (≥160mmHg systolic, ≥110mmHg diastolic, or >126mmHg mean) after the 20 th week of gestation, associated with clinical or laboratory evidence of end-organ damage.Ischemia and overperfusion are well-recognized underlying features in preeclampsia, and the vascular pathophysiology encompassing both events remains a subject of debate.Mean blood pressure at admission (MBPA), mean blood pressure elevation (MBPE) after the 20 th week of gestational age, as well as laboratory evidence of glomerular damage (24-hour urine protein test) and endothelial damage (LDH) are major criteria of severity in preeclampsia.However, these clinical and laboratory criteria are insufficient to establish the risk of preeclampsia progression and its vascular complications.
The full spectrum of ophthalmologic findings in preeclampsia was formerly attributed to retinal vasospasm, recognized as a main vascular event in severe preeclampsia and the hallmark of systemic vasospasm. (1,2)The relevance attributed to retinal vasospasm in the vascular pathophysiology of preeclampsia was supported by authors who proposed that such finding would be considered a formal indication for delivery.However, the presence of retinal arteriolar narrowing, as well as retinal hemorrhages and cotton wool spots, the main findings of hypertensive retinopathy, had lost relevance in favor of choriocapillaris ischemia (CCI) and retinal detachment (RD).These findings provide evidence of hypertensive choroidopathy, which are primarily determined by high blood pressure in a structure where conditions of vasospasm are impaired.
Choriocapillaris ischemia, a leading ophthalmologic finding in preeclampsia, occurs as white or yellow-white subretinal spots of well-defined margins, with a mean diameter of 800μm, coincident with choriocapillaris lobule diameter.Choriocapillaris ischemia presents as multiple spots located in posterior pole and midperiphery, often associated with multifocal or diffuse RD. (3) In fluorescent angiography, CCI in preeclampsia appears as areas of choroidal filling delay, followed by hyper-fluorescence and leakage of dye into the subretinal space and retinal RD. (4) On OCT, choroidal thickening is a well-established finding in severe preeclampsia, whereas filling defects of the choriocapillaris are observed on OCTA. (2,5)ood flow parameters in the ophthalmic artery (OA) mirror the behavior of choroidal perfusion.Ophthalmic artery-resistive index (OARI) and pulsatility index (OAPI), which are measures of vascular resistance, are the main parameters to assess distal vascular resistance.Among them, OARI, which assumes values between zero and one, has been the main parameter to assess vascular resistance in OA and short posterior ciliary arteries (SPCA).Ophthalmic artery-resistive index and OAPI, in addition to ophthalmic artery mean velocity (OAMV), provide a reliable estimation of choroidal flow volume.The study of blood flow parameters with orbital Doppler ultrasound (ODU) was first reported in preeclampsia by Hata et al., who obtained lower OAPI in preeclampsia compared to normal pregnancy, as well as in severe preeclampsia compared to mild preeclampsia. (6,7)he association between CCI and RD with lower OARI was first presented by Barbosa et al. (8)

METHODS
The study included 165 patients admitted to the Hospital das Clínicas of the Universidade Federal de Minas Gerais (UFMG), a reference center for the diagnosis and treatment of high-risk pregnancy and preeclampsia, from January 2002 to May 2006.Inclusion criteria were diagnosis of preeclampsia, according to the Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy, (9) and prenatal examinations with reliable clinical and laboratory data.Exclusion criteria were occurrence of seizures, headache, and clinical evidence of preeclampsia-related encephalopathy before ODU; labor onset and uterine contractions; antiphospholipid antibodies; disseminated intravascular coagulation; hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome; current and previous kidney and heart disease; gestational diabetes and diabetes mellitus, and glaucoma.The study was approved by the Research Ethics Committee of UFMG.All patients participated voluntarily, according to the terms of the Declaration of Helsinki.
Orbital Doppler ultrasound was performed immediately after hospital admission by the same examiner, who received no information regarding clinical data or medical history.A Medison 8800 color Doppler equipment was employed, coupled to a 7.5 MHz linear transducer applied to closed eyes covered with methylcellulose gel, with patients in the supine position.Ophthalmic artery was studied in its temporal segment, 14 to 20mm from the posterior scleral wall.Blood flow parameters were obtained in the arterial axis, proximal to ciliary branching, from regular spectral curves of the right eye, with proper angle correction.For the present study, OARI and OAMV measurements were recorded.Immediately after the ODU, an indirect binocular ophthalmoscopy was performed using a Keeler ophthalmoscope with a 20-diopter aspherical Volk lens, after installation of 1% tropicamide drops.Until 48 hours after the ODU, patients were submitted to a posterior segment biomicroscopy with a Haag-Streit slit lamp and a 90-diopter aspherical Volk lens, and findings of posterior pole and midperiphery were documented with color retinography, obtained with a Topcon 50 VT or 50 Xi retinal scanner.
The normality of distribution of predictive variables was assessed with the Anderson-Darling test.Comparisons between groups of patients with and without CCI in relation to the predictive variables OARI, OAMV, MBPA, MBPE, LDH, and 24-hour urine protein test were performed with Mann-Whitney test.The power of discrimination of each predictor variable in relation to the presence of CCI was evaluated with the estimate of area under the Receiver Operating Characteristic (ROC) curve (A E ) and their confidence intervals (A CI ).The cut-off points of ROC curves were obtained through the intercept of sensitivity and specificity curves for each predictor variable, in function of the occurrence of CCI.Each categorized variable assumed the value of one or zero, for higher and lower risks of CCI, respectively.
Three groups of logistic models were constructed: a) a binary logistic regression for CCI (y=1 if CCI present, y=0 if CCI absent); b) a binary logistic regression for CCI superimposed by RD (CCI-RD; (y=1 if CCI associated with RD, y=0 if CCI and RD absent); and c) an ordinal logistic regression for CCI-RD, CCI (y=2 and y=1 respectively, and y=0 if CCI and RD absent).Logistic models were established with variables categorized in function of the cut-off point of each ROC curve and then with categorized OARI fixed as a factor, and further continuous variables as covariates.Binary CCI, binary CCI-RD and ordinal CCI/CCI-RD models were established as pairs of OARI-unfactored and OARI-factored models, which were presented in their complete form, with the full set of variables, and then in their ultimate form, only with significant variables.
Estimates of β coefficients, estimates and confidence intervals of odd ratios (OR E and OR CI ), Wald statistics, G statistics, general measures of fit (Pearson, Deviance and Hosmer-Lemeshow), general measures of association (Sommers, Goodman-Kruskal Gamma and Kendall's Tau-a) were obtained for each model.Binary OARI-factored models were evaluated with A E and A CI and individual component analysis (changes in β coefficients, Pearson and Deviance, respectively Δβ, ΔPearson and ΔDeviance).All the analyses were obtained using SPSS 15 and Minitab 15 softwares.The present study was approved by the Ethics Committee of the Universidade Federal de Minas Gerais (ETIC078/05).

Ophthalmologic findings
Among the 165 patients in the series, CCI was identified in 46 (28%), from which 20 (43%) had associated RD.Among patients with RD, it was multifocal in 16 (80%) and diffuse in 4 (20%), respectively, at admission.Diffuse RD was characteristically bullous, with prominent shifting of the subretinal fluid, involving posterior pole and midperiphery, and including macula.Subretinal fluid was significantly opaque, producing white-yellowish subretinal inferior demarcation lines.Ten patients (62%) with multifocal RD at admission progressed to diffuse RD.Among four patients (20%) with flat diffuse RD at admission, two progressed to diffuse, bullous RD.All patients with multifocal or diffuse RD presented CCI.All patients with CCI or CCI-RD presented bilateral and symmetric findings.Retinal arteriolar narrowing in the posterior pole was identified in 34 (21%) patients in this series and was associated with significant retinal edema, characterized by increased striations in retinal nerve fiber layer.Images of CCI and CCI-RD are shown in figure 1.The association between retinal arteriolar narrowing and retinal edema suggest a bias in the evaluation of retinal vasospasm based on ophthalmoscopic findings.Analyses of retinal arteriolar narrowing with ODU, as well as clinical and laboratory predictors, were not performed in this study.

Differences in the predictor variables in function of the occurrence of choriocapillaris ischemia
Patients with and without CCI presented similar age (22.8±7.4 and 23.7±5.5 years old; p=0.556), as well as gestational age (32.6±8.4 and 33.7±7.8weeks; p=0.338).Significant differences were obtained between patients with and without CCI, in relation to OARI (0.53±0.004

General measures of association
Measures of Somers' D, Goodman-Kruskal Gamma, Kendall's Tau-a statistics in binary CCI, binary CCI-RD, and ordinal CCI-RD were similar (p-values >0.05).A significant increase in the ratio of concordant and discordant pairs was obtained between the full and the final binary OARI-unfactored model of CCI-RD (7.89 and 20.93), as well as between the full and the final ordinal OARIfactored models of CCI-RD (6.49 and 12.79).A significant high ratio of concordant and discordant pairs was also obtained in both full and final binary OARI-factored models of CCI-RD (14.49 and 12.46).In the other models, the ratios of concordant and discordant pairs were close to six.

Assessment of logistic model accuracy with ROC curves
Binary final OARI-factored and OARI-unfactored models were analyzed according to their discrimination accuracy between patients with and without CCI and CCI-DR.
Impressive high measures of A E were obtained in OARIfactored models for CCI (A E 0.855, A IC 0.771-0.899)and for CCI-RD (A E 0.901 and A IC 0.838-0.964) in both models, with similar A IC .Similar A E and A IC were obtained with and without the inclusion of OAMV in both models.As ROC curves are inappropriate for assessing ordinal logistic model accuracy, they were restricted to binary models.for CCI-DR.Measures of ΔPearson/E P higher than six were obtained in five points and two points, whereas Δdeviance/ E P higher than four were obtained in five and three points, respectively.Scatterplots of Δβ/E P , ΔPearson/E P and Δdeviance/ E P for CCI and CCI-RD are shown in Figures 1 and 3.

DISCUSSION
This study presents high frequencies of CCI and CCI-RD in a series of severe preeclampsia.(12) Choriocapillaris ischemia was recognized later than RD in the literature, and the association between CCI and RD has been under considered. (2,12)RD in preeclampsia is characteristically multifocal or diffuse and associated with CCI in the posterior pole and midperiphery. (1,3,13)The opaque subretinal fluid identified in this series supports the high permeability of both choriocapillaris and RPE in preeclampsia.Experimental studies demonstrated that CCI is produced by injection of latex microspheres in the vortex veins of rabbits. (14)The occurrence of RD superimposed on CCI occurred when choriocapillaris embolization was followed by shift of blood flow volume and choroidal overperfusion from thoracic aorta compression. (15,16)Angiographic studies in patients with preeclampsia demonstrated that CCI was associated with filling defects in early stages and leakage of dye to the subretinal space in late stages of the fluorescein angiogram. (17)Significant choroidal thickening was obtained in OCT and OCT-A in severe preeclampsia, consistent with choroidal overperfusion. (8,18)The association between CCI and RD with lower OARI was first presented by Barbosa et al. (8) The analysis of the relevance of main predictors to the occurrence of CCI and CCI-RD was performed with logistic regression.This technique occupies a prominent position among multivariate models due to its high applicability, flexibility, and robustness. (20,21)(22) These analyses were performed in this study, which provided solid evidence that OARI and MBPA are the major predictors of CCI and CCI-RD in severe preeclampsia.The higher frequency of such findings with OARI <0,56 and MBPA >137.5mmHgdemonstrated that CCI and CCI-RD are primarily related with choroidal overperfusion.With the aim to properly understand the conclusions of this study, a revision of the strategy should be performed.
In this series, variables were first introduced in their categorized forms, in reference to the cut-off points of ROC curves, to better summarize model variable distributions.The concept of the ROC curve, originated from signal detection theory, is based on the recognition of signal in presence of noise. (20,23)The main parameters obtained from ROC curves, A E and A CI , provide general accuracy measures of predictors, whereas sensitivity, specificity, and likelihood ratios of cut-off points provide information for clinical decision based on parameter data. (23)Due to the high A E and A CI obtained from the OARI ROC curve, as well as the impressive likelihood ratio of 4 related to the cut-off point of 0.56, OARI was established as a factor.Predictors were introduced in their categorized forms in OARI-unfactored models, and as continuous, transformed variables in OARI-factored models to better assess their relevance in the context of reduced vascular resistance. (20)Among predictive variables, OARI and MBPA presented the highest odds ratios, and the cutoff point of OARI was associated with an impressive high likelihood ratio, significantly above which was obtained for MBPA.These data support that OARI is the predictor that better summarizes the risk of CCI and CCI-RD.
Based on its unique performance in outcome discrimination, OARI was established as a factor in logistic model progression.Ophthalmic artery-resistive index-factorized models provided a better characterization of the additional relevant variables related to the outcome and allowed for the inclusion of OAMV as a significant, although secondary, predictor. (20,24)These findings suggest that, although vasodilation is the primary vascular event related to CCI and CCI-RD, the occurrence of vascular overflow, well documented by the combination of low OARI with high values of MBPA and OAMV, is the final event related to these outcomes.The higher performance of the ordinal model over the binary models supports overperfusion thresholds for the occurrence of CCI and CCI-RD.The ordinal OARI-factored model was established as the broader model comprising choroidal overperfusion spectrum.
The relevance of OARI and MBPA were highlighted in OARI-factored and OARI-unfactored models.OAMV was established as a significant predictor only in OARI-factored models.In binary CCI and CCI-RD, as well as ordinal CCI/ CCI-RD models, the OR E and upper limits of OR CI for predictors were lower in OARI-factored than OARI-unfactored models, which is consistent with higher model stability of OARI-factored models.OARI-factored CCI model presented higher OR E and OR CI balance than unfactored models.Even in binary CCI-RD models, in which the upper limits of OR CI for OARI and MBPA were unpredictably high, consistently lower measures were obtained in OARI-factored models.
Model validation encompasses structural and residual components.The structural component, which is expressed by equation coefficients, describes the mathematical function that characterizes the relations between the set of predictors and the outcomes.Wald statistics, G statistics and OR are related to the structural component.Wald statistics directly assess the significance of each coefficient in the model. (20)Odd ratios, which correspond to the natural logarithm base raised to the slope β exponent (eβ), providing an indirect assessment of coefficients. (20)R CI provides robust metrics of model convergence, in which an unpredictable high upper OR CI limit suggests model instability.
In this series, general measures of fit, Wald, and G statistics support good fit of both binary models, as well as the ordinal model.However, the behavior of OR CI in the binary CCI-RD model indicates impaired convergence and poor fit.Although no significant difference in the measures of association was obtained among models, the ratio of concordant and discordant pairs supported a better fit of final binary models over full binary models.The final model, by summarizing the set of significant predictors, provides the better fit.The metrics of general measures of association support the better fit of final models over full models.
General measures of association provide metrics from the analysis of predicted rankings and true rankings that classify pairs of observations as concordant or discordant, in function of the relation between predictor values and outcome probability. (20,21)Measures of association suggest that final models, which encompass only significant predictors, provide higher concordance than full models.In summary, both groups of measures support the better fit of the OARI-factored final ordinal model among other models.
The residual component refers to differences between individual observations and variable distribution pattern predictors and are presented, and such analysis includes Pearson, deviance and Hosmer-Lemeshow statistics. (20,21)hese metrics were consistent with a good fit of ordinal OARI-unfactored model and all OARI-factored binary models (p-values >0.05).No significant difference was obtained between full and final models.These findings are consistent with the adequacy of OARI-factored over OARI unfactored and ordinal over binary logistic models.
Similarly to the assessment of predictor accuracy in identifying an outcome, the assessment of binary logistic model accuracy in identifying the outcome can be performed with A E and A CI . (21)Although significant areas under ROC curves were obtained for CCI and CCI-RD binary models, impressive high A E and A IC obtained in CCI-RD was not related to high accuracy, but to model instability and lack of convergence.These metrics suggest that the binary model is insufficient to assess the occurrence of CCI-RD, and support, indirectly, that these outcomes should be evaluated with ordinal models. (5,24,25)nlike these general measures revised so far, the individual component analysis assesses the fit through the entire set of covariate patterns that compose the series. (21)hanges of βcoefficients, Pearson, and deviance in function of the E P (Δβ/E P, , ΔPearson/E P and Δdeviance/E P , respectively) are usually represented by scatterplots.Each point represents a particular covariate pattern obtained in one or more patients.Points in these scatterplots align in two major curves, one from the top left to the bottom right and another from the bottom left to the top right. (21)Δβ/E P higher than 1 implies a significant contribution for β coefficients, whereas more than 6 and 4 outliers in ΔPearson/P E and Δdeviance/P E , respectively, identify covariate patterns significantly distinct from the model structure. (20,21)n this series, the scatterplot Δβ/E P presented a cluster around 0.5P E in the binary CCI model, suggesting no significant contribution for β coefficients. (20,21)Conversely, in the binary CCI-RD model, Δβ/E P presented no cluster around 0.5P E , but highly significant outliers at the top left, which are related to an inaccurately high β coefficient to the MBPA. (20,21)The higher number of outliers in ΔPearson/E P and Δdeviance/E P in CCI-RD over CCI is consistent with a poorer fit in CCI-RD, as suggested by measures of convergence, fit and ROC curves.Furthermore, individual component analysis suggests that MBPA coefficients were overestimated, and a subgroup of patients with CCIF and CCIF-RD presented no significant increase of MBPA. (20,21)Individual component analysis supports OARI as the major predictor and ordinal OARI-factored as the most adequate model for the assessment of CCI and CCI-RD in severe preeclampsia.
Choroidal overperfusion can be achieved by blood flow parameters of the OA with ODU. (26)OA, the first division of the internal carotid artery, branches into ciliary trunks and then 16 to 20 SPCA, which penetrate the peridiscal posterior sclera to form the Haller-Zinn circle, as well as into the choroid to feed the choriocapillaris. (7,26,27)horoidal arterioles present no autoregulation, due to the absence of pre-capillary circumferential muscular fibers. (27)Choriocapillaris present a mean diameter of 20-25μm, significantly larger than retinal capillaries (mean 7-8μm), and highly fenestrated endothelial cells, with rare pericytes. (27,28)The choriocapillaris organization is lobular, in which a precapillary arteriole penetrates the center of the lobule and then branches radially at right angles on the choriocapillaris plane. (27)hese morphologic features imply a low vascular resistance in choroidal arterioles, as well as a lobular perfusion pressure primarily determined by blood pressure. (20,29,31)Due to the branching pattern of the OA, as well as the lack of autoregulation of choroidal arterioles, OA blood flow parameters mirror choroidal perfusion. (7)Low OARI and high OAMV, especially in the context of high blood pressure and volume centralization, are consistent with choroidal overperfusion. (32)The present study supports that, due to the unique morphological features of choroidal arteriole branching and lobular choriocapillaris, choroidal overperfusion is associated with endothelial damage and occlusion and probably occurs in its terminal segment, at the point of right angle branching at the emergence of choriocapillaris.
Main neurological manifestations of preeclampsia are well recognized in the spectrum of posterior reversible encephalopathy syndrome (PRES), which is pathophysiologically characterized by vascular brain remodeling, increased capillary density, brain overperfusion, damage of the blood-brain barrier, and parieto-occipital lobe edema. (4,33,34)In addition, systemic vasospasm, which is the determinant of systemic high blood pressure, produces a volume shift from peripheral to central territories and blood volume centralization.Damage of the blood-brain barrier in the context of high perfusion pressure impairs blood flow autoregulation and produces posterior overperfusion-related, vasogenic edema. (4,35)he clinical spectrum related to PRES encompasses significant and persistent headache, blurred vision, seizure (eclampsia), and coma, as well as ischemic and hemorrhagic vascular events. (4,34)Indeed, although defined as reversible, PRES is the major cause of maternal death and permanent deficits in gestational period and immediate postpartum. (4)OARI has been proposed as a major predictor of PRES in severe preeclampsia, based on multivariate logistic models. (36)PRES must be considered in the differential diagnosis of blurred vision in preeclampsia.
Preeclampsia had been recognized as a model of vasospasm.The full spectrum of ophthalmoscopic findings had been attributed to retinal vasospasm and ischemia. (25)fter the first reports of ODU presenting lower vascular resistance in OA, overperfusion was recognized as the basic event in vascular pathophysiology in preeclampsia, even though experimental studies demonstrated that choroidal overperfusion is related to CCI and RD. (6,37,38)The present study is aligned with a novel concept of vascular pathophysiology in preeclampsia, in which central overperfusion is the main determinant of clinical manifestations.Recent studies have changed the focus from retinal vasospasm to choroidal overperfusion, which is consistent with main central vascular events in preeclampsia.

CONCLUSION
The present study demonstrates, using a multivariate logistic approach, that ophthalmic artery-resistive index is a major predictor of choriocapillaris ischemia superimposed by retinal detachment, although a significant improvement was obtained with the inclusion of mean blood pressure at admission and ophthalmic artery-resistive index.Although high blood pressure is a benchmark of severe preeclampsia, it is well documented that main complications are not related with significant increase in mean blood pressure.Therefore, the relevance of mean blood pressure has been questioned in recent guidelines.The study supports that choriocapillaris ischemia and choriocapillaris ischemia superimposed by retinal detachment are related to an overperfusion-related choroidopathy characterized by multilobular endothelial choriocapillaris and retinal pigment epithelial damage, followed by leakage of fluid from reperfusion of ischemic lobules.This vascular pathophysiology has been consistently underrecognized in the spectrum of choriocapillaris ischemia and retinal detachment.The unique vascular architecture of the choriocapillaris, especially the branching pattern of the choroidal arterioles at right angles from the center of the lobule, as well as the lack of blood flow autoregulation, implies a higher incidence of choriocapillaris ischemia and choriocapillaris ischemia superimposed by retinal detachment in the context of diffuse choroidal overperfusion.Our study provides a significant contribution for a better understanding of the spectrum of vascular pathophysiology in this condition.

AKNOWLEDGEMENTS
We would like to thank Professor Sueli Mingoti and Professor Roberto Quinino for their support in the elaboration of this study.

Figure 1 .
Figure 1.Retinography of a patient with severe preeclampsia presenting subretinal spots consistent with choriocapillaris ischemia associated with flat retinal detachment.

Figure 2 .
Figure 2. Ocular Doppler ultrasound presenting the main ophthalmic artery blood flow parameters: peak systolic velocity, final diastolic velocity, systolic velocity and diastolic velocity ratio, resistive index, pulsatility index, and mean velocity.
Scatterplots of Δβ, ΔPearson and Δdeviance were obtained for the final binary OARI-factored models CCI and CCI-RD, in function of the estimated probability (E P ).In the scatterplots for Δβ/E P , the CCI model presented high clustering of points around 0.5 E P , whereas no clustering was obtained in the CCI-RD model.The top values of 0.26Δβ/E P, and 1.37Δβ/E P, and seven and nine points higher than 0.15Δβ/E P were obtained in CCI and CCI-RD models, respectively.The top values of ΔPearson/ E P and Δdeviance/E P were 22 and 6.5 in the CCI and 27 and 7.4

Table 1 .
The OA spectral curve, obtained with ODU, is presented in Figure2.The differences in the predictor variables in function of the presence of CCI are presented in Table1.Parameters of areas under ROC curves and measures of sensitivity, specificity, and likelihood ratios are presented in Table1.Predictor variables CCI: choriocapillaris ischemia; SD: standard deviation; OARI: ophthalmic artery resistive index; OAMV: ophthalmic artery mean velocity; MBPA: mean blood pressure at admission; MBPE: mean blood pressure elevation; LHD: lactate dehydrogenase; UPT: urine protein test; ROC: Receiver Operating Characteristic; A E and A SD : area under Receiver Operating Characteristic curve estimate and standard deviation; A LL and A UL upper and lower limits of Receiver Operating Characteristic curve confidence intervals; CP: cut-off point; Se: sensitivity; Sp: specificity; LH: likelihood ratio.Vs: systolic velocity; Vd: diastolic velocity; SD: systolic velocity and diastolic velocity ratio; RI: resistive index; PI: pulsatility index; Vm: mean velocity.

Table 4 .
Ordinal models for choriocapillaris ischemia and retinal detachment CCI-RD: choriocapillaris ischemia and retinal detachment; OARI: ophthalmic artery-resistive index; OR E : estimate confidence interval; OR LL : lower limits of odds ratio confidence interval OR UL : upper limits of odds ratio confidence interval; OAMV: ophthalmic artery mean velocity; MBPA: mean blood pressure at admission; MBPE: mean blood pressure elevation; LHD: lactate dehydrogenase; UPT: urine protein test.