Publications (25)73.18 Total impact
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Article: Blood Pressure, Vessel Caliber, and Retinal Thickness in Diabetes.
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ABSTRACT: PURPOSE: In this study, we examine the association of blood pressure (BP), retinal thickness (RT), and vessel caliber in patients with type 2 diabetes and high HbA1c (elevated long-term blood glucose) with or without mild or moderate nonproliferative diabetic retinopathy (NPDR). METHODS: Forty-three patients with type 2 diabetes and high HbA1c measures (23 without NPDR and 20 with mild to moderate NPDR) and 22 age-matched nondiabetic controls participated. The BP, RT (Stratus OCT3), fundus photography, and HbA1c were measured. Correlations between BP, HbA1c, vessel caliber, and RT were evaluated. RESULTS: Diastolic BP (DBP) is positively and significantly associated with RT in patients with NPDR (p < 0.02). Blood pressure was not associated with RT in patients without NPDR (p = 0.83). There is an association between higher HbA1c and higher DBP within the NPDR group (p < 0.02). Furthermore, HbA1c modifies the slope of the relationship between DBP and RT in NPDR patients. Greater venule diameters and loss of the correlation between decreased arteriole size and increased systolic blood pressure, seen in controls, were observed in patients with and without NPDR. CONCLUSIONS: The results of this study show that HbA1c and BP together have an impact on RT measures of patients with DR. These measures should be considered when evaluating RT in patients with DR both clinically and in future optical coherence tomography studies on this population.Optometry and vision science: official publication of the American Academy of Optometry 11/2012; · 1.53 Impact Factor -
Article: Association between Local Neuroretinal Function and Control of Adolescent Type 1 Diabetes.
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ABSTRACT: Purpose. To evaluate associations between neuroretinal function measured with multifocal electroretinogram (mfERG) and disease variables in adolescents with type 1 diabetes and no retinopathy. Methods. Fundus photographs, blood glucose (BG) concentration, HbA1c, and monocular mfERG were performed on 115 adolescent patients (mean age ± SD; 15.7 ± 1.8 years) and 30 controls (18.0 ± 2.8 years). All subjects had best-corrected visual acuity ≥ 20/20. The 45° mfERG stimulus included 103 hexagons, reversing between dark and bright according to a pseudorandom m-sequence. Amplitudes (AMPs) and implicit times (ITs) were derived from local mfERG response waveforms, and Z-scores were calculated. Retinal maps of abnormality frequencies were generated. Differences between controls and patients were evaluated using t-tests. Associations between mfERG and age, duration, and diabetes control were examined using linear regression analysis. Results. Mean mfERG IT was significantly longer in the patients compared with that in the controls (P = 0.019), but AMP was not different (P > 0.05). In all, 26 eyes (23%) of the patients had abnormal IT and 3 eyes (3%) had abnormal AMP. IT abnormalities were essentially distributed randomly across the retina. There were too few AMP abnormalities to examine their retinal distribution. IT was positively correlated with HbA1c (P < 0.0002) but not correlated with diabetes duration, BG, or age. Conclusions. Higher long-term blood glucose concentration is associated with degraded neuroretinal function in adolescents with type 1 diabetes and no retinopathy. Over 20% of these patients have abnormal neuroretinal function. It will be important to determine longitudinally whether the relationship between mfERG IT and diabetes control exists within individual adolescent patients.Investigative ophthalmology & visual science 09/2012; 53(11):7071-6. · 3.43 Impact Factor -
Article: Associations between Local Retinal Thickness and Function in Early Diabetes.
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ABSTRACT: Purpose. To investigate, using multifocal electroretinography (mfERG) and optical coherence tomography (OCT), potential spatial associations between local neuroretinal function and local retinal thickness in patients with diabetes. Methods. Forty-five patients without retinopathy (10 with Type 1 diabetes; 35 with Type 2 diabetes; 49.9 ± 10.9 years old) and 29 age-similar controls (47.0 ± 12.8 years old) were studied. N1-P1 amplitude (AMP) and P1 implicit time (IT) of mfERGs within the central approximately 20° diameter were compared to spatially corresponding full retinal thickness measurements acquired by Stratus OCT3. AMP and IT were converted to Z-scores and retinal thickness was converted to percentile values. Local abnormalities were defined as P ≤ 0.023. Subject group differences were examined using t-tests. Retinal thickness was compared to mfERGs to determine spatial associations. Results. Average retinal thicknesses were similar for all subject groups. The Type 1 group and controls had similar IT and AMP. The Type 2 group had reduced AMP and longer IT than the controls and the Type 1 group (P < 0.001). Local associations between retinal thickness and mfERGs were not significant within any subject group or individuals, even for abnormal locations (P ≥ 0.09). Abnormalities in most measures were greater in the patient groups than in the controls (P < 0.008) except retinal thinning in the Type 1 group. Conclusions. Local neuroretinal function is not associated with full retinal thickness measured locally in patients with diabetes and no retinopathy, even in abnormal locations. Full retinal thickness measured locally by OCT is not a surrogate for mfERGs in early diabetes. Neuroretinal function in Type 2 diabetes is worse than in Type 1 diabetes and controls. Fewer subjects in the Type 1 group could be a potential limitation.Investigative ophthalmology & visual science 08/2012; 53(10):6122-8. · 3.43 Impact Factor -
Article: Reproducibility of the mfERG between instruments
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ABSTRACT: Purpose First, to examine both the reproducibility of the multifocal electroretinogram (mfERG) recorded on different versions of the same instrument, and the repeatability of the mfERG recorded on a single instrument using two different amplifiers. Second, to demonstrate a means by which multicenter and longitudinal studies that use more than one recording instrument can compare and combine data effectively. Methods Three different amplifiers and two mfERG setups, one using VERIS™ 4.3 software (mfERG1) and another using VERIS™ Pro 5.2 software (mfERG2), were evaluated. A total of 73 subjects with normal vision were tested in three groups. Group 1 (n=42) was recorded using two amplifiers in parallel on mfERG1. Group 2 (n=52) was recorded on mfERG2 using a single amplifier. Group 3 was a subgroup of 21 subjects from groups 1 and 2 that were tested sequentially on both instruments. A fourth group of 26 subjects with diabetes were also recorded using the two parallel amplifiers on mfERG1. P1 implicit times and N1-P1 amplitudes of the 103 local first order mfERGs were measured, and the differences between the instruments and amplifiers were evaluated as raw scores and Z-scores based on normative data. Measurements of individual responses and measurements averaged over the 103 responses were analyzed. Results Simultaneous recordings made on mfERG1 with the two different amplifiers showed differences in implicit times but similar amplitudes. There was a mean implicit time difference of 2.5ms between the amplifiers but conversion to Z-scores improved their agreement. Recordings made on different days with the two instruments produced similar but more variable results, with amplitudes differing between them more than implicit times. For local response implicit times, the 95% confidence interval of the difference between instruments was approximately ±1 Z-score (±0.9ms) in either direction. For local response amplitude, it was approximately ±1.6 Z-scores (±0.3μV). Conclusions Different amplifiers can yield quite different mfERG P1 implicit times, even with identical band-pass settings. However, the reproducibility of mfERG Z-scores across recording instrumentation is relatively high. Comparison of data across systems and laboratories, necessary for multicenter or longitudinal investigations, is facilitated if raw data are converted into Z-scores based on normative data.Documenta Ophthalmologica 04/2012; 119(1):67-78. · 2.11 Impact Factor -
Article: Subclinical capillary changes in non-proliferative diabetic retinopathy.
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ABSTRACT: To establish adaptive optics scanning laser ophthalmoscopy as a method to detect and characterize microscopic signs of diabetic retinopathy in capillaries and cone photoreceptors in the parafovea. Recently, adaptive optics scanning laser ophthalmoscope (AOSLO) has enabled noninvasive assessment of photoreceptors, capillaries, and leukocytes in the retinas of live human subjects. Repeated application of AOSLO imaging along with comparison to fluorescein angiography was used to track individual capillaries near the foveal avascular zone (FAZ) from one eye affected with severe non-proliferative diabetic retinopathy. Fluorescein angiography was used to identify clinical signs of diabetic retinopathy, such as microaneurysms and intraretinal microvascular abnormalities, and corresponding regions were imaged and assessed using the AOSLO. In addition, the structural integrity of photoreceptors and the spatial distribution of leukocytes around the parafoveal capillary network were quantitatively assessed. Capillaries and cone photoreceptors were visualized using the AOSLO without the use of injected contrast agents. Although the majority of capillaries were stable over a period of 16 months, one capillary at the edge of the FAZ dropped out, leading to a small but significant increase in FAZ size. Longitudinal assessment of the capillaries also showed microaneurysm formation and disappearance as well as the formation of tiny capillary bends similar in appearance to intraretinal microvascular abnormalities. The leukocytes in the capillary network were found to preferentially travel through the same routes in all four visits, suggesting that these channels are robust against small changes to the surrounding capillaries. In this eye, cone photoreceptor spacing was increased in the fovea when compared with normal data but stable across all visits. AOSLO imaging can be used to longitudinally track capillaries, leukocytes, and photoreceptors in diabetic retinopathy. Capillary changes that can be detected include dropout of individual capillaries as well as formation and disappearance of microaneurysms.Optometry and vision science: official publication of the American Academy of Optometry 04/2012; 89(5):E692-703. · 1.53 Impact Factor -
Article: Neurodegenerative differences in the retinas of male and female patients with type 2 diabetes.
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ABSTRACT: The purpose of our study is to determine whether neuroretinal function, measured by the multifocal electroretinogram, differs between males and females with type 2 diabetes and no retinopathy. This study included 70 eyes from 70 adult subjects (14 control males, 22 control females, 16 males with type 2 diabetes, and 18 females with type 2 diabetes). A template-scaling technique was used to obtain first-order P1 implicit times and N1-P1 amplitudes from photopic multifocal electroretinograms within the central 45 degrees. The males with type 2 diabetes were significantly more abnormal than their female counterparts in two separate analyses of local neuroretinal function. First, the total number of retinal locations with an abnormally delayed implicit time (z score ≥ 2) was higher (P < 0.001) in the diabetic males (482 locations = 29.2%) compared to the diabetic females (298 locations = 16.1%). Second, in the response topographies that consisted of 103 means of local implicit times for each group, the diabetic males were significantly delayed (P < 0.025) at 23 corresponding positions (22.3%) compared to the diabetic females. At the same time, no corresponding stimulus locations were significantly delayed in the diabetic females compared to the diabetic males. Neuroretinal function is more abnormal in males than in females for adults with type 2 diabetes and no retinopathy. These results suggest that, relative to males, females may have some protection from, or resistance to, neurodegenerative changes that precede the development of background retinopathy in type 2 diabetes.Investigative ophthalmology & visual science 04/2012; 53(6):3040-6. · 3.43 Impact Factor -
Article: Interocular symmetry of abnormal multifocal electroretinograms in adolescents with diabetes and no retinopathy.
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ABSTRACT: To investigate, in adolescents with type 1 diabetes and no retinopathy, the spatial correspondence between abnormal multifocal electroretinogram (mfERG) responses in the two eyes. mfERG and fundus photographs were measured in both eyes of 68 adolescents with type 1 diabetes and no retinopathy (13 to 19 years old; best corrected visual acuity ≥ 20/20), and 30 age-matched controls. The mfERG stimulus was comprised of 103 hexagons, and subtended 45°. mfERG implicit times (IT) and amplitudes (AMP) were derived. Fifteen patients for IT, and five for AMP with at least one eye defined as abnormal (six or more locations with abnormal Z-scores; P < 0.03) were analyzed. Nasal retina had significantly more abnormal IT locations compared with temporal retina (P = 0.015), and the opposite was true with regard to abnormal AMP (P < 0.001). The proportion of abnormal responses in the superior retina was not significantly different from that in the inferior retina (P > 0.1 for IT and AMP). Interocular correspondence of locations with abnormal mfERG IT was significant for all 15 patients (P values <0.0001-0.012), and agreement between eyes was 68% to 94% (AC1 agreement coefficient: 0.48-0.94). Overall interocular correspondence was also significant (P < 0.0002), with 86% agreement (AC1 = 0.76). Overall interocular correspondence of locations with abnormal mfERG AMP was also significant (P < 0.0002). Interocular spatial correspondence of abnormal mfERG responses exists in adolescents with type 1 diabetes and no retinopathy. This is most apparent for IT abnormalities. This correspondence could be used in clinical trials, and raises the possibility of initiating treatment in both eyes at early disease stages as new topical treatments emerge.Investigative ophthalmology & visual science 12/2011; 53(1):316-21. · 3.43 Impact Factor -
Article: Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy.
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ABSTRACT: To establish, using adaptive optics scanning laser ophthalmoscopy (AOSLO), that the retinal parafoveal capillary network is altered before the onset of diabetic retinopathy in adult patients with type 2 diabetes. AOSLO videos were acquired in the parafoveal region of one eye from control subjects and from patients with type 2 diabetes and no retinopathy. Detailed images of the parafoveal capillary network were generated with custom motion contrast enhancement algorithms. The combination of AOSLO images and videos enabled the simultaneous assessment of several features of the parafoveal capillary network. Arteriovenous (AV) channels were identified by finding the least tortuous capillary channels connecting terminal arterioles to postcapillary venules. Measures of capillary dropout and capillary hemodynamics were also quantified. The average tortuosity of AV channels was 26% higher in patients with type 2 diabetes when compared with controls, even though there were no signs of diabetic retinopathy in any of the eyes that were assessed (P < 0.05). In addition, the metrics of capillary dropout showed small changes (between 3% and 7%), leukocyte speed 14% lower, and pulsatility 25% higher, but none of these differences was statistically significant. It is often difficult to find consistent changes in the retinal microvasculature due to large intersubject variability. However, with a novel application of AOSLO imaging, it is possible to visualize parafoveal capillaries and identify AV channels noninvasively. AV channels are disrupted in type 2 diabetes, even before the onset of diabetic retinopathy.Investigative ophthalmology & visual science 11/2011; 52(12):9257-66. · 3.43 Impact Factor -
Article: Early neural and vascular changes in the adolescent type 1 and type 2 diabetic retina.
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ABSTRACT: This cross-sectional study examines the existence and frequency of functional and structural abnormalities in the adolescent Type 1 diabetic retina. We also compare the results with those of adolescents with Type 2 diabetes. Thirty-two adolescents with Type 1 diabetes (5.7 ± 3.6 years; mean duration ± SD), 15 with Type 2 diabetes (2.1 ± 1.3 years), and 26 age-matched control subjects were examined. Multifocal electroretinogram responses from 103 retinal regions were recorded. Optical coherence tomography was used to measure retinal thickness. Vascular diameter around the optic nerve was also assessed. Nine of the 32 (28%) adolescents with Type 1 diabetes and 6 of the 15 (40%) with Type 2 diabetes had significant multifocal electroretinogram implicit time delays compared with 2 of the 26 controls (8%). Retinal thicknesses in both patient groups were significantly (P ≤ 0.01) thinner than controls. The Type 2 group also showed significant (P ≤ 0.03) retinal venular dilation (235.8 ± 5.9 μm) compared with controls (219.6 ± 4.0 μm). The present study illustrates that subtle but significant functional and structural changes occur very early in Type 1 diabetes. Adolescents with Type 2 diabetes appear to be more affected than those with Type 1 diabetes. Further longitudinal examination of the etiology and progression of these abnormalities is warranted.Retina (Philadelphia, Pa.) 08/2011; 32(1):92-102. · 2.93 Impact Factor -
Article: Prediction, by retinal location, of the onset of diabetic edema in patients with nonproliferative diabetic retinopathy.
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ABSTRACT: To formulate a model to predict the location of the onset of diabetic retinal edema (DE) in adults with diabetic retinopathy (DR), at risk for DE. In all, 46 eyes from 23 patients with DR were included. Subjects were followed semiannually until DE developed or the study concluded. The presence or absence of DE within the central 45 ° at the final visit was the outcome measure, and data from the prior visit were used as baseline. A logistic regression model was formulated to assess the relationship between DE development and: multifocal electroretinogram (mfERG) implicit time (IT) Z-score, mfERG amplitude (Amp) Z-score, sex, diabetes duration, diabetes type, blood glucose, HbA1c, age, systolic (SBP) and diastolic blood pressure, and grade of retinopathy. A total of 35 retinal zones were constructed from the mfERG elements and each was graded for DE. Data from 52 control subjects were used to calculate the maximum IT and minimum Amp Z-scores for each zone. Receiver operating characteristic curves from a fivefold cross-validation were used to determine the model's predictive properties. Edema developed in 5.2% of all retinal zones and in 35% of the eyes. The mfERG Amp, mfERG IT, SBP, and sex were together predictive of edema onset. Combined, these factors produce a model that has 84% sensitivity and 76% specificity. Together mfERG, SBP, and sex are good predictors of local edema in patients with DR. The model is a useful tool for assessing risk for edema development and a candidate measure to evaluate novel therapeutics directed at DE.Investigative ophthalmology & visual science 07/2011; 52(9):6825-31. · 3.43 Impact Factor -
Article: Multifocal VEP (mfVEP) reveals abnormal neuronal delays in diabetes.
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ABSTRACT: This pilot study examined the diagnostic role of multifocal visually evoked potentials (mfVEP) in a small number of patients with diabetes. mfVEP, mfERG, and fundus photographs of both eyes of five patients with diabetes, three with nonproliferative diabetic retinopathy (NPDR) and two without NPDR were examined. Thirteen control subjects were also examined. Eighteen zones were constructed from the 60-element mfVEP stimulus array. mfVEP implicit time (IT) and amplitude (SNR) differences were tested between subject groups. We also examined whether there was a difference in function for patches with and without retinopathy in the NPDR group. Lastly, we compared mfVEP and mfERG results in the same patients. We found significant mfVEP IT differences between controls and all patients with diabetes, controls and diabetics without retinopathy, and between controls and diabetics with retinopathy. The subject groups did not differ significantly in terms of SNR. In the retinopathy group, ITs from zones with retinopathy were significantly longer than ITs from zones without retinopathy (P = 0.016). mfERG IT was more frequently abnormal than mfVEP IT. In addition, mfERG hexagons were twice as likely to be abnormal if the corresponding mfVEP zone was abnormal (P < 0.05). mfVEP implicit times are significantly delayed in patients with diabetes even when there is no retinopathy. These cortical response results are similar, albeit considerably less abnormal, than those previously reported for retinal (mfERG) responses in patients with diabetes. A correlation exists between the location of abnormal mfERG hexagons and abnormal mfVEP zones.Documenta Ophthalmologica 12/2010; 121(3):189-96. · 2.11 Impact Factor -
Article: Multifocal electroretinograms predict onset of diabetic retinopathy in adult patients with diabetes.
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ABSTRACT: The authors' previous models predicted local formation of diabetic retinopathy (DR) in adults with diabetes and existing retinopathy. Here they derived a multivariate model for local prediction of DR onset in patients with no previous retinopathy. Seventy-eight eyes from 41 diabetes patients were tested annually for several years. The presence or absence of DR at the last study visit was the outcome measure, and measurements of risk factors from the previous visit were used for prediction. Logistic regression was used to assess the relationship between DR development and 7 factors: multifocal ERG (mfERG) implicit time (IT) Z-score, sex, diabetes duration, blood glucose, HbA1c, age, and diabetes type. Thirty-five retinal zones, spanning 45°, were constructed from the mfERG stimulus elements. The maximum IT Z-score for each zone was calculated based on data from 50 control subjects. ROC curve analysis, using fivefold cross-validation, was used to determine the model's predictive properties. Mild DR developed in 80 of 2730 retinal zones (3%) in 29 of 78 eyes (37%). Multivariate analysis showed mfERG IT to be predictive for DR development in a zone after adjusting for diabetes type. The multivariate model has a sensitivity of 80% and a specificity of 74%. mfERG IT is a good predictor of DR onset, 1 year later, in patients with diabetes without DR. It can be used to assess the risk for DR development in these patients and may be a valuable outcome measure in evaluation of novel prophylactic therapeutics directed at impeding DR.Investigative ophthalmology & visual science 10/2010; 52(2):772-7. · 3.43 Impact Factor -
Article: The fast oscillation of the EOG in diabetes with and without mild retinopathy.
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ABSTRACT: There is ample evidence that the retinal pigment epithelium (RPE) is affected in diabetes, and that epitheliopathy may be among the early changes. The fast oscillation (FO) of the electro-oculogram (EOG) reflects the activity of the RPE, most notably the mechanisms responsible for pumping fluid and ions in the retina-to-choroid direction. The FO was measured in three groups of subjects: normal controls, eyes of diabetic individuals with no evidence of retinopathy, and eyes of diabetics with mild background retinopathy. FO amplitude, light trough voltage and dark peak voltage in both diabetic groups were all significantly reduced, independent of retinopathy status. The peak to trough ratio was unaffected. These changes, reduced voltages and smaller light-evoked voltage changes, are consistent with a decrease in the resistance of the RPE and may relate to accumulation of fluid in the sub-retinal space.Documenta Ophthalmologica 06/2008; 116(3):231-6. · 2.11 Impact Factor -
Article: Local diabetic retinopathy prediction by multifocal ERG delays over 3 years.
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ABSTRACT: To derive and validate a model for use in predicting local retinal areas in which nonproliferative diabetic retinopathy (NPDR) lesions will develop over a 3-year period, by using primarily the implicit time (IT) of the multifocal electroretinogram (mfERG). Eighteen diabetic patients were examined at baseline and at three annual follow-ups. Ophthalmic examinations, including fundus photographs and mfERG testing, were performed at each visit. Thirty-five retinal zones were constructed from the 103-element stimulus array, and each zone was assigned the maximum IT z-score within it based on 30 age-similar control subjects. Logistic regression was used to investigate the development of retinopathy in relation to baseline mfERG IT delays and additional diabetic health variables. Receiver operating characteristic (ROC) curves were used to evaluate the models. Retinopathy developed in 77 of the 1208 retinal zones, of which 25 had recurring retinopathy. Multivariate analyses yielded baseline mfERG IT, duration of diabetes, and blood glucose concentration as the most important predictors of recurring retinopathy. mfERG ITs were not predictive of transient retinopathy. ROC curves based on the multivariate model for the prediction of recurring retinopathy resulted in an area under the curve of 0.95, sensitivity of 88%, and specificity of 98%. Ten-fold cross-validation confirmed the high sensitivity and specificity of the model. The development of recurring retinopathy over a 3-year period can be well predicted by using a multivariate model based on mfERG implicit time. Multifocal ERG delays are promising candidate measures for trials of novel therapeutics directed at preventing or slowing the progression of NPDR.Investigative Ophthalmology & Visual Science 05/2008; 49(4):1622-8. · 3.60 Impact Factor -
Article: Association between multifocal ERG implicit time delays and adaptation in patients with diabetes.
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ABSTRACT: Local first-order multifocal electroretinogram (mfERG) implicit time (K1-IT) delays have proved to be important and predictive indicators of retinal function in diabetes. To better understand the nature of these delays, the authors examined the spatial association between K1-IT and second-order amplitudes (K2-SNR; a measure of adaptation) in diabetic and control subjects. The authors studied K1-IT, K1 amplitude, and K2-SNRs of responses from 35 retinal zones. These were recorded from 20 diabetic patients without retinopathy, 20 patients with mild to moderate nonproliferative diabetic retinopathy (NPDR), and 30 healthy control subjects. The K1-IT and K2-SNR measurements were then adjusted according to normative and subject median values to reduce or remove the effects of retinal location, intersubject differences, and abnormally small K1 amplitudes. There was no significant association between K1-IT and K2-SNR in the control group (P > 0.05) and only a marginal association in the NoRet group (P = 0.05). In contrast, longer K1-ITs were significantly associated with reduced K2-SNRs in NPDR subjects (P < 0.01). In the NPDR eyes, zones without retinopathic lesions showed a significant association between K1-IT and K2-SNR (P < 0.01). The results suggest that an association between longer K1-IT and reduced K2-SNR (abnormal adaptation) develops after the appearance of NPDR, but this association does not depend on the presence of colocalized retinopathic lesions.Investigative Ophthalmology & Visual Science 11/2007; 48(11):5250-6. · 3.60 Impact Factor -
Article: A multifocal electroretinogram model predicting the development of diabetic retinopathy.
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ABSTRACT: The prevalence of diabetes has been accelerating at an alarming rate in the last decade; some describe it as an epidemic. Diabetic eye complications are the leading cause of blindness in adults aged 25-74 in the United States. Early diagnosis and development of effective preventatives and treatments of diabetic retinopathy are essential to save sight. We describe efforts to establish functional indicators of retinal health and predictors of diabetic retinopathy. These indicators and predictors will be needed as markers of the efficacy of new therapies. Clinical trials aimed at either prevention or early treatments will rely heavily on the discovery of sensitive methods to identify patients and retinal locations at risk, as well as to evaluate treatment effects. We report on recent success in revealing local functional changes of the retina with the multifocal electroretinogram (mfERG). This objective measure allows the simultaneous recording of responses from over 100 small retinal patches across the central 45 degrees field. We describe the sensitivity of mfERG implicit time measurement for revealing functional alterations of the retina in diabetes, the local correspondence between functional (mfERG) and structural (vascular) abnormalities in eyes with early nonproliferative retinopathy, and longitudinal studies to formulate models to predict the retinal sites of future retinopathic signs. A multivariate model including mfERG implicit time delays and 'person' risk factors achieved 86% sensitivity and 84% specificity for prediction of new retinopathy development over one year at specific locations in eyes with some retinopathy at baseline. A preliminary test of the model yielded very positive results. This model appears to be the first to predict, quantitatively, the retinal locations of new nonproliferative diabetic retinopathy development over a one-year period. In a separate study, the predictive power of a model was assessed over one- and two-year follow-ups. This permitted successful prediction of new retinopathy development in eyes with and without retinopathy at baseline. Finally, we briefly describe our current research efforts to (a) locally predict future sight-threatening diabetic macular edema, (b) investigate local retinal function change in adolescent patients with diabetes, and (c) better understand the physiological bases of the mfERG delays. The ability to predict the retinal locations of future retinopathy based on mfERG implicit time provides clinicians a powerful tool to screen, follow-up, and even consider early prophylactic treatment of the retinal tissue in diabetic patients. It also aids identification of 'at risk' populations for clinical trials of candidate therapies, which may greatly reduce their cost by decreasing the size of the needed sample and the duration of the trial.Progress in Retinal and Eye Research 10/2006; 25(5):425-48. · 9.45 Impact Factor -
Article: Multifocal electroretinogram and short-wavelength automated perimetry measures in diabetic eyes with little or no retinopathy.
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ABSTRACT: To compare severity and locations of abnormalities detected by the multifocal electroretinogram (mfERG) and short-wavelength automated perimetry (SWAP) in diabetic eyes with early or no retinopathy. One eye from each of 22 patients with diabetes mellitus who had early retinopathy and 18 patients with diabetes mellitus who had no retinopathy were tested on mfERG and SWAP. The mfERG implicit times were interpolated based on SWAP stimulus locations and compared with normative values obtained from 30 age-similar control subjects. The SWAP total threshold deviations were analyzed using an age-based control data set from 255 healthy subjects. The z scores of both measures were derived to allow measurement comparisons. Most responses for the 2 measurements were subnormal in both groups with diabetes mellitus. The 2 measurements showed a similar number of significant abnormalities (z score >/=2), about 40% and 20% of responses for diabetic patients with retinopathy and diabetic patients with no retinopathy, respectively. Local mfERG and SWAP results showed some spatial agreement for subjects with retinopathy (r = -0.38, P<.001) but not for those with no retinopathy. Both mfERG and SWAP are sensitive measurements of diabetic dysfunction, even prior to retinopathy. The lack of spatial correspondence between mfERG and SWAP abnormalities in diabetic patients with no retinopathy reflects overlapping, but different, retinal anomalies in early diabetic eye disease.Archives of Ophthalmology 12/2004; 122(12):1809-15. · 3.71 Impact Factor -
Article: Formulation and evaluation of a predictive model to identify the sites of future diabetic retinopathy.
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ABSTRACT: To formulate and test a model to predict the development of local patches of nonproliferative diabetic retinopathy (NPDR), based on multifocal electroretinogram (mfERG) implicit times and candidate diabetic risk factors. mfERGs and fundus photographs were obtained from 28 eyes of 28 diabetic patients during an initial and 12-month follow-up examination. mfERG implicit times were derived at 103 locations using a template-stretching method, and a z-score was calculated in comparison with 20 age-matched normal subjects. Thirty-five nonoverlapping retinal zones were constructed by grouping two to three adjacent stimulated locations, and each zone was assigned the maximum z-score within it. Zones containing initial retinopathy were excluded from further analysis. The probability that new retinopathy would develop in the remaining zones by the follow-up examination was modeled based on the mfERG implicit time z-score for the zone and other candidate diabetic risk factors determined during the initial visit. Data collected from four previously untested diabetic subjects and the other eye of eight previous subjects during their second year follow-up were used to test the predictive model. After 1 year, new retinopathy developed in 11 of the 12 NPDR eyes and 1 of the 16 eyes without initial retinopathy. After accounting for the correlation among zones within each eye, a predictive model was formulated with the variables mfERG implicit time, duration of diabetes, presence of retinopathy (NPDR or no retinopathy), and blood glucose level at initial visit. The area under the receiver operating characteristic (ROC) curve of this multivariate model is 0.90 (P <0.001). The predictive model has an expected sensitivity of 86% and a specificity of 84%, which was verified by the test data. The development of diabetic retinopathy over a 1-year period can be well predicted by a multivariate model. The inclusion of local mfERG implicit times allowed the model to identify the specific sites of future retinopathy.Investigative Ophthalmology & Visual Science 12/2004; 45(11):4106-12. · 3.60 Impact Factor -
Article: Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy.
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ABSTRACT: To study retinal dysfunction in diabetes and early nonproliferative diabetic retinopathy (NPDR) using a new method to analyze local multifocal electroretinogram oscillatory potentials (mfOPs). One eye of each of 26 normal subjects, 16 diabetic subjects without retinopathy (NoR), and 16 diabetic subjects with early NPDR was examined. Slow-flash multifocal electroretinograms (sf-mfERGs) were recorded from the central 45 degrees, and stereo fundus photographs of the diabetic eyes were taken. The first-order (K1), induced first-order (K1i), and second-order (K2) response components were extracted from each retinal location, and K1i and K2 were added to create Ks2. Responses from 35 contiguous areas were digitally filtered 90 to 225 Hz to isolate the mfOPs. The signal-to-noise ratio (SNR) of the mfOPs was calculated, and abnormality was defined as SNR below the fifth percentile of the normal subjects. Combining the K1i and K2 components to form Ks2 before isolation of the mfOPs by digital filtering increased the SNR. Mean Ks2 and K1 mfOP SNRs were abnormal in 25% and 19% of the NoR eyes, respectively, and both were abnormal in 62% of the NPDR eyes. The retinal distributions of the local Ks2 and K1 mfOP abnormalities overlapped, but they differed. Furthermore, local Ks2 mfOP abnormalities were preferentially associated with retinal sites containing NPDR but K1 mfOP abnormalities were not. The cells that contribute to the generation of local mfOPs are affected by diabetes and, to a greater degree, by early NPDR. The results suggest that fast adaptive mechanisms influencing the mfOPs are most abnormal at retinal sites containing NPDR.Investigative Ophthalmology & Visual Science 10/2004; 45(9):3259-65. · 3.60 Impact Factor -
Article: Comparison of mfERG waveform components and implicit time measurement techniques for detecting functional change in early diabetic eye disease.
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ABSTRACT: This study first compares two methods for measuring first order multifocal electroretinogram (mfERG) implicit time abnormalities in eyes with early diabetic retinopathy. Two analysis methods are used: template stretching (multiplicative scaling) of an 80 msec response epoch and template sliding (cross-correlation or additive scaling) of portions of responses containing the major waveform features. The study also compares the relative sensitivities of N1, P1 and N2 implicit time assessed by cross-correlation. The nature of the change in the mfERG waveform associated with diabetes is also assessed. MfERGs were recorded from 15 eyes of 15 individuals with diabetes and early non-proliferative retinopathy and 20 eyes of 20 healthy control subjects of similar age. Implicit time determined by template stretching is more frequently abnormal in the eyes of the diabetic subjects than the implicit time of any of the components assessed by template sliding. This is attributable to the lower variability of the template stretching implicit time measure in normals. Of the components, P1 is most often abnormal in the eyes of individuals with diabetes. Responses recorded from retinal areas with retinopathic signs are more often abnormal than those from other areas. Later components of the response are not delayed more than earlier ones. We conclude that template stretching is a sensitive measurement technique, but that it does not fully capture the effect of diabetes on the first order mfERG well.Documenta Ophthalmologica 06/2004; 108(3):223-30. · 2.11 Impact Factor
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Institutions
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2012
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Midwestern University
California, MD, USA
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2004–2012
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University of California, Berkeley
- School of Optometry
Berkeley, CA, USA
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