Differences in neuroretinal function between adult males and females.

PURPOSE: To determine whether neuroretinal function differs in healthy adult males and females younger and older than 50 years. METHODS: This study included one eye from each of 50 normal subjects (29 females and 21 males). Neuroretinal function was assessed using first-order P1 implicit times (ITs) and N1-P1 amplitudes (AMPs) obtained from photopic multifocal electroretinograms. To assess local differences, retinal maps of local IT and (separately) AMP averages were constructed for each subject group. To examine global differences, each subject's 103 ITs and (separately) AMPs were also averaged to create whole-eye averages. Subsequently, retinal maps and whole-eye averages of one subject group were compared with those of another. RESULTS: In subjects younger than 50 years, neuroretinal function differed significantly between the males and females: local ITs were significantly shorter at 83 of 103 tested retinal locations, and whole-eye IT averages were shorter (p = 0.015) in the males compared with the females. In contrast, no analysis indicated that the males and females older than 50 years were significantly different. A subanalysis showed that the females who reported a hysterectomy (n = 5) had the longest whole-eye ITs of all subject groups (p ≤ 0.0013). In the females who did not report a hysterectomy, neuroretinal function was worse in the females older than 50 years compared with the females younger than 50 years: local ITs were significantly longer at 62 of 103 retinal locations tested, and whole-eye IT averages tended to be greater (p = 0.04). Conversely, ITs were not statistically different between the younger and older males. N1-P1 amplitudes did not differ between the sexes. CONCLUSIONS: Multifocal electroretinogram IT differs between males and females, depending on the age group and hysterectomy status.

Association between local neuroretinal function and control of adolescent type 1 diabetes.

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.

Neurodegenerative differences in the retinas of male and female patients with type 2 diabetes.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Early neural and vascular changes in the adolescent type 1 and type 2 diabetic retina.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Interocular symmetry of abnormal multifocal electroretinograms in adolescents with diabetes and no retinopathy.

PURPOSE: To investigate, in adolescents with type 1 diabetes and no retinopathy, the spatial correspondence between abnormal multifocal electroretinogram (mfERG) responses in the two eyes. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

OCT reveals regional differences in macular thickness with age.

PURPOSE: To assist identification of macular thickness abnormalities by optical coherence tomography (OCT), we use techniques that improve spatial localization across the retina to establish any age-related retinal thickness changes in healthy eyes. METHODS: Retinal thickness was measured in 30 eyes of 30 healthy subjects aged 13 to 69 years. Using Stratus OCT 3, 12 radial scans centered at the foveola were acquired and points between scans were interpolated to create a topographic map of the central 20 degrees . The thickness map was divided into 37 hexagonal regions. A mean retinal thickness for each hexagon was computed. Retinal thickness vs. age was evaluated for the entire scanned area, five anatomical regions, and within individual hexagons. The retinal nerve fiber layer (RNFL) contribution to total retinal thinning was analyzed in the papillomacular region. RESULTS: There was a small but significant thinning of the overall macular area with increasing age (2.7 mum/decade; p = 0.027). Comparing the 10 youngest subjects (age 13 to 27 years) with the 10 oldest (age 51 to 68 years), retinal thicknesses in the temporal, superior, inferior, and foveal regions were not significantly different. However, the two age groups differed significantly in retinal thickness in the nasal region (p < 0.008). Across all subjects, retinal thickness in this region was linearly correlated with age, decreasing by 4.1 mum/decade (p < 0.002). Approximately 43% of the retinal thinning in the nasal region was attributed to RNFL loss. CONCLUSIONS: The method of OCT acquisition and analysis used in this study allows for greater spatial localization of change in retinal thickness associated with aging or pathological processes. Based on the results of this study, the macula thins with increasing age but does so nonuniformly. The greatest amount of thinning occurs nasal to the fovea. RNFL loss accounts for much, but not all the thinning in this area.

Adolescents with Type 2 diabetes: early indications of focal retinal neuropathy, retinal thinning, and venular dilation.

PURPOSE: The eye provides a unique window into the neural and vascular health of a patient with diabetes. The present study is the first of its kind to examine the neural retinal function, structure, and retinal vascular health in adolescents with Type 2 diabetes. METHODS: Focal neural responses from 103 discrete retinal regions of the eye were tested using multifocal electroretinography. Optical coherence tomography was utilized to measure retinal thickness. Digital fundus photographs were examined for the presence of retinopathy and to measure vascular caliber using retinal vessel analysis. Fifteen adolescents diagnosed with Type 2 diabetes, aged 13 to 21 years with a mean diabetes duration of 2.1 +/- 1.3 years, were tested. Twenty-six age-matched control subjects were also tested. RESULTS: Multifocal electroretinograms of the Type 2 diabetic group were significantly (P = 0.03) delayed by 0.49 milliseconds. The diabetic group also showed significant (both; P < or = 0.03) retinal thinning (10.3 microm) and significant venular dilation (16.2 microm). CONCLUSION: The present study shows early indications of focal retinal neuropathy, retinal thinning, and venular dilation in adolescents with Type 2 diabetes. Early detection of functional and structural changes will hopefully aid in the prevention of permanent damage or further functional loss.

Association between multifocal ERG implicit time delays and adaptation in patients with diabetes.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A multifocal electroretinogram model predicting the development of diabetic retinopathy.

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.

Lightness constancy in 4-month-old infants.

In the present study, discrete trial familiarization/novelty techniques were used to study lightness constancy in 4-month-old infants. The test stimuli were real objects (paper smiley faces) of two different reflectances, dark gray (17% reflectance) and light gray (54% reflectance). In Experiment 1, the test stimuli were viewed against a white (90% reflectance) surround, and in Experiment 2, against a black (4.6% reflectance) surround. In Experiments 1 and 2, the illumination was changed between familiarization and test phases of each trial. In Experiment 3, the reflectance of the surround was changed from white to mid gray (28.5% reflectance) between familiarization and test phases of each trial. With the white surround, the infants preferred the face with the novel reflectance, consistent with the presence of lightness constancy. With the black surround, the infants showed no preference between faces with novel reflectance vs. novel luminance. With the changing surround, the infants showed a small preference for the stimulus with the novel ratio, as opposed to the stimulus with the novel reflectance and the novel luminance. The results are discussed in the context of adult cues for lightness constancy, including white anchor points and local luminance ratios.

Infants' spontaneous color preferences are not due to adult-like brightness variations.

In the present work, we explore the perceptual bases of infants' spontaneous looking preferences among isoluminant chromatic stimuli (Bornstein, 1975). Three experiments were conducted. In Experiment 1, adult subjects made brightness matches between a white standard and each of six isoluminant chromatic stimuli. The classic variations of brightness with chromaticity were found. In Experiment 2, 12-week-old infants' spontaneous looking preferences were measured for white lights of different luminances. Preference increased with increasing luminance, suggesting that brightness differences are sufficient to create looking preferences among isochromatic stimuli. In Experiment 3, infants' preferences were tested for each of the six chromatic stimuli paired against white, at both isoluminance and (adult) isobrightness. All chromatic stimuli were preferred to white, and the pattern of preferences was similar for both isoluminance and isobrightness conditions. It is concluded that hue and/or saturation, rather than brightness, control infants' spontaneous looking preferences among chromatic stimuli.