Wendy W. Harrison

Menisci and fullness of the blink in dry eye.

Purpose. This study was to investigate the role of the upper meniscus in tear film formation and blinking. Methods. One microliter of 2% fluorescein was instilled under the upper lid of 15 dry eye (DE) and 15 control subjects. Subjects were instructed to blink partially and hold the eye open as long as possible, and analysis of tear breakup dynamics was used to quantify the area of breakup. This procedure was repeated following a full blink. Meniscus height was measured from digital videos. Results. Both menisci were significantly decreased in DE compared with controls (p < 0.02, t test). Tear breakup dynamics analysis showed that significantly greater areas of breakup occurred with full compared with incomplete blinks in DE (p < 0.003 Mann Whitney U test), but not in controls. Conclusions. A stable tear film can be deposited by the upper meniscus alone following a partial blink, without contribution from the lower meniscus. The increased tear stability of partial blinks in DE may be due to less stretching of the already fragile tear film compared with a full blink, which covers more surface area.

Prediction, by Retinal Location, of the Onset of Diabetic Edema in Patients with Nonproliferative Diabetic Retinopathy

PURPOSE 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. METHODS 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 models predictive properties. RESULTS 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. CONCLUSIONS 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.

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°. 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 &mgr;m/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 &mgr;m/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.

Multifocal pattern electroretinogram: cellular origins and clinical implications.

Purposes. The purposes of this article are to gain insight into the cellular origins of the multifocal pattern electroretinogram (mPERG) and evaluate its potential for clinical use. Methods. mPERGs were recorded from four anesthetized monkeys before and after pharmacologic blockade of light-driven activity of inner-retinal neurons and from 55 normal human subjects (19–91 years) and six patients with glaucoma (43–77 years of age). Stimuli consisted of counterphase-modulated black and white triangles organized in 61-scaled hexagons with mean luminance 100 cd/m2 and 100% contrast. The stimulus array subtended 31° vertically and 37 ° horizontally at 48 cm. The amplifier cutoff frequencies were 3 and 100 Hz. Responses were grouped as quadrants and the first slice of the second-order kernel was analyzed. Results. The mPERG responses of monkeys and humans were similar. In the monkey responses, there was an early positive potential (P1) around 25 ms and a later positive potential (P2) found selectively in the nasal field quadrants around 31 ms. These responses were seen around 22 and 36 ms in the human responses. After blockade of inner-retinal activity in monkeys, P1 amplitude was greatly reduced at all retinal locations and P2 was eliminated. P1 and P2 amplitudes were significantly reduced in the glaucomatous eyes relative to amplitudes of age-matched controls. Reductions in the amplitudes of P1 and P2 could easily discriminate between glaucomatous visual field quadrants with and without behavioral sensitivity losses. However, these alterations are likely to reflect diffuse losses. Conclusions. mPERG responses contain prominent contributions from inner-retinal neurons that can be reduced in glaucomatous eyes. These findings raise the possibility that the mPERG could be potentially useful in the objective estimation of neural damage in glaucoma. However, further refinement of recording techniques will be required if the mPERG is to be used to detect focal damage.

Associations between Local Retinal Thickness and Function in Early Diabetes

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.

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 females compared with the males. 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.

Correlation of tear osmolarity and dry eye symptoms in convention attendees.

Purpose To assess the correlation between tear osmolarity readings and symptoms of dry eye in a nonclinical convenience sample and to determine how well symptoms and osmolarity correlate with the self-assessment of dry eye. Methods Two hundred forty-nine attendees in the exhibit hall at an optometric educational meeting agreed to participate in a dry eye study. Contact lens wearers were excluded. Volunteers supplied demographic information and completed a 5-item Dry Eye Questionnaire (DEQ-5) and answered the question “Do you think you have dry eye” with a yes or no response. Osmolarity testing was done using the TearLab instrument on the right eye, then on the left eye. Pearson correlation analyses were performed to determine the relationship between variables. Results There was no correlation between DEQ-5 scores and average tear osmolarity (correlation coefficient, 0.02) and highest osmolarity (correlation coefficient, 0.03). The mean DEQ-5 score was significantly higher among subjects who self-reported dry eye (mean, 11.3; p < 0.0001) compared with those who did not (mean, 5.4; p < 0.0001). No differences were observed between the yes and no self-reported dry eye groups and average osmolarity (p = 0.23) and highest osmolarity (p = 0.14). Conclusions In this nonclinical population, there was no significant correlation between tear osmolarity and ocular symptoms as reported or between tear osmolarity and the self-assessment of dry eye.

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.

Blood Pressure, Vessel Caliber, and Retinal Thickness in Diabetes

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.

Arteriole tortuosity associated with diabetic retinopathy and cholesterol.

Purpose Earlier identification of diabetic eye disease is an important research effort. Retinopathy is widely acknowledged but retinal vessel changes are not evaluated as stringently. Here, we create a multivariate model for the association between retinal vessel tortuosity (RVT) and other health factors in patients with diabetes. Methods Three hundred eyes of 150 patients with diabetes were included. Three investigators independently reviewed telemedicine fundus photographs and scored the level of diabetic retinopathy (DR) and RVT. These scores were evaluated for agreement and averaged. Also collected were age, duration of diabetes, presence or absence of diabetic nephropathy or neuropathy, blood pressure, total cholesterol, and hemoglobin A1c. A regression model evaluating the association of tortuosity with other factors was created. Results There was very high agreement between the three graders for level of DR (&kgr; = 0.84). Agreement between the three graders for RVT varied substantially: poor for venous tortuosity (&kgr; = 0.23) and fair for arteriole tortuosity (&kgr; = 0.44) and overall gut tortuosity (&kgr; = 0.42). The overall gut tortuosity was the most reproducible for the graders with a correlation coefficient of 0.923. There were univariate associations between arteriole tortuosity and venous tortuosity, DR level, and cholesterol. The selected best multivariate model found arteriole tortuosity to be associated with DR and cholesterol levels. Conclusions First, RVT, particularly for venules, is difficult to grade consistently; therefore, future studies examining tortuosity should focus on arterioles. Second, the model indicates that there is an association between vessel changes, DR, and systemic cholesterol levels. Although DR and RVT are readily available to assess concurrently on a photograph, the addition of cholesterol to this model indicates that patients with RVT may warrant further follow-up on health factors, such as cholesterol levels.