Test-retest repeatability in macular retinal oximetry.

CLINICAL RELEVANCE: Evaluation of retinal macular oxygen saturation in healthy controls can aid in understanding the pathological changes seen in similar locations of those with vascular diseases like diabetes. BACKGROUND: The aim of this study was to determine the test-retest repeatability of localised retinal oximetry measurements in the macula on the Zilia Oximeter within healthy subjects of different races, 18-40 years old. Oxygen saturation was measured between three time points within the same locations of the right eye. METHODS: Twenty seven subjects were included (aged 26.3 ± 3.6 years). All were confirmed to have healthy retinas and at least 6/9 vision. Oximetry measurements were taken using the Zilia to acquire local oxygen saturation measurements (300 µm diameter) at four points 3.1 degrees from the fovea in the superior/temporal, superior/nasal, inferior/temporal, and inferior/nasal locations. Oximetry measurements were taken twice on the same day 20 minutes apart and then again 1-2 weeks later. Oximetry data was analysed with intraclass correlation between visits. To assess intrasubject repeatability, the Bland-Altman repeatability coefficient and coefficient of variation were calculated. RESULTS: Average Intraclass correlation for the three acquisition times of the right eye was 0.78. The averaged intrasubject repeatability coefficient for the three acquisition times was 8.4. The averaged coefficient of variation was 5.4%. CONCLUSION: The Zilia oximeter has good macular test-retest repeatability; however, multiple measurements may be needed to ensure accuracy.

Foveal avascular zone size and mfERG metrics in diabetes and prediabetes: a pilot study of the relationship between structure and function.

PURPOSE: Previous studies have demonstrated functional and structural retinal changes in type 2 diabetes (T2DM). However, less is understood in prediabetes, which is an important precursor to T2DM. Here, we evaluate the microvasculature structure of the foveal avascular zone (FAZ) and how it is correlated with retinal function as measured by the multifocal electroretinogram (mfERG) across levels of glucose dysfunction to uncover how T2DM and prediabetes alter this structure-function relationship. METHODS: 33 subjects were included: 9 controls, 12 prediabetes, 12 T2DM with no retinopathy or edema. Subjects were aged 30-70 years, had BCVA of 20/25 or better, and had no confounding ocular conditions. Blood was collected via fingerstick to determine Hemoglobin A1c (HbA1c), which was used along with previous diagnosis, to determine study grouping. Optical coherence tomography angiography (OCTA) was used to analyze the FAZ area and was corrected for refractive error. FAZ area was measured by hand using the Heidelberg Spectralis software. mfERG (VERIS 6.3) metrics implicit time (IT) and amplitude were evaluated in the foveal region, macular region, and averaged over the posterior pole of the right eye. Regression analysis was performed between each study group parameter to determine relationships, and t tests with corrections were used to compare groups. RESULTS: FAZ area (superficial plexus) was negatively correlated with mfERG posterior pole amplitude (p < 0.01, R2 = 0.30), foveal amp (p = 0.02 R2 = 0.17) and macular amplitude (p = 0.02 R2 = 0.18) across all 33 study subjects. FAZ and mfERG metrics were not significantly different between study groups in this cohort except for IT, which was more delayed in the diabetes group compared to other groups. CONCLUSION: FAZ area is correlated with mfERG amplitudes but not IT. This suggests a link between the structural metrics and retinal function. Longitudinal follow-up work would be helpful to determine the timing of these changes in prediabetes.

Fundus motion during mfERG testing.

PURPOSE: The purpose of this study was to assess eye movements during a multifocal ERG (mfERG) recording. This study evaluated the relationship between bivariate contour ellipse areas (BCEAs), mfERG amplitudes (Amps) and mfERG implicit times (ITs) with repeat testing and experienced subjects. METHODS: Thirty subjects were selected (15 experienced to ocular procedures and 15 novices). All were confirmed to have healthy retinas and at least 20/25 vision. MfERGs with a stimulus near 100% contrast and 4-min m-sequence were recorded on two different days using our common clinical technique, which did not constrain the head. VERIS with fundus monitoring system was used for recording with a Burian-Allen electrode. An external camera captured the fundus during each mfERG recording. The optic nerve head position was tracked in each video using a custom algorithm in order to determine BCEAs. Each subject performed one mfERG on two different days. MfERGs were analyzed for Amps and ITs for the fovea and whole eye. RESULTS: There was no correlation between the mfERG metrics and BCEAs with repeat testing. There were also no differences between the experienced and novice subjects for mfERG Amps, ITs or BCEAs. Eye movements between visits were highly correlated (multiple r = 0.67). BCEAs were larger during mfERGs (1.04 ± 0.8 deg2) than those observed in previous literature using brief viewing tasks (< 0.3 deg2). The proportion of time spent fixating within 1.0 and 2.0 degrees of the central hexagon was 68 and 93%, respectively. CONCLUSIONS: This study is the first to evaluate the stability of the retina while recording a mfERG in healthy subjects and indicates that the center of fixation during a mfERG stays within the central hexagon. Eye stability during an initial recording is the best indicator of stability on the second recording. The amount of movement during these recordings did not seem to affect the mfERG Amps or ITs. These data suggest clinical confidence with mfERGs when recording novice patients.

The Relationship Between Corneal Nerve Density and Hemoglobin A1c in Patients With Prediabetes and Type 2 Diabetes.

Purpose: Decreased corneal nerve fiber density and higher corneal epithelial dendritic cells have been reported in established patients with type 2 diabetes; however, alterations in the subbasal nerve plexus in prediabetes with healthy subjects or subjects with diabetes is limited. The study aimed to determine corneal nerve fiber density and morphology and dendritic cell density between healthy subjects and those with prediabetes or type 2 diabetes. Methods: Fifty-two subjects (aged 30-70 years) were recruited. Blood samples and body metrics were taken. Subjects were grouped as: healthy controls (hemoglobin A1c [HbA1c] < 5.7%), prediabetes (5.7-6.4%), and type 2 diabetes (> 6.4% or physician diagnosis). Central corneal subbasal nerve plexus was imaged using in vivo confocal microscopy. Corneal nerve fiber density and morphology, including interconnections and tortuosity, and dendritic cell density were assessed. Kruskal-Wallis tests were carried out to compare differences in the examined variables between groups. Spearman correlations were carried out to examine the associations between body metrics with HbA1c and corneal findings. Results: Seventeen healthy controls, 20 subjects with prediabetes, and 15 subjects with type 2 diabetes completed this study. Central corneal nerve fiber density was significantly lower in type 2 diabetes compared to prediabetes (P = 0.045) and healthy controls (P = 0.001). No differences were found in central corneal nerve fiber interconnections, tortuosity, or dendritic cell density between groups. There was a significant association between HbA1c and corneal nerve fiber density (rho = -0.45, P = 0.001) and body mass index (BMI; rho = -0.30, P = 0.04). Conclusions: Increased HbA1c values are associated with decreased corneal nerve fiber density across the spectrum of type 2 diabetes.

Functional retinal outcomes in patients with prediabetes and type 2 diabetes.

PURPOSE: Type 2 diabetes (T2DM) is a leading cause of visual impairment. Its precursor, prediabetes (preDM), is growing in numbers every year. While it is well known that T2DM causes changes in retinal function early in the disease process, it is likely that some of these changes emerge during the preDM stage. This study evaluates retinal function measures in patients with preDM to determine if there are differences in colour vision, contrast sensitivity (CS), and multifocal electroretinogram (mfERG) measures present before T2DM is diagnosed. METHODS: The L'Anthony desaturated D-15 test, Mars Chart CS test, and mfERG were administered on the right eye of 43 participants; 15 controls (HbA1c ≤ 5.6%), 17 with preDM (HbA1c 5.7%-6.4%), and 11 with T2DM (either physician diagnosed or with untreated HbA1c ≥ 6.5%). HbA1c values were measured at the time of the other tests. Colour vision confusion scores (CVCS) were calculated from the D-15 using the method developed by Torok. Multivariate regression (which controlled for age differences) was used to evaluate the relationship of HbA1c and functional measures. Kruskal-Wallis tests were also used to evaluate differences between groups with post-hoc analysis. RESULTS: CVCSs were significantly different between the three groups (p = 0.009). There was an association between higher CVCS and higher HbA1c values across all groups as well as specifically within the preDM group when controlling for age (R2  = 0.29, p = 0.01 and R2  = 0.39, p = 0.02 respectively). Multivariate regression of all of the functional tests together and HbA1c found only colour vision remained significant, indicating that the functional examination metrics may provide redundant data, with similar changes in prediabetes where colour vision may be the strongest indicator early in the process. CONCLUSIONS: Patients with prediabetes have functional changes that can be measured in the retina before the diagnosis of diabetes, with the L'Anthony D-15 colour vision test providing the strongest association with glucose dysregulation in this population. This has important implications for follow up and screening for diabetes within optometric practices. Further studies are needed to follow these patients over time to see how and when these metrics change.