Glycemic Variability and the Thickness of Retinal Layers in Cystic Fibrosis Patients with and without Cystic Fibrosis Related Diabetes.

PURPOSE: Patients with cystic fibrosis (CF) are at risk to develop CF related diabetes (CFRD) and subsequently even diabetic neuro- and/or vasculopathy. We sought to determine if there are typical signs of diabetes-related retinal alterations present in CF patients with preserved and impaired glycemic control. METHODS: During routine annual examination CF patients were offered an additional 7-day period of real time continuous glucose monitoring (rtCGM) and an ophthalmological examination including retinal optical coherence tomography (OCT). Patients were categorized according to the glycemic control, i.e. the results of an oral glucose tolerance test (OGTT) and rtCGM were taken into consideration. OCT data was analyzed by our previously published visual analysis software generating dedicated and spatially resolved deviation maps for visualization and quantification of differences in total retinal thickness and thickness of retinal nerve fiber layer (RNFL) as well as ganglion cell layer (GCL) in comparison to age-matched healthy controls and patients with either type 1 or type 2 diabetes mellitus. RESULTS: Results of the rtCGM and/or OGTT enabled discrimination between patients with normal glycemic control (CFNG; n = 6), with abnormal glycemic control (CFAG; n = 6) and overt CFRD (n = 4). OCT data indicates gradually increasing retinal thinning in all 3 groups, depending on the degree of glucose metabolism disorder compared to healthy controls. At the foveal region total retinal thickness and GCL thickness were significantly thinner in CFRD patients compared to CFNG patients (total retinal thickness: 260.4 µm (239.3-270.8) vs. 275.4 µm (254.3-289.5); GCL: 11.82 µm (11.16-15.25) vs. 17.30 µm (13.95-19.82); each p < 0.05). CONCLUSION: Although we investigated a rather small number of patients, we obtained evidence that intraretinal neurodegenerative changes occur in each of our subgroups (CFNG, CFAG, CFRD). Beyond this, our results favor the detrimental role of additional diabetes, as the deviations from healthy controls were most pronounced in the CFRD group and are similar to those seen in patients suffering from type 1 or type 2 diabetes.

Taxane-Induced Neuropathy and Its Ocular Effects-A Longitudinal Follow-up Study in Breast Cancer Patients.

A common severe neurotoxic side effect of breast cancer (BC) therapy is chemotherapy-induced peripheral neuropathy (CIPN) and intervention is highly needed for the detection, prevention, and treatment of CIPN at an early stage. As the eye is susceptible to neurotoxic stimuli, the present study aims to determine whether CIPN signs in paclitaxel-treated BC patients correlate with ocular changes by applying advanced non-invasive biophotonic in vivo imaging. Patients (n = 14, 10 controls) underwent monitoring sessions after diagnosis, during, and after therapy (T0-T3). Monitoring sessions included general anamnesis, assessment of their quality of life, neurological scores, ophthalmological status, macular optical coherence tomography (OCT), and imaging of their subbasal nerve plexus (SNP) by large-area confocal laser-scanning microscopy (CLSM). At T0, no significant differences were detected between patients and controls. During treatment, patients' scores significantly changed while the greatest differences were found between T0 and T3. None of the patients developed severe CIPN but retinal thickenings could be detected. CLSM revealed large SNP mosaics with identical areas while corneal nerves remained stable. The study represents the first longitudinal study combining oncological examinations with advanced biophotonic imaging techniques, demonstrating a powerful tool for the objective assessment of the severity of neurotoxic events with ocular structures acting as potential biomarkers.

Thickness of Intraretinal Layers in Patients with Type 2 Diabetes Mellitus Depending on a Concomitant Diabetic Neuropathy: Results of a Cross-Sectional Study Using Deviation Maps for OCT Data Analysis.

Optical coherence tomography (OCT) supports the detection of thickness changes in intraretinal layers at an early stage of diabetes mellitus. However, the analysis of OCT data in cross-sectional studies is complex and time-consuming. We introduce an enhanced deviation map-based analysis (MA) and demonstrate its effectiveness in detecting early changes in intraretinal layer thickness in adults with type 2 diabetes mellitus (T2DM) compared to common early treatment diabetic retinopathy study (ETDRS) grid-based analysis (GA). To this end, we obtained OCT scans of unilateral eyes from 33 T2DM patients without diabetic retinopathy and 40 healthy controls. The patients were categorized according to concomitant diabetic peripheral neuropathy (DN). The results of MA and GA demonstrated statistically significant differences in retinal thickness between patients and controls. Thinning was most pronounced in total retinal thickness and the thickness of the inner retinal layers in areas of the inner macular ring, selectively extending into areas of the outer macular ring and foveal center. Patients with clinically proven DN showed the strongest thinning of the inner retinal layers. MA showed additional areas of thinning whereas GA tended to underestimate thickness changes, especially in areas with localized thinning. We conclude that MA enables a precise analysis of retinal thickness data and contributes to the understanding of localized changes in intraretinal layers in adults with T2DM.

Deviation Maps for Understanding Thickness Changes of Inner Retinal Layers in Children with Type 1 Diabetes Mellitus.

Purpose: To analyze the use of deviation maps (DevMs) to understand thickness changes of inner retinal layers in optical coherence tomography (OCT) data. To test a new visual analytics (VA) method with reduced complexity of OCT data analysis by comparing the layer thickness of children with type 1 diabetes mellitus (T1DM) to matched controls. Methods: OCT was performed on unilateral eyes of 26 children with T1DM without diabetic retinopathy and 29 healthy children to obtain macular volume scans. Subsequently, segmented inner retinal layers were analyzed using VA. Deviation maps were generated to readily visualize thickness differences between both groups and to investigate thickness changes of individual patients in relation to the control group. Results: In DevMs of the patient group, the total retina (TR) demonstrated localized, irregular areas of thinning (mean ± standard deviation) involving foveal center, inner macula, and inferior-nasal outer macula (-9.31 ± 1.73 µm; p < 0.05). Similarly, retinal nerve fiber layer showed continuous and localized areas of thinning in both inner and outer macula, extending nasally (-5.45 ± 4.31 µm; p < 0.05). In DevMs of individual patients, the TR and inner retinal layers revealed remarkable changes in thickness that were present between patients at both late and early stages of diabetes. Conclusion: The VA method simplifies the in-depth analysis of OCT volume data from different groups and is effective in detecting retinal thickness changes in children with diabetes. It can be easily adopted in a clinical set-up and intuitively used in complex multidisciplinary studies.

Spectral-Domain Optical Coherence Tomography for Determination of Retinal Thickness in Pediatric Patients with Mild-To-Moderate Chronic Kidney Disease: A Cross-Sectional Study.

OBJECTIVE: Children with chronic kidney diseases (CKD) are at risk for neurological diseases at early adulthood. Spectral-domain optical coherence tomography (SD-OCT) of the retina is especially suitable for determination of intraretinal layer thickness. We wonder whether retinal thinning is already present in pediatric patients with mild-to-moderate CKD. PATIENTS AND METHODS: Children (n = 15; 14.9 ± 2.4 years) with mild-to-moderate CKD (median eGFR of 95ml/min/1.73m2; range: 28-187ml/min/1.73m2) due to glomerulopathy, congenital anomalies of kidney and urinary tract (CAKUT), or haemolytic uremic syndrome (HUS) underwent a detailed ophthalmologic examination including high-resolution SD-OCT. Three OCT scans were obtained from the right eyes of all patients. Within each scan, retinal layers were separated and the mean thickness was determined at the foveal, parafoveal, and perifoveal area. The results were compared to those we obtained previously from healthy children. RESULTS: At the parafoveal area, thickness (median, range) of the total retina (ALL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were reduced compared to healthy volunteers (339µm, (288-361µm) vs. 348µm, (320-385µm); 49.8µm (30.5-56.6µm) vs. 53.5µm (49.5-60.5µm) and 41.0µm (29.4-43.7µm) vs. 43.46µm (39.5-46.3µm); each p < 0.05). The intraretinal thickness measurements at the foveal and perifoveal areas revealed no statistically significant differences between patients and controls. CONCLUSION: Distinct changes within the parafoveal area of the total retina, GCL, and IPL are present in children with mild-to-moderate CKD. Prospective studies are required to assess the clinical significance of our findings.

The corneal subbasal nerve plexus and thickness of the retinal layers in pediatric type 1 diabetes and matched controls.

Optical coherence tomography (OCT) of the retina and corneal confocal laser scanning microscopy (CLSM) of the subbasal nerve plexus (SBP) are noninvasive techniques for quantification of the ocular neurodegenerative changes in individuals with type 1 diabetes mellitus (T1DM). In adult T1DM patients these changes are hardly related to T1DM only. Instead, ageing and/or lifestyle associated comorbidities have to be considered as putative confounding variables. Therefore, we investigated pediatric T1DM patients (n = 28; 14.2 ± 2.51 y; duration of disease: 5.39 ± 4.16 y) without clinical signs of diabetic retina disease, neuropathy, vasculopathy or nephropathy and compared our findings with those obtained in healthy controls (n = 46; 14.8 ± 1.89 y). The SBP was characterized by the averaged length, thickness, and tortuosity of nerve fibers as well as the number of branching and connecting points. OCT was used to determine the total thickness of the retina (ALL) and the thickness of each retinal layer. Both methods revealed signs of early neurodegenerative changes, e.g. thinning of distinct retinal layers at the pericentral ring and shortening of corneal nerve fibers that are already present in pediatric T1DM patients. Standardization of instruments and algorithms are urgently required to enable uniform comparison between different groups and define normative values to introduce in the clinical setting.

[Visual Analysis of Retinal OCT Data]. / Visuelle Analyse von retinalen OCT-Daten.

Optical coherence tomography (OCT) enables noninvasive high-resolution 3D imaging of the human retina, and thus plays a fundamental role in ophthalmology. Via OCT examination, even subtle retinal changes can be captured, which occur in very early stages of different diseases (e.g., glaucoma, diabetes mellitus, or age-related macular degeneration). Yet, analyzing the resulting data is challenging. Conventionally, OCT data are strongly aggregated via automated methods. While this reduces the amount of information to be analyzed, it also makes it difficult, if not impossible, to identify small and localized retinal changes. This might lead to wrong diagnoses, since these methods do not account for patient-specific characteristics. We address this problem by providing new and efficient visual-interactive methods. Particularly, we introduce dedicated visualizations that show different aspects of the data. In addition, we support patient-specific selections of relevant data regions. Selected regions are emphasized, or separately visualized to inspect retinal substructures in detail. By visually comparing the regions to reference data, even very small retinal changes can be detected. We demonstrate the utility of our approach by applying it to data of a study with pediatric patients suffering from diabetes mellitus type 1. Our results show that visual-interactive methods indeed help to analyze subtle retinal changes and, thus, support the diagnosis of diseases in an early stage.