Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 µm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 µm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 µm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 µm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

Variability in photocoagulation treatment of diabetic macular oedema.

PURPOSE: To establish whether differences in the assessment of diabetic macular oedema (DME) with either optical coherence tomography (OCT) or stereoscopic biomicroscopy lead to variability in the photocoagulation treatment of DME. METHODS: The differences in the assessment of DME with either OCT or stereoscopic biomicroscopy were analysed by calculating the surface areas and the overlap of retinal thickening. Photocoagulation treatment plans of retinal specialists were compared by evaluating the number and location of planned laser spots. RESULTS: The threshold for and dosage of photocoagulation differ depending upon whether the basis of retinal thickness diagnosis is clinical observation or OCT. The overlap in laser spot location based on the assessment of DME with OCT or biomicroscopy averages 51%. Among retinal specialists, the treatment plans differed in the laser spot count by six- to 11-fold. CONCLUSION: Diabetic macular oedema photocoagulation treatment threshold and dosage of laser spots differ depending on whether thickness assessments are based on stereoscopic slit-lamp biomicroscopy or OCT. In addition, retinal specialists differed in the number and placement of planned laser spots even when given identical information concerning DME and treatable lesions. This variability in the photocoagulation treatment of DME could lead to differences in patient outcome and laser study results.

The relationship between the optical density of cataract and its influence on retinal nerve fibre layer thickness measured with spectral domain optical coherence tomography.

PURPOSE: The purpose of this study was to model the influence of cataract on Spectral Domain Optical Coherence Tomography (SDOCT) image quality and Retinal Nerve Fibre Layer (RNFL) thickness measurements. METHODS: SDOCT images, made with two different devices (3DOCT-1000, Topcon and Cirrus HD-OCT), before and after cataract surgery were compared and judged against measurements from normal subjects using artificial filters simulating the effects of cataract. Optical density of the images was calculated based on a mathematical model described previously. RESULTS: In total, forty-eight eyes were included for pre- and postoperative cataract extraction measurements. OCT image quality significantly (p < 0.001) improved postoperative and postoperative RNFL thickness was significantly (p < 0.001) thicker in both groups of patients. The measurements using artificial filters showed a rather precise linear relation between change in filter induced optical density and change in RNFL thickness (R = 0.941, p < 0.001 for 3DOCT-1000 and R = 0.785, p < 0.001 for Cirrus HD-OCT). For the patient groups, the relation was less marked, 3DOCT-1000 Rs = 0.697, p < 0.03 and Cirrus HD-OCT Rs = 0.444, p < 0.03. The predictive potential based on the found linear relationship between OCT-effective optical density of cataract and the cataract-induced underestimation was however limited, and mean difference ± SD between predicted and measured RNFL thickness were 1.68 ± 7.55 (3DOCT-1000) and 3.71 ± 2.97 (Cirrus HD-OCT) micron. CONCLUSIONS: A linear relationship exists between OCT-effective optical density of cataract and underestimation of RNFL thickness measured with OCT. This finding holds promise to correct for cataract-induced changes in RNFL measurements, but will differ for each type of OCT device.

Effect of age on individual retinal layer thickness in normal eyes as measured with spectral-domain optical coherence tomography.

PURPOSE: To determine the effect of age on the thickness of individual retinal layers, measured with spectral-domain optical coherence tomography (SD-OCT), in a population of healthy Caucasians. METHODS: One hundred and twenty subjects with an age ranging between 18 and 81 years were examined with SD-OCT. Mean layer thickness was calculated for seven retinal layers, in the fovea (region 1 of the 9 Early Treatment Diabetic Retinopathy Study [ETDRS] regions); in the pericentral ring (ETDRS regions 2 to 5); and the peripheral ring (ETDRS regions 6 to 9) following automated segmentation using the Iowa Reference Algorithm. In addition, mean peripapillary retinal nerve fiber layer (RNFL) thickness was measured. The partial correlation test was performed on each layer to determine the effect of age on layer thickness, while correcting for spherical equivalent, sex, and Topcon image quality factor as confounders, followed by Bonferroni corrections to adjust for multiple testing. RESULTS: The thickness of the peripapillary RNFL (R = -0.332; P < 0.001); pericentral ganglion cell layer (R = -0.354, P < 0.001); peripheral inner plexiform layer (R = -0.328, P < 0.001); and foveal outer segment layer (R = -0.381, P < 0.001) decreased significantly with increasing age. Foveal RPE thickness (R = 0.467, P < 0.001) increased significantly with increasing age; other layers showed no significant differences with age. CONCLUSIONS: Several macular layers and the peripapillary RNFL thickness showed significant changes correlated with age. This should be taken into consideration when analyzing macular layers and the peripapillary RNFL in SD-OCT studies of retinal diseases and glaucoma.

Early neurodegeneration in the retina of type 2 diabetic patients.

PURPOSE: The purpose of this study was to determine whether diabetes type 2 causes thinning of retinal layers as a sign of neurodegeneration and to investigate the possible relationship between this thinning and duration of diabetes mellitus, diabetic retinopathy (DR) status, age, sex, and glycemic control (HbA1c). METHODS: Mean layer thickness was calculated for retinal layers following automated segmentation of spectral domain optical coherence tomography images of diabetic patients with no or minimal DR and compared with controls. To determine the relationship between layer thickness and diabetes duration, DR status, age, sex, and HbA1c, a multiple linear regression analysis was used. RESULTS: In the pericentral area of the macula, the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were thinner in patients with minimal DR compared to controls (respective difference 1.9 µm, 95% confidence interval [CI] 0.3-3.5 µm; 5.2 µm, 95% CI 1.0-9.3 µm; 4.5 µm, 95% CI 2.2-6.7 µm). In the peripheral area of the macula, the RNFL and IPL were thinner in patients with minimal DR compared to controls (respective difference 3.2 µm, 95% CI 0.1-6.4 µm; 3.3 µm, 95% CI 1.2-5.4 µm). Multiple linear regression analysis showed DR status to be the only significant explanatory variable (R = 0.31, P = 0.03) for this retinal thinning. CONCLUSIONS: This study demonstrated thinner inner retinal layers in the macula of type 2 diabetic patients with minimal DR than in controls. These results support the concept that early DR includes a neurodegenerative component.

Association of visual function and ganglion cell layer thickness in patients with diabetes mellitus type 1 and no or minimal diabetic retinopathy.

Diabetic retinopathy (DR) classically presents with micro-aneurysms, small haemorrhages and/or lipoprotein exudates. Several studies have indicated that neural loss occurs in DR even before vascular damage can be observed. This study evaluated the possible relationship between structure (spectral domain-optical coherence tomography) and function (Rarebit visual field test) in patients with type 1 diabetes mellitus and no or minimal diabetic retinopathy (DR). Results demonstrated loss of macular visual function and corresponding thinning of the ganglion cell layer (GCL) in the pericentral area of the macula of diabetic patients (Rs = 0.65, p < 0.001). In multivariable logistic regression analysis, GCL thickness remained an independent predictor of decreased visual function (OR 1.5, 95% CI 1.1-2.1). Early DR seems to include a neurodegenerative component.

Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes.

PURPOSE. To determine which retinal layers are most affected by diabetes and contribute to thinning of the inner retina and to investigate the relationship between retinal layer thickness (LT) and diabetes duration, diabetic retinopathy (DR) status, age, glycosylated hemoglobin (HbA1c), and the sex of the individual, in patients with type 1 diabetes who have no or minimal DR. METHODS. Mean LT was calculated for the individual retinal layers after automated segmentation of spectral domain-optical coherence tomography scans of patients with diabetes and compared with that in control subjects. Multiple linear regression analysis was used to determine the relationship between LT and HbA1c, age, sex, diabetes duration, and DR status. RESULTS. In patients with minimal DR, the mean ganglion cell layer (GCL) in the pericentral area was 5.1 mum thinner (95% confidence interval [CI], 1.1-9.1 mum), and in the peripheral macula, the mean retinal nerve fiber layer (RNFL) was 3.7 mum thinner (95% CI, 1.3-6.1 mum) than in the control subjects. There was a significant linear correlation (R = 0.53, P < 0.01) between GCL thickness and diabetes duration in the pooled group of patients. Multiple linear regression analysis (R = 0.62, P < 0.01) showed that DR status was the most important explanatory variable. CONCLUSIONS. This study demonstrates GCL thinning in the pericentral area and corresponding loss of RNFL thickness in the peripheral macula in patients with type 1 diabetes and no or minimal DR compared with control subjects. These results support the concept that diabetes has an early neurodegenerative effect on the retina, which occurs even though the vascular component of DR is minimal.

A model for the effect of disturbances in the optical media on the OCT image quality.

PURPOSE: The loss of quality of optical coherence tomography (OCT) images resulting from disturbances in the optical media has been modeled. METHODS: OCT measurements were performed in two healthy volunteers using time domain (TD)-OCT (StratusOCT; Carl Zeiss Meditec, Dublin, CA). Optical disturbances were approached in three ways simulated with filters. The studied effects were: light attenuation (absorptive and reflective filters), refractive aberrations (defocusing lenses), and light scattering/straylight (scattering filters). The same examiner scanned the subjects with the filters placed in front of the eye. The signal strength (SS) values of the scans were then collected. The strength of the filters were expressed in optical density (OD), determined for the 830 nm central wavelength of the OCT, (OD(lambda=830)). RESULTS: A linear relationship has been found between the OD(lambda=830) of the absorptive and reflective filters and the SS of the corresponding OCT images. Assuming that reduction of light from the OCT scanning spot on the retina is the critical factor, this light loss was determined for the scattering filters and defocusing lenses. A comparable linear relationship was found between the SS value and the OD(lambda=830) of these filters. CONCLUSIONS: The model indicates that the loss of OCT image quality in patients with disturbances in the optical media is explained by attenuation of the light in the OCT scanning spot on the retina. A linear relationship between the SS and the single pass logarithmic attenuation of the OCT signal is shown, according to SS=constant-(9.9 [-9.4 to -10.6] x OD(lambda=830)).

Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy.

PURPOSE: To determine whether type 1 diabetes preferentially affects the inner retinal layers by comparing the thickness of six retinal layers in type 1 diabetic patients who have no or minimal diabetic retinopathy (DR) with those of age- and sex-matched healthy controls. METHODS: Fifty-seven patients with type 1 diabetes with no (n = 32) or minimal (n = 25) DR underwent full ophthalmic examination, stereoscopic fundus photography, and optical coherence tomography (OCT). After automated segmentation of intraretinal layers of the OCT images, mean thickness was calculated for six layers of the retina in the fovea, the pericentral area, and the peripheral area of the central macula and were compared with those of an age- and sex-matched control group. RESULTS: In patients with minimal DR, the mean ganglion cell/inner plexiform layer was 2.7 microm thinner (95% confidence interval [CI], 2.1-4.3 microm) and the mean inner nuclear layer was 1.1 microm thinner (95% CI, 0.1-2.1 microm) in the pericentral area of the central macula compared to those of age-matched controls. In the peripheral area, the mean ganglion cell/inner plexiform layer remained significantly thinner. No other layers showed a significant difference. CONCLUSIONS: Thinning of the total retina in type 1 diabetic patients with minimal retinopathy compared with healthy controls is attributed to a selective thinning of inner retinal layers and supports the concept that early DR includes a neurodegenerative component.