Mirjam E. J. van Velthoven

Recent developments in optical coherence tomography for imaging the retina

Optical coherence tomography (OCT) was introduced in ophthalmology a decade ago. Within a few years in vivo imaging of the healthy retina and optic nerve head and of retinal diseases was a fact. In particular the ease with which these images can be acquired considerably changed the diagnostic strategy used by ophthalmologists. The OCT technique currently available in clinical practice is referred to as time-domain OCT, because the depth information of the retina is acquired as a sequence of samples, over time. This can be done either in longitudinal cross-sections perpendicular to, or in the coronal plane parallel to the retinal surface. Only recently, major advances have been made as to image resolution with the introduction of ultrahigh resolution OCT and in imaging speed, signal-to-noise ratio and sensitivity with the introduction of spectral-domain OCT. Functional OCT is the next frontier in OCT imaging. For example, polarization-sensitive OCT uses the birefringent characteristics of the retinal nerve fibre layer to better assess its thickness. Blood flow information from retinal vessels as well as the oxygenation state of retinal tissue can be extracted from the OCT signal. Very promising are the developments in contrast-enhanced molecular optical imaging, for example with the use of scattering tuneable nanoparticles targeted at specific tissue or cell structures. This review will provide an overview of these most recent developments in the field of OCT imaging focussing on applications for the retina.

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.

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.

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

Significance Diabetic retinopathy (DR), a primary cause of blindness, is characterized by microvascular abnormalities. Recent evidence suggests that retinal diabetic neuropathy (RDN) also occurs in people with diabetes, but little is known about the temporal relationship between DR and RDN. This longitudinal study in people with diabetes with no or minimal DR shows that RDN precedes signs of microvasculopathy and that RDN is progressive and independent of glycated hemoglobin, age, and sex. This finding was further confirmed in human donor eyes and in two experimental mouse models of diabetes. The results suggest that RDN is not ischemic in origin and represent a shift in our understanding of the pathophysiology of this complication of diabetes that potentially affects vision in all people with 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)-Leprdb/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.

Decreased optical coherence tomography‐measured pericentral retinal thickness in patients with diabetes mellitus type 1 with minimal diabetic retinopathy

Aim: A comparison of retinal thickness (RT) measurements with optical coherence tomography (OCT) in patients with type 1 diabetes mellitus (DM) and no or minimal diabetic retinopathy (DR) versus healthy controls. Methods: Fifty-three patients with type 1 DM with no or minimal DR underwent full ophthalmic examination, fundus photography and OCT. Mean RT measured by OCT was calculated for the central fovea, the fovea, the pericentral and the peripheral area of the macula, and compared to healthy controls. Results: Mean RT in the pericentral area was lower in patients with minimal DR (267 µm ± 20 µm; n = 23) compared to healthy controls (281 µm ±13 µm; p = 0.005; n = 28). Mean pericentral RT in patients without DR (276 µm ±14 µm; n = 30) was less than pericentral RT in healthy controls, but higher than in patients with minimal DR, without being statistically significant. None of the other regions showed a significant change. Conclusion: In this study a significantly decreased pericentral RT was measured in patients with minimal DR compared to healthy controls. This could be explained by a loss of intraretinal neural tissue in the earliest stage of DR.

Imaging the retina by en face optical coherence tomography.

Purpose: To present the possibilities of a new system that combines optical coherence tomography (OCT) and confocal ophthalmoscopy, producing en face OCT images in patients with retinal diseases. Methods: A prototype OCT Ophthalmoscope (OTI, Toronto, Canada) was used to scan patients with retinal conditions. The system uses a super luminescent diode (&lgr; = 820 nm; &Dgr;&lgr; = 20 nm) and currently scans at a rate of 2 frames per second. In each frame, the OCT Ophthalmoscope simultaneously produces a transversal OCT scan and a confocal image in the X/Y plane. Both images correspond pixel to pixel. Results: Between January 2002 and August 2003, >800 patients with various retinal diseases were scanned with the OCT Ophthalmoscope. Illustrative cases with regularly seen macular diseases are presented, such as macular hole and central serous retinopathy. Conclusion: Current difficulties as well as future possibilities of this new en face OCT ophthalmoscope are discussed. By presenting normal and pathologic transversal OCT images made by a prototype OCT Ophthalmoscope, we show that it can provide information not available using conventional OCT imaging.

Comparison of a new-generation sectorial addition multifocal intraocular lens and a diffractive apodized multifocal intraocular lens.

PURPOSE: To compare visual, refractive, and satisfactory outcomes between a new‐generation sectorial addition multifocal intraocular lens (IOL) (Lentis Mplus LS‐312; study group) and a diffractive apodized multifocal IOL (Restor SN6AD1; control group). SETTING: Private practice, Driebergen, and Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands. DESIGN: Comparative case series. METHODS: Refractive and visual outcomes at near and distance, patient satisfaction, and dysphotopsia scores were recorded 3, 6, and 12 months postoperatively. RESULTS: The study group comprised 90 eyes and the control group, 143 eyes. Three months postoperatively, the mean uncorrected distance visual acuity (UDVA) was not statistically significantly different between the study group and the control group (0.04 ± 0.15 logMAR [SD] versus 0.06 ± 0.25 logMAR). The control group had significantly better uncorrected near visual acuity than the study group at 30 cm (0.05 ± 0.14 logMAR versus 0.15 ± 0.08 logMAR) and 40 cm (0.05 ± 0.14 versus 0.16 ± 0.21) (P<.01 and P<.03, respectively). Patients in the control group were more satisfied with their vision (P<.001). Dissatisfaction was related to younger age at surgery and male sex (P<.0001 and P<.033 respectively). Dysphotopsia occurred in approximately 18% of cases in both groups. CONCLUSIONS: The new sectorial addition multifocal IOL performed comparably to the diffractive apodized multifocal IOL in terms of UDVA and the presence of dysphotopsia. The diffractive apodized multifocal IOL performed better at 30 cm and 40 cm reading distances and had higher patient satisfaction. Financial Disclosure: Dr. Lapid‐Gortzak has received speaker’s fees from Alcon, Simovision, Oculentis, and Medtechnika. Dr. Lapid‐Gortzak and Dr. van der Meulen have received an unrestricted research grant from Oculentis. Dr. van Velthoven has received speaker’s fees from Novartis (Netherlands). Drs. van der Linden, Nieuwendaal, and Mourits have no financial or proprietary interest in any material or method mentioned.

Thickness measurements of donor posterior disks after descemet stripping endothelial keratoplasty with anterior segment optical coherence tomography.

Purpose: To evaluate donor posterior disk thickness measured with anterior segment optical coherence tomography after Descemet stripping endothelial keratoplasty. Methods: Fifteen patients (17 eyes) after Descemet stripping endothelial keratoplasty, using manually dissected donor posterior disks, were measured with the Visante anterior segment optical coherence tomography (Carl Zeiss Meditec Inc, Dublin, CA). Optical coherence tomography scans were made in a radial pattern, 45 degrees apart, starting in the horizontal axis. Thickness measurements of the donor posterior disks were taken centrally and at fixed radii toward the periphery and were correlated to postoperative change in spherical equivalent (SE), best-corrected visual acuity (BCVA, in Snellen), and improvement in BCVA. Results: Median BCVA was 20/30 (range 20/60-20/20) postoperatively. Median postoperative improvement in BCVA was 4 lines (range 1-11). Median follow-up time was 15.5 months (range 6-32 months). Median postoperative change in SE was −0.25 diopters (range −4.25 to +3.00 diopters). Median central disk thickness was 128.3 μm (range 55-181 μm) and increased significantly toward the periphery: median disk thickness at the 1.5 mm radius was 140.8 μm (range 72-199 μm) and at the 3.0 mm radius was 161.5 μm (range 102-245 μm). No correlation was found between (central) donor disk thickness and postoperative BCVA or change in SE. A nonstatistically significant trend was seen toward more improvement in BCVA with thinner donor disks. Conclusions: Optical coherence tomography measurements of the manually dissected donor posterior disk showed significant variation in thickness, without a statistically significant effect on postoperative BCVA or improvement thereof. Central thickness varied significantly from the peripheral thickness within donor posterior disk.

Age and gender-specific reference values of orbital fat and muscle volumes in Caucasians

Aim To provide age and gender-specific reference values for orbital fat and muscle volumes (MV) in Caucasian adults. Patients and Methods Computed tomographic scans of 160 orbits from 52 men and 55 women, aged 20–80 years, not affected by orbital disease were evaluated. Orbital bony cavity volume (OV), fat volume (FV) and MV were calculated by a previously validated method using the software program Mimics. Ratios of FV to OV and of MV to OV were determined. Results OV, FV and MV were all significantly larger in men than in women (p<0.001), but FV/OV and MV/OV were similar in both sexes. OV and MV did not change with age, but FV increased with advancing age in both women (p<0.001) and men (p<0.001). Linear regression analysis with FV/OV and MV/OV ratios as dependent variables and age and gender as independent variables showed a significant correlation between age and FV/OV (r=0.52, p<0.0001) and age and MV/OV (r=−0.26, p=0.001). Conclusions Advancing age is associated with an increase of FV/OV and a minor decrease of MV/OV. Gender-specific differences in orbital FV and MV disappear once FV and MV are related to OV, by calculating the ratios FV/OV and MV/OV. Age-specific gender-neutral reference ranges (2.5 and 97.5 percentiles) of FV/OV and MV/OV are presented.

Overlay of conventional angiographic and en-face OCT images enhances their interpretation

BackgroundCombining characteristic morphological and functional information in one image increases pathophysiologic understanding as well as diagnostic accuracy in most clinical settings. En-face optical coherence tomography (OCT) provides a high resolution, transversal OCT image of the macular area combined with a confocal image of the same area (OCT C-scans). Creating an overlay image of a conventional angiographic image onto an OCT image, using the confocal part to facilitate transformation, combines structural and functional information of the retinal area of interest. This paper describes the construction of such overlay images and their aid in improving the interpretation of OCT C-scans.MethodsIn various patients, en-face OCT C-scans (made with a prototype OCT-Ophthalmoscope (OTI, Canada) in use at the Department of Ophthalmology (Academic Medical Centre, Amsterdam, The Netherlands)) and conventional fluorescein angiography (FA) were performed. ImagePro, with a custom made plug-in, was used to make an overlay-image. The confocal part of the OCT C-scan was used to spatially transform the FA image onto the OCT C-scan, using the vascular arcades as a reference. To facilitate visualization the transformed angiographic image and the OCT C-scan were combined in an RGB image.ResultsThe confocal part of the OCT C-scan could easily be fused with angiographic images. Overlay showed a direct correspondence between retinal thickening and FA leakage in Birdshot retinochoroiditis, localized the subretinal neovascular membrane and correlated anatomic and vascular leakage features in myopia, and showed the extent of retinal and pigment epithelial detachment in retinal angiomatous proliferation as FA leakage was subject to blocked fluorescence. The overlay mode provided additional insight not readily available in either mode alone.ConclusionCombining conventional angiographic images and en-face OCT C-scans assists in the interpretation of both imaging modalities. By combining the physiopathological information in the angiograms with the structural information in the OCT scan, zones of leakage can be correlated to structural changes in the retina or pigment epithelium. This strategy could be used in the evaluation and monitoring of patients with complex central macular pathology.