Hyperreflective Layer Research Articles

Using Optical Coherence Tomography to Assess Corneoscleral Morphology After Soft Contact Lens Wear

To evaluate the use of optical coherence tomography (OCT) for assessing the effect of different soft contact lenses on corneoscleral morphology. Ten subjects had anterior segment OCT B-scans taken in the morning and again after 6 h of soft contact lens wear. For each subject, three different contact lenses were used in the right eye on non-consecutive days, including a hydrogel sphere, a silicone hydrogel sphere, and a silicone hydrogel toric. After image registration and layer segmentation, analyses were performed of the first hyper-reflective layer (HRL), the epithelial basement membrane (EBL), and the epithelial thickness (HRL to EBL). A root mean square difference (RMSD) of the layer profiles and the thickness change between the morning and afternoon measurements were used to assess the effect of the contact lens on the corneoscleral morphology. The soft contact lenses had a statistically significant effect on the morphology of the anterior segment layers (p < 0.001). The average amounts of change for the three lenses (average RMSD values) for the corneal region were lower (3.93 ± 1.95 μm for the HRL and 4.02 ± 2.14 μm for the EBL) than those measured in the limbal/scleral region (11.24 ± 6.21 μm for the HRL and 12.61 ± 6.42 μm for the EBL). Similarly, averaged across the three lenses, the RMSD in epithelial thickness was lower in the cornea (2.84 ± 0.84 μm) than the limbal/scleral (5.47 ± 1.71 μm) region. Post hoc analysis showed that ocular surface changes were significantly smaller with the silicone hydrogel sphere lens than both the silicone hydrogel toric (p < 0.005) and hydrogel sphere (p < 0.02) for the combined HRL and EBL data. In this preliminary study, we have shown that soft contact lenses can produce small but significant changes in the morphology of the limbal/scleral region and that OCT technology is useful in assessing these changes. The clinical significance of these changes is yet to be determined.

Bildrekonstruktion des subbasalen Nervenplexus der Kornea mit erweitertem Bildfeld aus Fokusserien eines konfokalen Laser-Scanning-Mikroskops

Confocal laser scanning microscopy (CLSM) allows the in vivo analysis of nerve structures of the human cornea. In this way, pathological alterations of the peripheral nervous system that also affect the corneal subbasal nerve plexus (SNP) can be diagnosed non-invasively and possibly earlier than with other methods. The field of view of in vivo CLSM images of the cornea (ca. 0.4 × 0.4 mm²) is not sufficient for a reliable assessment. Two phenomena make the image assessment difficult: the presence of ridge-like tissue deformations in the neighbourhood of the SNP and image distortions that are induced by involuntary and unavoidable eye movements during image acquisition. This paper presents an image processing method for generating undistorted images of the SNP with an extended field of view. The presented method has been tested on five volunteers. Eight focus image stacks have been taken and processed from each subject using a Heidelberg Retina Tomograph with Rostock Cornea Module (HRT). An image registration scheme specifically adapted to the image acquisition system corrects the non-linear motion-induced image distortions and reconstructs a volume from each focus image stack. The epithelial basal boundary surface including the SNP appears as a distinctive hyper-reflective layer inside the reconstructed volume. Extracting this continuous layer generates a depth map and finally a two-dimensional image of the SNP. A final fusion step of the single reconstructed SNP images leads to laterally extended images. Out of 40 focus image stacks, 34 have been fully processed into two-dimensional SNP reconstruction images. Six focus image stacks could not be transformed into volumes because of extremely fast eye movements during the image acquisition that prevented the complete image registration of the stacks. The 34 SNP reconstruction images depict an average area of 94.7 % ( ± 6.2 %) with respect to the field of view of a single HRT image. The final fusion of the reconstructed images resulted in an average increase of the image area by a factor of 2.6 (ranging from 2.2 to 3.1). The presented image processing algorithms are capable of correcting the motion-induced image distortions and of generating larger two-dimensional images of the SNP even in presence of severe tissue deformations. These images provide the basis for a more reliable assessment of the corneal nerve fibres.

Rapid growth of choroidal melanoma during pregnancy*

Editor, A 29-week pregnant, 31-year-old woman presented with a superior juxtapapillary choroidal tumour (8 mm largest basal diameter (LBD) × 5 mm height) in her left eye with a visual acuity of 20/30 (Fig. 1A, B). The patient wanted to delay any treatment until delivery. Three months later (2 weeks after delivering a boy), the tumour size had increased to 13 mm × 12 mm. There was extensive serous retinal detachment and subretinal haemorrhage that reduced her visual acuity to detecting only hand motion (Fig. 1C, D). Pathology of enucleated eye confirmed choroidal melanoma of mixed cell type and fluorescence in situ hybridization for chromosome 3 indicated monosomy (ZytoVision, Bremerhaven, Germany). Immunohistochemistry indicated absence of both oestrogen (Thermo Scientific, SP1, 1:100) and progesterone receptors (Dako, PgR 636, 1:100). The mean microvascular density (MVD) from three most highly vascularized areas (CD34+) was 79 vessels/0.313 mm2. Using standard photographs for semiquantitative scoring system (Makitie et al. 2001), macrophage density (CD68+) was determined to be moderate. (A) Fundus photography of the left eye depicting a superior juxtapapillary choroidal mass with associated serous retinal detachment. (B) Ultrasonographic image of the tumour with medium internal reflection. The largest basal diameter (LBD) was 8 mm, and the height was 5 mm. (C) Fundus photography of the same eye taken 3 months later. Tumor size increased with the development of extensive serous retinal detachment and subretinal haemorrhage. (D) Ultrasonographic image of the enlarged tumour with 13 mm in LBD and 12 mm in height. Hyperreflective layer indicated by arrowhead represents subretinal haemorrhage. We suspected that male foetal cells from the maternal circulation participated in tumour angiogenesis; however, there was no Y chromosome detected in the tumour using a DNA quantification kit (Applied Biosystems, Foster city, CA, USA). The patient was monitored for 2 years and remains metastasis free. We assumed that the LBD represented both tumour length and width. Although it could have been coincidental, the growth of UM during pregnancy have been previously reported (Seddon et al. 1982), as has transformation of clinically stable choroidal nevus into melanoma during pregnancy (Shields et al. 1991). Despite suspicions that increased growth was the result of endocrine effects, we did not detect oestrogen or progesterone receptors, which is consistent with previous studies (Seddon et al. 1982). In addition to rising oestrogen and progesterone, secretion of melanocyte-stimulating hormone (MSH) also increases during pregnancy. MSH is responsible for hyperpigmentation in pregnant women, usually affecting the nipples, areola, and face. UM is of melanocytic origin, so it has the potential to respond to elevated MSH. During pregnancy, immunity is altered to favour type 2 helper cell pathway (Th2) over type 1 helper cell pathway (Th1)to tolerate the foetus. This Th1/Th2 imbalance could promote rapid tumour growth. Vascular changes are frequently observed during pregnancy because of increased blood volume and raised angiogenic factors from high demand of vascular placenta. Although these vascular changes can merely increase tumour oedema or subretinal exudation, they can promote tumour vascularity as well, which facilitates growth. MVD was relatively high in our case, considering median MVD of 40 vessels/0.313 mm2 for 134 UM in one series (Makitie et al. 1999). Tumour vascularity is also affected by foetal cell microchimerism; foetal progenitor cells can enter the maternal circulation, and a recent study reported that these cells engraft in maternal cutaneous melanoma and differentiate into endothelial cells (Nguyen Huu et al. 2009). However, we did not detect foetal cells in the tumour. Therefore, the mechanism for rapid growth of UM in our patient may be multifactorial, relating to complex endocrine signalling, altered immunity, and a favourable angiogenic environment. The cumulative mortality rate depends on the tumour size. We recommend that a newly diagnosed UM in pregnant state be re-examined in one month if the tumour is to be observed. Initiation of the treatment is warranted in rapidly enlarging tumours. Part of this work was presented at the International Congress of Ocular Oncology conference from the 8–12th of September 2009 in Cambridge, United Kingdom.

Spectral-Domain Optical Coherence Tomography Following Nd:YAG Laser Membranotomy in Valsalva Retinopathy

To describe spectral-domain optical coherence tomography (SD-OCT) findings following Nd:YAG laser membranotomy in premacular hemorrhage due to Valsalva retinopathy. Interventional case series of 7 eyes with premacular hemorrhage due to Valsalva retinopathy. Best-corrected Snellen visual acuity (BCVA) and color fundus photography were obtained before and after the laser treatment. SD-OCT scans were obtained at 1, 3, and 6 months following treatment. SD-OCT revealed a convex dome-shaped cavity lined by a hyperreflective layer in all cases, which persisted until the end of follow-up. Two patients complained of metamorphopsia, although BCVA improved dramatically in all cases. The site of laser puncture was visible in 2 patients. No abnormality was detected in the underlying retinal layers. SD-OCT reveals formation of a premacular cavity following laser puncture for premacular hemorrhage in Valsalva retinopathy, which may persist despite successful drainage of blood. This may later result in metamorphopsia in certain patients.

FUNDUS AUTOFLUORESCENCE AND OPTICAL COHERENCE TOMOGRAPHY OF CONGENITAL GROUPED ALBINOTIC SPOTS

The purpose of this study was to describe the findings of fundus autofluores-cence (FAF) and optical coherence tomography in a series of patients with congenital grouped albinotic spots. Three eyes of three patients with congenital grouped albinotic spots were evaluated with FAF and optical coherence tomography imaging to evaluate the nature of the albinotic spots. In all three eyes with congenital grouped albinotic spots, FAF imaging showed autofluorescent spots corresponding to the albinotic spots seen on stereo biomicroscopy. One eye also had additional spots detected on FAF imaging that were not visible on stereo biomicroscopy or color fundus photographs. Fundus autofluorescence imaging of the spots showed decreased general autofluorescence and decreased peripheral autofluorescence surrounding central areas of retained or increased autofluorescence. Optical coherence tomography showed a disruption in signal from the hyperreflective layer corresponding to the inner and outer segment junction and increased signal backscattering from the choroid in the area of the spots. Fluorescein angiography showed early and stable hyperfluorescence of the spots without leakage. In this case series, FAF showed decreased autofluorescence of the spots consistent with focal retinal pigment epithelium atrophy or abnormal material blocking normal autofluorescence and areas of increased autofluorescence suggesting retinal pigment epithelium dysfunction. The findings of optical coherence tomography and fluorescein angiography suggest photoreceptor and retinal pigment epithelium layer abnormalities. Fundus autofluorescence and optical coherence tomography are useful noninvasive diagnostic adjuncts that can aid in the diagnosis of congenital grouped albinotic spots, help determine extent of disease, and contribute to our understanding of its pathophysiology.

The first experience of an optical coherenсe tomography in diagnostics of the primary and residual retinoblastoma

Abstract Purpose To determine diagnostic features of the primary and residual retinoblastoma documented by optical coherence tomography (OCT). Methods 21 children with retinoblastoma were examined by OCT to analyze the changes in the retina before and during the different stages of treatment. In 21 eyes 36 foci have been examined: 9 were with primary retinoblastoma, 12 –residual tumours, 12‐ chorioretinal scar after local treatment by methods of brachytherapy and TTT, 3 ‐ calcified focus. Results Tomographical features of the primary retinoblastoma were: thickening of retina at the level of the inside layers was up to 645 ± 77,02 microns (р&lt;0,001) – 9. In 9 cases there was no differentiation but there was homogeneity of structure of retinal inside layers in the tumour centre. The chorioretinal scar after сhemotherapy and local treatment (12 patients) on tomograms were diagnosed as a flat bright red hyperreflective stripe replacing all layers of a retina. In 3 patients calcified focus was characterized by raised bright red hyperreflective layer under which the effect of a shade was marked on tomograms. In 12 patients with residual tumours the absence of differentiation of the inside layers of retina with the effect of a shade under undifferentiated inside layers of a retina, elevation of the inside layers of the retina into the vitreous, equal choroidal profile and on the periphery ‐ bright red flat hyperreflective retina were diagnosed. Conclusion The OCT allows to reveal changes in retina and to diagnose tumoral, paunch, calcified tissue at primary and residual retinoblastoma that is necessary for definition of further tactics of treatment.

High-Definition Optical Coherence Tomography Features in Vitelliform Macular Dystrophy

To correlate high-definition optical coherence tomography (HD OCT) and fundus examination findings at different phases of vitelliform macular dystrophy and to determine the anatomic location of vitelliform material. Prospective, noncomparative, observational case series. A complete ophthalmologic examination, including fundus biomicroscopy and HD OCT, was performed in 11 consecutive patients with a diagnosis of vitelliform macular dystrophy. Using HD OCT, we were able to demonstrate for the first time the presence of previtelliform lesions, characterized by a thicker layer between the retinal pigment epithelium (RPE) and the inner segment and outer segment (IS/OS) interface. At this stage, a normal-appearing RPE and IS/OS interface were found in two of four eyes. In all progressive stages from the vitelliform to the vitelliruptive, the vitelliform material was visualized by HD OCT as an highly reflective lesion located between the hyporeflective outer nuclear layer and the hyperreflective RPE layer, associated or not to an optically empty lesion. At these stages, a disrupted IS/OS interface and an almost normal appearance of all major intraretinal layers was detected. At the vitelliruptive and atrophic stages, on some parts, the HD OCT scan revealed hyperreflective mottling on the RPE layer, probably representing areas of focal RPE hypertrophy. The atrophic stage and the fibrotic stage were characterized by thinning of all the retinal layers and diffuse loss of the IS/OS interface. In our series, mean best-corrected visual acuity impairment showed a statistically significant correlation to the presence of focal disruption or diffuse loss of the IS/OS interface (P = .002), as well as to a more advanced stage of the disease (P = .01). A more advanced stage of the disease showed a strong statistically significant correlation to the presence of diffuse loss of the IS/OS interface (P < .001). Based on the HD OCT findings, we hypothesize that early changes in vitelliform macular dystrophy involve the layer between the RPE and the IS/OS interface, first with accumulation of material beneath the sensory retina, and then with disruption and attenuation of IS and OS; late changes seem to affect the RPE, which undergoes hypertrophy, disruption, and attenuation.

RPE TEARS AFTER PEGAPTANIB TREATMENT IN AGE-RELATED MACULAR DEGENERATION

To describe retinal pigment epithelial (RPE) tears in patients with age-related macular degeneration (AMD) status post pegaptanib (Macugen) injection. Six eyes from six patients who developed RPE tears while undergoing treatment with pegaptanib for AMD-related fibrovascular pigment epithelial detachment (PED) and occult choroidal neovascularization (CNV) were identified retrospectively. Diagnosis of pre-pegaptanib fibrovascular PED and post-pegaptanib RPE tears were made by clinical examination, fluorescein angiography (FA), and optical coherence tomography (OCT) imaging of the macula. Four patients developed an RPE tear within 8 weeks after the first pegaptanib injection, while RPE tears were found in two patients following a second injection. Only one of the patients reported acute vision loss, although three of six eyes had a decrease in objective visual acuity in the affected eye to the count fingers level. All six cases displayed the classic clinical and angiographic appearance of RPE tears. In addition, OCT imaging showed an irregular, hyperreflective RPE layer with a focal defect. RPE tears are known to occur in the setting of PED spontaneously or after laser treatment, but have only recently been described in association with intravitreal pegaptanib. OCT imaging of eyes status post pegaptanib therapy may be helpful in identifying this complication. Patients with AMD, especially those with occult CNV and fibrovascular PED, receiving pegaptanib therapy should be monitored for RPE tears, which may warrant deferral of further injections.

In vivo confocal microscopy findings in a patient with posterior amorphous corneal dystrophy

A 21-year-old man, with bilateral posterior amorphous corneal dystrophy, was studied by biomicroscopy, corneal topography and in vivo confocal microscopy. The best-corrected visual acuity was 6/21 in the right eye and 6/6.9 in the left eye. Biomicroscopy revealed bilateral, asymmetric, sheet-like opacification at the deep posterior stromal layer. The corneal topography displayed asymmetric against-the-rule astigmatism in the right eye and prominent steepening at the inferior paracentral cornea in both eyes. In vivo confocal microscopy of the corneas demonstrated microfolds and hyper-reflective layer at the posterior stroma just adjacent to the endothelial layer. The epithelium, Bowman's membrane, anterior stroma and the endothelial layer were normal. In vivo confocal microscopy is useful in evaluating the corneal dystrophies.

Correlation of endoscopic optical coherence tomography with histology in the lower-GI tract

Optical coherence tomography (OCT), a noninvasive optical imaging technique, provides high-resolution cross-sectional images of tissue microstructure. We developed a system for real-time endoscopic OCT (EOCT) of the human GI tract. During clinical trials, the structure of mucosa and submucosa, glands, blood vessels, pits, villi, and crypts was observed in a range of GI organs. Although EOCT images are thought to accurately depict actual histologic features, there are few data to support this assumption. Therefore, the present study correlated images acquired with an EOCT imaging system in vitro to corresponding histologic sections. EOCT images were obtained of fresh specimens of ileum, colon, and rectum that then were fixed in formalin and were processed for microscopic evaluation by using standard methods. The thickness of mucosa and of submucosa was determined for both EOCT images and histologic slides. The first hyper-reflective layer in the EOCT images was identified as mucosa. A close correlation (R 2=0.84) was observed between EOCT and histology. Furthermore, the submucosa and the muscularis propria could be identified as the next deepest hyporeflective band and a hyper-reflective layer, respectively, in EOCT images. The submucosa was found to be more compressible than mucosa, and its EOCT appearance was dependent on its content of adipose tissue. EOCT provides images that precisely correlate with the histologic structure of the mucosa and the submucosa of the GI tract.

Optical Coherence Tomography Findings in Solar Retinopathy

Solar retinopathy is characterized by involvement of the outer retinal layers. Optical coherence tomography may help delineate the retinal injury site in vivo. Optical coherence tomography was performed in three eyes of two patients with solar retinopathy. All three eyes demonstrated a characteristic excavation in the outer hyperreflective layer corresponding to the retinal complex.