Hyperreflective Deposits Research Articles

Evaluating Optical Coherence Tomography (OCT) Findings as Potential Biomarkers in Central Nervous System (CNS) Lymphoma with or Without Ocular Involvement

Purpose: To evaluate spectral domain optical coherence tomography (SD-OCT) findings as potential biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement. Methods: The patient cohort finder tool at Stanford University Hospital was used to identify patients with any type of lymphoma using the ICD-10 codes (C82-C88), from January 2004 to October 2017. A total of 14,820 patients were identified. Procedure code (92134) for optical coherence tomography (OCT) was then applied to identify patients who underwent OCT at the ophthalmology clinic/Byers Eye Institute. Clinic charts of 460 patients with lymphoma who had undergone OCT were reviewed to identify patients with confirmed diagnosis of PCNSL and divided into two groups (Group 1: with and Group 2: without ocular involvement). Their SD-OCTs from within 1 month of the diagnosis were analyzed for the presence of 1) Hyperreflective deposits in choroid, retinal pigment epithelium (RPE), outer retina and inner retina; 2) RPE thickening; 3) Vitreous debris; 4) Intraretinal fluid; 5) Ellipsoid zone disruption by masked graders. Chi-square was used to analyze the difference in characteristics between the groups. Results: Twenty-two eyes of 11 patients with PCNSL were included this study (6 eyes in group 1 and 16 eyes in group 2). Mean age of subjects was 65 years (Group1: 60 years and Group 2: 67 years). Five patients (45.45%) were female (Group1: 3 and Group2: 7). There was no statistically significant difference between the groups for the presence of hyperreflective deposits in choroid, RPE, outer and inner retina, and the presence of RPE thickening, intraretinal fluid and ellipsoid zone disruption. Vitreous debris was found more commonly in group 1 subjects (83%) than group 2 (31.25%) (p=0.029). All subjects in both groups showed hyperreflective deposits in the RPE demonstrating RPE infiltration. However, RPE thickening was noted only in 3 patients (Group1: 1 and Group2: 2). Conclusions: Our study has demonstrated that the OCT findings of hyperreflective deposits present in eye with IOL secondary to PCNSL are also observed in eyes with PCNSL without ocular disease. These hyperreflective deposits can serve as biomarkers and aid in the early detection of ocular involvement by PCNSL. Funding Statement: funding was received for this project Declaration of Interests: QDN is a recipient of a Physician Scientist Award from Research to Prevent Blindness, New York, NY, and serves on the Scientific Advisory Board for AbbVie, Bayer, Genentech, Regeneron, and Santen, among others. No other authors have received any financial funding or support. The Byers Eye Institute has received research funding support from Research Prevent Blindness, Inc. Ethics Approval Statement: It was conducted in compliance with the Declaration of Helsinki, the United States Code of Federal Regulations Title 21, and the Harmonized Tripartite Guidelines for Good Clinical Practice (1996). The study was approved by local institutional review board. An informed consent waiver was obtained as charts of the selected patients were reviewed retrospectively.

The findings of optical coherence tomography of retinal degeneration in relation to the morphological and electroretinographic features in RPE65-/- mice.

PurposeMutations of the gene encoding RPE65 cause Leber congenital amaurosis (LCA) retinitis pigmentosa (RP). The optical coherence tomography (OCT) is increasingly utilized to noninvasively evaluate various types of retinal diseases, including RP. The present study was conducted to characterize the OCT findings of the RPE65−/− mice—an animal model of LCA and RP—in relation to the morphological features based on histological and electron microscopic findings as well as electroretinography (ERG) features.Materials and methodsRPE65−/− mice were employed as a model of retinal degeneration. C57BL/6J mice were used as a wild-type control. OCT was performed on the RPE65−/− mice from postnatal day (P) 22 to 170. The longitudinal changes in the OCT images and fundus pictures were analyzed both qualitatively and quantitatively in comparison to those of C57BL/6J mice. The OCT images were also compared to the histological and electron microscopic findings. Full field combined rod and cone ERG was performed to analyze the relationship between morphology based on OCT and the amplitudes of the a- and b-waves.ResultsIn the RPE65−/− mice, the photoreceptor rod and cone layer appeared as a diffuse hyperreflective zone contiguous with the inner segment ellipsoid zone (IS-EZ) on OCT, even on P22, whereas the IS-EZ and interdigitation zone were clearly identified in the age-matched C57BL/6J mice. The histological analyses revealed that the regular arrangement of the photoreceptor inner and outer segments was gradually lost in the RPE65-/- mice. On electron microscopy, most of the rod outer segments were degenerated from P21 to P35, whereas outer segments became variably shorter after P49 although ultrastructure appeared to normalize. The thickness of the outer nuclear layer of RPE65−/− mice was slowly and progressively reduced in comparison to C57BL/6J mice. Although the thickness of the inner and outer segment layer of RPE65−/− mice was significantly decreased in comparison to C57BL/6J mice, the change was not progressive, at least until P170. Even at P35, the amplitudes of both a- and b-waves on ERG were severely deteriorated in comparison to those of C57BL/6J mice. Mottled depigmented spots appeared throughout the fundus in RPE65−/− mice after P72, and were detected as hyperreflective deposits under the retinal pigment epithelium on OCT.DiscussionThe pathological changes in the inner and outer segments layer of RPE65−/− mice were identified as diffuse hyperreflective changes on OCT. The rod outer segments showed degeneration in the early postnatal periods but became morphologically normalized in the disc structure after P49, although the sizes of the length of the rod outer segments were variable. OCT could not qualitatively differentiate the early degeneration of rods from the late variability in size of rods. Although the morphology of the photoreceptor outer segments was relatively preserved in the RPE65−/− mice, the amplitudes of ERG were severely disturbed. These structural and functional deficits may be derived from the defective supply of 11-cis-retinol to the photoreceptors.

Spectrally Resolved Fundus Autofluorescence in ABCA4-Related Retinopathy.

To investigate the green and red fluorescence emission component of hyperautofluorescent flecks in patients with ABCA4-related retinopathy. A confocal light-emitting diode (LED)-based retinal imaging system (EIDON) was used for image acquisition of patients with genetically confirmed ABCA4 mutations. Using 450-nm excitation wavelengths, spectrally resolved retinal autofluorescence images were acquired in two wavelength ranges: green emission fluorescent component (GEFC, 500-560 nm), and red emission fluorescent component (REFC, 560-700 nm). Image analysis included comparison of the two emission spectra, correlation with confocal EIDON LED color fundus images, and spectral-domain optical coherence tomography (OCT). Eighty eyes of 40 patients with ABCA4-related retinopathy were examined. A characteristic distribution of flecks with distinct pattern of fluorescence emission components was detected and quantified. Independent from disease manifestation, different proportions of GEFC and REFC were identified within single flecks. Centrally located flecks showed a higher proportion of GEFC and were characterized by local disruption of outer retinal bands in OCT. More peripheral flecks were more prominent in the REFC and correlated to subretinal hyperreflective deposits with only minor pathologic alterations of outer retinal layers. Individual flecks even showed spatial differences of the predominant fluorescent component. Spectrally resolved fundus autofluorescence intensity images feature characteristic distribution of GEFC and REFC in flecks, highlighting the heterogeneity of fluorophore distribution and providing more insight into the pathogenesis of ABCA4-related retinopathy. In view of upcoming therapeutic trials, longitudinal analysis of fluorescent components might facilitate monitoring of subtle disease progression and/or treatment effects.

HYPERREFLECTIVE DEPOSITION IN THE BACKGROUND OF ADVANCED STARGARDT DISEASE.

To describe an unusual manifestation of hyperreflective deposits in the subretinal space in a group of patients with clinically and genetically confirmed Stargardt disease. Retrospective review of color fundus, autofluorescence, infrared reflectance, red-free images, and spectral domain optical coherence tomography in 296 clinically diagnosed and genetically confirmed (2 expected disease-causing mutations in ABCA4) patients with Stargardt disease. Full-field electroretinogram (ffERG), medical history, and genotype data (in silico predictions) were further analyzed from the selected cohort. Eight of 296 patients (2.7%) were found to exhibit small crystalline deposits that were detectable on certain imaging modalities, such as color, infrared reflectance and red-free images, but not autofluorescence. The deposits were most prevalent in the superior region of the macula, and spectral domain optical coherence tomography revealed their presence in the subretinal space. All patients presented with these findings at a notably advanced disease stage with abnormal ffERG and a high proportion of highly deleterious ABCA4 alleles. Hyperreflective subretinal deposits may be a manifestation of advanced ABCA4 disease, particularly in regions susceptible to disease-related changes, such as lipofuscin accumulation.

A long history of dense deposit disease

BackgroundDense Deposit Disease is a rare condition affecting the Bruch’s membrane and the glomerular basement membrane. We report the progression of the ocular manifestations over a 30 year follow up period, longer than any previous report.Case presentationA 44 year old male presented with pigmentary changes at the macula noted by his optician. Best corrected visual acuity at presentation was good in both eyes. Fundoscopy showed pigmentary changes and drusen, and investigation using intravenous fundus fluorescein angiography did not demonstrate any choroidal neovascular membrane. The patient subsequently developed renal failure and received a dual renal transplant. The transplanted kidneys also failed over the coming year. The patient’s vision gradually deteriorated and comparison between the images in 2010 and 1985 demonstrated a clear progression of the macula changes. Optical coherence tomography showed multiple subretinal hyper reflective drusenoid deposits. These deposits were also noted to be autofluorescent on blue auto-fluorescence. The young age at presentation of drusen, combined with the history of recurrent kidney failure and progression of subretinal deposits led to a diagnosis of dense deposit disease.ConclusionsDense deposit disease is a rare condition affecting Bruch’s membrane, but should be considered in the differential diagnosis of any patient under the age of 50 years presenting with drusen.

A Mouse Model of Schnyder Corneal Dystrophy with the N100S Point Mutation

Schnyder corneal dystrophy (SCD) is a rare autosomal dominant disease in humans, characterized by abnormal deposition of cholesterol and phospholipids in cornea caused by mutations in the UbiA prenyltransferase domain containing 1 (UBIAD1) gene. In this study, we generated a mouse line carrying Ubiad1 N100S point mutation using the CRISPR/Cas9 technique to investigate the pathogenesis of SCD. In vivo confocal microscopy revealed hyper-reflective dot-like deposits in the anterior cornea in heterozygotes and homozygotes. No significant change was found in corneal epithelial barrier function or wound healing. Electron microscopy revealed abnormal mitochondrial morphology in corneal epithelial, stromal, and endothelial cells. Mitochondrial DNA copy number assay showed 1.27 ± 0.07 fold change in homozygotes versus 0.98 ± 0.05 variation in wild type mice (P < 0.05). Lipidomic analysis indicated abnormal metabolism of glycerophosphoglycerols, a lipid class found in mitochondria. Four (34:1, 34:2, 36:2, and 44:8) of the 11 glycerophosphoglycerols species identified by mass spectrometry showed a significant increase in homozygous corneas compared with heterozygous and wild-type mouse corneas. Unexpectedly, we did not find a difference in the corneal cholesterol level between different genotypes by filipin staining or lipidomic analysis. The Ubiad1N100S mouse provides a promising animal model of SCD revealing that mitochondrial dysfunction is a prominent component of the disease. The different phenotype in human and mouse may due to difference in cholesterol metabolism between species.

In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques

Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes – 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruch’s membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates.

Fluorescence Lifetimes of Drusen in Age-Related Macular Degeneration.

The purpose of this study was to characterize fundus autofluorescence lifetimes of retinal drusen in patients with AMD. Patients with AMD and retinal drusen and healthy controls of similar age were examined. A fluorescence lifetime imaging ophthalmoscope was used. Retinal autofluorescence was excited using a 473-nm pulsed laser, and fundus autofluorescence lifetimes of the central retina (30°) were measured in two distinct spectral channels (short: 498 to 560 nm [SSC]; long: 560 to 720 nm [LSC]). Mean retinal autofluorescence lifetimes, corresponding fundus autofluorescence intensity images, spectral domain optical coherence tomography, color fundus images, and clinical data were investigated. Patients were analyzed in two distinct groups (soft drusen and reticular pseudodrusen) and compared with control subjects. Sixty-four eyes of 64 patients with AMD and retinal drusen (age: mean ± SD, 78 ± 8.5 years; range, 59 to 94 years) were investigated and compared with a control group of 20 age-matched healthy subjects. Mean retinal autofluorescence lifetimes in patients with AMD was significantly prolonged compared with the healthy control eyes (mean ± SEM: SSC, 486 ± 18 vs. 332 ± 11 ps, P < 0.0001; LSC: 493 ± 9 vs. 382 ± 17 ps, P < 0.0001). Areas of drusen featured a wide range of fluorescence lifetime values. Long lifetimes were identified in areas of atrophy and in areas of intraretinal hyperreflective deposits. Short lifetimes corresponded to deposits within the photoreceptor outer segment band. Mean retinal autofluorescence lifetimes in AMD patients are significantly prolonged. Intraretinal deposits cause prolonged lifetimes, whereas deposits in the area of the outer photoreceptor segments lead to short fluorescence lifetimes.

OCT Angiography in angioid streaks without neovascular complications

PurposeTo describe the features of angioid streaks (AS) without neovascular complications using swept source optical coherence tomography.MethodsThis is a retrospective observational study.All patients underwent slit‐lamp and fundus examination, fundus photos, swept source optic coherence tomography (SS‐OCT) and OCT angiography (OCT‐A).Comparisons were made between en face OCT and OCT‐A images.ResultsSeven eyes had AS without neovascular complications, foveola was involved by the streak in 3 eyes of them.In en face OCT, we found hyper‐reflective points in 5 eyes in the deep plexus (DP), and in 2 eyes in the choriocapillaris (CC) giving a shadow in the level of the choriocapillaris in the corresponding OCT‐A.In the outer retina (OR), Streaks were detectable in patients having macular involving AS as hyposignal in the OR and the CC.Also, 5 eyes had CC diffuse rarefaction (CR) that seems more extensive than the masking from the hyper‐reflective material visible in the DP on en face‐OCT.An irregular vascular network (IVN), different from choroidal neovascularisation (CNV), was detected in 3 eyes with AS involving the macula in the level of the OR and CC. This IVN fills spaces between streaks. On structural OCT, it corresponds to flat elevation of the retinal pigmentary epithelium (RPE) with hyper reflective accumulations between the RPE and the Bruch membrane (BM).ConclusionsThis imaging tool provides new information about AS.We illustrate different findings including hyper reflective deposits, CR and IVN.CR suggests early and severe involvement of all the CC.

Fluorescence lifetimes of drusen in age‐related macular degeneration

PurposeFluorescence Lifetime Imaging Ophthalmoscopy (FLIO) allows non‐invasive in vivo measurement of fluorescence lifetimes of natural fluorophores of the retina upon excitation with a laser light. FLIO in different retinal diseases showed that the technique is useful to detect early metabolic changes and can differentiate between retinal deposits.The aim of this study was to characterize fluorescence lifetimes in retinal drusen due to age‐related macular degeneration (AMD).MethodsFLIO imaging was performed using a Fluorescence Lifetime Imaging Ophthalmoscope (Heidelberg Engineering, Germany). Autofluorescence was elicited with a 473 nm laser and decay times were measured in a short (498–560 nm) and in a long (560–720 nm) spectral channel. Fluorescence lifetime data was compared with autofluorescence intensity images, optical coherence tomography (OCT) and color fundus images. Soft drusen and reticular pseudodrusen were analysed and compared to an age matched control group.Results64 eyes from 64 patients with AMD and retinal drusen (age: mean ± SD 78 ± 8.5 years) were investigated and compared to 20 age matched healthy controls. Mean fluorescence lifetime in patients with AMD was significantly prolonged compared to the healthy control eyes (mean ± SEM; SSC 486 ± 18 ps vs 332 ± 11 ps, p &gt; 0.0001; LSC: 493 ± 9 ps vs 382 ± 17 ps, p &gt; 0.0001). Areas of drusen featured a broader range of fluorescence lifetime values. Long lifetimes were identified in areas of atrophy and intraretinal hyperreflective deposits. Areas of short lifetime corresponded to deposits within the photoreceptor outer segment band.ConclusionsMean retinal autofluorescence lifetimes in AMD were significantly prolonged compared to healthy control eyes. Intraretinal deposits caused prolonged lifetimes whereas deposits in the area of the outer photoreceptor segments lead to short fluorescence lifetimes.

Comparing optical coherence tomography findings in different aetiologies of infectious necrotising retinitis

AimsTo compare optical coherence tomography (OCT) features of active necrotising infectious retinitis (NIR) due to toxoplasmosis or herpesviruses and to determine distinctive OCT signs for these two causes of infectious...

Characterization of Corneal Involvement in Eyes With Mucous Membrane Pemphigoid by In Vivo Confocal Microscopy.

To describe the morphological features of the corneal epithelial layers, subbasal nerve plexus, stroma, and endothelium in patients with mucous membrane pemphigoid (MMP) as shown by in vivo confocal microscopy (IVCM). Central corneal images were captured from 10 healthy age-matched control eyes and 30 eyes with clinically diagnosed MMP by in vivo laser scanning confocal microscopy (HRT III RCM). Morphological changes of the corneal epithelial layers, stroma, and endothelium, characteristics of corneal nerves, and presence of inflammatory dendritic cells (DCs) were evaluated. Images obtained by IVCM from 40 eyes were analyzed. The eyes with MMP were divided into 2 groups based on clinical staging: 16 eyes with end-stage MMP and 14 eyes with non-end-stage MMP. Compared with controls, IVCM in eyes with end-stage MMP displayed severe conjunctivalization and neovascularization of the cornea, with otherwise limited identifiable cellular or structural elements. Those with non-end-stage MMP showed metaplasia of the corneal epithelial layers, presence of hyperreflective cells similar to conjunctival cells, intraepithelial defects, fibrosis of anterior stroma, and hyperreflective endothelial deposits. Images of the subbasal nerve plexus demonstrate significant reduction in density (1251.3 ± 806.9 μm/frame vs. 2688.8 ± 607.33 μm/frame, P < 0.001), increased tortuosity (2.76 ± 0.6 vs. 2.3 ± 0.42, not significant), decreased reflectivity (2.73 ± 0.4 vs. 3.46 ± 0.52, P < 0.01), and increased density of DCs (115 ± 88 cells/mm vs. 43.9 ± 28.14 cells/mm, P < 0.05) in MMP-affected eyes compared with controls. IVCM reveals profound and variable microstructural changes in the corneas of patients with MMP compared with normal controls. Our study demonstrated decreased corneal nerve density and elevated DC density in eyes with non-end-stage MMP compared with normal controls. Frequent scarring, conjunctivalization, and neovascularization observed in eyes with end-stage MMP preclude recognition by IVCM of the morphologic architecture of the corneal layers. Our findings suggest implications for using IVCM to evaluate and monitor patients with MMP.

Mapping of dendritic lesions in patients with herpes simplex keratitis using in vivo confocal microscopy.

PurposeTo produce a two-dimensional reconstruction map of dendritic lesions in patients with herpes simplex keratitis (HSK) using in vivo confocal microscopy.MethodsFour eyes of four patients (mean 65.8 years) with HSK presenting with a dendritic lesion were enrolled. Slit-lamp biomicroscopy and in vivo laser confocal microscopy were performed. Acquired confocal images at the level of the epithelium were arranged and mapped into subconfluent montages. Changes in the shape and degree of light reflection of abnormal cells and deposits around dendritic lesions as well as other corneal layers were qualitatively evaluated.ResultsMapping of dendritic lesion was successful in all cases, and the subconfluent montages clearly showed the larger image of dendritic lesion. In all cases, the dendritic lesion consisted of hyperreflective irregular epithelial cells, and was surrounded by distorted and elongated epithelial cells. In three cases, hyperreflective deposits were noted at the midline of the lesion. The corneal stroma showed a hyperreflective honeycomb pattern. In two cases, inflammatory cells were observed at the level of endothelial cell layer.ConclusionMapping of dendritic lesions in patients with HSK was successful in all patients using in vivo confocal microscopy. Cellular level observation of dendritic lesion at a relatively larger magnification may help understand the in vivo morphological change of HSK. Further study in more patients with HSK and nonherpetic dendritic lesion is needed to utilize confocal microscopy images in differential diagnosis and follow-up of the epithelial lesions with dendrite.

Flecks in Recessive Stargardt Disease: Short-Wavelength Autofluorescence, Near-Infrared Autofluorescence, and Optical Coherence Tomography.

We evaluated the incongruous observation whereby flecks in recessive Stargardt disease (STGD1) can exhibit increased short-wavelength autofluorescence (SW-AF) that originates from retinal pigment epithelium (RPE) lipofuscin, while near-infrared AF (NIR-AF), emitted primarily from RPE melanin, is usually reduced or absent at fleck positions. Flecks in SW- and NIR-AF images and spectral-domain optical coherence tomography (SD-OCT) scans were studied in 19 STGD1 patients carrying disease-causing ABCA4 mutations. Fleck spatial distribution and progression were recorded in serial AF images. Flecks observed in SW-AF images typically colocalized with darkened foci in NIR-AF images; the NIR-AF profiles were larger. The decreased NIR-AF signal from flecks preceded apparent changes in SW-AF. Spatiotemporal changes in fleck distribution usually progressed centrifugally, but in one case centripetal expansion was observed. Flecks in SW-AF images corresponded to hyperreflective deposits that progressively traversed photoreceptor-attributable bands in SD-OCT images. Outer nuclear layer (ONL) thickness negatively correlated with expansion of flecks from outer to inner retina. In the healthy retina, RPE lipofuscin fluorophores form in photoreceptor cells but are transferred to RPE; thus the SW-AF signal from photoreceptor cells is negligible. In STGD1, NIR-AF imaging reveals that flecks are predominantly hypofluorescent and larger and that NIR-AF darkening occurs prior to heightened SW-AF signal. These observations indicate that RPE cells associated with flecks in STGD1 are considerably changed or lost. Spectral-domain OCT findings are indicative of ongoing photoreceptor cell degeneration. The bright SW-AF signal of flecks likely originates from augmented lipofuscin formation in degenerating photoreceptor cells impaired by the failure of RPE.

Characteristics of the cornea in patients with pseudoexfoliation syndrome.

To quantify the morphological alterations in corneal nerve fibers and cells in patients with pseudoexfoliation syndrome (PEX) and their relationship with the presence of hyperreflective endothelial deposits observed using in vivo confocal microscopy. One eye each of 37 patients with PEX and 20 age-matched healthy control subjects was evaluated by in vivo corneal confocal microscopy. Patients with PEX were further classified into two groups: those with and without hyperreflective endothelial deposits. We evaluated the densities of basal epithelial cells, anterior and posterior stromal keratocytes, and endothelial cells and structure of sub-basal nerve fibers. The mean anterior and posterior stromal keratocyte and endothelial cell densities and corneal sub-basal nerve plexus variables were significantly lower in patients with PEX compared with those in healthy control subjects. The mean basal epithelial cell density did not significantly differ. Eyes with PEX presented decreased corneal sub-basal nerve plexus variables and cell densities in all corneas, except for the mean basal epithelial cell density. Further, a trend of lower corneal sub-basal nerve plexus measurements in patients with hyperreflective endothelial deposits compared with those without endothelial deposits was observed.

Bilateral Macular Roth Spots as a Manifestation of Subacute Endocarditis.

A 42-year-old man presented with a 2-day history of impaired vision in the right eye (OD). The best corrected visual acuity (BCVA) (LogMAR) was 1.1 for the right eye and 0.0 for the left eye (OS). Fundus examination revealed white-centered hemorrhages resembling Roth spots in both macular regions. The spectral-domain optical coherence tomography (SD-OCT) showed intraretinal pseudocysts and hyperreflective deposits in the areas corresponding to the Roth spots. Conducted blood tests revealed elevated D-dimer concentration, increased total number of neutrophils, high C-reactive protein concentration, and elevated erythrocyte sedimentation rate. Procalcitonin concentration, platelet count, and body temperature were within normal ranges. A blood culture was ordered and yielded Streptococcus mitis and intravenous antibiotics were started immediately. The patient started complaining of chest and left calf pain. The systemic examination revealed infective endocarditis accompanied by bicuspid aortic valve and paravalvular abscess formation. The patient underwent cardiac surgery with mechanical aortic valve implantation. After recovery, the patient's visual acuities improved fully. Control ophthalmic examination, including SD-OCT, showed no abnormalities.

Characterization of Punctate Inner Choroidopathy Using Enhanced Depth Imaging Optical Coherence Tomography

To perform qualitative and quantitative analyses of retinal and choroidal morphology in patients with punctate inner choroidopathy (PIC) using enhanced depth imaging optical coherence tomography (EDI-OCT). Cross-sectional, consecutive series. A total of 2242 patients attending 2 tertiary referral uveitis clinics at Moorfields Eye Hospital were screened; 46 patients with PIC diagnosis were identified, and 35 eyes (35 patients) had clinically inactive PIC had EDI-OCT images that met the inclusion criteria. Punctate inner choroidopathy lesions were qualitatively assessed for retinal features, such as (1) focal elevation of the retinal pigment epithelium (RPE), (2) focal atrophy of the outer retina/RPE, and (3) presence of sub-RPE hyperreflective deposits and choroidal features: (a) presence of focal hyperreflective dots in the inner choroid and (b) focal thinning of the choroid adjacent to PIC lesions. Quantitative analyses of the retina, choroid, and choroidal sublayers were performed, and associations with clinical and demographic data were examined. Prevalence of each lesion pattern and thickness of retinal and choroidal layers. A total of 90 discrete PIC lesions were captured; 46.6% of PIC lesions consisted of focal atrophy of the outer retina and RPE; 34.4% consisted of sub-RPE hyperreflective deposits; and 18.8% consisted of localized RPE elevation with underlying hyporeflective space. Focal hyperreflective dots were seen in the inner choroid of 68.5% of patients, with 17.1% of eyes presenting focal choroidal thinning underlying PIC lesions. By excluding high myopes, patients with "atypical" PIC had reduced retinal thickness compared with patients with "typical" PIC (246.65±30.2 vs. 270.05±24.6 μm; P = 0.04), and greater disease duration was associated with decreases in retinal thickness (r = -0.53; P = 0.01). A significant correlation was observed between best-corrected visual acuity and foveal retinal thickness (r = -0.40; P = 0.03). In a large series of patients with clinically inactive PIC, one fifth of the lesions analyzed revealed RPE elevation with underlying hyporeflective space, described before as a sign of activity and suggesting subclinical inflammation. Retinal thickness seems to be associated with disease type and duration of disease in non-highly myopic eyes. Improved visualization of the inner choroid using EDI-OCT may allow noninvasive assessment of inflammatory status.

SD-OCT Stages of Progression of Type 2 Macular Telangiectasia in a Patient followed for 3 Years

To describe the natural course of type 2 idiopathic macular telangiectasia (MT) using spectral-domain optical coherence tomography (SD-OCT). Analysis of the different stages of progression of type 2 MT during a period of 3 years using multimodal imaging, including SD-OCT correlated with angiographic and autofluorescence images. The analysis of the different steps was obtained initially from the first eye, then successively from the fellow eye when progressive changes appeared. The earliest visible alteration at SD-OCT was the interruption of the interface between inner segment and ellipsoid (IS/EL) (stage 1). The second stage was characterized by the complete interruption of both IS/EL interface and external limiting membrane (stage 2). At the next step, a wide disruption of the outer nuclear layer was noted (stage 3). The fourth stage showed a complete disorganization of the inner layers with aspect of fusion of the inner retinal layers associated with progressive atrophy of the outer layers (stage 4). Hyper-reflective deposits were found in both the internal and external retinal layers (stage 5). Small intraretinal cystoid spaces appeared in the different retinal layers (stage 6). This last feature was an earlier manifestation of the typical intraretinal cysts that are the well-known OCT appearance of type 2 MT. We describe the 6 steps of progression from earlier SD-OCT findings that led to a complete disorganization and fusion of the inner layers (probably due to changes in the Müller cells) to the typical intraretinal cysts.

Vitreal, retinal, and choroidal findings in active and scarred toxoplasmosis lesions: a prospective study by spectral-domain optical coherence tomography

The aim of our study was to investigate vitreal, retinal, and choroidal morphologic changes in active and scarred toxoplasmosis lesions using spectral-domain optical coherence tomography (SD-OCT). In this prospective study, 19 eyes of 15 consecutive patients with ocular toxoplasmosis were included. Complete ophthalmologic examination and SD-OCT were done at the initial visit and during follow-up. Retina and choroid SD-OCT protocols directed to macular area and lesions observed on clinical examination were used. Seventeen active lesions and 56 retinochoroidal scars were studied. In the acute phase, disruption, thickening, and hyper-reflectivity of the neurosensory retina with photoreceptor (PR) interruption and retinal pigment epithelial (RPE) elevation were found. The choroid became thickened and hyporeflective. During follow-up, neurosensory retinal layers thinning and disorganization, PR interruption, and RPE elevation and/or atrophy were demonstrated. The choroid returned to normal thickness and became more hyperreflective. Five active lesions presented with hyperreflective oval deposits within the vitreoretinal interface, adjacent to or far away from the lesions. During follow-up, the deposits became smaller, entered into the inner retina layers and faded with time until complete resolution. Multiple hyperreflective dots in the vitreous cavity, compatible with vitritis, and posterior hyaloid thickening were demonstrated in the acute phase, with complete resolution and detachment of the posterior hyaloid during follow-up. Four types of scars were specified according to outer retina-choroid interface changes; atrophic, elevated, deep, and combined (atrophic & elevated). Epiretinal membrane segments were found over active and scarred lesions. SD-OCT imaging showed toxoplasmic retinochoroidal lesions and scars to be complex and characterized acutely by thickening and disorganization of both the retina and underlying choroid, and following scar formation by varying degrees of thinning, often in conjunction with irregularity of the outer retinal layers.

RETINAL ARCHITECTURE RECOVERY AFTER GRID PHOTOCOAGULATION IN DIABETIC MACULAR EDEMA OBSERVED IN VIVO BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY

To identify the morphologic changes secondary to macular grid photocoagulation in diabetic macular edema in vivo using spectral domain optical coherence tomography. In this prospective cohort study, 13 consecutive patients with vision loss because of clinically significant macular edema associated with diabetes mellitus Type 2 underwent grid laser treatment (PASCAL). Best-corrected visual acuity, Spectralis optical coherence tomography, infrared fundus imaging, and biomicroscopy were performed at baseline, Day 1, Week 1, and Months 1, 2, and 3 after treatment. Fluorescein angiography was performed at baseline and at 3 months. Mean central 1-mm thickness decreased significantly from 438 ± 123 μm (mean ± SD) at baseline to 391 ± 111 μm (P < 0.05) at 3 months with a nonsignificant trend of best-corrected visual acuity improvement. A wipeout of the photoreceptor layer and the inner segment/outer segment line together with an alteration of the overlaying outer nuclear layer and external limiting membrane was seen at Day 1. The lesion was reduced to a focal hyperreflective deposit on the retinal pigment epithelium boundary. In 55% of lesions, the external limiting membrane as well as the previously interrupted inner segment/outer segment line revealed intact continuity at Month 3. In some areas, repair was incomplete indicated by a focal condensation interrupting the inner segment/outer segment line in the lesion center. In vivo imaging of morphologic lesion repair in human eyes after PASCAL grid laser of diabetic macular edema demonstrates progressive restoration of the external limiting membrane and inner segment/outer segment integrity as previously described in animal models.