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14 pages, 2160 KiB  
Article
Tracking Macular Sensitivity and Inner Retinal Thickness in Long-Term Type 1 Diabetes: A Five-Year Prospective Examination in Patients without Diabetic Retinopathy
by Guisela Fernández-Espinosa, Elvira Orduna-Hospital, María Sopeña-Pinilla, Marta Arias-Álvarez, Ana Boned-Murillo, María Dolores Díaz-Barreda, Ana Sánchez-Cano and Isabel Pinilla
Life 2024, 14(9), 1152; https://doi.org/10.3390/life14091152 - 12 Sep 2024
Viewed by 257
Abstract
The aim of the study is to compare macular sensitivity and retinal thickness in patients with long-term type 1 diabetes mellitus (DM1) without diabetic retinopathy (DR) after 5 years of follow-up. Thirty-two eyes from 32 long-term DM1 patients without DR were included. All [...] Read more.
The aim of the study is to compare macular sensitivity and retinal thickness in patients with long-term type 1 diabetes mellitus (DM1) without diabetic retinopathy (DR) after 5 years of follow-up. Thirty-two eyes from 32 long-term DM1 patients without DR were included. All participants underwent a complete ophthalmological examination, including microperimetry and spectral domain optical coherence tomography (SD-OCT). The data were compared with results from 5 years prior. The mean age of the DM1 patients was 43.19 ± 10.17 years, with a mean disease duration of 29.84 ± 8.98 years and good glycemic control. In 2023, patients exhibited a significantly worse best corrected visual acuity (BCVA) compared to 2018 (p < 0.001). DM1 patients did not show statistically significant changes in macular sensitivity over the 5-year follow-up period. Macular integrity showed significant differences between the two time points (p = 0.045). Retinal thickness showed significant differences, particularly in inner retinal layers (IRL) across most of the ETDRS areas. Long-term DM1 patients without DR lesions showed worsened macular integrity and a lower BCVA in 2023. Additionally, they displayed significant alterations in retinal thicknesses, especially in the IRL, between 2018 and 2023. These findings suggest that even in the absence of visible DR, long-term DM1 patients may experience subclinical retinal changes and functional deterioration over time, highlighting the importance of regular monitoring for the early detection and management of potential complications. Full article
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Figure 1
<p>(<b>A</b>) Sensitivity points from a right eye measured by MAIA microperimeter with the 3 concentric rings (C: central, I: internal, and E: external). (<b>B</b>) The distribution of the 37 sensitivity points represented in an ETDRS grid: 1 in the center (yellow), 12 in the 1° radius (red), 12 in the 3° radius (blue), and 12 in the 5° radius (green). One degree is equivalent to a radius of 0.3 mm; 3° to a radius of 0.9 mm; and 5° to a circle with a 1.5 mm radius. The center point and the 1° sensitivity points (0.6 mm diameters) correspond to the ETDRS 1 mm diameter center ring, and the localized sensitivity points at 3 and 5° (diameters of 1.8 and 3 mm, respectively) to the 3 mm diameter parafoveal ring of the ETDRS grid. Abbreviations: S, superior; T, temporal; I, inferior; N, nasal.</p>
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<p>The tomographic profile obtained by Spectralis SD-OCT; the automatic segmentation was performed using its software version 6.8.1.0. The abbreviations for all layers of the automated macular segmentation provided by Spectralis SD-OCT software can be found on the right margin. Abbreviations: ILM, inner limiting membrane; RNFL, retinal nerve fiber layer; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ELM, external limiting membrane; PR1, photoreceptor inner segments; PR2, photoreceptor outer segments; RPE, retinal pigment epithelium; BM, Bruch membrane.</p>
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<p>Retinal sensitivity in dB measured by the MAIA microperimeter in different MAIA areas represented in box plots. (<b>A</b>) Central ring and central point. (<b>B</b>) Internal ring. (<b>C</b>) External ring. The 2018 values are shown in green and 2023 values in blue. No values reached statistical significance. Abbreviations: MP: microperimetry; SE: superior external; TE: temporal external; IE: inferior external; NE: nasal external; SI: superior internal; TI: temporal internal; II: inferior internal; NI: nasal internal; C: central; SC: superior central; TC: temporal central; IC: inferior central; NC: nasal central; C Global: central global.</p>
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<p>(<b>A</b>) Scatter plot and regression lines of the best corrected visual acuity (BCVA) and macular integrity in 2018 (green) and 2023 (blue). The formula of the line at both time points are presented in the figure. (<b>B</b>) The violin plot representation of the BCVA in 2018 (green) and 2023 (blue). (<b>C</b>) The violin plot representation of macular integrity (MI) in 2018 (green) and 2023 (blue).</p>
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<p>The mean, standard deviation (SD), and <span class="html-italic">p</span>-values of total retinal thickness, inner retinal layers (IRL) thickness, outer retinal layers (ORL) thickness, and retinal nerve fiber layer (RNFL) thickness in μm measured by Spectralis SD-OCT and represented in the ETDRS grids from a right eye and in 2018 and in 2023. The <span class="html-italic">p</span>-values of less than 0.05 were deemed statistically significant and are shown in red and bold.</p>
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29 pages, 457 KiB  
Review
Integrated Assessment of OCT, Multimodal Imaging, and Cytokine Markers for Predicting Treatment Responses in Retinal Vein Occlusion Associated Macular Edema: A Comparative Review of Anti-VEGF and Steroid Therapies
by Marion R. Munk, Lala Ceklic, Richard Stillenmunkes, Varun Chaudhary, Nadia Waheed, Jay Chhablani, Marc D. de Smet and Anne Tillmann
Diagnostics 2024, 14(17), 1983; https://doi.org/10.3390/diagnostics14171983 - 7 Sep 2024
Viewed by 452
Abstract
Retinal vein occlusion (RVO) is a significant cause of vision loss, characterized by the occlusion of retinal veins, leading to conditions such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Macular edema (ME), a prevalent consequence of RVO, is [...] Read more.
Retinal vein occlusion (RVO) is a significant cause of vision loss, characterized by the occlusion of retinal veins, leading to conditions such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Macular edema (ME), a prevalent consequence of RVO, is the primary cause of vision impairment in affected patients. Anti-VEGF agents have become the standard treatment, showing efficacy in improving visual acuity (VA) and reducing ME. However, a subset of patients exhibit a suboptimal response to anti-VEGF therapy, necessitating alternative treatments. Corticosteroids, which address inflammatory pathways implicated in ME, have shown promise, particularly in cases resistant to anti-VEGF. This review aims to identify biomarkers that predict treatment response to corticosteroids in RVO-associated ME, utilizing multimodal imaging and cytokine assessments. Baseline imaging, including SD-OCT and OCT-A, is essential for evaluating biomarkers like hyperreflective foci (HRF), serous retinal detachment (SRF), and central retinal thickness (CRT). Elevated cytokine levels, such as IL-6 and MCP-1, correlate with ME severity and poor anti-VEGF response. Early identification of these biomarkers can guide timely transitions to corticosteroid therapy, potentially enhancing treatment outcomes. The practical conclusion of this review is that integrating biomarker assessment into clinical practice enables personalized treatment decisions, allowing for earlier and more effective management of RVO-associated ME by transitioning patients to corticosteroid therapy when anti-VEGF agents are insufficient. Advanced diagnostics and machine learning may further refine personalized treatment strategies, improving the management of RVO-associated ME. Full article
(This article belongs to the Special Issue Updates on the Diagnosis and Management of Retinal Diseases)
16 pages, 6525 KiB  
Article
Recurrent and Concurrent Prediction of Longitudinal Progression of Stargardt Atrophy and Geographic Atrophy towards Comparative Performance on Optical Coherence Tomography as on Fundus Autofluorescence
by Zubin Mishra, Ziyuan Chris Wang, Emily Xu, Sophia Xu, Iyad Majid, SriniVas R. Sadda and Zhihong Jewel Hu
Appl. Sci. 2024, 14(17), 7773; https://doi.org/10.3390/app14177773 - 3 Sep 2024
Viewed by 356
Abstract
Stargardt atrophy and geographic atrophy (GA) represent pivotal endpoints in FDA-approved clinical trials. Predicting atrophy progression is crucial for evaluating drug efficacy. Fundus autofluorescence (FAF), the standard 2D imaging modality in these trials, has limitations in patient comfort. In contrast, spectral-domain optical coherence [...] Read more.
Stargardt atrophy and geographic atrophy (GA) represent pivotal endpoints in FDA-approved clinical trials. Predicting atrophy progression is crucial for evaluating drug efficacy. Fundus autofluorescence (FAF), the standard 2D imaging modality in these trials, has limitations in patient comfort. In contrast, spectral-domain optical coherence tomography (SD-OCT), a 3D imaging modality, is more patient friendly but suffers from lower image quality. This study has two primary objectives: (1) develop an efficient predictive modeling for the generation of future FAF images and prediction of future Stargardt atrophic (as well as GA) regions and (2) develop an efficient predictive modeling with advanced 3D OCT features at ellipsoid zone (EZ) for the comparative performance in the generation of future enface EZ maps and prediction of future Stargardt atrophic regions on OCT as on FAF. To achieve these goals, we propose two deep neural networks (termed ReConNet and ReConNet-Ensemble) with recurrent learning units (long short-term memory, LSTM) integrating with a convolutional neural network (CNN) encoder–decoder architecture and concurrent learning units integrated by ensemble/multiple recurrent learning channels. The ReConNet, which incorporates LSTM connections with CNN, is developed for the first goal on longitudinal FAF. The ReConNet-Ensemble, which incorporates multiple recurrent learning channels based on enhanced EZ enface maps to capture higher-order inherent OCT EZ features, is developed for the second goal on longitudinal OCT. Using FAF images at months 0, 6, and 12 to predict atrophy at month 18, the ReConNet achieved mean (±standard deviation, SD) and median Dice coefficients of 0.895 (±0.086) and 0.922 for Stargardt atrophy and 0.864 (±0.113) and 0.893 for GA. Using SD-OCT images at months 0 and 6 to predict atrophy at month 12, the ReConNet-Ensemble achieved mean and median Dice coefficients of 0.882 (±0.101) and 0.906 for Stargardt atrophy. The prediction performance on OCT images is comparably good to that on FAF. These results underscore the potential of SD-OCT for efficient and practical assessment of atrophy progression in clinical trials and retina clinics, complementing or surpassing the widely used FAF imaging technique. Full article
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<p>A schematic of the recurrent neural network architecture. The first T to T + N columns from the top blue squares to the bottom purple squares represent multiple encoding pathways, one for each timestep. At each layer of the encoding pathway, the outputs of the encoding pathway convolutions are combined using a 2D convolutional-LSTM layer. The output of this layer is concatenated with the input of the corresponding decoding pathway convolution, as shown in the right three columns.</p>
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<p>The ensemble neural network structure. The OCT feature maps include traditional mean intensity maps and additional minimum intensity, maximum intensity, median intensity, standard deviation, skewness, kurtosis, gray-level entropy, and thickness of the EZ.</p>
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<p>A schematic of the prediction algorithm, where i in the subscript indicates the initial prediction results from ReconNet1 and f in the subscript indicates the final prediction results from ReConNet2.</p>
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<p>Example results of ReConNet. Input FAF images and labels, initial prediction, final prediction, and ground truth comparison for ReConNet with Stargardt atrophy (<b>Top</b>) and GA (<b>Bottom</b>).</p>
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<p>Example results of ReConNet. Input FAF images and labels, initial prediction, final prediction, and ground truth comparison for ReConNet with Stargardt atrophy (<b>Top</b>) and GA (<b>Bottom</b>).</p>
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<p>Example results after ReConNet-Ensemble. Input OCT feature maps, initial prediction, final prediction, and ground truth comparison for ensemble ReConNet with Stargardt atrophy. Input labels are not pictured.</p>
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<p>Example results after ReConNet1-Interval. (<b>Top</b>) Input modified FAF images, labels, interval growth prediction, and ground truth comparison with Stargardt atrophy. (<b>Middle</b> and <b>Bottom</b>) Input-modified FAF images, labels, interval growth prediction, and ground truth comparison with GA. Eighteen-month FAF images are shown for reference.</p>
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6 pages, 6332 KiB  
Brief Report
Changes in Macular Pigment Optical Density after Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration: A Pilot Study
by Gilda Cennamo, Michele Rinaldi, Flavia Chiosi and Ciro Costagliola
J. Clin. Med. 2024, 13(16), 4893; https://doi.org/10.3390/jcm13164893 - 19 Aug 2024
Viewed by 449
Abstract
Background: This study aimed to evaluate the effects of faricimab intravitreal injections in patients with exudative age macular degeneration (nAMD) after the loading dose using spectral domain optical coherence tomography (SD-OCT) and macular pigment optical density (MPOD). Methods: In this observational prospective [...] Read more.
Background: This study aimed to evaluate the effects of faricimab intravitreal injections in patients with exudative age macular degeneration (nAMD) after the loading dose using spectral domain optical coherence tomography (SD-OCT) and macular pigment optical density (MPOD). Methods: In this observational prospective study, we enlisted a total of 12 consecutive eyes of 12 patients (six females, six males; mean age 70.47 ± 2.46 years) affected by nAMD who consecutively presented to the Eye Clinic of the University of Naples “Federico II” and Monaldi Hospital of Naples, from June 2023 to December 2023. All patients received four once-monthly intravitreal injections of faricimab (6 mg/0.05 mL) (loading phase). At baseline and 1 month after the fourth faricimab monthly injection, all patients underwent assessment of best correct visual acuity (BCVA) and ophthalmic examination, including slit-lamp biomicroscopy, intraocular pressure (IOP), fundus biomicroscopy, SD-OCT, and MPOD. Results: A total of 12 eyes of 12 patients (six women, six men; mean age 70.47 ± 2.46 years) were included in this study. A statistically significant raise in BCVA and MOPD parameters was shown between baseline and after the loading phase (p < 0.001). Conclusions: Intravitreal injections of faricimab led in the short term to a significant functional and MPOD improvement along with a decrease in central macular thickness (CMT) and thus appears to be an effective treatment option without relevant adverse effects. MOPD may be considered as a prognostic factor associated with a good visual prognosis after intravitreal injections treatment. Full article
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<p>Multicolor imaging, spectral optical coherence tomography (SD-OCT), OCT angiography (OCTA), and macular pigment (MPOD) of active macular neovascularization in the right eye of a male 70-year-old patient before intravitreal injections of faricimab. The blue arrow shows intraretinal fluid and upper reflective material at the level of the external limiting membrane (ELM) and ellipsoid zone (EZ). OCTA reveals a dense vascular network in the macular region. MPOD shows a marked reduction in MPOD volume (blue color).</p>
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<p>Multicolor imaging, structural SD-OCT, OCTA, and macular pigment of the same eye after loading phase of faricimab. SD- OCT shows a resolution of subretinal fluid (blue arrow) and integrity of ELM (red arrow) and EZ (yellow arrow). OCTA reveals a reduction in the branching capillary network and MPOD shows an increase in macular pigment volume (green color).</p>
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11 pages, 4416 KiB  
Article
Novel and Previously Known Mutations of the KCNV2 Gene Cause Various Variants of the Clinical Course of Cone Dystrophy with Supernormal Rod Response in Children
by Almaqdad Alsalloum, Ilya Mosin, Kristina Shefer, Natalia Mingaleva, Alexander Kim, Sofya Feoktistova, Boris Malyugin, Ernest Boiko, Shamil Sultanov, Olga Mityaeva and Pavel Volchkov
J. Clin. Med. 2024, 13(16), 4592; https://doi.org/10.3390/jcm13164592 - 6 Aug 2024
Viewed by 669
Abstract
Background/Objectives: Cone dystrophy with supernormal rod response (CDSRR) is a rare autosomal recessive retinal disorder characterized by a delayed and markedly decreased photoreceptor response. In this article, we aim to describe the clinical course and associated molecular findings in children with cone [...] Read more.
Background/Objectives: Cone dystrophy with supernormal rod response (CDSRR) is a rare autosomal recessive retinal disorder characterized by a delayed and markedly decreased photoreceptor response. In this article, we aim to describe the clinical course and associated molecular findings in children with cone dystrophy with supernormal rod response associated with recessive mutations in the KCNV2 gene, which encodes a subunit (Kv8.2) of the voltage-gated potassium channel. Methods: The genetic testing of two patients included the next-generation sequencing of a retinal dystrophy panel and direct Sanger sequencing to confirm KCNV2 gene variants, in addition to an electroretinogram (ERG) and spectral domain optical coherence tomography (SD-OCT). Results: Cone dystrophy with supernormal rod response is associated with identified variants in the KCNV2 gene. The genetic analysis of the first case identified a compound heterozygous mutation in the KCNV2 gene, including a de novo nonsense duplication at cDNA position 1109, which led to the premature termination of the p.Lys371Ter codon in the second extracellular domain of the protein. Two patients showed changes in the full-field electroretinogram, especially in the first case, which demonstrated a close to supernormal total electroretinogram amplitude. This study increased the range of the KCNV2 mutation database, added an unreported de novo substitution pattern to KCNV2 gene variants, and linked it to the evaluated clinical studies. Conclusions: The initial clinical manifestations were varied, but both patients presented with hypermetropia and slight exotropia. The ERG findings are characteristic of KCNV2 mutations, and patients exhibited an increased b-wave latency in DA3.0 ERG (combined rod–cone response). Full article
(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Retinal Degeneration)
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<p>Fundus photos, fundus autofluorescence (FAF) and optical coherence tomography (OCT) of the first case in both eyes. (<b>a</b>,<b>b</b>) Fundusoscopy shows that the optic disc is pink, with clear contours and normal retinal vessels; (<b>c</b>,<b>d</b>) FAF shows an enlarged macular reflex that is somewhat darkened and blurred; (<b>e</b>,<b>f</b>) OCT shows the perspicuous thinning of the retina in all layers, and is more pronounced in the foveal zone.</p>
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<p>Fundus photos, fundus autofluorescence (FAF) and optical coherence tomography (OCT) of the second case in both eyes. (<b>a</b>,<b>b</b>) The last fundoscopy reveals a standard optic disc and retinal vessel morphology with macular and foveal reflexes absent. (<b>c</b>,<b>d</b>) FAF presents symmetrical abnormal spots of hypoautofluorescence surrounded by a ring of hyperautofluorescence; (<b>e</b>,<b>f</b>) OCT shows a slight decrease in the average thickness of the neuroepithelium with the absence of the myoid and ellipsoid zones of the fovea.</p>
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<p>Full−field ERG in the first and second cases is comparable with a normal ERG. The first patient ERG was close to supernormal. The scotopic rod–cone response revealed an increase in the latency of the a− and b− waves. ERG is subnormal; the amplitudes of a–b waves are reduced. The flicker response amplitude was found to be reduced compared to the norm. The second patient’s ERG revealed a decrease in the amplitude and an increase in the latent period of the b-wave in both cone and rod responses. The amplitude of the flicker ERG response decreased compared to the age norm.</p>
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<p>Direct sequencing of the <span class="html-italic">KCNV2</span> gene in the first and second patients. The first patient revealed a de novo mutation, c.1109dup, and another at position c.859C&gt;T, forming a complex heterozygous mutation in the proband. The second patient revealed a complex heterozygous mutation, containing c.754A&gt;T and c.775G&gt;A substitutions. Substitutions are marked with asterisks.</p>
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<p>Schematic diagram of the <span class="html-italic">KCVN2</span> potassium channel subunit. The structure of the alpha subunit of the potential-dependent potassium channel is represented by N-terminal A- and B-boxes (NABs), transmembrane domains (S1–S6), extracellular domains, and a P loop motif between S5 and S6. The approximate location of mutations (black dots) related to the patients is shown in the diagrammatic structure in blue and red for the first and second cases, respectively.</p>
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19 pages, 5473 KiB  
Article
Arylphthalide Delays Diabetic Retinopathy via Immunomodulating the Early Inflammatory Response in an Animal Model of Type 1 Diabetes Mellitus
by Francisco Martín-Loro, Fátima Cano-Cano, María J. Ortega, Belén Cuevas, Laura Gómez-Jaramillo, María del Carmen González-Montelongo, Jan Cedric Freisenhausen, Almudena Lara-Barea, Antonio Campos-Caro, Eva Zubía, Manuel Aguilar-Diosdado and Ana I. Arroba
Int. J. Mol. Sci. 2024, 25(15), 8440; https://doi.org/10.3390/ijms25158440 - 2 Aug 2024
Viewed by 695
Abstract
Diabetic retinopathy (DR) is one of the most prevalent secondary complications associated with diabetes. Specifically, Type 1 Diabetes Mellitus (T1D) has an immune component that may determine the evolution of DR by compromising the immune response of the retina, which is mediated by [...] Read more.
Diabetic retinopathy (DR) is one of the most prevalent secondary complications associated with diabetes. Specifically, Type 1 Diabetes Mellitus (T1D) has an immune component that may determine the evolution of DR by compromising the immune response of the retina, which is mediated by microglia. In the early stages of DR, the permeabilization of the blood–retinal barrier allows immune cells from the peripheral system to interact with the retinal immune system. The use of new bioactive molecules, such as 3-(2,4-dihydroxyphenyl)phthalide (M9), with powerful anti-inflammatory activity, might represent an advance in the treatment of diseases like DR by targeting the immune systems responsible for its onset and progression. Our research aimed to investigate the molecular mechanisms involved in the interaction of specific cells of the innate immune system during the progression of DR and the reduction in inflammatory processes contributing to the pathology. In vitro studies were conducted exposing Bv.2 microglial and Raw264.7 macrophage cells to proinflammatory stimuli for 24 h, in the presence or absence of M9. Ex vivo and in vivo approaches were performed in BB rats, an animal model for T1D. Retinal explants from BB rats were cultured with M9. Retinas from BB rats treated for 15 days with M9 via intraperitoneal injection were analyzed to determine survival, cellular signaling, and inflammatory markers using qPCR, Western blot, or immunofluorescence approaches. Retinal structure images were acquired via Spectral-Domain–Optical Coherence Tomography (SD-OCT). Our results show that the treatment with M9 significantly reduces inflammatory processes in in vitro, ex vivo, and in vivo models of DR. M9 works by inhibiting the proinflammatory responses during DR progression mainly affecting immune cell responses. It also induces an anti-inflammatory response, primarily mediated by microglial cells, leading to the synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). Ultimately, in vivo administration of M9 preserves the retinal integrity from the degeneration associated with DR progression. Our findings demonstrate a specific interaction between both retinal and systemic immune cells in the progression of DR, with a differential response to treatment, mainly driven by microglia in the anti-inflammatory action. In vivo treatment with M9 induces a switch in immune cell phenotypes and functions that contributes to delaying the DR progression, positioning microglial cells as a new and specific therapeutic target in DR. Full article
(This article belongs to the Special Issue Advances in the Pathophysiology and Treatment of Diabetic Retinopathy)
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<p>M9 effects on cellular viability and nitrites production in LPS-stimulated microglial and macrophage cells. Viability was determined using crystal violet staining in Bv.2 microglial cells (<b>A</b>) and Raw264.7 macrophage cells (<b>B</b>). Cells were treated for 24 h with different concentrations of M9 (0.1–25 μM). Nitrites accumulation was analyzed and compared to the basal levels in Bv.2 microglial cells (<b>C</b>) and Raw264.7 macrophage cells (<b>D</b>). Cell cultures were treated with LPS (200 ng/mL), M9 (10 μM), or LPS plus M9 (1 and 10 μM) for 24 h. The results are presented as mean ± S.E.M. The fold change relative to the basal condition is shown. (<span class="html-italic">n</span> = 4 independent experiments) * <span class="html-italic">p</span> ≤ 0.05 vs. basal, <sup>#</sup> <span class="html-italic">p</span> ≤ 0.05 vs. LPS, and <sup>φ</sup> <span class="html-italic">p</span> ≤ 0.05 vs. LPS + M9 (1 μM) treatment (one-way ANOVA followed by Bonferroni <span class="html-italic">t</span>-test). ns (no significant differences).</p>
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<p>Protective effects of M9 against LPS stimulation of proinflammatory mediators in microglial and macrophage cells. <span class="html-italic">Nos2</span> mRNA values were determined using qRT-PCR in Bv.2 microglial cells (<b>A</b>) and Raw264.7 macrophage cells (<b>B</b>) after treatment with LPS (200 ng/mL), M9 (10 µM), or LPS plus M9 for 24 h. iNOS protein levels were analyzed using Western blot in protein extracts from above Bv.2 microglial cells (<b>C</b>) or Raw264.7 macrophage cells (<b>D</b>) treated with LPS, M9, or LPS + M9. α-tubulin was used as loading control. <span class="html-italic">Il1b</span>, <span class="html-italic">Il6</span>, and <span class="html-italic">Tnfa</span> mRNA levels were determined using qRT-PCR in Bv.2 microglial cells (<b>E</b>) and Raw264.7 macrophage cells (<b>F</b>). Data were normalized to <span class="html-italic">Gapdh</span> gene expression. The results are presented as means ± S.E.M (<span class="html-italic">n</span> = 5 independent experiments). Fold changes are calculated relative to the basal value. * <span class="html-italic">p</span> ≤ 0.05 vs. basal treatment, <sup>#</sup> <span class="html-italic">p</span> ≤ 0.05 vs. LPS treatment (one-way ANOVA followed by Bonferroni <span class="html-italic">t</span>-test).</p>
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<p>Protective effects of M9 against LPS-mediated activation of the inflammasome in microglia and macrophage cells. Bv.2 microglial cells and Raw264.7 macrophage cells were treated for 24 h with LPS (200 ng/mL) or LPS plus M9 (10 µM). (<b>A</b>) Bv.2 microglial cells and (<b>B</b>) Raw264.7 macrophage cells; <span class="html-italic">Nlrp3</span> mRNA levels were determined using qRT-PCR. Data were normalized to <span class="html-italic">Gapdh</span> gene expression. Protein extracts from Bv.2 microglia cells (<b>C</b>) and Raw264.7 macrophage cells (<b>D</b>) were analyzed using Western blot with antibody against IL1β. α-Tubulin was used as a loading control. The results are presented as mean ± S.E.M. The fold change relative to the basal condition is shown. * <span class="html-italic">p</span> ≤ 0.05 vs. basal treatment, <sup>#</sup> <span class="html-italic">p</span> ≤ 0.05 vs. LPS treatment (one-way ANOVA followed by Bonferroni <span class="html-italic">t</span>-test).</p>
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<p>The anti-inflammatory response is mediated by HO-1 and arginase-1 in Bv.2 microglial and Raw264.7 macrophage cells. Bv.2 microglial cells and Raw264.7 macrophage cells were treated for 24 h with LPS (200 ng/mL) or LPS plus M9 (10 µM). Protein extracts from Bv.2 microglial cells (<b>A</b>,<b>E</b>) and Raw264.7 macrophage cells (<b>B</b>,<b>F</b>) were analyzed using Western blot with antibodies against HO-1 and arginase-1. α-Tubulin was used as a loading control. <span class="html-italic">Arg1</span> mRNA levels in Bv.2 microglial cells (<b>C</b>) and Raw264.7 macrophage cells (<b>D</b>) were determined using qRT-PCR. Data were normalized to <span class="html-italic">Gapdh</span> gene expression The results are presented as mean ± S.E.M. The fold change relative to the basal condition is shown. * <span class="html-italic">p</span> ≤ 0.05 vs. basal treatment, <sup>#</sup> <span class="html-italic">p</span> ≤ 0.05 vs. LPS treatment (one-way ANOVA followed by Bonferroni <span class="html-italic">t</span>-test).</p>
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<p>M9 inhibited the activation of NFkB-mediated signaling with P38α-MAPK phosphorylation in LPS-stimulated microglial cells. Bv.2 microglial cells were treated for 24 h with LPS (200 ng/mL) or LPS plus M9 (10 µM) for the time course indicated. (<b>A</b>) Protein extracts were analyzed using Western blot with antibodies against phosphorylated(p)-P38α MAPK, total P38α-MAPK, (<b>B</b>) phosphorylated (p)-JNK, and total JNK. α-Tubulin was used as a loading control. The results are presented as mean ± S.E.M. The ratios between the indicated proteins and the fold changes relative to the basal values are shown. * <span class="html-italic">p</span> ≤ 0.05 vs. basal treatment, <sup>&amp;</sup> <span class="html-italic">p</span> ≤ 0.05 vs. LPS treatment (one-way ANOVA followed by Bonferroni <span class="html-italic">t</span>-test). (<b>C</b>) Confocal immunofluorescence assessment of the nuclear translocation of P65-NFkB (green channel). Nuclear regions were determined by counterstaining nuclear DNA with DAPI (blue channel). White arrows indicate the P65-NFkB nuclear or cytoplasmic localization.</p>
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<p>Macrophage-conditioned medium stimulated with LPS or LPS + M9 induces the inflammatory response of the microglia. Macrophage markers in the retina from 7-week-old BB and WT rats. (<b>A</b>) <span class="html-italic">Mcp1</span> and <span class="html-italic">Cd68</span> mRNA values were determined using qRT-PCR. (<span class="html-italic">n</span> = 5 retina per condition). Bv.2 microglial cells were treated for 24 h with conditioned medium from Raw264.7 cells cultured previously with LPS (200 ng/mL) or LPS plus M9 (10 µM) for 24 h. (<b>B</b>) Nitrite accumulation was analyzed and related to the basal levels, and <span class="html-italic">Nos2</span> mRNA values were determined using qRT-PCR. Data were normalized to <span class="html-italic">Gapdh</span> gene expression. (<b>C</b>) Anti-inflammatory mediators <span class="html-italic">Arg1</span> and <span class="html-italic">Hmox1 mRNA</span> values were analyzed using qRT-PCR. (<b>D</b>) Proinflammatory cytokines <span class="html-italic">Il1b</span>, <span class="html-italic">Tnfa</span>, and <span class="html-italic">Il6</span> mRNA values were determined using qRT-PCR. Data were normalized to <span class="html-italic">Gapdh</span> gene expression. The results are presented as mean ± S.E.M (<span class="html-italic">n</span> = 4 independent experiments). Fold changes are calculated relative to the basal value. * <span class="html-italic">p</span> ≤ 0.05 vs. basal treatment, <sup>#</sup> <span class="html-italic">p</span> ≤ 0.05 vs. LPS<sub>Cond</sub> treatment, <sup>&amp;</sup> <span class="html-italic">p</span> ≤ 0.05 vs. basal<sub>Cond</sub> treatment (one-way ANOVA followed by Bonferroni <span class="html-italic">t</span>-test; or <span class="html-italic">t</span>-test).</p>
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<p>M9 treatment in retinal explants from BB rats decreased inflammatory events and induced anti-inflammatory response. Retinal explants from 7-week-old BB rats were treated for 24 h with M9 (20 μM) or vehicle. (<b>A</b>) <span class="html-italic">Il1b</span>, <span class="html-italic">Tnfa</span>, <span class="html-italic">Il6</span>, and <span class="html-italic">Nlpr3</span> mRNA values were determined using qRT-PCR. Data were normalized to <span class="html-italic">Gapdh</span> gene expression. (<b>B</b>) Protein extracts were analyzed using Western blot with antibodies against iNOS, arginase-1, or HO-1. α-Tubulin was used as a loading control. The results are presented as mean ± S.E.M (<span class="html-italic">n</span> = 5 retina per condition). The fold change relative to the basal condition is shown. * <span class="html-italic">p</span> ≤ 0.05 vs. BB retinal explant basal condition value (<span class="html-italic">t-</span>test). (<b>C</b>) Retinal explants from 7-week-old BB rats were treated for 24 h with M9 (20 μM) (right panel) or with vehicle (left panel). Immunostaining for GFAP (green) was carried out in whole retinas. Representative images are shown (<span class="html-italic">n</span> = 5 retinas per condition).</p>
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<p>M9 treatment reduces in vivo DR progression in BB rats. BB rats were treated with M9 (600 µg/kg/day) via i.p. for 15 days. (<b>A</b>) Total, INL, and ONL retinal thickness measured on SD-OCT. The results are presented as mean ± S.E.M. * <span class="html-italic">p</span> ≤ 0.05 vs. BB rat 7-weeks old, <sup>#</sup> <span class="html-italic">p</span> ≤ 0.05 vs. BB rat vehicle value. (<b>B</b>) <span class="html-italic">Il1b</span>, <span class="html-italic">Tnfa</span>, and <span class="html-italic">Nlpr3</span> mRNA values were determined using qRT-PCR. Data were normalized to <span class="html-italic">Gapdh</span> gene expression. Fold changes are calculated relative to the basal value. * <span class="html-italic">p</span> ≤ 0.05 vs. BB rat vehicle condition value (<span class="html-italic">t</span>-test). (<b>C</b>) Protein extracts were analyzed using Western blot with antibodies against arginase-1, HO-1, or NLRP3. α-Tubulin was used as a loading control. (<b>D</b>) GFAP immunostaining (green) in retinal sections counterstained with DAPI (blue). (<b>E</b>) Immunostaining and (<b>F</b>) quantification of arginase-1 (red) (arginase-1<sup>+</sup>) and IBA-1 (IBA-1<sup>+</sup>) (green) positive cells in retinal sections counterstained with DAPI (blue). Data are expressed as mean ± SD (<span class="html-italic">n</span> = 6 retinas per condition). * <span class="html-italic">p</span>-value &lt; 0.05, Student’s <span class="html-italic">t</span>-test between IBA-1<sup>+</sup> and arginase-1<sup>+</sup> cell subtypes. Scale = 20 μm. Dashed boxes indicate the zoom area showed. White arrows indicate the immune colocalization for arginase-1<sup>+</sup> and IBA-1<sup>+</sup> cells (yellow). ONL (outer nuclear layer), INL (inner nuclear layer), and GCL (ganglion cell layer).</p>
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16 pages, 5670 KiB  
Article
Age-Related Retinal Layer Thickness Changes Measured by OCT in APPNL-F/NL-F Mice: Implications for Alzheimer’s Disease
by Lidia Sánchez-Puebla, Rosa de Hoz, Elena Salobrar-García, Alberto Arias-Vázquez, María González-Jiménez, Ana I. Ramírez, José A. Fernández-Albarral, José A. Matamoros, Lorena Elvira-Hurtado, Takaomi C. Saido, Takashi Saito, Carmen Nieto Vaquero, María I. Cuartero, María A. Moro, Juan J. Salazar, Inés López-Cuenca and José M. Ramírez
Int. J. Mol. Sci. 2024, 25(15), 8221; https://doi.org/10.3390/ijms25158221 - 27 Jul 2024
Viewed by 821
Abstract
In Alzheimer’s disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining [...] Read more.
In Alzheimer’s disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans. Full article
(This article belongs to the Special Issue Advances in Animal Models in Biomedical Research, 2nd Edition)
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<p>Representation of retinal-sector thickness in the different retinal layers of C57BL/6J mice at 6, 9, 12, 15, 17, and 20 months of age. For each time studied, n = 6. (RNFL-GCL: retinal nerve fiber layer and ganglion cell layer complex; IPL: inner plexiform layer; INL: inner nuclear layer; OPL: outer plexiform layer; ONL: outer nuclear layer. N1: inner nasal ring; N2: outer nasal ring; S1: inner superior ring; S2: outer superior ring; T1: inner temporal ring; T2: outer temporal ring; I1: inner inferior ring; and I2: outer inferior ring.) Significance values were set to * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Representation of retinal-sector thickness in the different retinal layers of <span class="html-italic">APP<sup>NL-F/NL-F</sup></span> mice at 6, 9, 12, 15, 17, and 20 months of age. For each time studied, n = 6. (RNFL-GCL: retinal nerve fiber layer and ganglion cell layer complex; IPL: inner plexiform layer; INL: inner nuclear layer; OPL: outer plexiform layer; ONL: outer nuclear layer. N1: inner nasal ring; N2: outer nasal ring; S1: inner superior ring; S2: outer superior ring; T1: inner temporal ring; T2: outer temporal ring; I1: inner inferior ring; and I2: outer inferior ring.) Significance values were set to * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Representative images of the SD-OCT analysis and colorimetric representation of the retinal layers’ thickness differences in each study group between the <span class="html-italic">APP<sup>NL-F/NL-F</sup></span> and WT groups. At each study time and in each group, n = 6. (RNFL-GCL: retinal nerve fiber layer and ganglion cell layer complex; IPL: inner plexiform layer; INL: inner nuclear layer; OPL: outer plexiform layer; and ONL: outer nuclear layer. ETDRS rings of 1-, 2-, and 3-mm diameters.) Blue tones: thinning; red tones: thickening. Significance values were set to • <span class="html-italic">p</span> &lt; 0.05 and •• <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Illustrative diagram of the structural findings of the retina of the <span class="html-italic">APP<sup>NL-F/NL-F</sup></span> murine model compared to the WT model. The timeline reveals early neurodegenerative processes caused by the accumulation of beta-amyloid oligomers, followed by neuroinflammatory processes mediated by the activation of macro- and microglia and, ultimately, the accumulation of beta-amyloid plaques, leading to the neurodegeneration of the outer retina and the death of photoreceptors. Blue tones: thinning; red tones: thickening. Significance values were set to • <span class="html-italic">p</span> &lt; 0.05 and •• <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>(<b>A</b>). Mouse retinal layer observed via optical coherence tomography (OCT). (<b>B</b>) Retinal sectors: superior (S), temporal (T), inferior (I), and nasal (N). (1) Sectors of the inner ring (2 mm in diameter) and (2) sectors of the outer ring (3 mm in diameter). The central gray circle has not been analyzed because it corresponds to the exit of the vessels. (ILM: inner limiting membrane; RNFL-GCL: retinal nerve fiber layer and ganglion cell layer complex; IPL: inner plexiform layer; INL: inner nuclear layer; OPL: outer plexiform layer; ONL: outer nuclear layer; ELM: external limiting membrane; and BM: Bruch’s membrane.)</p>
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8 pages, 418 KiB  
Article
Comparison of Eye Axial Length Measurements Taken Using Partial Coherence Interferometry and OCT Biometry
by Nicola Rizzieri and Alessio Facchin
Vision 2024, 8(3), 46; https://doi.org/10.3390/vision8030046 - 26 Jul 2024
Viewed by 789
Abstract
This study evaluates the inter-device measurement properties of partial coherence interferometry (PCI) and spectral domain optical coherence tomography (SD-OCT) in measuring axial length, particularly for myopia management. We recruited 82 eyes from 41 adult participants with a mean age of 31.0 ± 17.6 [...] Read more.
This study evaluates the inter-device measurement properties of partial coherence interferometry (PCI) and spectral domain optical coherence tomography (SD-OCT) in measuring axial length, particularly for myopia management. We recruited 82 eyes from 41 adult participants with a mean age of 31.0 ± 17.6 years and a mean spherical equivalent of −2.20 ± 2.28 D. Axial length was measured using SD-OCT and PCI for both the right and left eyes. Agreement between the two measurements was assessed using Bland–Altman analysis, and graphs and values were compared with linear mixed models. The results show a near-to-zero and non-significant bias between measurements. The 95% limits of agreement showed a value of 0.06 mm. Both devices can accurately measure the axial length. OCT biometry performed with SD-OCT can be successfully interchanged with partial coherence interferometry, but they should be cautiously interchanged when performing longitudinal comparisons. Full article
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<p>A Bland–Altman plot of the measurements of axial length (mm) obtained by B-OCT and PCI. The AL mean value is shown in the abscissa, while the difference between AL measurements is shown in the ordinate (B-OCT minus PCI). From top to bottom, the three horizontal dashed lines denote the upper limit of agreement (LoA), the mean bias, and the lower limit of agreement. Linear regression is represented by the continuous red line.</p>
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15 pages, 2576 KiB  
Article
Quantification of Human Photoreceptor–Retinal Pigment Epithelium Macular Topography with Adaptive Optics–Optical Coherence Tomography
by Zhuolin Liu, Samira Aghayee, Somayyeh Soltanian-Zadeh, Katherine Kovalick, Anant Agrawal, Osamah Saeedi, Catherine Cukras, Emily Y. Chew, Sina Farsiu and Daniel X. Hammer
Diagnostics 2024, 14(14), 1518; https://doi.org/10.3390/diagnostics14141518 - 15 Jul 2024
Viewed by 901
Abstract
Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important [...] Read more.
Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important for understanding the etiology, mechanisms, and progression of many retinal diseases. However, the three-dimensional cellular morphology of the PR-RPE complex in living human eyes has not been completely described due to limitations in imaging techniques. We used the cellular resolution and depth-sectioning capabilities of a custom, high-speed Fourier domain mode-locked laser-based adaptive optics–optical coherence tomography (FDML-AO-OCT) platform to characterize human PR-RPE complex topography across the temporal macula from eleven healthy volunteers. With the aid of a deep learning algorithm, key metrics were extracted from the PR-RPE complex of averaged AO-OCT volumes including PR and RPE cell density, PR outer segment length (OSL), and PR/RPE ratio. We found a tight grouping among our cohort for PR density, with a mean (±SD) value of 53,329 (±8106) cells/mm2 at 1° decreasing to 8669 (±737) cells/mm2 at 12°. We observed a power function relationship between eccentricity and both PR density and PR/RPE ratio. We found similar variability in our RPE density measures, with a mean value of 7335 (±681) cells/mm2 at 1° decreasing to 5547 (±356) cells/mm2 at 12°, exhibiting a linear relationship with a negative slope of −123 cells/mm2 per degree. OSL monotonically decreased from 33.3 (±2.4) µm at 1° to 18.0 (±1.8) µm at 12°, following a second-order polynomial relationship. PR/RPE ratio decreased from 7.3 (±0.9) µm at 1° to 1.5 (±0.1) µm at 12°. The normative data from this investigation will help lay a foundation for future studies of retinal pathology. Full article
(This article belongs to the Special Issue High-Resolution Retinal Imaging: Hot Topics and Recent Developments)
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<p>AO-OCT image acquisition example for a 33-year-old volunteer (8195). (<b>A</b>) Spectralis SLO image with nine AO-OCT imaging regions overlaid (black border). (<b>B</b>) Cross-sectional AO-OCT B-scan view of the PR-RPE complex along the temporal raphe at the region denoted by a white dashed line in (<b>A</b>). (<b>C</b>) Montage of RPE mosaics with AO-OCT. (<b>D</b>) Magnified 250 × 250 µm subregions of PR (top) and RPE (bottom) mosaic from three selected locations at fovea, 6T, and 12T. PR en face images were generated by average intensity projection across the inner segment/outer segment junction (IS/OS) and cone outer segment tip (COST) layers. The whole montage of PR and RPE of all study volunteers are provided in the <a href="#app1-diagnostics-14-01518" class="html-app">Supplementary Materials</a>. Scale bars = 200 µm.</p>
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<p>AO-OCT image processing and analysis approach for extracting outer retinal cell morphology. (<b>A</b>) Spectralis SLO image of a 32-year-old volunteer (1060) with AO-OCT imaging region overlay (black border). (<b>B</b>) AO-OCT montage of RPE mosaics showing 13 selected ROIs where PR-RPE complex quantification was performed. Magenta- and cyan-colored regions delineate areas used for cone photoreceptor and RPE quantification, respectively. For each ROI, the PR and RPE en face images are segmented and extracted from the average AO-OCT volume. Representative PR and RPE quantification results at (<b>C</b>) 3T, (<b>D</b>) 7T, and (<b>E</b>) 11T. For (<b>C</b>–<b>E</b>), images in rows from the left to right show RPE mosaic, Voronoi map with each RPE cell marked in cyan color, PR mosaic with cell centers marked in magenta color, superimposed RPE Voronoi map and PR locations, and segmented PR outer segments at the B-scans marked with the dashed white lines.</p>
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<p>AO-OCT measurement of PR-RPE complex morphology with retinal eccentricity. (<b>A</b>) Cone PR density, (<b>B</b>) RPE density, (<b>C</b>) cone PR OSL, and (<b>D</b>) PR/RPE ratio. The black symbols are the mean values for our study cohort. The solid black lines represent the power/linear/polynomial fits to the mean data using Pearson’s correlation coefficient.</p>
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<p>Reproducibility of AO-OCT PR-RPE complex measurements. (<b>A</b>–<b>C</b>) PR density, OSL, and RPE density measurements for three AO-OCT imaging sessions (light blue/orange symbols) and mean ± SD (dark-blue/brown symbol) for seven volunteers with overall cohort mean (solid line) and SD (dashed line). (<b>D</b>–<b>F</b>) Plot of normalized value (<math display="inline"><semantics> <mrow> <mi>x</mi> <mo>/</mo> <mover> <mi>x</mi> <mo>¯</mo> </mover> </mrow> </semantics></math>) vs. <span class="html-italic">x</span>, where <math display="inline"><semantics> <mrow> <mover> <mi>x</mi> <mo>¯</mo> </mover> </mrow> </semantics></math> denotes mean value, illustrating the spread of repeat measurements for PR density (d), OSL, and RPE density (d) measurements. Dashed lines indicate overall cohort ±SD.</p>
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<p>AO-OCT measurement of RPE density as compared to (<b>A</b>) in vivo studies [<a href="#B17-diagnostics-14-01518" class="html-bibr">17</a>,<a href="#B18-diagnostics-14-01518" class="html-bibr">18</a>,<a href="#B20-diagnostics-14-01518" class="html-bibr">20</a>,<a href="#B21-diagnostics-14-01518" class="html-bibr">21</a>,<a href="#B22-diagnostics-14-01518" class="html-bibr">22</a>,<a href="#B23-diagnostics-14-01518" class="html-bibr">23</a>,<a href="#B26-diagnostics-14-01518" class="html-bibr">26</a>,<a href="#B27-diagnostics-14-01518" class="html-bibr">27</a>,<a href="#B30-diagnostics-14-01518" class="html-bibr">30</a>] and (<b>B</b>) ex vivo studies [<a href="#B39-diagnostics-14-01518" class="html-bibr">39</a>,<a href="#B40-diagnostics-14-01518" class="html-bibr">40</a>,<a href="#B41-diagnostics-14-01518" class="html-bibr">41</a>,<a href="#B42-diagnostics-14-01518" class="html-bibr">42</a>,<a href="#B43-diagnostics-14-01518" class="html-bibr">43</a>,<a href="#B44-diagnostics-14-01518" class="html-bibr">44</a>,<a href="#B45-diagnostics-14-01518" class="html-bibr">45</a>,<a href="#B46-diagnostics-14-01518" class="html-bibr">46</a>]. The dashed lines denote ± SD from the mean.</p>
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<p>Comparison of AO-OCT measurements with published literature for (<b>A</b>) cone PR density [<a href="#B29-diagnostics-14-01518" class="html-bibr">29</a>], (<b>B</b>) PR/RPE ratio [<a href="#B21-diagnostics-14-01518" class="html-bibr">21</a>,<a href="#B22-diagnostics-14-01518" class="html-bibr">22</a>,<a href="#B27-diagnostics-14-01518" class="html-bibr">27</a>,<a href="#B30-diagnostics-14-01518" class="html-bibr">30</a>], and (<b>C</b>) PR OSL [<a href="#B27-diagnostics-14-01518" class="html-bibr">27</a>,<a href="#B47-diagnostics-14-01518" class="html-bibr">47</a>,<a href="#B48-diagnostics-14-01518" class="html-bibr">48</a>]. The solid line denotes mean values and the dashed lines represent ±SD for the entire study cohort.</p>
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18 pages, 14132 KiB  
Article
Retinal Vascular and Structural Changes in the Murine Alzheimer’s APPNL-F/NL-F Model from 6 to 20 Months
by Lidia Sánchez-Puebla, Inés López-Cuenca, Elena Salobrar-García, María González-Jiménez, Alberto Arias-Vázquez, José A. Matamoros, Ana I. Ramírez, José A. Fernández-Albarral, Lorena Elvira-Hurtado, Takaomi C. Saido, Takashi Saito, Carmen Nieto-Vaquero, María I. Cuartero, María A. Moro, Juan J. Salazar, Rosa de Hoz and José M. Ramírez
Biomolecules 2024, 14(7), 828; https://doi.org/10.3390/biom14070828 - 10 Jul 2024
Viewed by 1185
Abstract
Alzheimer’s disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at [...] Read more.
Alzheimer’s disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models. Full article
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<p>Summary of materials and methods. The upper part shows the study groups and study times. In the lower part are the images of the vascular plexuses obtained by OCTA (SVC: superficial vascular complex, ICP: intermediary capillary plexus and DCP: deep capillary plexus) and the OCT segmentation of the inner and outer retina (ILM: inner limiting membrane, ELM: external limiting membrane, and BM: Bruch’s membrane).</p>
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<p>Representative SVC OCTA images and interval scatter plot from WT and <span class="html-italic">APP<sup>NL-F/NL-F</sup></span> mice at 6, 9, 12, 15, 17, and 20 months of age. Vessel area, total number of junctions, branching index, total vessel length, average vessel length, total number of end points, and lacunarity were quantified with AngioTool. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001. SVC: superficial vascular complex. (n = 6 for each study group at each time point. The error bars correspond to the standard deviation).</p>
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<p>Representative ICP OCTA images and interval scatter plot from WT and <span class="html-italic">APP<sup>NL-F/NL-F</sup></span> mice at 6, 9, 12, 15, 17, and 20 months of age. Vessel area, total number of junctions, branching index, total vessel length, average vessel length, total number of end points, and lacunarity were quantified with AngioTool. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01. ICP: intermediate capillary plexus. (n = 6 for each study group at each time point. The error bars correspond to the standard deviation).</p>
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<p>Representative DCP OCTA images and interval scatter plot from WT and APP<sup>NL-F/NL-F</sup> mice at 6, 9, 12, 15, 17, and 20 months of age. Vessel area, total number of junctions, branching index, total vessel length, average vessel length, total number of end points, and lacunarity were quantified with AngioTool. * <span class="html-italic">p</span> &lt; 0.05. DCP: deep capillary plexus. (n = 6 for each study group at each time point. The error bars correspond to the standard deviation).</p>
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<p>Colorimetric representation of inner and outer retinal thickness differences in each study time point between the <span class="html-italic">APP<sup>NL-F/NL-F</sup></span> and WT groups. ETDRS rings of 1, 2, and 3 mm diameters. Blue tones: thinning. Red tones: thickening. * <span class="html-italic">p</span>-value &lt; 0.05, ** <span class="html-italic">p</span>-value &lt; 0.01. The central circle has not been analyzed as it corresponds to the exit of the vessels. (ILM: inner limiting membrane, ELM: external limiting membrane, and BM: Bruch’s membrane).</p>
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9 pages, 2080 KiB  
Article
The Usefulness of 55° Wide-Field Spectral-Domain Optical Coherence Tomography in Monitoring the Features of Peripheral Subretinal Fluid Remnants after Rhegmatogenous Retinal Detachment Surgery
by Valentina Carta, Filippo Lixi, Pasquale Loiudice, Francesca Frongia, Filippo Tatti, Chiara Delpiano, Pierluca Cremonesi and Enrico Peiretti
Diagnostics 2024, 14(13), 1385; https://doi.org/10.3390/diagnostics14131385 - 29 Jun 2024
Viewed by 937
Abstract
Background: This study aimed to assess the effectiveness of 55° wide-field (WF) spectral-domain (SD) optical coherence tomography (OCT) for detecting peripheral subretinal fluid (SRF) after surgery for rhegmatogenous retinal detachment (RRD). Methods: In this retrospective observational study, the retinal periphery was examined to [...] Read more.
Background: This study aimed to assess the effectiveness of 55° wide-field (WF) spectral-domain (SD) optical coherence tomography (OCT) for detecting peripheral subretinal fluid (SRF) after surgery for rhegmatogenous retinal detachment (RRD). Methods: In this retrospective observational study, the retinal periphery was examined to evaluate the possible presence of persistent SRF after surgery. OCT scans were acquired in infrared mode to use any peripheral vessel as a landmark for better repeatability in monitoring fluid remnants. Results: A total of 80 patients (10% with high myopia) were examined using 55° WF SD OCT after successful pars plana vitrectomy (83.8%) or scleral buckling (16.3%) for RRD. A total of 18 patients (22.5%), 16 of whom underwent pars plana vitrectomy and 2 who underwent scleral buckling, showed SRF at the OCT examination during the follow-up. Potential risk factors associated with SRF persistence were analyzed, revealing a significative association with young age (p = 0.009). After a follow-up period of 7.05 ± 2.44 months (ranging from 3 to 12 months), a complete resorption in all patients (100%) within 12 months was observed. Best-corrected visual acuity significantly improved in both groups over time. Conclusion: Using 55° WF SD-OCT successfully assessed the course of SRF reabsorption, offering a viable alternative for all those realities where technologies such as ultra-wide-field (UWF) OCT are not available. Full article
(This article belongs to the Special Issue Optical Coherence Tomography in Diagnosis of Ophthalmology Disease)
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<p>(<b>A</b>) Postoperative best-corrected visual acuity (BCVA) in subjects with subretinal fluid (SRF). (<b>B</b>) The survival probability of persistent subretinal fluid (SRF).</p>
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<p>The 55° spectral-domain (SD) optical coherence tomography (OCT) infrared reflectance (IR)-guided scans displayed subretinal fluid (SRF) evolution after pars plana vitrectomy (PPV) 25 G. The same points marked by arrowheads on the IR images were used to monitor the evolution of fluid collections over time as precisely as possible. A 30-year-old patient with macula-off rhegmatogenous retinal detachment (RRD) 1 week (<b>A</b>), 1 month (<b>B</b>), 3 months (<b>C</b>) and 6 months (<b>D</b>) after surgery showing complete reabsorption of SRF.</p>
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<p>Infrared reflectance (IR) and 55° spectral-domain (SD) optical coherence tomography (OCT) images of a 21-year-old patient with macula-off rhegmatogenous retinal detachment (RRD), 2 weeks after SB showing SRF at the posterior pole (<b>A</b>) and the far temporal periphery (<b>B</b>), and at 10 months (<b>C</b>,<b>D</b>), unveiling a complete reabsorption of the fluid.</p>
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9 pages, 1208 KiB  
Article
Reproducibility of Portable OCT and Comparison with Conventional OCT
by Marie Nakamura, Takao Hirano, Yoshiaki Chiku, Yoshiaki Takahashi, Hideki Miyasaka, Shinji Kakihara, Ken Hoshiyama and Toshinori Murata
Diagnostics 2024, 14(13), 1320; https://doi.org/10.3390/diagnostics14131320 - 21 Jun 2024
Viewed by 1038
Abstract
Optical coherence tomography (OCT) is an indispensable instrument in ophthalmology; however, some facilities lack permanent OCT devices. ACT100, a portable SD-OCT system, allows for medical examinations at hospitals that do not have OCT and house calls. We investigated the usefulness of ACT100 by [...] Read more.
Optical coherence tomography (OCT) is an indispensable instrument in ophthalmology; however, some facilities lack permanent OCT devices. ACT100, a portable SD-OCT system, allows for medical examinations at hospitals that do not have OCT and house calls. We investigated the usefulness of ACT100 by examining the reproducibility of retinal thickness measurements in 35 healthy participants with normal eyes using ACT100 and Cirrus. Using two OCTs, the OCT imaging of both eyes of each subject was performed. Macular retinal thickness was evaluated using the average value in nine lesions of the Early Treatment Diabetic Retinopathy Study (ETDRS) circle. Both models captured images in all cases. In the right eye, mean retinal thickness was significantly lower than in the ACT100 group in all regions; however, the measured values correlated well. The intraclass correlation coefficients showed the same high reliability as the Cirrus. The coefficients of variation (CVs) of both models showed little variation and high stability; however, the CV of ACT100 was significantly higher. The left eye was almost identical. Macular retinal thickness measured using ACT100 showed slightly greater variability than that by Cirrus; the reproducibility was good and correlated well with that of Cirrus. This technique is a suitable alternative to conventional OCT. Full article
(This article belongs to the Special Issue Optical Coherence Tomography in Diagnosis of Ophthalmology Disease)
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<p>(<b>a</b>) A main box and a probe of ACT100. (<b>b</b>) The carrying case of ACT100.</p>
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<p>Early Treatment Diabetic Retinopathy (ETDRS) grid. (<b>a</b>) Delineation of the nine macular sectors, according to the ETDRS, within which we measured macular layer thickness. (<b>b</b>) Nine ETDRS sectors in the right eye. (<b>c</b>) Nine ETDRS sectors in the left eye. Green indicates that the retina is of normal thickness.</p>
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13 pages, 21488 KiB  
Article
Assessment of Early Glaucomatous Optic Neuropathy in the Dog by Spectral Domain Optical Coherence Tomography (SD-OCT)
by Annie Oh, Christine D. Harman, Kristin L. Koehl, Jiayan Huang, Leandro B. C. Teixeira, Laurence M. Occelli, Eric S. Storey, Gui-Shuang Ying and András M. Komáromy
Micromachines 2024, 15(6), 780; https://doi.org/10.3390/mi15060780 - 13 Jun 2024
Viewed by 783
Abstract
Background: Inherited primary open-angle glaucoma (POAG) in Beagle dogs is a well-established large animal model of glaucoma and is caused by a G661R missense mutation in the ADAMTS10 gene. Using this model, the study describes early clinical disease markers for canine glaucoma. Methods: [...] Read more.
Background: Inherited primary open-angle glaucoma (POAG) in Beagle dogs is a well-established large animal model of glaucoma and is caused by a G661R missense mutation in the ADAMTS10 gene. Using this model, the study describes early clinical disease markers for canine glaucoma. Methods: Spectral-domain optical coherence tomography (SD-OCT) was used to assess nine adult, ADAMTS10-mutant (median age 45.6 months, range 28.8–52.8 months; mean diurnal intraocular pressure (IOP): 29.9 +/− SEM 0.44 mmHg) and three related age-matched control Beagles (mean diurnal IOP: 18.0 +/− SEM 0.53 mmHg). Results: Of all the optic nerve head (ONH) parameters evaluated, the loss of myelin peak height in the horizontal plane was most significant (from 154 +/− SEM 38.4 μm to 9.3 +/− SEM 22.1 μm; p < 0.01). There was a strong significant negative correlation between myelin peak height and IOP (Spearman correlation: −0.78; p < 0.003). There were no significant differences in the thickness of any retinal layers evaluated. Conclusions: SD-OCT is a useful tool to detect early glaucomatous damage to the ONH in dogs before vision loss. Loss in myelin peak height without inner retinal thinning was identified as an early clinical disease marker. This suggests that initial degenerative changes are mostly due to the loss of myelin. Full article
(This article belongs to the Section B:Biology and Biomedicine)
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<p>Schematic diagram of spectral-domain optical coherence tomography (SD-OCT). Line charge-coupled device (CCD) detector. (Referenced from Zheng S et al. [<a href="#B26-micromachines-15-00780" class="html-bibr">26</a>]).</p>
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<p>Example of optic nerve head (ONH) measurements in a control dog. (<b>a</b>) cSLO image showing the location of the circular 12° OCT RNFL scan: ONH area (yellow shade); (<b>b</b>) cSLO image of a line scan: 0° (solid green line) and 90° (dashed green line) line scans; (<b>c</b>) Vitreoretinal reference plane (blue line): myelin peak height (yellow line) and ONH cup depth (green line). (<b>d</b>) Vitreoretinal reference plane (blue line): cross-sectional area of the ONH cup (green shade). (<b>e</b>) Neuroretinal rim reference plane (red line): myelin peak distance (length of red line) and ONH cup depth (purple line). (<b>f</b>) Neuroretinal rim reference plane (red line): cross-sectional area of the ONH cup (blue shade). Calibration bars = 200 μm.</p>
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<p>Example of optic nerve head (ONH) measurements in a control dog. (<b>a</b>) cSLO image showing the location of the 12 standard radial scans: four of these line scans were selected for measurements (white arrows; 0°, 45°, 90°, 135°). (<b>b</b>) Connected ends of the retinal pigment epithelium/choriocapillaris layer (blue line). One-hundred fifty micrometer reference plane (white line). Optic cup diameter (green line). Perpendicular lines from the ends of the retinal pigment epithelium/choriocapillaris layer to the inner limiting membrane (yellow lines). Cross-sectional neuroretinal rim area (red shade). Calibration bars = 200 μm.</p>
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<p>Example of retinal layer measurements in a control dog. (<b>a</b>) cSLO image of the 12° circular RNFL OCT scan: two distinct points per quadrant void of retinal blood vessels were identified. (<b>b</b>) FRT (red shade) extends from the ILM (red dots) to the RPE (purple dots). IRT (yellow shade) extends from the ILM (red dots) to the posterior surface of the IPL (yellow dots). ONL (green shade) is measured from its anterior (green dots) to the posterior surface (blue dots). Calibration bars = 200 μm.</p>
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<p>Scatterplot showing a significant negative correlation between intraocular pressure (IOP) and myelin peak height.</p>
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<p>Volume scans of three-dimensional SD-OCT images of the ONH. Two normal (<b>a</b>,<b>d</b>) and three affected ONHs (<b>b</b>,<b>c</b>,<b>e</b>) at various ages and stages of disease are shown. Right eye (OD); years old (YO).</p>
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<p>Histologic and SD-OCT comparison of the ONH. Normal (<b>a</b>,<b>c</b>,<b>e</b>,<b>g</b>) and age-matched mutant Beagle dogs (<b>b</b>,<b>d</b>,<b>f</b>,<b>h</b>). The 3.2-year-old and 3.3-year-old mutant dogs exhibit mild flattening of myelin on histology (<b>b</b>) and SD-OCT (<b>f</b>), respectively, in contrast to the 4.5-year-old mutant dog, which has marked myelin loss and cupping (arrows) of the ONH on both histology (<b>d</b>) and SD-OCT (<b>h</b>). Calibration bars = 200 μm. Right eye (OD); Left eye (OS); years old (YO).</p>
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<p>Histologic (superior retina) and SD-OCT (peripapillary) comparison of the retina. Normal (<b>a</b>,<b>c</b>,<b>e</b>,<b>g</b>) and age-matched mutant Beagle dogs (<b>b</b>,<b>d</b>,<b>f</b>,<b>h</b>). On histologic sections, there was thinning of the inner retina in the affected tissues (<b>b</b>,<b>d</b>) compared to age-matched controls (<b>a</b>,<b>c</b>) in both the early and later stages of the disease. This was not observed on SD-OCT when comparing the affected tissues (<b>f</b>,<b>h</b>) with age-matched controls (<b>e</b>,<b>f</b>) at the ages assessed. Calibration bars = 50 μm. Right eye (OD); Left eye (OS); years old (YO).</p>
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15 pages, 18635 KiB  
Article
Understanding the Dermoscopic Patterns of Basal Cell Carcinoma Using Line-Field Confocal Tomography
by Lorenzo Barbarossa, Martina D’Onghia, Alessandra Cartocci, Mariano Suppa, Linda Tognetti, Simone Cappilli, Ketty Peris, Javiera Perez-Anker, Josep Malvehy, Gennaro Baldino, Caterina Militello, Jean Luc Perrot, Pietro Rubegni and Elisa Cinotti
Tomography 2024, 10(6), 826-838; https://doi.org/10.3390/tomography10060063 - 22 May 2024
Viewed by 1147
Abstract
Basal cell carcinoma (BCC) is the most frequent malignancy in the general population. To date, dermoscopy is considered a key tool for the diagnosis of BCC; nevertheless, line-field confocal optical coherence tomography (LC-OCT), a new non-invasive optical technique, has become increasingly important in [...] Read more.
Basal cell carcinoma (BCC) is the most frequent malignancy in the general population. To date, dermoscopy is considered a key tool for the diagnosis of BCC; nevertheless, line-field confocal optical coherence tomography (LC-OCT), a new non-invasive optical technique, has become increasingly important in clinical practice, allowing for in vivo imaging at cellular resolution. The present study aimed to investigate the possible correlation between the dermoscopic features of BCC and their LC-OCT counterparts. In total, 100 histopathologically confirmed BCC cases were collected at the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic and LC-OCT criteria were retrospectively evaluated, and their frequencies were calculated. The mean (SD) age of our cohort was 65.46 (13.36) years. Overall, BCC lesions were mainly located on the head (49%), and they were predominantly dermoscopically pigmented (59%). Interestingly, all dermoscopic features considered had a statistically significant agreement with the LC-OCT criteria (all p < 0.05). In conclusion, our results showed that dermoscopic patterns may be associated with LC-OCT findings, potentially increasing accuracy in BCC diagnosis. However, further studies are needed in this field. Full article
(This article belongs to the Special Issue Imaging in Cancer Diagnosis)
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<p>Superficial basal cell carcinoma: LC-OCT image and dermoscopic correlation. LC-OCT examination reveals the presence of lobules with an inner gray core featuring the peculiar <span class="html-italic">millefeuille</span> pattern (white asterisks). Blood vessels are visualized as well-defined, hyporeflective elongated structures of various sizes localized within the dermis and next to the lobules (white arrows).</p>
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<p>Superficial basal cell carcinoma: LC-OCT image and dermoscopic correlation (<b>a</b>). Dermoscopy shows pink–white areas, whereas LC-OCT examination reveals the presence of medium-reflective superficial lobules attached to the epidermis with a <span class="html-italic">millefeuille</span> pattern (white asterisks) (<b>a</b>). Histological image, hematoxylin–eosin (x4) (<b>b</b>).</p>
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<p>Micronodular basal cell carcinoma: LC-OCT image and its dermoscopic correlation. LC-OCT shows a milia-like cyst characterized by hyper-reflective roundish areas with an onion-like shape (white circle) corresponding to keratin. A white roundish area is visible in the corresponding dermoscopic section (<b>a</b>). Clinical image (<b>b</b>). Histological image. (<b>c</b>) Hematoxylin–eosin (x4).</p>
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<p>Nodular basal cell carcinoma: LC-OCT images and their dermoscopic correlation with pigmented and non-pigmented areas of the lesion (<b>a</b>,<b>b</b>). Hyper-reflective roundish small areas corresponding to melanophages are visible under LC-OCT inside the lobules in the part of the tumor that is pigmented when using dermoscopy (<b>a</b>). Histological correlation shows numerous melanophages (yellow arrows) (<b>c</b>). Medium-reflective roundish lobules, clefting, and hyper-reflective stroma are visible under LC-OCT in the adjacent area without pigment when using dermoscopy (<b>b</b>). Histological correlation of the non-pigmented lobule (red arrow) (<b>c</b>).</p>
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<p>Superficial basal cell carcinoma: LC-OCT image and dermoscopic correlation. Dermoscopy shows maple-leaf-like areas, which, via LC-OCT, appear as medium-reflective lobules with a maple-leaf shape attached to the epidermis (white asterisk) (<b>a</b>). Histological image, hematoxylin–eosin (x4) (<b>b</b>).</p>
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<p>Superficial basal cell carcinoma: LC-OCT image and its dermoscopic correlation (<b>a</b>,<b>b</b>). Dermoscopy shows a concentric structure, which on vertical (<b>a</b>) and 3D (<b>b</b>) LC-OCT images appears as a medium-reflective lobule connected to the epidermis around a central dilated hair follicle (white asterisk).</p>
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<p>Nodular basal cell carcinoma: LC-OCT image and its dermoscopic correlation (<b>a</b>). Dermoscopy shows multiple blue–gray dots referring to roundish hyper-reflective areas within the lobule, which, when using LC-OCT, correspond to melanophages (white circle) (<b>a</b>). Clinical image (<b>b</b>). Histological image. (<b>c</b>) Hematoxylin–eosin (x4).</p>
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<p>Nodular basal cell carcinoma: LC-OCT image and its dermoscopic (<b>a</b>) and histologic (<b>b</b>) correlation (yellow arrows). Dermoscopy shows multiple blue–gray dots that appear as roundish hyper-reflective areas within the lobule, which, (<b>a</b>) when using LC-OCT, correspond to melanophages upon histological examination ((<b>b</b>), hematoxylin and eosin staining).</p>
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<p>Superficial basal cell carcinoma: LC-OCT images and their dermoscopic correlation (<b>a</b>,<b>b</b>). Dermoscopy shows a blue-whitish veil, which, when using LC-OCT, corresponds to lobules with hyper-reflective particles inside occupying the entire visible dermis (white asterisks) (<b>a</b>,<b>b</b>).</p>
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13 pages, 2579 KiB  
Article
Ellipsoid Zone Integrity and Visual Function in Dry Age-Related Macular Degeneration
by Sari Yordi, Yavuz Cakir, Gagan Kalra, Hasan Cetin, Ming Hu, Joseph Abraham, Jamie Reese, Sunil K. Srivastava and Justis P. Ehlers
J. Pers. Med. 2024, 14(5), 543; https://doi.org/10.3390/jpm14050543 - 19 May 2024
Cited by 3 | Viewed by 1095
Abstract
In this longitudinal retrospective image analysis, conducted on patients diagnosed with dry age-related macular degeneration (AMD) and 5 years of follow-up imaging data, the study aimed to investigate the relationship between ellipsoid zone (EZ) integrity on spectral domain optical coherence tomography (SD-OCT) and [...] Read more.
In this longitudinal retrospective image analysis, conducted on patients diagnosed with dry age-related macular degeneration (AMD) and 5 years of follow-up imaging data, the study aimed to investigate the relationship between ellipsoid zone (EZ) integrity on spectral domain optical coherence tomography (SD-OCT) and visual acuity (VA). Using a machine learning-enabled feature extraction tool, quantitative EZ parameters were derived from SD-OCT images. The analysis revealed significant correlations between EZ integrity metrics and VA. Eyes with excellent VA (≥20/25 Snellen) exhibited higher EZ integrity, including less EZ attenuation, thicker ellipsoid zone-retinal pigment epithelium (EZ-RPE) thickness, and higher EZ intensity, in contrast to eyes with worse VA (≤20/40 Snellen). Additionally, eyes with geographic atrophy (GA) in the foveal region displayed compromised EZ integrity compared to those without GA. Notably, baseline EZ integrity metrics were predictive of future VA loss. These findings suggest that quantitative SD-OCT measurements of EZ integrity could potentially detect early changes in dry AMD and serve as valuable indicators for predicting future functional outcomes. Furthermore, these measurements hold promise for use in clinical trial screenings, offering insights into the progression of the disease and its impact on visual acuity. This study underscores the importance of EZ integrity assessment in understanding and managing dry AMD. Full article
(This article belongs to the Section Disease Biomarker)
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<p>Examples of two eyes (two subjects) with different levels of EZ attenuation and corresponding VA values. Example 1 (<b>A</b>–<b>C</b>) and Example 2 (<b>D</b>–<b>F</b>). SD-OCT B-scan of foveal slices from each example (<b>A</b>,<b>D</b>) with their EZ intensity maps (<b>B</b>,<b>E</b>) and EZ-RPE thickness maps (<b>C</b>,<b>F</b>). SD-OCT: spectral domain optical coherence tomography; EZ: ellipsoid zone; RPE: retinal pigment epithelium; BM: Bruch’s membrane; GA: geographic atrophy.</p>
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<p>Bar graphs comparing the mean partial and total EZ attenuation in eyes with excellent VA (≥80 letters or 20/25 Snellen) and eyes with worse VA (≤70 letters or 20/40 Snellen), stratified by all eyes, eyes with foveal GA, and eyes with no GA. *** <span class="html-italic">p</span> value ≤ 0.001; ** <span class="html-italic">p</span> value ≤ 0.01; * <span class="html-italic">p</span> value ≤ 0.05. EZ: ellipsoid zone; VA: visual acuity; GA: geographic atrophy.</p>
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<p>Bar graphs comparing the mean central subfield/macular EZ-RPE thickness in eyes with excellent VA (≥80 letters or 20/25 Snellen) and eyes with worse VA (≤70 letters or 20/40 Snellen) stratified by all eyes, eyes with foveal GA, and eyes with no GA. *** <span class="html-italic">p</span> value ≤ 0.001; ** <span class="html-italic">p</span> value ≤ 0.01; EZ: ellipsoid zone; RPE: retinal pigment epithelium; VA: visual acuity; GA: geographic atrophy.</p>
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<p>Bar graphs comparing the mean EZ intensity index in eyes with excellent VA (≥80 letters or 20/25 Snellen) and eyes with worse VA (≤70 letters or 20/40 Snellen), stratified by all eyes, eyes with foveal GA, and eyes with no GA. *** <span class="html-italic">p</span> value ≤ 0.001; ** <span class="html-italic">p</span> value ≤ 0.01; * <span class="html-italic">p</span> value ≤ 0.05. EZ: ellipsoid zone; VA: visual acuity; GA: geographic atrophy.</p>
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<p>Examples of two subjects (two eyes) with varying EZ attenuation at Year 0 showing different progression of VA during 5-year follow-up. Example 1 shows minimal EZ attenuation and excellent VA at Year 0 (85 letters or 20/20 Snellen) (<b>A</b>) with subsequent maintenance of excellent VA at Year 5 (80 letters or 20/25 Snellen) (<b>B</b>). Example 2 shows more significant EZ attenuation and worse VA at Year 0 (70 letters or 20/40 Snellen) (<b>C</b>) with &gt;2-line worsening of VA by Year 5 (58 letters of 20/80 Snellen) (<b>D</b>). EZ-RPE thickness maps on top right of (<b>A</b>–<b>D</b>) indicate areas of EZ attenuation. SD-OCT: spectral domain optical coherence tomography; EZ: ellipsoid zone.</p>
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