Retinal Layer Research Articles

Reactive retinal vasodilation may mask capillary loss in eyes without diabetic retinopathy and isolated neurodegeneration

Reactive retinal vasodilation occurs in healthy individuals when the demand for oxygen surpasses the supply that the vascular bed can provide. This phenomenon may also occur in individuals with diabetes who do not have diabetic retinopathy, potentially masking circulation deficiencies caused by early capillary closure. As a result, eyes with reactive retinal vasodilation may show a seemingly normal circulation area, while also displaying other diabetes-related changes such as neurodegeneration. Our hypothesis suggests that in eyes without overt ischemia, which is one of the phenotypes of diabetic retinal disease, neurodegeneration could be the result of undetected ischemia in the presence of reactive retinal vasodilation. We propose methodologies to investigate this hypothesis, including the assessment of retinal capillaries using optical coherence tomography angiography, as well as the measurement of neurodegeneration markers such as retinal sensitivity, electroretinogram amplitude reductions, and retinal layer thinning. Additionally, we outline an approach for estimating the contribution of large retinal vessels to the percentage of circulation within a measured retinal area, using variables such as vessel length density and vessel area density. If our hypothesis is confirmed, it could lead to the early identification of ischemia before the onset of diabetic retinopathy and offer an opportunity to assess interventions when endothelial and neural damage can still be mitigated.

Case report of visual quality in a patient with nephronophthisis 12- associated retinopathy secondary to TTC21B mutation.

Nephronophthisis 12 is a rare condition and only two cases have been reported to associate with retinopathy. Herein we present the third case in scientific literature, and the first with vision-quality exams. The case was a 28-year-old male with the mutations c.626C > T (p.Pro209Leu) and c.1317T > G (p.Tyr439*). Bilateral atrophy of outer retinal layers and retinal pigmented epithelium were observed, resembling a bull's eye maculopathy. Visual acuity, as well as contrast sensitivity dropped with mesopic conditions. He presented more difficulties in differentiating colors within blue-yellow range, and some degree of halos were detected. Multifocal electroretinogram detected little retinal function, and visual field detected a full scotoma. He referred poorer quality of life due to emotional wellbeing, more than to difficulties in reading or accessing information. Although rare, nephronophthisis 12 may be caused by genetic mutations that associate severe retinopathy.

Evaluation of the Electroconvulsive Therapy's Impact on Retinal Structures in First-Episode Psychosis Patients Using Optical Coherence Tomography.

Schizophrenia is a complex disorder thought to have neurodevelopmental and neurodegenerative aspects. Optical coherence tomography (OCT) measurements of schizophrenia patients revealed that the retinal layers of these patients were thinner than those of healthy controls. This study aimed to examine retinal changes in first-episode psychosis patients treated with electroconvulsive therapy (ECT) via OCT. Thirty first-episode psychosis patients (13 men, 17 women) aged 18 to 65 years who had no comorbidities and no smoking, alcohol, or substance use disorders and who were treated with ECT were included in the study. The patients were evaluated using OCT before treatment and after an average of 7.4 sessions of ECT in remission, and the results were compared. Statistically significant increases were observed in retinal layer thickness, inner plexiform layer, outer plexiform layer, and total retinal thickness within the 1 mm ring (P = .015, P = .045, and P = .025, respectively). The inner nuclear layer thickness significantly increased within the 6 mm ring (P = .037). In conclusion, ECT noticeably affected retinal structures, particularly according to similar measurements, indicating potential improvements in and the ability to reverse neuronal degeneration after one month of treatment. This study highlights the potential impact of ECT on retinal structures in individuals experiencing first-episode psychosis, as it can enhance specific retinal layers and reverse neuronal degeneration.

Non-exudative OCT findings in neovascular AMD.

In this narrative review we describe the main optical coherence tomography biomarkers appearing in eyes with neovascular age-related macular degeneration (AMD) that do not directly correspond to exudation. We highlight those signs that may mimic exudation and therefore do not require active treatment, such as outer retinal tubulations, pseudocysts, lipid globules, or hyporeflective wedges. Other signs may indicate impending exudation such as hyperreflective foci or shallow irregular retinal pigment epithelium elevation, and therefore should be carefully monitored. We also review and summarize the different origins of subretinal hyperreflective material and describe the main signs of degeneration seen in eyes with AMD, such as outer retinal tubulation, thinning of the retinal layers, outer retinal atrophy, and choroidal changes.

Extracting full information from OCT scans-signs of early age-related macular degeneration within inner retinal layers by local neighbourhood statistics. Part II: Results.

Associations between the occurrence of early age related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported, based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, we designed an omics-type approach for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole. A nested case-control study was designed with 200 early AMD cases and 200 healthy controls. For each participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At every position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first-order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for each descriptor at every graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini-Yekutieli procedure. In terms of the amount and disparity of true discoveries, overall non-equivalence was found for early AMD and healthy groups. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise. Between the retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoon and speckle bear essential parts of the total information. We pursued a constructive, completely documented, traceable and repeatable approach without invoking artificial intelligence methods.

Extracting full information from OCT scans-signs of early age-related macular degeneration within inner retinal layers by local neighbourhood statistics. Part I: Methodology.

Associations between the occurrence of early age-related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, an omics-type approach was designed for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole. A nested case-control study was designed with 200 early AMD cases and 200 healthy controls. For every participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At each position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first-order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for every descriptor at each graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini-Yekutieli procedure. In terms of the amount and disparity of true discoveries, overall non-equivalence of early AMD and healthy groups was found. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise. Between retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within the OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but also the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoons and speckle bear essential parts of total information. A constructive, completely documented, traceable and repeatable approach was pursued without invoking artificial intelligence methods.

A novel homozygous missense variant in POC1B causes cone dystrophy in a consanguineous Pakistani family

ABSTRACT Background Cone dystrophy is a heterogeneous hereditary retinal disorder with disease symptoms appearing in the late first or early second decades of life. Methods A consanguineous Pakistani family with three affected individuals underwent detailed clinical and genetic investigation. Results The proband, a 63-years old male, showed severely reduced day vision, a visual acuity of counting fingers (CF), color vision deficiency, high myopia and photophobia. Fundus images showed bilateral peripapillary atrophy, bilateral dull foveal reflex, tilted disc, tessellated fundus, and hyperfluorescence at the peripheral superior temporal arcade and leak at an early stage. OCT macula and angiography findings suggested traction near the disc in the right eye and sub-retinal fluid at the fovea in the left eye. Retinal layers were normal toward the periphery but disorganized near the disc. Full visual field tests showed bilateral central scotoma, while single visual field tests indicated bilateral generalized depression of the visual field. The proband showed normal bilateral intraocular pressure, normal choroidal vessels, and unremarkable anterior segment. Exome sequencing identified a novel homozygous missense variant (POC1B:NM_172240.3:c.1391T>C;p.L464P) in the proband. Existing evidence supported pathogenicity of the identified variant in the family. Conclusion In conclusion, we document a first-ever Pakistani family with POC1B-related cone dystrophy.

Respiratory Chain Complex I Deficiency in Leber Hereditary Optic Neuropathy: Insights from Ophthalmologic and Molecular Investigations in Tunisia

BackgroundLeber hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) rare disease due to the pathogenic variant of the NADH dehydrogenase enzyme. LHON is characterized by a sudden central vision loss due to focal degeneration of the retinal ganglion cell layer and optic nerve. Symptoms usually appear between the age of 18 and 35 years. Some individuals present the mtDNA mutations but not presented the LHON clinical features. The heteroplasmic or homoplasmic character of the mutations among patients explains why they develop the disease or not even though they carry the pathogenic variant.MethodsThis study was performed in collaboration with the department of ophthalmology of Farhat Hached Hospital, Sousse, Tunisia. Screening for the common mutations in Mt-ND1 gene (m.3460G > A), Mt-ND4 gene (m.11778G > A) and Mt-ND6 gene (m.14484T > C) was performed in five Tunisian families by standard RFLP PCR, followed by direct sequencing of the entire of these genes. Indeed, bioinformatics tools were used to predict the potential functional impact of the identified mutations on the Human mitochondrial respiratory complex I protein.Resultsone novel p.L601M (m.1413 C > A) and four previously reported mutations were identified in this study including: rs199476112G > A (m.11778G > A); rs202227543G > A (m.14258G > A); rs1603224763 (m.14510 dup) and NC_012920.1: m.3244G > C. In this present report, only one patient was found carrying the primary point mutation (m. 11778G > A). The ophthalmologic findings showing major fundus changes included hyperemic optic discs; disc pseudo-oedema and microangiopathy leading to optic disc atrophy. The analyses of the stability of protein upon identified mutations using DynaMut tool server demonstrated that these variations induce a rigidification in the region where they are located.ConclusionThis is the first Tunisian report of mtDNA mutations identified in Tunisia causing the LHON. The main factors involved in the pathophysiological mechanisms of this disease are genetic, epigenetic, hormonal and environmental influences.

Predictive risk scores for visual prognosis after photodynamic therapy for central serous chorioretinopathy.

To comprehensively evaluate baseline characteristics of patients with central serous chorioretinopathy (CSC) and develop predictive risk scores to identify visual prognosis. This single-institute, retrospective cohort study included 144 eyes of 144 patients with CSC who underwent photodynamic therapy and achieved serous retinal detachment resolution. We developed and assessed the performance of several risk scores for best-corrected visual acuity (BCVA) outcomes six months post-treatment: i) BCVA improvement (≤-1.0 logMAR), and ii) BCVA deterioration (≥+ 1.0 logMAR). The BCVA improvement models used photoreceptor outer segment thickness, loss of photoreceptor outer segment, and neurosensory retinal thickness (NSRT), while the BCVA deterioration models included outer nuclear layer thickness and NSRT. The BCVA improvement models demonstrated a corrected area under the curve (AUC) of 0.786 (95% confidence interval [CI]: 0.699-0.864), with 80.4% sensitivity, and 71.2% specificity. The BCVA deterioration models achieved a corrected AUC of 0.864 (95% CI: 0.742-0.958), with 85.7% sensitivity, and 83.5% specificity. The predictive models for CSC exhibited favorable performance in predicting individual visual prognoses. A thinner outer nuclear layer may be associated with BCVA deterioration, whereas preservation of the photoreceptor outer segment may be correlated with BCVA improvement. WHAT IS KNOWN : Pre-treatment best-corrected visual acuity, thickness of each sensory retinal layer, time fromonset to treatment, and macular atrophy were each found to be associated with visualprognosis for patients with central serous chorioretinopathy (CSC). The current study comprehensively assessed potential prognostic factors and precisely identified individual likelihood of visual prognosis. The study found that different regions of the sensory retina were associated with either worsening or improving visual acuity. Accurately predicting visual outcomes after photodynamic therapy for CSC would help healthcare providers create personalized treatment plans and enable patients to make informed decisions about their treatment based on their expected visual results.

Evaluation of post-operative foveal location and microstructural changes after pars plana vitrectomy for rhegmatogenous retinal detachment using enhanced-depth imaging optical coherence tomography

BackgroundPatients who had successful rhegmatogenous retinal detachment (RRD) surgery often complained of metamorphopsia due to postoperative fovea displacement and alteration of the foveal microstructure. The papillo-foveal distance (PFD) is correlated bilaterally. Therefore, PFD from the fellow healthy eye could be used to determine the change of foveal position in eyes with successful RRD repair. Ultra-high-resolution optical coherence tomography (UHR-OCT) could explain incomplete visual recovery by demonstrating foveal misalignment and changes in foveal microstructure. The rationale of the study is to assess the changes in the foveal location and microstructural layers after successful retinal reattachment and correlate them with visual dysfunction.Patients and methodsA prospective interventional cross-sectional controlled study included patients who had successful retinal reattachment and complained of defective vision or metamorphopsia. The primary outcome measure is to evaluate the post-operative foveal location. The secondary outcome measures are the assessment of metamorphopsia, the evaluation of the foveal microstructural changes, and the correlation between foveal shift, metamorphopsia, foveal microstructure, and visual function. We used a standard Amsler chart to detect subjective metamorphopsia and a modified Amsler chart to quantify metamorphopsia. We used the enhanced-depth imaging optical coherence tomography (EDI-OCT) to detect changes in PFD and the foveal microstructure. p < 0.05.ResultsThe study included 50 study eyes and 50 control eyes. The male gender constituted 70%. The mean age was 53 years. The mean baseline BCVA was 0.001. The incidence of foveal displacement was 70%. Disorganized retinal inner layers (DRIL) occurred in 56% of eyes, and disorganized retinal outer layers (DROL) occurred in 72% of eyes. The mean postoperative BCVA was 0.3. The subjective metamorphopsia was mild in 39%, moderate in 24%, severe in 33%, and very severe in 3% of eyes. The mean quantitative metamorphopsia was 587 mm. PVR correlated significantly with the foveal shift. DROL correlated significantly with subjective metamorphopsia. There was a statistically significant difference between subjective metamorphopsia and quantitative metamorphopsia.ConclusionFoveal displacement and metamorphopsia after successful retinal reattachment pose significant morbidity. UHR-OCT is pivotal in evaluating the anatomical outcome after successful retinal re-attachment surgery and its relation to visual function.

An eye’s look unmasks the mystery: correlation between serum amyloid beta peptide, hippocampal volume and retinal thickness in Alzheimer`s disease

BackgroundAlzheimer’s disease (AD) is the commonest worldwide neurodegenerative disorder. Nevertheless, it usually face difficulties to guarantee a secured initial diagnosis. For this reason, neurologists are in dire need for developing potential biomarkers that could be relied upon confidentially in early diagnosis of AD. Hopefully, this will open the gate for novel modifying therapy to fight with all their might. In this current study, we aimed to correlate plasma levels of tau and Aβ with the changes that occur in hippocampal volume and thickness of retinal fiber layers in patients who clinically diagnosed with AD spectrum. A cross-sectional study enrolled 60 AD patients who fulfilled inclusion and exclusion criteria were subjected to cognitive, radiologic, laboratory and optical coherence tomography (OCT) assessments.ResultsTau, Aβ1–40, and Aβ1–40/Aβ1–42 ratio are significant discriminators of AD at cutoff values of >23.45, > 84.4, and > 1.95, respectively. MRI hippocampal volume in both right and left sides are also good discriminators of AD at cutoff values of ≤ 2.997, and ≤ 2.994, respectively. A significant correlations were reported between tau with Aβ1–40, Aβ1–42, MMSE and MRI right and left hippocampal volumes. On comparing moderate versus mild AD, there was a high significant levels of tau, Aβ1–42, Aβ1–40/Aβ1–42 ratio.ConclusionsWe clarify that several biomarkers could be potentially used for confirming the diagnosis of AD. Assessment of plasma amyloid level, detection of hippocampal atrophy and retinal nerve fiber layer thickness changes are promising tools for early diagnosis of AD.

Alterations of endocannabinoid signaling and microglia reactivity in the retinas of AD-like mice precede the onset of hippocampal β-amyloid plaques.

Extra-cerebral manifestations of Alzheimer's disease (AD) develop in the retina, which is, therefore, considered a "window to the brain". Recent studies demonstrated the dysregulation of the endocannabinoid (eCB) system (ECS) in AD brain. Here, we explored the possible alterations of ECS and the onset of gliosis in the retina of AD-like mice. Tg2576 (TG) mice overexpressing the amyloid precursor protein (APP) were used at the age of 12 months, when hippocampal β-amyloid plaques had not been developed yet. Analysis of retinal gliosis showed a significant increase in the number of IBA1 (+) microglia cells in TG versus wild type (WT). Gliosis was not associated with retinal β-amyloid plaques, evident retinal degenerative signatures, or excitotoxicity; instead, oxidative stress burden was observed as increased acrolein levels. Analysis of the ECS (receptors/metabolic enzymes) through western blotting (WB) revealed the up-regulation of cannabinoid receptor 2 (CB2) and monoacylglycerol lipase (MAGL), the enzyme responsible for the degradation of 2-arachidonoylglycerol (2-AG), in TG retinas. Fluorescence intensity analysis of anti-CB2 and anti-MAGL immuno-stained cryosections was consistent with WB, showing their up-regulation throughout the retinal layers. No statistically significant differences were found for the other enzymes/receptors of the ECS under study. However, linear regression analysis for individual animals showed a significant correlation between CB2 and fatty acid amide hydrolase (FAAH), diacylglycerol lipase α/β (DAGLα/β), and APP; instead, a significant negative correlation was found between MAGL and APP. Finally, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) demonstrated a significant reduction of 2-AG in TG retinas (~0.34 ng/mg) compared to WT (~1.70 ng/mg), while a trend toward increase was found for the other eCB anandamide (AEA). Overall, our data indicate that gliosis and ECS dysregulation-in particular of CB2, MAGL and 2-AG-occur in the retina of AD-like mice before retinal degeneration and development of hippocampal β-amyloid plaques.

Clinical and imaging characteristics associated with foveal neovascularization in proliferative diabetic retinopathy.

To assess the prevalence of foveal neovascularization (FNV) and its associated clinical features in proliferative diabetic retinopathy (PDR) eyes. Cross-sectional observational study. Participants underwent ultra-widefield photography, optical coherence tomography (OCT), and swept-source OCT angiography (SS-OCTA). FNV was defined as a hyperreflective lesion breaching the internal limiting membrane and displaying flow signal on OCTA, within 1-mm of foveal avascular zone. Vascular metrics were obtained from the ARI Network portal. Ischemic index (ISI) and inner choroid flow deficit percentage were calculated using FIJI from 12 × 12 and 6 × 6-mm scans, respectively. Logistic regression models were used to compare eyes with and without FNV. We included 249 eyes of 164 patients (age: 58 [50-65] years). FNV was identified in 20 eyes (8%). Univariate logistic regression revealed significant associations between FNV and younger age (p = 0.03), higher maximal HbA1c (p = 0.04), worse visual acuity (VA) (p = 0.01), presence of disorganization of retinal inner layers (DRIL) (p = 0.01), no macular posterior vitreous detachment (PVD) (p = 0.03), neovascularization elsewhere (NVE) and at the disc (NVD) (p = 0.01 and p = 0.001), and greater ISI (p = 0.04). In multivariable analysis, a significant association remained between FNV and worse VA (p = 0.04), NVD (p < 0.001), DRIL (p < 0.001), and absence of macular PVD (p = 0.01). No associations were found with SS-OCTA vascular metrics. This study provides a comprehensive characterization of FNV in PDR. FNV was identified in 8% of our cohort, being more prevalent in younger patients with severe PDR, as evidenced by NVD and DRIL presence. The absence of macular PVD may explain its association with younger age. What is known • Neovascularization at the fovea occurs rarely in proliferative diabetic retinopathy. • OCT and OCT-angiography can be used to evaluate foveal neovascularization, which may be associated with choroidal vascular abnormalities. What is new • Foveal neovascularization was seen in 8% of eyes with proliferative diabetic retinopathy in this cohort. • Risk factors for foveal neovascularization included younger age, absence of macular posterior vitreous detachment, presence of neovascularization of the disc, and presence of disorganization of retinal inner layers. • We did not identify an association between foveal neovascularization and choroidal perfusion abnormalities in this study.

Retinal ganglion cell-derived semaphorin 6A segregates starburst amacrine cell dendritic scaffolds to organize the mouse inner retina.

To form functional circuits, neurons must settle in their appropriate cellular locations, and then project and elaborate neurites to contact their target synaptic neuropils. Laminar organization within the vertebrate retinal inner plexiform layer (IPL) facilitates pre- and postsynaptic neurite targeting, yet the precise mechanisms underlying establishment of functional IPL subdomains are not well understood. Here, we explore mechanisms defining the compartmentalization of OFF and ON neurites generally, and OFF and ON direction-selective neurites specifically, within the developing mouse IPL. We show that semaphorin 6A (Sema6A), a repulsive axon guidance cue, is required for delineation of OFF versus ON circuits within the IPL: in the Sema6a null IPL, the boundary between OFF and ON domains is blurred. Furthermore, Sema6A expressed by retinal ganglion cells (RGCs) directs laminar segregation of OFF and ON starburst amacrine cell dendritic scaffolds, which themselves serve as a substrate upon which other retinal neurites elaborate. These results demonstrate that RGCs, the first type of neuron born within the retina, play an active role in functional specialization of the IPL.

Paramagnetic rim lesions are associated with inner retinal layer thinning and progression independent of relapse activity in multiple sclerosis.

Paramagnetic rim lesions (PRLs) are chronic active lesions associated with a severe disease course in multiple sclerosis (MS). This study was undertaken to investigate an association between retinal layer thinning (annualized loss of peripapillary retinal nerve fiber layer [aLpRNFL] and ganglion cell-inner plexiform layer [aLGCIPL]) and PRLs in patients with MS (pwMS). In this study, pwMS with brain magnetic resonance imaging and ≥2 optical coherence tomography scans were included. Cox proportional hazard regression models were performed using progression independent of relapse activity (PIRA) as the dependent variable, and aLpRNFL, aLGCIPL, or the number of PRLs as independent variables, adjusted for covariates. We analyzed data from 97 pwMS (mean age = 35.2 years [SD = 9.9], 71.1% female, median disease duration = 2.3 years [interquartile range = 0.9-9.0]). The number of PRLs was associated with aLpRNFL and aLGCIPL. PIRA was observed in 18 (18.6%) pwMS, with aLpRNFL (hazard ratio [HR] = 1.44 per %/year), aLGCIPL (HR = 1.61 per %/year), and the number of PRLs (HR = 1.24 per PRL) being associated with increased risk of PIRA. The number of PRLs is associated with inner retinal layer thinning and increased risk of PIRA. A combination of PRLs and retinal layer thinning could serve as a surrogate for pwMS at highest risk of disability progression.

Examination of optical coherence tomography findings in patients with pregabalin use disorder.

Pregabalin abuse is a rapidly growing health problem worldwide, and little is known about the effects of prolonged high-dose use in patients with pregabalin use disorder. In this study, the effects of pregabalin abuse on retinal layers were investigated in patients with pregabalin use disorder (PGUD). This study included 35 controls and 34 patients with PGUD, according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Optic coherence tomography (OCT) measurements including the retinal nerve fiber layer (RNFL), ganglion cell layer-inner plexiform layer (GCL-IPL) and ganglion cell complex (GCC) were performed. RNFL thickness was evaluated in four quadrants (inferior, superior, nasal, temporal). GCL-IPL and GCC thickness were evaluated in six sectors (superior, superonasal, inferonasal, inferior, inferotemporal, superotemporal). GCC inferonasal (p = 0.040, r = 0.354), GCC inferior (p = 0.018, r = 0.402) GCL-IPL inferior (p = 0.031, r = 0.370) and GCL-IPL inferotemporal (p = 0.029, r = 0.376) thickness were positively correlated with the duration of pregabalin use. There was no significant sector or quadrant-wise difference between groups (p > 0.05). Our findings emphasized the drug's potential neuroprotective effect. It should be taken into consideration that neurodegenerative changes due to substance use disorder occur with long-term. Longitudinal prospective studies investigating dose-duration relationship are needed.

Interpretable multimodal classification for age-related macular degeneration diagnosis.

Explainable Artificial Intelligence (XAI) is an emerging machine learning field that has been successful in medical image analysis. Interpretable approaches are able to "unbox" the black-box decisions made by AI systems, aiding medical doctors to justify their diagnostics better. In this paper, we analyze the performance of three different XAI strategies for medical image analysis in ophthalmology. We consider a multimodal deep learning model that combines optical coherence tomography (OCT) and infrared reflectance (IR) imaging for the diagnosis of age-related macular degeneration (AMD). The classification model is able to achieve an accuracy of 0.94, performing better than other unimodal alternatives. We analyze the XAI methods in terms of their ability to identify retinal damage and ease of interpretation, concluding that grad-CAM and guided grad-CAM can be combined to have both a coarse visual justification and a fine-grained analysis of the retinal layers. We provide important insights and recommendations for practitioners on how to design automated and explainable screening tests based on the combination of two image sources.

Structural effects of intraretinal cysts on outer retinal layers in eyes with diabetic macular edema

BackgroundDiabetic macular edema (DME) is the main cause of visual loss in individuals with diabetic retinopathy (DR). This study aims to investigate the effects of central macular intraretinal cysts on the underlying outer retinal layer (ORL) in patients with diabetic macular edema (DME).MethodsIn this retrospective and cross-sectional study, diabetic patients with or without DR were categorized into three groups: without DME (group 1), with DME but without any cyst featuring a plateau in the lower region (group 2), and patients with cyst featuring an inferior cyst plateau (group 3), defined as a flat conformation at its posterior aspect. Variables such as central macular intraretinal cyst height, inferior cyst plateau, and ORL thickness were measured, and ellipsoid zone (EZ) disruption was assessed via Spectral-domain optical coherence tomography (SD-OCT) and compared between groups. Correlations between OCT-measured variables and best-corrected visual acuity (BCVA) were investigated.ResultsA total of 164 eyes were included: 48 in group 1, 47 in group 2 and 69 in group 3. Compared with Groups 1 and 2, Group 3 presented a greater intraretinal cyst height (p < 0.001), a thinner mean ORL beneath the cysts (p < 0.0001) and more frequent EZ disruption (p < 0.0001), which was associated with lower BCVA values. Cyst height, cyst plateau and ORL thickness were significantly correlated with BCVA (p < 0.0001). EZ disruption was associated with the cyst height, the cyst plateau and the underlying ORL thickness. Correlations were observed between cyst height and ORL thickness (r = − 0.32, p < 0.001), between cyst height and cyst plateau (r = 0.60, p < 0.001), and between cyst plateau and ORL thickness (r = − 0.56, p < 0.001). Every increase of 10 μm in plateau width and in cyst height results in reductions of 0.16 μm and 0.29 μm in ORL thickness, respectively, independent of the other parameters. The optimal cutoff point for cyst height that best discriminates plateau formation was determined to be 130.5 μm, with a sensitivity of 89.9% and specificity of 83%.ConclusionsIn patients with DME, large central intraretinal cysts may assume a flat configuration in their lower region, termed a plateau, and are associated with photoreceptor damage due to compression, which can result in visual impairment. These findings can be understood based on modified Hertz’s mechanical contact theory.

Barriers in Healthcare to the Use of Optical Coherence Tomography Angiography in Multiple Sclerosis.

Optical coherence tomography angiography (OCT-A) is a state-of-the-art imaging technique for the retinal vasculature to accurately segment the capillary network and assign it to retinal layers. OCT-A is a promising technique to better understand neurological diseases with visual system manifestations, such as multiple sclerosis (MS), and to identify and characterize vascular biomarkers. Initial studies suggested vascular changes in MS and its differential diagnoses such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Here we review clinical and technical aspects of OCT-A imaging and discuss the potential for the MS field as well as barriers that need to be overcome before OCT-A can be established in clinical application.

Developing a 10-Layer Retinal Segmentation for MacTel Using Semi-Supervised Learning.

Automated segmentation software in optical coherence tomography (OCT) devices is usually developed for and primarily tested on common diseases. Therefore segmentation accuracy of automated software can be limited in eyes with rare pathologies. We sought to develop a semisupervised deep learning segmentation model that segments 10 retinal layers and four retinal features in eyes with Macular Telangiectasia Type II (MacTel) using a small labeled dataset by leveraging unlabeled images. We compared our model against popular supervised and semisupervised models, as well as conducted ablation studies on the model itself. Our model significantly outperformed all other models in terms of intersection over union on the 10 retinal layers and two retinal features in the test dataset. For the remaining two features, the pre-retinal space above the internal limiting membrane and the background below the retinal pigment epithelium, all of the models performed similarly. Furthermore, we showed that using more unlabeled images improved the performance of our semisupervised model. Our model improves segmentation performance over supervised models by leveraging unlabeled data. This approach has the potential to improve segmentation performance for other diseases, where labeled data is limited but unlabeled data abundant. Improving automated segmentation of MacTel pathology on OCT imaging by leveraging unlabeled data may enable more accurate assessment of disease progression, and this approach may be useful for improving feature identification and location on OCT in other rare diseases as well.