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Abstract Background The potential diagnostic value of plasma amyloidogenic beta residue 42/40 ratio (Aβ42/Aβ40 ratio), neurofilament light (NfL), tau phosphorylated at threonine-181 (p-tau181), and threonine-217 (p-tau217) has been extensively discussed in the literature. We have also previously described the association between retinal biomarkers and preclinical Alzheimer’s disease (AD). The goal of this study was to evaluate the association, and a multimodal model of, retinal and plasma biomarkers for detection of preclinical AD. Methods We included 82 cognitively unimpaired (CU) participants (141 eyes; mean age: 67 years; range: 56–80) from the Atlas of Retinal Imaging in Alzheimer’s Study (ARIAS). Blood samples were assessed for concentrations of Aβ42/Aβ40 ratio, NfL, p-tau181, and p-tau217 (ALZpath, Inc.) using Single molecule array (SIMOA) technology. The Spectralis II system (Heidelberg Engineering) was used to acquire macular centered Spectral Domain Optical Coherence Tomography (SD-OCT) images for evaluation of putative retinal gliosis surface area and macular retinal nerve fiber layer (mRNFL) thickness. For all participants, correlations (adjusted for age and correlation between eyes) were assessed between retinal and blood-based biomarkers. A subgroup cohort of 57 eyes from 32 participants with recent Aβ positron emission tomography (PET) results, comprising 18 preclinical patients (Aβ PET + ve, 32 eyes) and 14 controls (Aβ PET -ve, 25 eyes) with a mean age of 69 vs. 66, p = 0.06, was included for the assessment of a multimodal model to distinguish between the two groups. For this subgroup cohort, receiver operating characteristic (ROC) analysis was performed to compare the multimodal model of retinal and plasma biomarkers vs. each biomarker alone to distinguish between the two groups. Results Significant correlation was found between putative retinal gliosis and p-tau217 in the univariate mixed model (β = 0.48, p = 0.007) but not for the other plasma biomarkers (p > 0.05). This positive correlation was also retained in the multivariate mixed model (β = 0.43, p = 0.022). The multimodal ROC model based on retinal (gliosis area, inner inferior RNFL thickness, inner superior RNFL thickness, and inner nasal RNFL thickness) and plasma biomarkers (p-tau217 and Aβ42/Aβ40 ratio) had an excellent AUC of 0.97 (95% CI = 0.93–1.01; p

Ocular comorbidities can happen as congenital defective gene associations. We present a 37-year-old female patient who was mentally challenged and had coexisting achromatopsia gene abnormality on genetic analysis. She was operated in childhood for congenital cataract, and posterior chamber intraocular lens (IOL) was implanted at 10 years of age elsewhere. The patient presented 27 years later with luxated IOL with endothelial decompensation. There was a coexisting steep and thin cornea noted on corneal topography. She was managed with pre-Descemet's endothelial keratoplasty with transpositioning of posterior chamber IOL to glued IOL with single-pass four-throw pupilloplasty. Postoperatively, the cornea was clear with centered glued IOL. The lesser postanesthetic challenges and faster rehabilitation are obtained in combination procedures with reduced complications in such rare scenarios.

Abstract Background Compared to standard neuro-diagnostic techniques, retinal biomarkers provide a probable low-cost and non-invasive alternative for early Alzheimer’s disease (AD) risk screening. We have previously quantified the periarteriole and perivenule capillary free zones (mid-peripheral CFZs) in cognitively unimpaired (CU) young and older adults as novel metrics of retinal tissue oxygenation. There is a breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion or dropout in AD leading to potential enlargement of the mid-peripheral CFZs. We hypothesized the mid-peripheral CFZs will be enlarged in CU older adults at high risk for AD compared to low-risk individuals. Methods 20 × 20° optical coherence tomography angiography images consisting of 512 b-scans, 512 A-scans per b-scan, 12-µm spacing between b-scans, and 5 frames averaged per each b-scan location of the central fovea and of paired major arterioles and venules with their surrounding capillaries inferior to the fovea of 57 eyes of 37 CU low-risk (mean age: 66 years) and 50 eyes of 38 CU high-risk older adults (mean age: 64 years; p = 0.24) were involved in this study. High-risk participants were defined as having at least one APOE e4 allele and a positive first-degree family history of AD while low-risk participants had neither of the two criteria. All participants had Montreal Cognitive Assessment scores ≥ 26. The mid-peripheral CFZs were computed in MATLAB and compared between the two groups. Results The periarteriole CFZ of the high-risk group (75.8 ± 9.19 µm) was significantly larger than that of the low-risk group (71.3 ± 7.07 µm), p = 0.005, Cohen’s d = 0.55. The perivenule CFZ of the high-risk group (60.4 ± 8.55 µm) was also significantly larger than that of the low-risk group (57.3 ± 6.40 µm), p = 0.034, Cohen’s d = 0.42. There were no significant differences in foveal avascular zone (FAZ) size, FAZ effective diameter, and vessel density between the two groups, all p > 0.05. Conclusions Our results show larger mid-peripheral CFZs in CU older adults at high risk for AD, with the potential for the periarteriole CFZ to serve as a novel retinal vascular biomarker for early AD risk detection.

(1) Background: Previously, VESsel GENeration (VESGEN) software was used to map and quantify vascular changes observed on fluorescein angiography (FA) in subjects (n = 15 eyes) with retinal pathology ranging from mild non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). In the current study, we used VESGEN for the assessment of individuals with early-stage NPDR imaged by FA (Cohort 1) and by optical coherence tomography angiography (OCTA; Cohort 2). (2) Methods: Cohort 1 included type 2 diabetics (T2D), represented 21 eyes (ranging from no DR to moderate DR), and also included nondiabetic controls (NDC; n = 15 eyes). Cohort 2 consisted of 23 eyes from T2D subjects (including no DR subjects and moderate DR subjects) and NDC (n = 18 eyes). (3) Results: In the FA-VESGEN study, total tortuosity (Tv) of microvessels (G ≥ 6) increased in T2D with mild DR compared to the controls. In contrast, the VESGEN analysis of OCTA images showed that vessel length (characterized as density) was lower in T2D subjects before the diagnosis of DR and following the diagnosis of DR when compared to the controls. Additionally, T2D showed a significant decrease in vessel area (density). (4) Conclusions: FA elucidated the vessel morphology of small-generation microvessels to a greater degree than OCTA; however, OCTA identified changes in vessel density better than FA. VESGEN analysis can be used with both standard FA and OCTA to facilitate our understanding of early events in DR, including before the clinical diagnosis of DR.

Background: Corneal angiogenesis occurs as a sequel to an insult and it brings with it cells that mediate immunity as well as repair and aids in flushing toxins out. These vessels are formed in haste and leak lipid and cells, ultimately resulting in loss of transparency, lipid keratopathy and immunogenicity. So, they may need treatment prior to an optical keratoplasty. Purpose: To demonstrate the procedure of Fine Needle Diathermy (FND) to treat corneal neovascularization, its indications and contraindications. Synopsis: FND uses coagulating current from a monopolar cautery unit to occlude the afferent and efferent blood vessels. FND works best at the stage of mature vessel formation. The needle is placed across a tuft of vessels or parallel to a single large vessel, being mindful of the depth and direction. FND is avoided in necrotic tissue where the blood vessel is needed for healing process. Occlusion of the vessel in these situations may result in tissue melt. Highlights: Corneal neovascularization follows the stages of latent phase, active neovascularization, mature vessel formation and then regression. The treatment modality depends on the stage of angiogenesis. FND works best for neovascularization due to infectious keratitis. Keratoplasty is best performed 3 to 4 months later when regression of corneal vascularization occurs. Video Link: https://youtu.be/2RK6d_a2Gdc