Neuropathological hallmarks in the post-mortem retina of neurodegenerative diseases.

The retina is increasingly recognised as a potential source of biomarkers for neurodegenerative diseases. Hallmark protein aggregates in the retinal neuronal tissue could be imaged through light non-invasively. Post-mortem studies have already shown the presence of specific hallmark proteins in Alzheimer's disease, primary tauopathies, synucleinopathies and frontotemporal lobar degeneration. This study aims to assess proteinopathy in a post-mortem cohort with different neurodegenerative diseases and assess the presence of the primary pathology in the retina. Post-mortem eyes were collected in collaboration with the Netherlands Brain Bank from donors with Alzheimer's disease (n = 17), primary tauopathies (n = 8), synucleinopathies (n = 27), frontotemporal lobar degeneration (n = 8), mixed pathology (n = 11), other neurodegenerative diseases (n = 6), and cognitively normal controls (n = 25). Multiple cross sections of the retina and optic nerve tissue were immunostained using antibodies against pTau Ser202/Thr205 (AT8), amyloid-beta (4G8), alpha-synuclein (LB509), pTDP-43 Ser409/410 and p62-lck ligand (p62) and were assessed for the presence of aggregates and inclusions. pTau pathology was observed as a diffuse signal in Alzheimer's disease, primary tauopathies and controls with Alzheimer's disease neuropathological changes. Amyloid-beta was observed in the vessel wall and as cytoplasmic granular deposits in all groups. Alpha-synuclein pathology was observed as Lewy neurites in the retina in synucleinopathies associated with Lewy pathology and as oligodendroglial cytoplasmic inclusions in the optic nerve in multiple system atrophy. Anti-pTDP-43 generally showed typical neuronal cytoplasmic inclusion bodies in cases with frontotemporal lobar degeneration with TDP-43 and also in cases with later stages of limbic-associated TDP-43 encephalopathy. P62 showed inclusion bodies similar to those seen with anti-pTDP-43. Furthermore, pTau and alpha-synuclein pathology were significantly associated with increasing Braak stages for neurofibrillary tangles and Lewy bodies, respectively. Mixed pathology cases in this cohort consisted of cases (n = 6) with high Braak LB stages (> 4) and low or moderate AD pathology, high AD pathology (n = 1, Braak NFT 6, Thal phase 5) with moderate LB pathology, or a combination of low/moderate scores for different pathology scores in the brain (n = 4). There were no cases with advanced co-pathologies. In seven cases with Braak LB ≥ 4, LB pathology was observed in the retina, while tau pathology in the retina in the mixed pathology group (n = 11) could not be observed. From this study, we conclude that the retina reflects the presence of the major hallmark proteins associated with neurodegenerative diseases. Although low or moderate levels of copathology were found in the brains of most cases, the retina primarily manifested protein aggregates associated with the main neurodegenerative disease. These findings indicate that with appropriate retinal imaging techniques, retinal biomarkers have the potential to become highly accurate indicators for diagnosing the major neurodegenerative diseases of the brain.

Investigating the use of comprehensive motion monitoring for intrafraction 3D drift assessment of hypofractionated prostate cancer patients on a 1.5T magnetic resonance imaging radiotherapy system.

This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often > 2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections.

Polarization-sensitive optical coherence tomography and scleral collagen fiber orientation in osteogenesis imperfecta.

Osteogenesis imperfecta (OI), a rare genetic connective tissue disorder, primarily arises from pathogenic variants affecting the production or structure of collagen type I. In addition to skeletal fragility, individuals with OI may face an increased risk of developing ophthalmic diseases. This association is believed to stem from the widespread presence of collagen type I throughout various parts of the eye. However, the precise consequences of abnormal collagen type I on different ocular tissues remain unknown. Of particular significance is the sclera, where collagen type I is abundant and crucial for maintaining the structural integrity of the eye. Recent research on healthy individuals has uncovered a unique organizational pattern of collagen fibers within the sclera, characterized by fiber arrangement in both circular and radial layers around the optic nerve head. While the precise function of this organizational pattern remains unclear, it is hypothesized to play a role in providing mechanical support to the optic nerve. The objective of this study is to investigate the impact of abnormal collagen type I on the sclera by assessing the fiber organization near the optic nerve head in individuals with OI and comparing them to healthy individuals. Collagen fiber orientation of the sclera was measured using polarization-sensitive optical coherence tomography (PS-OCT), an extension of the conventional OCT that is sensitive to materials that exhibit birefringence (axial changes in light refraction). Birefringence was quantified and used as imaging contrast to extract collagen fiber orientation as well as the thickness of the radially oriented scleral layer. Three individuals with OI, exhibiting different degrees of disease severity, were assessed and analyzed, along with seventeen healthy individuals. Mean values obtained from individuals with OI were descriptively compared to those of the healthy participant group. PS-OCT revealed a similar orientation pattern of scleral collagen fibers around the optic nerve head between OI individuals and healthy individuals. However, two OI participants exhibited reduced mean birefringence of the radially oriented scleral layer compared to the healthy participant group (OI participant 1 oculus dexter et sinister (ODS): 0.34°/µm, OI participant 2: ODS 0.26°/µm, OI participant 3: OD: 0.29°/µm, OS: 0.28°/µm, healthy participants: ODS 0.38 ± 0.05°/µm). The radially oriented scleral layer was thinner in all OI participants although within ±2 standard deviations of the mean observed in healthy individuals (OI participant 1 OD: 101 µm, OS 104 µm, OI participant 2: OD 97 µm, OS 98 µm, OI participant 3: OD: 94 µm, OS 120 µm, healthy participants: OD 122.8 ± 13.6 µm, OS 120.8 ± 15.1 µm). These findings imply abnormalities in collagen organization or composition, underscoring the necessity for additional research to comprehend the ocular phenotype in OI.

Theoretical and experimental determination of the confocal function of OCT systems for accurate calculation of sample optical properties.

The attenuation coefficient of biological tissue could serve as an indicator of structural and functional changes related to the onset or progression of disease. Optical coherence tomography (OCT) provides cross sectional images of tissue up to a depth of a few millimeters, based on the local backscatter properties. The OCT intensity also depends on the confocal function, which needs to be characterised to determine correctly the exponential decay of the intensity based on Lambert-Beer. We present a model for the confocal function in scattering media based on the illumination with a Gaussian beam and the power transfer into a single mode fibre (SMF) of the backscattered light for an incoherently back scattered Gaussian beam using the Huygens-Fresnel principle and compare that model with the reflection from a mirror. We find that, contrary to previous literature, the confocal functions characterised by the Rayleigh range in the two models are identical. Extensive OCT focus series measurements on a mirror, Spectralon and Intralipid dilutions confirm our model, and show that for highly scattering samples the confocal function characterised by the Rayleigh range becomes depth dependent. From the diluted Intralipid measurements the attenuation coefficients are extracted using a singly scatter model that includes the previously established confocal function. The extracted attenuation coefficients were in good agreement for weakly scattering samples (µ s < 2 mm-1).

Frequency of Agreement Between Structural and Functional Glaucoma Testing: A Longitudinal Study of 3D OCT and Current Clinical Tests.

PURPOSE: To evaluate how often tests of structure and function detect glaucoma progression at the same study visit. Tests include current glaucoma clinical tests and a new 3-dimensional (3D) optical coherence tomography (OCT) rim measurement. DESIGN: Prospective cohort study. METHODS: For 124 open-angle glaucoma patients at a single institution, one eye was randomly selected for each patient. Patients were included if they had open-angle glaucoma and if they had at least 4 yearly study visits. Study visits included a full dilated eye exam, disc photography (DP), Humphrey visual field (HVF 24-2) testing, 2D OCT retinal nerve fibre layer (RNFL) thickness measurements, and 3D OCT neuroretinal rim measurements (i.e., minimum distance band or MDB). For each test at each study visit, eyes were classified as progressors or non-progressors using event-based analysis. Agreement occurred if tests progressed in the same eye at the same study visit. Agreements between all compared tests were calculated as percentages of agreement. RESULTS: The study included 124 open-angle glaucoma eyes, which had an average follow-up period of 66.9 ± 16.4 months. Structural tests (i.e., DP, global RNFL thickness, and global MDB rim thickness) progressed at the same visit as the functional test (i.e., HVF testing) in only 5.0% (3/60) to 16.0% (13/81) of eyes. Global MDB thickness and global RNFL thickness showed similar agreement with functional HVF testing (i.e., 16.0% [13/81] and 8.3% [7/84], respectively), and global MDB thickness showed better structure-function agreement with HVF testing than between DP and HVF testing (i.e., 5.0% [3/60], P = 0.04). For all paired comparisons between testing methods, eyes with moderate glaucoma showed similar or better agreement than eyes with mild or severe glaucoma. CONCLUSIONS: Clinical tests of structure and function do not usually progress at the same clinic visit. Most of the time, glaucoma progression is only detected by one or two tests.

Treatment planning evaluation and experimental validation of the magnetic resonance-based intrafraction drift correction.

Background and purpose: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC. Materials and methods: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes. Results: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%. Conclusion: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.

Gating and intrafraction drift correction on a 1.5 T MR-Linac: Clinical dosimetric benefits for upper abdominal tumors.

This work reports on the first seven patients treated with gating and baseline drift correction on the high-field MR-Linac system. Dosimetric analysis showed that the active motion management system improved congruence to the planned dose, efficiently mitigating detrimental effects of intrafraction motion in the upper abdomen.

Confocal corrected attenuation coefficient imaging in phantoms and in vivo using chromatic focal shift calibration.

Optical coherence tomography (OCT) is conventionally used for structural imaging of tissue. Calibrating the intensity values of OCT images can give information on the tissue's inherent optical properties, such as the attenuation coefficient, which can provide an additional parameter to quantify possible pathological changes. To obtain calibrated intensity values, the focus position and Rayleigh length of the incident beam need to be known. We explore the feasibility of extracting the focus position from an OCT scan acquired with a single focus setting using the chromatic aberration of the system. The chromatic focal shift of an OCT system is exploited to achieve different focus positions for sub-spectrum reconstructed OCT images. The ratios of these images are used to estimate the focus position. Reconstruction of a high-resolution B-scan from coherent addition of sub-spectrum confocal function corrected B-scans and subsequent high-resolution OCT attenuation coefficient imaging is demonstrated. Furthermore, we introduce a method to experimentally determine the chromatic focal shifts of an OCT system in phantoms and an in vivo human retina. These shifts are compared to the theoretically expected shifts calculated with ray tracing.

In vivo polarisation sensitive optical coherence tomography for fibrosis assessment in interstitial lung disease: a prospective, exploratory, observational study.

INTRODUCTION: Endobronchial polarisation sensitive optical coherence tomography (EB-PS-OCT) is a bronchoscopic imaging technique exceeding resolution of high-resolution CT (HRCT) by 50-fold. It detects collagen birefringence, enabling identification and quantification of fibrosis. STUDY AIM: To assess pulmonary fibrosis in interstitial lung diseases (ILD) patients with in vivo EB-PS-OCT using histology as reference standard. PRIMARY OBJECTIVE: Visualisation and quantification of pulmonary fibrosis by EB-PS-OCT. SECONDARY OBJECTIVES: Comparison of EB-PS-OCT and HRCT detected fibrosis with histology, identification of ILD histological features in EB-PS-OCT images and comparison of ex vivo PS-OCT results with histology. METHODS: Observational prospective exploratory study. Patients with ILD scheduled for transbronchial cryobiopsy or surgical lung biopsy underwent in vivo EB-PS-OCT imaging prior to tissue acquisition. Asthma patients were included as non-fibrotic controls. Per imaged lung segment, fibrosis was automatically quantified assessing the birefringent area in EB-PS-OCT images. Fibrotic extent in corresponding HRCT areas and biopsies were compared with EB-PS-OCT detected fibrosis. Microscopic ILD features were identified on EB-PS-OCT images and matched with biopsies from the same segment. RESULTS: 19 patients were included (16 ILD; 3 asthma). In 49 in vivo imaged airway segments the parenchymal birefringent area was successfully quantified and ranged from 2.54% (no to minimal fibrosis) to 21.01% (extensive fibrosis). Increased EB-PS-OCT detected birefringent area corresponded to increased histologically confirmed fibrosis, with better predictive value than HRCT. Microscopic ILD features were identified on both in vivo and ex vivo PS-OCT images. CONCLUSIONS: EB-PS-OCT enables pulmonary fibrosis quantification, thereby has potential to serve as an add-on bronchoscopic imaging technique to diagnose and detect (early) fibrosis in ILD.

α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies.

There is increasing interest in studying retinal biomarkers for various neurodegenerative diseases. Specific protein aggregates associated with neurodegenerative diseases are present in the retina and could be visualised in a non-invasive way. This study aims to assess the specificity and sensitivity of retinal α-synuclein aggregates in neuropathologically characterised α-synucleinopathies, other neurodegenerative diseases and non-neurological controls. Post-mortem eyes (N = 99) were collected prospectively through the Netherlands Brain Bank from donors with Parkinson's disease (and dementia), dementia with Lewy bodies, multiple system atrophy, Alzheimer's disease, other neurodegenerative diseases and non-neurological controls. Multiple retinal and optic nerve cross-sections were immunostained with anti-α-synuclein antibodies (LB509, KM51, and anti-pSer129) and assessed for aggregates and inclusions. α-Synuclein was observed as Lewy neurites in the retina and oligodendroglial cytoplasmic inclusions in the optic nerve and was highly associated with Lewy body disease (P < 0.001) and multiple system atrophy (P = 0.001). In all multiple system atrophy cases, the optic nerve showed oligodendroglial cytoplasmic inclusions, while retinal Lewy neurites were absent, despite coincidental brain Lewy pathology. With high specificity (97%) and sensitivity (82%), retinal/optic nerve α-synuclein differentiates primary α-synucleinopathies from other cases and controls. α-Synuclein pathology occurs specifically in the retina and optic nerve of primary α-synucleinopathies as opposed to other neurodegenerative diseases-with and without α-synuclein co-pathology-and controls. The absence of retinal Lewy neurites in multiple system atrophy could contribute to the development of an in vivo retinal biomarker that discriminates between Lewy body disease and multiple system atrophy.

Deep learning for automated contouring of neurovascular structures on magnetic resonance imaging for prostate cancer patients.

Background and purpose: Manual contouring of neurovascular structures on prostate magnetic resonance imaging (MRI) is labor-intensive and prone to considerable interrater disagreement. Our aim is to contour neurovascular structures automatically on prostate MRI by deep learning (DL) to improve workflow and interrater agreement. Materials and methods: Segmentation of neurovascular structures was performed on pre-treatment 3.0 T MRI data of 131 prostate cancer patients (training [n = 105] and testing [n = 26]). The neurovascular structures include the penile bulb (PB), corpora cavernosa (CCs), internal pudendal arteries (IPAs), and neurovascular bundles (NVBs). Two DL networks, nnU-Net and DeepMedic, were trained for auto-contouring on prostate MRI and evaluated using volumetric Dice similarity coefficient (DSC), mean surface distances (MSD), Hausdorff distances, and surface DSC. Three radiation oncologists evaluated the DL-generated contours and performed corrections when necessary. Interrater agreement was assessed and the time required for manual correction was recorded. Results: nnU-Net achieved a median DSC of 0.92 (IQR: 0.90-0.93) for the PB, 0.90 (IQR: 0.86-0.92) for the CCs, 0.79 (IQR: 0.77-0.83) for the IPAs, and 0.77 (IQR: 0.72-0.81) for the NVBs, which outperformed DeepMedic for each structure (p < 0.03). nnU-Net showed a median MSD of 0.24 mm for the IPAs and 0.71 mm for the NVBs. The median interrater DSC ranged from 0.93 to 1.00, with the majority of cases (68.9%) requiring manual correction times under two minutes. Conclusions: DL enables reliable auto-contouring of neurovascular structures on pre-treatment MRI data, easing the clinical workflow in neurovascular-sparing MR-guided radiotherapy.

Sub-diffraction computational imaging via a flexible multicore-multimode fiber.

An ultra-thin multimode fiber is an ideal platform for minimally invasive microscopy with the advantages of a high density of modes, high spatial resolution, and a compact size. In practical applications, the probe needs to be long and flexible, which unfortunately destroys the imaging capabilities of a multimode fiber. In this work, we propose and experimentally demonstrate sub-diffraction imaging through a flexible probe based on a unique multicore-multimode fiber. A multicore part consists of 120 Fermat's spiral distributed single-mode cores. Each of the cores offers stable light delivery to the multimode part, which provides optimal structured light illumination for sub-diffraction imaging. As a result, perturbation-resilient fast sub-diffraction fiber imaging by computational compressive sensing is demonstrated.

Swept-source multimode fiber imaging.

High-resolution compressive imaging via a flexible multimode fiber is demonstrated using a swept-laser source and wavelength dependent speckle illumination. An in-house built swept-source allowing for independent control of bandwidth and scanning range is used to explore and demonstrate a mechanically scan-free approach for high-resolution imaging through an ultrathin and flexible fiber probe. The computational image reconstruction is shown by utilizing a narrow sweeping bandwidth of [Formula: see text] nm while acquisition time is decreased by 95% compared to conventional raster scanning endoscopy. Demonstrated narrow-band illumination in the visible spectrum is vital for the detection of fluorescence biomarkers in neuroimaging applications. The proposed approach yields device simplicity and flexibility for minimally invasive endoscopy.

A Common Active Intermediate in the Oxidation of Alkenes, Alcohols and Alkanes with H2O2 and a Mn(II)/Pyridin-2-Carboxylato Catalyst.

The mechanism and the reactive species involved in the oxidation of alkenes, and alcohols with H2O2, catalysed by an in situ prepared mixture of a MnII salt, pyridine-2-carboxylic acid and a ketone is elucidated using substrate competition experiments, kinetic isotope effect (KIE) measurements, and atom tracking with 18O labelling. The data indicate that a single reactive species engages in the oxidation of both alkenes and alcohols. The primary KIE in the oxidation of benzyl alcohols is ca. 3.5 and shows the reactive species to be selective despite a zero order dependence on substrate concentration, and the high turnover frequencies (up to 30 s-1) observed. Selective 18O labelling identifies the origin of the oxygen atoms transferred to the substrate during oxidation, and is consistent with a highly reactive, e. g., [MnV(O)(OH)] or [MnV(O)2], species rather than an alkylperoxy or hydroperoxy species.

Field-position dependent apodization in dark-field digital holographic microscopy for semiconductor metrology.

Measuring overlay between two layers of semiconductor devices is a crucial step during electronic chip fabrication. We present dark-field digital holographic microscopy that addresses various overlay metrology challenges that are encountered in the semiconductor industry. We present measurement results that show that the point-spread function of our microscope depends on the position in the field-of-view. We will show that this novel observation can be explained by a combination of the finite bandwidth of the light source and a wavelength-dependent focal length of the imaging lens. Moreover, we will also present additional experimental data that supports our theoretical understanding. Finally, we will propose solutions that reduce this effect to acceptable levels.

Magnetic Resonance-Guided Adaptive Radiation Therapy for Prostate Cancer: The First Results from the MOMENTUM study-An International Registry for the Evidence-Based Introduction of Magnetic Resonance-Guided Adaptive Radiation Therapy.

PURPOSE: Magnetic resonance (MR)-guided radiation therapy (MRgRT) is a new technique for treatment of localized prostate cancer (PCa). We report the 12-month outcomes for the first PCa patients treated within an international consortium (the MOMENTUM study) on a 1.5T MR-Linac system with ultrahypofractionated radiation therapy. METHODS AND MATERIALS: Patients treated with 5 × 7.25 Gy were identified. Prostate specific antigen-level, physician-reported toxicity (Common Terminology Criteria for Adverse Events [CTCAE]), and patient-reported outcomes (Quality of Life Questionnaire PR25 and Quality of Life Questionnaire C30 questionnaires) were recorded at baseline and at 3, 6, and 12 months of follow-up (FU). Pairwise comparative statistics were conducted to compare outcomes between baseline and FU. RESULTS: The study included 425 patients with localized PCa (11.4% low, 82.0% intermediate, and 6.6% high-risk), and 365, 313, and 186 patients reached 3-, 6-, and 12-months FU, respectively. Median prostate specific antigen level declined significantly to 1.2 ng/mL and 0.1 ng/mL at 12 months FU for the nonandrogen deprivation therapy (ADT) and ADT group, respectively. The peak of genitourinary and gastrointestinal CTCAE toxicity was reported at 3 months FU, with 18.7% and 1.7% grade ≥2, respectively. The QLQ-PR25 questionnaire outcomes showed significant deterioration in urinary domain score at all FU moments, from 8.3 (interquartile range [IQR], 4.1-16.6) at baseline to 12.4 (IQR, 8.3-24.8; P = .005) at 3 months, 12.4 (IQR, 8.3-20.8; P = .018;) at 6 months, and 12.4 (IQR, 8.3-20.8; P = .001) at 12 months. For the non-ADT group, physician- and patient-reported erectile function worsened significantly between baseline and 12 months FU. CONCLUSIONS: Ultrahypofractionated MR-guided radiation therapy for localized PCa using a 1.5T MR-Linac is effective and safe. The peak of CTCAE genitourinary and gastrointestinal toxicity was reported at 3 months FU. Furthermore, for patients without ADT, a significant increase in CTCAE erectile dysfunction was reported at 12 months FU. These data are useful for educating patients on expected outcomes and informing study design of future comparative-effectiveness studies.

Phosphorylated tau in the retina correlates with tau pathology in the brain in Alzheimer's disease and primary tauopathies.

The retina is a potential source of biomarkers for the detection of neurodegenerative diseases. Accumulation of phosphorylated tau (p-tau) in the brain is a pathological feature characteristic for Alzheimer's disease (AD) and primary tauopathies. In this study the presence of p-tau in the retina in relation to tau pathology in the brain was assessed. Post-mortem eyes and brains were collected through the Netherlands Brain Bank from donors with AD (n = 17), primary tauopathies (n = 8), α-synucleinopathies (n = 13), other neurodegenerative diseases including non-tau frontotemporal lobar degeneration (FTLD) (n = 9), and controls (n = 15). Retina cross-sections were assessed by immunohistochemistry using antibodies directed against total tau (HT7), 3R and 4R tau isoforms (RD3, RD4), and phospho-epitopes Ser202/Thr205 (AT8), Thr217 (anti-T217), Thr212/Ser214 (AT100), Thr181 (AT270), Ser396 (anti-pS396) and Ser422 (anti-pS422). Retinal tau load was compared to p-tau Ser202/Thr205 and p-tau Thr217 load in various brain regions. Total tau, 3R and 4R tau isoforms were most prominently present in the inner plexiform layer (IPL) and outer plexiform layer (OPL) of the retina and were detected in all cases and controls as a diffuse and somatodendritic signal. Total tau, p-tau Ser202/Thr205 and p-tau Thr217 was observed in amacrine and horizontal cells of the inner nuclear layer (INL). Various antibodies directed against phospho-epitopes of tau showed immunoreactivity in the IPL, OPL, and INL. P-tau Ser202/Thr205 and Thr217 showed significant discrimination between AD and other tauopathies, and non-tauopathy cases including controls. Whilst immunopositivity was observed for p-tau Thr212/Ser214, Thr181 and Ser396, there were no group differences. P-tau Ser422 did not show any immunoreactivity in the retina. The presence of retinal p-tau Ser202/Thr205 and Thr217 correlated with Braak stage for NFTs and with the presence of p-tau Ser202/Thr205 in hippocampus and cortical brain regions. Depending on the phospho-epitope, p-tau in the retina is a potential biomarker for AD and primary tauopathies.