Cellular Determinants of Visual Outcomes in Eyes with Epiretinal Membrane: Insights from Adaptive Optics OCT.

Objective: In this study, we aimed to evaluate cellular alterations in the foveal neuroglia of eyes with idiopathic epiretinal membrane (ERM) and examine their correlation with visual function. We also aimed to identify prognostic markers for visual outcomes postvitrectomy. Design: A prospective longitudinal study. Subjects: The study comprised 84 subjects, including 50 eyes diagnosed with idiopathic ERM and 34 healthy eyes serving as controls. Methods: The foveal neuroglial changes in eyes with idiopathic ERM were determined using adaptive optics OCT (AO-OCT) by comparing them with healthy eyes. For patients with ERM, the ERM and inner limiting membrane were removed during vitrectomy in all eyes. Main Outcome Measures: Foveal microstructures on AO-OCT images, best-corrected visual acuity (BCVA) and M-CHARTS scores, evaluated preoperatively and at 1, 3, and 6 months postoperatively, and associations between foveal neuroglial changes and these parameters. Results: Adaptive optics OCT revealed discernible differences in the foveal cones of the eyes with ERM and their healthy counterparts. The thickness of the ellipsoid zone (EZ) band was augmented in eyes with ERM. The alignment of the Müller cells was more vertical and the density of the foveal cone cell nuclei was higher in eyes with ERM than in healthy eyes. Within the AO-OCT parameters, the higher cone nuclei count correlated with worse M-CHARTS scores, both preoperatively and 6 months postoperatively (P = 0.004, 0.010, respectively). Greater EZ thickness was significantly associated with poorer 6-month postoperative BCVA (P = 0.005). Conclusions: Adaptive optics OCT can be used to precisely identify cellular alterations in eyes with ERM that are closely related to visual function impairments. These cellular insights enhance our understanding of ERM pathology and offer promising prognostic indicators of visual outcome after vitrectomy.

Severe Circulatory Disturbance in Optic Disc, Retina, and Choroid Following Sub-Tenon Triamcinolone Acetonide Injection for Posterior Scleritis.

PURPOSE: To report a rare case of optic disc and chorioretinal vascular occlusions in the right eye following sub-Tenon injection of triamcinolone acetonide (STTA) in an older male patient with scleritis and to discuss the associated risk factors and potential alternative therapies. METHODS: The medical history and clinical examination, including fundoscopy, fluorescein angiography (FA), and indocyanine green angiography (ICGA), were conducted to diagnose and evaluate the extent of vascular occlusion after STTA. An extensive literature review was undertaken to ascertain the associated risks and consider other treatment options for scleritis. RESULTS: Severe circulatory disturbances in the optic disc and chorioretinal regions of the right eye developed after STTA for exacerbated scleritis, as confirmed by FA and ICGA, resulting in a significant decrease in visual acuity. A complex medical history encompassing ophthalmic and systemic health issues may have contributed to this negative outcome. A literature review pointed out the potential complications of STTA and highlighted alternative approaches to scleritis management. CONCLUSIONS: Cautious application of STTA in treating scleritis is crucial, especially in patients with pre-existing vascular or ocular conditions. Thus, a multidisciplinary approach and a careful assessment of various treatment options are vital to minimize the risk of severe complications and improve patient outcomes.

Blood flow alterations in cavernous sinus dural arteriovenous fistula: Optical coherence tomography angiography findings.

Purpose: This case report details the diagnostic process for a patient with an initial diagnosis of scleritis who was unresponsive to typical treatment modalities, culminating in the identification of a cavernous sinus dural arteriovenous fistula (CS-DAVF). The case highlights the role of anterior segment optical coherence tomography angiography (OCTA) in the diagnosis of this vascular anomaly and in monitoring the response to treatment. Observations: A 45-year-old man with persistently elevated intraocular pressure (IOP) and ocular congestion in the left eye was unresponsive to treatment for scleritis. The persistent ocular symptoms and new-onset tinnitus prompted further investigation. Anterior segment OCTA revealed vascular anomalies, and magnetic resonance imaging confirmed a CS-DAVF. The patient underwent endovascular treatment for the CS-DAVF. This intervention led to a significant reduction in IOP in the left eye and the resolution of ocular congestion. Conclusions and importance: This case highlights the diagnostic complexities of ophthalmic symptoms that mimic those of other conditions. Furthermore, it demonstrates the essential role of anterior segment OCTA in the accurate diagnosis and effective management of CS-DAVF and highlights the need for comprehensive diagnostic approaches in ophthalmology.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): Estimation of pathological lesion stage from brain images.

BACKGROUND: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a disease responsible for cognitive impairment in adult humans. It is caused by mutations in the colony stimulating factor 1 receptor gene (CSF1R) or alanyl-transfer (t) RNA synthetase 2 (AARS2) gene and affects brain white matter. Settlement of stages of the pathological brain lesions (Oyanagi et al. 2017) from the findings of brain imaging will be inevitably essential for prognostication. METHODS: MRI images of eight patients with ALSP were analyzed semiquantitatively. White matter degeneration was assessed on a scale of 0 to 4 (none, patchy, large patchy, confluent, and diffuse) at six anatomical points, and brain atrophy on a scale 0 to 4 (none, slight, mild, moderate, and severe) in four anatomical areas. The scores of the two assessments were then summed to give total MRI scores of 0-40 points. Based on the scores, the MRI features were classified as Grades (0-4). Regression analysis was applied to mutual association between mRS, white matter degeneration score, brain atrophy score, the total MRI score and disease duration. RESULTS: White matter degeneration score, brain atrophy score, and the total MRI score were significantly correlated with the disease duration. MRI Grades (2-4) based on the total MRI scores and the features of the images were well correlated with the pathological lesion stages (II - IV); i.e., 'large patchy' white matter degeneration in the frontal and parietal lobes (MRI Grade 2) corresponded to pathological Stage II, 'confluent' degeneration (Grade 3) to Stage III, and 'diffuse' degeneration (Grade 4) to Stage IV. CONCLUSION: MRI Grades (2-4) resulted from the total MRI scores were well correlated with the pathological lesion Stages (II - IV).

Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane.

BACKGROUND: Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries. METHODS AND DESIGN: This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications. DISCUSSION: The results of this study will support the surgical decisions and procedures in ERM practices.

Vitreous hemorrhage in retinal vein occlusion without visible traction from the posterior vitreous membrane: An optical coherence tomography angiography case report study.

Background: We report an unusual case of retinal vein occlusion (RVO) associated with vitreous hemorrhage (VH) without visible traction from the posterior vitreous membrane (PVM) at the bleeding point, challenging our current understanding of VH pathophysiology. Case presentation: A 52-year-old man presented with VH in the right eye. A detailed examination using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography revealed branch RVO with non-perfused areas (NPAs) extending peripherally and neovascularization elsewhere (NVE). OCTA showed NVE infiltrating the vitreous cavity, leading to substantial bleeding without visible PVM traction at the bleeding point. The NVE was successfully removed following vitrectomy, and visual acuity improved from 20/20 to 20/13 preoperatively, along with a postoperative improvement in floaters. Conclusions: This unique case of RVO suggests the possibility of VH occurring independent of PVM contractions at the bleeding point, challenging the traditional understanding of VH. This finding underscores the potential role of OCTA in diagnosing and managing retinal vascular diseases, underscoring the need for further investigations into the underlying mechanisms, with potential implications for personalized therapeutic strategies.

A Descriptive Study of the Characteristics of Homicide-Suicide in Forensic Autopsy Cases.

Homicide followed by suicide (HS) is a tragic event with varied characteristics across countries and regions. Compared to Western countries, there are limited studies on HS in Asian countries. Therefore, this study aimed to clarify the characteristics of recent HS cases by examining forensic autopsy records from 2008 to 2020 collected from the Department of Legal Medicine, Chiba University, in Japan. A total of 77 HS cases were identified, involving 77 perpetrators (52 completed suicides, 25 attempted suicides), with 28 perpetrator and 89 victim autopsies. Our findings showed that older adults accounted for nearly half of the victims; victims were mostly females, whereas most perpetrators were male. The most common HS relationship was that between a parent and a child. Autopsy findings showed that the most common cause of death was strangulation, and illegal drugs were detected only in a few cases; however, psychotropic drugs were detected in child victims. No obvious evidence of past child physical abuse by caregivers was found. In contrast, intimate partner violence (IPV) was present, with a history of IPV found in half of HS cases involving adult intimate partner relationships. Notably, gender differences in age and relationship to the victim were identified. Likewise, some perpetrators may have expressed their plans and intentions for HS before the event, which may represent an important sign for HS prevention. However, to accurately reveal the course of HS, nationwide integrated statistics, forensic autopsies, including toxicological analyses of the deceased; and forensic psychiatric perspectives, including psychological autopsy, are required.

Selenoneine Is Methylated in the Bodies of Mice and then Excreted in Urine as Se-Methylselenoneine.

Oral intake of purified selenoneine and seafoods has been reported to result in selenoneine accumulation in erythrocytes in mice and human. In addition, Se-methylselenoneine was suggested to be produced as a metabolite of selenoneine in the urine and whole blood of humans. In order to confirm the molecular mechanism of production of Se-methylselenoneine, a stable isotope (Se-76) labeled selenoneine was biosynthesized using genetically modified fission yeast and administered to mice. The Se-76-labeled Se-methylselenoneine was detected in urine but Se-78 and Se-80-labeled Se-methylselenoneine arising from natural isotopes of Se was hardly detected. These results suggest that Se-methylselenoneine was a metabolite and the excreted form of selenoneine. The methylation of selenoneine in mice administered selenoneine continuously was evaluated by the analyses of organs using an online liquid chromatograph system with an inductively coupled plasma mass spectrometer (LC-ICP-MS). These experiments indicate that selenoneine is methylated in the liver and (or) kidneys.

Distribution and Effects of Selenoneine by Ingestion of Extract from Mackerel Processing Residue in Mice.

Selenoneine is an organic selenium compound contained in blood and dark muscle of fish. It has a strong antioxidative capacity and is considered useful as a new functional food material. However, the distribution and effects of selenoneine in the mammalian body have not been thoroughly examined. In this study, a selenoneine-rich mackerel extract was developed and fed to mice at 0.07% in standard rodent chow (ME diet) for 32 days to examine its distribution in the body. Selenoneine was distributed in the liver, kidney, and spleen in mice fed with mackerel extract, but it was not distributed in the plasma or erythrocytes. Moreover, concentrations of the major selenium-containing protein were not affected by the mackerel extract. The results of this study suggest that selenoneine is absorbed in the body following ingestion of low doses in crude material and preferentially accumulates in organs and later distributes in erythrocytes. Biochemical analyses of plasma in male mice showed that the glucose level was significantly increased and LDL-cholesterol level was significantly decreased by ME diet feeding. The results indicate that male mice are sensitive to ME diet.

Quantification of dilated deep capillaries in diabetic retinopathy on optical coherence tomography angiography.

Morphological changes in capillaries are one of major clinical signs in diabetic retinopathy (DR). In this study, we quantified the dilated deep capillaries on optical coherence tomography angiography (OCTA) images. Central 3 × 3 mm en face images were obtained using a swept source OCTA device in 105 eyes of 99 patients with DR. Capillaries with a greater diameter in the deep layers were defined as the dilated deep capillaries, using stepwise image processing. The relative areas of automatically selected capillaries with a great diameter were calculated as the index of the dilated deep capillaries. Most eyes with DR had string-like or dot-like dilated deep capillaries in the OCTA images, which appeared to be dilated capillary segments or microaneurysms histologically. They were distributed more densely in the parafovea than in the central sector, while there were no differences between individual quadrants. The index of the dilated deep capillaries was higher in eyes with DR than in nondiabetic eyes. The index in the central subfield was modestly associated with visual acuity, diabetic macular edema, and proliferative diabetic retinopathy. The quantitative dilated deep capillaries are designated as a biomarker of vision-threatening DR.

Inference of Capillary Nonperfusion Progression on Widefield OCT Angiography in Diabetic Retinopathy.

Purpose: The purpose of this study was to explore the spatial patterns of the nonperfusion areas (NPAs) on widefield optical coherence tomography angiography (OCTA) images in diabetic retinopathy (DR) and to investigate their associations with NPA progression and DR severity. Methods: We prospectively enrolled 201 eyes from 158 patients with DR. Widefield images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of 20-mm (1614 pixels) en face images. Nonperfusion squares (NPSs) were defined as 10 × 10-pixel squares without retinal vessels. Eyes with high-dimensional spatial data were mapped onto a two-dimensional space using the uniform manifold approximation and projection algorithm and divided by clustering. The patterns of NPA distribution were statistically compared between clusters. Results: All eyes were mapped onto a two-dimensional space and divided into six clusters based on the similarity of NPA distribution. Eyes in clusters 1 and 2 had minimal and small NPAs, respectively. Eyes in clusters 3 and 4 exhibited NPAs in the temporal and inferotemporal regions, respectively. Eyes in cluster 5 displayed NPAs in both superonasal and inferonasal areas. The unique NPA distributions in each cluster encouraged us to propose eight possible pathways of NPA progression. DR severity was not equal between clusters (P < 0.001), for example, 8 (15.7%) of 51 eyes and 15 (65.2%) of 23 eyes had PDR in clusters 1 and 5, respectively. Conclusions: Dimensionality reduction and subsequent clustering based on the NPA distribution on widefield OCTA enabled the inference of possible NPA progression in DR.

A case of Epstein-Barr virus-associated primary vitreoretinal lymphoma in an immunosuppressed patient.

PURPOSE: To describe a rare case of Epstein-Barr virus (EBV)-positive primary vitreoretinal lymphoma (PVRL) in an immunosuppressed patient. METHODS: Observational case report. RESULTS: A 64-year-old man under immunosuppressive therapy for rheumatic arthritis was referred for 2-month of blurred vision and decreased visual acuity in the right eye. Only mutton-fat keratic precipitates and mild vitreous opacity were found in the right eye without (sub-)retinal or sub-retinal pigment epithelial lesions. Vitreous biopsy and systemic workup suggested the diagnosis of PVRL of diffuse large B cell lymphoma (DLBCL) subform. Neoplastic cells stained positive for EBV antigens, EBV-encoded small RNA and Epstein-Barr nuclear antigen 2, consistent with EBV-positive DLBCL. Intravitreal methotrexate was effective in improving ocular symptoms. CONCLUSION: Our case provided evidence on the association of EBV infection with PVRL.

[A case of behavioral variant frontotemporal dementia presenting with frequent laughter during conversations].

We describe a case of behavioral variant frontotemporal dementia (bvFTD) presenting with frequent laughter during conversations. A 72-year-old male patient visited our hospital because of aspontaneity and abnormal behaviors. His medical history revealed epilepsy attacks approximately five years prior, which improved following administration of antiepileptic drugs. At the age of 67 years, the patient began exhibiting aspontaneity and abnormal behaviors, such as leaving a teahouse without paying for his coffee. Neurological examinations indicated moderate dementia and bradykinesia while walking. The patient frequently laughed during conversations with his wife and doctor, creating the impression that he was euphoric. His laughter was neither explosive nor obsessive, and did not involve loss of consciousness or seizures. MRI of the head revealed symmetrical atrophy of the bilateral frontal lobes. SPECT demonstrated decreased cerebral blood flow in the bilateral frontal lobes, particularly in the outer and inner frontal convexities. Based on the patient's clinical history and imaging results, a diagnosis of bvFTD was established. Our literature review identified only one research paper discussing the frequency of laughter in frontotemporal dementia, which suggested that patients with bvFTD laugh less often. However, several reports indicated that patients with FTD exhibit euphoric behaviors more frequently compared to those with other forms of dementia. We hypothesize that euphoric patients with bvFTD may laugh more frequently during conversations, reflecting disorders of emotional expression and a loss of empathy.

Association of Retinal Pigment Epithelium Reflectivity on Optical Coherence Tomography with Recurrence of Vogt-Koyanagi-Harada Disease: A Retrospective Observational Study.

Purpose: Despite the necessity of optical coherence tomography (OCT) for diagnosis and longitudinal monitoring in patients with Vogt-Koyanagi-Harada (VKH) disease, no studies have identified useful OCT markers for predicting recurrence in these patients. Although the precise reason for this remains unclear, one possibility is that infiltration of inflammatory cells into the choroid attenuates the OCT signal, making it difficult to precisely assess the structure of the choroid. Therefore, this study aimed to investigate changes in retinal pigment epithelium (RPE) reflectivity immediately above the choroid in eyes with acute VKH disease, as well as the association between RPE reflectivity and VKH disease recurrence. Patients and Methods: This single-centered retrospective observational study included 20 treatment-naïve patients with acute VKH disease presenting with serous retinal detachment (SRD) in the posterior pole at the initial visit between October 2015 and January 2020, as well as 15 healthy control eyes. All patients were followed up for at least 6 months and received treatment with intravenous methylprednisolone followed by oral administration of prednisolone. Swept-source OCT images through the fovea were used to measure central retinal thickness, central choroidal thickness, and RPE reflectivity. Results: During an observation period of 37.2 ± 30.8 months, recurrence of inflammation was observed in 11 patients (55.0%). Initial visual acuity was worse in patients who developed recurrence than in those who did not (P=0.024). On initial OCT images, RPE reflectivity differed significantly between patients with and without recurrence (1.75 ± 0.42 vs 1.35 ± 0.20; P=0.018), while there were no significant differences in other chorioretinal parameters, such as central retinal thickness and choroidal thickness. Conclusion: RPE reflectivity on OCT images may be useful for predicting the recurrence of inflammation in patients with VKH disease.

[A case of crossed aphasia following infarction in the right anterior cerebral artery territory].

We report a patient presenting with crossed aphasia following infarction in the territory of the right anterior cerebral artery (ACA). A right-handed 68-year-old woman without a history of correction had acute disturbance of consciousness, left hemiparesis predominant in the lower extremity, speech disorder and left unilateral spatial neglect during the admission due to hypertensive emergency. No other family member was left-handed. MRI of the head revealed acute phase infarction in the territory of the right ACA: mesial frontal lobe including the supplementary motor area, anterior cingulate gyrus, and the corpus callosum. Language symptoms in the subacute phase included difficulty in initiation, slow speech rate, loss of intonation and phonetic paraphasia, and accompanying errors in comprehension, repetition, reading, and writing letters. These symptoms suggested "anomalous" type crossed aphasia. No limb apraxia, construction disorder or left unilateral spatial neglect was observed in this period. Only a few cases of crossed aphasia due to infarction in the territory of the ACA have been reported so far. However, language and concomitant symptoms differs, depending on each case, suggesting a difference in individual cerebral lateralization.

Pathological Neurovascular Unit Mapping onto Multimodal Imaging in Diabetic Macular Edema.

Diabetic retinopathy is a form of diabetic microangiopathy, and vascular hyperpermeability in the macula leads to retinal thickening and concomitant reduction of visual acuity in diabetic macular edema (DME). In this review, we discuss multimodal fundus imaging, comparing the pathogenesis and interventions. Clinicians diagnose DME using two major criteria, clinically significant macular edema by fundus examination and center-involving diabetic macular edema using optical coherence tomography (OCT), to determine the appropriate treatment. In addition to fundus photography, fluorescein angiography (FA) is a classical modality to evaluate morphological and functional changes in retinal capillaries, e.g., microaneurysms, capillary nonperfusion, and fluorescein leakage. Recently, optical coherence tomography angiography (OCTA) has allowed us to evaluate the three-dimensional structure of the retinal vasculature and newly demonstrated that lamellar capillary nonperfusion in the deep layer is associated with retinal edema. The clinical application of OCT has accelerated our understanding of various neuronal damages in DME. Retinal thickness measured by OCT enables us to quantitatively assess therapeutic effects. Sectional OCT images depict the deformation of neural tissues, e.g., cystoid macular edema, serous retinal detachment, and sponge-like retinal swelling. The disorganization of retinal inner layers (DRIL) and foveal photoreceptor damage, biomarkers of neurodegeneration, are associated with visual impairment. Fundus autofluorescence derives from the retinal pigment epithelium (RPE) and its qualitative and quantitative changes suggest that the RPE damage contributes to the neuronal changes in DME. These clinical findings on multimodal imaging help to elucidate the pathology in the neurovascular units and lead to the next generation of clinical and translational research in DME.

Effect of Duration of Macular Detachment on Visual Prognosis after Surgery for Macula-Off Retinal Detachment: Japan-Retinal Detachment Registry.

PURPOSE: To evaluate the association between the duration of macular detachment (DMD) and visual prognosis in patients with macula-off rhegmatogenous retinal detachment (RD). DESIGN: Prospective observational cohort study. PARTICIPANTS: This study analyzed 719 eyes with macula-off rhegmatogenous RD registered with the Japan-Retinal Detachment Registry created by the Japan Retina and Vitreous Society. METHODS: We included patients with macular detachment without a history of prior surgery, except cataract surgery and vitrectomy. Reoperation cases, hereditary RD, and macular hole RD were excluded. We compared the visual prognosis between patients with DMD of N days or less and those with DMD of N + 1 days or more (N = 2-5). For these 4 comparisons, the inverse probability of treatment weighting (IPTW) methodology was employed, to balance 20 baseline characteristics between the shorter and longer DMD groups. The baseline characteristics included age, sex, axial length, baseline visual acuity, operative procedures, and detailed characteristics of RD. P-values < 0.01 were considered statistically significant. MAIN OUTCOME MEASURES: The best-corrected visual acuity (BCVA) 6 months after surgery. RESULTS: The final analysis included 719 eyes. For all comparisons, the patients' backgrounds were well balanced after IPTW with standardized differences < 0.10. The IPTW regression analysis revealed that the BCVA after 6 months was significantly better after surgeries for DMD of ≤ 2 days than that for DMD of ≥ 3 days. Similarly, the 6-month BCVA for surgeries for DMD of ≤ 3 days was significantly better than that for surgeries for DMD of ≥ 4 days (differences in logarithm of the minimum angle of resolution: -0.113, P = 9.1 × 10-7; -0.076, P = 1.6 × 10-3, respectively). On the other hand, there were no statistically significant differences for the other comparisons. CONCLUSIONS: Earlier surgical treatment within 3 days from the onset of macular detachment should be considered, after accounting for social circumstances, such as weekends. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Clinically Significant Nonperfusion Areas on Widefield OCT Angiography in Diabetic Retinopathy.

Purpose: To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. Design: Prospective, cross-sectional, observational study. Participants: One hundred and forty-four eyes of 114 patients with diabetes. Methods: Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. Main Outcome Measures: The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. Results: The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102-1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001-1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. Conclusions: The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Symptomatology and Neuropathology of patients presenting with focal cortical signs.

Here, we describe two patients who presented with focal cortical signs and underwent neuropathological examination. Case 1 was a 73-year-old woman with progressive speech disorder and abnormal behavior. She showed agraphia of the frontal lobe type, featured by the omission of kana letters when writing, other than pyramidal tract signs, pseudobulbar palsy, and frontal lobe dementia. Neuropathological examination, including TAR DNA-binding protein 43 (TDP-43) immunohistochemistry, revealed bilateral frontal and anterior temporal lobe lesions accentuated in the precentral gyrus and posterior part of the middle frontal gyrus. Both upper and lower motor neurons showed pathological changes compatible with amyotrophic lateral sclerosis. Case 2 was a 62-year-old man with progressive speech disorder and hand clumsiness. He had a motor speech disorder, compatible with apraxia of speech, and limb apraxia of the limb-kinetic and ideomotor type. Neuropathological examination revealed degeneration in the left frontal lobe, including the precentral gyrus, anterior temporal, and parietal lobe cortices. Moreover, numerous argyrophilic neuronal intracytoplasmic inclusions (Pick body) and ballooned neurons were observed in these lesions and the limbic system. The pathological diagnosis was Pick disease involving the peri-Rolandic area and parietal lobe. In these two cases, the distribution of neuropathological changes in the cerebral cortices correlated with the clinical symptoms observed.