A selective ER-phagy exerts neuroprotective effects via modulation of α-synuclein clearance in parkinsonian models.

The endoplasmic reticulum (ER) is selectively degraded by ER-phagy to maintain cell homeostasis. α-synuclein accumulates in the ER, causing ER stress that contributes to neurodegeneration in Parkinson's disease (PD), but the role of ER-phagy in α-synuclein modulation is largely unknown. Here, we investigated the mechanisms by which ER-phagy selectively recognizes α-synuclein for degradation in the ER. We found that ER-phagy played an important role in the degradation of α-synuclein and recovery of ER function through interaction with FAM134B, where calnexin is required for the selective FAM134B-mediated α-synuclein clearance via ER-phagy. Overexpression of α-synuclein in the ER of the substantia nigra (SN) resulted in marked loss of dopaminergic neurons and motor deficits, mimicking PD characteristics. However, enhancement of ER-phagy using FAM134B overexpression in the SN exerted neuroprotective effects on dopaminergic neurons and recovered motor performance. These data suggest that ER-phagy represents a specific ER clearance mechanism for the degradation of α-synuclein.

Immune activation during Pseudomonas infection causes local cell wall remodeling and alters AGP accumulation.

The plant cell boundary generally comprises constituents of the primary and secondary cell wall (CW) that are deposited sequentially during development. Although it is known that the CW acts as a barrier against phytopathogens and undergoes modifications to limit their invasion, the extent, sequence, and requirements of the pathogen-induced modifications of the CW components are still largely unknown, especially at the level of the polysaccharide fraction. To address this significant knowledge gap, we adopted the compatible Pseudomonas syringae-Arabidopsis thaliana system. We found that, despite systemic signaling actuation, Pseudomonas infection leads only to local CW modifications. Furthermore, by utilizing a combination of CW and immune signaling-deficient mutants infected with virulent or non-virulent bacteria, we demonstrated that the pathogen-induced changes in CW polysaccharides depend on the combination of pathogen virulence and the host's ability to mount an immune response. This results in a pathogen-driven accumulation of CW hexoses, such as galactose, and an immune signaling-dependent increase in CW pentoses, mainly arabinose, and xylose. Our analyses of CW changes during disease progression also revealed a distinct spatiotemporal pattern of arabinogalactan protein (AGP) deposition and significant modifications of rhamnogalacturonan sidechains. Furthermore, genetic analyses demonstrated a critical role of AGPs, specifically of the Arabinoxylan Pectin Arabinogalactan Protein1, in limiting pathogen growth. Collectively, our results provide evidence for the actuation of significant remodeling of CW polysaccharides in a compatible host-pathogen interaction, and, by identifying AGPs as critical elements of the CW in plant defense, they pinpoint opportunities to improve plants against diverse pathogens.

Cell- and development-specific degradation controls the levels of mixed-linkage glucan in sorghum leaves.

Mixed-linkage glucan (MLG) is a component of the cell wall (CW) of grasses and is composed of glucose monomers linked by ß-1,3 and ß-1,4 bonds. MLG is believed to have several biological functions, such as the mobilizable storage of carbohydrates and structural support of the CW. The extracellular levels of MLG are largely controlled by rates of synthesis mediated by cellulose synthase-like (CSL) enzymes, and turnover by lichenases. Economically important crops like sorghum accumulate MLG to variable levels during development. While in sorghum, like other grasses, there is one major MLG synthase (CSLF6), the identity of lichenases is yet unknown. To fill this gap, we identified three sorghum lichenases (SbLCH1-3) and characterized them in leaves in relation to the expression of SbCSLF6, and the abundance of MLG and starch. We established that SbLCH1-3 are secreted to the apoplast, consistent with a role of degrading MLG extracellularly. Furthermore, while SbCSLF6 expression was associated with cell development, the SbLCH genes exhibited distinct development-, cell-type-specific and diel-regulated expression. Therefore, our study identifies three functional sorghum MLG lichenases and highlights that MLG accumulation in sorghum leaves is likely controlled by the activity of lichenases that tune MLG levels, possibly to suit distinct cell and developmental needs in planta. These findings have important implications for improving the growth, yield, and composition of sorghum as a feedstock.

Multiple horizontal gene transfer events have shaped plant glycosyl hydrolase diversity and function.

Plant glycosyl hydrolases (GHs) play a crucial role in selectively breaking down carbohydrates and glycoconjugates during various cellular processes, such as reserve mobilization, pathogen defense, and modification/disassembly of the cell wall. In this study, we examined the distribution of GH genes in the Archaeplastida supergroup, which encompasses red algae, glaucophytes, and green plants. We identified that the GH repertoire expanded from a few tens of genes in early archaeplastidians to over 400 genes in modern angiosperms, spanning 40 GH families in land plants. Our findings reveal that major evolutionary transitions were accompanied by significant changes in the GH repertoire. Specifically, we identified at least 23 GH families acquired by green plants through multiple horizontal gene transfer events, primarily from bacteria and fungi. We found a significant shift in the subcellular localization of GH activity during green plant evolution, with a marked increase in extracellular-targeted GH proteins associated with the diversification of plant cell wall polysaccharides and defense mechanisms against pathogens. In conclusion, our study sheds light on the macroevolutionary processes that have shaped the GH repertoire in plants, highlighting the acquisition of GH families through horizontal transfer and the role of GHs in plant adaptation and defense mechanisms.

Biomarkers determining treatment interval of diabetic macular edema after initial resolution by anti-vascular endothelial growth factor.

PURPOSE: To identify predictive factors that help determine the interval of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection after the initial resolution of diabetic macular edema (DME). METHODS: This retrospective case-control study enrolled treatment-naïve DME patients who had achieved DME resolution after intravitreal anti-VEGF injections. Patients were classified into the recurrence and no-recurrence groups, depending on the development of recurrent DME after deferring intravitreal anti-VEGF injection. The demographics and clinical features, including optical coherence tomography findings, were compared between the two groups. RESULTS: We enrolled 105 eyes. Sixty eyes (57.1%) belonged to the no-recurrence group, and 45 (42.9%), belonged to the recurrence group. The severity of diabetic retinopathy at baseline was related to early DME recurrence (P = 0.009). At the treatment deferring point, the non-recurrence group had both thinner central subfield thickness (289.5 ± 27.2 µm vs. 307.0 ± 38.2 µm, P = 0.011) and thinner central retinal thickness (214.9 ± 41.4 µm vs. 231.8 ± 41.2 µm, P = 0.043) compared to the recurrence group. Intraretinal cyst was observed in 34 eyes (56.7%) in the no-recurrence group and 42 eyes (93.3%) in the recurrence group at the deferring point (P < 0.001). CONCLUSION: A low risk of early DME recurrence is anticipated in the eyes with foveal thinning and no intraretinal cyst when anti-VEGF injection is deferred. These predictive biomarkers can be useful for patient monitoring and determining treatment strategies for DME patients.

Macular hole with epiretinal proliferation: diagnostic value of en-face optical coherence tomography and clinical characteristics.

PURPOSE: To elucidate the clinical features and surgical outcomes of full-thickness macular hole (FTMH) with epiretinal proliferation (EP) diagnosed by both en-face and B-mode optical coherence tomography (OCT). METHOD: This retrospective cohort study classified idiopathic FTMHs into two groups, based on B-scan and en-face OCT imaging: FTMH with EP (EP group) and without EP (non-EP group). The preoperative features, as well as postoperative outcomes up to 12 months, were compared between the two groups. RESULT: Among 318 eyes of idiopathic FTMH that met the inclusion criteria, 59 eyes (18.6%) were in the EP group, and others were in the non-EP group. In 9 eyes (15.3%) out of the EP group, EP was not detected in the preoperative B-mode OCT but was identified through the en-face OCT. Baseline features showed a higher male proportion (47.5% vs. 27.8%, P = 0.005) and a lower incidence of vitreofoveal traction (P < 0.001) in the EP group than in the non-EP group. The EP group showed worse visual recovery than the non-EP group (- 0.23 vs. - 0.41 logarithm of the minimum angle of the resolution at 12 months, P = 0.001). CONCLUSION: The en-face OCT enhances diagnostic accuracy of EP in FTMH eyes, especially in the case with smaller extent of EP. Eyes with FTMH with EP showed a worse visual recovery than FTMH without EP.

RISK OF EXUDATION IN EYES WITH NONEXUDATIVE POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To investigate the characteristics and natural history of treatment-naive nonexudative polypoidal choroidal vasculopathy (PCV) and to determine biomarkers predicting exudative conversion. METHODS: Patients diagnosed with nonexudative PCV based on indocyanine green angiography and optical coherence tomography were included. Incidence of exudative conversion in nonexudative PCV patients and cumulative estimates for overall risk were assessed. Indocyanine green angiography and optical coherence tomography imaging-based features were analyzed to identify risk factors for exudative conversion. RESULTS: The study included 42 eyes of 40 patients with nonexudative PCV. The mean follow-up duration was 54.3 ± 35.5 months. Of the 42 eyes with nonexudative PCV, exudative conversion developed in 23 eyes (54.8%) after 42.2 ± 28.3 months (range, 8-103 months). Kaplan-Meier analysis showed that the exudation-free survival at 5 years after baseline was estimated to be 53.6%. Multivariate regression analysis showed that sequentially increased protrusion of retinal pigment epithelium in the polyp area was a significant risk factor for exudation in nonexudative PCV (odds ratio = 10.16; 95% CI 1.78-57.81; P = 0.01). CONCLUSION: Exudative conversion has been noted in nearly half of the nonexudative PCV cases in 5 years. The progressive protrusion of polypoidal lesions on optical coherence tomography examination may be a significant biomarker for predicting the near-term onset of exudation.

Disruption of Brachypodium lichenase alters metabolism of mixed-linkage glucan and starch.

Mixed-linkage glucan, which is widely distributed in grasses, is a polysaccharide highly abundant in cell walls of grass endosperm and young vegetative tissues. Lichenases are enzymes that hydrolyze mixed-linkage glucan first identified in mixed-linkage glucan-rich lichens. In this study, we identify a gene encoding a lichenase we name Brachypodium distachyon LICHENASE 1 (BdLCH1), which is highly expressed in the endosperm of germinating seeds and coleoptiles and at lower amounts in mature shoots. RNA in situ hybridization showed that BdLCH1 is primarily expressed in chlorenchyma cells of mature leaves and internodes. Disruption of BdLCH1 resulted in an eight-fold increase in mixed-linkage glucan content in senesced leaves. Consistent with the in situ hybridization data, immunolocalization results showed that mixed-linkage glucan was not removed in chlorenchyma cells of lch1 mutants as it was in wild type and implicate the BdLCH1 enzyme in removing mixed-linkage glucan in chlorenchyma cells in mature vegetative tissues. We also show that mixed-linkage glucan accumulation in lch1 mutants was resistant to dark-induced degradation, and 8-week-old lch1 plants showed a faster rate of starch breakdown than wild type in darkness. Our results suggest a role for BdLCH1 in modifying the cell wall to support highly metabolically active cells.

Impact of Age-Related Macular Degeneration and Related Visual Disability on the Risk of Depression: A Nationwide Cohort Study.

PURPOSE: To evaluate the prospective association of age-related macular degeneration (AMD) and related visual disability (VD) with the risk of depression. DESIGN: This nationwide population-based cohort study used authorized clinical data provided by the Korean National Health Insurance Service. PARTICIPANTS: A total of 3 599 589 individuals older than 50 years participated in the Korean National Health Screening Program in 2009. METHODS: Age-related macular degeneration diagnosis and the presence of accompanying VD were verified using diagnostic codes and disability registration data. Data on covariates, including age, sex, income level, residential area, systemic comorbidities, and behavioral factors, were collected from health screening results and claims data. Patients were followed up until December 2019, and incident cases of depression were identified using registered diagnostic codes. The prospective association of AMD and related VD with new-onset depression was investigated using the multivariable-adjusted Cox proportional hazard model. MAIN OUTCOME MEASURES: Hazard ratios and 95% confidence intervals (CIs) for depression development according to the presence of AMD and VD. RESULTS: During an average follow-up period of 8.52 years, 1 037 088 patients received new diagnoses of depression. Patients with previous diagnoses of AMD showed a greater risk of new-onset depression, with a hazard ratio of 1.15 (95% CI, 1.13-1.17) compared with the control group in the fully adjusted model. Patients with AMD and accompanying VD showed a further increased risk of depression, with a hazard ratio of 1.23 (95% CI, 1.16-1.30). CONCLUSIONS: Individuals with a diagnosis of AMD have a higher risk of depression developing in the future. The risk of depression is increased further in patients with AMD who demonstrate VD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Effects of Dihydropyridines on the Motor and Cognitive Outcomes of Patients with Parkinson's Disease.

BACKGROUND: Dihydropyridines (DHPs) may have neuroprotective effects against Parkinson's disease (PD). OBJECTIVE: This study investigated the effects of DHPs on nigrostriatal dopaminergic denervation and longitudinal motor and cognitive outcomes in PD. METHODS: We classified 476 patients with drug-naive PD who had undergone dopamine transporter imaging into three groups. They were selected according to a prior diagnosis of hypertension and use of DHPs and were matched using propensity scores: patients without hypertension (HTN-; n = 50) and patients with hypertension treated without DHP (HTN+/DHP-; n = 50) or with DHP (HTN+/DHP+; n = 50). Multiple linear regression and linear mixed model analyses were performed to determine intergroup differences in baseline dopamine transporter availability and longitudinal changes in the levodopa-equivalent dose, respectively. Using Kaplan-Meier analyses, we compared the risks of levodopa-induced dyskinesia, wearing off, and dementia-free survival during the 5.06 years of the mean follow-up period. The Cox regression model determined the independent effects of DHPs on dementia conversion. RESULTS: Dopamine transporter availability in all striatal subregions was comparable between the HTN-, HTN+/DHP-, and HTN+/DHP+ groups. The risks of levodopa-induced dyskinesia and wearing off, as well as longitudinal changes in the levodopa-equivalent dose, did not differ between the groups. The HTN+/DHP+ group had a lower risk of developing dementia than the HTN+/DHP- (Bonferroni-corrected Plog-rank  = 0.036) group. The use of DHP was independently associated with a lower risk of dementia conversion after controlling for other antihypertensive drugs and confounding factors (hazard ratio, 0.242; 95% confidence interval, 0.087-0.668; P = 0.006). CONCLUSIONS: DHPs may be associated with better long-term cognitive outcomes in hypertensive patients with PD. © 2023 International Parkinson and Movement Disorder Society.

SPONTANEOUS REATTACHMENT OF RHEGMATOGENOUS RETINAL DETACHMENT: Observations of the Vitreoretinal Interface.

PURPOSE: To describe the clinical characteristics and posterior vitreous findings of spontaneous reattachment of rhegmatogenous retinal detachment (SRRRD). METHODS: Eighty-six eyes from 80 patients who were diagnosed with SRRRD (SRRRD group) and 92 eyes from 92 patients who had undergone successful scleral buckling for rhegmatogenous retinal detachment ( group for comparison) were included. Ultrawide field fundus imaging and spectral domain optical coherence tomography were performed to evaluate fundus characteristics and vitreoretinal interface. RESULTS: A significant difference was found in the proportion of complete posterior vitreous attachment between the SRRRD and rhegmatogenous retinal detachment groups (44.2% vs. 19.6%, P < 0.001). The incidence of atypical epiretinal tissue (AET) in the SRRRD group was 14% (12 of 86 eyes), whereas none of the eyes in the rhegmatogenous retinal detachment group exhibited AET. In SRRRD eyes with AET, the visual acuity was lower (logarithm of the minimum angle of resolution, 0.51 ± 0.57 vs. 0.14 ± 0.15, P < 0.001), the mean age was higher (years, 61.7 vs. 39.4, P < 0.001), and the SRRRD lesion extent was wider (clock hours, 5.67 vs. 3.70, P = 0.004) than in SRRRD eyes without AET. CONCLUSION: Compared with the rhegmatogenous retinal detachment group, the SRRRD group had a higher incidence of posterior vitreous attachment. Furthermore, AET was a significant comorbidity in the eyes with SRRRD, particularly in the elderly and the area of presumed reattachment over two quadrants and was related to worse functional outcomes.

The synthesis of xyloglucan, an abundant plant cell wall polysaccharide, requires CSLC function.

Xyloglucan (XyG) is an abundant component of the primary cell walls of most plants. While the structure of XyG has been well studied, much remains to be learned about its biosynthesis. Here we employed reverse genetics to investigate the role of Arabidopsis cellulose synthase like-C (CSLC) proteins in XyG biosynthesis. We found that single mutants containing a T-DNA in each of the five Arabidopsis CSLC genes had normal levels of XyG. However, higher-order cslc mutants had significantly reduced XyG levels, and a mutant with disruptions in all five CSLC genes had no detectable XyG. The higher-order mutants grew with mild tissue-specific phenotypes. Despite the apparent lack of XyG, the cslc quintuple mutant did not display significant alteration of gene expression at the whole-genome level, excluding transcriptional compensation. The quintuple mutant could be complemented by each of the five CSLC genes, supporting the conclusion that each of them encodes a XyG glucan synthase. Phylogenetic analyses indicated that the CSLC genes are widespread in the plant kingdom and evolved from an ancient family. These results establish the role of the CSLC genes in XyG biosynthesis, and the mutants described here provide valuable tools with which to study both the molecular details of XyG biosynthesis and the role of XyG in plant cell wall structure and function.

Correlations with REM sleep behavior disorder severity in isolated rapid eye movement sleep behavior disorders patients.

OBJECTIVES: The pathogenesis of isolated rapid eye movement sleep behavior disorders (iRBD) is poorly understood. The severity of RBD may reflect its pathogenesis. METHODS: We compared motor function and non-motor symptoms (NMSs) between iRBD patients and healthy volunteers. We correlated motor function, NMSs, and striatal dopaminergic activity with RBD severity using video-polysomnography. RESULTS: Twenty-one iRBD patients and 17 controls participated. The Unified Parkinson's Disease Rating Scale part III scores were higher in patients compared to controls (p < 0.001). There was no difference in upper extremity function between patients and controls (right, p = 0.220; left, p = 0.209), but gait was slower in iRBD patients (walking time, p < 0.001; number of steps, p < 0.001). The mean value of the Korean version of the Mini-Mental State Exam and Clinical Dementia Rating were lower in patients (p = 0.006, p = 0.003, respectively). Patients with were also more depressed (p = 0.002), had decreased olfactory function (p < 0.001), reported more frequent sleep/fatigue episodes (p < 0.001), worse attention/memory capacity (p < 0.001), gastrointestinal problems (p = 0.009), urinary problems (p = 0.007), and pain (p = 0.083). Further, iRBD patients reported more frequent sleep-related disturbances (p = 0.004), but no difference in daytime sleepiness (p = 0.663). Disease severity was correlated with pain (r = 0.686, p = 0.002) and visuospatial function (r= -0.507, p = 0.038). There were no correlations between RBD severity and striatal dopaminergic activities (p > 0.09). CONCLUSIONS: iRBD is a multisystem neurodegenerative disorder, and gait abnormalities may be a disease characteristic, possibly related to the akinetic-rigid phenotype of Parkinson's disease. The correlation between pain/visuospatial dysfunction and RBD severity may be related to its pathogenesis.

Healthy Spouses can be Considered as Living Liver Donors.

BACKGROUND: Spousal donors have gradually been accepted as an alternative living liver donors to alleviate the organ shortage and prevent donations from children. No information is available regarding the effects of spousal donation on donor safety and recipient outcomes. Our purpose in this study was to determine how spousal liver grafts in living donor liver transplantation (LDLT) affect donor safety and recipient outcomes compared with those of LDLT from children. METHODS: We retrospectively analyzed 656 patients, including spouses and children, who underwent a right or extended right hepatectomy for living liver donation between January 2009 and December 2018. RESULTS: Spouses represented 18.8% (n = 123) of living liver donors. Female donors comprised 78.9% (n = 97) of spousal donors, and the proportion of male donors in the children group was 72.6% (n = 387). The mean donor operation time of the spousal group was shorter than that of the children group (330 min vs. 358 min; P = 0.011), and the complication rate in the spousal group was lower than that in the children group (12.2% vs. 22.9%; P = 0.006). However, there were no differences in severe complication rates, hospitalization, or liver function tests between the 2 groups at 3 months after donor surgery. The overall survival of recipients in the spousal group was not reduced compared to that of recipients in the children group. CONCLUSION: The present study suggests that, with careful selection, spousal donation is feasible and safe in LDLT.

Long-term outcomes of polypoidal choroidal vasculopathy in comparison with typical exudative age-related macular degeneration.

PURPOSE: To compare long-term outcomes between typical exudative age-related macular degeneration (TexAMD) and polypoidal choroidal vasculopathy (PCV), and to investigate factors related to the outcomes. METHODS: This retrospective study included 319 eyes (164 with TexAMD and 155 with PCV) treated with anti-vascular endothelial growth factor and followed more than 5 years. The primary outcome was visual acuity (VA) change from baseline to final visit. Linear regression analyses were used to determine factors associated with final VA. RESULTS: Baseline logMAR VA was 0.7 ± 0.5 in the TexAMD group and 0.5 ± 0.4 in the PCV group (p < 0.001). After a mean follow-up of 9 years, final VA was also significantly worse in the TexAMD group than in the PCV group (0.9 ± 0.6 vs. 0.6 ± 0.5; p < 0.001). The PCV group showed longer maintenance of improved vision and later onset of significant visual decline than the TexAMD group. In multivariate analysis, loss to follow-up, worse baseline VA, macular atrophy, and subretinal fibrosis were significantly associated with poor final VA in both groups. CONCLUSION: PCV eyes showed relatively favorable long-term visual outcome than TexAMD eyes. The results of this study emphasized the importance of compliance with treatment, along with other well-known prognostic factors.

PARAFOVEAL INNER RETINAL THINNING AS THE BIOMARKER PREDICTING LESS RECURRENCE OF MACULAR EDEMA IN CENTRAL RETINAL VEIN OCCLUSION AFTER DISCONTINUING ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR.

PURPOSE: To identify the predictive factors for the recurrence of macular edema after the cessation of antivascular endothelial growth factor treatment in eyes with central retinal vein occlusion (CRVO). METHODS: This retrospective study included participants who had discontinued intravitreal bevacizumab injections for complete resolution of macular edema related to CRVO at 3 months after the last injection. Fifty-two eyes were enrolled in this study and classified into two groups based on the recurrence of macular edema within 1 year after the stopping point, when the decision to discontinue injections was made. Clinical characteristics and optical coherence tomographic parameters at baseline and at the stopping point were investigated. RESULTS: Multivariate logistic regression analysis demonstrated that, at baseline, old age was associated with a significantly higher risk of macular edema recurrence (odds ratio, 1.092; P = 0.022). At the stopping point, parafoveal inner retinal thickness (odds ratio: 1.043, P = 0.014) and the presence of ellipsoid zone disruption (odds ratio: 5.922, P = 0.032) were predictive factors for recurrence. The receiver operating characteristic curve showed that parafoveal inner retinal thinning of >7 µm compared with that in the fellow eye was significantly associated with decreased recurrence of macular edema. CONCLUSION: Parafoveal inner retinal thinning and intact ellipsoid zone after resolution of macular edema by antivascular endothelial growth factor treatment were predictive of a lower risk of recurrence of macular edema in CRVO. These intuitive biomarkers may help predict future disease courses and design optimal treatment strategies.

EN-FACE IMAGING OF ATYPICAL EPIRETINAL TISSUE IN LAMELLAR MACULAR HOLE.

PURPOSE: To elucidate the significance of en-face optical coherence tomography imaging of atypical epiretinal tissue (AET) in the lamellar macular hole (LMH). METHODS: This study involved 29 eyes of 29 patients who underwent surgical treatment for LMH with AET. Best-corrected visual acuity, metamorphopsia assessment (M-score), and optical coherence tomography were evaluated before and 6 months after surgery. The novel en-face optical coherence tomography parameters, such as the area of AET and hyperreflective fringe, were correlated with clinical factors before and after LMH surgery. RESULTS: Preoperatively, hyperreflective fringe was noted in 25 (86.2%) patients. The splitting of the inner retina, disruption of the ellipsoid zone, the extent of foveal cavitation, symptom duration, and change in best-corrected visual acuity were correlated with the area of AET (all P < 0.05). Multivariate regression analysis revealed that a larger area of AET was associated with longer symptom duration and less improvement in postoperative vision (all P < 0.05). CONCLUSION: The area of AET may represent the chronicity of LMH and is significantly associated with visual outcomes after LMH surgery. This novel en-face optical coherence tomography parameter can be used as a predictive factor for surgical outcomes in LMH with AET.

OCULAR MANIFESTATIONS OF ASP38ALA AND THR59LYS FAMILIAL TRANSTHYRETIN AMYLOIDOSIS.

PURPOSE: To describe the ophthalmic manifestations of familial transthyretin amyloidosis (FTA) mutations, including Asp38Ala and Thr59Lys, which have not been previously reported to have ocular involvement. METHODS: This is an observational case series of prospectively collected data of 16 patients with FTA who were taking tafamidis for mild peripheral neuropathy and underwent a comprehensive ophthalmic examination at a single tertiary center, between January 2013 and March 2020. The ocular involvement of each FTA mutation type and the specific manifestations were the main outcome measures. RESULTS: Six of 16 patients with FTA manifested ocular involvement. Ocular involvement was noted in two of three patients with Glu89Lys mutations having retinal deposits, retinal hemorrhages, and corneal opacity. Three of nine patients with Asp38Ala mutations and one of two patients with Thr59Lys mutations showed ocular involvement that had not been previously described. The ophthalmic findings included glaucoma, anterior lens capsule opacity, vitreous opacity, and retinal deposits. The decrease in vascular flow due to perivascular cuffing of the amyloid deposits was detected by optical coherence tomography angiography. CONCLUSION: The current study newly described that two transthyretin mutation types of FTA, Asp38Ala and Thr59Lys, may manifest with ocular findings such as anterior lens capsule opacity and retinal deposits.

A Case of Pathologically Confirmed Corticobasal Degeneration Initially Presenting as Progressive Supranuclear Palsy Syndrome.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) overlap clinically with parkinsonism or extrapyramidal signs and pathologically with tauopathy. Asymmetric parkinsonism and cortical dysfunctions are classical features of CBD. However, symmetric parkinsonism, frequent falls, and supranuclear gaze palsy are key features of PSP. Despite biochemically classified as 4R tauopathies, tufted astrocytes of PSP and astrocytic plaque of CBD show pathologically important differences. Herein, we report a 68-year-old man with pathologically confirmed CBD. He was clinically suspected to have PSP because of progressive gait disturbances, frequent falls, and vertical saccade limitation. Neurological examination performed at age 71 revealed symmetrical bradykinesia, axial rigidity, and postural instability with worsening of early existing symptoms. Magnetic resonance imaging of the brain taken at age 70 detected midbrain and left frontotemporal atrophy and right middle cerebral artery infarction. Left frontotemporoparietal hypometabolism and asymmetrically decreased fluoro-propyl-carbomethoxy-iodophenyl-tropane uptake in the basal ganglia were observed. The autopsy was performed at the time of his death (at age 72), which revealed severe pallor of the substantia nigra and mildly hypopigmented locus ceruleus. AT8 immunohistochemistry and Gallyas staining revealed tau-positive neuronal and glial inclusions, astrocytic plaques, ballooned neurons, and numerous threads in both gray and white matter. No abnormal inclusions were revealed by beta-amyloid, α-synuclein and TDP-43 immunohistochemistry. In our case, cerebral infarction, periventricular and deep white matter ischemic changes, and midbrain atrophy were likely to produce PSP-CBD overlapping symptoms. However, our patient was finally confirmed to have CBD based on pathological findings such as astrocytic plaques.

One Autopsy Proved Neocortical Lewy Body Disease Without the Involvement of the Olfactory Bulb and Brainstem.

Lewy bodies (LBs) and Lewy neurites (LNs) are pathological hallmarks of Parkinson's disease (PD) or dementia with LBs (DLB). Incidental Lewy body disease (iLBD) is defined when LBs and LNs are found in the brain of normal elderly individuals. A 65-year-old man presented with autopsy-proven Lewy body pathology (LBP). He had never complained of cognitive impairments or parkinsonian motor symptoms, and he had always maintained independence in activities of daily living. Hypopigmentations in the locus coeruleus and substantia nigra were discovered during the autopsy. The patient showed severe-to-extremely severe LBs in the neocortex and limbic areas, except in the nucleus basalis of Meynert, amygdala, and brainstem, according to microscopic findings. Hence, using several of the previously known staging systems, it was difficult to classify the patient's LBP type. Furthermore, these findings were unique because they had never been observed before in iLBD.