Phloroglucinol attenuates oligomeric amyloid beta peptide1-42-induced astrocytic activation by reducing oxidative stress.

Astrocytes are the most abundant cell type in the central nervous system (CNS) and their major function is to maintain homeostasis of the CNS by exerting various functions. Simultaneously, reactive astrocytes are well known to be involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). Reactive astrocytes, induced by amyloid beta peptide (Aß), the main component of the neuritic plaques found in AD, induce neuroinflammation, producing cytokines that lead to neuronal cell death in AD. Phloroglucinol,a polyphenol monomer and a component of phlorotannin, is found at sufficient levels in Ecklonia cava of the Laminariaceae family. Recently, several studies have reported that phloroglucinol has the ability to trap free radicals in lung fibroblasts or cancer cells. However, the effects of phloroglucinol in astrocytes have not yet been studied. Here, we found that phloroglucinol inhibits the generation of ROS induced by oligomeric Aß1-42 (oAß1-42) treatment in primary astrocytes. Futhermore, phloroglucinol was shown to ameliorate the protein expression of glial fibrillary acidic protein, a marker of reactive astrocytes, after treatment with oAß1-42. These results indicate that phloroglucinol exerts antioxidant effects in primary cultured astrocytes and attenuates the astrocytic activation induced by oAß1-42.

Inhibition of STAT3 phosphorylation attenuates impairments in learning and memory in 5XFAD mice, an animal model of Alzheimer's disease.

The pathophysiological roles of astrocytes in the reactive state are thought to have important significance in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). However, the detailed mechanisms underlying the transition of astrocytes from the resting state to the reactive state during neurodegenerative disease largely remain to be defined. Here, we investigated the pathways involved in activating astrocytes from the resting state to the reactive state in primary cultured astrocytes treated with oligomeric Aß and in the hippocampus of 5XFAD mice. Treatment with oligomeric Aß induced an increase in reactive astrocytes, as assessed by the protein level of glial fibrillary acidic protein (GFAP) and this increase was caused by STAT3 phosphorylation in primary cultured astrocytes. The administration of Stattic, an inhibitor of STAT3, rescued the activation of astrocytes in primary cultured astrocytes and in the hippocampus of 6-month-old 5XFAD mice as well as impairments in learning and memory. Collectively, these results demonstrated that reactive astrocytes in the AD brain are induced via STAT3 and the impairments in learning and memory observed in 5XFAD mice are rescued by STAT3 inhibition, suggesting that the inhibition of STAT3 phosphorylation in astrocytes may be a novel therapeutic target for cognitive impairment in AD.

Diagnostic performance of Mac-2 binding protein glycosylation isomer (M2BPGi) in screening liver fibrosis in health checkups.

BACKGROUND: Mild-to-moderate fibrosis is rarely diagnosed because the disease is asymptomatic in the early stage. The serum level of Mac-2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis. The aim of this study was to determine the diagnostic performance of M2BPGi in screening liver fibrosis using magnetic resonance elastography (MRE) as a reference standard and to compare it with using the aspartate aminotransferase-to-platelet ratio (APRI) and the Fibrosis-4 index (FIB-4) in health checkups. METHODS: This cross-sectional study consecutively selected subjects at health examinations who underwent MRE and M2BPGi testing at eight health promotion centers in Korea between January and September 2019. The serum M2BPGi level was measured using the chemiluminescence enzyme immunoassay method. The measured levels were indexed using the cutoff index (COI). COI values of M2BPGi were compared with the MRE results. RESULTS: The median (interquartile) values of COI for fibrosis stages F0 (normal liver stiffness), F1 (mild fibrosis), F2 (significant fibrosis), and ≥F3 (advanced fibrosis) were 0.49 (0.34-0.61), 0.48 (0.38-0.68), 0.64 (0.43-1.03), and 1.01 (0.75-1.77), respectively (P < .0001). The AUCs of the COI for the screening of fibrosis stage ≥F1, ≥F2, and ≥F3 were 0.591, 0.698, and 0.853, respectively. Using a threshold of 0.75 for COI to exclude advanced fibrosis had a sensitivity, specificity, and negative predictive value of 80.0%, 77.9%, and 98.9%, respectively. The AUC for excluding advanced fibrosis was better for M2BPGi than for FIB-4 and APRI. CONCLUSION: Serum M2BPGi was useful for screening significant and advanced fibrosis in health checkups.

Fetal neural stem cells from a mouse model of 15q11-13 duplication syndrome exhibit altered differentiation into neurons and astrocytes.

The duplication of human chromosome 15q11-13 is known to be associated with an estimated 1.1% of autism cases. Here, we investigated whether differentiation into neurons and astrocytes is altered in fetal neural stem cells (FNSCs) isolated from the mouse model of 15q11-13 duplication syndrome (patDp/+ mice). In patDp/+ mice-derived FNSCs, multipotency was maintained for a longer period, the population of neurons was downregulated, and that of astrocytes was upregulated significantly after differentiation induction. These results suggest that the dysregulation of FNSCs differentiation could affect cortical development and behavioral deficits in the early postnatal stage shown in the patDp/+ mice.

COMPARISON OF SHORT-TERM EFFICACY BETWEEN ORAL SPIRONOLACTONE TREATMENT AND PHOTODYNAMIC THERAPY FOR THE TREATMENT OF NONRESOLVING CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To compare the short-term therapeutic efficacy of oral spironolactone treatment with that of half-dose photodynamic therapy (PDT) in patients with nonresolving central serous chorioretinopathy. METHODS: This retrospective, interventional, comparative study included 41 patients with nonresolving central serous chorioretinopathy who exhibited subretinal fluid accumulation for more than 3 months. Of the 41 patients, 18 (18 eyes) received oral spironolactone treatment and 23 (23 eyes) received half-dose PDT. Treatment outcomes, including the central macular thickness, subretinal fluid height, subfoveal choroidal thickness, and best-corrected visual acuity, were measured at baseline and 1 and 3 months after treatment. RESULTS: There were no differences in baseline characteristics between the two groups. The central macular thickness and the subretinal fluid height significantly decreased at 1 and 3 months after treatment. The central macular thickness at 1 month was lesser in the PDT group than in the spironolactone group. The subfoveal choroidal thickness decreased at 1 and 3 months only in the PDT group, whereas best-corrected visual acuity showed a significant improvement at 3 months in both groups. CONCLUSION: Our results suggest that the short-term efficacy of oral spironolactone treatment for the management of nonresolving central serous chorioretinopathy is comparable with that of half-dose PDT, with an excellent safety profile.

DIFFERENTIAL DIAGNOSIS FOR VITREORETINAL LYMPHOMA WITH VITREORETINAL FINDINGS, IMMUNOGLOBULIN CLONALITY TESTS, AND INTERLEUKIN LEVELS.

PURPOSE: To analyze vitreoretinal findings, immunoglobulin clonality tests, and interleukin (IL) levels for diagnosing vitreoretinal lymphoma (VRL). METHODS: Forty-three patients who underwent diagnostic vitrectomy for suspected VRL were retrospectively reviewed. Of those patients finally diagnosed with VRL and nonlymphoma, ophthalmic evaluation and cytology results, IL-6 and IL-10 levels, and immunoglobulin heavy chain and immunoglobulin kappa light chain clonality assays were compared. RESULTS: Sub-retinal pigment epithelium infiltration and veil-pattern vitreous opacity were specific vitreoretinal findings in patients with VRL. The area under the receiver operating characteristic curve of the IL-10-to-IL-6 ratio and of IL-10 levels was 0.972 and 0.931, respectively. A combined immunoglobulin heavy chain and immunoglobulin kappa light chain assay showed increased sensitivity, whereas the determined specificity of immunoglobulin kappa light chain, at 94.12%, was much higher than the 78.95% of immunoglobulin heavy chain. Patients with VRL with atypically elevated IL-6 levels showed extensive and severe sub-retinal pigment epithelium infiltration. CONCLUSION: Newly screened immunoglobulin kappa light chain clonality assays may be useful to distinguish VRL from uveitis with high specificity. When sub-retinal pigment epithelium or retinal infiltration is severe and extensive, the IL-10-to-IL-6 ratio may not be typical and should be carefully interpreted.

Transient Anosmia Induces Depressive-like and Anxiolytic-like Behavior and Reduces Amygdalar Corticotropin-Releasing Hormone in a ZnSO4-Induced Mouse Model.

Olfactory loss is known to affect both mood and quality of life. Transient anosmia was induced in mice to study the resulting changes in mood, behavior, and on a molecular level. Transient anosmia was induced by a single intranasal instillation of ZnSO4 in BALB/c mice. Hematoxylin and eosin (HE) staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression-related behavior; while the open field, and elevated plus maze tests were used to evaluate anxiety-related behavior. The mRNA levels of amygdalar corticotropin-releasing hormone (CRH) and hypothalamic glucocorticoid receptor (GR) were quantified using real-time PCR to confirm relevant molecular change. Olfactory loss was confirmed 1-2.5 weeks after induction, and this loss was subsequently reversed over time. The results of the behavioral tests indicated increased depression-like and reduced anxiety-like behavior at week 1. Accordingly, PCR data identified decreased amygdalar CRH expression at week 1. These results suggest that transient anosmia induces both depressive and anxiolytic behavior as a result of decreased amygdalar CRH in a mouse model of anosmia.

Dendritic spine anomalies and PTEN alterations in a mouse model of VPA-induced autism spectrum disorder.

Mounting evidence suggests that the etiology of autism spectrum disorders (ASDs) is profoundly influenced by exposure to environmental factors, although the precise molecular and cellular links remain ill-defined. In this study, we examined how exposure to valproic acid (VPA) during pregnancy is associated with an increased incidence of ASD. A mouse model was established by injecting VPA at embryonic day 13, and its behavioral phenotypes including impaired social interaction, increased repetitive behaviors and decreased nociception were observed at postnatal days 21-42. VPA-treated mice showed dysregulation of synaptic structure in cortical neurons, including a reduced proportion of filopodium-type and stubby spines and increased proportions of thin and mushroom-type spines, along with a decreased spine head size. We also found that VPA-treatment led to decreased expression of phosphate and tensin homolog (PTEN) and increased levels of p-AKT protein in the hippocampus and cortex. Our data suggest that there is a correlation between VPA exposure and dysregulation of PTEN with ASD-like behavioral and neuroanatomical changes, and this may be a potential mechanism of VPA-induced ASD.

Neuregulin 1 regulates amyloid precursor protein cell surface expression and non-amyloidogenic processing.

The amyloid precursor protein (APP) is a key molecule in Alzheimer's disease. The prevailing view is that APP is initially transported to the plasma membrane as a full-length protein. Its localization at the cell surface can trigger downstream signaling and APP cleavage. Our previous work has shown that Neuregulin 1 (NRG1) has neuroprotective effects in an Alzheimer's disease model. In the present study, we examine whether NRG1 signaling is involved in APP expression and non-amyloidogenic processing in neuronal cells. Here we show that NRG1 increased the cell surface expression of APP without changing the total amount of APP mRNA or protein expression in SH-SY5Y cells and in rat primary cortical neurons. In addition, NRG1 significantly increased the levels of the secreted form of APP, sAPPα, in the conditioned media but did not change the expression of ADAM10 on the cell surface or in the cell lysates. Furthermore, we found that the protein level of NRG1 was reduced in the hippocampus of Alzheimer's disease (AD) patients. Our results demonstrate that NRG1 increased APP expression on the cell surface and sAPPα secretion into the media of neuronal cell cultures. Taken together, these results suggest a role for NRG1 in non-amyloidogenic processing.

Alterations in protein phosphorylation in the amygdala of the 5XFamilial Alzheimer's disease animal model.

Alzheimer's disease is the most common disease underlying dementia in humans. Two major neuropathological hallmarks of AD are neuritic plaques primarily composed of amyloid beta peptide and neurofibrillary tangles primarily composed of hyperphosphorylated tau. In addition to impaired memory function, AD patients often display neuropsychiatric symptoms and abnormal emotional states such as confusion, delusion, manic/depressive episodes and altered fear status. Brains from AD patients show atrophy of the amygdala which is involved in fear expression and emotional processing as well as hippocampal atrophy. However, which molecular changes are responsible for the altered emotional states observed in AD remains to be elucidated. Here, we observed that the fear response as assessed by evaluating fear memory via a cued fear conditioning test was impaired in 5XFamilial AD (5XFAD) mice, an animal model of AD. Compared to wild-type mice, 5XFAD mice showed changes in the phosphorylation of twelve proteins in the amygdala. Thus, our study provides twelve potential protein targets in the amygdala that may be responsible for the impairment in fear memory in AD.

Neuregulin 1 Controls Glutamate Uptake by Up-regulating Excitatory Amino Acid Carrier 1 (EAAC1).

Neuregulin 1 (NRG1) is a trophic factor that is thought to have important roles in the regulating brain circuitry. Recent studies suggest that NRG1 regulates synaptic transmission, although the precise mechanisms remain unknown. Here we report that NRG1 influences glutamate uptake by increasing the protein level of excitatory amino acid carrier (EAAC1). Our data indicate that NRG1 induced the up-regulation of EAAC1 in primary cortical neurons with an increase in glutamate uptake. These in vitro results were corroborated in the prefrontal cortex (PFC) of mice given NRG1. The stimulatory effect of NRG1 was blocked by inhibition of the NRG1 receptor ErbB4. The suppressed expression of ErbB4 by siRNA led to a decrease in the expression of EAAC1. In addition, the ablation of ErbB4 in parvalbumin (PV)-positive neurons in PV-ErbB4(-/-) mice suppressed EAAC1 expression. Taken together, our results show that NRG1 signaling through ErbB4 modulates EAAC1. These findings link proposed effectors in schizophrenia: NRG1/ErbB4 signaling perturbation, EAAC1 deficit, and neurotransmission dysfunction.

Involvement of 14-3-3 in tubulin instability and impaired axon development is mediated by Tau.

14-3-3 proteins act as adapters that exert their function by interacting with their various protein partners. 14-3-3 proteins have been implicated in a variety of human diseases including neurodegenerative diseases. 14-3-3 proteins have recently been reported to be abundant in the neurofibrillary tangles (NFTs) observed inside the neurons of brains affected by Alzheimer's disease (AD). These NFTs are mainly constituted of phosphorylated Tau protein, a microtubule-associated protein known to bind 14-3-3. Despite this indication of 14-3-3 protein involvement in the AD pathogenesis, the role of 14-3-3 in the Tauopathy remains to be clarified. In the present study, we shed light on the role of 14-3-3 proteins in the molecular pathways leading to Tauopathies. Overexpression of the 14-3-3σ isoform resulted in a disruption of the tubulin cytoskeleton and prevented neuritic outgrowth in neurons. NMR studies validated the phosphorylated residues pSer214 and pSer324 in Tau as the 2 primary sites for 14-3-3 binding, with the crystal structure of 14-3-3σ in complex with Tau-pSer214 and Tau-pSer324 revealing the molecular details of the interaction. These data suggest a rationale for a possible pharmacologic intervention of the Tau/14-3-3 interaction.

Subfoveal choroidal thickness as a predictor of treatment response to anti-vascular endothelial growth factor therapy for polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether subfoveal choroidal thickness predicted treatment response to anti-vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV). METHODS: This retrospective observational case series included 66 eyes of 60 patients who were diagnosed with new-onset PCV and who were followed for a minimum of 6 months. Patients received three monthly intravitreal injections of 0.5 mg ranibizumab or 1.25 mg bevacizumab, at baseline, month 1, and month 2. "Good responders" were defined as those who showed complete resolution of subretinal and/or intraretinal fluid at month 3 after the loading injections, whereas "poor responders" were defined as those who showed persistent retinal fluid on optical coherence tomography (OCT) at month 3 after treatment. Differences in best-corrected visual acuity, indocyanine green angiography, and spectral domain-OCT findings at baseline were analyzed between the two groups. RESULTS: The mean patient age was 68.2 ± 9.7 years, and the mean follow-up period was 27 ± 21 months. The mean subfoveal choroidal thickness was 273 ± 117 µm, and choroidal vascular hyperpermeability was observed in 35 eyes (53.0 %). Thirty-three eyes (50 %) showed good response to treatment, and a thinner subfoveal choroid at baseline significantly correlated with favorable treatment response (P = 0.024). However, there was no significant relationship between treatment response and choroidal vascular hyperpermeability (P = 0.999). CONCLUSIONS: The subfoveal choroid was found to be significantly thinner among patients who achieved complete resolution of macular exudation after three loading injections of anti-VEGF agents.

Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling.

Despite the pivotal functions of the NMDA receptor (NMDAR) for neural circuit development and synaptic plasticity, the molecular mechanisms underlying the dynamics of NMDAR trafficking are poorly understood. The cell adhesion molecule neuroligin-1 (NL1) modifies NMDAR-dependent synaptic transmission and synaptic plasticity, but it is unclear whether NL1 controls synaptic accumulation or function of the receptors. Here, we provide evidence that NL1 regulates the abundance of NMDARs at postsynaptic sites. This function relies on extracellular, NL1 isoform-specific sequences that facilitate biochemical interactions between NL1 and the NMDAR GluN1 subunit. Our work uncovers NL1 isoform-specific cis-interactions with ionotropic glutamate receptors as a key mechanism for controlling synaptic properties.

Chronic anosmia induces depressive behavior and reduced anxiety via dysregulation of glucocorticoid receptor and corticotropin-releasing hormone in a mouse model.

BACKGROUND: Olfactory loss is highly prevalent, and comorbid mood disorders are common. Considering olfactory input is highly interconnected with the limbic system, and that the limbic system manages mood, it is predictable that impairments in the sense of smell may result in mood changes. METHODOLOGY: Chronic olfactory deficits were induced by repeated intranasal irrigation of ZnSO4 for 12 weeks in BALB/c mice. H&E staining, OMP staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression, as well as open field, elevated plus maze tests were applied to assess anxiety. The mRNA levels of glucocorticoid receptor (GR) and corticotropin releasing hormone (CRH) were measured by real-time PCR to confirm relevant molecular changes. RESULTS: Disruption of the olfactory epithelium and olfactory loss was confirmed in histological studies and potato chip finding test. Behavioral tests show that the chronic anosmic state caused increased depression and reduced anxiety. PCR data showed that mRNA levels of GR in the hypothalamus and CRH in the amygdala were significantly decreased. CONCLUSIONS: These results propose that ZnSO4-induced chronic anosmia can cause a depressive and anxiolytic state via decreased hypothalamic GR and amygdalar CRH.

Should endometrial clear cell carcinoma be classified as Type II endometrial carcinoma?

Endometrial clear cell carcinomas (ECCCs) are considered to be Type II endometrial carcinomas, like uterine serous adenocarcinoma (SCA), and therefore aggressive clinical management is indicated. However, according to the limited clinical, immunohistochemical, and molecular data available in the literature, ECCCs show overlapping features of SCA and endometrioid adenocarcinomas. Therefore, questions regarding their designation as the Type II carcinomas have been raised. We performed immunohistochemical staining for hepatocyte nuclear factor-1ß and napsin A for the histologic confirmation of clear cell carcinoma (CCC), and analyzed immunohistochemical findings for estrogen receptor, progesterone receptor, HER2/neu, p53, p16, ARID1A, PTEN, DNA mismatch-repair proteins along with other prognostic factors. We performed DNA sequencing for the K-RAS, BRAF, PIK3CA, and PTEN genes for 16 pure CCCs. No patients with pure CCC experienced recurrent disease or died of the disease (0/16, 0%). ECCCs had SCA-like features with rare expression of estrogen receptor/progesterone receptor (18.8%/6.3%) and no K-RAS mutations, intermediate features regarding expressions of p53 (37.5%) and p16 (25%), and endometrioid adenocarcinoma-like features regarding losses of PTEN (81.3%), ARID1A (25%) and mismatch-repair protein (68.8%), expression of microsatellite instability-high (25%), HER2/neu (12.5%), and PIK3CA mutations (18.8%). Pure ECCC should not be regarded as Type II carcinoma, because it shares the immunohistochemical and molecular characteristics of Type I endometrioid adenocarcinoma and Type II SCA.

A highly annotated whole-genome sequence of a Korean individual.

Recent advances in sequencing technologies have initiated an era of personal genome sequences. To date, human genome sequences have been reported for individuals with ancestry in three distinct geographical regions: a Yoruba African, two individuals of northwest European origin, and a person from China. Here we provide a highly annotated, whole-genome sequence for a Korean individual, known as AK1. The genome of AK1 was determined by an exacting, combined approach that included whole-genome shotgun sequencing (27.8x coverage), targeted bacterial artificial chromosome sequencing, and high-resolution comparative genomic hybridization using custom microarrays featuring more than 24 million probes. Alignment to the NCBI reference, a composite of several ethnic clades, disclosed nearly 3.45 million single nucleotide polymorphisms (SNPs), including 10,162 non-synonymous SNPs, and 170,202 deletion or insertion polymorphisms (indels). SNP and indel densities were strongly correlated genome-wide. Applying very conservative criteria yielded highly reliable copy number variants for clinical considerations. Potential medical phenotypes were annotated for non-synonymous SNPs, coding domain indels, and structural variants. The integration of several human whole-genome sequences derived from several ethnic groups will assist in understanding genetic ancestry, migration patterns and population bottlenecks.

Subfoveal choroidal thickness in idiopathic choroidal neovascularization and treatment outcomes after intravitreal bevacizumab therapy.

PURPOSE: To determine subfoveal choroidal thickness in idiopathic choroidal neovascularization (CNV) and evaluate visual and anatomical outcomes in patients with idiopathic CNV after intravitreal bevacizumab. METHODS: Retrospective observation case series. Seventeen eyes of 17 patients with idiopathic CNV were treated with a single intravitreal bevacizumab injection, followed by additional doses based on optical coherence tomography findings, including intraretinal fluid, subretinal fluid, or pigment epithelial detachment. We analyzed best-corrected visual acuity, central subfield thickness, and subfoveal choroidal thickness at presentation and final visit. Seventeen unaffected fellow eyes and 17 healthy eyes constituted the control group for subfoveal choroidal thickness. RESULTS: The subfoveal choroidal thickness was significantly thinner in eyes with idiopathic CNV (237.59 ± 53.84 µm) than in the unaffected fellow eyes (281.71 ± 59.01 µm, P = 0.001) or normal control eyes (290.38 ± 58.94 µm, P = 0.028). Mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.46 initially to 0.26 after treatment (P = 0.024). Mean central subfield thickness decreased from 387.88 ± 97.52 µm at baseline to 261.41 ± 31.18 µm after treatment (P < 0.001). CONCLUSION: Subfoveal choroidal thickness is reduced and may be associated with the pathophysiology of idiopathic CNV. Intravitreal bevacizumab resulted in significant visual and anatomical improvement in patients with idiopathic CNV.

Identification of Underlying Causes of Spontaneous Submacular Hemorrhage by Indocyanine Green Angiography.

PURPOSE: To investigate the causes of acute spontaneous submacular hemorrhage with indocyanine green angiography (ICGA). METHODS: Retrospective observation case series. A total of 51 eyes from 51 patients with newly developed spontaneous submacular hemorrhage were enrolled. Best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography, spectral domain optical coherence tomography (OCT), and ICGA at baseline were analyzed. The extent of hemorrhage using fundus photography, height of hemorrhage, and central foveal thickness measured by OCT was analyzed to compare the diagnostic and nondiagnostic groups. RESULTS: The mean logarithm of the minimum angle of resolution (logMAR) BCVA at presentation was 1.21 ± 0.74 (Snellen equivalent, 20/324); the mean follow-up period was 23.9 ± 23.9 months. The cause of submacular hemorrhage was diagnosed in 43 of 51 eyes (84.3%) based on ICGA at presentation. The initial diagnoses were correct in 93% of eyes. In 3 cases, the initial diagnosis of age-related macular degeneration (AMD) was changed to polypoidal choroidal vasculopathy (PCV) based on follow-up ICGA. The central foveal thickness was significantly greater in the nondiagnostic group (1,102.4 vs. 666.7 µm, respectively; p = 0.008). The most common cause of submacular hemorrhage was neovascular AMD (52.9%), followed by PCV (37.3%), macroaneurysm (5.9%), and lacquer crack (3.9%). The mean final visual acuity was generally worse in patients with submacular hemorrhage with typical AMD (visual acuity 20/618) or PCV (visual acuity 20/240) compared to that in patients with retinal macroaneurysm (visual acuity 20/100) or lacquer crack (visual acuity 20/72). CONCLUSIONS: ICGA at initial presentation helps identify causes of submacular hemorrhage, allowing differential treatment approaches that may improve outcomes and safety.

Clinical and spectral-domain optical coherence tomography findings in patients with focal choroidal excavation.

OBJECTIVE: To describe the clinical and spectral-domain optical coherence tomography (SD-OCT) findings in patients with focal choroidal excavation (FCE). DESIGN: Retrospective case series. PARTICIPANTS: Forty-one eyes of 38 patients with FCE identified in 2 tertiary medical centers in Korea. METHODS: Clinical features, SD-OCT findings, and associated macular disorders of FCE were analyzed and detailed. MAIN OUTCOME MEASURES: Statistical associations among clinical features, including lesion type, size, and choroidal thickness, and frequency of association with central serous chorioretinopathy (CSC), choroidal neovascularization (CNV), and polypoidal choroidal vasculopathy (PCV). RESULTS: Mean patient age was 50.1 years (range, 25-76 years). The mean spherical equivalent of refractive error was -3.7 diopters (range, -10.0 to +1.5 diopters). Three patients (8%) had bilateral lesions, and 1 patient (3%) had 2 distinct lesions in the same eye. The mean FCE width and depth were 757 µm and 107 µm, respectively, with a positive correlation between width and depth (P = 0.003). The mean subfoveal choroidal thickness of FCE eyes was 284 µm, which was not statistically different from that of age-, sex-, and refractive error-matched normal subjects. Choroidal thickness in FCE was less in eyes with hyperreflective choroidal tissue under the excavation that was present in 22 eyes (54%) versus eyes without excavation (128 vs. 190 µm, respectively; P = 0.009). Twelve FCEs (29%) were the nonconforming type, revealing separation between the photoreceptor tips and the retinal pigment epithelium on SD-OCT. Nonconforming FCE was associated with visual symptoms (P < 0.001) and the presence of concurrent CSC (P = 0.001). Ten eyes (24%) were associated with CSC, and 9 eyes (22%) were associated with CNV, including 1 eye with PCV features. One eye with FCE and type 1 CNV developed a new excavation, and the excavated area in 1 eye with PCV enlarged slightly during follow-up. CONCLUSIONS: Focal choroidal excavation is a relatively common entity and frequently associated with choroidal diseases, including CSC, CNV, and PCV. Although FCE is classically thought to be a congenital malformation, acquired FCE forms possibly exist.