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Competing Interests: Financial disclosures/conflicts of interest: None reported.

Purpose: The aim of this study was to identify the risk factors for postkeratorefractive surgery ectasia in unsuspicious tomographies and to report a new index coined diameter of peak locations (DPLs)., Methods: All patients who underwent keratorefractive surgery between 2011 and 2018 at Care-Vision Laser Centers, Israel, and later developed ectasia were included. For each ectasia case, 3 matched controls were selected. Demographic and preoperative, intraoperative, and postoperative data were collected. Multivariate analysis was performed to evaluate the interdependence of the variables., Results: The retrospective study included 19 ectasia and 58 control eyes. There were no significant differences between the groups in ablation depth ( P = 0.73), preoperative spherical equivalent ( P = 0.12), percent tissue altered ( P = 0.71), residual stromal bed ( P = 0.73), and Ectasia Risk Score System ( P = 0.60). The anterior and the posterior symmetry index were significantly higher ( P < 0.001), and DPL was significantly tighter in the ectasia group ( P = 0.01). Binary multiple logistic regression found the symmetry index of the posterior cornea and DPL to be better predictors than age, percent tissue altered, Ectasia Risk Score System, residual stromal bed, and ablation depth., Conclusions: A higher posterior symmetry index and a tighter DPL are predictors of ectasia in patients with otherwise normal tomographies. A tight DPL implies a weak area in the cornea, which is thin and slightly bulging, increasing the risk of this area becoming ectatic., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The medial amygdala (MeA) is a sexually dimorphic brain region that regulates fear responses, emotional memories, and social behaviors. It is known to be larger and contains more cells in males. The MeA integrates information through input connections from olfactory regions, bed nucleus of the stria terminalis, ventral hippocampus, and thalamic and hypothalamic structures. We hypothesize that in addition to the size differences, there are differences in regional connectivity between the sexes. In this study, we utilized G-deleted rabies monosynaptic retrograde tracing to compare amygdala presynaptic cells in male and female whole mouse brains. We report differences in connection patterns to the amygdala, with higher overall connectivity (presynaptic per starter) in males and a larger fraction of inputs originating from the bed nucleus of the stria terminalis, lateral septum, and medial preoptic area. Furthermore, we examined input connections to the orbital cortex (ORB), a brain region shown to be larger in volume in females, and found the opposite trend, where females had more total inputs. Together, our findings extend the evidence for sexual dimorphism in the brain to the neuronal wiring pattern, with likely impacts on behavior and disease susceptibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Aloni, Tibi, Hochgerner and Zeisel.)

Background: Fulminant idiopathic intracranial hypertension (FIIH) is characterized by rapid, severe, progressive vision loss and often treated surgically. Cerebral transverse venous stenting (CTVS) is efficacious in IIH patients, but emergent CTVS in FIIH is rarely reported. We present our experience with emergent CTVS in patients with FIIH., Methods: Since 01/2019, an institutional protocol allowed emergent CTVS in FIIH patients with bilateral transverse sinus stenosis and gradient pressure > 15 on digital subtraction angiography (DSA). We retrospectively analyzed a prospective registry of all IIH patients with details of neurological and neuro-ophthalmological assessments before and after treatment, and subjective assessments of headache and tinnitus were made pre-and post-procedure., Results: 259 IIH patients, including 49 who underwent CTVS, were registered. Among them, five female patients met inclusion criteria for FIIH and underwent emergent CTVS. FIIH patients were younger (18.8 ± 1.64 vs 27.7 ± 4.85, p < 0.01), mean BMI was lower (30.8 ± 10.57 vs 34.6 ± 4.3, p < 0.01), and lumbar puncture opening pressure higher (454 ± vs 361 ± 99.4, p < 0.01) than that of IIH patients. They presented with acute visual loss, severe headache, papilledema, significant bilateral transverse sinus stenosis on CT-venography, and mean dominant side gradient pressure of 26.4 ± 6.2 on DSA. CTVS was performed without significant complications, resulting in remarkable improvement in headache, optical coherence tomography, and visual fields within 1 week. At 1-year follow-up (four patients) and 6-month follow-up (1 patient), there was complete resolution of papilledema and headache, and marked improvement in visual acuity., Conclusions: In these patients, emergent-CTVS was a safe and effective treatment option for FIIH. Further evaluation is warranted., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The mouse brain is by far the most intensively studied among mammalian brains, yet basic measures of its cytoarchitecture remain obscure. For example, quantifying cell numbers, and the interplay of sex, strain, and individual variability in cell density and volume is out of reach for many regions. The Allen Mouse Brain Connectivity project produces high-resolution full brain images of hundreds of brains. Although these were created for a different purpose, they reveal details of neuroanatomy and cytoarchitecture. Here, we used this population to systematically characterize cell density and volume for each anatomical unit in the mouse brain. We developed a DNN-based segmentation pipeline that uses the autofluorescence intensities of images to segment cell nuclei even within the densest regions, such as the dentate gyrus. We applied our pipeline to 507 brains of males and females from C57BL/6J and FVB.CD1 strains. Globally, we found that increased overall brain volume does not result in uniform expansion across all regions. Moreover, region-specific density changes are often negatively correlated with the volume of the region; therefore, cell count does not scale linearly with volume. Many regions, including layer 2/3 across several cortical areas, showed distinct lateral bias. We identified strain-specific or sex-specific differences. For example, males tended to have more cells in extended amygdala and hypothalamic regions (MEA, BST, BLA, BMA, and LPO, AHN) while females had more cells in the orbital cortex (ORB). Yet, inter-individual variability was always greater than the effect size of a single qualifier. We provide the results of this analysis as an accessible resource for the community., Competing Interests: DE, HH, EA, NS, AZ No competing interests declared, (© 2023, Elkind et al.)

Background: A multitude of terms have been used to describe automated visual field abnormalities. To date, there is no universally accepted system of definitions or guidelines. Variability among clinicians creates the risk of miscommunication and the compromise of patient care. The purposes of this study were to 1) assess the degree of consistency among a group of neuro-ophthalmologists in the description of visual field abnormalities and 2) to create a consensus statement with standardized terminology and definitions., Methods: In phase one of the study, all neuro-ophthalmologists in Israel were asked to complete a survey in which they described the abnormalities in 10 selected automated visual field tests. In phase 2 of the study, the authors created a national consensus statement on the terminology and definitions for visual field abnormalities using a modified Delphi method. In phase 3, the neuro-ophthalmologists were asked to repeat the initial survey of the 10 visual fields using the consensus statement to formulate their answers., Results: Twenty-six neuro-ophthalmologists participated in the initial survey. On average, there were 7.5 unique descriptions for each of the visual fields (SD 3.17), a description of only the location in 24.6% (SD 0.19), and an undecided response in 6.15% (SD 4.13). Twenty-two neuro-ophthalmologists participated in the creation of a consensus statement which included 24 types of abnormalities with specific definitions. Twenty-three neuro-ophthalmologists repeated the survey using the consensus statement. On average, in the repeated survey, there were 5.9 unique descriptions for each of the visual fields (SD 1.79), a description of only the location in 0.004% (SD 0.01), and an undecided response in 3.07% (SD 2.11%). Relative to the first survey, there was a significant improvement in the use of specific and decisive terminology., Conclusions: The study confirmed a great degree of variability in the use of terminology to describe automated visual field abnormalities. The creation of a consensus statement was associated with improved use of specific terminology. Future efforts may be warranted to further standardize terminology and definitions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the North American Neuro-Opthalmology Society.)

Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) have been recognized over the past 10 years as distinct inflammatory, demyelinating diseases of the central nervous system (CNS). Antibodies against MOG are found mostly in patients with optic neuritis (ON), acute disseminated encephalomyelitis (ADEM), and aquaporin-4 antibody (AQP4-abs)-seronegative neuromyelitis optica spectrum disorders (NMOSD). However, data on the disease course and disability outcomes of these patients are scarce. Aim: To describe clinical and paraclinical features associated with MOG antibodies (abs) in a cohort of patients in Israel, and to assess baseline prognostic features of MOG-ab-associated diseases after a first acute demyelinating event. Methods: MOG-abs were identified in serum using a cell-based assay, and clinical data were collected from the patients' medical records. Results: Of 683 patients with demyelinating diseases tested for MOG-abs, 53 were positive (7.7%), with ON the most common presenting phenotype (68%). The age range of MOG-abs seropositive patients was 1-66 years, with increased prevalence in children (19% compared to 6.7% in adults) ( p < 0.01). The highest prevalence of seropositivity was observed in children aged younger than 10 years (25.5%), followed by those aged 31-40 years (16.6%). Conclusions: MOGAD are distinct autoimmune diseases that occurs at all stages of life with a significantly higher prevalence in children; the main clinical presenting phenotype in the entire cohort is ON and young children most often presented with ON or ADEM. Our data highlight the need for repeated evaluation of MOG-abs in patients with acquired CNS demyelinating disorders, especially in children under 10 and adults between 31 and 40 years of age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Brill, Ganelin-Cohen, Dabby, Rabinowicz, Zohar-Dayan, Rein, Aloni, Karmon and Vaknin-Dembinsky.)

Objective: Visual status is routinely evaluated by neuro-ophthalmologic examination and computerized visual field (VF) tests in patients with chiasmal compression secondary to pituitary macroadenoma. Currently, no relevant data exists to accurately quantify the extent of optic apparatus compromise to further guide clinical decision-making. We aimed to assess for a possible quantitative correlation between optic chiasm geometric properties on magnetic resonance imaging (MRI) and VF deficits., Methods: Visual assessments and concurrent MRI scans were retrospectively reviewed from patients treated for pituitary macroadenoma in a single medical institution. Chiasm width, chiasm minimal and maximal height, and chiasm angle were measured on MRI coronal plane images by 3 independent reviewers (for the sake of variability analysis). VF numerical summary parameters were also retrieved., Results: A total of 30 patients were included in the final analysis. Average VF index was 70% (±30), and averaged mean deviation was 10.0 db (±9). Chiasm angle and width (which together represents the bending and stretching of the chiasm by the upward directed compression; both of which demonstrated high inter- and intraobserver agreement) showed strong correlation with VF loss. Chiasmal compression index derived from those parameters showed even stronger correlation., Conclusions: The strong correlation demonstrated by our results of this relatively simple radiologic measurement with VF status, despite the relatively small cohort, calls for further investigation in this promising direction, and may facilitate with basic assessment and clinical decision-making for patients with equivocal neuro-ophthalmologic evaluation, as well as with poor compliance., (Copyright © 2020. Published by Elsevier Inc.)

Disruption in calcium homeostasis is linked to several pathologies and is suggested to play a pivotal role in the cascade of events leading to Alzheimer's disease (AD). Synaptopodin (SP) residing in dendritic spines has been associated with ryanodine receptor (RyR), such that spines lacking SP release less calcium from stores. In this work, we mated SPKO with 3xTg mice (3xTg/SPKO) to test the effect of SP deficiency in the AD mouse. We found that 6-month-old male 3xTg/SPKO mice restored normal spatial learning in the Barns maze, LTP in hippocampal slices, and expression levels of RyR in the hippocampus that were altered in the 3xTg mice. In addition, there was a marked reduction in 3xTg-associated phosphorylated tau, amyloid β plaques, and activated microglia in 3xTg/SPKO male and female mice. These experiments indicate that a reduction in the expression of SP ameliorates AD-associated phenotype in 3xTg mice. SIGNIFICANCE STATEMENT This study strengthens the proposed role of calcium stores in the development of AD-associated phenotype in the 3xTg mouse model, in that a genetic reduction of the functioning of ryanodine receptors using synaptopodin-knock-out mice ameliorates AD symptoms at the behavioral, electrophysiological, and morphological levels of analysis., (Copyright © 2019 the authors.)

Introduction: Fulminant intracranial hypertension is a rare, acute presentation of idiopathic intracranial hypertension with rapid and devastating visual loss that can lead to blindness. As vision deteriorates quickly and often irreversibly, prevention of further visual loss requires emergent treatment to decrease intracranial pressure. The case presented is that of an 18 years old male with new symptoms of headaches and visual obscurations that had rapid progressive visual loss with findings of severe bilateral swollen discs. Brain MRI and MRV ruled out intracranial mass and cerebral venous thrombosis. A lumbar puncture confirmed highly increased ICP. Due to the fulminant clinical presentation, he underwent an urgent fenestration of both optic nerves with improvement of vision in both eyes. The patient's clinical scenario accentuates the importance of prompt recognition of this rare disorder and the need for immediate surgical intervention to prevent further visual loss and blindness.

Mitochondrial Carrier Homolog 2 (MTCH2) acts as a receptor for the BH3 interacting-domain death agonist (BID) in the mitochondrial outer membrane. Loss of MTCH2 affects mitochondria energy metabolism and function. MTCH2 forebrain conditional KO (MTCH2 BKO) display a deficit in hippocampus-dependent cognitive functions. Here we study age-related MTCH2 BKO behavioral and electrophysiological aspects of hippocampal functions. MTCH2 BKO exhibit impaired spatial but not motor learning and an impairment in long-term potentiation (LTP) in hippocampal slices. Moreover, MTCH2 BKO express an increase in activated microglia, in addition to a reduction in neuron density in the hippocampus, but do not express amyloid-β plaques or neurofibrillary tangles. These results highlight the role of mitochondria in the normal hippocampus-dependent memory formation., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Mitochondrial Carrier Homolog 2 (MTCH2) is a novel regulator of mitochondria metabolism, which was recently associated with Alzheimer's disease. Here we demonstrate that deletion of forebrain MTCH2 increases mitochondria and whole-body energy metabolism, increases locomotor activity, but impairs motor coordination and balance. Importantly, mice deficient in forebrain MTCH2 display a deficit in hippocampus-dependent cognitive functions, including spatial memory, long term potentiation (LTP) and rates of spontaneous excitatory synaptic currents. Moreover, MTCH2-deficient hippocampal neurons display a deficit in mitochondria motility and calcium handling. Thus, MTCH2 is a critical player in neuronal cell biology, controlling mitochondria metabolism, motility and calcium buffering to regulate hippocampal-dependent cognitive functions.

GSK-3 (glycogen synthase kinase-3) is a serine/threonine kinase which is a critical regulator in neuronal signaling, cognition, and behavior. We have previously shown that unlike other vertebrates that harbor both α and β GSK-3 genes, the α gene is missing in birds. Therefore, birds can be used as a new animal model to study the roles of GSK-3β in behavior and in regulating adult neurogenesis. In the present study, we inhibited GSK-3β in brains of adult male zebra finches (Taeniopygia guttata) and accordingly investigated how this inhibition affects behavior and cell proliferation. Our results show that GSK-3 inhibition: (1) affects specific aspects of singing behavior, which might be related to social interactions in birds, and (2) differentially affects cell proliferation in various parts of the ventricular zone. Taken together, our study demonstrates a role of GSK-3β in regulating singing behavior and neuronal proliferation in birds and highlights the importance of GSK-3β in modulating cognitive abilities as well as social behavior., (© 2015 S. Karger AG, Basel.)

Purpose: To establish a rat model of acute increase in intraocular pressure (IOP) and to investigate the therapeutic window for protection against death of retinal ganglion cells (RGCs) by vaccination with glatiramer acetate (Cop-1) or by treatment with brimonidine or MK-801., Design: Animal study, laboratory investigation., Methods: IOP was transiently increased in anesthetized Lewis rats by infusing normal saline (0.9%) into the anterior chamber of the eye for one hour. RGC survival was assessed one week and two weeks later by counting the RGCs retrogradely labeled with rhodamine dextran., Main Outcome Measures: RGC survival., Results: IOP rose to 100 cm H(2)O (76 mm Hg) and returned to baseline after 24 hours. The RGC count decreased by 23% a week after the insult and by a further 7% after the second week. Vaccination with Cop-1 on the day of the insult prevented 50% of the IOP-induced RGC loss. Similar neuroprotection was achieved by daily intraperitoneal injections of brimonidine, but not with MK-801., Conclusions: A transient increase in IOP to 100 cm H(2)O causes death of RGCs in rats. A single immunization with Cop-1 or daily injections of brimonidine protected up to 50% of potentially doomed RGCs from IOP-induced death, suggesting that not all of the cell death in the untreated model results from the IOP insult directly, but that some of it is caused by insult-induced environmental cytotoxicity, which is unrelated to glutamate toxicity or at least to NMDA receptors. These findings can be applied immediately as a basis for acute glaucoma therapy.

To elucidate the role of auxin in flower morphogenesis, its distribution patterns were studied during flower development in Arabidopsis thaliana (L.) Heynh. Expression of DR5::GUS was regarded to reflect sites of free auxin, while immunolocalization with auxin polyclonal antibodies visualized conjugated auxin distribution. The youngest flower bud was loaded with conjugated auxin. During development, the apparent concentration of free auxin increased in gradual patterns starting at the floral-organ tip. Anthers are major sites of high concentrations of free auxin that retard the development of neighboring floral organs in both the acropetal and basipetal directions. The IAA-producing anthers synchronize flower development by retarding petal development and nectary gland activity almost up to anthesis. Tapetum cells of young anthers contain free IAA which accumulates in pollen grains, suggesting that auxin promotes pollen-tube growth towards the ovules. High amounts of free auxin in the stigma induce a wide xylem fan immediately beneath it. After fertilization, the developing embryos and seeds show elevated concentrations of auxin, which establish their axial polarity. This developmental pattern of auxin production during floral-bud development suggests that young organs which produce high concentrations of free IAA inhibit or retard organ-primordium initiation and development at the shoot tip.

Acute or chronic glaucoma is often associated with an increase in intraocular pressure (IOP). In many patients, however, therapeutic pressure reduction does not halt disease progression. Neuroprotection has been proposed as a complementary therapeutic approach. We previously demonstrated effective T-cell-based neuroprotection in experimental animals vaccinated with the synthetic copolymer glatiramer acetate (copolymer-1, Cop-1), a weak agonist of self-antigens. This study was undertaken to test different routes and modes of vaccination with Cop-1 as treatment modalities for protection against retinal ganglion cell (RGC) death caused by chronic elevation of IOP in rats, and to determine whether anatomical neuroprotection is accompanied by functional neuroprotection. In a chronic model of unilaterally high IOP, Cop-1 vaccination, with or without an adjuvant, protected rats against IOP-induced loss of RGCs by eliciting a systemic T-cell-mediated response capable of cross-reacting with self-antigens residing in the eye. In rats deprived of T cells, Cop-1 (unlike treatment with alpha2-adrenoreceptor agonists) was not protective of RGCs, substantiating the contention that its beneficial effect is not conferred directly but is T-cell-mediated. Pattern electroretinography provided evidence of functional protection. Thus, vaccination with adjuvant-free Cop-1 can protect RGCs from the consequences of elevated IOP in rats. This protection is manifested both morphologically and functionally. These findings can be readily implemented for the development of a therapeutic vaccination to arrest the progression of glaucoma.

Background: Macular edema is the main cause of visual impairment in diabetic patients. Its treatment is mainly based on laser photocoagulation. Intravitreal triamcinolone acetonide (TA) has recently been proposed as a new treatment for eyes with diabetic macular edema resistant to conventional laser photocoagulation., Aim: To evaluate the one year efficacy and safety of a single TA injection administered for diffuse diabetic macular edema unresponsive to prior laser treatment., Design: Interventional case series., Methods: Setup: University medical center out-patient clinic., Participants: Twenty-one patients with bilateral diffuse diabetic macular edema., Intervention: A single intravitreal injection of triamcinolone acetonide., Main Outcome Measures: Visual acuity measured by ETDRS score, retinal area evaluation clinically and retinal thickness evaluation by Retinal Thickness Analysis (RTA) at 3 and 12 months following injection. Secondary outcomes were intraocular pressure control and cataract progression., Results: Three months following injection, the mean improvement in visual acuity was 4.7 +/- 11.7 letters in the study group as compared to 0.2 +/- 11.4 in the control group (p = 0.18). No difference was noticed one year following injection. Clinical assessment of the retinal area of edema revealed a substantial difference between patients and controls at 3 months (p = 0.0006) and at one year (p = 0.05). RTA evaluation revealed improvement in retinal thickness solely at the 3 months exam. Four eyes developed high intraocular pressure and required treatment (p = 0.054). No difference in cataract progression was noted between the two groups (p = 0.69)., Conclusions: Injection of TA may improve visual acuity for a limited time. Increased intraocular pressure is a frequent side effect. During a one year follow-up, no evidence of ocular toxicity was noted in eyes with diffuse diabetic macular edema.

To clarify how root-synthesized cytokinins (CKs) are transported to young shoot organs, CK distribution patterns were analysed in free-CK-responsive ARR5::GUS transformants of Arabidopsis thaliana (L.) Heynh. together with free plus bound CKs using specific CK monoclonal antibodies. Plants were subjected to two different growth conditions, completely protected from any air movement, or exposed to gentle wind 3 h before harvesting. In wind-protected plants the strongest ARR5::GUS expression was found in the root cap statocytes, spreading upwards in the vascular cylinder. This pattern in roots was congruent with that found by CK immunolocalization. Shoots of wind-protected plants displayed either no or only low ARR5::GUS expression in the stem vascular bundles, nodal ramifications, and the bases of flower buds; shoot vascular bundles showed patterns of acropetally decreasing staining and the apical parts of buds and leaves were free from ARR5::GUS expression. In wind-exposed plants ARR5::GUS expression was considerably increased in shoots, also in basal-to-apical decreasing gradients. Immunolabelled shoots showed differential staining, with the strongest label in the vascular bundles of stems, leaves, and buds. The fact of the apparent absence of free CK in the buds of wind-protected plants and the typical upward decreasing gradients of free and conjugated CKs suggest that the bulk of the CK is synthesized in the root cap, exported through the xylem and accumulates at sites of highest transpiration where cuticles do not yet exist or do not protect against water loss.

Advancement in the treatment of blindness depends on the development of new technologies that enable early detection, follow-up, and treatment of disease. The authors describe direct, noninvasive imaging of four parameters: blood flow, blood oximetry, metabolic state, and hidden vasculature, particularly capillaries. These are functional parameters of the retina known to be degraded by retinal disease. The new Retinal Function Imager (Optical Imaging, Ltd., Rehovot, Israel) can image all four parameters as intrinsic reflectance intensity differences over the retina's surface. During the past 2 decades, imaging of small optical signals has been a powerful tool for high-resolution functional mapping in the neocortex. In this article, this technology is applied to the retina and demonstrates a general tool for noninvasively probing retinal function in many modalities. Imaging functional changes before anatomic consequences arise holds promise as a powerful tool for early diagnosis and treatment of retinal disease.

The models explaining root gravitropism propose that the growth response of plants to gravity is regulated by asymmetric distribution of auxin (indole-3-acetic acid, IAA). Since cytokinin has a negative regulatory role in root growth, we suspected that it might function as an inhibitor of tropic root elongation during gravity response. Therefore, we examined the free-bioactive-cytokinin-dependent ARR5::GUS expression pattern in root tips of transformants of Arabidopsis thaliana (L.) Heynh., visualized high cytokinin concentrations in the root cap with specific monoclonal antibodies, and complemented the analyses by external application of cytokinin. Our findings show that mainly the statocytes of the cap produce cytokinin, which may contribute to the regulation of root gravitropism. The homogenous symmetric expression of the cytokinin-responsive promoter in vertical root caps rapidly changed within less than 30 min of gravistimulation into an asymmetrical activation pattern, visualized as a lateral, distinctly stained, concentrated spot on the new lower root side of the cap cells. This asymmetric cytokinin distribution obviously caused initiation of a downward curvature near the root apex during the early rapid phase of gravity response, by inhibiting elongation at the lower side and promoting growth at the upper side of the distal elongation zone closely behind the root cap. Exogenous cytokinin applied to vertical roots induced root bending towards the application site, confirming the suspected inhibitory effect of cytokinin in root gravitropism. Our results suggest that the early root graviresponse is controlled by cytokinin. We conclude that both cytokinin and auxin are key hormones that regulate root gravitropism.

Purpose: To describe a case of atypical systemic amyloidosis in a patient who presented with recurrent subcutaneous bleeding of the eyelids and auricles., Design: Observational case report., Methods: A 52-year-old man with chronic cardiac failure, hypertension, weight loss, and impotence presented with recurrent bleeding of the eyelids and auricles, and was investigated for suspected amyloidosis., Results: Biopsy specimens taken from the bone marrow, salivary gland, abdominal subcutaneous fat, and gastric mucosa, and eyelids were all negative for Congo red. Results of a conjunctival biopsy, which were returned after the patient's death, and cardiac muscle autopsy were positive for Congo red staining, indicating amyloidosis., Conclusion: The findings in this case show that the presentation of amyloidosis may be atypical. Ophthalmologists should consider a diagnosis of amyloidosis in patients with periorbital bleeding, even if biopsies are negative for Congo red. A conjunctival biopsy may be useful in establishing a diagnosis of primary systemic amyloidosis.