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Dedicated post-operative radiological evaluation following ophthalmologic procedures is relatively uncommon. However, given the ever-growing ophthalmologic procedural advancements and the increasing utilization of neuroimaging for myriad indications, the orbits are often imaged incidentally in a delayed post-procedural state. Regardless of the clinical scenario, it is important for neuroradiologists and other specialists commonly exposed to orbital imaging to be aware of both expected and abnormal post-operative imaging findings because misinterpreted normal features or unrecognized complications can result in vision-threatening delays in treatment or mismanagement. In this review article, we discuss many common ophthalmologic procedures, their indications, and most likely complications. We also provide illustrative operative photographs and radiological imaging examples. By understanding the surgical intent, recognizing the devices that are commonly used, and developing familiarity with the appearance of post-operative complications, pitfalls in interpretation can be avoided and patient outcomes ultimately improved.

Summary Purpose Hyaluronic acid (HA) fillers can be reversed with hyaluronidase, but their dose responses are not well-characterized. We evaluated 12 fillers’ in vitro responses to varying doses of recombinant human hyaluronidase (RHH). Methods For the 12 HA gels, 0.2 mL aliquots were placed on six slides. Samples received no injection, saline injection, or RHH (2.5, 5, 10, or 20 units). The most resistant gels received 40 units of RHH on a seventh slide. Photos of gels were taken from bird's-eye and lateral views with a ruler at multiple time points. Results Restylane-L and Restylane Lyft were the most easily dissolvable HA fillers. Both demonstrated a significant response to 2.5 units RHH/0.2 mL. Juvederm Ultra, Belotero, Restylane Silk, and Restylane Defyne had moderate resistance to RHH. Restylane Refyne, Juvederm Ultra Plus, Vollure, Versa, and Voluma were most resistant, requiring more than 20 units RHH/0.2 mL for complete dissolution. Volbella was moderately resistant up to 20 units RHH but demonstrated pronounced dissolution with 40 units RHH. Conclusions This study visually and objectively demonstrates the in vitro response of HA to dissolution by hyaluronidase. Fillers were categorized into least, moderate, and most resistant to RHH. Interesting findings include markedly different degrees of liquefaction for products used for similar indications (such as Restylane Lyft being more liquefied than Voluma), and Belotero easily flattening but retaining texture. Combined with in vivo data, this may help calculate hyaluronidase doses needed for controlled, partial reversal of commercially available HA gels.

Introduction: Point-of-care ultrasound is becoming increasingly popular, and we sought to examine its role in evaluating ocular and periocular structures and facial vasculature. With the large number of point-of-care ultrasound devices available, it is difficult to determine which devices may be best suited for ophthalmic and facial aesthetic applications. This study compares five popular handheld point-of-care ultrasound devices to help guide clinicians in choosing the device best suited for their needs. Methods: We compared five point-of-care ultrasound devices: Butterfly IQ+ (Butterfly, Burlington, MA), L15 (Clarius Mobile Health, Vancouver, British Columbia, Canada), L20 (Clarius Mobile Health, Vancouver, British Columbia, Canada), Lumify (Philips, Amsterdam, Netherlands) and Vscan Air (GE, Boston, MA). Three ophthalmologists obtained the following views on three volunteers: eight arteries, four ocular and periocular structures and areas of filler injections. The image quality of each view was graded on a four-point Likert-type scale. In addition, graders filled out a survey. The data were analysed using analysis of variance tests with the significance level set to p Results: In terms of overall image quality, the L20 received the highest mean rating, followed by the L15, Vscan Air, Butterfly IQ+ and the Lumify ( p Conclusions: The L20 received the highest image quality rankings. While image quality is an important aspect of point-of-care ultrasound device selection, other factors such as cost, wireless capabilities, range of presets and battery life should also be considered.

Objective: We evaluated the safety and efficacy of an augmented BroadBand Light (BBL™) protocol on the upper and lower eyelids in improving meibomian gland dysfunction (MGD) and/or dry eye disease ...

BackgroundBasal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment.MethodsWe conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy. We examined the efficacy and safety of PD-1 therapy, as well as clinical and pathological variables in association with outcomes. Progression-free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated using Kaplan-Meier methodology. Toxicity was graded per Common Terminology Criteria for Adverse Events V.5.0.ResultsA total of 29 patients with BCC who were treated with PD-1 inhibition were included for analysis, including 20 (69.0%) with locally advanced and 9 (31.0%) with metastatic disease. The objective response rate was 31.0%, with five partial responses (17.2%), and four complete responses (13.8%). Nine patients had stable disease (31.0%), with a disease control rate of 62.1%. The median DOR was not reached. Median PFS was 12.2 months (95% CI 0.0 to 27.4). Median OS was 32.4 months (95% CI 18.1 to 46.7). Two patients (6.9%) developed grade 3 or higher toxicity, while four patients (13.8%) discontinued PD-1 inhibition because of toxicity. Higher platelets (p=0.022) and any grade toxicity (p=0.024) were significantly associated with disease control rate.ConclusionsThe clinical efficacy of PD-1 inhibition among patients with advanced or metastatic BCC in this real-world cohort were comparable to published trial data. Further investigation of PD-1 inhibition is needed to define its optimal role for patients with this disease.

Purpose: To determine the clinical course of patients with chorioretinal folds (CRF) in thyroid eye disease (TED).Methods: A multi-center retrospective case series of patients with TED who develope...

Current treatments for meibomian gland dysfunction have several limitations, creating a necessity for other advanced treatment options. The purpose of this study is to determine the effectiveness of focused ultrasound stimulation for the treatment of dry eye disease caused by meibomian gland dysfunction. An in vivo study of nine Dutch Belted rabbits was conducted with focused ultrasound stimulation of the meibomian glands. A customized line-focused ultrasonic transducer was designed for treatment. Fluorescein imaging, Schirmer’s test, and Lipiview II ocular interferometer were used to quantify outcomes from three aspects: safety, tear production, and lipid layer thickness. Both tear secretion and lipid layer thickness improved following ultrasound treatment. Five to 10 min after the ultrasound treatment, the mean values of lipid layer thickness increased from 55.33 ± 11.15 nm to 95.67 ± 22.77 nm ( p

An isolated defect in the lateral orbital wall is an uncommon occurrence, although cases of orbital floor, roof, and medial wall spontaneous dehiscence have been described in the literature. Here, we describe a lateral orbital wall defect in a patient with thyroid eye disease - which may be related to bony remodeling or may represent a rare congenital anomaly. Computed tomography (CT) prior to decompression surgery revealed a defect in the left lateral orbital wall. At the time of orbital decompression, prolapse of buccal fat into the orbit was noted once the subperiosteal plane was entered along the lateral orbital wall in the area of this bony defect. Literature review revealed only a few previous reports of lateral wall abnormalities, including two involving the inferior orbital fissure; one other case was associated with Down syndrome, and other reports consist of sphenoid hypoplasia associated with neurofibromatosis.

Mucoceles of the paranasal sinus commonly involve the frontal sinuses, the ethmoid sinuses, and rarely the maxillary or sphenoid sinuses. They often present with sinus pain or pressure, but rarely can present with more severe symptoms such as changes in mental status or vision due to expansion and invasion through the skull base or orbit. A 62-year-old male presented with optic neuropathy, a relative afferent pupillary defect with proptosis and lateral gaze palsy of the left eye. The patient was found to have a large mucocele extending from the left posterior ethmoid sinus into the left orbital apex. Urgent endoscopic sinus surgery was performed jointly between Oculoplastics and Otolaryngology. Post-operatively, the patient had improvement in diplopia, extraocular motion, and proptosis with stable vision. This case demonstrates the importance of early identification and intervention in a rare presentation of a sinus mucocele to prevent serious complications such as vision loss.

Glaucoma surgeries, such as trabeculectomy, are performed to lower intraocular pressure to reduce risk of vision loss. These surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. Here, we characterized the development and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed from a primary lymphatic vessel that grows from the nasal-side medial canthus region at birth. This primary lymphatic vessel immediately branches out, invades the limbus and conjunctiva, and bidirectionally encircles the cornea. As a result, the distribution of the ocular lymphatics is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic sprouts are produced mainly from the nasal-side limbal lymphatics, posing the nasal side of the eye as more responsive to fluid drainage and inflammatory stimuli. Consistent with this polarized distribution of the ocular lymphatics, a higher drainage efficiency was observed in the nasal side than the temporal side of the eye when injected with a fluorescent tracer. In contrast, blood vessels are evenly distributed at the anterior surface of the eyes. Also, we found that these distinct vascular distribution patterns were conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a glaucoma surgery site to improve fluid drainage.

Summary Purpose Several injectable hyaluronic acid dermal fillers exist in the market, each with different rheologic and cross-linking properties. Their reversibility is useful for managing complications. We sought to determine the response of three different hyaluronic acid gels to varying doses of hyaluronidase. Methods Each of 18 arms of nine subjects were prospectively randomized to receive intradermal injections of hyaluronic acid gel (Restylane-L, Juvederm Ultra, Juvederm Voluma). Seven sites on each arm were randomized to receive 0.2 mL of hyaluronic acid gel in anticipation of dissolution 1 week later with varying doses of hyaluronidase (Hylenex), 2.5, 5, 10, or 20 units or to be a control site. The outcome measures of diameter, elevation, and firmness were measured pre-injection and at varying time points to beyond 4 years. Subjects, graders, and injectors were masked. Results The most dramatic changes for all fillers occurred starting at the 30-min time point through 3 h time point, with continued gradual degradation through week 2. A mild dose response was found for Juvederm and Restylane; however, a clear dose response was seen from 2.5 to 10 units for Voluma, with 2.5 units showing features more like those of saline only or no hyaluronidase control. One Restylane arm had controls lasting four years. Conclusions All fillers had a dose response, with Voluma exhibiting it most clearly. Voluma required higher doses of hyaluronidase for dissolution, i.e., more than 20 units per 0.2 mL of filler. Restylane appeared to respond most readily to hyaluronidase, at the dose of even 2.5 units, but it also was fastest to dissolve on its own.

Melanomas of the conjunctiva and eyelid present unique management challenges for the ophthalmologist and ocular oncologist. Surgical excision, a mainstay of treatment, may be disfiguring with variable rates of local recurrence.1 Conjunctival melanomas have a local recurrence rate ranging from 18% to 83% with data largely coming from patients treated with excision with or without cryotherapy.2–4 Cutaneous melanomas of the eyelid skin have a local recurrence rate ranging from 7% to 78% depending on technique and extent of excision.5–7 The rate of regional lymph node metastasis was 41% in a study of conjunctival melanoma patients treated primarily with local excision, the authors compared their finding to rates in cutaneous melanoma of the head and neck which ranged from 14% to 44% or eyelid skin melanoma at 29%.4 Efforts to improve outcomes of these tumors have continually advanced with surgical techniques and adjunctive treatments such as topical therapy, radiation, and systemic chemotherapy.8 Recent advances in immunotherapy, specifically checkpoint inhibitors, has allowed for primary and adjuvant treatment of cutaneous melanomas with medical therapy. These have been successful in the setting of metastatic cutaneous melanoma and other cancers. This review of the literature summarizes the current understanding and use of checkpoint inhibitors, with a particular focus for the ophthalmic surgeon. Immune checkpoint inhibitors are relatively new therapies, developed with the rationale of stimulating a patient’s own immune system to better respond to malignancies. This strategy progressed from the discovery of specific receptor proteins that promote immune tolerance, that is, inhibit immune responsiveness, which tumors may take advantage of to proliferate unhindered. Monoclonal antibodies were developed to block these cellular checkpoints. Clinically available therapies include ipilimumab, which targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), nivolumab, pembrolizumab, and cemiplimab, which target programmed cell death-1 (PD-1), and atezolizumab, avelumab, and durvalumab, which target programmed cell death ligand-1 (PD-L1). Checkpoint inhibitors have demonstrated efficacy in a range of malignancies including non–small cell lung cancer, urothelial cancer, renal cell cancer, squamous cell carcinoma of the head and neck, Merkel cell carcinoma, and metastatic cutaneous melanoma.9 In recent years there has been emerging interest in checkpoint inhibitor therapy for oculoplastic applications, specifically eyelid and conjunctival melanomas.10 However, there is limited clinical experience with the use of these drugs for this indication. Eyelid and conjunctival melanomas were not specifically studied in the trials leading to the development of these therapies, resulting in limited knowledge of their potential benefits and risks. This chapter reviews the available literature regarding checkpoint inhibitors for eyelid and conjunctival melanomas.

Dermal fillers have become increasingly popular as a cosmetic treatment for facial rejuvenation. Although these injections are generally considered to be safe, as the number of injections has increased, so has the rate of complications. Ischemic complications of fillers is critical and include vision loss, ophthalmoplegia, skin necrosis, and cerebral infarction. Knowing the anatomy well to optimally prevent and manage these serious complications. Prevention includes knowledge of the vascular anatomy of the facial area, as well as certain injection techniques such as aspiration, use of a smaller needle, and adoption of a larger cannula. The use of ultrasound has been a recent innovation in preventing and treating filler complications as well. The reversibility of fillers should also be considered when choosing a filler. Some hyaluronic acid (HA) fillers, including the newer ones on the market, are difficult to reverse and non-HA fillers and fat are irreversible. This review aims to discuss facial anatomy, the various ischemic filler complications, the prevention and management of these complications, and the relatively recent use of imaging as an adjunct.

Purpose The aim of this study is to investigate whether volumetric enhancement of the infraorbital rim area or, alternatively, of the deep medial cheek, results in greater improvement of tear trough deformity. Methods This prospective, single-blind study recruited 12 patients seeking correction of tear trough deformity. Pretreatment standardized photographs were obtained after which patients were randomized to receive hyaluronic acid gel filler augmentation of the tear trough on one side and hyaluronic acid gel augmentation of the cheek on the contralateral side. The patients were then re-examined at 3 weeks postinjection when standardized photographs were taken again. Following the photographs, filler was added to the side and location where they were not used at the original treatment, resulting in added volume in both the cheek and the tear trough. The patients returned 3 weeks later when final photographs were taken. The pre- and post-treatment images were randomized and evaluated by 3 masked observers asked to evaluate the depth of tear trough. Results There was a significant improvement in the depth of the tear trough rating after initial treatment on the side treated in the tear trough (p = 0.0001). There was not a significant change in depth of tear trough rating, however, on the side receiving cheek only treatment (p = 0.0963). There was a statistically significant change in tear trough rating after both tear trough and cheek had been treated on each side (p = 0.001). There was no statistically significant difference between sides after lid and cheek treatment had been completed on each side (p = 0.5986). Intraclass correlation between reviewers for all subjects was excellent at 0.94. Tear trough injections were more technique sensitive than cheek volume augmentation to achieve satisfactory results. There were no complications from cheek volume enhancement. Varying degrees of ecchymosis were encountered with tear trough injections. Conclusions When the patient's primary concern is the appearance of the tear trough, and the physician is limited to treating either the tear trough or the cheek alone, it appears that treatment in the tear trough offers greater improvement in the appearance of the tear trough deformity when compared with treatment in the cheek alone.

A variety of surgical adjuncts can be added to upper eyelid blepharoplasty with the goal of enhancing surgical results and patient satisfaction. All of these procedures are minimally invasive and most are performed through a standard eyelid crease incision. These procedures can be added to stabilize or conservatively lift the outer brow, prevent the stigmata of postoperative volume loss, improve the brow-eyelid transition and contour, and reposition a prolapsed lacrimal gland. The procedures are generally straightforward, easily learned, and complication free. Familiarity with these techniques provides the aesthetic eyelid surgeon with added options to improve surgical results.

Eyebrow and upper eyelid aging occurs in all tissue planes, and manifests most commonly in skin quality, tissue volume loss (soft tissue and bone), and tissue descent. All these involutional changes are amenable to less-invasive (nonsurgical) interventions with natural and aesthetically pleasing results. It is critical for aesthetic facial surgeons to familiarize themselves with these procedures because they are in high demand by patients. This article outlines current concepts of nonsurgical management options for brow and upper eyelid aging. The anatomy and age-related changes in these structures are reviewed, and minimally invasive techniques to address these changes are detailed.

Orbital decompression for thyroid-associated orbitopathy (TAO) is commonly performed for disfiguring proptosis, congestion, and optic neuropathy. Although one decompression typically achieves goals, a small percentage requires repeat decompression. We performed a 10-year retrospective chart review of all orbital decompressions for TAO at a single tertiary referral institution. Four-hundred and ninety-five orbits (330 patients) were decompressed for TAO, with 45 orbits (37 patients) requiring repeat decompression. We reviewed the repeat cases for indications, clinical activity scores, approach, walls decompressed, and outcomes. Nine percent of orbits required repeat decompression for proptosis (70%), optic neuropathy (25%) or congestion (45%). Sixty-four percent were for recurrence of disease, 36% were for suboptimal decompression. Three incisional approaches were used: lateral upper eyelid crease, inferior transconjunctival, and transcaruncular, with inferior transconjunctival being most common. Of the three walls removed, deep lateral, inferior, and medial, the deep lateral wall was most common (51%). A repeat lateral decompression was the most frequent pattern. Of 37 patients requiring repeat decompression, 40% had diplopia prior to repeat, and an additional 24% developed diplopia after the repeat. Whereas previous studies published by our group cited only 2.6% of deep lateral wall orbital decompressions leading to new-onset primary gaze diplopia, repeat orbital decompressions have a much higher rate of post-operative diplopia. The new onset primary gaze diplopia after repeat decompression group had a higher average preoperative CAS (3.3 vs. 2.4, p 0.01), higher mean blood loss (56 vs. 19 mL, p = 0.04), more frequent medial wall decompressions (47% vs. 29%, p = 0.33), and greater proptosis reduction (2.4 vs. 1.7 mm, p = 0.24).

Craniosynostosis refers to the premature fusion of cranial sutures and is often associated with ophthalmologic comorbidities. These associations include, but are not limited to, significant refractive errors, strabismus, ocular adnexal and orbital malformations, and structural abnormalities of the globe. Diagnosis and treatment of the various craniosynostoses and related syndromes can be difficult and is often managed by utilizing a team of physicians who specialize in craniofacial disorders. The role of the ophthalmologist in monitoring the visual development of these patients is extremely important. He or she must be knowledgeable of the common and potentially sight-threatening ocular findings in craniosynostosis.

We present a new clinical-radiological correlation method (AnaCOM) that aims at establishing structure-function relationships. We validated AnaCOM by assessing the location of lesions that are associated with altered performances in a well-studied task: the verbal fluency task. We retrospectively reviewed 64 brain-damaged patients who had focal lesions in a variety of cortical sites due to stroke, hemorrhage or tumor surgery. All patients were tested for verbal fluency at the time of the MRI examination. MRI volumes were normalized using a mask covering brain lesions and artifacts. The brain lesions were then segmented using the normalized MRI. In each patient, a verbal fluency score was assigned to each voxel in the segmented area. Subsequently, segmentations were superimposed and voxels were gathered in clusters defined by the overlap of the patients' lesion. For each cluster, the scores were statistically compared to those obtained by controls for the same task. This process allowed the construction of cluster-by-cluster statistical maps of anatomo-clinical correlations. As expected, the statistical map indicated that two regions were significantly associated with a deficit in the fluency task: one located in Broca's area and the other in the preSMA. AnaCOM does not require a priori selection of the location of lesions or task scores. The method complements the functional imaging techniques, as it tells which regions are necessary for a given function and it explores cortical regions as well as the white matter.

Cerebral amyloid angiopathy (CAA) is the accumulation of amyloid-β peptide (Aβ) in the vessel wall of arteries in the brain. Because CAA is commonly associated with Alzheimer's disease (AD), characterized by parenchymal deposition of the same peptide in the form of senile plaques, there is considerable interest in the relationship of the two deposits in generating human disease. The study of CAA is of particular importance for immunotherapeutic approaches to AD, because reports of anti-Aβ immunotherapy in mice and humans have suggested that, whereas CAA appeared resistant to clearance, its response to this treatment promoted potential adverse effects, including meningoencephalitis. We used multiphoton microscopy and longitudinal imaging to monitor CAA in a mouse model of amyloid deposition to evaluate the effects of anti-Aβ passive immunotherapy. We found detectable clearance of CAA deposits within 1 week after a single administration of antibody directly to the brain, an effect that was short-lived. Chronic administration of antibody over 2 weeks led to more robust clearance without evidence of hemorrhage or other destructive changes. We found that the progressive clearance of Aβ from vessels follows distinct kinetics from what has been previously reported for clearance of plaques (parenchymal deposits of Aβ). This quantitativein vivoimaging approach directly demonstrates that CAA in a transgenic mouse model can be cleared with an optimized immunotherapy.

The AIDS dementia complex (ADC) is one of the most common neurological complications in patients with AIDS. However, little is known about the clinical features of ADC in China. We prospectively studied six patients with confirmed ADC out of a total of 36 AIDS patients treated from 1999 to 2003. All patients had short-term memory loss and poor concentration, with preserved alertness. Motor disability was identified in three patients. Of the six ADC patients, two had accompanying vacuolar myelopathy. All of the patients died, with a mean age at death of 41.8 years. The median survival of these ADC patients from the time of diagnosis was 4.7 months. In this context, we suggest that early diagnosis and highly active antiretroviral therapy treatment is an urgent priority in developing countries.

Globe prolapse into the maxillary sinus after trauma is rare and usually portends a very poor visual prognosis. The authors present an unusual case of late restoration of central vision after such trauma. A 20-year-old man presented after motorcycle injury with a large right floor and medial orbital wall fracture with displacement of the globe into the maxillary sinus. The patient had no light perception on initial exam and was emergently taken to the operating room for globe exploration. No globe rupture was found, and the right orbital floor and medial wall fractures were repaired. Three days of intravenous methylprednisolone at 250 mg every 6 hours was administered postoperatively with no change in visual status, and the patient was discharged home on a rapid oral prednisone taper. At postoperative week 6, vision had returned to 20/20 OD centrally. Visual field testing revealed a central tunnel of vision. The patient's visual function continues to remain stable 2 years after the initial trauma.

GABA transporter-1 (GAT1) plays a key role in GABA reuptake, and deletion of GAT1 leads to a largely increased GABA-induced tonic conductance in the GAT1(-/-) mice. We hypothesized that homeostatic plasticity of GABA(A) receptor-mediated inhibition takes place to balance the increased tonic inhibition and maintains stability of the nervous system. In this study, we employed the loss of righting reflex assay and compared the behavioral difference of three animal models, mice with acute, partial, and permanent GAT1 deficiency, to confirm our hypothesis. Our data demonstrated that both acute and partial block of GAT1 increased the sensitivity of mice to GABAergic sedative/hypnotic drugs, whereas permanent GAT1 dysfunction in the GAT1(-/-) mice decreased the sensitivity to some extent. These results confirmed our presumption about the down-regulation of phasic GABAergic transmission in the GAT1 knockout mice. Moreover, electrophysiological measurements performed on slices from motor cortex suggested that it was the reduced GABA release, but not change of postsynaptic GABA receptors, which led to the down-regulation of phasic inhibition in GAT1(-/-) mice.

Transgenic mice carrying disease-linked forms of genes associated with Alzheimer disease often demonstrate deposition of the beta-amyloid as senile plaques and cerebral amyloid angiopathy. We have characterized the natural history of beta-amyloid deposition in APPswe/PS1dE9 mice, a particularly aggressive transgenic mouse model generated with mutant transgenes for APP (APPswe: KM594/5NL) and PS1 (dE9: deletion of exon 9). Ex vivo histochemistry showed Abeta deposition by 4 months with a progressive increase in plaque number up to 12 months and a similar increase of Abeta levels. In vivo multiphoton microscopy at weekly intervals showed increasing beta-amyloid deposition as CAA and plaques. Although first appearing at an early age, CAA progressed at a significantly slower rate than in the Tg2576 mice. The consistent and early onset of beta-amyloid accumulation in the APPswe/PS1dE9 model confirms its utility for studies of biochemical and pathological mechanisms underlying beta-amyloid deposition, as well as exploring new therapeutic treatments.

We review the clinical, radiologic, and neuropathologic features of the hereditary and sporadic forms of cerebral amyloid angiopathy (CAA) associated with vascular deposition of the beta-amyloid peptide. Amino acid substitutions at 4 sites in the beta-amyloid precursor protein, all situated within the beta-amyloid peptide sequence itself, have been shown to cause heritable forms of CAA. The vascular diseases caused by these mutations are associated primarily with cerebral hemorrhages, white matter lesions, and cognitive impairment, and only variable extents of the plaque and neurofibrillary pathologies characteristic of Alzheimer disease. Sporadic CAA typically presents 20 or more years later than hereditary CAA, but is otherwise characterized by a comparable constellation of recurrent cerebral hemorrhages, white matter lesions, and cognitive impairment. The clinical, radiologic and pathologic similarities between hereditary and sporadic CAA suggest that important lessons for this common age-related process can be learned from the mechanisms by which mutation makes beta-amyloid tropic or toxic to vessels.