Macular edema after rhegmatogenous retinal detachment repair: risk factors, OCT analysis, and treatment responses.

PURPOSE: To investigate risk factors, imaging characteristics, and treatment responses of cystoid macular edema (CME) after rhegmatogenous retinal detachment (RRD) repair. METHODS: Consecutive, retrospective case-control series of patients who underwent pars plana vitrectomy (PPV) and/or scleral buckling (SB) for RRD, with at least six months of follow-up. Clinical and surgical parameters of patients with and without CME (nCME), based on spectral-domain optical coherence tomography (OCT), were compared. RESULTS: Of 99 eyes enrolled, 25 had CME while 74 had nCME. Patients with CME underwent greater numbers of surgeries (P < 0.0001). After adjusting for number of surgeries, macula-off RRD (P = 0.06), proliferative vitreoretinopathy (PVR) (P = 0.09), surgical approach (PPV and/or SB, P = 0.21), and tamponade type (P = 0.10) were not statistically significant, although they all achieved significance on univariate analysis (P = 0.001 or less). Intraoperative retinectomy (P = 0.009) and postoperative pseudophakia or aphakia (P = 0.008) were more frequent in the CME group, even after adjustment. Characteristics of cCME on OCT included diffuse distribution, confluent cysts, and absence of subretinal fluid or intraretinal hyperreflective foci. Macular thickness improved significantly with intravitreal triamcinolone (P = 0.016), but not with anti-vascular endothelial growth factor agents (P = 0.828) or dexamethasone implant (P = 0.125). After adjusting for number of surgeries and macular detachment, final visual acuities remained significantly lower in the CME vs nCME group (P = 0.012). CONCLUSION: Risk factors of CME include complex retinal detachment repairs requiring multiple surgeries, and pseudophakic or aphakic lens status. Although this cCME was associated with poor therapeutic response, corticosteroids were the most effective studied treatments.

BRANCH RETINAL ARTERY WALL RUPTURE AND SUBSEQUENT OCCLUSION DURING PARS PLANA VITRECTOMY WITH MEMBRANE PEEL.

PURPOSE: To report a case of branch retinal artery wall rupture and subsequent branch retinal artery occlusion occurring during a routine pars plana vitrectomy with epiretinal membrane and internal limiting membrane peeling. METHODS: Case report. Multimodal imaging including fluorescein angiography, spectral domain optical coherence tomography (OCT), en face OCT, and OCT angiography were performed. RESULTS: An 86-year-old woman presented with a symptomatic epiretinal membrane in the right eye. Pars plana vitrectomy with epiretinal membrane and internal limiting membrane peel was performed. During the peel, spontaneous preretinal and intraretinal hemorrhage emanating from an adjacent branch retinal artery developed. At postoperative Week 1, OCT showed retinal thinning and hyperreflectivity suggestive of vascular accident. At postoperative Year 1, OCT imaging revealed retinal atrophy while fluorescein angiography demonstrated the arterial occlusion, and OCT angiography illustrated reduction in retinal perfusion in the region of the branch retinal artery occlusion. CONCLUSION: The authors report an unusual case of retinal arterial wall rupture and hemorrhaging during routine pars plana vitrectomy with membrane peel resulting in a branch retinal artery occlusion and subsequent retinal atrophy. Surgeons must limit stress on the underlying retina during membrane peel to avoid this surgical complication.

Early hydroxychloroquine retinopathy: optical coherence tomography abnormalities preceding Humphrey visual field defects.

BACKGROUND/AIMS: Hydroxychloroquine (HCQ) retinopathy may result in severe and irreversible vision loss, emphasising the importance of screening and early detection. The purpose of this study is to report the novel finding of early optical coherence tomography (OCT) abnormalities due to HCQ toxicity that may develop in the setting of normal Humphrey visual field (HVF) testing. METHODS: Data from patients with chronic HCQ exposure was obtained from seven tertiary care retina centres. Ten patients with HCQ-associated OCT abnormalities and normal HVF testing were identified. Detailed analysis of the OCT findings and ancillary tests including colour fundus photography, fundus autofluorescence, multifocal electroretinography and microperimetry was performed in these patients. RESULTS: Seventeen eyes from 10 patients illustrated abnormalities with OCT and normal HVF testing. These OCT alterations included (1) attenuation of the parafoveal ellipsoid zone and (2) loss of a clear continuous interdigitation zone. Several eyes progressed to advanced parafoveal outer retinal disruption and/or paracentral visual field defects. CONCLUSION: Patients with high risk HCQ exposure and normal HVF testing may develop subtle but characteristic OCT abnormalities. This novel finding indicates that, in some cases of early HCQ toxicity, structural alterations may precede functional impairment. It is therefore important to employ a screening approach that includes OCT to assess for these early findings. Ancillary testing should be considered in cases with suspicious OCT changes and normal HVFs.

Association of Optical Coherence Tomography Angiography of Collaterals in Retinal Vein Occlusion With Major Venous Outflow Through the Deep Vascular Complex.

Importance: Analysis of collateral vessel formation following retinal vein occlusion may advance our understanding of the venous outflow anatomy in the macula. Objective: To determine the location of collateral vessels with optical coherence tomography (OCT) angiography imaging. Design, Setting, and Participants: Observational retrospective cohort study. Collateral vessel formation was studied with OCT angiography (OCTA) in patients with retinal vein occlusion (RVO). The study took place at 2 retinal practices (Vitreous Retina Macula Consultants of New York and Stein Eye Institute, University of California, Los Angeles), with patient records retrieved from March 2015 to August 2017. Data analysis was completed in November 2017. Exposures: Collaterals identified with fundus photography and/or fluorescein angiography were analyzed with OCTA to determine their course through the superficial vascular plexus (SVP) and the deep vascular complex (DVC). Main Outcomes and Measures: Collateral vessel pathways through the SVP and DVC were analyzed with cross-sectional and en face OCT and OCTA segmentation and color-coded volume renderings prepared from raw OCTA voxel data. Results: From 23 eyes (22 branch and 1 hemispheric retinal vein occlusion ) of 23 patients (mean [SD] age, 73 [11] years), 101 collateral vessels were identified and analyzed (mean [SD], 4.4 [2.0]; range, 2-9 collateral per eye). On OCTA, the collaterals appeared as curvilinear dilated flow signals that connected veins across the horizontal raphe or veins on opposite sides of an occluded venous segment within the same retinal hemisphere. Of the 101 collaterals analyzed, all showed greater flow signal in the DVC, and all had some portion of their course identified within the DVC. No collaterals were found exclusively in the SVP. Volume renderings for 3 cases confirmed qualitatively that retinal collateral vessels course through the retina predominantly at the level of the DVC. Conclusions and Relevance: Based on a limited number of cases, all collateral vessels associated with retinal vein occlusion were found to course through the DVC. The absence of collaterals isolated to the SVP supports a serial arrangement of the SVP and DVC, with venous drainage predominantly coursing through the DVC.

Suspended Scattering Particles in Motion: A Novel Feature of OCT Angiography in Exudative Maculopathies.

OBJECTIVE: To characterize features of extra-vascular optical coherence tomography angiography (OCTA) signals corresponding to hyperreflective intraretinal fluid across various exudative maculopathies. DESIGN: Multicenter, retrospective, observational study. PARTICIPANTS: Eyes with various forms of exudative maculopathy including diabetic retinopathy (DR), retinal vein occlusion (RVO), and neovascular-age related macular degeneration (nvAMD). METHODS: Patients with extra-vascular OCTA signal identified on en face OCTA images were included in this study. This signal was readily distinguishable from projection artifacts. The regions with the extra-vascular motion signal on OCTA were named "Suspended Scattering Particles in Motion (SSPiM)." Depth-encoded, color, en face OCTA images (3mm × 3mm) centered on the fovea and their corresponding structural OCT scans were used to quantify features of SSPiM and its corresponding hyperreflective fluid. Longitudinal data were collected when available. MAIN OUTCOME MEASURES: Anatomic location, the association with hyperreflective material, changes in location and appearance of SSPiM over time, and replication of SSPiM OCTA signal in an in vitro phantom. RESULTS: Seventy-six eyes in 62 patients with various forms of exudative maculopathy were evaluated; 60 eyes with DR, 9 eyes with RVO, and 5 eyes nvAMD, 1 eye with macroaneurysm, and 1 eye with radiation retinopathy. Intraretinal accumulations of fluid with increased OCT signal intensity corresponded to regions of SSPiM in several exudative maculopathies. An in vitro phantom model demonstrates that particulate matter in suspension can generate similar OCTA signal. SSPiM showed an anatomic preference for vascular-avascular junctions. The hyperreflective fluid corresponding to SSPiM appeared more frequently in Henle's fiber layer (HFL) than the inner nuclear layer (INL) and was highly associated with hyperreflective material (HRM) found bordering the fluid. In five of eight longitudinal cases, the resolution of SSPiM resulted in the formation of confluent HRM. Clinically, this appeared as hard exudate on funduscopic images. CONCLUSIONS: Clinical data suggest that SSPiM is a novel imaging feature of retinal vascular diseases that was not appreciated prior to the use of OCTA. We characterized several novel features of SSPiM and demonstrated that at least in some cases it resolves with residual hard exudate.

Multimodal Imaging of Nonneovascular Age-Related Macular Degeneration.

Nonneovascular (dry) AMD is a retinal disease with potential for significant central visual impairment. The hallmarks of this disease are macular drusen, RPE alterations, and geographic atrophy (GA). Classification schemes for nonneovascular AMD have evolved over the years as major advances in retinal imaging have enabled a greater understanding of disease pathophysiology. The original classifications of nonneovascular AMD were based on color fundus photography (CFP), while more modern schemes rely on a multimodal imaging approach. Effective diagnosis and management of nonneovascular AMD requires a thorough understanding of its multimodal imaging features as detailed in this review. Future imaging modalities and imaging biomarkers that may aid in diagnosis and management are also discussed.

Donor Variation and Optimization of Human Mesenchymal Stem Cell Chondrogenesis in Hyaluronic Acid.

Mesenchymal stem cells (MSCs) are an attractive cell type for cartilage repair that can undergo chondrogenesis in a variety of three-dimensional (3D) scaffolds. Hyaluronic acid (HA) hydrogels provide a biologically relevant interface for cell encapsulation. While previous studies have shown that MSC-laden HA constructs can mature in vitro to match native mechanical properties using cells from animal sources, clinical application will depend on the successful translation of these findings to human cells. Though numerous studies have investigated chondrogenesis of human MSC (hMSC)-laden constructs, their functional outcomes were quite inferior to those using animal sources, and donor-specific responses to 3D HA hydrogels have not been fully investigated. To that end, hMSCs were derived from seven donors, and their ability to undergo chondrogenesis in pellet culture and HA hydrogels was evaluated. Given the initial observation of overt cell aggregation and/or gel contraction for some donors, the impact of variation in cell and HA macromer concentration on functional outcomes during chondrogenesis was evaluated using one young/healthy donor. The findings show marked differences in functional chondrogenesis of hMSCs in 3D HA hydrogels based on donor. Increasing cell density resulted in increased mechanical properties, but also promoted construct contraction. Increasing the macromer density generally stabilized construct dimensions and increased extracellular matrix production, but limited the distribution of formed matrix at the center of the construct and reduced mechanical properties. Collectively, these findings suggest that the use of hMSCs may require tuning of cell density and gel mechanics on a donor-by-donor basis to provide for the most robust tissue formation for clinical application.

Nascent Type 3 Neovascularization in Age-Related Macular Degeneration.

PURPOSE: To describe the preclinical and very early stages of type 3 neovascularization using multimodal retinal imaging to expand our understanding of the pathogenesis of this disorder and potentially to prevent late treatment. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients diagnosed with treatment-naïve type 3 neovascularization in the setting of age-related macular degeneration were identified at 4 retina referral centers. Inclusion criteria were: patients older than 55 years with at least 1 OCT and OCT angiography (OCTA) examination before the onset of clinically active type 3 neovascularization (i.e., preclinical stage). METHODS: Patients underwent a complete ophthalmologic examination including at least OCT and OCTA at the baseline and preclinical stage examinations, and dye angiographies when available. Demographics and clinical findings were analyzed. MAIN OUTCOME MEASURES: Description of multimodal imaging features of nascent type 3 neovascularization. RESULTS: Fifteen eyes (15 patients; mean age, 83 ± 9 years) were included. At the baseline, mean BCVA was 0.32 ± 0.17 logarithm of the minimum angle of resolution and central macular thickness was 313 ± 50 µm. Preclinical (i.e., prebaseline) structural OCT illustrated the presence of intraretinal hyperreflective foci (HRF) at the site of type 3 neovascularization development in all patients. These foci were characterized by hyperfluorescence on dye angiography and by detectable flow on OCTA, identified with either the avascular slab (20%) or with both the deep retinal capillary plexus (DCP) and avascular slabs (80%). Typically, HRF with detectable flow on OCTA were characterized by the absence of intraretinal exudation (or very mild microcystic changes) until the lesion progressed from the DCP into the retinal pigment epithelium (RPE) and sub-RPE space. Of note, in 1 patient we observed the complete resolution of HRF despite the presence of OCTA flow and dye angiography hyperfluorescence detected at the preclinical stage examination. CONCLUSIONS: Hyperreflective foci on structural OCT may represent early intraretinal neovascularization originating from the DCP, namely nascent type 3 neovascularization; these lesions can progress to active type 3 neovascularization or more rarely may regress without functional impairment. An advanced multimodal imaging approach is useful in detecting nascent type 3 lesions, which should be followed up carefully and treated as soon as possible if flow progresses to the RPE and sub-RPE space to prevent progression to late stages.

Role of dexamethasone in the long-term functional maturation of MSC-laden hyaluronic acid hydrogels for cartilage tissue engineering.

The purpose of study was to investigate the maturation of mesenchymal stem cells (MSC) laden in HA constructs with various combinations of chemically defined medium (CM) components and determine the impact of dexamethasone and serum on construct properties. Constructs were cultured in CM with the addition or withdrawal of media components or were transferred to serum containing media that partially represents an in vivo-like condition where pro-inflammatory signals are present. Constructs cultured in CM+ (CM with TGF-ß3) and DEX- (CM+ without dexamethasone) conditions produced robust matrix, while those in ITS/BSA/LA- (CM+ without ITS/BSA/LA) and Serum+ (10% FBS with TGF-ß3) produced little matrix. While construct properties in DEX- were greater than those in CM+ at 4 weeks, properties in CM+ and DEX- reversed by 8 weeks. While construct properties in DEX- were greater than those in CM+ at 4 weeks, the continued absence or removal of dexamethasone resulted in marked GAG loss by 8 weeks. Conversely, the continued presence or new addition of dexamethasone at 4 weeks further improved or maintained construct properties through 8 weeks. Finally, when constructs were converted to Serum (in the continued presence of TGF-ß3 with or without dexamethasone) after pre-culture in CM+ for 4 weeks, GAG loss was attenuated with addition of dexamethasone. Interestingly, however, collagen content and type was not impacted. In conclusion, dexamethasone influences the functional maturation of MSC-laden HA constructs, and may help to maintain properties during long-term culture or with in vivo translation by repressing pro-inflammatory signals. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1717-1727, 2018.

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN A PERIVENULAR FERN-LIKE DISTRIBUTION WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To report a case of central retinal vein occlusion resulting in a perivenular pattern of paracentral acute middle maculopathy lesions best identified with en face optical coherence tomography (OCT). METHODS: Retrospective case report. Optos ultra-widefield fluorescein angiography, spectral domain OCT, en face OCT, and OCT angiography were performed. RESULTS: A 41-year-old man presented with decreased vision in the right eye for 2 weeks. Funduscopic examination of the affected right eye was notable for subtle retinal whitening in the macula, mild retinal venous dilation and tortuosity, and few scattered retinal dot and blot hemorrhages consistent with an acute central retinal vein occlusion. Widefield fluorescein angiography demonstrated delayed arterial and venous filling but no evidence of significant peripheral retinal vascular ischemia. En face OCT segmented at the inner nuclear layer illustrated a remarkable and precise perivenular distribution of fern-like paracentral acute middle maculopathy with periarterial sparing, whereas en face OCT segmented at the outer nuclear layer demonstrated florid cystoid macular edema. At 6-week follow-up, OCT demonstrated patchy areas of atrophic inner nuclear layer and spontaneous resolution of the cystoid macular edema. Optical coherence tomography angiography at the level of the deep capillary plexus illustrated remarkable flow reduction of the deep capillary plexus in mainly a perivenular distribution. CONCLUSION: The authors report a case of a central retinal vein occlusion with mild retinal findings associated with a remarkable perivenular pattern of paracentral acute middle maculopathy with en face OCT. Follow-up OCT angiography demonstrated significant flow reduction of the deep capillary plexus in a perivenular pattern. The perivenular pattern of paracentral acute middle maculopathy lesions with en face OCT can be an important finding suggestive of a central retinal vein occlusion.

Quantitative Analysis of Three Distinct Retinal Capillary Plexuses in Healthy Eyes Using Optical Coherence Tomography Angiography.

Purpose: To identify and quantify the three distinct retinal capillary plexuses and the foveal avascular zone (FAZ) in healthy subjects according to age using optical coherence tomography angiography (OCTA) with novel projection artifact removal (PAR) software and improved segmentation. Methods: All eyes in this cross-sectional study underwent OCTA imaging using RTVue XR Avanti with novel PAR AngioVue software. OCTA scans were analyzed and the three main parafoveal retinal capillary plexuses were segmented and vessel density and FAZ area were calculated. Results: A total of 152 normal eyes from 95 subjects (39 males, 56 females, mean age 42 ± 25 years) were included. The mean vessel density was 15.48 ± 2.04 mm-1 in the superficial retinal capillary plexus (SCP), 15.28 ± 1.82 mm-1 in the intermediate retinal capillary plexus (ICP), and 16.33 ± 2.32 mm-1 in the deep retinal capillary plexus (DCP) for 3 × 3-mm OCTA images. Analysis of 3 × 3-mm scans yielded a mean FAZ area of 0.270 ± 0.101 mm2. The average reduction in vessel density per year of age with 3 × 3-mm OCTA scans was 0.04 mm-1 (0.22%) in the SCP, 0.05 mm-1 (0.27%) in the ICP, and 0.06 mm-1 (0.30%) in the DCP. The average increase in FAZ area per year of age was 0.0015 mm2 (0.72%). Conclusions: Novel PAR software may provide improved visualization of all three major parafoveal retinal capillary plexuses including the ICP. Using this technology, SCP, ICP, and DCP vessel density decreased with increasing age while FAZ area increased with age.

Foveal and Peripapillary Vascular Decrement in Migraine With Aura Demonstrated by Optical Coherence Tomography Angiography.

Purpose: Migraine, particularly with aura, has been associated with ocular and systemic ischemic complications, but there are limited data on the ocular vasculature in migraine. We used optical coherence tomography angiography (OCTA) to assess perfusion of the macula and optic nerve in migraine patients, with (MA) and without (MO) aura, compared to healthy controls (HC). Methods: We recruited 15 MA (mean age 42 years), 12 MO (mean age 46 years), and 22 HC (mean age 39 years) participants from neurology and neuro-ophthalmology clinics. Participants underwent optical coherence tomography and 3 × 3 mm OCTA of the macula and optic nerve. Foveal avascular zone area was automatically measured using AngioVue software, and vessel density was calculated as blood vessel length divided by scan area (mm-1) after skeletonization of OCTA images. Results: On macular OCTA, MA participants had an enlarged foveal avascular zone area when compared with HC (0.300 ± 0.019 vs. 0.220 ± 0.066 mm2, P = 0.006). In addition, superficial foveal vessel density was decreased in MA participants when compared with MO participants (7.8 ± 0.31 vs. 9.3 ± 0.44, P = 0.04) and HC (7.8 ± 0.31 vs. 9.4 ± 0.21 mm-1, P = 0.002). On optic nerve OCTA, the MA participants had reduced superior peripapillary vessel density when compared with the MO participants (12.0 ± 0.45 vs. 14.0 ± 0.38 mm-1, P = 0.031) and HC (12.0 ± 0.45 vs. 14.1 ± 0.53 mm-1, P = 0.035). There were no significant differences between the MO and HC groups. Conclusions: Migraine with, but not without, aura was associated with foveal and peripapillary vascular decrements, which may possibly mediate increased risk of ocular and systemic vascular complications in these patients. OCTA could potentially be useful as a biomarker for migraine with aura.

Amalric Triangular Syndrome Associated With Outer Nuclear Layer Infarction.

An 85-year-old man presented with temporal headache and bilateral paracentral scotomas. Clinical examination, laboratory testing, and temporal artery biopsy confirmed the diagnosis of giant cell arteritis. Fluorescein angiography illustrated Amalric triangular choroidal infarction of the left eye. Spectral-domain optical coherence tomography of the left eye demonstrated outer nuclear layer abnormalities adjacent to the choroidal infarct. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:668-670.].

Relationship Between Optic Nerve Appearance and Retinal Nerve Fiber Layer Thickness as Explored with Spectral Domain Optical Coherence Tomography.

PURPOSE: To study the relationship between the appearance of the optic nerve and the retinal nerve fiber layer (RNFL) thickness determined by spectral domain optical coherence tomography (OCT). METHODS: Records from patients with spectral domain-OCT imaging in a neuro-ophthalmology practice were reviewed. Eyes with glaucoma/glaucoma suspicion, macular/optic nerve edema, pseudophakia, and with refractive errors > 6D were excluded. Optic nerve appearance by slit lamp biomicroscopy was related to the RNFL thickness by spectral domain-OCT and to visual field results. RESULTS: Ninety-one patients (176 eyes; mean age: 49 ± 15 years) were included. Eighty-three eyes (47%) showed optic nerve pallor; 89 eyes (50.6%) showed RNFL thinning (sectoral or average peripapillary). Average peripapillary RNFL thickness in eyes with pallor (mean ± SD = 76 ± 17 µm) was thinner compared to eyes without pallor (91 ± 14 µm, P < 0.001). Optic nerve pallor predicted RNFL thinning with a sensitivity of 69% and a specificity of 75%. Optic nerve appearance predicted RNFL thinning (with a sensitivity and specificity of 81%) when RNFL had thinned by ∼ 40%. Most patients with pallor had RNFL thinning with (66%) or without (25%) visual field loss; the remainder had normal RNFL and fields (5%) or with visual field abnormalities (4%). CONCLUSIONS: Optic nerve pallor as a predictor of RNFL thinning showed fair sensitivity and specificity, although it is optimally sensitive/specific only when substantial RNFL loss has occurred. TRANSLATIONAL RELEVANCE: Finding an acceptable relationship between the optic nerve appearance by ophthalmoscopy and spectral domain-OCT RNFL measures will help the clinician's interpretation of the information provided by this technology, which is gaining momentum in neuro-ophthalmic research.

Prion propagation can occur in a prokaryote and requires the ClpB chaperone.

Prions are self-propagating protein aggregates that are characteristically transmissible. In mammals, the PrP protein can form a prion that causes the fatal transmissible spongiform encephalopathies. Prions have also been uncovered in fungi, where they act as heritable, protein-based genetic elements. We previously showed that the yeast prion protein Sup35 can access the prion conformation in Escherichia coli. Here, we demonstrate that E. coli can propagate the Sup35 prion under conditions that do not permit its de novo formation. Furthermore, we show that propagation requires the disaggregase activity of the ClpB chaperone. Prion propagation in yeast requires Hsp104 (a ClpB ortholog), and prior studies have come to conflicting conclusions about ClpB's ability to participate in this process. Our demonstration of ClpB-dependent prion propagation in E. coli suggests that the cytoplasmic milieu in general and a molecular machine in particular are poised to support protein-based heredity in the bacterial domain of life.

Retinal structure in vitamin A deficiency as explored with multimodal imaging.

PURPOSE: To define the retinal structural abnormalities in a patient with vitamin A deficiency. METHODS: The patient had a complete ophthalmic examination, electroretinography (ERG), short-wave fundus autofluorescence (SW-AF) and spectral domain optical coherence tomography (SD-OCT) imaging. Serum vitamin A levels were measured. RESULTS: A 63-year-old man with alcoholic cirrhosis, sclerosing cholangitis and chronic pancreatitis experienced blurred vision and nyctalopia for over a year. There was no family history of eye disorders or consanguinity. His best-corrected visual acuity was 20/20 in each eye; color vision as determined with Ishihara color plates was normal in each eye. Anterior segment examination was unremarkable. He was pseudophakic in both eyes. Standard ERGs showed non-detectable rod function, a cone-mediated dark-adapted response to the standard flash and borderline reduced cone function. Serum vitamin A levels were below 0.06 mg/L (normal 0.3-1.2 mg/L). Fundus examination revealed numerous round yellow-white lesions along the superior arcade and nasal to the optic nerve in both eyes. These lesions were hypoautofluorescent on SW-AF. SD-OCT cross sections demonstrated that they were focal disruptions distal to the ellipsoid band of the photoreceptors with hyperreflective images bulging up the ellipsoid and region. The retinal pigment epithelium and the inner retina appeared intact. Limited and gradual vitamin A supplementation for over a month (20 000 IU/day) led to a dramatic improvement in retinal function and to the resolution of the symptoms. The retinal lesions remained unchanged. CONCLUSIONS: Imaging of this patient with nyctalopia and severe rod dysfunction suggests that the retinal white lesions known to occur in vitamin A deficiency localize to the photoreceptor layer, particularly the outer segment. On OCT, they are reminiscent of lesions observed in genetic diseases with retinoid cycle dysfunction and of drusenoid subretinal deposits, an abnormality commonly associated with age-related macular degeneration.

Modulation of murine Alzheimer pathogenesis and behavior by surgery.

OBJECTIVE: Previous research suggests that a link between anesthetic exposure and Alzheimer disease exists. Because anesthetics are rarely given alone, we ask whether addition of surgery further modulates Alzheimer disease. BACKGROUND: Cognitive dysfunction occurs after surgery in humans. Anesthesia alone produces cognitive decline in both older wild-type (WT) mice and rats, and the addition of surgery produces transient decline in young, adult WT mice. Because neuroinflammation has been implicated and occurs early in Alzheimer disease, we hypothesized that the neuroinflammatory stress associated with surgery would accelerate the progression of Alzheimer disease. METHODS: Cecal ligation and excision were performed on presymptomatic 5- to 11-month-old triple-transgenic Alzheimer disease (3×TgAD) and C57BL/6 WT mice under desflurane anesthesia. Surgery animals were compared with aged-matched 3×TgAD and WT mice exposed to air or desflurane alone. Cognitive function was assessed via Morris water maze at 2 and 13 weeks postoperatively. Amyloid and tau pathology and inflammation and synaptic markers were quantified with immunohistochemistry, Luminex assay, enzyme-linked immunosorbent assay, or Western blot assays. RESULTS: A significant cognitive impairment in 3×TgAD mice that underwent surgery compared with air or desflurane controls persisted to at least 14 weeks after surgery. Microglial activation, amyloidopathy, and tauopathy were enhanced by surgery as compared with desflurane alone. No differences between surgery, anesthetic, or air controls were detected in WT mice CONCLUSIONS: Surgery causes a durable increment in Alzheimer pathogenesis, primarily through a transient activation of neuroinflammation.

Genetic reporter system for positioning of proteins at the bacterial pole.

UNLABELLED: Spatial organization within bacteria is fundamental to many cellular processes, although the basic mechanisms underlying localization of proteins to specific sites within bacteria are poorly understood. The study of protein positioning has been limited by a paucity of methods that allow rapid large-scale screening for mutants in which protein positioning is altered. We developed a genetic reporter system for protein localization to the pole within the bacterial cytoplasm that allows saturation screening for mutants in Escherichia coli in which protein localization is altered. Utilizing this system, we identify proteins required for proper positioning of the Shigella autotransporter IcsA. Autotransporters, widely distributed bacterial virulence proteins, are secreted at the bacterial pole. We show that the conserved cell division protein FtsQ is required for localization of IcsA and other autotransporters to the pole. We demonstrate further that this system can be applied to the study of proteins other than autotransporters that display polar positioning within bacterial cells. IMPORTANCE: Many proteins localize to specific sites within bacterial cells, and localization to these sites is frequently critical to proper protein function. The mechanisms that underlie protein localization are incompletely understood, in part because of the paucity of methods that allow saturation screening for mutants in which protein localization is altered. We developed a genetic reporter assay that enables screening of bacterial populations for changes in localization of proteins to the bacterial pole, and we demonstrate the utility of the system in identifying factors required for proper localization of the polar Shigella autotransporter protein IcsA. Using this method, we identify the conserved cell division protein FtsQ as being required for positioning of IcsA to the bacterial pole. We demonstrate further that the requirement for FtsQ for polar positioning applies to other autotransporters and that the method can be applied to polar proteins other than autotransporters.