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1.
Ophthalmol Retina ; 3(2): 140-145, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30931417

RESUMO

Objective: To evaluate the outcomes of patients undergoing pneumatic retinopexy (PR) performed by vitreoretinal fellows at 6 academic centers in the United States. Design: Retrospective, multicenter, consecutive case series. Participants: 483 patients with primary retinal detachments who underwent PR by 49 vitreoretinal fellows from 6 U.S. training sites between 2002 and 2016. Methods: We reviewed medical records of patients and recorded baseline clinical characteristics (age, sex, baseline visual acuity, lens status, presence of lattice degeneration, presence of vitreous hemorrhage, location of retinal breaks, macular status, and size of detachment), visual and anatomic outcomes at 3-months after PR, as well as training level and PR experience of the fellow at the time of the procedure. Main Outcome Measures: Single-procedure anatomic success and visual acuity at 3-months follow-up, and association with clinical and training-related factors. Results: Vitreoretinal fellows performed a variable number of PR, with a median of 7 cases per fellow (range 1-24). Single-procedure anatomic success was 66.8%, and mean LogMAR visual outcome was 0.43 (Snellen equivalent 20/54) at 3 months. Factors that were independently associated with single-procedure success include phakic lens status (P = 0.01), smaller size of retinal detachment (P = 0.02), and the fellow's procedure experience (P = 0.01). The only factor associated with worse visual outcome was baseline visual acuity (P < 0.001). Conclusion: Vitreoretinal fellows perform variably few pneumatic retinopexies but have outcomes comparable to reported rates by experienced specialists. Procedure experience of individual fellows may impact anatomic outcomes.

2.
J Neurophysiol ; 121(5): 1718-1734, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30786219

RESUMO

Two macroscopic parameters describe the interstitial diffusion of substances in the extracellular space (ECS) of the brain, the ECS volume fraction α and the diffusion tortuosity λ. Past methods based on sampling the extracellular concentration of a membrane-impermeable ion tracer, such as tetramethylammonium (TMA+), can characterize either the dynamic α(t) alone or the constant α and λ in resting state but never the dynamic α(t) and λ(t) simultaneously in short-lived brain events. In this work, we propose to use a sinusoidal method of TMA+ to provide time-resolved quantification of α(t) and λ(t) in acute brain events. This method iontophoretically injects TMA+ in the brain ECS by a sinusoidal time pattern, samples the resulting TMA+ diffusion waveform at a distance, and analyzes the transient modulations of the amplitude and phase lag of the sampled TMA+ waveform to infer α(t) and λ(t). Applicability of the sinusoidal method was verified through computer simulations of the sinusoidal TMA+ diffusion waveform in cortical spreading depression. Parameter sensitivity analysis identified the sinusoidal frequency and the interelectrode distance as two key operating parameters. Compared with other TMA+-based methods, the sinusoidal method can more accurately capture the dynamic α(t) and λ(t) in acute brain events and is equally applicable to other pathological episodes such as epilepsy, transient ischemic attack, and brain injury. Future improvement of the method should focus on high-fidelity extraction of the waveform amplitude and phase angle. NEW & NOTEWORTHY An iontophoretic sinusoidal method of tetramethylammonium is described to capture the dynamic brain extracellular space volume fraction α and diffusion tortuosity λ. The sinusoidal frequency and interelectrode distance are two key operating parameters affecting the method's accuracy in capturing α(t) and λ(t). High-fidelity extraction of the waveform amplitude and phase lag is critical to successful sinusoidal analyses.

3.
J Neurophysiol ; 121(5): 1735-1747, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30786223

RESUMO

Extracellular diffusion in the brain is customarily characterized by two parameters, the extracellular space (ECS) volume fraction α and the diffusion tortuosity λ. How these two parameters are temporarily modified and correlated in a physiological/pathological event remains unclear to date. Using tetramethylammonium (TMA+) as an ECS ion tracer in a newly updated iontophoretic sinusoidal method, we studied in this work the dynamic α(t) and λ(t) in rat somatosensory cortex during spreading depression (SD). Temporal variations of α(t) and λ(t), as evoked by SD, were obtained through analyses of the extracellular TMA+ diffusion waveform resulting from a sinusoidally modulated point source. Most of the time, cortical SD induced coordinated α(t) decreases and λ(t) increases. In rare occasions, SD induced sole decreases of α(t) with no changes in λ(t). The independent modulation of α(t) and λ(t) was neither associated with cortical anatomy nor with the specific shape of the SD field potential wave. Changes of α(t) and λ(t) often took place acutely at the onset of SD, followed by a more transient modulation. Compared with the prior iontophoretic methods of TMA+, the sinusoidal method provides time-resolved quantification of α(t) and λ(t) in relative terms but also raises a higher property requirement on the TMA+-selective microelectrode. The sinusoidal method could become a valuable tool in the studies of the dynamic ECS response in various brain events. NEW & NOTEWORTHY An iontophoretic sinusoidal method was applied to study the dynamic changes of two extracellular space parameters, the extracellular volume fraction α(t) and tortuosity λ(t), in the brain during cortical spreading depression. Both parameters showed coordinated (most often) and independent (rarely) modulations in spreading depression. The sinusoidal method is equally applicable to other acute pathological events and a valuable tool to study the functional role of extracellular space in brain events.

4.
Ophthalmology ; 126(4): 576-588, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30659849

RESUMO

PURPOSE: To evaluate the long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy (CSC). DESIGN: Retrospective, longitudinal study. PARTICIPANTS: A total of 133 participants (217 eyes) with chronic CSC. METHODS: A retrospective review of clinical and multimodal imaging data of patients with chronic CSC managed by 3 of the authors between May 1977 and March 2018. Multimodal imaging comprised color photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence (FAF), and OCT. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at the final visit; change in BCVA between first visit and 1-, 5-, and 10-year follow-up visits; and causes of vision loss at final visit. RESULTS: Data from 6228 individual clinic visits were analyzed. Mean age of patients at the first visit was 60.7 years, and mean period of follow-up from first to last visit was 11.3 years. The cohort included 101 male patients (75.9%). At the final visit, 106 patients (79.7%) maintained driving-standard vision with BCVA of 20/40 or better in at least 1 eye, and 17 patients (12.8%) were legally blind with BCVA of 20/200 or worse in both eyes. Mean BCVA at first visit was not significantly different from mean BCVA at 1- or 5-year follow-up visits (both P ≥ 0.65) but was significantly better than the mean BCVA at the 10-year follow-up visit (P = 0.04). Seventy-nine percent of eyes with 20/40 or better vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Ninety-two percent of eyes with 20/200 or worse vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Cystoid macular degeneration, choroidal neovascularization (CNV), outer retinal disruption on OCT, and FAF changes were associated with poorer vision at the final visit (all P ≤ 0.001). Multivariable analysis revealed that greater age at first visit was associated with greater BCVA change at the 10-year follow-up visit (P = 0.001). CONCLUSIONS: Chronic CSC can be a sight-threatening disease leading to legal blindness. Age at presentation and outer retinal changes on multimodal imaging were associated with long-term BCVA changes and may be predictors of long-term visual outcomes.

5.
Surv Ophthalmol ; 64(1): 117-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28684101

RESUMO

A 54-year-old white man presented with a "blind spot" temporally in his left eye. Best-corrected visual acuity in the affected eye was 20/20, and Humphrey visual field revealed an enlarged blind spot. Funduscopic examination revealed subtle peripapillary pigmentary changes corresponding to a well-demarcated peripapillary region of hyperautofluorescence and hypoautofluorescence on fundus autofluorescence. Outer retinal degenerative changes were detected on spectral-domain optical coherence tomography. A diagnosis of acute zonal occult outer retinopathy was made based on clinical history and imaging studies.


Assuntos
Retina/patologia , Escotoma/diagnóstico , Campos Visuais/fisiologia , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Escotoma/fisiopatologia , Tomografia de Coerência Óptica/métodos , Testes de Campo Visual
6.
Retina ; 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29965938

RESUMO

PURPOSE: To evaluate depth of field, lateral resolution, and image quality of a heads-up 3D visualization system for vitreoretinal surgery using physician survey and optical measurement outcomes. METHODS: Depth of field and lateral resolution were compared between the standard ocular viewing system and the digital 3D system at ×5, ×13, and ×18 magnification by 6 retinal surgeons. Optical techniques were used as well as a survey of surgeon impression. Surgeon impression surveys were performed after 6 weeks of surgical use of the device. RESULTS: Physician questionnaire survey scores for depth of field at high magnification were better for the digital 3D system and equivalent for all other categories. Measured lateral resolution was 36.7 mm and 16.6 mm at ×5 magnification (P < 0.001), 14.3 mm and 6.4 mm at ×13 magnification (P < 0.001), and 9.8 mm and 4.2 mm (P < 0.001) at ×18 magnification for the digital 3D and oculars, respectively. Measured depth of field was 4.00 mm and 6.78 mm at ×5 magnification (P = 0.027), 0.72 mm and 0.86 mm at ×13 (P = 0.311), and 0.28 mm and 0.40 mm at ×18 magnification (P = 0.235) for the oculars and digital 3D, respectively. CONCLUSION: Lateral resolution of the digital 3D system was half that of the ocular viewing system and there was some improvement in depth of field with the digital system. Surgeon impression suggested that the digital system was superior when evaluating depth of field at high magnification.

7.
Retina ; 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30028411

RESUMO

PURPOSE: To characterize the natural history and response of age-related macular degeneration-associated peripapillary choroidal neovascularization to anti-vascular endothelial growth factor therapy. METHODS: This was a retrospective case series of patients with peripapillary choroidal neovascularization secondary to neovascular age-related macular degeneration. All patients underwent complete ophthalmologic examination and retinal imaging including fluorescein angiography and spectral domain optical coherence tomography at each visit. Eyes with subretinal or intraretinal macular fluid were treated with anti-vascular endothelial growth factor monotherapy using a modified as-needed treatment algorithm. RESULTS: Thirty-three eyes of 27 patients were included. The median age was 82 years (range, 62-94), and the median duration of follow-up was 65 months (range, 6-165). Fourteen eyes (58%) without fovea-involving fluid at baseline subsequently developed exudation after a median observation period of 16 months (range, 4-107). Ten of 24 eyes (42%) without initial macular fluid remained dry during the entire follow-up. The median number of injections required until complete fluid reabsorption was 3 (range, 1-21) during the first treatment cycle. The median time to fluid recurrence was 6 months (range, 3-74). CONCLUSION: Peripapillary choroidal neovascularization secondary to wet age-related macular degeneration has a slow progression, may not require treatment for a prolonged period, and responds rapidly to anti-vascular endothelial growth factor treatment with good visual outcomes.

8.
Retina ; 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30015764

RESUMO

PURPOSE: To assess early retinal microvascular and functional changes in diabetic patients without clinical evidence of diabetic retinopathy with optical coherence tomography angiography and central visual analyzer. METHODS: This was an observational case-control study of diabetic patients without diabetic retinopathy and nondiabetic controls. Patients underwent optical coherence tomography angiography imaging and visual acuity testing using the central visual analyzer. The foveal avascular zone area and the capillary density in the superficial and deep capillary plexuses were measured manually by a masked grader. RESULTS: Sixty eyes from 35 diabetic patients were included in the study group, and 45 eyes from 31 nondiabetic patients were included in the control group. The foveal avascular zone area was not significantly different between the diabetic group and controls (both P > 0.05). The mean capillary density in the deep capillary plexus was significantly lower in diabetic eyes compared with control eyes (P = 0.04). The mean visual acuity in all central visual analyzer modules was significantly decreased in diabetic patients compared with controls (all P < 0.05). CONCLUSION: Optical coherence tomography angiography was able to detect retinal microvascular changes in the deep capillary plexus, and the central visual analyzer showed signs of decreased visual acuity under conditions simulating suboptimal contrast and glare in diabetic patients without diabetic retinopathy.

9.
Retina ; 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29554078

RESUMO

PURPOSE: To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices. METHODS: This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula. RESULTS: The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images. CONCLUSION: Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.

10.
Surv Ophthalmol ; 2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-29024674

RESUMO

A 68-year-old woman with a recent history of blurring in the left eye had undergone mastectomy for breast cancer 20 years ago. A series of bone metastases started 5 years after her diagnosis. Examination of the optic nerve head of the left eye revealed an isolated peripapillary mass. Indocyanine green angiography displayed vessels within the mass, and fluorescein angiography demonstrated hyperfluorescence of the mass from vascular leakage plus lobular spots of blocked fluorescence. B-scan ultrasound revealed a hyperechoic-elevated nodular mass on the optic disc. Spectral-domain optical coherence tomography displayed a mass of spherules. Magnetic resonance imaging of the brain demonstrated metastatic tumors. She was diagnosed with an optic disk metastasis from her breast carcinoma.

11.
Retina ; 37(11): 2025-2034, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28098736

RESUMO

PURPOSE: To describe atypical cases of multiple evanescent white dot syndrome (MEWDS) associated with foveal exudation, increased choroidal thickness, and secondary Type 2 (subretinal) neovascularization. METHODS: Four cases of atypical MEWDS were studied at a retina referral center. Patients underwent evaluation with multimodal retinal imaging, including fluorescein angiography, indocyanine green angiography, spectral-domain and enhanced depth imaging optical coherence tomography (OCT). Two patients were imaged with OCT angiography. RESULTS: Four patients (3 female, 1 male) with a median age of 23.5 years presented with acute onset, painless, decreased central vision. All cases demonstrated fundus findings consistent with MEWDS on color photography, indocyanine green angiography, fluorescein angiography, fundus autofluorescence, and structural OCT imaging. On structural OCT, all 4 patients were noted to have hyperreflective subretinal material and increased subfoveal choroidal thickness ranging from 307 µm to 515 µm. Type 2 neovascularization was diagnosed in all four patients using fluorescein angiography, indocyanine green angiography, and/or OCT angiography. Two patients had poor visual acuity at the last follow-up despite resolution of characteristic clinical findings of MEWDS. CONCLUSION: A subset of patients with atypical MEWDS may develop persistent poor vision due to subfoveal exudation and secondary Type 2 neovascularization. Patients showing increased choroidal thickness at presentation may be more susceptible to this unusual presentation.


Assuntos
Neovascularização de Coroide/diagnóstico , Angiofluoresceinografia/métodos , Fóvea Central/patologia , Líquido Sub-Retiniano/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adolescente , Adulto , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Síndrome , Adulto Jovem
12.
Retina ; 37(7): 1287-1296, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27749694

RESUMO

PURPOSE: To describe anatomical relationships of retinal neovascular complexes (NVCs) and the posterior vitreous in proliferative diabetic retinopathy using spectral domain optical coherence tomography. METHODS: Cross-sectional study. Neovascular complexes were imaged using spectral domain optical coherence tomography in 51 eyes of 37 patients. The relationship of NVCs to the posterior vitreous cortex and posterior vitreous spaces, such as the premacular bursa, prevascular vitreous fissures, and perimacular cisterns, was analyzed. RESULTS: In the 77 NVCs evaluated, 61 (79%) had grown along the outer surface of the posterior hyaloid face, and vitreoschisis was present in 37 (48%). The "wolf's jaw" configuration was present in 9% and resulted from NVC arising from the arcades and proliferating along the posterior hyaloid face. By contrast, NVCs that invaded the bursa originated from smaller venous tributaries more distant from the arcades. The premacular bursa and prevascular vitreous fissure/perimacular cistern were invaded infrequently, respectively, in 15% and 38% (P = 0.137). CONCLUSION: Tomographic analysis of diabetic NVCs showed that most NVCs arise and grow along the posterior hyaloid face and that vitreoschisis is more prevalent than what has been found in ultrasound studies. The wolf's jaw configuration does not seem to result from the invasion of the bursa, as previously suggested.


Assuntos
Retinopatia Diabética/diagnóstico , Retina/patologia , Neovascularização Retiniana/diagnóstico , Tomografia de Coerência Óptica/métodos , Corpo Vítreo/patologia , Estudos Transversais , Retinopatia Diabética/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Retiniana/etiologia
13.
Retina ; 37(8): 1451-1463, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27880741

RESUMO

PURPOSE: To evaluate the spectrum of macular chorioretinal lesions occurring in idiopathic multifocal choroiditis using optical coherence tomography angiography (OCTA) to evaluate those showing neovascular flow. METHODS: This was a descriptive, retrospective study of 18 eyes of 14 patients with multifocal choroiditis. Macular lesions were characterized as subretinal pigment epithelium, subretinal, or mixed and evaluated during active and presumed inactive states of multifocal choroiditis. Correlations between structural optical coherence tomography and OCTA were performed. In select cases, correlations between OCTA, fluorescein angiography, and fundus autofluorescence were evaluated. In 5 eyes, quantitative measurements of neovascular lesions were compared at baseline and following intravitreal anti-vascular endothelial growth factor therapy. RESULTS: Mean patient age was 48 years (SD: 13.8; 86% women). Optical coherence tomography angiography flow signatures consistent with neovascularization were identified in 83% of eyes, including in 0% of subretinal pigment epithelium, 91% of subretinal, and 100% of mixed lesions. Lesions that did not demonstrate definitive signs of fluorescein angiography leakage were frequently found to have neovascularization using OCTA. There was no change in quantitative measurements of neovascular lesions after anti-vascular endothelial growth factor therapy (all tested variables P > 0.05). CONCLUSION: Optical coherence tomography angiography may be a useful imaging modality for understanding the pathophysiology of multifocal choroiditis and monitoring its clinical course.


Assuntos
Corioide/patologia , Corioidite/diagnóstico , Angiofluoresceinografia/métodos , Retina/patologia , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Progressão da Doença , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade Visual
14.
Mater Sci Eng C Mater Biol Appl ; 71: 289-297, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27987710

RESUMO

A novel rapid hemostatic and mild polyurethane-urea foam (PUUF) wound dressing was prepared by the particle leaching method and vacuum freeze-drying method using 4, 4-Methylenebis(cyclohexyl isocyanate), 4,4-diaminodicyclohexylmethane and poly (ethylene glycol) as raw materials. And X-ray diffraction (XRD), tensile test, differential scanning calorimetry (DSC) and thermogravimetry (TG) were used to its crystallinity, stress and strain behavior, and thermal properties, respectively. Platelet adhesion, fibrinogen adhesion and blood clotting were performed to evaluate its hemostatic effect. And H&E staining and Masson Trichrome staining were used to its wound healing efficacy. The results revealed the pore size of PUUF is 50-130µm, and its porosity is 71.01%. Porous PUUF exhibited good water uptake that was benefit to adsorb abundant wound exudates to build a regional moist environment beneficial for wound healing. The PUUF wound dressing exhibit better blood coagulation effect than commercial polyurethane dressing (CaduMedi). Though both PUUF and CaduMedi facilitated wound healing generating full re-epithelialization within 13days, PUUF was milder and lead to more slight inflammatory response than CaduMedi. In addition, PUUF wound dressing exhibited lower cytotoxicity than CaduMedi against NIH3T3 cells. Overall, porous PUUF represents a novel mild wound dressing with excellent water uptake, hemostatic effect and low toxicity, and it can promote wound healing and enhance re-epithelialization.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Técnicas Hemostáticas , Poliuretanos , Ureia , Cicatrização/efeitos dos fármacos , Animais , Bandagens , Humanos , Camundongos , Células NIH 3T3 , Poliuretanos/química , Poliuretanos/farmacologia , Porosidade , Ureia/química , Ureia/farmacologia
15.
Am J Ophthalmol ; 164: 89-98, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26868959

RESUMO

PURPOSE: To describe the natural course, visual outcomes, and anatomic changes and provide histologic correlates in eyes with intraretinal hyperreflective foci associated with acquired vitelliform lesions. DESIGN: Retrospective cohort study and imaging-histology correlation in a single donor eye. METHODS: participants: Patients with intraretinal hyperreflective foci and acquired vitelliform lesions from 2 tertiary referral centers were evaluated from January 2002 to January 2014. MAIN OUTCOME MEASURES: The chronology of clinical and imaging features of retinal anatomic changes and the pattern of intraretinal hyperreflective foci migration were documented using spectral-domain optical coherence tomography (OCT). One donor eye with intraretinal hyperreflective foci was identified in a pathology archive by ex vivo OCT and was studied with high-resolution light and electron microscopic examination. RESULTS: Intraretinal hyperreflective foci were associated with acquired vitelliform lesions in 25 of 254 eyes (9.8%) with a strong female preponderance (86% of patients). Focal disruptions to the ellipsoid zone and external limiting membrane overlying the acquired vitelliform lesions were observed prior to the occurrence of intraretinal hyperreflective foci in 75% of cases. Histologic evaluation showed that intraretinal hyperreflective foci represent cells of retinal pigment epithelium origin that are similar to those found in the vitelliform lesions themselves and contain lipofuscin granules, melanolipofuscin granules, and melanosomes. The occurrence of intraretinal hyperreflective foci was not a significant determinant of final visual acuity (P = .34), but development of outer retinal atrophy was (P = .003). CONCLUSIONS: Intraretinal hyperreflective foci associated with acquired vitelliform lesions are of retinal pigment epithelium origin, and the natural course and functional changes are described.


Assuntos
Retina/patologia , Distrofia Macular Viteliforme/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Corioide/patologia , Estudos de Coortes , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Óptica , Estudos Retrospectivos , Doadores de Tecidos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Distrofia Macular Viteliforme/fisiopatologia
16.
J Virol ; 90(6): 3123-37, 2016 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-26739048

RESUMO

UNLABELLED: Immune responses of natural killer (NK) cell are controlled by the balance between activating and inhibitory receptors, but the expression of these receptors varies between cells within an individual. Although NK cells are a component of the innate immune system, particular NK cell subsets expressing Ly49H are positively selected and increase in frequency in response to cytomegalovirus infection in mice. Recent evidence suggests that in humans certain NK subsets also have an increased frequency in the blood of human cytomegalovirus (HCMV)-infected individuals. However, whether these subsets differ in their capacity of direct control of HCMV-infected cells remains unclear. In this study, we developed a novel in vitro assay to assess whether human NK cell subsets have differential abilities to inhibit HCMV growth and dissemination. NK cells expressing or lacking NKG2C did not display any differences in controlling viral dissemination. However, when in vitro-expanded NK cells were used, cells expressing or lacking the inhibitory receptor leukocyte immunoglobulin-like receptor 1 (LIR1) were differentially able to control dissemination. Surprisingly, the ability of LIR1(+) NK cells to control virus spread differed between HCMV viral strains, and this phenomenon was dependent on amino acid sequences within the viral ligand UL18. Together, the results here outline an in vitro technique to compare the long-term immune responses of different human NK cell subsets and suggest, for the first time, that phenotypically defined human NK cell subsets may differentially recognize HCMV infections. IMPORTANCE: HCMV infection is ubiquitous in most populations; it is not cleared by the host after primary infection but persists for life. The innate and adaptive immune systems control the spread of virus, for which natural killer (NK) cells play a pivotal role. NK cells can respond to HCMV infection by rapid, short-term, nonspecific innate responses, but evidence from murine studies suggested that NK cells may display long-term, memory-like responses to murine cytomegalovirus infection. In this study, we developed a new assay that examines human NK cell subsets that have been suggested to play a long-term memory-like response to HCMV infection. We show that changes in an HCMV viral protein that interacts with an NK cell receptor can change the ability of NK cell subsets to control HCMV while the acquisition of another receptor has no effect on virus control.


Assuntos
Antígenos CD/metabolismo , Proteínas do Capsídeo/metabolismo , Citomegalovirus/imunologia , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos/imunologia , Receptores Imunológicos/metabolismo , Humanos , Células Matadoras Naturais/química , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Subpopulações de Linfócitos/química , Complexo Principal de Histocompatibilidade
18.
Retin Cases Brief Rep ; 10(3): 217-20, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26510002

RESUMO

BACKGROUND/PURPOSE: To report the swept-source optical coherence tomography (SS-OCT) findings in a case of acute toxoplasmosis chorioretinitis. METHODS: A 35-year-old male presented with acute blurry vision and floaters in his left eye. Ophthalmic examination, color photographs, spectral-domain OCT (SD-OCT), enhanced depth imaging OCT (EDI-OCT), SS-OCT and wide-field fluorescein angiography images were obtained to diagnose and follow the subsequent changes of toxoplasmosis chorioretinitis over a 2-month period. RESULTS: Initial imaging with different modalities of SD- and EDI-OCT including radial vitreous scans and horizontal high-speed B-scan raster lines demonstrated thickening of the posterior hyaloid and acute vitreous cells emanating from the retinal blood vessels, thickening and disorganization of the retinal layers within the chorioretinal lesion, and increased sub-lesional choroidal thickness, respectively. SS-OCT demonstrated all of these same findings in a single 12-mm B-scan. Topical steroids were initiated and imaging over the next 2 months showed separation of the posterior hyaloid, decrease in vitreous cell, and atrophy of the chorioretinal lesion. CONCLUSION: We report the first SS-OCT images of an acute case of toxoplasmosis chorioretinitis. SS-OCT can visualize the choroidal, retinal, and vitreous changes in a single scan, compared with the different imaging algorithms required with SD-OCT.


Assuntos
Coriorretinite/parasitologia , Corioide/diagnóstico por imagem , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Toxoplasmose Ocular/diagnóstico por imagem , Corpo Vítreo/diagnóstico por imagem , Adulto , Coriorretinite/diagnóstico por imagem , Humanos , Masculino
20.
Genome Biol ; 16: 33, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25786205

RESUMO

Epigenomic data from ENCODE can be used to associate specific combinations of chromatin marks with regulatory elements in the human genome. Hidden Markov models and the expectation-maximization (EM) algorithm are often used to analyze epigenomic data. However, the EM algorithm can have overfitting problems in data sets where the chromatin states show high class-imbalance and it is often slow to converge. Here we use spectral learning instead of EM and find that our software Spectacle overcame these problems. Furthermore, Spectacle is able to find enhancer subtypes not found by ChromHMM but strongly enriched in GWAS SNPs. Spectacle is available at https://github.com/jiminsong/Spectacle.


Assuntos
Algoritmos , Cromatina/metabolismo , Anotação de Sequência Molecular , Doenças Autoimunes/genética , Linhagem Celular , Elementos Facilitadores Genéticos , Epigênese Genética , Genética Populacional , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas , Especificidade da Espécie , Sítio de Iniciação de Transcrição
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