Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
bioRxiv ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38798486

RESUMO

Post-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase infarct volume, blood-brain barrier disruption, and hemorrhage formation, and to impair motor recovery. Post-stroke hyperglycemia also increased superoxide formation by peri-infarct microglia/macrophages. In contrast, post-stroke hyperglycemia did not increase superoxide formation or exacerbate motor impairment in p47 phox-/- mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex. These results suggest that hyperglycemia occurring hours-to-days after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism contribute to worsened functional outcome.

2.
Ocul Immunol Inflamm ; : 1-9, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36893445

RESUMO

INTRODUCTION: Currently, little is known regarding bone health surveillance for glucocorticoid-exposed non-infectious uveitis (NIU) patients or their baseline risks of skeletal fragility outcomes. METHODS: Using claims data, we calculated rates of dual-energy x-ray absorptiometry (DXA) screening for glucocorticoid-exposed NIU and rheumatoid arthritis (RA) patients. Separately, we compared risks of skeletal fragility metrics amongst NIU patients, RA patients, and controls, independent of glucocorticoid use. RESULTS: The adjusted hazard ratio (aHR) of NIU patients to have a DXA scan was 0.64 (95% CI, 0.63-0.65; p < .001) compared to RA patients. The aHR for any skeletal fragility outcome amongst NIU patients was 0.97 (p < .02) compared to normal controls, while RA patients had excess risk (aHR, 1.15; p < .001). CONCLUSIONS: NIU patients are 36% less likely to receive a DXA scan after high-dose glucocorticoid exposure compared with RA patients. No elevated risk of osteoporosis for NIU patients was found compared to normal controls.

3.
Prog Neurobiol ; 202: 102070, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33951536

RESUMO

Oxidative stress and α-synuclein aggregation both drive neurodegeneration in Parkinson's disease, and the protein kinase c-Abl provides a potential amplifying link between these pathogenic factors. Suppressing interactions between these factors may thus be a viable therapeutic approach for this disorder. To evaluate this possibility, pre-formed α-synuclein fibrils (PFFs) were used to induce α-synuclein aggregation in neuronal cultures. Exposure to PFFs induced oxidative stress and c-Abl activation in wild-type neurons. By contrast, α-synuclein - deficient neurons, which cannot form α-synuclein aggregates, failed to exhibit either oxidative stress or c-Abl activation. N-acetyl cysteine, a thiol repletion agent that supports neuronal glutathione metabolism, suppressed the PFF - induced redox stress and c-Abl activation in the wild-type neurons, and likewise suppressed α-synuclein aggregation. Parallel findings were observed in mouse brain: PFF-induced α-synuclein aggregation in the substantia nigra was associated with redox stress, c-Abl activation, and dopaminergic neuronal loss, along with microglial activation and motor impairment, all of which were attenuated with oral N-acetyl cysteine. Similar results were obtained using AAV-mediated α-synuclein overexpression as an alternative means of driving α-synuclein aggregation in vivo. These findings show that α-synuclein aggregates induce c-Abl activation by a redox stress mechanism. c-Abl activation in turn promotes α-synuclein aggregation, in a feed-forward interaction. The capacity of N-acetyl cysteine to interrupt this interaction adds mechanistic support its consideration as a therapeutic in Parkinson's disease.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Animais , Cisteína , Dopamina , Neurônios Dopaminérgicos/metabolismo , Camundongos , Oxirredução , Doença de Parkinson/tratamento farmacológico , Substância Negra/metabolismo , alfa-Sinucleína/metabolismo
4.
Adv Neurobiol ; 23: 169-185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31667809

RESUMO

It has been known for over 50 years that brain has significant glycogen stores, but the physiological function of this energy reserve remains uncertain. This uncertainty stems in part from several technical challenges inherent in the study of brain glycogen metabolism, and may also stem from some conceptual limitations. Factors presenting technical challenges include low glycogen content in brain, non-homogenous labeling of glycogen by radiotracers, rapid glycogenolysis during postmortem tissue handling, and effects of the stress response on brain glycogen turnover. Here, we briefly review aspects of glycogen structure and metabolism that bear on these technical challenges, and discuss ways these can be overcome. We also highlight physiological aspects of glycogen metabolism that limit the conditions under which glycogen metabolism can be useful or advantageous over glucose metabolism. Comparisons with glycogen metabolism in skeletal muscle provide an additional perspective on potential functions of glycogen in brain.


Assuntos
Encéfalo/metabolismo , Glicogênio/metabolismo , Glicogenólise
5.
Ophthalmic Surg Lasers Imaging Retina ; 49(7): 540-543, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30021043

RESUMO

The authors present an unusual case of bilateral macular choroidal infarction as a manifestation of giant cell arteritis (GCA). Due to sequential bilateral presentation, multimodal imaging with spectral-domain optical coherence tomography allows for simultaneous evaluation of progressive stages of outer retinal damage caused by choroidal hypoperfusion seen on fluorescein and indocyanine green angiography. This case report demonstrates that GCA should be considered in the differential diagnosis of placoid maculopathies. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:540-543.].


Assuntos
Corioide/irrigação sanguínea , Arterite de Células Gigantes/diagnóstico , Infarto/diagnóstico , Biópsia , Corantes/administração & dosagem , Angiofluoresceinografia , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/administração & dosagem , Humanos , Verde de Indocianina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Artérias Temporais/patologia , Tomografia de Coerência Óptica , Acuidade Visual
6.
PLoS One ; 13(2): e0192098, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29466365

RESUMO

Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs) from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects. Despite these differences, CD8+ T cells stimulated with either HIV-1 or cross-reactive peptides effectively suppressed HIV-1 replication in autologous CD4+ T cells. These data suggest that exposure to cross-reactive microbial antigens can modulate HIV-1-specific immunity.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Reações Cruzadas , Infecções por HIV/imunologia , HIV-1/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , HIV-1/imunologia , HIV-1/fisiologia , Humanos , Replicação Viral/efeitos dos fármacos
7.
Am J Ophthalmol ; 179: 179-189, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28501392

RESUMO

PURPOSE: To identify determinants of adverse outcomes in acute retinal necrosis (ARN), presenting characteristics and incidence rates of vision loss and ocular complications in a cohort of polymerase chain reaction (PCR)-positive eyes were analyzed. DESIGN: Retrospective observational cohort study. METHODS: Forty-one eyes of 36 patients with clinically diagnosed ARN, PCR-positive for herpes simplex virus or varicella zoster virus and evaluated between January 2002 and June 2013, were included. Main outcome measures included incidence rates of vision loss and retinal detachment (RD). RESULTS: Presenting visual acuity was generally poor (20/50 to >20/200 in 27%; 20/200 or worse in 56%). The incidence rate of ≤20/200 was 0.66/eye-year (EY), (95% confidence interval [CI], 0.32/EY to 1.22/EY); the rate of light perception or no light perception vision was 0.07/EY (95% CI, 0.02/EY to 0.16/EY). During follow-up, 59% of eyes developed at least 1 RD (rate = 0.40/EY, 95% CI, 0.19/EY to 0.58/EY). Eyes with retinitis involving ≥25% of the retina at presentation detached at nearly 12 times the rate, as compared to those with <25% retinal involvement (0.70/EY vs 0.06/EY; P = .001). Development of an RD was the greatest determinant of adverse visual outcomes, with 4% of eyes, that had experienced at least 1 RD, achieving a best-corrected visual acuity of ≥20/40 compared to 53% of eyes that never detached (P = .0003). CONCLUSIONS: Poor outcomes in ARN were common in this cohort. RD confers the greatest risk of incident vision loss, and once 25% or more of the retina is involved the risk of RD and visual loss increases significantly.


Assuntos
DNA Viral/análise , Infecções Oculares Virais/complicações , Herpes Simples/genética , Herpes Zoster Oftálmico/complicações , Herpesvirus Humano 3/genética , Síndrome de Necrose Retiniana Aguda/diagnóstico , Acuidade Visual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/virologia , Feminino , Seguimentos , Herpes Zoster Oftálmico/diagnóstico , Herpes Zoster Oftálmico/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Síndrome de Necrose Retiniana Aguda/etiologia , Estudos Retrospectivos , Adulto Jovem
9.
Ophthalmic Surg Lasers Imaging Retina ; 47(7): 682-5, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27434903

RESUMO

Posterior ophthalmomyiasis interna is a rare, potentially devastating infestation of the posterior segment by fly larvae. The authors report the first demonstration of spectral-domain optical coherence tomography (SD-OCT) (Spectralis; Heidelberg Engineering, Heidelberg, Germany), wide-field angiography (Optos, Dunfermline, Scotland) and photography, and fundus autofluorescence with temporal progression during a period of 6 months. A 12-year-old white female presented with acute, painless vision loss with hand motions visual acuity. No larva was visible, so she was treated with oral ivermectin. Visual acuity improved to 20/80. OCT demonstrated hyporeflective spaces of the outer retina and retinal pigment epithelium, which resolved during 1-month period with improved ellipsoid layer by 6 months. Fundus autofluorescence demonstrated linear hypoautofluorescent tracks. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:682-685.].


Assuntos
Infecções Oculares Parasitárias/diagnóstico , Miíase/diagnóstico , Segmento Posterior do Olho/patologia , Epitélio Pigmentado da Retina/patologia , Animais , Criança , Infecções Oculares Parasitárias/parasitologia , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Larva , Fotografação , Segmento Posterior do Olho/parasitologia , Epitélio Pigmentado da Retina/parasitologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual
10.
Am J Ophthalmol ; 168: 183-190, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27210277

RESUMO

PURPOSE: To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. DESIGN: Modified Delphi process. METHODS: A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. RESULTS: There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. CONCLUSIONS: Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Retinianas/diagnóstico , Autoanticorpos/sangue , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Consenso , Técnica Delphi , Humanos , Síndromes Paraneoplásicas Oculares/diagnóstico , Retina/imunologia , Doenças Retinianas/imunologia
11.
Am J Ophthalmol Case Rep ; 3: 22-24, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29503901

RESUMO

PURPOSE: To report a case of retinal vasculitis associated with birdshot chorioretinitis which was responsive to topical difluprednate alone. OBSERVATIONS: Two months after initiation of topical difluprednate, fluorescein angiography demonstrated resolution of retinal vasculitis in both treated eyes. Worsening of vasculitis with attempted taper of difluprednate and subsequent control with prior dosing confirmed the response. CONCLUSIONS AND IMPORTANCE: Despite potential adverse effects of steroid-induced glaucoma and cataract formation, topical difluprednate in the treatment of retinal vasculitis and other posterior uveitides may have efficacy.

12.
BMJ Case Rep ; 20152015 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-25969485

RESUMO

We report a case of cytomegalovirus (CMV) intraocular infection in an otherwise healthy 51-year-old patient, presenting atypically as isolated intermediate uveitis without retinitis or retinal vasculitis. The patient had a confirmed CMV infection as a cause of her intraocular inflammation via PCR DNA testing of an aqueous sample. Appropriate oral antiviral therapy was initiated, and resulted in complete resolution of inflammation and improvement in visual acuity. Prophylactic therapy was instituted thereafter.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Infecções Oculares Virais/diagnóstico , Uveíte Intermediária/virologia , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções Oculares Virais/tratamento farmacológico , Feminino , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Humanos , Imunocompetência , Pessoa de Meia-Idade , Uveíte Intermediária/diagnóstico , Uveíte Intermediária/tratamento farmacológico , Valganciclovir
13.
Am J Ophthalmol ; 159(2): 334-43.e1, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25447116

RESUMO

PURPOSE: To describe the clinical outcomes of ocular syphilis. DESIGN: Retrospective chart review. METHODS: The charts of patients with ocular syphilis (regardless of human immunodeficiency virus [HIV] status) seen in a uveitis referral center between 1984 and 2014 were reviewed. RESULTS: The study included 35 patients (61 eyes). Panuveitis was the most common type of ocular inflammation (28 eyes), independent of HIV status. Thirty-three of 35 patients received systemic antibiotics with 24 patients treated with intravenous (IV) penicillin only. When compared to the HIV-positive patients, HIV-negative patients with ocular syphilis were older (P < .001), were more likely to be female (P = .004), and had poorer visual acuity at presentation (P = .01). During follow-up, the incidence rates of visual impairment were 0.29 per eye-year (EY; 95% confidence interval [CI]: 0.06/EY-0.86/EY) and 0.12/EY (95% CI: 0.01/EY-0.42/EY) among the HIV-negative and the HIV-positive patients, respectively. The incidence of blindness was 0.07/EY (95% CI: 0.009/EY-0.27/EY) and 0.06/EY (95% CI: 0.002/EY-0.35/EY) among the HIV-negative and the HIV-positive patients, respectively. Longer duration of uveitis prior to diagnosis and chorioretinitis in the macula at presentation were associated with ≥ 2 Snellen lines of visual loss (P < .01) and visual acuity loss to 20/50 or worse (P = .03) in HIV-negative patients, respectively. CONCLUSIONS: Syphilis is an uncommon cause of ocular inflammation in both HIV-negative and HIV-positive patients. Visual loss and ocular complications were common among HIV-negative patients even with systemic antibiotic treatment. Delay of diagnosis and chorioretinitis in the macula were associated with visual loss in these patients.


Assuntos
Infecções Oculares Bacterianas/diagnóstico , Pan-Uveíte/diagnóstico , Sífilis/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Feminino , Soropositividade para HIV , Humanos , Incidência , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Pan-Uveíte/tratamento farmacológico , Pan-Uveíte/epidemiologia , Penicilina G Benzatina/uso terapêutico , Estudos Retrospectivos , Sífilis/tratamento farmacológico , Sífilis/epidemiologia , Transtornos da Visão/epidemiologia , Acuidade Visual , Adulto Jovem
14.
Ophthalmology ; 121(10): 1885-91, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24953794

RESUMO

OBJECTIVE: To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory noninfectious scleritis. DESIGN: Prospective, dose-ranging, randomized, double-masked phase I/II clinical trial. PARTICIPANTS: Twelve patients with noninfectious scleritis refractory to systemic corticosteroid and ≥1 other systemic immunosuppressive agent were enrolled from January 2007 to March 2010. INTERVENTION: Subjects were randomly assigned to 500 (n = 5) or 1000 mg (n = 7) dosing arms of rituximab intravenous infusions (500 or 1000 mg), given at study days 1 and 15. Initial responders with breakthrough inflammation after study week 24 were offered treatment with an additional cycle of 2 open-label rituximab 1000 mg infusions. MAIN OUTCOME MEASURES: Primary outcomes were reduction of inflammation, as measured with a validated scleritis disease grading scale (SGS) and reduction in corticosteroid dose by ≥50%. Patients were characterized as responders to study therapy if ≥1 of these endpoints showed improvement and neither showed evidence of worsening. Secondary outcomes were improvement in visual acuity, reduction in pain, and improvement in patient and physician-reported global health assessment. RESULTS: Of 12 enrolled patients, 9 met the SGS endpoint at or before week 24, and 4 additionally were able to reduce corticosteroid dose by ≥50%. With regard to secondary outcome measures, 11 and 9 patients showed improvement in patient and physician global health scores, respectively, and 7 patients had reduction in pain. Of 9 initial responders, 7 experienced breakthrough inflammation after 24 weeks and were treated with a second cycle of rituximab infusions. Four patients had significant objective or subjective worsening within 8 weeks of receiving rituximab; this event was averted in subsequent patients by treatment with peri-infusional oral corticosteroid. No other significant adverse events were noted. No differences in efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. CONCLUSIONS: Rituximab was effective treatment for 9 of 12 enrolled patients with refractory, noninfectious scleritis at 24 weeks, although 7 required reinfusion with rituximab to maintain inflammatory control. The treatment was well-tolerated, and peri-infusional inflammatory exacerbations were managed successfully with oral corticosteroids. Further long-term studies are warranted to determine the safety and efficacy of rituximab in treating noninfectious scleritis and other ocular inflammatory diseases.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Fatores Imunológicos/administração & dosagem , Esclerite/tratamento farmacológico , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rituximab , Índice de Gravidade de Doença , Adulto Jovem
15.
Am J Ophthalmol ; 158(3): 637-43.e1, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24875002

RESUMO

PURPOSE: To describe the clinical presentation of uveitis with coincident onset of raised and indurated tattooed skin. DESIGN: Case series. METHODS: Seven consecutive patients were evaluated at a tertiary ophthalmologic facility with coincident uveitis and cutaneous tattoo induration over an 18-month period. All subjects underwent complete ophthalmic examination and a focused systemic medical evaluation including serologic testing and imaging studies. Two participants underwent biopsy of their tattoos. The patients' clinical courses and responses to treatment over a follow-up period of 1-20 months are reported (mean follow-up = 9 months). Main outcome measures included degree of intraocular inflammation, ocular complications, visual acuity, clinically observable tattooed skin changes, and biopsy results. RESULTS: Five of 7 patients had bilateral nongranulomatous anterior uveitis: 4 with chronic and 1 with recurrent disease. The remaining 2 patients had bilateral chronic granulomatous panuveitis. Biopsies of raised and indurated tattoos were performed in 2 patients and demonstrated noncaseating granulomatous inflammation surrounding tattoo ink in the dermis. The skin changes resolved in all patients, with a faster response noted in those treated with high-dose oral prednisone for intraocular inflammation. Five patients subsequently experienced recurrent flares of intraocular inflammation in conjunction with the recurrence of raised and indurated tattoos. CONCLUSIONS: These cases represent a subset of patients in whom skin tattooing may have incited an immune response leading to simultaneous inflammation of the eyes and tattooed skin.


Assuntos
Fluocinolona Acetonida/uso terapêutico , Tatuagem/efeitos adversos , Uveíte Anterior/etiologia , Adulto , Biópsia , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Prognóstico , Recidiva , Estudos Retrospectivos , Pele/efeitos dos fármacos , Pele/patologia , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológico , Acuidade Visual , Adulto Jovem
16.
Retina ; 34(8): 1666-74, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24743642

RESUMO

PURPOSE: To study the clinical features and incidence rate of ocular complications in patients with punctate inner choroidopathy. METHODS: This is a retrospective cohort study conducted in a single-center academic practice setting. Patients diagnosed with punctate inner choroidopathy at the Wilmer Eye Institute, Johns Hopkins University from 1984 to 2012 were identified. Demographics and clinical features including the presence of choroidal neovascularization (CNV) and structural complications were collected. Main outcome measures, including visual impairment and incidence rate of ocular complications, were analyzed. RESULTS: Thirty-one patients (59 eyes) were included in the study. Follow-up data were available for 24 patients (47 eyes) with a mean follow-up time of 3.4 years (range, 2 months to 8.7 years). In the affected eyes with follow-up, the incidence rate of visual impairment to 20/50 or worse was 0.06 per eye-year (EY) (95% confidence interval, 0.022/EY-0.114/EY). The incidence rate of visual loss to 20/200 or worse was 0.006/EY (95% confidence interval, 0.0001/EY-0.034/EY). Thirty-six eyes (77%) had an ultimate visual acuity of 20/40 or better. All of the 13 patients with more than ≥ 3 years of follow-up had a visual acuity of ≥ 20/40 in at least 1 eye at 3 years after presentation. Two thirds of the follow-up patients (67%) on immunomodulatory drug therapy did not have new or recurrent CNV. However, this was not a statistically significant difference. Three eyes with follow-up had recurrence of CNV for an incidence rate of 0.04/EY (95% confidence interval, 0.008/EY-0.12/EY). Two eyes developed new CNV during follow-up for an incidence rate of 0.02/EY (95% confidence interval, 0.002/EY-0.066/EY). CONCLUSION: The visual prognosis in most cases of punctate inner choroidopathy is very good. The incidence rate of new CNV and recurrent CNV was 0.02/EY and 0.04/EY, respectively.


Assuntos
Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/epidemiologia , Corioidite/complicações , Pessoas com Deficiência Visual/estatística & dados numéricos , Administração Oral , Adulto , Inibidores da Angiogênese/uso terapêutico , Corioidite/diagnóstico , Corioidite/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Coroidite Multifocal , Prevalência , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Transtornos da Visão/diagnóstico , Transtornos da Visão/epidemiologia , Acuidade Visual/fisiologia , Adulto Jovem
17.
JAMA Ophthalmol ; 132(5): 572-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24652467

RESUMO

IMPORTANCE: Orbital inflammation is a potentially blinding and disfiguring disease process that is often treated with systemic corticosteroids and immunosuppression; better treatments are needed. OBJECTIVE: To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory orbital inflammation. DESIGN, SETTING, AND PARTICIPANTS: A dose-ranging, randomized, double-masked phase 1/2 clinical trial was conducted at a tertiary referral ophthalmology clinic. Ten individuals with orbital inflammation refractory to systemic corticosteroids and at least 1 other immunosuppressive agent were enrolled from January 2007 to March 2010. INTERVENTIONS: Rituximab infusions were administered on study days 1 and 15 at doses of either 500 mg or 1000 mg. Initial responders with recurrent inflammation after week 24 were permitted reinfusion with an additional cycle of 2 open-label 1000-mg rituximab infusions. MAIN OUTCOMES AND MEASURES: The primary outcomes were reduction of inflammation measured with a validated orbital disease grading scale and corticosteroid dose reduction by at least 50%. The secondary outcomes were visual acuity, reduction in pain, and participant- and physician-reported global health assessment. RESULTS: Of 10 enrolled patients, 7 demonstrated improvement on the orbital disease grading scale at the 24-week end point with rituximab therapy. Of these 7 individuals, 4 were receiving corticosteroids at study inception and all achieved successful dose reduction. For the secondary outcome measures in the 10 participants, 7 patients and 8 patients improved in self-rated and physician global health scores, respectively, and 7 patients had reduction in pain by 25% or more at 24 weeks. Four patients who were positive responders at the week 24 end point experienced breakthrough inflammation after week 24 and received reinfusions between 24 and 48 weeks. Vision remained stable in all participants. Three of 10 patients had short-term objective or subjective worsening 2 to 8 weeks after receiving rituximab infusions, which was averted in subsequent patients with oral corticosteroids administered during the infusion and did not affect the eventual positive treatment outcome. No significant differences with regard to efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. CONCLUSIONS AND RELEVANCE: Rituximab was safe and effective in 7 of 10 patients with noninfectious orbital disease, although 4 required reinfusion with rituximab to maintain control of orbital inflammation. Substantial toxicity was not noted. Rituximab should be considered in the treatment of refractory orbital inflammation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00415506.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Pseudotumor Orbitário/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20 , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Fatores Imunológicos/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Pseudotumor Orbitário/patologia , Recidiva , Estudos Retrospectivos , Rituximab , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Acuidade Visual
18.
Ocul Immunol Inflamm ; 22(3): 236-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24564426

RESUMO

PURPOSE: To describe a case of Rosai-Dorfman-associated sclerouveitis in an HIV-infected patient. DESIGN: Case report. METHODS: A 49-year-old man with HIV had bilateral eye pain, redness, photophobia, and multiple systemic complaints. He underwent serial ocular examinations, abdomen/pelvis CT scan, and lymph node biopsy. RESULTS: Ophthalmologic evaluation revealed bilateral, nongranulomatous anterior uveitis and anterior scleritis. Biopsy of a retroperitoneal lymph node identified on CT revealed mixed inflammatory infiltrate composed of histiocytes, lymphocytes, and plasma cells involving fibroadipose tissue, indicating Rosai-Dorfman disease. CONCLUSIONS: This is the first report of sclerouveitis in Rosai-Dorfman disease. Rosai-Dorfman is typically self-limiting, occurring rarely in HIV.


Assuntos
Infecções por HIV/complicações , Histiocitose Sinusal/complicações , Esclerite/etiologia , Uveíte/etiologia , Biópsia , Histiocitose Sinusal/diagnóstico , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Esclerite/diagnóstico , Tomografia Computadorizada por Raios X , Uveíte/diagnóstico
19.
J Ophthalmic Inflamm Infect ; 4(1): 2, 2014 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-24468306

RESUMO

BACKGROUND: We describe the spectral domain optical coherence tomography (SD-OCT) findings in three patients with acute syphilitic posterior placoid chorioretinitis (ASPPC). The SD-OCT images demonstrate the pathologic changes in ASPPC with a high level of anatomic detail and may provide information about the pathophysiology of the disease. FINDINGS: We report a series of three consecutive patients seen at the Wilmer Eye Institute in 2012 and 2013 who presented with clinical and laboratory findings consistent with a diagnosis of unilateral ASPPC. Two of the three patients had HIV co-infection with good immune recovery. SD-OCT images from their initial (pre-treatment) presentation demonstrated thickening and hyperreflective nodularity of the choroid-retinal pigment epithelium (RPE) complex, with focal disruption of the overlying photoreceptor inner segment-outer segment junction in the areas corresponding to the retinal lesions seen on clinical examination. These changes improved with intravenous antibiotic treatment over a 3-month period of follow-up. CONCLUSIONS: SD-OCT imaging in ASPPC demonstrates reversible, focal thickening, and nodularity of the RPE with disruption of the overlying photoreceptor inner segment-outer segment junction. We believe that these SD-OCT images support the concept that ASPPC involves an inflammatory process at the level of the choroid-RPE with resultant structural and functional changes in the retinal photoreceptors. Further study with OCT imaging may be helpful in better understanding this disease.

20.
Ocul Immunol Inflamm ; 21(4): 257-63, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23617776

RESUMO

PURPOSE: To describe the effectiveness of periocular corticosteroid injections for the control of intraocular inflammation associated with noninfectious uveitis. METHODS: A total of 81 patients (109 eyes) who received a periocular injection were evaluated for active inflammation, visual acuity, intraocular pressure, degree of intraocular inflammation, and the presence of ocular complications, including macular edema. RESULTS: Of all eyes, 36% (95%CI: 25%, 45%) demonstrated clinical resolution of inflammation at the 1-month visit after first injection, and 48% (95%CI: 37%, 59%) at 3 months. For multiple injections, 50% (95%CI: 28%, 72%) demonstrated resolution of inflammation at 1 month after the last injection, and 41% (95%CI: 20%, 63%) resolution of inflammation at 3 months after the last injection. Of the 49 eyes that initially responded, the estimated median time to recurrence was 7.6 months. CONCLUSIONS: Approximately half of the treated eyes had resolution of intraocular inflammation at 3 months after corticosteroid injection.


Assuntos
Triancinolona Acetonida/administração & dosagem , Uveíte/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Injeções Intraoculares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Uveíte/fisiopatologia , Acuidade Visual , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA