RESUMO
The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.
Assuntos
Artrite , Mutação , Proteína Adaptadora de Sinalização NOD2 , Linhagem , Sarcoidose , Sinovite , Uveíte , Humanos , Artrite/genética , Artrite/diagnóstico , Artropatia Neurogênica/genética , Artropatia Neurogênica/diagnóstico , Doenças do Sistema Nervoso Central , Sequenciamento do Exoma , Doenças Hereditárias Autoinflamatórias , Linfedema/genética , Linfedema/diagnóstico , Proteína Adaptadora de Sinalização NOD2/genética , Sarcoidose/genética , Sarcoidose/diagnóstico , Sinovite/genética , Sinovite/diagnóstico , Uveíte/genética , Uveíte/diagnósticoRESUMO
PURPOSE: To draw attention to the higher proportion of Fuchs heterochromic iridocyclitis (FHI) cases in patients with multiple sclerosis (MS). MATERIALS AND METHODS: Retrospective study of data collected at the Center for the Diagnosis and Treatment of Uveitis. RESULTS: An analysis of the medical records of 3016 patients with uveitis (in the years 2003-2020) was performed with a focus on MS. MS-associated uveitis was diagnosed in 90 patients (3%): anterior uveitis (n = 7), intermediate uveitis (n = 23), retinal vasculitis (n = 24), and panuveitis (n = 36). A clinical examination revealed signs of FHI in the anterior segment in 11 out of 90 cases (12%). Atypical manifestations of FHI included a higher incidence of bilateral involvement (45%), retinal vasculitis (27%), and vitreous snowballs (18%). The diagnosis of FHI preceded the diagnosis of MS in 4 cases. The median latency was 10.5 (range 8-15) years. In 4 patients, the diagnosis of demyelinating disease was established within one year of the diagnosis of FHI. We recommended a neurological examination for optic neuritis (n = 1), paresthesia (n = 3), relapse of motor deficit (n = 1), and screening of etiology in cases with involvement of the posterior segment (n = 3). In the other 3 cases, the diagnosis of MS preceded the diagnosis of FHI, with a median latency of 13 (range 8-19) years. CONCLUSION: We detected clinical symptoms of FHI in 12% of uveitis cases associated with MS, more often in bilateral manifestations of intraocular inflammation. Based on our experience, we recommend an investigation of the medical history of patients with FHI for manifestations of sensitive, sensory and motor deficits, especially in bilateral cases.
Assuntos
Iridociclite , Esclerose Múltipla , Vasculite Retiniana , Uveíte , Humanos , Iridociclite/complicações , Iridociclite/diagnóstico , Estudos Retrospectivos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Vasculite Retiniana/complicaçõesRESUMO
AIM OF THE STUDY: Comparative cross-sectional study of retinal parameters in Huntington's disease and their evaluation as marker of disease progression. CLINICAL RATIONALE FOR THE STUDY: Huntington's disease (HD) is a neurodegenerative disorder with dominant motor and neuropsychiatric symptoms. Involvement of sensory functions in HD has been investigated, however studies of retinal pathology are incongruent. Effect sizes of previous findings were not published. OCT data of the subjects in previous studies have not been published. Additional examination of structural and functional parameters of retina in larger sample of patients with HD is warranted. MATERIALS AND METHODS: This is a prospective cross-sectional study that included: peripapillary retinal nerve fiber layer thickness (RNFL) and total macular volume (TMV) measured by spectral domain optical coherence tomography (OCT) of retina, Pelli-Robson Contrast Sensitivity test, Farnsworth 15 Hue Color discrimination test, ophthalmology examination and Unified Huntington's disease Rating Scale (UHDRS). Ninety-four eyes of 41 HD patients examined in total 47 visits and 82 eyes of 41 healthy controls (HC) examined in total 41 visits were included. Analyses were performed by repeated measures linear mixed effects model with age and gender as covariates. False discovery rate was corrected by Benjamini-Hochberg procedure. RESULTS: HD group included 21 males and 20 females (age 50.6±12.0 years [mean ± standard deviation], disease duration 7.1±3.6 years, CAG triplet repeats 44.1±2.4). UHDRS Total Motor Score (TMS) was 30.0±12.3 and Total Functional Capacity 8.2±3.2. Control group (HC) included 19 males and 22 females with age 48.2±10.3 years. There was no statistically significant difference between HD and HC in age. The effect of the disease was not significant in temporal segment RNFL thickness. It was significant in the mean RNFL thickness and TMV, however not passing false discovery rate adjustment and with small effect size. In the HD group, the effect of disease duration and TMS was not significant. The Contrast Sensitivity test in HD was within normal limits and the 15-hue-test in HD did not reveal any specific pathology. CONCLUSIONS: The results of our study support possible diffuse retinal changes in global RNFL layer and in macula in Huntington's disease, however, these changes are small and not suitable as a biomarker for disease progression. We found no other structural or functional changes in retina of Huntington's disease patients using RNFL layer and macular volume spectral domain OCT and Contrast Sensitivity Test and 15-hue-test. CLINICAL IMPLICATIONS: Current retinal parameters are not appropriate for monitoring HD disease progression.
Assuntos
Doença de Huntington , Tomografia de Coerência Óptica , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Doença de Huntington/patologia , Estudos Transversais , Estudos Prospectivos , Fibras Nervosas/patologia , Retina/patologia , Biomarcadores , Progressão da DoençaRESUMO
AIMS: To analyse the hallmarks of ocular manifestations of and therapeutic modalities for syphilis in the last two decades. The clinical features of syphilitic uveitis, and association with the human immunodeficiency virus (HIV) coinfection are described. METHODS: Retrospective study of 16 patients diagnosed with ocular syphilis confirmed by serological tests in the General University Hospital in Prague between the years 2004 and 2021. General characteristics of ocular and systemic manifestations and visual functions were analysed. RESULTS: An increasing incidence of syphilitic uveitis correlates with a general rise in syphilis cases. In our study, the ocular manifestation of syphilis was panuveitis (44%), posterior uveitis (31%) and anterior uveitis (25%). Posterior uveitis was found in 3 patients (19%) associated with preretinal infiltrates, that are often present in syphilitic uveitis. The worst visual outcomes were among patients with human immunodeficiency virus (HIV) coinfection and/or neurosyphilis, however the data were not significant. Optic disc edema was present in 56%, macular involvement in 37% of patients. Overall, 31% of patients in our cohort had persistent visual field defects due to impairment of their optic nerve or macula despite the final median Snellen visual acuity of 1.0. Two out of sixteen patients were treated with corticosteroids in addition to antibiotics. CONCLUSION: Posterior uveitis with preretinal infiltrates and optic disc edema should arouse suspicion of ocular syphilis. Recent data show the advantages of adjacent systemic corticosteroid treatment for severe forms of syphilitic uveitis and/or neuritis. Our observation supports this finding.
Assuntos
Coinfecção , Infecções Oculares Bacterianas , Infecções por HIV , Papiledema , Sífilis , Uveíte Posterior , Uveíte , Humanos , Sífilis/complicações , Sífilis/tratamento farmacológico , Sífilis/diagnóstico , Papiledema/complicações , Estudos Retrospectivos , Coinfecção/complicações , República Tcheca/epidemiologia , Uveíte/tratamento farmacológico , Uveíte/etiologia , Uveíte/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/epidemiologia , Uveíte Posterior/complicações , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológicoRESUMO
BACKGROUND: Acute anterior uveitis (AAU) is a relatively common extra-musculoskeletal manifestation of axial spondyloarthritis (axSpA); however, data on the prevalence of active sacroiliitis in patients with AAU are limited. METHODS: 102 patients with AAU and 39 healthy subjects (HS) underwent clinical assessment and sacroiliac joint MRI. Patients with absence of active sacroiliitis were reassessed after two years. International Spondyloarthritis Society (ASAS) classification criteria for axSpA (regardless of patient's age) and expert opinion for definitive diagnosis of axSpA were applied. RESULTS: Although chronic back pain was equally present in both groups, bone marrow edema (BME) in SIJ and BME highly suggestive of axSpA was found in 52 (51%) and in 33 (32%) patients with AAU compared with 11 (28%) and none in HS, respectively. Out of all AAU patients, 41 (40%) patients fulfilled the ASAS classification criteria for axSpA, and 29 (28%) patients were considered highly suggestive of axSpA based on clinical features. Two out of the 55 sacroiliitis-negative patients developed active sacroiliitis at the two-year follow-up. CONCLUSIONS: One-third of patients with AAU had active inflammation on SIJ MRI and clinical diagnosis of axSpA. Therefore, patients with AAU, especially those with chronic back pain, should be referred to a rheumatologist, and the examination should be repeated if a new feature of SpA appears.
RESUMO
The aim of this study was to identify RS1 pathogenic variants in Czech patients with X-linked retinoschisis (XLRS) and to describe the associated phenotypes, including natural history, in some cases. Twenty-one affected males from 17 families were included. The coding region of RS1 was directly sequenced and segregation of the identified mutations was performed in available family members. In total, 12 disease-causing variants within RS1 were identified; of these c.20del, c.275G>A, c.[375_379del; 386A>T], c.539C>A and c.575_576insT were novel, all predicted to be null alleles. The c.539C>A mutation occurred de novo. Three patients (aged 8, 11 and 19 years) were misdiagnosed as having intermediate uveitis and treated with systemic steroids. Repeat spectral domain optical coherence tomography examinations in four eyes documented the transition from cystoid macular lesions to macular atrophy in the fourth decade of life. Four individuals were treated with topical dorzolamide and in two of them, complete resolution of the cystic macular lesions bilaterally was achieved, while one patient was noncompliant. Rebound phenomenon after discontinuation of dorzolamide for 7 days was documented in one case. Misdiagnosis of XLRS for uveitis is not uncommon; therefore, identification of disease-causing variants is of considerable benefit to the affected individuals.
Assuntos
Retinosquise/genética , Adolescente , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Criança , Pré-Escolar , República Tcheca , Proteínas do Olho/genética , Frequência do Gene , Humanos , Lactente , Mutação , Linhagem , Retinosquise/tratamento farmacológico , Retinosquise/patologia , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Tiofenos/administração & dosagem , Tiofenos/uso terapêutico , Tomografia de Coerência ÓpticaRESUMO
INTRODUCTION: The EyeCOPE study characterized noninfectious intermediate posterior, or panuveitis (NIIPPU) before biologic agents were widely available. METHODS: This retrospective, observational study included adults with NIIPPU attending a routine ophthalmological visit. Data were collected from the study visit and medical records. RESULTS: Of 565 patients, 58.8% were female, and the mean age was 41.3 years; 33.8% had idiopathic uveitis and 45.8% had panuveitis. The median time from symptom onset to diagnosis and treatment was 27.0 and 30.5 days, respectively. Patients received immunosuppressants and systemic/local corticosteroids. Most patients experienced substantial decline in ocular function (mean best corrected visual acuity, 0.4 logMAR). Mean total work productivity impairment among employed patients was 31.0%. Most patients reported ocular complications (70.8%) such as vision loss and cataracts. CONCLUSIONS: Despite treatment, most patients with NIIPPU experienced a decline in ocular function and ocular complications. There is an unmet need for additional NIIPPU treatment, such as targeted monoclonal antibodies.
RESUMO
AIMS: Cases of infectious uveitis in immunodeficient patients may present with atypical clinical features because the clinical course of disease is usually affected by the compromised immune system. Therefore, it is sometimes difficult to determine the correct diagnosis. The aim of this study was to evaluate a prevalence of immunodeficient HIV-negative individuals among patients with infectious uveitis and to assess diagnostic and therapeutic approaches. METHODS: A retrospective study. RESULTS: In years 2003-2017, we diagnosed 594 patients with infectious uveitis. In 35 of them, infectious uveitis occurred on the basis of immunodeficiency (malignancy, immunosuppressive therapy etc.). The most common infectious uveitis was cytomegalovirus retinitis, followed by acute retinal necrosis, herpetic anterior uveitis, endogenous fungal endophthalmitis, toxoplasmic retinochoroiditis, progressive outer retinal necrosis and syphilis. In indicated cases, intraocular fluid examination was a valuable diagnostic tool. After initiation of treatment, improvement of BCVA was observed in 13 eyes, stabilization in 13 eyes and deterioration in 11 eyes. In some patients who experienced adverse effects of medication, the recommended doses were decreased. CONCLUSION: Our experience shows that patients with diagnoses of acute retinal necrosis or progressive outer retinal necrosis have a poor visual prognosis. The occurrence of cytomegalovirus retinitis signifies a very unfavorable survival prognosis in patients who underwent hematopoietic stem cell transplantation; the patients in our study died within 1 year from cytomegalovirus retinitis diagnosis.
Assuntos
Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/etiologia , Infecções Oculares Virais/terapia , Hospedeiro Imunocomprometido , Uveíte/diagnóstico , Uveíte/etiologia , Uveíte/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , República Tcheca , Infecções Oculares Virais/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Uveíte/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Vitreoretinal lymphomas belong to the family of central nervous system (CNS) lymphomas. The optimal approach for the treatment of isolated primary vitreoretinal lymphoma is unclear because of the lack of large comparative clinical series. Combination of intravitreal and systemic chemotherapy is recommended in many reports. The aim of our retrospective study was to compare the survival rate and prognosis of patients with vitreoretinal lymphoma with and without CNS involvement. METHODS: Twenty patients with vitreoretinal lymphomas were observed between the years 2004and2016, 10 patients with primary vitreoretinal lymphoma and 10 with primary CNS lymphoma. To compare survival rates, we included 53 patients diagnosed with primary CNS lymphoma without vitreoretinal involvement between the years 2002and2011 from our haemato-oncology department. RESULTS: The 5-year survival rate was estimated 71% in patients with vitreoretinal lymphoma in our observation. Significantly longer 5-year overall survival (PË0.01) was observed in patients with vitreoretinal lymphoma compared with patients with primary CNS lymphoma without vitreoretinal involvement. Progression-free survival was almost equal in both groups of patients with primary vitreoretinal lymphoma and primary CNS lymphoma (P=0.363). The relapse of lymphoma was frequent (50%-60%) with the median time to first relapse of 31 months. Combined treatment (local and systemic) in patients without CNS involvement significantly prolonged progression-free survival in our study (PË0.05). CONCLUSION: Combined treatment of primary vitreoretinal lymphoma significantly delays the relapse of lymphoma compared with local therapy alone. Intraocular involvement brings significant positive prognostic value when overall survival is compared.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Intraocular/tratamento farmacológico , Recidiva Local de Neoplasia/fisiopatologia , Neoplasias da Retina/tratamento farmacológico , Corpo Vítreo/efeitos dos fármacos , Idoso , Intervalo Livre de Doença , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/mortalidade , Neoplasias Oculares/fisiopatologia , Feminino , Citometria de Fluxo , Humanos , Linfoma Intraocular/mortalidade , Linfoma Intraocular/fisiopatologia , Injeções Intravítreas , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Procarbazina/administração & dosagem , Prognóstico , Neoplasias da Retina/mortalidade , Neoplasias da Retina/fisiopatologia , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagem , Acuidade Visual/fisiologia , Corpo Vítreo/patologiaRESUMO
PURPOSE: To present a possible coincidence of cytomegalovirus retinitis and intraocular lymphoma in a patient with systemic non-Hodgkin's lymphoma. CASE PRESENTATION: A 47-year-old woman presented with decreased visual acuity associated with white retinal lesions in both eyes. A history of pneumonia of unknown aetiology closely preceded the deterioration of vision. Five years previously the patient was diagnosed with follicular non-Hodgkin's lymphoma. She was treated with a chemotherapy regimen comprised of cyclophosphamide, adriamycin, vincristin, and prednisone with later addition of the anti-CD20 antibody rituximab. She experienced a relapse 19 months later with involvement of the retroperitoneal lymph nodes, and commenced treatment with rituximab and 90Y-ibritumomab tiuxetan. A second relapse occurred 22 months after radioimmunotherapy and was treated with a combination of fludarabine, cyclophosphamide, and mitoxantrone followed by rituximab. The patient experienced no further relapses until the current presentation (April, 2010).Pars plana vitrectomy with vitreous fluid analysis was performed in the right eye. PCR testing confirmed the presence of cytomegalovirus in the vitreous. Atypical lymphoid elements, highly suspicious of malignancy were also found on cytologic examination. Intravenous foscarnet was administered continually for three weeks, followed by oral valganciclovir given in a dose of 900 mg twice per day. In addition, the rituximab therapy continued at three monthly intervals. Nevertheless, cessation of foscarnet therapy was followed by a recurrence of retinitis on three separate occasions during a 3-month period instigating its reinduction to the treatment regime after each recurrence. CONCLUSIONS: Cytomegalovirus retinitis is an opportunistic infection found in AIDS patients as well as in bone marrow and solid organ transplant recipients being treated with systemic immunosuppressive drugs. This case presents a less common incidence of cytomegalovirus retinitis occurring in a patient with non-Hodgkin's lymphoma. We demonstrated a possible coexistence of cytomegalovirus retinitis and intraocular lymphoma in this particular patient. The final diagnosis was based on clinical manifestations together with the course of uveitis and its response to treatment alongside the results of vitreous fluid analysis. This report highlights the importance of intraocular fluid examination in cases with nonspecific clinical manifestations. Such an examination allows for the detection of simultaneously ongoing ocular diseases of differing aetiologies and enables the prompt initiation of effective treatment.
Assuntos
Retinite por Citomegalovirus/complicações , Neoplasias Oculares/complicações , Linfoma não Hodgkin/complicações , Anticorpos Monoclonais Murinos/administração & dosagem , Antineoplásicos/administração & dosagem , Antivirais/administração & dosagem , Citomegalovirus/isolamento & purificação , Retinite por Citomegalovirus/terapia , Neoplasias Oculares/terapia , Feminino , Foscarnet/administração & dosagem , Ganciclovir/administração & dosagem , Ganciclovir/análogos & derivados , Humanos , Linfoma não Hodgkin/terapia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Rituximab , Valganciclovir , VitrectomiaRESUMO
PURPOSE: To assess the diagnostic yield of vitreous fluid analysis and the therapeutic effect of pars plana vitrectomy in patients with suspected intraocular inflammation. METHODS: During 2004-2008, pars plana vitrectomy was performed in 89 patients (101 eyes) out of 1233 patients with uveitis. Vitreous specimens were analyzed by cytologic and histopathologic examination, microbiologic culture, polymerase chain reaction, antibody determination, and flow cytometry. Vitrectomy was performed in 85 eyes for both diagnostic and therapeutic purposes; the remaining 16 eyes underwent only diagnostic pars plana vitrectomy. Preoperative and postoperative best-corrected Snellen visual acuity was compared. RESULTS: Preoperative diagnoses were infection in 40 patients, malignant masquerade syndrome in 10 patients, and idiopathic uveitis in 39 patients. Vitreous analysis contributed to the determination of diagnosis in 54 patients (61%). Final diagnoses were infection in 42 patients, malignant masquerade syndrome in 6 patients, benign masquerade syndrome in 16 patients, and idiopathic uveitis in 25 patients. Vitreous fluid collected from each eye underwent approximately 2.2 (range 1-6) laboratory tests. Therapeutic reasons for vitrectomy were the treatment of complications of uveitis in 42 eyes and/or intravitreal application of anti-infectious or cytostatic drugs in 49 eyes. Overall, the visual acuity improved in 45% of eyes, remained unchanged in 45% of eyes, and decreased in 10% of eyes in 3 months after surgery. CONCLUSIONS: Pars plana vitrectomy with carefully selected testing is a valuable tool for assessment of diagnosis in a large proportion of patients with uveitis. Moreover, the therapeutic effect of vitrectomy can improve the visual outcomes in these patients.