RESUMO
Primary cilia are sensory organelles that extend from the cellular membrane and are found in a wide range of cell types. Cilia possess a plethora of vital components that enable the detection and transmission of several signaling pathways, including Wnt and Shh. In turn, the regulation of ciliogenesis and cilium length is influenced by various factors, including autophagy, organization of the actin cytoskeleton, and signaling inside the cilium. Irregularities in the development, maintenance, and function of this cellular component lead to a range of clinical manifestations known as ciliopathies. The majority of people with ciliopathies have a high prevalence of retinal degeneration. The most common theory is that retinal degeneration is primarily caused by functional and developmental problems within retinal photoreceptors. The contribution of other ciliated retinal cell types to retinal degeneration has not been explored to date. In this review, we examine the occurrence of primary cilia in various retinal cell types and their significance in pathology. Additionally, we explore potential therapeutic approaches targeting ciliopathies. By engaging in this endeavor, we present new ideas that elucidate innovative concepts for the future investigation and treatment of retinal ciliopathies.
Assuntos
Cílios , Ciliopatias , Doenças Neurodegenerativas , Retina , Cílios/metabolismo , Cílios/patologia , Humanos , Ciliopatias/genética , Ciliopatias/metabolismo , Ciliopatias/patologia , Animais , Retina/metabolismo , Retina/patologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/patologia , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/etiologia , Transdução de SinaisRESUMO
Aland island eye disease (AIED), an incomplete form of X-linked congenital stationary night blindness (CSNB2A), and X-linked cone-rod dystrophy type 3 (CORDX3) display many overlapping clinical findings. They result from mutations in the CACNA1F gene encoding the α1F subunit of the Cav1.4 channel, which plays a key role in neurotransmission from rod and cone photoreceptors to bipolar cells. Case report: A 57-year-old Caucasian man who had suffered since his early childhood from nystagmus, nyctalopia, low visual acuity and high myopia in both eyes (OU) presented to expand the diagnostic process, because similar symptoms had occurred in his 2-month-old grandson. Additionally, the patient was diagnosed with protanomalous color vision deficiency, diffuse thinning, and moderate hypopigmentation of the retina. Optical coherence tomography of the macula revealed retinoschisis in the right eye and foveal hypoplasia in the left eye. Dark-adapted (DA) 3.0 flash full-field electroretinography (ffERG) amplitudes of a-waves were attenuated, and the amplitudes of b-waves were abolished, which resulted in a negative pattern of the ERG. Moreover, the light-adapted 3.0 and 3.0 flicker ffERG as well as the DA 0.01 ffERG were consistent with severely reduced responses OU. Genetic testing revealed a hemizygous form of a stop-gained mutation (c.4051C>T) in exon 35 of the CACNA1F gene. This pathogenic variant has so far been described in combination with a phenotype corresponding to CSNB2A and CORDX3. This report contributes to expanding the knowledge of the clinical spectrum of CACNA1F-related disease. Wide variability and the overlapping clinical manifestations observed within AIED and its allelic disorders may not be explained solely by the consequences of different mutations on proteins. The lack of distinct genotype-phenotype correlations indicates the presence of additional, not yet identified, disease-modifying factors.
Assuntos
Albinismo Ocular , Oftalmopatias Hereditárias , Doenças Genéticas Ligadas ao Cromossomo X , Miopia , Cegueira Noturna , Doenças Retinianas , Retinose Pigmentar , Retinosquise , Masculino , Humanos , Pré-Escolar , Lactente , Pessoa de Meia-Idade , Canais de Cálcio Tipo L/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/genética , Retina/metabolismo , MutaçãoRESUMO
BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by microcephaly, white matter lesions, numerous intracranial calcifications, chilblain skin lesions and high levels of interferon-α (IFN-α) in the cerebrospinal fluid (CSF). However, ocular involvement is reported significantly less frequently. CASE PRESENTATION: We present a case of a neonate with hypotrophy, microcephaly, frostbite-like skin lesions, thrombocytopenia, elevated liver enzymes and hepatosplenomegaly. Magnetic resonance imaging (MRI) of the brain showed multiple foci of calcification, white matter changes, cerebral atrophy, and atrophic dilatation of the ventricular system. The inflammatory parameters were not elevated, and the infectious etiology was excluded. Instead, elevated levels of IFN-α in the serum were detected. Based on the related clinical symptoms, imaging and test findings, the diagnosis of AGS was suspected. Genetic testing revealed two pathogenic mutations, c.490C>T and c.222del (novel mutation), in the three prime repair exonuclease 1 (TREX1) gene, confirming AGS type 1 (AGS1). An ophthalmologic examination of the child at 10 months of age revealed an impaired pupillary response to light, a corneal haze with Haab lines in the right eye (RE), pale optic nerve discs and neuropathy in both eyes (OU). The intraocular pressure (IOP) was 51 mmHg in the RE and 49 in the left eye (LE). The flash visual evoked potential (FVEP) showed prolonged P2 latencies of up to 125% in the LE and reduced amplitudes of up to approximately 10% OU. This girl was diagnosed with congenital glaucoma, and it was managed with a trabeculectomy with a basal iridectomy of OU, resulting in a reduction and stabilization in the IOP to 12 mmHg in the RE and 10 mmHg in the LE without any hypotensive eyedrops. CONCLUSIONS: We present the clinical characteristics, electrophysiological and imaging findings, as well as the genetic test results of a patient with AGS1. Our case contributes to the extended ophthalmic involvement of the pathogenic c.490C>T and c.222del mutations in TREX1.
RESUMO
Background: Noonan syndrome (NS) represents a fairly common genetic disorder with a highly variable phenotype. Its features include inherited heart defects, characteristic facial features, short stature, and mild retardation of motor skills. Case presentation: A 16-year-old Caucasian girl with NS reported visual deterioration, photophobia, and pain in the right eye (RE). The initial best-corrected visual acuity (BCVA) was 0.3 in the RE. An examination demonstrated conjunctival and ciliary body hyperemia, keratic precipitates, and flare in the anterior chamber. In addition, post-hemorrhagic floaters, tortuous vessels, and an epiretinal membrane in the RE were present. Diagnosis of unilateral anterior uveitis was made, and this resolved after the use of topical steroids and cycloplegic drops. Due to the presence of retinal telangiectasias and extraocular exudates (consistent with Coats' disease (CD) stage 2A) in the RE, laser therapy was performed. The patient remains under constant follow-up, and after one year, the BCVA in the RE was 0.7. Conclusions: Here, we report the clinical characteristics, genetic findings, and retinal imaging results of a patient with NS. To our knowledge, this is, to date, the first report of an association of NS with a PTPN11 mutation with anterior uveitis and CD.
RESUMO
PURPOSE: The aim of this study was to evaluate changes in the thickness of the peripapillary retinal nerve fiber layer (pRNFL) in children with a diagnosis of juvenile idiopathic arthritis (JIA) who were positive for human leukocyte antigen (HLA)-B27, treated for the first episode of unilateral acute anterior uveitis (AAU). MATERIALS AND METHODS: This retrospective study included 41 children (aged 5 to 14 years; mean age 8.32 ± 2.4 years) with HLA-B27 positivity and unilateral JIA-AAU, and 40 healthy children. Optical coherence tomography (OCT) imaging was performed during active inflammation and subsequent noninflammatory phases (6 months after the resolution of inflammatory symptoms in the anterior segment of the eye). RESULTS: There was a marked difference in mean pRNFL thickness between eyes with AU in the active phase, unaffected fellow eyes and the control group (110.22 ± 5.95 µm, 102.39 ± 4.39 µm and 95.83 ± 8.84 µm, respectively; p < 0.001). The thickness of pRNFL in eyes with AU in the active phase in all sectors was greater compared to unaffected fellow eyes (p < 0.001) and normal eyes (p < 0.001). In addition, it was demonstrated that pRNFL thickness was significantly increased in the superior and temporal sectors in the unaffected fellow eyes compared to the control group (128.73 ± 13.16 µm vs. 121.48 ± 13.35 µm and 71.37 ± 4.02 µm vs. 64.98 ± 9.12 µm, respectively). Even during the inactive phase, eyes with AU, compared to the healthy control group, had significantly greater pRNFL thickness in the inferior sector (129.78 ± 11.98 µm vs. 122.3 ± 14.59 µm; p = 0.018), along with the temporal sector (70.88 ± 5.48 µm vs. 64.98 ± 9.12 µm; p = 0.001). CONCLUSIONS: An increase in pRNFL thickness in children with unilateral JIA-AAU who were positive for HLA-B27 antigen can be observed in both eyes compared to healthy controls, and this change may persist even after the inflammatory symptoms have resolved. Measurements of pRNFL thickness resulting from JIA-AU-associated glaucoma should be performed during quiescent periods to avoid subclinical changes in pRNFL thickness caused by inflammation. However, when reviewing the results, it should be noted that changes in pRNFL parameters may be present despite evidence of a resolution of inflammation.
RESUMO
The pattern dystrophies (PDs) are a group of primarily autosomal dominant inherited macular diseases that cause the deposition of lipofuscin in retinal pigment epithelium (RPE) and may lead to significant vision loss in later life. Patients can develop choroidal neovascularization (CNV) and/ or geographic atrophy (GA) and for this reason they are often misdiagnosed as age-related macular degeneration (AMD). We presented a case of a 66-year-old patient complaining of vision loss in the right eye (RE) for 8 months. At the initial examination, his best corrected visual acuity (BCVA) was 0.6 in the RE. Optical coherence tomography angiography (OCTA), fundus autofluorescence (FAF) and fundus fluorescein angiography (FFA) allowed to diagnose butterfly-shaped PD in both eyes with choroidal neovascularization (CNV) in the RE. The patient was treated with three intravitreal anti-vascular epithelial growth factor (anti-VEGF, ranibizumab) injections during six weeks intervals, which improved and stabilized the BCVA of the RE to 0.7 during the over two-year observation period. Our report contributes to the still limited data regarding CNV associated with butterfly-shaped PDs and the results of treatment with ranibizumab. Abbreviations: AMD = age-related macular degeneration, anti-VEGF = anti-vascular epithelial growth factor, AOFVD = adult-onset foveomacular vitelliform dystrophy, BCVA = best corrected visual acuity, CNV = choroidal neovascularization, FAF = fundus autofluorescence, FFA = fundus fluorescein angiography, GA = geographic atrophy, LE = left eye, MIDD = maternally inherited diabetes and deafness, OCT = optical coherence tomography, OCTA = optical coherence tomography angiography, OU = oculus uterque, both eyes, PD = pattern dystrophy, PDSFF = pattern dystrophy simulating fundus flavimaculatus, PDT = photodynamic therapy, PRPH2 = peripherine-2, RE = right eye, RPE = retinal pigment epithelium, VA = visual acuity.
Assuntos
Neovascularização de Coroide , Anormalidades do Olho , Atrofia Geográfica , Distrofia Macular Viteliforme , Adulto , Humanos , Idoso , Ranibizumab , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Distrofia Macular Viteliforme/complicações , Distrofia Macular Viteliforme/diagnóstico , Distrofia Macular Viteliforme/tratamento farmacológico , Tomografia de Coerência Óptica , Angiofluoresceinografia , Anormalidades do Olho/complicações , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Injeções Intravítreas , Inibidores da Angiogênese/uso terapêuticoRESUMO
A 60-year-old white woman presented to the emergency department with painless decrease of visual acuity in the left eye (LE). The diagnosis of a non-arteritic anterior ischemic optic neuropathy in the LE was established based on the clinical picture and the results of static perimetry, fluorescein angiography, visual evoked potential, and magnetic resonance imaging (MRI) of the brain and orbit. Six months later, the patient reported visual impairment in the right eye (RE). Best corrected visual acuity (BCVA) in the RE was 5/10. Gadolinium-enhanced MRI showing inflammation of both optic nerves and the optic chiasm in correlation with positivity for immunglobulin G antibody against aquaporin-4 led to the diagnosis of late-onset neuromyelitis optica spectrum disorder. High-dose intravenous methylprednisolone therapy followed by oral tapering was administered and oral azathioprine was started to reduce the risk of further relapse. At discharge, BCVA was 5/5 in the RE. The patient remains under the care of neurology and ophthalmology clinics, with no recurrences for two years. The possibility of neuromyelitis optica spectrum disorder with optic neuritis in older patients is important in the differential diagnosis of ischemic optic neuropathy.
Assuntos
Neuromielite Óptica , Neurite Óptica , Neuropatia Óptica Isquêmica , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/terapia , Neuropatia Óptica Isquêmica/diagnóstico , Potenciais Evocados Visuais , Neurite Óptica/diagnóstico , Aquaporina 4RESUMO
Background: Cone-rod dystrophies (CRDs) are a heterogeneous group of inherited retinal diseases (IRDs) characterized by cone photoreceptor loss, that is followed by subsequent rod photoreceptor impairment. Case presentation: A 49-year-old man complaining of diminution of vision in both eyes (OU) was referred to our outpatient clinic. He reported visual loss for 5 years, but it was most progressive during the last few months. The best-corrected visual acuity (BCVA) at presentation was 0.4 in the right eye (RE) and 1.0 in the left eye (LE). Fundus fluorescein angiography (FFA) revealed granular hyperfluorescence in the macula and concomitant areas of capillary atrophy. Flash full-field electroretinography (ffERG) showed lowering of a and b waves as well as prolonged peak time in light-adapted conditions. However, outcomes of dark-adapted ERGs were within normal limits. Based on the constellation of clinical, angiographic, and electrophysiological tests findings, a diagnosis of IRD was suspected. Genetic testing showed a homozygous, pathogenic c.783G>A mutation in the cadherin-related family member 1 (CDHR1) gene, which confirmed CRD type 15 (CRD15). Conclusions: We demonstrate the clinical characteristics, retinal imaging outcomes, and genetic test results of a patient with CRD15. Our case contributes to expanding our knowledge of the clinical involvement of the pathogenic mutation c.783G>A in CDHR1 variants.
Assuntos
Distrofias de Cones e Bastonetes , Masculino , Humanos , Pessoa de Meia-Idade , Distrofias de Cones e Bastonetes/genética , Distrofias de Cones e Bastonetes/patologia , Tomografia de Coerência Óptica , Retina , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Mutação , Testes Genéticos , Proteínas Relacionadas a Caderinas , Proteínas do Tecido Nervoso/genéticaRESUMO
Background: Mowat-Wilson syndrome (MWS) is extremely rare multisystemic autosomal dominant disorder caused by mutations in the Zinc Finger E-Box Binding Homeobox 2 (ZEB2) gene. Ocular pathologies are one of the symptoms that appear in the clinical picture of MWS individuals, but not many have been described so far. Pathologies such as optic nerve or retinal epithelium atrophy, iris or optic disc coloboma as well as congenital cataracts have been most frequently described until now. Therefore, we would like to report the first case of bilateral developmental cataract in a 9-year-old girl with MWS who underwent successful cataract surgery with intraocular lens implantation. Case Presentation: A 9-year-old girl, diagnosed with p.Gln694Ter mutation in ZEB2 gene and suspicion of MWS was referred to the Children's Outpatient Ophthalmology Clinic for ophthalmological evaluation. Her previous assessments revealed abnormalities of the optic nerve discs. The patient was diagnosed with atrophy of the optic nerves, convergent strabismus, and with-the-rule astigmatism. One year later, during the follow-up visit, the patient was presented with decreased visual acuity (VA), developmental total cataract in the right eye and a developmental partial cataract in the left eye. This resulted in decreased VA confirmed by deteriorated responses in visual evoked potential (VEP) test. The girl underwent a two-stage procedure of cataract removal, first of one eye and then of the other eye with artificial lens implants. In the 2 years following the operation, no complications were observed and, most remarkably, VA improved significantly. Conclusions: The ZEB2 gene is primarily responsible for encoding the Smad interaction protein 1 (SIP1), which is involved in the proper development of various eye components. When mutated, it results in multilevel abnormalities, also in the proper lens formation, that prevent the child from normal vision development. This typically results in the formation of congenital cataracts in children with MWS syndrome, however, our case shows that it also leads to the formation of developmental cataracts. This is presumably due to the effect of the lack of SIP1 on other genes, altering their downstream expression and is a novel insight into the importance of the SIP1 in the occurrence of ocular pathologies. To the best of our knowledge, this is the first case of bilateral developmental cataract in the context of MWS. Moreover, a novel mutation (p.Gln694Ter) in the ZEB2 gene was found corresponding to this syndrome entity. This report allows us to gain a more comprehensive insight into the genetic spectrum and the corresponding phenotypic features in MWS syndrome patients.
Assuntos
Catarata , Proteínas Repressoras , Humanos , Criança , Feminino , Proteínas de Homeodomínio/genética , Potenciais Evocados Visuais , Catarata/complicações , Catarata/genética , Mutação/genética , Atrofia , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genéticaRESUMO
We report a case of a 25-year-old woman with sudden and painless diminution in vision and central scotoma in her left eye (LE). She was a smoker and had been taking combined oral contraceptive (COC) pills for 1 year. On admission, the best-corrected visual acuity (BCVA) was 1,5/50 in the LE. Posterior segment examination revealed optic disc edema with flame-shaped retinal hemorrhages, mildly tortuous and dilated retinal veins. Moreover, retinal edema in the peripapillary and perimacular region, foci of hemorrhages and Roth's spots in the posterior pole, as well as pale superior papillomacular bundle were observed. Fundus fluorescein angiography (FFA) confirmed the delayed flow of contrast through the cilioretinal artery in the LE. The clinical picture suggested left central retinal vein (CRVO) with cilioretinal artery occlusion (CLRAO). All laboratory and imaging tests were normal except for homozygous methylenetetrahydrofolate reductase (MTHFR) gene mutation (A1298C genotypes). However, serum homocysteine (Hcy) level was normal. Low molecular weight heparin (LMWH) treatment was administered. Retinal lesions, as well as BCVA improved, but central scotoma remained. Abbreviations: aPTT = activated partial thromboplastin time, BCVA = best-corrected visual acuity, CBC = complete blood count, CLRAO = cilioretinal artery occlusion, COC = combined oral contraceptive, CRA = central retinal artery, CRP = serum C-reactive protein, CRVO = central retinal vein occlusion, CT = computed tomography, CTA = computed tomography angiography, ECG = electrocardiography, ESR = erythrocyte sedimentation rate, FERG = flash electroretinogram, FFA = fundus fluorescein angiography, GCA = ganglion cell analysis, GCL = ganglion cell layer, Hcy = homocysteine, ICGA = indocyanine green angiography, INR = international normalized ratio, IOP = intraocular pressure, IPL = inner plexiform layer, LE = left eye, LMWH = low molecular weight heparin, mfERG = multifocal electroretinogram, MTHFR = methylenetetrahydrofolate reductase, OCT = optical coherence tomography, RE = right eye, VF = visual field.
Assuntos
Oclusão da Artéria Retiniana , Veia Retiniana , Adulto , Artérias Ciliares , Anticoncepcionais Orais Combinados , Feminino , Heparina de Baixo Peso Molecular , Homocisteína , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2) , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/patologia , Oclusão da Artéria Retiniana/terapia , Veia Retiniana/patologia , EscotomaRESUMO
PURPOSE: Patients taking a medicinal product in a homecare setting typically use a medical device to facilitate the injection process. Reductions in wireless connectivity costs, combined with the rapid adoption of smartphones with connectivity to cloud-based services, are enabling these drug delivery devices to now be connected to a digital ecosystem as connected combined products (CCPs). The purposes of this article are to identify the challenges in developing and releasing these products when they straddle different regulatory frameworks and standards and to highlight gaps in the European Union regulations. METHODS: Industry subject matter experts from pharmaceutical, medical device, and consultancy companies, who are members of the Medtech & Pharma Platform Association, formed 4 working groups to address current best practice for developing and releasing CCPs and the different relevant regulatory frameworks. The 4 areas studied were clinical and regulatory, usability and human factors engineering, development and life cycle management, and cybersecurity. FINDINGS: Development teams require new skills to create innovative products that have a good safety profile and are simple to use, such as design thinking to understand user needs and systems engineering to manage complexity and ensure interoperability. Risk management process should integrate cybersecurity, data privacy, and data integrity, whereas design control processes should enable asynchronous development cycles for hardware and software components. Regulatory frameworks exist for individual components within the CCP. However, for a complex product, regulatory guidance is needed when combining components with different risk and safety profiles and to ensure that the responsibilities and liabilities of companies contributing components are clear. The efficient management of software changes and product updates, as well as dealing with end-of-life hardware and backward compatibility to older software versions, needs agile approaches when it comes to regulatory updates. IMPLICATIONS: The regulatory uncertainties and development processes outlined in this article need to be addressed. We call for joint discussions among the various stakeholders in the fields of medicinal products, medical devices, and in vitro diagnostics, as well as standalone software, data protection, and cybersecurity experts, together with regulators and lawmakers in the European Union to meet in focused discussion groups with the aim of devising pragmatic solutions and regulations for the benefit of the sector and hence the patients it serves.
Assuntos
Ecossistema , Humanos , Preparações FarmacêuticasRESUMO
Background and Objectives: The aim of the study is to assess macular ganglion cell and inner plexiform layer (mGCIPL) thickness in deprivational amblyopic eyes (AE), fellow non-amblyopic eyes (FE) and normal eyes (NE) using spectral. domain optical coherence tomography (SD-OCT). Materials and Methods: Twenty two children (64% boys) who underwent surgical removal of unilateral congenital or developmental cataracts and exhibited visual impairment despite postoperative visual rehabilitation were included in the study. Cataract surgery was performed in patients aged 55.82 ± 35.85 months (range 6 to 114 months). The mean age of the study group was 9.73 ± 2.85 years (range 5 to 15 years). The comparison group consisted of 22 healthy age- and gender-matched children. The best corrected visual acuity (BCVA) after surgery was: 0.75 ± 0.27 (range 0.3 to 1.3) in AE, 0.1 ± 0.13 (range 0 to 0.5) in FE and 0.04 ± 0.07 (range 0 to 0.2) in NE. OCT scans were performed in all patients and subsequently corrected for axial length related magnification errors. Results: The average thickness of mGCIPL was 70.6 ± 11.28 µm in AE; 77.50 ± 6.72 µm in FE and 81.73 ± 5.18 µm in NE. We found that mGCIPL was statistically significantly thinner in deprivation AE compared to FE (p = 0.038) and NE (p = 0.0005). The minimum thickness of mGCIPL was respectively: 62.68 ± 13.2 µm, 70.3 ± 7.61 µm, and 74.5 ± 5.47, and also differed between AE and FE (p = 0.023) and AE and NE (p = 0.0004). Also, measurements in the inferior, inferotemporal, and superotemporal sectors showed thinning of mGCIPL in AE compared to NE. Conclusions: This analysis may suggest that deprivational amblyopia caused by unilateral congenital or developmental cataract in children may be associated with mGCIPL thinning.
Assuntos
Ambliopia , Catarata , Masculino , Humanos , Criança , Pré-Escolar , Adolescente , Feminino , Ambliopia/complicações , Células Ganglionares da Retina , Acuidade Visual , Fibras Nervosas , Catarata/complicações , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: Long-term use of topical, especially benzalkonium chloride (BAC)-preserved, antiglaucoma medications can cause a negative impact on the ocular surface. The aim of the study was to assess the effect of topical carbonic anhydrase inhibitors (CAIs) on selected oxidative stress biomarkers in the tear film. METHODS: The patients were divided into four sex-matched groups: group C (n = 25) - control group - subjects who did not use topical antiglaucoma medications, group DL (n = 14) - patients using preservative-free dorzolamide, group DL + BAC (n = 16) - patients using topical BAC-preserved dorzolamide, group BL + BAC (n = 17) - patients using BAC-preserved brinzolamide. Subjects in all the study groups have been using the eye drops two times daily for 6-12 months. The oxidative stress biomarkers in the tear film samples were measured: total protein (TP) concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl (-SH) groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response (TAR), and Oxidative Stress Index (OSI). RESULTS: The advanced oxidation protein products content, Total Oxidant Status as well as superoxide dismutase and catalase activities in the group DL + BAC and BL + BAC were higher in comparison with the group C. The total sulfhydryl groups content was lower in the group DL + BAC and BL + BAC when compared to group C. Oxidative Stress Index was higher in the groups DL + BAC and BL + BAC in comparison with the groups DL and C. CONCLUSIONS: Use of topical benzalkonium chloride-preserved carbonic anhydrase inhibitors increases oxidative stress in the tear film.
Assuntos
Compostos de Benzalcônio , Inibidores da Anidrase Carbônica , Compostos de Benzalcônio/farmacologia , Biomarcadores , Humanos , Soluções Oftálmicas , Estresse Oxidativo , Sulfonamidas , Tiazinas , TiofenosRESUMO
Choroidal neovascularization (CNV) is a very rare but sight-threatening complication of ocular syphilis. We reported the case of a 51-year-old woman who presented with a 2-week history of visual loss in the right eye (RE). Fundus examination demonstrated vitritis and the optic disc margin blurring. Fundus fluorescein angiography (FFA) showed the presence of optic nerve edema, macular edema, and diffused impairment of the blood-retinal barrier with leakage areas, which led to the diagnosis of bilateral neuroretinitis. Optical coherence tomography (OCT) of the right macula evidenced irregularities of the retinal pigment epithelium (RPE), subretinal fluid and hyperreflective material. Besides, workup indicated positive serology for syphilis and the patient received combined treatment of ceftriaxone, systemic and topical steroids as well as cycloplegic medications. The woman did not consent to lumbar puncture or intravitreal anti-vascular epithelial growth factor (anti-VEGF) injection, therefore the prognosis for improvement of visual acuity is poor. Abbreviations: anti-VEGF = anti-vascular epithelial growth factor, AMD = age related macular degeneration, BCVA = best corrected visual acuity, CNS = central nervous system, CNV = choroidal neovascularization, CSF = cerebrospinal fluid, FFA = fundus fluorescein angiography, FTA-ABS = fluorescent treponemal antibody absorption, HIV = human immunodeficiency virus, iCNV = inflammatory CNV, IOP = intraocular pressure, LE = left eye, MRI = magnetic resonance imaging, OCT = optical coherence tomography, OCTA = optical coherence tomography angiography, RE = right eye, RPE = retinal pigment epithelium, RPR = rapid plasma regain, TP-PA = Treponema pallidum particle agglutination, VDRL = Venereal Disease Research Laboratory.
Assuntos
Neovascularização de Coroide , Sífilis , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Pessoa de Meia-Idade , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio VascularRESUMO
The original version of the article can be found at: https://doi.org/10.13075/mp.5893.01037.
RESUMO
BACKGROUND: Although nasolacrimal duct probing is the standard treatment for congenital nasolacrimal duct obstruction (CNLDO) among children, the optimal timing of this procedure has been a topic of debate. The aim of the study was to analyze the clinical efficacy of nasolacrimal duct probing among patients with CNLDO symptoms at various ages. METHODS: An 8-year retrospective study involved 2434 patients (3009 eyes), who underwent nasolacrimal duct probing conducted under topical anesthesia in the operating theatre. The study group consisted of 1148 girls (47.2%) and 1286 boys (52.8%) from 2 weeks to 41 months (average age was 8 ± 5.6 months). The participants were divided into nine age groups: 0-2 months, 3-6 months, 7-9 months, 10-12 months, 13-15 months, 16-18 months, 19-21 months, 22-24 months and over 24 months. RESULTS: Bilateral obstruction was present among 575 (23.6%) children and was associated with a higher percentage of unsuccessful procedures compared to patients with unilateral obstruction (16.9% vs 10.2%, p < 0.001 Chi-square test). The success rate of the initial probing was 87.2% for all children and it was shown that it decreased with age. In the above age groups, it was 87.9%; 91.4%; 89.6%; 86%; 76.3%; 71.3%; 70.3%; 70.2%; 65.4%, respectively. CONCLUSIONS: Probing is a safe and effective procedure. However, age at the time of the initial intervention and bilateral surgery constitute significant risk factors for failed probing. Probing between 7 and 9 months appears to be reasonable treatment strategy for children without recurrent infections. Early surgical intervention may be considered for patients with additional signs.
Assuntos
Dacriocistorinostomia , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Obstrução dos Ductos Lacrimais/terapia , Masculino , Ducto Nasolacrimal/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Isothiazolinones are preservatives which are present in cosmetics, household chemicals and many other industrial products. Initially, a mixture of methylchloroisothiazolinone and methylisothiazolinone (MCI/MI - Kathon CG) was used, and then, from the beginning of the 21st century, only methylisothiazolinone. Due to a significant increase in the number of contact dermatitis caused by allergy to this compound, it was withdrawn from leave-on cosmetics, and its concentration in rinse-off cosmetics was reduced. The aim of the study was to analyze the incidence of contact allergy to isothiazolinones among patients in the Nofer Institute of Occupational Medicine, Lódz, the intensification of patch test results and hypersensitivity depending on the occupation, and to assess the contribution of immediate allergy to the occurrence of that hypersensitivity. MATERIAL AND METHODS: In a group of 1137 patients (832 females and 305 males) with suspected contact dermatitis, diagnosed in 2014-2018, patch tests series including methylchloroisothiazolinone/methylisothiazolinone (0.01%) and methylisothiazolinone (0.2%), produced by Chemotechnique Diagnostics, Sweden, were performed. In a group of 29 individuals with contact allergy to isothiazolinones, prick tests with methylisothiazolinone (0.001%, 0.01%, 0.1%, 1%) (Sigma-Aldrich, Germany) were conducted. RESULTS: Of the 1137 subjects, 95 (8.3%) were allergic to isothiazolinones, slightly more often females - 71 (8.5%) than males - 24 (7.9%). In total, 150 positive patch tests with isothiazolinones (13.2%) were obtained. The number of positive results with methylisothiazolinone alone (7.8%) was higher than the number with methylisothiazolinone from Kathon CG (5.4%). Among the subjects sensitized to methylisothiazolinone alone strongly positive patch tests (+++) concerned 60.7%. In the female group, office workers (42.3%) and medical staff (18.3%) predominated, and in the male group - locksmiths, turners, mechanics and similar ones (45.8%), and construction workers (25.0%). Prick tests with methylisothiazolinone were negative, and they became positive after 3-5 h. CONCLUSIONS: Isothiazolinones, particularly methylisothiazolinone, are significant causal factors of contact allergy, including that of occupational origin. They have strongly allergenic properties, and in patch tests they often give very severe inflammatory reactions. The issue of the role of immediate allergy in the pathogenesis of isothiazolinones sensitization requires further research. Med Pr. 2020;71(5):603-11.
Assuntos
Alérgenos/efeitos adversos , Anti-Infecciosos/efeitos adversos , Cosméticos/efeitos adversos , Dermatite Ocupacional/diagnóstico , Dermatite Ocupacional/etiologia , Desinfetantes/efeitos adversos , Conservantes Farmacêuticos/efeitos adversos , Adulto , Dermatite Ocupacional/epidemiologia , Dermatite Ocupacional/terapia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologiaRESUMO
CONTEXT: Mammalian target of rapamycin complex 1 (mTORC1) activity is often increased in the adrenal cortex of patients with primary aldosteronism (PA), and mTORC1 inhibition decreases aldosterone production in adrenocortical cells, suggesting the mTORC1 pathway as a target for treatment of PA. OBJECTIVE: To investigate the effect of mTORC1 inhibition on adrenal steroid hormones and hemodynamic parameters in mice and in patients with PA. DESIGN: (i) Plasma aldosterone, corticosterone, and angiotensin II (Ang II) were measured in mice treated for 24 hours with vehicle or rapamycin. (ii) Plasma aldosterone levels after a saline infusion test, plasma renin, and 24-hour urine steroid hormone metabolome and hemodynamic parameters were measured during an open-label study in 12 patients with PA, before and after 2 weeks of treatment with everolimus and after a 2-week washout. MAIN OUTCOME MEASURES: (i) Change in plasma aldosterone levels. (ii) Change in other steroid hormones, renin, Ang II, and hemodynamic parameters. RESULTS: Treatment of mice with rapamycin significantly decreased plasma aldosterone levels (P = 0.007). Overall, treatment of PA patients with everolimus significantly decreased blood pressure (P < 0.05) and increased renin levels (P = 0.001) but did not decrease aldosterone levels significantly. However, prominent reduction of aldosterone levels upon everolimus treatment was observed in four patients. CONCLUSION: In mice, mTORC1 inhibition was associated with reduced plasma aldosterone levels. In patients with PA, mTORC1 inhibition was associated with improved blood pressure and renin suppression. In addition, mTORC1 inhibition appeared to reduce plasma aldosterone in a subset of patients.
Assuntos
Everolimo/uso terapêutico , Hiperaldosteronismo/tratamento farmacológico , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Sirolimo/uso terapêutico , Adulto , Aldosterona/sangue , Angiotensina II/sangue , Animais , Pressão Sanguínea/efeitos dos fármacos , Everolimo/farmacologia , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hiperaldosteronismo/sangue , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Projetos Piloto , Estudo de Prova de Conceito , Renina/sangue , Sirolimo/farmacologiaRESUMO
INTRODUCTION: Bronchoalveolar lavage (BAL) is used in the diagnosis of interstitial lung diseases. BAL is diagnostic when ≥ 60% of the instilled volume is recovered. There are no reliable markers useful to predict whether BAL volume is going to be diagnostic. Our goal was to search for pulmonary function markers which could anticipate whether the recovered volume of instilled fluid would be ≥ 60% of administered volume. MATERIAL AND METHODS: BAL volumes and quality were analyzed in the context of disease, medical condition and lung function test results of the subjects hospitalized at the Pulmonology Ward from January 2015 to October 2016. The patients' average age was 61 (29-89). RESULTS: Among 80 procedures, diagnostic BAL (≥ 60%) has been obtained in 58 cases. The analysis of the group of patients with an interstitial lung disease confirmed that there is a correlation between decreasing BAL recovered volume and an increase of RV[%pred] (r = -0.34) and RV/TLC[%pred] (r = -0.41); p < 0.05. There was no significant correlation with DLCO. RV/TLC[%pred] was the parameter with the highest predictive value for an anticipated correct BAL recovery. The curve analysis of the receiver operating characteristic (ROC) showed a diagnostic accuracy (AUC 0.73, 95% CI 0.61-0.86). CONCLUSIONS: Pulmonary hyperinflation may have a predictive role in anticipating a proper recovery of the BAL fluid volume.