RESUMO
Nitisinone, although unapproved for use in alkaptonuria (AKU), is currently the only homogentisic acid lowering therapy with a potential to modify disease progression in AKU. Therefore, safe use of nitisinone off-label requires identifying and managing tyrosine keratopathy. A 22-year-old male with AKU commenced 2 mg daily nitisinone after full assessment. He was issued an alert card explaining potential ocular symptoms such as red eye, tearing, ocular pain and visual impairment and how to manage them. On his first and second annual follow-up visits to the National Alkaptonuria Centre (NAC), there was no corneal keratopathy on slit lamp examination. On his third follow-up annual visit to the NAC, he was found to have typical dendritiform corneal keratopathy in both eyes which was asymptomatic. Nitisinone was suspended until a repeat slit lamp examination, 2 weeks later, confirmed that the keratopathy had resolved. He recommenced nitisinone 2 mg daily with a stricter low protein diet. On his fourth annual follow-up visit to the NAC, a routine slit lamp examination showed mild corneal keratopathy in the left eye. This is despite him reporting no ocular symptoms. This case highlights the fact that corneal keratopathy can occur without symptoms and any monitoring plan with off-label use of nitisinone in AKU will need to take this possibility into account. This is also the first time that typical corneal keratopathy has been described with the use of low dose nitisinone in AKU without symptoms.
RESUMO
OBJECTIVE: To see if a public awareness campaign might be justified around Halloween with regard to the dangers of egg throwing. METHOD: A prospective study was carried out of all patients who attended the St Paul's Eye Unit's Primary Care Department with ocular injuries resulting from a thrown egg over a 14-month period from November 2004. All injuries were classified as minor, intermediate or major and patients were followed up until discharge. RESULTS: 13 ocular injuries that were attributed to assault with a raw egg were reported. In all the 13 cases, the eggs had been thrown by strangers. 12 of the patients were men and the average age of the victims was 27.9 years. 9 patients were injured in the left eye and there were no bilateral injuries. On presentation, only 1 patient had a visual acuity of 6/6, 7 presented at 6/9, with the remainder having 6/18 or worse. All the patients had closed globe injuries. 8 injuries were classified as major injuries. 4 patients had permanent sequelae, with one suffering permanent, severe visual loss. CONCLUSIONS: Although most of our patients showed improvement in visual acuity, there were severe injuries, with the potential for severe ocular morbidity. We conclude that there is sufficient injury caused by this prank to warrant a public health message. At the least this practice should not be promoted by the press.
Assuntos
Comportamento Perigoso , Ovos , Traumatismos Oculares/etiologia , Ferimentos não Penetrantes/etiologia , Adolescente , Adulto , Traumatismos Oculares/fisiopatologia , Feminino , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índices de Gravidade do Trauma , Acuidade Visual , Ferimentos não Penetrantes/fisiopatologiaAssuntos
Infarto Cerebral/complicações , Corpos Geniculados , Acidente Vascular Cerebral/etiologia , Transtornos da Visão/etiologia , Encéfalo/patologia , Infarto Cerebral/patologia , Eletrocardiografia , Lateralidade Funcional/fisiologia , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/patologia , Ultrassonografia Doppler Transcraniana , Transtornos da Visão/patologia , Testes Visuais , Campos VisuaisRESUMO
PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF) possesses mitogenic, motogenic, and morphogenic properties and has recently been implicated in various retinal diseases. The role of HGF/SF in proliferative vitreoretinal disease was investigated. METHODS: Sections of epiretinal membranes were stained immunohistochemically for cytokeratins, to identify HRPE cells, and for HGF/SF receptor (c-Met). Cultured HRPE cells were stained for c-Met and investigated for shape change in response to HGF/SF, by using image analysis. The dose-response relationship for HRPE cells to HGF/SF was investigated by a cell migration assay and the specificity of this response evaluated by a neutralization experiment. Subretinal fluid (SRF) and vitreous from patients with retinal detachment and proliferative vitreoretinopathy (PVR) plus vitreous from eyes obtained after death, eyes with macular hole, and eyes with proliferative diabetic retinopathy (PDR) were investigated for the presence of HGF/SF using an enzyme-linked immunosorbent assay (ELISA). HGF/SF activity was measured using an MDCK cell scatter assay. RESULTS: HRPE cells in epiretinal membranes and in culture expressed c-Met. Cultured HRPE cells responded to HGF/SF by an epithelial-to-mesenchymal shape change and by cell migration, a response that increased with increasing concentrations of HGF/SF. This response was reduced in the presence of neutralizing antibody. There was evidence of HGF/SF in increasing concentrations in more severe PVR and in PDR when measured by ELISA, and, conversely, there was evidence of correspondingly decreasing HGF/SF activity when measured by MDCK cell scatter assay in these diseases. CONCLUSIONS: HGF/SF is present in normal and pathologic vitreous. HRPE cells respond by shape change and cell migration to HGF/SF. Concentrations of HGF/SF increase in proliferative vitreoretinal disease and increase in turn with increased severity of the disease, but HGF/SF bioactivity decreases (consistent with activator depletion). These findings are consistent with the hypothesis that HGF/SF may play a role in the HRPE mesenchymal transformation that typifies PVR.
Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Vitreorretinopatia Proliferativa/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Membrana Epirretiniana/metabolismo , Fator de Crescimento de Hepatócito/farmacologia , Humanos , Técnicas Imunoenzimáticas , Queratinas/metabolismo , Rim/metabolismo , Pessoa de Meia-Idade , Epitélio Pigmentado Ocular/efeitos dos fármacos , Epitélio Pigmentado Ocular/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Descolamento Retiniano/metabolismo , Corpo Vítreo/metabolismoRESUMO
BACKGROUND/AIMS: Previous reports have suggested that the success rate for trabeculectomy is poorer in younger age groups but these studies often have heterogeneous groups representing different types of glaucoma with variable surgical prognosis. Therefore, the relation between age and the success of trabeculectomy in the single diagnostic category of primary open angle glaucoma (POAG) without identifiable risk factors was examined for failure in the age range 46-85 years. METHODS: The records of 208 patients who had undergone a first trabeculectomy for POAG were examined retrospectively. Age ranged from 46 to 85 (mean 66.7 years). The outcome of surgery was examined at final available follow up and at 1 and 2 years after surgery. Trabeculectomy was considered a success if intraocular pressure was < or = 21 mm Hg with or without additional medical treatment ("cumulative" success) and an "absolute" success if intraocular pressure was < = 21 mm Hg without additional medical treatment. RESULTS: Cumulative success for trabeculectomy was 92.3% at final follow up and 96.6% at 2 year follow up; absolute success rate was 66.3% at final follow up and 71.6% at 2 years. There was no significant trend for greater success of trabeculectomy in the older age groups (cumulative success at 2 year follow up, chi 2 for linear trend 1.07 (p = 0.3) nor was the drop in intraocular pressure following surgery significantly greater with increasing age (analysis of variance for intraocular pressure lowering from presentation to 2 years' follow up (Kruskal-Wallis, t = 5.9, p = 0.55). Patients with pseudoexfoliation were excluded from the main analysis as these patients have been shown to have a lower final intraocular pressure following trabeculectomy, a finding which was confirmed in this study.
Assuntos
Glaucoma de Ângulo Aberto/cirurgia , Trabeculectomia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Campos VisuaisRESUMO
We describe a patient with ultra-rare disease, alkaptonuria, who developed tyrosine keratopathy following nitisinone therapy of 2 mg on alternate days. His vision became impaired approximately 7 weeks following the commencement of nitisinone and ophthalmological examination at week nine showed characteristic dendritic keratopathy associated with tyrosinaemia. The corneal lesion as well as his visual symptoms normalized completely following discontinuation of nitisinone. This is the first documented report of keratopathy due to acquired tyrosinaemia due to very low-dose nitisinone.
RESUMO
AIMS: The aim of this study is to describe the incidence and characteristics of neovascularization in the fellow eye of patients with retinal angiomatous proliferation (RAP). METHODS: This is a retrospective study conducted on all patients with a diagnosis of unilateral RAP commencing treatment in a single centre between November 2002 and January 2010. Clinical biomicroscopic examination, fluorescein angiography, and if required, indocyanine green angiography, and optical coherence tomography were used to evaluate all patients. RESULTS: In all, 37 patients had a follow-up of ≥1 year, 28 ≥2 years, and 11 ≥3. Patients who developed RAP in the fellow eye were: 2 of 37 (5.4%) within 1 year of follow-up, 4 of 28 (14.2%) within 2 years, and 4 of 11 (36.3%) within 3 years. CONCLUSION: In our case series, the risk of neovascularization in the fellow eye of patients with unilateral RAP increased with time. Approximately one-third of patients with a 3-year follow-up developed a bilateral disease. Our findings warrant further large-scale investigation.
Assuntos
Degeneração Macular/complicações , Neovascularização Retiniana/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Angiofluoresceinografia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neovascularização Retiniana/etiologia , Estudos Retrospectivos , Risco , Tomografia de Coerência ÓpticaRESUMO
AIMS: To investigate effectiveness in routine clinical practice of verteporfin photodynamic therapy (PDT) for neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: Patients commencing PDT for nAMD in a single UK centre entered a prospective observational 7-year study and were followed for 2 years. Best-corrected visual acuity (BCVA) and contrast sensitivity (CS) were measured at each visit by accredited technicians after full protocol refraction on standardised charts. Reasons for failure to complete the course of therapy were documented. RESULTS: 1008 patients entered the study between 1999 and 2006. 81% and 52% completed 12 and 24 months' follow-up respectively (excluding administrative censoring). Results at 12 and 24 months respectively were: maintenance of BCVA 62%, 63%; drop in mean BCVA (letters) 10.1, 9.4; numbers of treatments 2.9, 3.5. The mean CS remained stable. No correlation of change in BCVA outcome between first and second treated eyes in 82 bilateral cases was detected. Loss to follow-up was significantly associated with age, CS and distance from the treating centre. CONCLUSIONS: PDT delivered in clinical practice is at least as effective as that reported in randomised clinical trials and uses fewer treatments.
Assuntos
Neovascularização de Coroide/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Fotoquimioterapia/métodos , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/fisiopatologia , Sensibilidades de Contraste/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Degeneração Macular/complicações , Degeneração Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Verteporfina , Acuidade Visual/efeitos dos fármacosRESUMO
We present a comparison of one quadrant sub-Tenon's anaesthesia and peribulbar anaesthesia. Patient discomfort during injection of anaesthetic and during cataract surgery was assessed using a 10-point visual analogue scale ranging from no pain to the worst pain imaginable. Data are available for 74 patients undergoing cataract surgery under peribulbar anaesthesia and for 55 patients in whom sub-Tenon's anaesthesia was used. Pain scores for administration of anaesthetic were significantly lower (Kruskal-Wallis H-test, p < 0.01) for sub-Tenon's anaesthesia (mean 1.4) compared with the peribulbar technique (mean 2.4). However, a similar number of patients experienced pain of greater than 3 for the two techniques (10 (18.5%) for sub-Tenon's and 14 (18.9%) for peribulbar). Per-operative pain scores for sub-Tenon's anaesthesia (mean 0.5) were lower than those for peribulbar anaesthesia (mean 1.2) but not significantly so (Kruskal-Wallis H-test, p = 0.073). Significantly fewer patients, however, experienced pain of greater than 3 (Fisher exact test, p < 0.05) in the sub-Tenon's group. In addition less anaesthetic solution and a shorter interval from administration to surgery was required in the sub-Tenon's group. Sub-Tenon's anaesthesia appears to be a more effective method of anaesthesia than the peribulbar method.
Assuntos
Anestesia Local/métodos , Extração de Catarata , Idoso , Idoso de 80 Anos ou mais , Anestesia Local/efeitos adversos , Anestésicos Locais/administração & dosagem , Feminino , Humanos , Injeções/efeitos adversos , Complicações Intraoperatórias , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Dor/etiologia , Dor Pós-Operatória , Estudos ProspectivosRESUMO
AIMS: To report on the clinical efficacy of verteporfin photodynamic therapy (PDT) in the treatment of choroidal neovascularisation (CNV) in an NHS setting and to compare treatment rates and outcomes with those in the published literature. PATIENTS AND METHODS: Patients with a visual acuity of 6/60 or better Snellen equivalent and predominantly classic or classic/no occult CNV within 200 microm of the centre of the fovea were enrolled and followed for a minimum of 12 months. Assessment at baseline and all follow-up visits comprised refraction protocol logMAR visual acuity, contrast sensitivity, and stereoscopic fluorescein angiography. RESULTS: A total of 170 eyes of 159 patients were enrolled with CNV due to: 147 age-related macular degeneration (AMD) (90 classic/no occult, 21 recurrent after confluent laser, 36 predominantly classic with occult), 10 pathological myopia, and 13 others. Response to treatment (loss of < 15 letters) at 12 months was 73% overall, 76% in AMD, 70% in classic/no occult, and 89% in predominantly classic. The mean number of treatments in the first year was 2.7. Contrast sensitivity was unchanged. CONCLUSIONS: Verteporfin PDT delivered in a NHS setting can be at least as effective as and requires fewer treatments than reported in the literature.
Assuntos
Neovascularização de Coroide/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/fisiopatologia , Sensibilidades de Contraste , Seguimentos , Humanos , Degeneração Macular/complicações , Miopia/complicações , Recidiva , Verteporfina , Acuidade VisualRESUMO
Between March 1993 and September 1994 we treated 25 cases of lenses in the vitreous cavity. Nineteen of the 25 were the result of dislocation during phacoemulsification. During this time, we adopted a single surgical algorithm involving vitrectomy, heavy liquids and ultrasound fragmentation. The aims of this retrospective study were to test the validity of our surgical algorithm and to report on outcomes and complications. The indications for vitreous surgery were raised intraocular pressure, uveitis and poor vision. Vitreous surgery was carried out at a mean of 29 days following phacoemulsification. Six patients required heavy liquids and 5 needed ultrasound fragmentation. Vitreous surgery undertaken less than 17 days after phacoemulsification had an increased likelihood of requiring heavy liquids and/or fragmentation (p < 0.02). The greatest threat to a favourable visual outcome was retinal detachment, which was significantly associated with fragmentation and use of heavy liquids (p < 0.02). The presence of an intraocular lens (IOL) reduced the surgical options for removal of the lens fragments, and IOL should not be inserted where lens matter dislocates. The study suggests that we should avoid fragmentation and, provided the intraocular pressure and uveitis can be controlled, that vitreous surgery should be deferred for 2-3 weeks following phacoemulsification.
Assuntos
Subluxação do Cristalino/cirurgia , Facoemulsificação/efeitos adversos , Vitrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Seguimentos , Humanos , Subluxação do Cristalino/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual , Vitrectomia/efeitos adversosRESUMO
Teicoplanin is a glycopeptide antibiotic, similar to vancomycin, but safer and better tolerated. The purpose of this study was to evaluate the penetration of teicoplanin into the vitreous when administered topically and intravenously. Twenty-five patients undergoing routine vitrectomy were recruited. Twenty were given intravenous teicoplanin: five 1 h pre-operatively, five 12 h pre-operatively, five 24 h pre-operatively and five 24 h as well as 48 h pre-operatively. Five received teicoplanin drops half-hourly for the 6 h immediately preceding vitrectomy. Undiluted vitreous specimens were obtained at the beginning of each vitrectomy procedure. Teicoplanin levels were measured using a biological assay with Staphylococcus aureus as the indicator organism. Teicoplanin activity was detected in 8 of the 20 specimens from those patients receiving the intravenous antibiotic. Teicoplanin did not penetrate readily into the vitreous cavities in these eyes despite the blood-ocular barrier being compromised in some patients, although there was evidence of accumulation with time. No activity was detected in the vitreous of those patients who received topical teicoplanin.
Assuntos
Antibacterianos/farmacocinética , Teicoplanina/farmacocinética , Corpo Vítreo/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Esquema de Medicação , Humanos , Injeções Intravenosas , Pessoa de Meia-Idade , Soluções Oftálmicas , Teicoplanina/administração & dosagem , VitrectomiaRESUMO
The histidine phosphocarrier protein (HPr) is an essential element in sugar transport by the bacterial phosphoenolpyruvate:sugar phosphotransferase system. Ligand fishing, using surface plasmon resonance, was used to show the binding of HPr to a nonphosphotransferase protein in extracts of Escherichia coli; the protein was subsequently identified as glycogen phosphorylase (GP). The high affinity (association constant approximately 10(8) M-1), species-specific interaction was also demonstrated in electrophoretic mobility shift experiments by polyacrylamide gel electrophoresis. Equilibrium ultracentrifugation analysis indicates that HPr allosterically regulates the oligomeric state of glycogen phosphorylase. HPr binding increases GP activity to 250% of the level in control assays. Kinetic analysis of coupled enzyme assays shows that the binding of HPr to GP causes a decrease in the Km for glycogen and an increase in the Vmax for phosphate, indicating a mixed type activation. The stimulatory effect of E. coli HPr on E. coli GP activity is species-specific, and the unphosphorylated form of HPr activates GP more than does the phosphorylated form. Replacement of specific amino acids in HPr results in reduced GP activation; HPr residues Arg-17, Lys-24, Lys-27, Lys-40, Ser-46, Gln-51, and Lys-72 were established to be important. This novel mechanism for the regulation of GP provides the first evidence directly linking E. coli HPr to the regulation of carbohydrate metabolism.