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1.
Eye (Lond) ; 30(6): 784-95, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27174381

ABSTRACT

PurposeTo evaluate the ability of baseline clinical, morphological, and functional factors to predict the conversion to primary open-angle glaucoma (POAG) in ocular hypertensive (OHT) patients.MethodsThis single-center prospective longitudinal observational study included 116 eyes of 116 OHT patients followed for a 10-year period. All patients had intraocular pressure (IOP) ≥24 mm Hg in one eye and >21 mm Hg in the other eye, normal visual fields (VFs) and normal optic disc (OD) appearance in both eyes at baseline. All OHT patients were untreated at baseline with subsequent treatment upon need according to clinical judgement. Only one eye per subject was randomly selected. Patient age, gender, IOP, central corneal thickness (CCT), and ibopamine test results were collected at baseline. All patients underwent standard automated perimetry, short-wavelength automated perimetry (SWAP), frequency-doubling technology, confocal scanning laser ophthalmoscopy (CSLO), and scanning laser polarimetry (SLP) at baseline and every 6 months thereafter. Main outcome measure was the conversion to POAG, defined as the development of reproducible VF and/or OD abnormalities attributable to glaucoma. Cox proportional hazards models were used to identify the baseline factors predictive of POAG conversion.ResultsDuring the 10-year follow-up, 25% of eyes converted to POAG. In multivariate Cox models, baseline factors that were significant predictors of POAG development included: older age (hazard ratio (HR) 1.0, 99% confidence intervals (CIs) 1.0-1.2, per 1 year older); SWAP Glaucoma Hemifield test 'outside normal limits' (HR 4.3, 99% CIs 1.2-17.9); greater SLP 'Inter-eye Symmetry' (HR 1.1, 99% CIs 0.4-3.0, per 1 unit lower); lower CSLO Rim Volume (HR 1.1, 99% CIs 0.3-3.2, per 0.1 mm(3) lower); and greater CSLO cup-to-disc ratio (HR 6.0, 99% CIs 3.6-16.8, per 0.1 unit greater).ConclusionsThe baseline parameters that proved to be useful in assessing the likelihood of an OHT patient to develop POAG included age, functional variables provided by SWAP, and structural variables provided by SLP and CSLO. In this cohort of patients, baseline IOP, CCT, and ibopamine provocative test results were not significant predictors of POAG conversion.


Subject(s)
Glaucoma, Open-Angle/diagnosis , Ocular Hypertension/diagnosis , Aged , Deoxyepinephrine/administration & dosage , Deoxyepinephrine/analogs & derivatives , Disease Progression , Female , Follow-Up Studies , Humans , Intraocular Pressure/physiology , Male , Middle Aged , Mydriatics/administration & dosage , Ophthalmoscopy , Prospective Studies , Risk Factors , Tonometry, Ocular , Visual Field Tests , Visual Fields/physiology
2.
Clin Exp Ophthalmol ; 44(3): 166-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26575026

ABSTRACT

BACKGROUND: The ibopamine challenge test correlates well with a patient's peak diurnal intraocular pressure (IOP) measurement. We aimed to investigate the effect that a functioning trabeculectomy has on the ibopamine challenge test. DESIGN: Non-randomized prospective clinical trial evaluating a diagnostic test. PARTICIPANTS: Thirteen patients were recruited through glaucoma clinics at the Flinders Medical Centre. Of these, seven required surgical management with trabeculectomy surgery, whilst the remainder were managed medically. METHODS: Patients underwent IOP measurement, and then two drops of Ibopamine 2% solution were instilled into the study eye of each patient. After 45 min, IOP was reassesed. A positive challenge test was considered to be a rise in IOP of greater than 3 mmHg. Changes from baseline were determined and compared between groups. Twelve months later, this test was then repeated in all patients. MAIN OUTCOME MEASURE: Change in IOP after ibopamine challenge. RESULTS: Following the ibopamine challenge, IOP increased by 9.2 mmHg (SD 2.8) (100% positive) for medically managed patients and 7.2 mmHg (SD 2.0) (100% positive) for surgically managed patients (P = 0.18). The surgically managed group then underwent trabeculectomy surgery. Twelve months later, the ibopamine challenge was repeated. Following the repeat ibopamine challenge, IOP increased by 7.2 mmHg (SD 2.3) for medically managed patients and 0.3 mmHg (SD 1.3) for surgically managed patients (P < 0.0001). The medically managed group remained 100% positive, whilst the surgically manage group became 0% positive (Fisher Exact P = 0.044). CONCLUSIONS: A glaucoma patient with a positive ibopamine challenge will show a negative challenge result when re-tested following trabeculectomy surgery.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Dopamine Agonists/administration & dosage , Glaucoma/diagnosis , Glaucoma/surgery , Intraocular Pressure/drug effects , Trabeculectomy , Aged , Aged, 80 and over , Antihypertensive Agents/administration & dosage , Deoxyepinephrine/administration & dosage , Disease Progression , Female , Glaucoma/physiopathology , Humans , Male , Prospective Studies , Tonometry, Ocular
3.
J Glaucoma ; 25(5): e441-5, 2016 05.
Article in English | MEDLINE | ID: mdl-26709501

ABSTRACT

PURPOSE: To evaluate the diagnostic ability of the ibopamine provocative test for early glaucoma detection. METHOD: A sample of 44 patients with suspicious optic discs was recruited and compared with 37 controls with normal optic discs and no ocular pathology. The ibopamine test was performed in all patients who were then followed up with diagnostic tests for glaucoma, visual fields, and spectral-domain optical coherence tomography. RESULTS: Early glaucoma was diagnosed in 26 patients. The sensitivity of the ibopamine test to discriminate patients who had early glaucoma was 78.7%, with a specificity of 71.6%. In multivariable analyses adjusted for demographic and clinical variables, participants with a positive ibopamine test at baseline had an 8-fold higher risk of glaucoma compared with those who had a negative test; glaucoma risk was highest among ibopamine-positive subjects with initial clinical diagnostic impression of glaucoma. CONCLUSIONS: The ibopamine test showed an adequate diagnostic performance to detect individuals at increased risk of glaucoma in a very early stage of the disease. While further studies are required, the provocative ibopamine test for the diagnosis of early glaucoma is promissory.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Diagnostic Techniques, Ophthalmological , Dopamine Agonists/administration & dosage , Glaucoma, Open-Angle/diagnosis , Intraocular Pressure/drug effects , Aged , Deoxyepinephrine/administration & dosage , Female , Humans , Male , Middle Aged , Optic Disk/pathology , Sensitivity and Specificity , Tomography, Optical Coherence/methods , Tonometry, Ocular , Visual Fields
4.
Clin Exp Ophthalmol ; 43(9): 808-14, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26140527

ABSTRACT

BACKGROUND: An ibopamine challenge is a novel technique for assessing glaucoma using ibopamine, a topical drug which temporarily increases aqueous production. We aimed to determine whether change in intraocular pressure (IOP) and/or optic cup volume (OCV) during the test differentiated between glaucoma patients at different stages of disease; namely, glaucoma suspects (GS), glaucoma patients who are stable (SG) and glaucoma patients who have demonstrated rapid progression (PG). DESIGN: Non-randomized clinical trial evaluating a diagnostic test. PARTICIPANTS: Sixty-one patients were recruited through glaucoma clinics at the Flinders Medical Centre (24 GS, 24 SG and 13 PG). METHODS: Patients underwent IOP measurement and OCV assessment using optical coherence tomography. Two drops of ibopamine 2% solution were instilled into the study eye of each patient. After 45 min, IOP and OCV were reassessed. Changes from baseline were compared between groups. MAIN OUTCOME MEASURE: Change in IOP and OCV after ibopamine challenge. RESULTS: Following the ibopamine challenge, IOP increased by 1.8 mmHg for GS patients, 4.5 mmHg for SG patients (P = 0.003) and 8.1 mmHg for PG patients (P < 0.0001). OCV increased by 0.2% for GS patients, 0.6% for SG patients and 5.5% for PG patients. This was not significantly different between GS patients and SG patients; however, it was significantly different between GS patients and PG patients (P < 0.0001), and between SG and PG patients (P = 0.001). CONCLUSION: GS patients may be differentiated from those with SG or PG by their IOP response, and SG may be differentiated from PG patients by their change in OCV following an ibopamine challenge.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Dopamine Agonists/administration & dosage , Glaucoma/diagnosis , Intraocular Pressure/drug effects , Ocular Hypertension/diagnosis , Aged , Aged, 80 and over , Deoxyepinephrine/administration & dosage , Disease Progression , Female , Humans , Male , Middle Aged , Ophthalmic Solutions , Pupil/drug effects , Tomography, Optical Coherence , Tonometry, Ocular , Visual Fields
5.
Eur J Ophthalmol ; 23(6): 819-22, 2013.
Article in English | MEDLINE | ID: mdl-23813108

ABSTRACT

PURPOSE: To determine the change in pattern electroretinogram (PERG) amplitude during the ibopamine test in patients with ocular hypertension (OHT). METHODS: A total of 32 eyes (16 patients) with OHT (8 male, 8 female), mean age 54.19 years (range 22-76 years), mean baseline intraocular pressure (IOP) 23 ± 2 mm Hg, received a PERG assessment in both eyes every 5 minutes from baseline to 60 minutes. All the patients were pretreated by thymoxamine eyedrops to avoid the mydriatic effect of ibopamine. All the data were evaluated by descriptive statistics and paired t test. The results were considered with a significance level of p<0.05. RESULTS: All the patients enrolled matched the inclusion criteria and they did not have any local or systemic effects with the ibopamine test. The mean PERG amplitude decreased significantly from baseline after 45 minutes during the ibopamine test (paired t test = 0.05). The results were statistically not correlated with the positivity to the ibopamine test (p = 0.5). CONCLUSIONS: These data stress that, even in presence of a moderate and transient IOP increase, inner retinal function of patients with OHT may be transiently affected.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Electroretinography , Intraocular Pressure/drug effects , Mydriatics/administration & dosage , Ocular Hypertension/physiopathology , Retina/physiopathology , Adolescent , Adult , Aged , Deoxyepinephrine/administration & dosage , Female , Humans , Male , Middle Aged , Ophthalmic Solutions , Pattern Recognition, Visual/physiology , Tonometry, Ocular , Young Adult
6.
Cornea ; 29(9): 1069-71, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20567201

ABSTRACT

PURPOSE: To report a case of pigmented deposits on a type I Boston keratoprosthesis (KPro) associated with the use of topical ibopamine as a treatment for hypotony. METHODS: Case report and literature review. RESULTS: The dopamine-like agent ibopamine caused black deposits on the bandage lens and on the front plate of the Boston KPro that resulted in reduced visual acuity. Change to a daily disposable contact lens and regular cleaning of the KPro front plate with diluted baby shampoo eliminated this problem. CONCLUSION: This is the first report of this complication with topical ibopamine use and should be considered when ibopamine is used chronically for hypotony.


Subject(s)
Artificial Organs , Deoxyepinephrine/analogs & derivatives , Dopamine Agonists/adverse effects , Melanosis/chemically induced , Prostheses and Implants , Prosthesis Failure , Administration, Topical , Deoxyepinephrine/administration & dosage , Deoxyepinephrine/adverse effects , Dopamine Agonists/administration & dosage , Humans , Male , Melanins/chemistry , Melanosis/diagnosis , Middle Aged , Ocular Hypotension/drug therapy
7.
Rev. bras. oftalmol ; 69(3): 165-169, maio-jun. 2010. tab
Article in Portuguese | LILACS | ID: lil-553465

ABSTRACT

OBJETIVO: Avaliar o efeito da ibopamina a 2 por cento tópica e comparar a variação na pressão intraocular (PIO) em olhos com glaucoma primário de ângulo aberto assimétrico (GPAA). MÉTODOS: Quinze pacientes (30 olhos) com GPAA com evolução assimétrica da neuropatia entre os dois olhos, onde comparamos em cada paciente a resposta a ibopamina e o defeito perimétrico, caracterizado por uma diferença de pelo menos 5dB de MD entre os olhos. O teste estatístico utilizado foi o t Student bicaudal e para significância estatística estabeleceu-se p <0,05. RESULTADOS: Em 80 por cento dos casos, (12/15 pacientes) o olho mais afetado pelo defeito perimétrico apresentou um aumento da PIO e/ou uma variaçã da PIO pós-ibopamina maior, sendo o resultado estatisticamente significativo (p<0,0001 e p = 0,0006), respectivamente. CONCLUSÃO: Este estudo mostrou que o defeito perimétrico no GPAA é significativamente relacionado com a positividade do teste de ibopamina sendo que olhos com maior defeito no campo visual apresentam maiores picos de PIO (max-PIO) pós-ibopamina e/ou uma maior variação em relação a sua PIO prévia ao teste (v-PIO).


OBJECTIVE: To evaluate the topic 2 percent ibopamine effect in the intraocular pressure (IOP) of eyes with assimetric primary open-angle glaucoma (POAG). METHODS: 15 patients (30 eyes) with primary open-angle glaucoma showing assimetric nerve disease evolution were assessed. We compared in all patients, the ibopamine response and the visual field defect between both eyes. The visual field, to be considered, should have at least 5 dB in MD difference between them. The statistical analysis was done with the Two-Tailed Student Test, with a Statistics significance of p<0.05. RESULTS: In 80 percent of the cases, (12/15 patients), the most affected eye in the visual field presented a greater variation and/or higher intraocular pressure after the ibopamine provocative test. The difference was statistically significant (p<0.00001 and p= 0.0006) respectively. CONCLUSION: This study showed that the visual field defect in GPAA is significantly connected with the positivity of the ibopamine test. The most affected eyes in the visual field presented a higher intraocular pressure (max-PIO) and/or a greater variation (v-PIO) after the ibopamine provocativetest.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged, 80 and over , Deoxyepinephrine/administration & dosage , Deoxyepinephrine/analogs & derivatives , Glaucoma, Open-Angle/drug therapy , Intraocular Pressure , Mydriatics , Ophthalmic Solutions/administration & dosage , Visual Fields
8.
Eur J Ophthalmol ; 20(1): 120-3, 2010.
Article in English | MEDLINE | ID: mdl-19882519

ABSTRACT

PURPOSE: To compare the mydriatic effects of 2% ibopamine and collyrium containing 10% phenylephrine + 0.5% tropicamide and to study the associated drug in patients with ocular pseudoexfoliation (PEX) syndrome. METHODS: This was a prospective, comparative, interventional clinical study. The study group consisted of 20 patients with ocular PEX syndrome. Intervention procedures included administration of 10% phenylephrine-0.5% tropicamide versus 2% ibopamine versus 2% ibopamine followed by the combination drug. Main outcome measurement was mydriatic efficacy measured in terms of mean pupil diameter. Adverse effects on intraocular pressure (IOP) were measured with a Goldmann applanation tonometer. Mean premedication pupil diameters in all patients were less than 3.5 mm. RESULTS: Instillation of 10% phenylephrine-0.5% tropicamide caused significantly greater mydriasis than 2% ibopamine (pupil diameters: 6.17 mm, SD=1.14 versus 5.33 mm, SD=1.34; p<0.001). Combined use of both collyria significantly increased mydriasis (7.19 mm; SD=0.69) compared with that induced by either of the products alone (p<0.001). Inadequate mydriasis (pupil diameters < 5.5 mm) was observed in 2 patients after administration of 10% phenylephrine-0.5% tropicamide and in 10 following instillation of 2% ibopamine, but the addition of 10% phenylephrine -0.5% tropicamide to ibopamine-treated eyes resulted in adequate dilation in all cases. IOP increases of 4 mmHg over baseline values were observed in 12 (60%) patients after 2% ibopamine. CONCLUSIONS: In patients with ocular PEX, instillation of 2% ibopamine exerts a significant additive effect on mydriasis induced with 10% phenylephrine-0.5% tropicamide with only minimal increases in IOP.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Exfoliation Syndrome/complications , Mydriatics/administration & dosage , Pupil/drug effects , Aged , Deoxyepinephrine/administration & dosage , Drug Combinations , Female , Humans , Intraocular Pressure , Male , Ophthalmic Solutions/administration & dosage , Phenylephrine/administration & dosage , Prospective Studies , Tonometry, Ocular , Treatment Outcome , Tropicamide/administration & dosage
9.
Arq Bras Oftalmol ; 72(3): 365-9, 2009.
Article in Portuguese | MEDLINE | ID: mdl-19668968

ABSTRACT

PURPOSE: To evaluate the influence of 2% ibopamine eye drops on the results of computerized visual field exams. METHODS: Normal volunteers from CEROF-UFG were selected, with no variance in the ophthalmologic examination that could affect the visual field test. The volunteers underwent computerized visual field test before and after dilation with 2% ibopamine eye drop or cyclopentolate, with a minimum interval of three days between them and in a random order. Global indices and number of altered points were compared between the groups. RESULTS: Thirty eyes of 30 normal individuals were selected. There was no statistically significant difference on Mean Deviation (MD) before and after dilation with ibopamine (MD: -1.05 +/- 0.26 dB vs. -1.47 +/- 0.20 dB, P=0.08). However, after cycloplegia (MD: -3.19 +/- 0.29 dB), there was a significant difference on MD (P<0.001 for both ibopamine and pre-dilation). No significant difference was detected in the Pattern Standard Deviation when comparing ibopamine with pre-dilation and cycloplegia values, but it was statistically significant comparing pre-dilation to cycloplegia (P=0.04). The number of altered points in the Pattern Deviation graphic were not significant comparing all pairs. There was a statistically significant difference in the number of altered points in the total deviation graphic before dilation and after cycloplegia (n: 8.86 +/- 1.51 vs. 25.72 +/- 2.96 points, P<0.001), and comparing cycloplegia with ibopamine (ibopamine: 9.75 +/- 1.85 points, P<0.001). CONCLUSION: Ibopamine 2% eye drops seem to not modify the results of visual field tests in normal individuals.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Mydriatics/administration & dosage , Visual Field Tests/methods , Visual Fields/drug effects , Adult , Cyclopentolate/administration & dosage , Data Interpretation, Statistical , Deoxyepinephrine/administration & dosage , Female , Humans , Image Processing, Computer-Assisted , Male , Ophthalmic Solutions/administration & dosage , Time Factors
10.
Arq. bras. oftalmol ; 72(3): 365-369, May-June 2009. graf
Article in Portuguese | LILACS | ID: lil-521473

ABSTRACT

OBJETIVO: Avaliar os efeitos do uso do colírio de ibopamina a 2 por cento nos resultados da campimetria visual computadorizada em indivíduos normais. MÉTODOS: Voluntários oriundos do CEROF-UFG, sem alterações ao exame oftalmológico que pudessem afetar o campo visual foram selecionados. Os indivíduos foram submetidos a exame de perimetria computadorizada SITA-standard 24-2 antes e após dilatação com o colírio de ibopamina a 2 por cento ou ciclopentolato, com intervalo mínimo de 3 dias entre si e em ordem aleatória. Índices globais e número de pontos alterados foram comparados entre os grupos. RESULTADOS: Foram avaliados 30 olhos de 30 indivíduos normais. Não houve diferença estatisticamente significativa entre o "mean deviation" (MD) nos pacientes não dilatados e nos mesmos após a instilação da ibopamina (MD: -1,05 ± 0,26 dB vs. -1,47 ± 0,20 dB, P=0,08), o que ocorreu após cicloplegia (MD: -3,19 ± 0,29 dB), P<0,001 para ambos. Na avaliação entre cicloplegia e pré-dilatação, nota-se significância para o "pattern standard deviation" (P=0,04), o que não ocorreu na avaliação com ibopamina. O número de pontos alterados no "pattern deviation" não apresentou diferença significativa entre todos os pares. Quanto ao número de pontos do "total deviation", houve diferença estatisticamente significativa antes da dilatação e após o uso do cicloplégico (n: 8,86 ± 1,51 vs. 25,72 ± 2,96 pontos, P<0,001) e entre olhos após a instilação do cicloplégico e da ibopamina (ibopamina: 9,75 ± 1,85 pontos, P<001). CONCLUSÃO: O colírio de ibopamina 2 por cento aparentemente não afeta os resultados da perimetria computadorizada em indivíduos normais.


PURPOSE: To evaluate the influence of 2 percent ibopamine eye drops on the results of computerized visual field exams. METHODS: Normal volunteers from CEROF-UFG were selected, with no variance in the ophthalmologic examination that could affect the visual field test. The volunteers underwent computerized visual field test before and after dilation with 2 percent ibopamine eye drop or cyclopentolate, with a minimum interval of three days between them and in a random order. Global indices and number of altered points were compared between the groups. RESULTS: Thirty eyes of 30 normal individuals were selected. There was no statistically significant difference on Mean Deviation (MD) before and after dilation with ibopamine (MD: -1.05 ± 0.26 dB vs. -1.47 ± 0.20 dB, P=0.08). However, after cycloplegia (MD: -3.19 ± 0.29 dB), there was a significant difference on MD (P<0.001 for both ibopamine and pre-dilation). No significant difference was detected in the Pattern Standard Deviation when comparing ibopamine with pre-dilation and cycloplegia values, but it was statistically significant comparing pre-dilation to cycloplegia (P=0.04). The number of altered points in the Pattern Deviation graphic were not significant comparing all pairs. There was a statistically significant difference in the number of altered points in the total deviation graphic before dilation and after cycloplegia (n: 8.86 ± 1.51 vs. 25.72 ± 2.96 points, P<0.001), and comparing cycloplegia with ibopamine (ibopamine: 9.75 ± 1.85 points, P<0.001). CONCLUSION: Ibopamine 2 percent eye drops seem to not modify the results of visual field tests in normal individuals.


Subject(s)
Adult , Female , Humans , Male , Deoxyepinephrine/analogs & derivatives , Mydriatics/administration & dosage , Visual Field Tests , Visual Fields/drug effects , Cyclopentolate/administration & dosage , Data Interpretation, Statistical , Deoxyepinephrine/administration & dosage , Image Processing, Computer-Assisted , Ophthalmic Solutions/administration & dosage , Time Factors
11.
Int J Cardiol ; 131(3): 336-44, 2009 Jan 24.
Article in English | MEDLINE | ID: mdl-18192039

ABSTRACT

UNLABELLED: In patients with atherosclerotic disease, a high pulse pressure is an important predictor of cardiovascular events. However, in patients with chronic heart failure (CHF) a low pulse pressure is related to worse outcome, although no distinction was made between ischaemic and non ischaemic heart failure. We therefore aimed to compare the prognostic value of pulse pressure (PP) between those with ischaemic and non ischaemic advanced heart failure. METHOD AND RESULTS: Pulse pressure was analysed for its effect on mortality, adjusting for other modifiers of risk, using Cox proportional hazards regression analysis of data collected from 1901 patients with NYHA class III or IV heart failure (mean age 65 years, mean ejection fraction 26%). In ischaemic heart failure (n=1118), low mean arterial pressure (MAP) was an independent predictor of overall mortality (Hazard Ratio (HR) 0.88 per 10 mm Hg; p=0.04), while pulse pressure was not. In contrast, in non ischaemic heart failure (n=783), a low pulse pressure was an independent predictor of overall mortality (HR 0.84 per 10 mm Hg; p=0.036), while mean arterial pressure was not. In addition, higher NYHA class and lower pulse pressure (HR 0.87 per 10 mm Hg; p=0.002) were the only independent predictors for first heart failure hospitalisation in both ischaemic and non ischaemic patients. CONCLUSION: Low pulse pressure is a readily obtainable risk marker of death in advanced non ischaemic heart failure. Mean arterial pressure remains an important component of blood pressure in predicting mortality, especially in those with heart failure of an ischaemic aetiology. It is postulated that pulse pressure may reflect a deleterious haemodynamic state, in non-atherosclerotic heart failure patients.


Subject(s)
Blood Pressure , Heart Failure/mortality , Heart Failure/physiopathology , Myocardial Ischemia/complications , Administration, Oral , Adolescent , Adult , Aged , Aged, 80 and over , Deoxyepinephrine/administration & dosage , Deoxyepinephrine/analogs & derivatives , Deoxyepinephrine/therapeutic use , Disease Progression , Dopamine Agonists/administration & dosage , Dopamine Agonists/therapeutic use , Female , Heart Failure/complications , Heart Failure/drug therapy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Young Adult
12.
Neuroscience ; 146(4): 1743-57, 2007 Jun 08.
Article in English | MEDLINE | ID: mdl-17467183

ABSTRACT

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy"), is a widely abused, psychoactive recreational drug that is known to induce neurotoxic effects. Human and rat hepatic metabolism of MDMA involves N-demethylation to 3,4-methylenedioxyamphetamine (MDA), which is also a drug of abuse. MDMA and MDA are O-demethylenated to N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA) and alpha-methyldopamine (alpha-MeDA), respectively, which are both catechols that can undergo oxidation to the corresponding ortho-quinones. Ortho-quinones may be conjugated with glutathione (GSH) to form glutathionyl adducts, which can be transported into the brain and metabolized to the correspondent N-acetylcysteine (NAC) adducts. In this study we evaluated the neurotoxicity of nine MDMA metabolites, obtained by synthesis: N-Me-alpha-MeDA, alpha-MeDA and their correspondent GSH and NAC adducts. The studies were conducted in rat cortical neuronal cultures, for a 6 h of exposure period, under normal (36.5 degrees C) and hyperthermic (40 degrees C) conditions. Our findings show that thioether MDMA metabolites are strong neurotoxins, significantly more than their correspondent parent catechols. On the other hand, N-Me-alpha-MeDA and alpha-MeDA are more neurotoxic than MDMA. GSH and NAC conjugates of N-Me-alpha-MeDA and alpha-MeDA induced a concentration dependent delayed neuronal death, accompanied by activation of caspase 3, which occurred earlier in hyperthermic conditions. Furthermore, thioether MDMA metabolites time-dependently increased the production of reactive species, concentration-dependently depleted intracellular GSH and increased protein bound quinones. Finally, thioether MDMA metabolites induced neuronal death and oxidative stress was prevented by NAC, an antioxidant and GSH precursor. This study provides new insights into the neurotoxicity mechanisms of thioether MDMA metabolites and highlights their importance in "ecstasy" neurotoxicity.


Subject(s)
Hallucinogens/metabolism , Hallucinogens/toxicity , N-Methyl-3,4-methylenedioxyamphetamine/metabolism , N-Methyl-3,4-methylenedioxyamphetamine/toxicity , Neurons/drug effects , 3,4-Methylenedioxyamphetamine/administration & dosage , Acetylcysteine/pharmacology , Adenosine Triphosphate/metabolism , Animals , Caspase 3/metabolism , Cell Death/drug effects , Cells, Cultured , Cerebral Cortex/cytology , Deoxyepinephrine/administration & dosage , Deoxyepinephrine/analogs & derivatives , Dose-Response Relationship, Drug , Drug Interactions , Embryo, Mammalian , Free Radical Scavengers/pharmacology , Glutathione/metabolism , Hallucinogens/chemistry , N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage , N-Methyl-3,4-methylenedioxyamphetamine/chemistry , Rats , Rats, Wistar , Temperature , Time Factors
13.
Klin Monbl Augenheilkd ; 224(4): 255-9, 2007 Apr.
Article in German | MEDLINE | ID: mdl-17458787

ABSTRACT

BACKGROUND: Ibopamine is an alpha-adrenergic agent and causes an elevation of intraocular pressure in eyes with increased outflow resistance. It has been proposed as a test substance for the detection of early ocular hydrodynamic disorders. PATIENTS AND METHODS: A total of 64 normal-tension glaucoma suspect eyes without anti-hypertensive treatment were enrolled. A daily pressure curve was registered with measurements at 7:00 am, 8:00 am, 12:00 am, 17:00 pm using an applanation tonometer and a contour tonometer followed by instillation of ibopamine 2% in both eyes. Tonometry was performed every 15 minutes during the following hour. An IOP increase of > 2.0 mmHg was considered positive. RESULTS: The positive test group showed a significant pressure increase from 18.04 to 22.06 mmHg. Ocular pulse amplitude increased from 2.96 to 3.97 mmHg and was positively correlated with the pressure. Intraocular pressure was unchanged in the negative test group. Central corneal thickness was not significantly different in the two groups (p = 0.32). CONCLUSIONS: Ibopamine 2% eye drops have a positive pressure effect in 50% of suspected normal-tension glaucoma eyes and may differentiate between eyes with normal trabecular outflow capacity and eyes with increased resistance in the trabecular meshwork that are prone to pressure peaks and deterioration to glaucoma.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Glaucoma/diagnosis , Intraocular Pressure/drug effects , Tonometry, Ocular/methods , Deoxyepinephrine/administration & dosage , Female , Humans , Male , Middle Aged , Mydriatics/administration & dosage , Reproducibility of Results , Sensitivity and Specificity , Vasodilator Agents/administration & dosage
14.
Arq Bras Oftalmol ; 69(5): 695-9, 2006.
Article in English | MEDLINE | ID: mdl-17187138

ABSTRACT

PURPOSE: To compare intraocular pressure (IOP) rise in normal individuals and primary open-angle glaucoma patients and the safety and efficacy of ibopamine eye drops in different concentrations as a provocative test for glaucoma. METHODS: Glaucoma patients underwent (same eye) the ibopamine provocative test with two concentrations, 1% and 2%, in a random sequence at least 3 weeks apart, but not more than 3 months. The normal individuals were randomly submitted to one of the concentrations of ibopamine (1% and 2%). The test was considered positive if there was an IOP rise greater than 3 or 4 mmHg at 30 or 45 minutes to test which subset of the test has the best sensitivity (Se)/specificity (Sp). RESULTS: There was no statistically significant difference in any of the IOP measurements, comparing 1% with 2% ibopamine. The IOP was significantly higher at 30 and 45 minutes with both concentrations (p < 0.001). The best sensitivity/specificity ratio was achieved with the cutoff point set as greater than 3 mmHg at 45 minutes with 2% ibopamine (area under the ROC curve: 0.864, Se: 84.6%; Sp:73.3%). All patients described a slight burning after ibopamine's instillation. CONCLUSION: 2% ibopamine is recommended as a provocative test for glaucoma. Because both concentrations have similar ability to rise IOP, 1% ibopamine may be used to treat ocular hypotony.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Dopamine Agonists , Glaucoma, Open-Angle/diagnosis , Intraocular Pressure/drug effects , Mydriatics , Aged , Deoxyepinephrine/administration & dosage , Dopamine Agonists/administration & dosage , Female , Glaucoma, Open-Angle/drug therapy , Humans , Male , Middle Aged , Mydriatics/administration & dosage , Ophthalmic Solutions , Prospective Studies , Sensitivity and Specificity , Time Factors , Vision Tests
15.
Klin Monbl Augenheilkd ; 223(5): 422-4, 2006 May.
Article in German | MEDLINE | ID: mdl-16705521

ABSTRACT

BACKGROUND: Ibopamine is a non-selective dopamine- and adrenalin-receptor agonist that has been shown to cause pupillary dilation and an increase in aqueous humour secretion. This novel drug can be used as a mydriatic agent, as a provocative test in open-angle glaucoma, and for the treatment of persisting ocular hypotony. HISTORY AND SIGNS: This 47-year-old man had a history of uveitis associated with Crohn's disease. Six years after deep sclerectomy for uveitic secondary glaucoma, he developed severe hypotony in his left eye with drop of visual acuity (VA). The hypotony did not respond to topical steroid treatment. 2 % Ibopamine solution was ordered t. i. d. concomitant to 1 % prednisolone acetate. THERAPY AND OUTCOME: Intraocular pressure (IOP) began to rise after 3 weeks of Ibopamine treatment and returned to normal (12 mmHg) with continuous recovery of VA after 8 weeks. Ibopamine was discontinued at an IOP of 16 mmHg after a course of 12 weeks. IOP and VA remained stable during the 12-month follow-up period. CONCLUSIONS: Ibopamine 2 % eye drops in combination with topical steroids are a therapeutic option in uveitis-associated ocular hypotony.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Ocular Hypotension/etiology , Ocular Hypotension/prevention & control , Uveitis/complications , Uveitis/drug therapy , Administration, Topical , Chronic Disease , Deoxyepinephrine/administration & dosage , Humans , Male , Mydriatics/administration & dosage , Treatment Outcome
16.
Arq Bras Oftalmol ; 69(2): 193-6, 2006.
Article in Portuguese | MEDLINE | ID: mdl-16699669

ABSTRACT

PURPOSE: To evaluate the ibopamine provocative test for the diagnosis of glaucoma in glaucoma patients using antiglaucomatous drugs. METHODS: Two 2% ibopamine eyedrops were instilled 5 minutes apart in one eye selected at random in both glaucoma and normal subjects. The intraocular pressure (IOP) was assessed prior to the drops and 30, 60 and 180 minutes after instillation. The test was considered positive when there was an intraocular pressure increase of greater than 4 mmHg at any one of the time-points. The amount of intraocular pressure change was compared to the types of medical treatment. RESULTS: Fifty-eight eyes were included (38 glaucoma patients and 20 normal individuals). The intraocular pressure rise was significantly higher in glaucoma patients (p<0.001 at all times). The sensitivity and specificity of the ibopamine test were 68% (87% if we exclude eyes using prostaglandin analogues) and 95%, respectively. Glaucoma patients using prostaglandin analogues did not present a significant intraocular pressure elevation. CONCLUSION: The ibopamine provocative test may be an auxiliary test in glaucoma diagnosis. Despite the small sample size, concurrent use of prostaglandin analogues apparently reduces the test's sensitivity.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Dopamine Agonists , Glaucoma/diagnosis , Intraocular Pressure/drug effects , Prostaglandins, Synthetic/therapeutic use , Tonometry, Ocular , Deoxyepinephrine/administration & dosage , Glaucoma/drug therapy , Humans , Sensitivity and Specificity , Time Factors
17.
Arq. bras. oftalmol ; 69(2): 193-196, mar.-abr. 2006. tab, graf
Article in Portuguese | LILACS | ID: lil-426715

ABSTRACT

OBJETIVO: Avaliar o desempenho do teste provocativo da ibopamina em pacientes com glaucoma usuários de drogas hipotensoras. MÉTODOS: Pacientes glaucomatosos foram recrutados do Centro de Referência em Oftalmologia (CEROF) da Universidade Federal de Goiás, e suas drogas hipotensoras em uso registradas. Indivíduos normais foram amigos e parentes dos pacientes. A seguir, foram instiladas duas gotas de ibopamina 2 por cento com intervalo de 5 minutos. A pressão intra-ocular (Pio) foi medida previamente, e após 30, 60 e 180 minutos. No nosso estudo, o teste da ibopamina foi considerado positivo quando a pressão intra-ocular excedeu 4 mmHg em pelo menos uma das medidas. RESULTADOS: Cinquenta e oito olhos de 58 indivíduos (38 glaucomatosos e 20 normais) foram incluídos no estudo. O aumento da pressão intra-ocular foi maior nos pacientes com glaucoma aos 30, 60 e 180 minutos (p<0,001 em todas as ocasiões). O aumento da pressão intra-ocular foi estatisticamente maior aos 30 minutos nos indivíduos que não utilizavam análogos das prostaglandinas (p=0,01). A sensibilidade do teste foi de 68 por cento (87 por cento se excluirmos pacientes em uso de análogos das prostaglandinas), e a especificidade de 95 por cento. CONCLUSÃO: O teste provocativo da ibopamina 2 por cento pode ser ferramenta auxiliar no diagnóstico do glaucoma. Apesar da pequena amostra estudada, sugere-se que olhos em uso de análogos das prostaglandinas têm reduzido a sensibilidade do mesmo.


Subject(s)
Humans , Deoxyepinephrine/analogs & derivatives , Dopamine Agonists , Glaucoma/diagnosis , Intraocular Pressure/drug effects , Prostaglandins, Synthetic/therapeutic use , Tonometry, Ocular , Deoxyepinephrine/administration & dosage , Deoxyepinephrine , Glaucoma/drug therapy , Sensitivity and Specificity , Time Factors
18.
Am J Ophthalmol ; 141(3): 571-3, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16490513

ABSTRACT

PURPOSE: To study whether topical ibopamine effectively increases the intraocular pressure in patients with ocular hypotony after vitreoretinal surgery, uveitis, or penetrating trauma. DESIGN: A prospective randomized, double-blind, placebo controlled, crossover study. METHODS: In ten patients with ocular hypotony, an ibopamine 2% solution or placebo eyedrop was administered at 8 am and frequent applanation tonometry was performed during 10 hours on 2 days, 2 weeks apart. RESULTS: The mean IOP integral after administration of ibopamine was 2.4 mm Hg higher (95% CI for median difference in AUC over 480 minutes [P = .010]) compared with placebo. CONCLUSIONS: The results of the study show that an ibopamine 2% eyedrop twice a day may increase the IOP for a period of over 8 hours in patients with hypotony.


Subject(s)
Deoxyepinephrine/analogs & derivatives , Dopamine Agonists/therapeutic use , Eye Injuries, Penetrating/complications , Intraocular Pressure/drug effects , Ocular Hypotension/drug therapy , Uveitis/complications , Vitrectomy/adverse effects , Administration, Topical , Adult , Aged , Chronic Disease , Cross-Over Studies , Deoxyepinephrine/administration & dosage , Deoxyepinephrine/therapeutic use , Dopamine Agonists/administration & dosage , Double-Blind Method , Female , Humans , Male , Middle Aged , Ocular Hypotension/etiology , Prospective Studies , Tonometry, Ocular , Visual Acuity
19.
Br J Pharmacol ; 144(2): 231-41, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15665862

ABSTRACT

1. This study investigated whether the immediate and long-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamines in mouse brain are due to the parent compound and the possible contribution of a major reactive metabolite, 3,4-dihydroxymethamphetamine (HHMA), to these changes. The acute effect of each compound on rectal temperature was also determined. 2. MDMA given i.p. (30 mg kg(-1), three times at 3-h intervals), but not into the striatum (1, 10 and 100 microg, three times at 3-h intervals), produced a reduction in striatal dopamine content and modest 5-HT reduction 1 h after the last dose. MDMA does not therefore appear to be responsible for the acute monoamine release that follows its peripheral injection. 3. HHMA does not contribute to the acute MDMA-induced dopamine depletion as the acute central effects of MDMA and HHMA differed following i.p. injection. Both compounds induced hyperthermia, confirming that the acute dopamine depletion is not responsible for the temperature changes. 4. Peripheral administration of MDMA produced dopamine depletion 7 days later. Intrastriatal MDMA administration only produced a long-term loss of dopamine at much higher concentrations than those reached after the i.p. dose and therefore bears little relevance to the neurotoxicity. This indicates that the long-term effect is not attributable to the parent compound. HHMA also appeared not to be responsible as i.p. administration failed to alter the striatal dopamine concentration 7 days later. 5. HHMA was detected in plasma, but not in brain, following MDMA (i.p.), but it can cross the blood-brain barrier as it was detected in the brain following its peripheral injection. 6. The fact that the acute changes induced by i.p. or intrastriatal HHMA administration differed indicates that HHMA is metabolised to other compounds which are responsible for changes observed after i.p. administration.


Subject(s)
Biogenic Monoamines/metabolism , Corpus Striatum/drug effects , Deoxyepinephrine/analogs & derivatives , Deoxyepinephrine/administration & dosage , N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage , Animals , Brain/drug effects , Brain/metabolism , Corpus Striatum/metabolism , Deoxyepinephrine/chemistry , Dose-Response Relationship, Drug , Drug Administration Schedule , Injections, Intraperitoneal , Injections, Intraventricular , Male , Mice , Mice, Inbred C57BL , N-Methyl-3,4-methylenedioxyamphetamine/chemistry , Time Factors
20.
Ophthalmic Res ; 37(1): 17-22, 2005.
Article in English | MEDLINE | ID: mdl-15627837

ABSTRACT

BACKGROUND: To evaluate the ability of topical ibopamine 2% to detect outflow resistance by comparing it with the tonography test in eyes with ocular hypertension (OHT). METHODS: 62 eyes with OHT and 33 control eyes were included in this prospective study. Tonography was done manually as a standard outflow facility measurement. We used a C value of 0.18 mul/min/mm Hg or less and a P(o)/C value of 100 and above as a positive tonographic test. The ibopamine test performed on the following day was considered positive if there was an intraocular pressure (IOP) change of at least 3 mm Hg. RESULTS: The sensitivity of the tonography and ibopamine tests was 69 and 53%, respectively, in eyes with OHT. The specificity of both tests was 97%. Although the sensitivity of the tonography test is higher than that of the ibopamine test, the difference between both was not statistically significant in these eyes (p = 0.409). Positive results in tonography were associated with higher IOP, while the results were not dependent on the IOP in the ibopamine test. Both tests together were positive in 33.87% (21 eyes) and negative in 11.29% (7 eyes) in 62 eyes with OHT. CONCLUSION: This study revealed that the ibopamine provocation test can detect outflow system resistance in eyes with OHT comparable with tonography which is a traditional outflow facility measurement. Ibopamine, however, can detect the eye with outflow impairment by a different and IOP-independent way, while tonography depends on IOP.


Subject(s)
Aqueous Humor/metabolism , Deoxyepinephrine/analogs & derivatives , Dopamine Agonists , Intraocular Pressure , Ocular Hypertension/diagnosis , Tonometry, Ocular , Administration, Topical , Adult , Aged , Deoxyepinephrine/administration & dosage , Dopamine Agonists/administration & dosage , Glaucoma, Open-Angle/diagnosis , Humans , Intraocular Pressure/drug effects , Middle Aged , Ophthalmic Solutions/administration & dosage , Prospective Studies , Sensitivity and Specificity
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