<p>Two different principles were studied. 1st - statistical analysis techniques were used to obtain medical results from a patient population. 2nd - the patient population was used to study the statistical analysis techniques. </p><p>Medical conclusions: latanoprost and timolol treatment showed a statistically significant and clinically useful mean IOP-reduction in a typical worldwide clinical trial population. Latanoprost reduced the IOP 1.6 mm Hg more than timolol. The IOP-reduction was maintained with timolol and slightly enforced with latanoprost up to 6 months of treatment. The mean IOP-reduction was maintained during 2 years of latanoprost treatment. The overall risk of withdrawal due to insufficient IOP-reduction with latanoprost was 8%. </p><p>The statistical methodological issues are of a general and reoccurring character in trial design of the IOP-reduction: should the statistical hypothesis testing be based on the mean intraocular pressure (IOP) or the proportion of patients who reach a specific IOP level, should the estimate of the IOP or IOP-reduction be based on single eyes, mean of bilaterally eligible and identically treated eyes or the difference between an eye with active treatment and a placebo treated contralateral eye, and is mean of replicated recordings useful? Statistical methodological conclusions: the most effective response variable varies with the selected patient population. Therefore, the trial design process should include a comparison of the variability, test power and required sample size for the possible response variables in a sample of the target population. At minimum a statistical consideration should be done.</p>

Glucocorticoids (GCs) have been widely used as a therapeutic agent for diverse inflammatory ocular diseases. However, a high percentage of patients undergoing this treatment develop high intraocular pressure (IOP), which if left unsupervised may lead to glaucoma. It is believed that the IOP elevation in response to GC treatment has a genetic determinant. In order to test this hypothesis, we analyzed in 52 patients the presence of single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor gene (GR), the principal mediator of GCs uptake by the cells. We studied six GR SNPs previously reported to be associated with sensitivity and resistance to GCs: GluArg22/23GluLys (codon 22-23), Asn363Ser (codon 363), IVS2+646C>G (intron 2/BclI), IVS3-46G>C (intron 3), IVS4-16G>T (intron 4), Asn766Asn (Codon 766). Nevertheless, the results of this preliminary study did not show any specific correlation between SNPs in the GR gene and IOP elevation. Therefore, we proceeded to perform a whole genome SNP screen with the DNA samples of these patients to search for possible target genes responsible for the elevated IOP after GC treatment. As a result, we identified forty-eight SNPs in thirty-three genes that correlate with the high IOP response. The gene showing the strongest association is a poorly known G-protein coupled receptor. In addition, four SNPs hit a single transporter gene. Other candidate genes identified are a translation elongation factor, an F-box protein, an oxysterol binding protein, and a solute carrier family gene. These results support our hypothesis that IOP elevation following GC treatment is a genetically determined response. GCs are a common treatment for innumerable medical conditions; we believe that a genetic association between GC treatment and its physiological response may be important for improving treatment management and drug development for retinal diseases as well as for other medical ailments. However, further studies need to be performed to analyze in depth the association between the candidate genes identified in this study and the steroid response.

Two different principles were studied. 1st - statistical analysis techniques were used to obtain medical results from a patient population. 2nd - the patient population was used to study the statistical analysis techniques. Medical conclusions: latanoprost and timolol treatment showed a statistically significant and clinically useful mean IOP-reduction in a typical worldwide clinical trial population. Latanoprost reduced the IOP 1.6 mm Hg more than timolol. The IOP-reduction was maintained with timolol and slightly enforced with latanoprost up to 6 months of treatment. The mean IOP-reduction was maintained during 2 years of latanoprost treatment. The overall risk of withdrawal due to insufficient IOP-reduction with latanoprost was 8%. The statistical methodological issues are of a general and reoccurring character in trial design of the IOP-reduction: should the statistical hypothesis testing be based on the mean intraocular pressure (IOP) or the proportion of patients who reach a specific IOP level, should the estimate of the IOP or IOP-reduction be based on single eyes, mean of bilaterally eligible and identically treated eyes or the difference between an eye with active treatment and a placebo treated contralateral eye, and is mean of replicated recordings useful? Statistical methodological conclusions: the most effective response variable varies with the selected patient population. Therefore, the trial design process should include a comparison of the variability, test power and required sample size for the possible response variables in a sample of the target population. At minimum a statistical consideration should be done.

La neuropathie optique glaucomateuse est une pathologie du système visuel entrainant une cécité irréversible qui affectera 80 millions de personnes en 2020. Le principal facteur de risque du glaucome est l'élévation de la pression intraoculaire qui mène à la mort progressive des cellules ganglionnaires de la rétine (CGR) du nerf optique jusqu'aux voies visuelles dans le cerveau. Il a été montré que le glaucome partageait des mécanismes neuro-inflammatoires communs avec les pathologies neurodégénératives. Nous avons émis l'hypothèse que ces mécanismes contribueraient à la progression du glaucome. L'objectif de ma thèse a été d'analyser les processus neuro-inflammatoires observés de la rétine jusqu'aux colliculus supérieurs sur un modèle expérimental d'hypertension oculaire unilatérale chez le rat obtenu après la cautérisation des veines épisclérales. Par des approches de biologie cellulaire et moléculaire, nous avons montré que ce modèle animal se caractérise par 1) une atteinte neuronale des CGR de l'oeil cautérisé; 2) l'augmentation de marqueurs pro-inflammatoires dans la rétine de l'oeil cautérisé, dans la rétine de l'oeil controlatéral, dans le nerf optique et dans les colliculus supérieurs et 3) la transmission de la neuro-inflammation à l'oeil controlatéral se fait majoritairement par les fibres des CGR qui projettent dans les deux colliculus supérieurs. Toutes ces données mettent en évidence le rôle complexe joué par le colliculus supérieur chez le rat dans la propagation de la neuro-inflammation induite par l'hypertension oculaire unilatérale. / Glaucoma is a visual system disorder leading to irreversible blindness and affecting 80 millions people worldwide by 2020. The major risk factor is elevated intraocular pressure leading to progressive retinal ganglion cell (RGC) death from the optic nerve (ON) to visual pathways in the brain. Glaucoma has been reported to share neuroinflammatory mechanisms with neurodegenerative disorders. We therefore hypothesize that mechanisms in central visual pathways may contribute to the spread of glaucoma disease. The aim of the present study was to analyze the neuroinflammation processes that occur from the pathological retina to the superior colliculi (SCs) in a rat model of unilateral ocular hypertension induced by episcleral vein cauterization. By molecular and cell biology methods, we have shown that this animal model is characterized by 1) neuronal damage of CGR from the cauterized eye; 2) the increase in proinflammatory markers in the retina of the cauterized eye, in the retina of the contralateral eye, in the optic nerve and in the superior colliculus and 3) transmission of neuroinflammation in contralateral eye is done mainly by CGR fibers that project into the two superior colliculus. All these data evidence the complex role played by the SCs, in rat, in the propagation of neuroinflammatory events induced by unilateral ocular hypertension.

Die vorliegende Arbeit diskutiert methodische Aspekte und Ergebnisse eigener pharmakoepdemiologischer Untersuchungen zum Risiko von okulärer Hypertension, Glaukom und Katarakt unter verschiedenen Darreichungsformen von Glukokortikoiden. Prospektive Studien der frühen 60er Jahre haben gezeigt, daß die Verabreichung topischer Glukokortikoide am Auge bei ca. einem Drittel der Bevölkerung zu einem Augeninnendruckanstieg führt. Bei langdauernder Therapie kann sich ein Kortikosteroidglaukom entwickeln, das in seiner Symptomatik und den klinischen Befunden einem primären Offenwinkelglaukom entspricht. Für orale Glukokortikoide untersuchten wir das Risiko von okulärer Hypertension und Offenwinkelglaukom in einer großen Fall-Kontroll-Studie, die 9.793 augenärztliche Patienten mit neu diagnostizierter okulärer Hypertension und Offenwinkelglaukom einschloß und 38.325 augenärztliche Kontrollpatienten ohne diese Erkrankungen. Die Einnahme oraler Glukokortikoide war mit einem Risikoanstieg von über 40% verbunden. Es zeigte sich ein deutlicher Anstieg des Risikos mit zunehmender Glukokortikoid-Tagesdosis: Für Patienten, die mehr als 80 mg Hydrokortisonäquivalent pro Tag erhalten hatten, war das Risiko über 80% erhöht. Unsere Berechnungen zeigten, daß unter solch hohen Dosen 93 zusätzliche Fälle von okulärer Hypertension oder Offenwinkelglaukom pro 10.000 Patienten und Jahr auftreten können. In derselben Fall-Kontroll-Studie analysierten wir auch das Risiko für inhalative und nasale Glukokortikoide. Zwar ist für diese Glukokortikoidformen das Risiko systemischer Glukokortikoidnebenwirkungen durch die topische Applikation deutlich reduziert, doch legen verschiedene klinisch-pharmakologische Untersuchungen nahe, daß inhalative Glukokortikoide in hoher Dosierung systemische Effekte ausüben können. Verschiedene Einzelfallberichte ließen ein erhöhtes Risiko von okulärer Hypertension und Glaukom für inhalative und nasale Glukokortikoide möglich erscheinen. Unsere Fall-Kontroll-Studie zeigte, daß inhalative Glukokortikoide, wenn sie in hohen Tagesdosen kontinuierlich über 3 Monate verabreicht werden, das Risiko von okulärer Hypertension und Offenwinkelglaukom um über 40% erhöhen. Wir beobachteten kein erhöhtes Risiko für nasale Glukokortikoide. In einer weiteren Fall-Kontroll-Studie untersuchten wir das Kataraktrisiko für inhalative Glukokortikoide. Orale Glukokortikoide sind ein etablierter Risikofaktor für eine Katarakt. Für inhalative Glukokortikoide lagen widersprüchliche Studienergebnisse vor. Während mehrere kleine Studien an Kindern kein erhöhtes Risiko gezeigt hatten, war in einer großen populationsbasierten australischen Studie ein erhöhtes Kataraktrisiko unter inhalativen Glukokortikoiden beobachtet worden. Wir konnten das Ergebnis der australischen Studie in unserer Fall-Kontroll-Studie bestätigen, die 3.677 Fallpatienten und 21.868 Kontrollpatienten einschloß. Eine Verabreichung inhalativer Glukokortikoide über mehr als 3 Jahre führte zu einer Verdreifachung des Risikos einer Kataraktextraktion. Das Risiko war nur für hohe Dosen inhalativer Glukokortikoide statistisch signifikant erhöht, nicht jedoch für niedrige bis mittlere Tagesdosen. Zusammengefaßt zeigen die Ergebnisse unserer Studien, daß inhalative Glukokortikoide in hoher Dosierung trotz topischer Applikation zu systemischen Glukokortikoidkomplikationen am Auge führen können. Dies läßt es geboten erscheinen, bei Patienten, die inhalative Glukokortikoide in hoher Dosierung erhalten, augenärztliche Kontrolluntersuchungen durchführen zu lassen / This work presents methodological aspects and results of own pharmacoepidemiologic studies investigating the risk of ocular hypertension, glaucoma and cataract for different forms of glucocorticoids.. Prospective studies of the early 60ies have shown that administration of topical glucorticoids at the eye will lead to ocular hypertension in about one third of the population. If ophthalmic glucocorticoid treatment is prolonged, a corticosteroid glaucoma may develop which closely resembles primary open-angle glaucoma.. We investigated the risk of ocular hypertension or open-angle glaucoma for oral glucocorticoids in a large case-control-study which included 9,793 ophthalmology patients with newly diagnosed ocular hypertension or open-angle glaucoma and 38,325 ophthalmology patients without these diseases (controls). Intake of oral glucocorticoids led to an increase in risk by over 40%. The risk increased markedly with the daily dose of glucocorticoid. For patients who had received more than 80 mg hydrocortisone-equivalent per day, the risk was more than 80% elevated. Our calculations showed that for such high doses, 93 additional cases of ocular hypertension or glaucoma per 10,000 patients and year may be expected. In the same case-control study, we analysed the risk of ocular hypertension and open-angle glaucoma for inhaled and nasal glucocorticoids. These forms of glucocorticoids have been developed to reduce the risk of systemic glucocorticoid complications by topical administration. Some clinical pharmacology studies have shown that high doses of inhaled glucocorticoids may cause systemic effects. Some published case reports suggested an increased risk of ocular hypertension and glaucoma for inhaled and nasal glucocorticoids. Our case-control study showed that high dose, continuous administration of inhaled glucocorticoids for more than 3 months increases the risk of ocular hypertension or open angle glaucoma by more than 40%. We did not observe an increased risk for nasal glucocorticoids. In another case-control study, we investigated the risk of cataract for inhaled glucocorticoids. Oral glucocorticoids are an established risk factor for cataract. For inhaled glucocorticoids, there have been contradictory results from several studies. Whereas some small studies in children did not show an increased risk, a population-based larger study from Australia demonstrated an elevated risk. We confirmed this increase in risk in our case-control study which included 3,677 elderly cases and 21,868 elderly controls. We observed a more than 3-fold risk of cataract extraction in patients who had been treated with inhaled glucocorticoids for more than three years. The risk was significantly increased only for high daily doses of glucocorticoids, but not for low-to-medium doses. In summary, the results of our studies show that high doses of inhaled glucocorticoids despite their topical administration may lead to systemic complications of glucocorticoids at the eye. Therefore it is recommended to have patients who are prescribed high daily doses of inhaled glucocorticoids examined by an ophthalmologist.

Made available in DSpace on 2016-04-28T20:18:32Z (GMT). No. of bitstreams: 1 2006-Maria Alice Fusco de Souza.pdf: 1870301 bytes, checksum: a5cdc0a6b5d34e7bd2f9f4705c4edc2d (MD5) Previous issue date: 2006-08-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / It is recognized the role of prostaglandins in lowering de intraocular pressure, and more recently, the observation of constitutive expression of COX-2 in the healthy eyes and the absence of this isoenzyme in glaucomatous eyes. These discoveries bring the hypothesis that the use of anti-inflammatory drugs may cause, as unwanted effects, ocular hypertension through the inhibition of COX expression and the reduction of prostaglandins production. The increase of intraocular pressure, even in a transient way, is a risk factor for the development of the glaucoma. In order to observe a possible ocular hypertension associated with the use of anti-inflammatory drugs, 28 beagle dogs were selected from the kennel of the Laboratory of Development of Parasiticide Products, Department of Animal Parasitology, Veterinary Institute, Universidade Federal Rural do Rio de Janeiro. On day 0 (zero) the totality of animals had their intraocular pressure measured using applanation tonometry at 8 a.m. and 4 p.m., for evaluation of intraocular pressure before treatment; on the following day 10 animals received meloxican, associated with wet feeding, on dosage of 0.2 mg Kg-1 and 0.1 mg weight on the remainder of the four days, nine dogs received prednisone, associated with wet feeding, on dosage of 1,0 mg Kg-1 during five days and nine dogs received only wet feeding. On the fifth day of treatment the totality of dogs had their intraocular pressure measured again using applanation tonometry at 8 a.m. and 4 p.m. For all groups, including control-group, the highest average values of intraocular pressure were observed on day 5 (five). The difference between intra-ocular pressure mensurations of the 08 hours and of the 16 hours was significant, independent of treatment and of the considered day. The use of both steroidal or non-steroidal anti-inflammatory were not capable of causing ocular hypertension and some factors can be incriminated, such as route of administration, dosage and duration of therapy chosen, besides genetic inheritance and absence of glaucomatous disorder between the selected dogs. / ? reconhecido o papel hipotensor ocular das prostaglandinas e mais recentemente, a observa??o da express?o de COX-2 constitutiva em olhos saud?veis e aus?ncia desta isoenzima em olhos glaucomatosos. Estas descobertas geram a hip?tese de que o uso de antiinflamat?rios apresente como efeito colateral, a hipertens?o ocular pela inibi??o da express?o da COX e diminui??o da produ??o de prostaglandinas. O aumento de press?o intra-ocular, mesmo que transit?rio, ? um fator de risco para o desenvolvimento do glaucoma. Para poss?vel observa??o da hipertens?o ocular com o uso de antiinflamat?rios, foram selecionados 28 c?es da ra?a beagle pertencentes ao Canil do Laborat?rio de Desenvolvimento de Produtos Parasiticidas do Departamento de Parasitologia Animal do Instituto de Veterin?ria da Universidade Federal Rural do Rio de Janeiro. No dia 0 (zero) todos os animais tiveram a press?o intra-ocular mensurada com o uso do ton?metro de aplana??o ?s 08 horas e ?s 16 horas, para avalia??o da press?o intra-ocular antes do tratamento; no dia seguinte dez c?es receberam meloxicam, junto ? por??o de ra??o ?mida, na dosagem de 0,2 mg/Kg e 0,1mg/Kg nos restantes quatro dias, nove c?es receberam prednisona, junto ? por??o de ra??o ?mida, na dosagem de 1,0 mg/Kg durante cinco dias e nove c?es receberam somente a por??o de ra??o ?mida. No quinto dia do tratamento todos os animais tiveram novamente a press?o intra-ocular mensurada com o uso do ton?metro de aplana??o ?s 08 horas e ?s 16 horas. Em todos os grupos, incluindo o grupo-controle, as maiores m?dias de press?o intra-ocular foram observadas no dia 5 (cinco). A diferen?a dos valores de press?o intra-ocular observada entre as medi??es das 08 horas e das 16 horas foi significativa, independente do tratamento e do dia considerado. O uso dos antiinflamat?rios esteroidal e n?o-esteroidal n?o foi capaz de causar hipertens?o ocular e alguns fatores podem ser incriminados, como via de administra??o, dosagem e dura??o do tratamento utiliz ados, al?m da heran?a gen?tica e aus?ncia de doen?a glaucomatosa nos c?es selecionados.

En esta tesis estudiamos la población total de las células ganglionares de la retina (CGR) en rata y ratón, y desarrollamos un modelo experimental de hipertensión ocular mediante fotocoagulación láser. La población de CGR proyecta masivamente a los colículos superiores. Se observa una estría visual en la retina dorsal donde se encuentra las densidades más altas de CGR. La pequeña población de CGR ipsilateral se distribuye mayoritariamente en la periferia de la retina temporal. El aumento de la presión intraocular induce una compresión de los axones en la cabeza del nervio óptico que provoca una alteración del transporte axonal retrógrado, que induce una degeneración sectorial localizada y difusa de las CGR, preferentemente en la retina dorsal, así como de sus axones. La pérdida selectiva de las CGR en la capa de CGR, sugiere que la causa de la muerte de las CGR no se debe a una isquemia retiniana. / In this thesis we have studied the total population of retinal ganglion cells (RGCs) in rat and mouse, and developed an experimental model of ocular hypertension by laser photocoagulation. The RGC population projects massively to the superior colliculi. There is a visual streak in the dorsal retina where the highest densities of RGCs are found. The small population of ipsilateral RGCs is distributed mainly in the periphery of the temporal retina. The increase of intraocular pressure induces a compression of the axons at the optic nerve head that causes a disturbed retrograde axonal transport, inducing a localized, diffuse and sectorial degeneration of RGCs and their axons, preferably in the dorsal retina. The selective loss of RGCs in the RGC layer, suggests that the cause of the RGC loss is not due to retinal ischemia.

OBJETIVO: avaliar a reprodutibilidade da curva tensional modificada e do teste de sobrecarga hídrica em portadores de glaucoma de ângulo aberto ou hipertensos oculares, sem uso de hipotensor ocular, em dois dias consecutivos. MÉTODOS: análise prospectiva de pacientes portadores de glaucoma de ângulo aberto ou hipertensos oculares, submetidos à curva tensional modificada (medida da pressão intraocular às 8h, 11h, 14h e 16h), seguida do teste de sobrecarga hídrica (três medidas com intervalo de 15 minutos, iniciando-se 15 minutos após a ingestão, em cinco minutos, de um litro de água em temperatura ambiente), realizados pelo mesmo examinador, em dois dias consecutivos. Foram avaliadas: a reprodutibilidade da pressão intraocular em cada horário de medida durante a curva tensional modificada; a reprodutibilidade da pressão intraocular média, flutuação e pico de pressão durante a curva tensional modificada; a reprodutibilidade da flutuação e do pico de pressão durante o teste de sobrecarga hídrica. Calculou-se o coeficiente de correlação intraclasse para cada parâmetro. RESULTADOS: oitenta e oito olhos de 88 pacientes foram estudados. Destes, 64 eram portadores de glaucoma de ângulo aberto. A média das idades dos participantes foi 68,7+10,8 (51-79) anos. 65% dos pacientes eram do sexo feminino. A curva tensional modificada apresentou coeficiente de correlação intraclasse igual a 0,80, 0,82, 0,83 e 0,86 para as medidas realizadas às 8h, 11h, 14h e 16h, respectivamente (p < 0,001). A flutuação da pressão durante a curva tensional modificada, calculada pela diferença entre as pressões máxima e mínima e pelo desvio-padrão da média das medidas diurnas de pressão, a pressão média e o pico pressórico apresentaram coeficientes 0,60, 0,62, 0,91 e 0,85, respectivamente (p < 0,001). Durante o teste de sobrecarga hídrica, a flutuação apresentou coeficiente de 0,37 e o pico pressórico, 0,79. (p < 0,001). CONCLUSÕES: neste estudo, as medidas de pressão intraocular realizadas durante a curva tensional modificada, a média e o pico apresentaram excelentes níveis de reprodutibilidade. O pico pressórico durante o teste de sobrecarga hídrica apresentou também excelente reprodutibilidade. A flutuação, tanto na curva tensional modificada, quanto no teste de sobrecarga hídrica, apresentou os menores índices de reprodutibilidade / OBJECTIVE: to evaluate the reproducibility of the modified daily tension curve and the water drinking test in patients with open-angle glaucoma or ocular hypertension, not under topical treatment, during two consecutive days. METHODS: prospective analysis of open-angle glaucoma or ocular hypertensive patients, submitted to a modified daily tension curve (intraocular pressure measurements at 8AM, 11AM, 2PM and 4PM), followed by the water drinking test (three intraocular pressure measurements with 15 minutes intervals, 15 minutes after ingestion of one liter of tap water), performed by the same examiner, within two consecutive days. The following parameters were evaluated for reproducibility: intraocular pressure obtained at each time-point during the modified daily tension curve; mean, peak and pressure fluctuation during the curve and peak and fluctuation during the water drinking test. Reproducibility was assessed using the intraclass correlation coefficient. RESULTS: eighty-eight eyes from 88 patients were studied. From these, 64 presented open-angle glaucoma. Mean age was 68.7+10.8 (51-79) years. 65% patients were female. Intraclass correlation coefficients were 0.80, 0.82, 0.83 and 0.86 for intraocular pressure measurements at 8AM, 11AM, 2PM and 4PM, respectively (p<0.001) Fluctuation calculated as the difference between maximum and minimum intraocular pressures, fluctuation calculated as the standard deviation of the four daily measurements, mean and peak pressures presented coefficients of 0.60, 0.62, 0.91 and 0.85, respectively (p<0.001). During the water drinking test, coefficient values for fluctuation and peak pressure were 0.37 and 0.79 (p<0.001). CONCLUSIONS: in this study, intraocular pressure measurements during a modified daily tension curve, mean intraocular pressure and pressure peaks presented excellent reproducibility levels; pressure peaks during the water drinking test also presented excellent reproducibility level, whereas fluctuation, both during the modified daily tension curve and during the water drinking test, was the least reproducible parameter

OBJETIVO: avaliar a reprodutibilidade da curva tensional modificada e do teste de sobrecarga hídrica em portadores de glaucoma de ângulo aberto ou hipertensos oculares, sem uso de hipotensor ocular, em dois dias consecutivos. MÉTODOS: análise prospectiva de pacientes portadores de glaucoma de ângulo aberto ou hipertensos oculares, submetidos à curva tensional modificada (medida da pressão intraocular às 8h, 11h, 14h e 16h), seguida do teste de sobrecarga hídrica (três medidas com intervalo de 15 minutos, iniciando-se 15 minutos após a ingestão, em cinco minutos, de um litro de água em temperatura ambiente), realizados pelo mesmo examinador, em dois dias consecutivos. Foram avaliadas: a reprodutibilidade da pressão intraocular em cada horário de medida durante a curva tensional modificada; a reprodutibilidade da pressão intraocular média, flutuação e pico de pressão durante a curva tensional modificada; a reprodutibilidade da flutuação e do pico de pressão durante o teste de sobrecarga hídrica. Calculou-se o coeficiente de correlação intraclasse para cada parâmetro. RESULTADOS: oitenta e oito olhos de 88 pacientes foram estudados. Destes, 64 eram portadores de glaucoma de ângulo aberto. A média das idades dos participantes foi 68,7+10,8 (51-79) anos. 65% dos pacientes eram do sexo feminino. A curva tensional modificada apresentou coeficiente de correlação intraclasse igual a 0,80, 0,82, 0,83 e 0,86 para as medidas realizadas às 8h, 11h, 14h e 16h, respectivamente (p < 0,001). A flutuação da pressão durante a curva tensional modificada, calculada pela diferença entre as pressões máxima e mínima e pelo desvio-padrão da média das medidas diurnas de pressão, a pressão média e o pico pressórico apresentaram coeficientes 0,60, 0,62, 0,91 e 0,85, respectivamente (p < 0,001). Durante o teste de sobrecarga hídrica, a flutuação apresentou coeficiente de 0,37 e o pico pressórico, 0,79. (p < 0,001). CONCLUSÕES: neste estudo, as medidas de pressão intraocular realizadas durante a curva tensional modificada, a média e o pico apresentaram excelentes níveis de reprodutibilidade. O pico pressórico durante o teste de sobrecarga hídrica apresentou também excelente reprodutibilidade. A flutuação, tanto na curva tensional modificada, quanto no teste de sobrecarga hídrica, apresentou os menores índices de reprodutibilidade / OBJECTIVE: to evaluate the reproducibility of the modified daily tension curve and the water drinking test in patients with open-angle glaucoma or ocular hypertension, not under topical treatment, during two consecutive days. METHODS: prospective analysis of open-angle glaucoma or ocular hypertensive patients, submitted to a modified daily tension curve (intraocular pressure measurements at 8AM, 11AM, 2PM and 4PM), followed by the water drinking test (three intraocular pressure measurements with 15 minutes intervals, 15 minutes after ingestion of one liter of tap water), performed by the same examiner, within two consecutive days. The following parameters were evaluated for reproducibility: intraocular pressure obtained at each time-point during the modified daily tension curve; mean, peak and pressure fluctuation during the curve and peak and fluctuation during the water drinking test. Reproducibility was assessed using the intraclass correlation coefficient. RESULTS: eighty-eight eyes from 88 patients were studied. From these, 64 presented open-angle glaucoma. Mean age was 68.7+10.8 (51-79) years. 65% patients were female. Intraclass correlation coefficients were 0.80, 0.82, 0.83 and 0.86 for intraocular pressure measurements at 8AM, 11AM, 2PM and 4PM, respectively (p<0.001) Fluctuation calculated as the difference between maximum and minimum intraocular pressures, fluctuation calculated as the standard deviation of the four daily measurements, mean and peak pressures presented coefficients of 0.60, 0.62, 0.91 and 0.85, respectively (p<0.001). During the water drinking test, coefficient values for fluctuation and peak pressure were 0.37 and 0.79 (p<0.001). CONCLUSIONS: in this study, intraocular pressure measurements during a modified daily tension curve, mean intraocular pressure and pressure peaks presented excellent reproducibility levels; pressure peaks during the water drinking test also presented excellent reproducibility level, whereas fluctuation, both during the modified daily tension curve and during the water drinking test, was the least reproducible parameter