Biological drug therapy for ocular angiogenesis: Anti-VEGF agents and novel strategies based on nanotechnology.

Currently, biological drug therapy for ocular angiogenesis treatment is based on the administration of anti-VEGF agents via intravitreal route. The molecules approved with this purpose for ocular use include pegaptanib, ranibizumab, and aflibercept, whereas bevacizumab is commonly off-label used in the clinical practice. The schedule dosage involves repeated intravitreal injections of anti-VEGF agents to achieve and maintain effective concentrations in retina and choroids, which are administrated as solutions form. In this review article, we describe the features of different anti-VEGF agents, major challenges for their ocular delivery and the nanoparticles in development as delivery system of them. In this way, several polymeric and lipid nanoparticles are explored to load anti-VEGF agents with the aim of achieving sustained drug release and thus, minimize the number of intravitreal injections required. The main challenges were focused in the loading the molecules that maintain their bioactivity after their release from nanoparticulate system, followed the evaluation of them through studies of formulation stability, pharmacokinetic, and efficacy in in vitro and in vivo models. The analysis was based on the information published in peer-reviewed published papers relevant to anti-VEGF treatments and nanoparticles developed as ocular anti-VEGF delivery system.

[Ocular ischemic syndrome: clinical manifestations, diagnosis and evolution after treatment.] / Síndrome de isquemia ocular: manifestaciones clínicas, diagnóstico y evolución tras el tratamiento.

Ocular ischemia syndrome is caused by ocular chronic hypoperfusion due to stenosis or occlusion of the ipsilateral common or internal carotid artery. We present the case of a 58-year-old male with recurrent unilateral amaurosis fugax, ophthalmological examination compatible with chronic ocular ischemia, and severe stenosis of ipsilateral internal carotid artery. After angioplasty and stenting of the carotid stenosis, the findings resolved.

El síndrome de isquemia ocular es causado por la hipoperfusión ocular crónica debido a estenosis u oclusión de arteria carótida común o interna ipsilateral. Presentamos el caso de un varón de 58 años con episodios de amaurosis fugax unilateral, exploración oftalmológica compatible con isquemia ocular crónica y estenosis severa de arteria carótida interna ipsilateral. Tras la angioplastia y stent de la zona de estenosis carotídea, los hallazgos resolvieron.

Avaliação da pressão intraocular e da pressão de perfusão ocular durante a hemodiálise / Evaluation of intraocular pressure and ocular perfusion pressure during hemodialysis

Resumo Objetivo: Avaliar a variação da pressão intraocular e da pressão de perfusão ocular durante sessão de hemodiálise, nos períodos pré, intra (a cada hora) e pós dialítico, em pacientes tratados em Serviços de Referência em hemodiálise da cidade de Fortaleza - CE. Métodos: O estudo foi longitudinal e prospectivo. 45 pacientes foram submetidos à hemodiálise. Todos os pacientes foram recrutados a fazer um exame oftalmológico, além da aferição da pressão intraocular com o Tonopen. Resultados: A amostra foi composta por 26 homens e 19 mulheres com idade média de 51,8 anos. O estudo revelou que há uma diferença importante entre a pressão intraocular pré e pós hemodiálise, diminuindo em média 2,59 mmHg. Ao analisar a pressão de perfusão ocular, foi encontrado um aumento médio de 1,85 mmHg entre o início e o término da hemodiálise. Conclusão: De acordo com o presente estudo, o processo de hemodiálise é um procedimento aparentemente seguro em relação à alteração da pressão intraocular e da pressão de perfusão ocular, como causadores de patologias oculares, principalmente o glaucoma.

Abstract Objective: To evaluate the variation of intraocular pressure and ocular perfusion pressure during hemodialysis sessions, in the pre, intra (hourly) and post dialytic periods, in patients treated at Hemodialysis Reference Services in Fortaleza - CE. Methods: The study was longitudinal and prospective. 45 patients underwent hemodialysis. All patients were recruited to undergo an ophthalmologic examination, in addition to the intraocular pressure measurement with Tonopen. Results: The sample consisted of 26 men and 19 women with a mean age of 51.8 years. The study revealed that there is an important difference between pre and post hemodialysis intraocular pressure, decreasing by an average of 2.59 mmHg. When analyzing ocular perfusion pressure, an average increase of 1.85 mmHg was found between the onset and end of hemodialysis. Conclusion: According to the present study, the hemodialysis process is an apparently safe procedure in relation to altered intraocular pressure and ocular perfusion pressure, as causes of ocular pathologies, mainly glaucoma.

Intraocular Penetration of a vNAR: In Vivo and In Vitro VEGF165 Neutralization.

Variable new antigen receptor domain (vNAR) antibodies are novel, naturally occurring antibodies that can be isolated from naïve, immune or synthetic shark libraries. These molecules are very interesting to the biotechnology and pharmaceutical industries because of their unique characteristics related to size and tissue penetrability. There have been some approved anti-angiogenic therapies for ophthalmic conditions, not related to vNAR. This includes biologics and chimeric proteins that neutralize vascular endothelial growth factor (VEGF)165, which are injected intravitreal, causing discomfort and increasing the possibility of infection. In this paper, we present a vNAR antibody against human recombinant VEGF165 (rhVEGF165) that was isolated from an immunized Heterodontus francisci shark. A vNAR called V13, neutralizes VEGF165 cytokine starting at 75 µg/mL in an in vitro assay based on co-culture of normal human dermal fibroblasts (NHDFs) and green fluorescence protein (GFP)-labeled human umbilical vein endothelial cells (HUVECs) cells. In the oxygen-induced retinopathy model in C57BL/6:Hsd mice, we demonstrate an endothelial cell count decrease. Further, we demonstrate the intraocular penetration after topical administration of 0.1 µg/mL of vNAR V13 by its detection in aqueous humor in New Zealand rabbits with healthy eyes after 3 h of application. These findings demonstrate the potential of topical application of vNAR V13 as a possible new drug candidate for vascular eye diseases.

Contrast-enhanced ocular ultrasonography in brachycephalic dogs

Background: Contrast Enchantment Ultrasonography (CEUS) allows for detection of vascular flows that are difficult to detect with traditional methods. There were no reports found in the literature of the use of CEUS to evaluate the vascular pattern of the eye of brachycephalic dogs. The objective of this paper is to describe ultrasound findings observed in the eyes of healthy brachycephalic dogs subjected to CEUS.Materials, Methods & Results: Thirty adult brachycephalic dogs were subjected to physical, laboratorial, and ophthalmic examination. The eye structures were evaluated using CEUS after intravenous administration of Sonovue®. Contrast enhancement was seen in 52 eyes with a homogeneous and centrifugal filling pattern. Structures adequately enhanced consisted of the optic nerve, the retina-choroid-sclera complex (RCSC), and the ciliary body. The optic nerve was hyperenhanced and the other structures were isoenhanced. The wash-in time, peak enhancement time, and wash-out time were similar for both right and left eyes. Mean values and standard deviation were calculated for contrast wash-in time, peak enhancement time, and wash-out time in the optic nerve, RCSC, and ciliary body.Discussion: Ultrasound is an important diagnostic resource for veterinary ophthalmology and provides relevant information for the detection of pathological conditions of the eyes of animals. The contrast-enhanced ultrasound allows evaluation of tissues at the capillary level (macro and microcirculation), complementing the vascular ultrasound scan. This study brings original information on contrast-enhanced ultrasound findings for evaluation of eyes in dogs, creating novel diagnostic possibilities for the use of this imaging technique in veterinary ophthalmology.[...](AU)

Contrast-enhanced ocular ultrasonography in brachycephalic dogs

Background: Contrast Enchantment Ultrasonography (CEUS) allows for detection of vascular flows that are difficult to detect with traditional methods. There were no reports found in the literature of the use of CEUS to evaluate the vascular pattern of the eye of brachycephalic dogs. The objective of this paper is to describe ultrasound findings observed in the eyes of healthy brachycephalic dogs subjected to CEUS.Materials, Methods & Results: Thirty adult brachycephalic dogs were subjected to physical, laboratorial, and ophthalmic examination. The eye structures were evaluated using CEUS after intravenous administration of Sonovue®. Contrast enhancement was seen in 52 eyes with a homogeneous and centrifugal filling pattern. Structures adequately enhanced consisted of the optic nerve, the retina-choroid-sclera complex (RCSC), and the ciliary body. The optic nerve was hyperenhanced and the other structures were isoenhanced. The wash-in time, peak enhancement time, and wash-out time were similar for both right and left eyes. Mean values and standard deviation were calculated for contrast wash-in time, peak enhancement time, and wash-out time in the optic nerve, RCSC, and ciliary body.Discussion: Ultrasound is an important diagnostic resource for veterinary ophthalmology and provides relevant information for the detection of pathological conditions of the eyes of animals. The contrast-enhanced ultrasound allows evaluation of tissues at the capillary level (macro and microcirculation), complementing the vascular ultrasound scan. This study brings original information on contrast-enhanced ultrasound findings for evaluation of eyes in dogs, creating novel diagnostic possibilities for the use of this imaging technique in veterinary ophthalmology.[...]

Maternal ophthalmic artery Doppler ultrasonography in preeclampsia and pregnancy outcomes.

OBJECTIVE: To examine the association of ophthalmic artery (OA) Doppler measure - the ratio of velocity peaks (PR) - to adverse pregnancy outcomes in preeclampsia. STUDY DESIGN AND MAIN OUTCOMES: Prospective cohort study of 56 women with preeclampsia that underwent Doppler measurements of OA flow, medial to optic nerve. PR results were classified as normal (PR < 0.78), abnormal (PR 0.78-0.98), or highly abnormal (PR ≥ 0.99). Attending clinicians were blinded to OA Doppler results. The primary endpoints were (1) a composite of adverse maternal outcomes-central nervous system injury (eclampsia or posterior reversible encephalopathy syndrome), HELLP syndrome, hypertensive crisis, maternal admission to the intensive care unit, and maternal death-and (2) a composite of adverse perinatal outcomes-birth weight <10th percentile for gestational age, neonatal acidemia, 5-min Apgar score <7, admission of infants weighing >2500 g to the neonatal intensive care, preterm birth <32 weeks, fetal or neonatal death. RESULTS: Adverse maternal outcomes became more frequent as the PR values increased (p=.005). The occurrence of hypertensive crisis after hospital admission (secondary endpoint) was also positively associated with PR values (p=.001). Adverse perinatal outcomes were not associated with PR values (p=.551), but women in the highly abnormal PR group (PR ≥ 0.99) had the earliest deliveries (p=.001) and the smallest newborns (p=.004). All women in the highly abnormal PR group (n=16) had an adverse outcome. CONCLUSIONS: Maternal OA Doppler PR ≥ 0.99 in preeclampsia may identify women at increased risk of adverse maternal outcomes and pregnancies at the greatest risk of preterm birth.

Effects of obesity on retrobulbar flow hemodynamics: color Doppler ultrasound evaluation.

PURPOSE: To evaluate intraocular pressure (IOP) and extraocular orbital vessels with color Doppler ultrasound (CDU) and investigate the effects of obesity on retrobulbar blood flow. METHODS: Fifty-nine patients were included in this prospective study. Patients were divided into two groups according to body mass index: Group 1 (31 obese patients) and Group 2 (28 non-obese patients). IOP was measured with a Goldmann applanation tonometer, and CDU was used to evaluate the retrobulbar vessels. RESULTS: The mean IOP was 18 ± 6.68 mmHg in the obese group and 13.71 ± 1.60 mmHg in the control group (p<0.001). When the CDU values for the central retinal artery were compared between the groups, the pulsatility index was found to be significantly lower in the obese group than in the control group (p<0.001). When the CDU values for the ophthalmic artery (OA) were compared between the groups, the peak systolic velocity (p<0.001) and end-diastolic velocity (p=0.002) values were found to be significantly lower in the obese group than in the control group. CONCLUSIONS: Obese patients have a higher mean IOP and lower flow velocity than non-obese patients. Increased IOP together with decreased retrobulbar blood flow, particularly in obese individuals, may increase the risk of glaucoma development.

Effects of obesity on retrobulbar flow hemodynamics: color Doppler ultrasound evaluation / Efeitos da obesidade na hemodinâmica do fluxo retrobulbar: avaliação por ultrassom doppler colorido

ABSTRACT Purpose: To evaluate intraocular pressure (IOP) and extraocular orbital vessels with color Doppler ultrasound (CDU) and investigate the effects of obesity on retrobulbar blood flow. Methods: Fifty-nine patients were included in this prospective study. Patients were divided into two groups according to body mass index: Group 1 (31 obese patients) and Group 2 (28 non-obese patients). IOP was measured with a Goldmann applanation tonometer, and CDU was used to evaluate the retrobulbar vessels. Results: The mean IOP was 18 ± 6.68 mmHg in the obese group and 13.71 ± 1.60 mmHg in the control group (p<0.001). When the CDU values for the central retinal artery were compared between the groups, the pulsatility index was found to be significantly lower in the obese group than in the control group (p<0.001). When the CDU values for the ophthalmic artery (OA) were compared between the groups, the peak systolic velocity (p<0.001) and end-diastolic velocity (p=0.002) values were found to be significantly lower in the obese group than in the control group. Conclusions: Obese patients have a higher mean IOP and lower flow velocity than non-obese patients. Increased IOP together with decreased retrobulbar blood flow, particularly in obese individuals, may increase the risk of glaucoma development.

RESUMO Objetivo: Avaliar a pressão intraocular (PIO) e vasos orbitários extraoculares com ultrassom Doppler colorido (UDC) e investigar os efeitos da obesidade sobre o fluxo sanguíneo retrobulbar. Métodos: Cinquenta e nove pacientes foram incluídos neste estudo prospectivo. Os pacientes foram divididos em dois grupos de acordo com o índice de massa corpo ral (IMC): Grupo 1 (31 pacientes obesos) e Grupo 2 (28 não obesos). As pressões intraoculares (PIOs) foram medidas com tonômetro de aplanação de Goldmann e o UDC foi utilizada para a avaliação de vasos retrobulbar. Resultados: As PIOs foram 18 ± 6,68 mmHg nos pacientes obesos e 13,71 ± 1,60 mmHg nos grupos controle (p<00,001). Quando os valores da artéria central da retina (ACR) foram comparados entre os grupos controle e obeso. O índice pulsátil (PI) foi marcadamente menor no grupo obeso (p<00,001). Quando os valores da artéria oftálmica (AO) dos grupos obesos e de controle foram comparados. Os valores de Velocidade do pico sistólico (PSV) (p<00,001) e velocidade diastólica final (EDV) (p=00,002) foram significativamente mais baixos no grupo obeso. Conclusão: Pacientes obesos têm maior PIO do que os pacientes não obesos. Os pacientes obesos têm diminuição nas velocidades de fluxo da AO. O aumento da PIO. Juntamente com a diminuição do fluxo sanguíneo retrobulbar, especialmente em indivíduos obesos, pode aumentar o risco de desenvolvimento de glaucoma.

Evaluation of choroidal and retinal thickness measurements in adult hemodialysis patients using spectral-domain optical coherence tomography.

PURPOSE: To assess the effect of hemodialysis on retinal and choroidal thicknesses using spectral-domain optical coherence tomography (SD-OCT). METHODS: In this prospective interventional study, 25 hemodialysis patients (17 male, 8 female) were enrolled. All participants underwent high-speed, high-resolution SD-OCT (λ=840 mm; 26.000 A-scans/s; 5 µm resolution) before and after hemodialysis. Choroidal thickness was measured perpendicularly from the outer edge of the retinal pigment epithelium to the choroid-sclera boundary at the fovea and at five additional points: 500 µm and 1000 µm nasal to the fovea and 500 µm, 1000 µm, and 1500 µm temporal to the fovea. Two masked physicians performed the measurements. Choroidal and retinal thicknesses before and after hemodialysis were compared. RESULTS: The median choroidal thicknesses before and after hemodialysis were 182 µm (range, 103-374 µm) and 161 µm (range, 90-353 µm), respectively (P<0.001). The median retinal thicknesses were 246 µm (range, 179-296 µm) before and 248 µm (range, 141-299 µm) after hemodialysis (P>0.05). Systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, heart rate, and ocular perfusion pressure significantly decreased after hemodialysis (P<0.001). Intraocular pressure did not vary significantly (P=0.540). CONCLUSION: Hemodialysis seems to cause a significant decrease in choroidal thickness, whereas it has no effect on retinal thickness. This significant decrease in choroidal thickness might be due to the extensive fluid absorption in hemodialysis, which could result in decreased ocular blood flow.

Evaluation of choroidal and retinal thickness measurements in adult hemodialysis patients using spectral-domain optical coherence tomography / Avaliação de medidas de coroide e espessura da retina em pacientes em hemodiálise adultos usando tomografia de coerência óptica de domínio espectral

ABSTRACT Purpose: To assess the effect of hemodialysis on retinal and choroidal thicknesses using spectral-domain optical coherence tomography (SD-OCT). Methods: In this prospective interventional study, 25 hemodialysis patients (17 male, 8 female) were enrolled. All participants underwent high-speed, high-resolution SD-OCT (λ=840 mm; 26.000 A-scans/s; 5 µm resolution) before and after hemodialysis. Choroidal thickness was measured perpendicularly from the outer edge of the retinal pigment epithelium to the choroid-sclera boundary at the fovea and at five additional points: 500 µm and 1000 µm nasal to the fovea and 500 µm, 1000 µm, and 1500 µm temporal to the fovea. Two masked physicians performed the measurements. Choroidal and retinal thicknesses before and after hemodialysis were compared. Results: The median choroidal thicknesses before and after hemodialysis were 182 µm (range, 103-374 µm) and 161 µm (range, 90-353 µm), respectively (P<0.001). The median retinal thicknesses were 246 µm (range, 179-296 µm) before and 248 µm (range, 141-299 µm) after hemodialysis (P>0.05). Systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, heart rate, and ocular perfusion pressure significantly decreased after hemodialysis (P<0.001). Intraocular pressure did not vary significantly (P=0.540). Conclusion: Hemodialysis seems to cause a significant decrease in choroidal thickness, whereas it has no effect on retinal thickness. This significant decrease in choroidal thickness might be due to the extensive fluid absorption in hemodialysis, which could result in decreased ocular blood flow.

RESUMO Objetivo: Avaliar o efeito da hemodiálise (HD) na espessura da retina (RT) e na espessura da coroide (CT) usando tomografia de coerência óptica de domínio espectral (SD-OCT). Método: Neste estudo prospectivo intervencionista foram incluídos 25 pacientes em HD (17 homens e 8 mulheres). Todos os participantes foram submetidos a SD-OCT com dispositivo de alta resolução (λ=840 mm; 26.000 A-scans/seg e resolução de 5 µm), antes e após HD. A CT foi medida perpendicularmente a partir da borda externa do epitélio pigmentar da retina até o limite coroide-esclera na fóvea e em mais de 5 pontos localizados 500 µm nasal à fóvea, 1.000 µm nasal à fóvea; 500 µm temporal à fóvea, 1.000 µm temporal à fóvea, e 1.500 µm temporal à fóvea. Dois médicos realizaram as medidas sem o conhecimento do diagnóstico. Os dados da CT e RT, antes e após a HD foram comparados. Resultados: As CTs medianas antes e após a HD foram 182 µm (variação de 103-374 µm) e 161 µm (variação de 90-353 µm), respectivamente (p<0,001). A RT foi 246 µm (variação de 179-296 µm) antes e 248 µm (variação de 141-299 µm) após a HD (p>0,05). A pressão arterial sistólica, pressão arterial diastólica, as médias de pressão arterial média, frequência cardíaca e pressão de perfusão ocular diminuíram significativamente após HD (p<0,001). A pressão intraocular não alterou significativamente (p=0,540). Conclusão: A HD parece causar uma redução significativa da CT, e não ter efeito sobre a RT. Esta redução significativa da CT pode ser devida à grande absorção de fluido durante a HD, o que pode resultar numa diminuição do fluxo sanguíneo ocular.

Hemodynamics of the pectinis oculi artery in American pekin ducks (Anas platyrhynchos domestica).

OBJECTIVE: To measure blood velocity parameters of the main detectable branch of the pectinis oculi artery and compare with values found in other arteries in other species to form a hypothesis of the function of the pecten oculi in birds. METHODS: Eleven American pekin ducks (Anas platyrhynchos domestica) without ocular diseases were examined with ocular Doppler ultrasonography. The pectinate artery resistive index (RI) and pulsatility index (PI) were calculated. RESULTS: The mean of RI and PI values resulted, respectively, in: left eye (0.43 ± 0.07; 0.58 ± 0.13), right eye (0.37 ± 0.09; 0.47 ± 0.14), and both eyes (0.40 ± 0.08; 0.53 ± 0.14). DISCUSSION: The low RI and PI values found in the main branch of the pectinis oculi artery compared with other arteries in other tissues suggest a high metabolic activity in the pecten oculi, and it could indicate a nutritional function and/or intraocular pressure regulation.

Trombose parcial do seio cavernoso / Cavernous sinus thrombosis

A trombose do seio cavernoso (TSC) é uma situação clínica rara, resultando normalmente da complicação de um processo infeccioso dos seios paranasais. Outras causas incluem alterações pró-trombóticas, anemia e trauma. Os sinais e sintomas são extremamente variados e inespecíficos, sendo o seu diagnóstico efetuado através de ressonância magnética nuclear (RMN). Os autores apresentam um caso clínico de uma doente com 75 anos de idade, que recorre ao serviço de urgência devido à dor em olho direito vermelho associado à cefaléias frontais com quatro dias de evolução. Ao exame oftalmológico observou-se defeito pupilar aferente relativo no olho direito (OD); na biomicroscopia vasos episclerais dilatados, catarata nuclear e à fundoscopia um edema discreto da papila com apagamento do rebordo nasal, hemorragias punctiformes dispersas e tortuosidade vascular em OD. A realização de angio-RMN confirmou o diagnóstico tendo a doente sido tratada com enoxaparina. Apesar do tratamento da TSC ser um tratamento etiológico, foi demonstrado que a anticoagulação está associada à diminuição da taxa de mortalidade.

Cavernous sinus thrombosis (CST) is a rare condition, usually results from a late complication of an infection of the paranasal sinuses. Other causes include prothrombotic disorders, anemia and trauma. The signs and symptoms are extremely varied and nonspecific, being the diagnosis made through magnetic resonance imaging (MRI). The authors present a 75-year-old woman, admitted in the emergency room complaining of ocular pain in the right eye (RE), red eye and frontal headache. She presented on ophthalmic examination of the RE: dilated episcleral vessels, nuclear cataract and a relative afferent pupillary defect. Fundoscopy examination of the RE revealed disc edema with nasal disc margin blurred, small dot hemorrhages and vascular tortuosity. The MRI angiography confirmed the diagnosis and the patient was treated with low molecular weight heparin. Despite treatment of CST is directed to the causal situation, being shown that anticoagulation is associated with reduction in mortality.

Intraocular pressure and ocular perfusion during hemodialysis.

AIM: To evaluate the intraocular pressure and ocular perfusion pressure during a hemodialysis. METHODS: Sixty-seven eyes from thirty-five patients were evaluated at the beggining of hemodialysis, 2 hours and 4 hours after initiation. Intraocular pressure was evaluated using a Tonopen. Systolic and diastolic arterial pressures were measured with a manual sphygmomanometer. The ocular perfusion pressure was estimated by measuring the difference between 2/3 of the mean arterial pressure and the intraocular pressure values. Generalized estimating equations were used to evaluate the difference between the repeated measurements using the appropriate correction for inter-eye dependency. RESULTS: There was no statistically significant difference in ocular perfusion pressure, in intraocular pressure (p=0.93) and in systolic arterial pressure (p=0.92) at the three time points (p=0.69). But, when analyzing the extreme values, some patients exhibited lower diastolic perfusion pressures at all time points. CONCLUSION: Our results did not support the view that significant changes in ocular perfusion pressure and intraocular pressure occur during hemodialysis session. However, we observed that some patients exhibited lower diastolic perfusion pressures, which could be a poor prognostic factor for glaucoma patients.

Vascular resistance of central retinal artery is reduced in postmenopausal women after use of estrogen.

OBJECTIVE: The aim of this study was to evaluate the effect of estrogen on the vascular resistance of the central retinal artery in postmenopausal women, compared with placebo, using transorbital ultrasound with Doppler velocimetry. METHODS: We performed a prospective, randomized, triple-blinded placebo-controlled study. A total of 51 healthy postmenopausal women (follicle-stimulating hormone, >40 IU/L) with a mean (SD) age of 53.6 (4.8) years were studied. Participants were randomly allocated into two groups: placebo (n = 23) and estrogen (0.625 mg conjugated estrogens; n = 28). Transorbital Doppler velocimetric ultrasound was performed before and after treatment in sitting and supine positions. RESULTS: The mean age was similar in both groups. The pulsatility index of the central retinal arteries had a significant decrease after the use of estrogen, when women were evaluated in the sitting position. Women who received placebo did not show any difference in pulsatility index of the central retinal arteries after treatment. When the same comparison was done with participants in the supine position, no difference was observed in either group. CONCLUSIONS: Our study demonstrates that estrogen reduces the vascular resistance of the central retinal artery in postmenopausal women because of a vasodilatory effect.

Intraocular pressure and ocular perfusion during hemodialysis / Pressão intraocular e perfusão ocular durante hemodiálise

AIM: To evaluate the intraocular pressure and ocular perfusion pressure during a hemodialysis. METHODS: Sixty-seven eyes from thirty-five patients were evaluated at the beggining of hemodialysis, 2 hours and 4 hours after initiation. Intraocular pressure was evaluated using a Tonopen. Systolic and diastolic arterial pressures were measured with a manual sphygmomanometer. The ocular perfusion pressure was estimated by mea suring the difference between 2/3 of the mean arterial pressure and the intraocular pressure values. Generalized estimating equations were used to evaluate the difference between the repeated measurements using the appropriate correction for inter-eye dependency. RESULTS: There was no statistically significant difference in ocular perfusion pressure, in intraocular pressure (p=0.93) and in systolic arterial pressure (p=0.92) at the three time points (p=0.69). But, when analyzing the extreme values, some patients exhibited lower diastolic perfusion pressures at all time points. CONCLUSION: Our results did not support the view that significant changes in ocular perfusion pressure and intraocular pressure occur during hemodialysis session. However, we observed that some patients exhibited lower diastolic perfusion pressures, which could be a poor prognostic factor for glaucoma patients.

OBJETIVO: Avaliar a pressão intraocular e a pressão de perfusão ocular durante uma sessão de hemodiálise. MÉTODOS: Sessenta e sete olhos de trinta e cinco pacientes foram avaliados no início, após 2 horas e após 4 horas do início de uma sessão de hemodiálise. A pressão intraocular foi avaliada usando o aparelho Tonopen. Pressões arteriais sistólica e diastólica foram aferidas usando esfigmomanômetro manual. A pressão de perfusão ocular foi estimada por meio do cálculo da diferença entre 2/3 da pressão arterial média e valores da pressão intraocular. Equações de estimação generalizada foram usadas para avaliar a diferença entre medidas repetidas usando correção apropriada para dependência entres olhos. RESULTADOS: Não houve diferença estatisticamente significativa na pressão de perfusão ocular, PIO (p=0,93) e na pressão arterial sistólica (p=0,92) nos três períodos medidos da hemodiálise (p=0,69). Mas, quando analisados valores extremos, alguns pacientes exibiram pressões diastólicas menores em todos os períodos aferidos. CONCLUSÃO: Nossos resultados não apontaram mudanças significativas na pressão de perfusão ocular e pressão intraocular durante a hemodiálise. No entanto, foi observado que alguns pacientes exibiram pressões diastólicas menores, o que pode ser um fator de prognóstico ruim para pacientes com glaucoma.

Anestesia peribulbar com ropivacaína: estudo da ação vasoconstritora / Ropivacaine in peribulbar anesthesia: vasoconstrictive properties / Anestesia peribulbar con ropivacaína: estudio de la acción vasoconstrictora

JUSTIFICATIVA E OBJETIVOS: A anestesia peribulbar pode reduzir o fluxo sanguíneo ocular (FSO) por elevação da pressão intraocular (PIO) ou ação de fármacos. A ropivacaína tem baixa toxicidade e ação vasoconstritora intrínseca ainda não comprovada sobre vasculatura ocular. Medidas da amplitude de pulso ocular (APO) permitem avaliação indireta do FSO. O objetivo deste estudo é avaliar, via FSO, a ação vasoconstritora da ropivacaína em anestesia peribulbar. MÉTODO: Quarenta olhos submetidos a bloqueio peribulbar com 7 mL de solução anestésica, sem vasoconstritor, foram separados aleatoriamente em dois grupos: ropivacaína (n = 20) e bupivacaína (n = 20). Foram avaliados PIO, pressão de perfusão ocular (PPO), APO, variáveis hemodinâmicas e grau de acinesia antes e aos 5 e 10 minutos após bloqueio peribulbar. Para avaliação dos parâmetros oculares, utilizou-se tonômetro de contorno dinâmico. A sedação foi idêntica nos dois grupos. RESULTADOS: Não houve variação significativa dos parâmetros hemodinâmicos e da intensidade de bloqueio motor entre os grupos. Aos 5 e 10 minutos houve diferença de PIO, PPO e APO entre os grupos (p < 0,05). A variação da PIO aos 5 e 10 minutos foi, respectivamente, de -0,88 por cento e -4,54 por cento com ropivacaína e 17,61 por cento e 16,56 por cento com bupivacaína. A alteração da PPO após 5 e 10 minutos foi de 1,5 por cento e 4,2 por cento com ropivacaína, e de -7 por cento e -6 por cento com bupivacaína. A APO variou -55,59 por cento e -59,67 por cento com ropivacaína aos 5 e 10 minutos, e -34,71 por cento e -28,82 por cento com bupivacaína. CONCLUSÕES: A ropivacaína reduziu mais intensamente a amplitude de pulso ocular, apesar das pequenas alterações de PIO e PPO. A diminuição do fluxo sanguíneo ocular pela ropivacaína pode ser atribuída ao seu efeito vasoconstritor.

BACKGROUND AND OBJECTIVES: Peribulbar anesthesia can reduce ocular blood flow (OBF) by increasing intraocular pressure (IOP) or due to the action of drugs. Ropivacaine has low toxicity and intrinsic vasoconstrictive properties, yet to be proven on the ocular vasculature. Measurements of ocular pulse amplitude (OPA) allow the indirect evaluation of the OBF. The objective of the present study was to evaluate through the OBF the vasoconstrictive properties of ropivacaine in peribulbar anesthesia. METHODS: Forty eyes undergoing peribulbar anesthesia with 7 mL of anesthetic solution without vasoconstrictor were randomly divided into two groups: ropivacaine (n = 20) and bupivacaine (n = 20). The IOP, ocular perfusion pressure (OPP), OPA, hemodynamic parameters, and the degree of akinesia before and 5 and 10 minutes after the blockade were evaluated. A dynamic contour tonometer was used to evaluate ocular parameters. Sedation was similar in both groups. RESULTS: A significant variation in hemodynamic parameters and intensity of the motor blockade was not observed between groups. Differences in IOP, OPP, and OPA (p < 0.05) were observed between both groups at 5 and 10 minutes. The variation of IOP at 5 and 10 minutes was -0.88 percent and -4.54 percent, respectively with ropivacaine, and 17.61 percent and 16.56 percent with bupivacaine. The change in OPP after 5 and 10 minutes was 1.5 percent and 4.2 percent with ropivacaine, and -7 percent and -6 percent with bupivacaine. Ocular pulse amplitude varied -55.59 percent and -59.67 percent with ropivacaine at 5 and 10 minutes, and -34.71 percent and -28.82 percent with bupivacaine. CONCLUSIONS: Ropivacaine reduced more intensely the ocular pulse amplitude despite little changes in IOP and OPP. The reduction in ocular blood flow caused by ropivacaine can be attributed to its vasoconstrictive effect.

JUSTIFICATIVA Y OBJETIVOS: La anestesia peribulbar puede reducir el flujo sanguíneo ocular (FSO) por elevación de la presión intraocular (PIO) o por la acción de fármacos. La ropivacaína tiene una baja toxicidad y una acción vasoconstrictora intrínseca que todavía no ha sido comprobada sobre la vasculatura ocular. Medidas de la amplitud del pulso ocular (APO) permiten una evaluación indirecta del FSO. El objetivo de este estudio es evaluar, vía FSO, la acción vasoconstrictora de la ropivacaína en la anestesia peribulbar. MÉTODO: Cuarenta pacientes, sometidos a bloqueo peribulbar con 7 mL de solución anestésica, sin vasoconstrictor, fueron divididos aleatoriamente en dos grupos: Ropivacaína (n = 20) y bupivacaína (n = 20). Se evaluaron PIO, presión de perfusión ocular (PPO), APO, variables hemodinámicas y el grado de acinesia antes y a los 5 y 10 minutos posteriores al bloqueo peribulbar. Para la evaluación de los parámetros oculares, se utilizó el tonómetro de contorno dinámico. La sedación fue idéntica en los dos grupos. RESULTADOS: No se registró variación significativa de los parámetros hemodinámicos y de la intensidad del bloqueo motor. A los 5 y 10 minutos, se registró una diferencia de PIO, PPO y APO entre los grupos (p < 0,05). La variación de la PIO a los 5 y 10 minutos fue, respectivamente, de -0,88 por ciento y -4,54 por ciento con ropivacaína y de 17,61 por ciento y 16,56 por ciento con bupivacaína. La alteración de la PPO después de 5 y 10 minutos fue de 1,5 por ciento y 4,2 por ciento con ropivacaína, y de -7 por ciento y -6 por ciento con bupivacaína. La APO varió -55,59 por ciento y -59,67 por ciento con ropivacaína a los 5 y 10 minutos, y -34,71 por ciento y -28,82 por ciento con bupivacaína. CONCLUSIONES: La ropivacaína redujo más intensamente la amplitud del pulso ocular, a pesar de las pequeñas alteraciones de PIO y PPO. La disminución del flujo sanguíneo ocular por la ropivacaína puede ser atribuida a su efecto vasoconstrictor.

Ropivacaine in peribulbar anesthesia - vasoconstrictive properties.

BACKGROUND AND OBJECTIVES: Peribulbar anesthesia can reduce ocular blood flow (OBF) by increasing intraocular pressure (IOP) or due to the action of drugs. Ropivacaine has low toxicity and intrinsic vasoconstrictive properties, yet to be proven on the ocular vasculature. Measurements of ocular pulse amplitude (OPA) allow the indirect evaluation of the OBF. The objective of the present study was to evaluate through the OBF the vasoconstrictive properties of ropivacaine in peribulbar anesthesia. METHODS: Forty eyes undergoing peribulbar anesthesia with 7 mL of anesthetic solution without vasoconstrictor were randomly divided into two groups: ropivacaine (n = 20) and bupivacaine (n = 20). The IOP, ocular perfusion pressure (OPP), OPA, hemodynamic parameters, and the degree of akinesia before and 5 and 10 minutes after the blockade were evaluated. A dynamic contour tonometer was used to evaluate ocular parameters. Sedation was similar in both groups. RESULTS: A significant variation in hemodynamic parameters and intensity of the motor blockade was not observed between groups. Differences in IOP, OPP, and OPA (p < 0.05) were observed between both groups at 5 and 10 minutes. The variation of IOP at 5 and 10 minutes was -0.88% and -4.54%, respectively with ropivacaine, and 17.61% and 16.56% with bupivacaine. The change in OPP after 5 and 10 minutes was 1.5% and 4.2% with ropivacaine, and -7% and -6% with bupivacaine. Ocular pulse amplitude varied -55.59% and -59.67% with ropivacaine at 5 and 10 minutes, and -34.71% and -28.82% with bupivacaine. CONCLUSIONS: Ropivacaine reduced more intensely the ocular pulse amplitude despite little changes in IOP and OPP. The reduction in ocular blood flow caused by ropivacaine can be attributed to its vasoconstrictive effect.

Twenty-four-hour ocular perfusion pressure in primary open-angle glaucoma.

AIM: To compare the 24 h intraocular pressure (IOP), blood pressure (BP), and perfusion pressure (PP) of primary open-angle glaucoma (POAG) patients and healthy individuals. METHODS: 24 healthy individuals and 29 POAG patients underwent IOP and BP measurements every 2 h, starting at 08:00 until 06:00 of the next morning. IOP measurements were made by a masked observer with a Goldmann tonometer at the slit-lamp from 08:00 to 22:00 and with the Perkins tonometer in supine position from 24:00 to 06:00. Systolic and diastolic BP (SBP and DBP) measurements were performed with an automated device. RESULTS: Mean IOPs in POAG patients were significantly higher at all time intervals (p<0.001). The mean SBP was significantly higher in POAG patients from 04:00 to 10:00, and also at 14:00 and 18:00 (p<0.05). In POAG patients, the mean DBP was significantly higher at 08:00 and 10:00, but was significantly lower at 04:00 (p<0.05). In POAG patients, the mean systolic perfusion pressure (SPP) was significantly higher at 08:00 and 10:00 (p<0.01), whereas the mean diastolic perfusion pressure (DPP) was significantly lower from 24:00 to 06:00 (p<0.05). CONCLUSION: Although higher SPPs are observed in POAG patients during the morning, lower DPPs are found during the night.

Avaliação da veia oftálmica superior por meio do Doppler colorido nas diferentes formas e estágios da orbitopatia de Graves / Evaluation of the superior ophthalmic vein by color Doppler in different forms and stages of Graves orbitopathy

INTRODUÇÃO: A orbitopatia de Graves é uma doença autoimune cujas manifestações clínicas ocorrem por infiltração tecidual inflamatória. Apresenta estágio ativo inicial e estágio sequelar posteriormente, podendo se manifestar nas formas clínicas miogênica ou lipogênica. A inflamação da órbita pode gerar importante congestão, agravando manifestações clínicas e comprometendo o sucesso da terapia específica em alguns pacientes. O objetivo deste trabalho é a avaliação da congestão orbitária feita pelo estudo das características do fluxo sanguíneo na veia oftálmica superior, por meio do Doppler colorido de órbitas, nos grupos de pacientes com orbitopatia de graves em fase ativa, em fase sequelar miogênica e em fase sequelar lipogênica, além do grupo controle. MÉTODOS: Estudo transversal prospectivo realizado entre maio de 2006 e abril de 2008 no Serviço de Órbita do HCFMUSP. Noventa órbitas de 46 pacientes com orbitopatia de Graves foram incluídas, assim como 38 órbitas de 20 pacientes do grupo controle. Foi feito exame oftalmológico completo e avaliação pelo DCO em todos os pacientes. Pacientes com orbitopatia de Graves foram divididos em grupos com doença em atividade e doença em estágio sequelar nas apresentações miogênicas ou lipogênicas. O sentido, as velocidades máxima e mínima do fluxo sanguíneo na veia oftálmica superior, e o intervalo entre as mesmas, foram aferidos. Os achados foram comparados entre os diferentes grupos e analisados também em relação à restrição muscular, exoftalmometria, escore de atividade clínica, idade, sexo, lado estudado, comorbidades e tabagismo. RESULTADOS: Foi encontrada diferença no sentido do fluxo sanguíneo da veia oftálmica superior (p<0,001), na velocidade máxima (p=0,001), na velocidade mínima (p=0,002) e no intervalo entre a velocidade máxima e a mínima do mesmo (p<0,001) entre os grupos de estudo. A velocidade máxima do fluxo sanguíneo apresentou correlação com a restrição muscular (p=0,003), o escore de atividade...

INTRODUCTION: Graves orbitopathy is an autoimmune disease whose clinical manifestations are secondary to inflammatory tissue infiltration. It presents an initial active stage and a later latent stage, and can manifest myogenic or lipogenic clinical forms. Inflammation of the orbit can generate significant congestion, worsening clinical manifestations and limiting the success of specific therapy in some patients. The objective of this study is to evaluate orbital congestion studying the characteristics of blood flow in the superior ophthalmic vein with the color Doppler in groups of patients with Graves Orbitopathy in active stage, lipogenic latent stage and myogenic latent stage, and patients from the control group. METHODS: Transversal study made between May 2006 and April 2008 in the Orbit Department of University of São Paulo Medical School. Ninety orbits from 46 patients with Graves orbitopathy and 38 orbits from 20 patients of the control group were included. All patients underwent complete ophthalmological exams including color Doppler of the orbits. Patients with Graves orbitopathy were divided in active stage, latent lipogenic stage and latent myogenic stage groups. The direction of venous blood flow in the superior ophthalmic vein and its maximum and minimum velocities - including the interval between them - were measured. The results were compared among the groups and analyzed also in relation to muscular restriction, exophthalmometry, clinical activity score, age, sex, studied orbit side, comorbidities and use of tobacco. RESULTS: There was difference in blood flow direction of the superior ophthalmic vein (p<0,001), blood flow maximum speed (p=0,001), blood flow minimum speed (p=0,002) and blood flow speed interval (p<0,001) among the groups of this study. Blood flow maximum speed presented correlation with muscle restriction (p=0,003), clinical...