Browsing by Author "Marques-Neves, Carlos"
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- Amlodipine effects on vasomotion in rabbit externalPublication . Delgado, Esmeralda; Marques-Neves, Carlos; Rocha, Isabel; Sales-Luís, José; Silva-Carvalho, LuísBackground In order to understand the role of ocular blood flow in normal and pathological conditions, knowledge of the pharmacological control mechanisms involved in the ocular vascular bed is essential. The present study was designed to investigate the reactivity of the rabbit external ophthalmic artery and its collaterals to amlodipine, in order to answer two questions: (1) What are amlodipine effects upon perfusion pressure and spontaneous oscillations in the in situ perfused rabbit eyes? (2) Can intraarterial amlodipine counteract ET-1 induced vasoconstriction? Methods Rabbit external ophthalmic arteries (n=12) in a head-mounted preparation were cannulated and perfused with warmed tyrode. Vasomotor response curves to intraarterial injections of amlodipine 3 mg/ml followed by phenylephrine 250 μg (group A, n=6) and to amlodipine 3 mg/ml after an intraarterial injection of endothelin-1 (ET-1) 27 μg/ml (group B, n=6) were obtained. For statistical analysis, the paired t-test and Fourier analysis of frequency spectrums of spontaneous oscillations were used. Results Before any drug administration, spontaneous oscillations were observed in the 12 rabbit models. In group A, amlodipine elicited vasodilation and a decrease in frequency and amplitude of the oscillations. In group B, ET-1 induced an increase in vasoconstrictor tone and vasomotion became more evident.With amlodipine after ET-1, we obtained vasodilation and abolition of the vasospasm. Conclusions Our study has two main conclusions: (1) amlodipine, an L-type calcium channel blocker, caused intense vasodilation and decreased both frequency and amplitude of the spontaneous oscillations observed in the rabbit external ophthalmic artery and its collaterals, and (2) when we applied amlodipine in arteries previously contracted by the administration of ET-1, vascular resistance greatly decreased and spontaneous oscillations were abolished. Since ET-1 levels are increased in several ischemic ocular diseases, amlodipine might be beneficial in these patients, allowing a protective action against vasospasm.
- Anti-TNF drugs for chronic uveitis in adults : a systematic review and meta-analysis of randomized controlled trialsPublication . Leal, Ines; Rodrigues, Filipe Brogueira; Sousa, David Cordeiro; Duarte, Gonçalo Silva; Romão, Vasco C.; Marques-Neves, Carlos; Costa, João; Fonseca, João EuricoBackground: We aimed to assess efficacy and safety of anti-tumor necrosis factor (TNF) drugs for adult chronic non-infectious uveitis (NIU). Methods: CENTRAL, MEDLINE, and EMBASE, were searched from inception to January 2019. Double-masked randomized placebo-controlled trials, assessing any anti-TNF vs. best medical intervention/standard of care in adults with chronic NIU were considered. The PRISMA and SAMPL guidelines were followed. The risk of bias was assessed using the Cochrane risk of bias tool. Overall quality of the evidence was assessed according to GRADE. PROSPERO registration: #CRD42016039068. The primary efficacy and safety outcomes were preservation of visual acuity (VA) and withdrawals due to adverse events, respectively. Meta-analysis of efficacy analysis was not performed due to significant clinical heterogeneity between studies' population and interventions. Results: A total of 1,157 references were considered and 3 studies were included. The overall risk of bias was moderate. In active NIU, adalimumab group showed an increased likelihood of VA preservation (risk ratio (RR) 1.75, 95%CI 1.32 to 2.32, n = 217), whereas the etanercept group did not (RR 0.81, 95%CI 0.57 to 1.14, n = 20). In inactive NIU, adalimumab was associated with increased likelihood of VA preservation (RR 1.31, 95%CI 1.12 to 1.53, n = 226). The rate of adverse events did not differ between anti-TNF and control arms (RR 1.03, 95%CI 0.94 to 1.13, n = 410). Conclusions: There is high quality evidence that adalimumab decreases the risk of worsening VA in active and inactive NIU and very low quality evidence that the risk of etanercept worsening VA in inactive NIU is not different from placebo. Moderate quality evidence suggests that anti-TNF agents are not different from placebo on the risk of study withdrawal.
- Asymptomatic chronic red eye: a surgical technique case reportPublication . Matos, Diogo Bernardo; Guerra, Paulo; José, Patrícia; Ferreira, Rui; Quintas, Ana; Marques-Neves, CarlosIntroduction and importance: Ocular Surface Squamous-cell Neoplasia (OSSN) is an infrequent diagnosis whose clinical suspicion assumes great importance and should not be overlooked. The following case-report aims to describe the diagnosis and treatment of a patient with OSSN whose complaints were mild in comparison to the severity of the disease. The chosen surgical technique was paramount for a disease-free outcome while minimizing the scarring effects of surgical removal. Case presentation: Patient presented mild discomfort right eye and painless persistent hyperaemia. Slit-lamp observation showed a clear diagnosis and lesion's extent evaluated through multimodal imaging. After surgical excision the patient underwent topical ocular treatment with mitomycin-C for a higher margin of safety even before the pathology results were available. Discussion: Ancillary exam technology improvement has allowed a higher margin of safety while determining the extent of OSSN lesions. In the absence of clear diagnostic criteria and guidelines, clinical reasoning and OSSN awareness are critical for timely diagnosis and treatment, as several treatment options are available, allowing an increasing number of patients to be treated non-invasively. In this case-report, we highlight the importance of early-recognition and the reasoning for choosing a combined treatment option with a higher margin of safety. Conclusion: Early recognition and prompt treatment of OSSN lesions is of paramount importance to avoid ocular invasiveness and potentially preclude both ocular and systemic complication. The choice of a combined surgical and medical approach may provide a higher margin of safety for suitable cases. This patient is currently disease-free at 6-month follow-up.
- Complete blood count parameters as biomarkers of retinopathy of prematurity: a Portuguese multicenter studyPublication . Fevereiro-Martins, Mariza; Santos, Ana Carolina; Marques-Neves, Carlos; Guimarães, Hercília; Bicho, Manuel; Afonso, Conceição; Ferreira, Joana; Santo, Rita Espírito; Jorge Teixeira, Filipa; Rosa, Rita; Carneiro, Cristina Vaz; Ferreira, Marta; Matos, Teresa; Neiva, Luísa; Pereira, Sandra; Aires, Sofia; Parreira, Ricardo; Melnik, Zuzana; Faria, João; Teixeira, Joana; Barros, Pedro; Almeida, Juliana; Malheiro, Bruna; Rodrigues, Patrícia Cunha; Albuquerque, Luís; Freitas, Alice; Kotchekova, Nadezda; Freitas, Rui; Silveira, Ana Cristina; Ferreira, Ana; Morais, Benvinda; Teixeira, Susana; Mota, Mafalda; Guerra, Maria; Coimbra, Lúcia; Gigante, João; Ferreira, Muriel; Lapa, Patrícia; Monteiro, Madalena; Alfaiate, Mário; Rodrigues, Teresa; Pina, Teresa; Rosário, Marta; Silva, Renato; Breda, Jorge; Bazenga, Filipa; Pinto, João AntónioPurpose: To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP). Methods: Multicenter, prospective, observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed. Results: A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin concentration (p < 0.001), lymphocytes (p = 0.035), and platelets (p = 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (p = 0.044), red blood cell distribution width (RDW) (p < 0.001), erythroblasts (p < 0.001), neutrophils (p = 0.030), neutrophils-lymphocytes ratio (p = 0.028), and basophils (p = 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression. Conclusion: In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.
- Efficacy and safety of intravitreal anti-tumour necrosis factor drugs in adults with non-infectious uveitis : a systematic reviewPublication . Leal, Ines; Rodrigues, Filipe Brogueira; Sousa, David Cordeiro; Romão, Vasco C.; Duarte, Gonçalo Silva; Carreño, Ester; Dick, Andrew D.; Marques-Neves, Carlos; Costa, João; Fonseca, João EuricoAnti-tumour necrosis factor (TNF) drugs have been extensively used in non-infectious uveitis (NIU), when corticosteroids or conventional immunosuppressive drugs cannot adequately control inflammation or intolerable side-effects occur. However, systemic anti-TNF therapies are also associated with a myriad of side-effects. Therefore, intravitreal administration of anti-TNF biologics has been employed to minimize patient morbidity and systemic adverse effects, while maintaining therapeutic effectivity. We undertook a systematic review to determine evidence of efficacy and safety of intravitreal administration of anti-TNF drugs in adults with NIU. We conducted this systematic review according to the PRISMA guidelines. The protocol was registered with PROSPERO (CRD42016041946). We searched CENTRAL, MEDLINE and EMBASE, from inception to April 2017, as well as clinical trial registries and grey literature. The qualitative analysis included all studies of adult patients with a diagnosis of NIU and who received intravitreal anti-TNF drugs with a 4-week minimum follow-up. A total of 4840 references were considered for title and abstract screening. Seven full texts were screened, and five studies were considered for analysis. All studies were open-label, single-centre, prospective, non-randomized, interventional case series with a follow-up between 4 and 26 weeks, employing either adalimumab in two studies and infliximab in three. Three studies showed a treatment effect of anti-TNF intravitreal injections, while one study revealed short-term improvement and one study revealed no efficacy of anti-TNF intravitreal therapy. None of the studies reported ocular adverse effects but only two studies included electrophysiological assessment in the safety analysis and no study assessed systemic human anti-drug antibodies. The available evidence is not sufficiently robust to conclude about the clinical effectivity of intravitreal anti-TNF in NIU and so no recommendation can be made. In conclusion, intravitreal injection of anti-TNF antibodies remains a possible treatment option to be explored through robust clinical investigation.
- Endothelin-1 effects on spontaneous oscillations in choroidal arteriolesPublication . Delgado, Esmeralda; Marques-Neves, Carlos; Rocha, Isabel; Sales-Luís, José; Silva-Carvalho, LuisPurpose: This study characterizes the effects of endothelin-1 (ET-1) on the perfusion pressure of the choroidal vasculature using in situ perfused isolated rabbit eyes. Methods: Rabbit external ophthalmic arteries (n = 12) in a head-mounted preparation were cannulated and perfused with warmed tyrode. The three-way polypropylene catheter was further connected to a pressure transducer and the effect of intraluminal pressure as a measure of total vascular resistance was assessed. Response curves to intra-arterial injections of ET-1 (group A; n = 6) and to an intravitreal injection followed by an intra-arterial injection of ET-1 (group B; n = 6) were obtained. Data were studied using paired t-test and fast Fourier transform. Results: Before any drugs were administered, spontaneous oscillations were observed in the 12 rabbit models. In group A, ET-1 induced a short and weak vasodilating effect followed by a strong and long-lasting vasoconstrictor tone. Vasomotion became more evident, showing a higher frequency and shorter amplitude of oscillations. In group, B the intravitreal injection produced no significant changes in registered pressure or vasomotion characteristics. The intra-arterial injection produced effects similar to those observed in group A. Conclusion: Our study has three main findings: (i) the choroidal vasculature demonstrated spontaneous oscillations in perfusion pressure in basal conditions in all rabbit eye models; (ii) ET-1 applied intra-arterially induced a short drop in perfusion pressure followed by a long withstanding contraction; and (iii) intra-arterial ET-1 modulated the frequency and amplitude of the spontaneous oscillations, causing a faster rate of pulsatility.
- Genetic modulation of the erythrocyte phenotype associated with retinopathy of prematurity—a multicenter Portuguese cohort studyPublication . Fevereiro-Martins, Mariza; Santos, Ana Carolina; Marques-Neves, Carlos; Guimarães, Hercília; Bicho, ManuelThe development of retinopathy of prematurity (ROP) may be influenced by anemia or a low fetal/adult hemoglobin ratio. We aimed to analyze the association between DNA methyltransferase 3 β (DNMT3B) (rs2424913), methylenetetrahydrofolate reductase (MTHFR) (rs1801133), and lysine-specific histone demethylase 1A (KDM1A) (rs7548692) polymorphisms, erythrocyte parameters during the first week of life, and ROP. In total, 396 infants (gestational age < 32 weeks or birth weight < 1500 g) were evaluated clinically and hematologically. Genotyping was performed using a MicroChip DNA on a platform employing iPlex MassARRAY®. Multivariate regression was performed after determining risk factors for ROP using univariate regression. In the group of infants who developed ROP red blood cell distribution width (RDW), erythroblasts, and mean corpuscular volume (MCV) were higher, while mean hemoglobin and mean corpuscular hemoglobin concentration (MCHC) were lower; higher RDW was associated with KDM1A (AA), MTHFR (CC and CC + TT), KDM1A (AA) + MTHFR (CC), and KDM1A (AA) + DNMT3B (allele C); KDM1A (AA) + MTHFR (CC) were associated with higher RDW, erythroblasts, MCV, and mean corpuscular hemoglobin (MCH); higher MCV and MCH were also associated with KDM1A (AA) + MTHFR (CC) + DNMT3B (allele C). We concluded that the polymorphisms studied may influence susceptibility to ROP by modulating erythropoiesis and gene expression of the fetal/adult hemoglobin ratio.
- Influence of functional variations in genes of neurotrophins and neurotransmitter systems on the development of retinopathy of prematurityPublication . Fevereiro-Martins, Mariza; Santos, Ana Carolina; Marques-Neves, Carlos; Guimarães, Hercília; Bicho, ManuelRetinal neurodevelopment, vascularization, homeostasis, and stress response are influenced by factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), and erythropoietin (EPO). As retinopathy of prematurity (ROP) is a neurovascular retinal disease, this study analyzed the contributions of NGF (rs6330), BDNF (rs7934165), TH (rs10770141), and EPO (rs507392) genetic functional polymorphisms to the modulation of hematological and biochemical parameters of the first week of life and their association with ROP development. A multicenter cohort of 396 preterm infants (gestational age < 32 weeks or birth weight < 1500 g) was genotyped using MicroChip DNA and iPlex MassARRAY® platform. Multivariate regression followed univariate assessment of ROP risk factors. NGF (GG) genotype was associated with a higher ROP risk (OR = 1.79), which increased further (OR = 2.38) when epistatic interactions with TH (allele C) and BDNF (allele G) were present. Significant circulating biomarker differences, including bilirubin, erythrocytes, monocytes, neutrophils, lymphocytes, and platelet markers, were found between ROP and non-ROP groups, with variations depending on the polymorphism. These findings suggest that NGF (rs6330) and its interactions with related genes contribute to ROP risk, providing valuable insights into the genetic and biological mechanisms underlying the disease and identifying potential predictive biomarkers.
- Intrinsic vasomotricity and adrenergic effects in a model of isolated rabbit eyePublication . Delgado, Esmeralda; Marques-Neves, Carlos; Rocha, Isabel; Sales-Luis, José; Silva-Carvalho, LuísPurpose: We aimed to investigate the responsiveness of the ocular arteries to adrenergic drugs in a model of perfused isolated rabbit eye. Methods: Rabbit external ophthalmic arteries (n = 15) in a head-mounted preparation were cannulated and the retinal and uveal vasculature perfused at a constant flow with warmed tyrode. The three-way polypropylene catheter was further connected to a pressure transducer and intraluminal pressure was taken as a measure of vascular resistance. Effects of intra-arterial injections of phenylephrine (group A, n = 5), prazosin (group B, n = 5) and phentolamine (group C, n = 5) on the recorded pressure were obtained. Student’s paired-t test and one-way analysis of variance were used for statistical analysis (p < 0.05). Results: Intrinsic vasomotricity was observed in all preparations prior to any drug administration. Phenylephrine produced an increase in total vascular resistance. Intrinsic vasomotricity became more evident, showing a lower frequency but higher amplitude of oscillations. Evoked vasomotor responses with phenylephrine (250 lg ⁄ ml) were inhibited by intra-arterial administration of the selective a1-adrenergic antagonist, prazosin (0.5 mg⁄ ml), as well as the non-selective a-adrenergic antagonist phentolamine (6 mg⁄ ml). Conclusions: Rabbit external ophthalmic arteries showed spontaneous contractions under constant perfusion. Phenylephrine elicited a vasoconstrictor response that was inhibited by adrenergic antagonists. In addition, the intrinsic vasomotricity was enhanced by phenylephrine and blocked by adrenergic antagonists. These results show that under in vitro perfusion the territory presents similar responses to adrenergic drugs to those observed in in vivo models and also provides evidence of myogenic autoregulatory properties in the rabbit ophthalmic artery and ⁄ or choroid
- A non-infectious uveitis multidisciplinary clinic in a tertiary referral center: clinical impact and added valuePublication . Leal, Ines; Romão, Vasco C.; Sousa Mano, Sofia; Khmelinskii, Nikita; Campanilho-Marques, Raquel; Ponte, Cristina; Macieira, Carla; Oliveira Ramos, Filipa; Vieira De Sousa, Elsa Cristina; Rosa, Carlos Miranda; Rodrigues, Walter; Pinto, Luis; Marques-Neves, Carlos; Fonseca, João EuricoNon-infectious uveitis (NIU) is a group of sight-threatening diseases that generates significant burden for the healthcare systems due to its adverse outcomes, irreversible structural complications in the eye with loss of visual function, limited clinical expertise and low-grade evidence for best practice. The usefulness of multidisciplinary care, specifically close collaboration between Rheumatologists and Ophthalmologists in NIU, has been emphasized in the literature. In this paper, the assessment tools and protocols used in our clinic are depicted and an overview of our activity with a brief description of the patients included in our registry, between 2018 and 2020 is provided. The cohort of 290 patients assessed in our NIU clinic, their demographics, sources of referral, details about immunosuppression treatment, and internal and external collaborations is described. This experience-based manuscript aims to describe the general functioning of our multidisciplinary NIU clinic, highlighting the benefits and drawbacks of multidisciplinary team management in patients with NIU, ultimately initiating a dialogue on what an NIU clinic should be and providing information for newly NIU clinics start-up. In conclusion, establishing a standardized and multidisciplinary clinic in NIU allows to systematically observe and follow-up this infrequent disease at a tertiary hospital level, thus improving quality of care delivery and research avenues.