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- Relationship between intraocular pressure and anterior lamina cribrosa depth : a cross-sectional observational study in a healthy Portuguese populationPublication . Sousa, David Cordeiro; Leal, Ines; Marques-Neves, Carlos; Pinto, Filomena; Pinto, LuisPurpose: To investigate the association between anterior lamina cribrosa depth (ALCD), determined with enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT), and intraocular pressure (IOP) in a healthy Portuguese population. Methods: In this cross-sectional observational study conducted between January and July 2015, 2 optic nerve head (ONH)-centered EDI-OCT cross-scans were performed and ALCD was defined as the perpendicular distance between the line connecting both edges of Bruch's membrane opening and the anterior border of the lamina cribrosa at the maximum depth point. A multivariate regression model was performed to assess the association of IOP and ALCD. Results: The studied population included 59 subjects (35 women) with a mean age of 61.7 ± 15.1 years. Mean vertical and horizontal maximum ALCD was 444.5 ± 92.2 μm and 427.6 ± 82.7 μm, respectively. When controlling for age and spherical equivalent, maximum vertical and horizontal ALCD were positively correlated with intraocular pressure (R2>0.20) by 8.58 μm (95% confidence interval [CI] 2.80-14.36 μm; p<0.01) and 8.25 μm (95% CI 2.71-13.78 μm; p<0.01) per mm Hg of IOP, respectively. Conclusions: Our sample of healthy subjects presented a statistically significant positive correlation between IOP and ALCD when controlling for possible confounding factors. These results may trigger further studies to better elucidate the role of IOP in the morphologic and functional dynamics of the ONH.
- Retropupillary iris claw intraocular lens implantation in aphakia for dislocated intraocular lensPublication . Faria, Mun Yueh; Ferreira, Nuno Pinto; Pinto, Joana Medeiros; Sousa, David Cordeiro; Leal, Ines; Neto, Eliana; Marques-Neves, CarlosBackground: Nowadays, dislocated intraocular lenses (IOLs) and inadequate capsular support are becoming a challenge for every ophthalmic surgeon. Explantation of dislocated IOL and iris claw IOL (ICIOL) are the techniques that have been used in our ophthalmic department. The aim of this study is to report our technique for retropupillar ICIOL. Methods: This study is a retrospective case series. A total of 105 eyes with dislocated IOL from the patients at the Department of Ophthalmology in Santa Maria Hospital, a tertiary reference hospital in Lisbon, Portugal, from January 2012 until January 2016, had been analyzed. Of these 105 eyes, 66 eyes had dislocated one-piece IOL and 39 eyes had dislocated three-piece IOL. The latter underwent iris suture of the same IOL and were excluded from this study. The remaining 66 eyes with dislocated one-piece IOL underwent pars plana vitrectomy, that is, explantation of dislocated IOL through corneal incision and an implantation of retropupillary ICIOL. Operative data and postoperative outcomes included best corrected visual acuity, IOL position, intraocular pressure, pigment dispersion, clinical signs of endothelial cell loss, and anterior chamber depth. Results: The mean follow-up was 23 months (range: 6–48 months). The mean preoperative best corrected visual acuity was 1.260±0.771 logMAR, and postoperative best corrected visual acuity was 0.352±0.400 logMAR units. Mean vision gain was 0.909 logMar units. The patients had the following complications: 1) retinal detachment was found in one patient, 2) corneal edema was found in three patients, 3) high intraocular pressure was observed in twelve patients, 4) subluxation of the IOL was observed in one patient, and 5) macular edema was found in three eyes. Conclusion: The results demonstrate that retropupillary ICIOL is an easy and effective method for the correction of aphakia in patients not receiving capsule support. The safety of this procedure must be interpreted in the context of a surgery usually indicated in complicated cases.
- 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.
- Tubulointerstitial nephritis and uveitis TINU syndrome : a reviewPublication . Amaro, David; Carreño, Ester; Steeples, Laura R.; Oliveira Ramos, Filipa; Marques-Neves, Carlos; Leal, InesInflammation of renal interstitium and uveal tissue establishes the two components of tubulointerstitial nephritis and uveitis (TINU) syndrome. Although believed to occur more frequently in young females, a broad spectrum of patients can be affected. Both renal and eye disease can be asymptomatic and may not manifest simultaneously, having independent progressions. Renal disease manifests as acute kidney injury and may cause permanent renal impairment. Eye inflammation can manifest in different anatomical forms, most commonly as bilateral anterior uveitis and may progress to a chronic course. TINU syndrome accounts for approximately 1%–2% of uveitis in tertiary referral centres. A literature review covering the clinical features, pathogenesis, diagnosis and treatment is presented.
- A protocol to evaluate retinal vascular response using optical coherence tomography angiographyPublication . Sousa, David Cordeiro; Leal, Ines; Moreira, Susana; Vale, Sónia do; Silva-Herdade, Ana S.; Aguiar, Patrício; Dionísio, Patrícia; Pinto, Luis; Castanho, Miguel A. R. B.; Marques-Neves, CarlosIntroduction: Optical coherence tomography angiography (OCT-A) is a novel diagnostic tool with increasing applications in ophthalmology clinics that provides non-invasive high-resolution imaging of the retinal microvasculature. Our aim is to report in detail an experimental protocol for analyzing both vasodilatory and vasoconstriction retinal vascular responses with the available OCT-A technology. Methods: A commercial OCT-A device was used (AngioVue®, Optovue, CA, United States), and all examinations were performed by an experienced technician using the standard protocol for macular examination. Two standardized tests were applied: (i) the hypoxia challenge test (HCT) and (ii) the handgrip test, in order to induce a vasodilatory and vasoconstriction response, respectively. OCT-A was performed at baseline conditions and during the stress test. Macular parafoveal vessel density of the superficial and deep plexuses was assessed from the en face angiograms. Statistical analysis was performed using STATA v14.1 and p < 0.05 was considered for statistical significance. Results: Twenty-four eyes of 24 healthy subjects (10 male) were studied. Mean age was 31.8 ± 8.2 years (range, 18–57 years). Mean parafoveal vessel density in the superficial plexus increased from 54.7 ± 2.6 in baseline conditions to 56.0 ± 2.0 in hypoxia (p < 0.01). Mean parafoveal vessel density in the deep plexuses also increased, from 60.4 ± 2.2 at baseline to 61.5 ± 2.1 during hypoxia (p < 0.01). The OCT-A during the handgrip test revealed a decrease in vessel density in both superficial (55.5 ± 2.6 to 53.7 ± 2.9, p < 0.001) and deep (60.2 ± 1.8 to 56.7 ± 2.8, p < 0.001) parafoveal plexuses. Discussion: In this work, we detail a simple, non-invasive, safe, and non-costly protocol to assess a central nervous system vascular response (i.e., the retinal circulation) using OCT-A technology. A vasodilatory response and a vasoconstriction response were observed in two physiologic conditions—mild hypoxia and isometric exercise, respectively. This protocol constitutes a new way of studying retinal vascular changes that may be applied in health and disease of multiple medical fields.
- Retinal vascular reactivity in type 1 diabetes patients without retinopathy using optical coherence tomography angiographyPublication . Sousa, David Cordeiro; Leal, Ines; Moreira, Susana; Vale, Sónia do; Silva-Herdade, Ana S.; Aguiar, Patrício; Dionísio, Patrícia; Pinto, Luis; Castanho, Miguel A. R. B.; Marques-Neves, CarlosPurpose: We hypothesize that patients with type 1 diabetes (T1D) may have abnormal retinal vascular responses before diabetic retinopathy (DR) is clinically evident. Optical coherence tomography angiography (OCTA) was used to dynamically assess the retinal microvasculature of diabetic patients with no clinically visible retinopathy. Methods: Controlled nonrandomized interventional study. The studied population included 48 eyes of 24 T1D patients and 24 demographically similar healthy volunteers. A commercial OCTA device (AngioVue) was used, and two tests were applied: (1) the hypoxia challenge test (HCT) and (2) the handgrip test to induce a vasodilatory or vasoconstrictive response, respectively. The HCT is a standardized test that creates a mild hypoxic environment equivalent to a flight cabin. The handgrip test (i.e., isometric exercise) induces a sympathetic autonomic response. Changes in the parafoveal superficial and deep capillary plexuses in both tests were compared in each group. Systemic cardiovascular responses were also comparatively evaluated. Results: In the control cohort, the vessel density of the median parafoveal superficial and deep plexuses increased during hypoxia (F1,23 = 15.69, P < 0.001 and F1,23 = 16.26, P < 0.001, respectively). In the T1D group, this physiological response was not observed in either the superficial or the deep retinal plexuses. Isometric exercise elicited a significant decrease in vessel density in both superficial and deep plexuses in the control group (F1,23 = 27.37, P < 0.0001 and F1,23 = 27.90, P < 0.0001, respectively). In the T1D group, this response was noted only in the deep plexus (F1,23 = 11.04, P < 0.01). Conclusions: Our work suggests there is an early impairment of the physiological retinal vascular response in patients with T1D without clinical diabetic retinopathy.
- 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.
- 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.
- Optical coherence tomography angiography study of the retinal vascular plexuses in type 1 diabetes without retinopathyPublication . Sousa, David Cordeiro; Leal, Ines; Moreira, Susana; Vale, Sónia do; Silva-Herdade, Ana S.; Dionísio, Patrícia; Castanho, Miguel A. R. B.; Pinto, Luis; Marques-Neves, CarlosAim Previous data suggest the existence of retinal vascular changes and impaired autoregulation in the very early stages of diabetic retinopathy (DR). We compared the retinal plexuses between patients with type 1 diabetes (T1D) without DR and a demographically similar healthy cohort, using optical coherence tomography angiography (OCT-A). Methods Patients with T1D and no signs of DR were prospectively recruited from an outpatient clinic. Using OCT-A (AngioVue®), the parafoveal superficial (SCP) and deep (DPC) capillary plexus as well as the foveal avascular zone (FAZ) and perimeter were gathered. Mean comparison tests and linear regression analysis were used as statistical tests (STATA v14). Results Studied population included 48 subjects (24 T1D). The analysis of SCP revealed an attenuation of the capillary network compared with the control group in both parafoveal (51.8 ± 4.5 vs. 55.8 ± 3.2, p < 0.001) and perifoveal (51.9 ± 3.3 vs. 53.9 ± 1.9, p = 0.01) regions. A similar finding was observed in the DCP for both parafoveal (56.4 ± 4.3 vs. 60.4 ± 2.2, p < 0.001) and perifoveal (54.7 ± 3.9 vs. 60.8 ± 3.4, p = 0.001) sectors. Also, a longer time since T1D diagnosis was associated with a larger FAZ area (p = 0.055) and perimeter (p = 0.03). Conclusions Significant differences in the retinal microvasculature were observed between healthy subjects and T1D patients using OCT-A, even before clinically detectable disease on fundus biomicroscopy.