Publications by authors named "Inês Leal"

41 Publications

Topical corticosteroids with topical cyclosporine A versus topical corticosteroids alone for immunological corneal graft rejection.

Eur J Ophthalmol 2021 Jul 7:11206721211023320. Epub 2021 Jul 7.

Ophthalmology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal.

Purpose: To assess the efficacy and safety of supplementing topical cyclosporine A (CsA) to topical corticosteroids (CS), in the prophylaxis and treatment of corneal graft rejection following penetrating keratoplasty (PK).

Methods: Meta-analysis. Search was performed in PubMed, CENTRAL, ClinicalTrials.gov, reference lists of articles and conference proceedings. Primary outcomes: 1-year rejection-free survival rate (prophylaxis); resolution rate of rejection episodes (treatment). Secondary outcomes: 6- and 24-month rejection-free graft survival rate, number of rejection episodes during follow-up, time-to-resolution of rejection episode, 12- and 24-months graft survival rate, adverse events. Subgroup analyses were planned for high-risk grafts; primary vs. secondary prophylaxis of graft rejection episodes; and CsA concentrations of 0.05%, 1%, and 2%.

Results: Five studies of moderate methodological quality were included (one retrospective, four RCT), assessing 459 eyes (CS + CsA 226, CS 233). In the prophylaxis setting, supplemental CsA was associated with a higher rejection-free survival rate at 12-months (RR 1.25, 95% CI: 1.00-1.56,  = 0.05) and 24-months post-PK (RR 1.56, 95% CI: 1.15-2.11,  < 0.01), though no differences were found at the 6-months timepoint ( = 0.93). This effect was mostly verified using CsA 2% in the high-risk subset of patients. In the treatment setting, no differences were found in the resolution rate of rejection episodes ( = 0.23). No differences existed on drug-related adverse events.

Conclusion: In the prophylaxis of rejection episodes post-PK, the combined regimen of CS + CsA was associated with a higher 1- and 2-year rejection-free graft survival rate. Subgroup analysis mostly supported the use of CsA 2% for high-risk grafts. Further studies are needed to validate these results.
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http://dx.doi.org/10.1177/11206721211023320DOI Listing
July 2021

Intravitreal Fluocinolone 0.19mg Implant in the Management of Chronic Non-Infectious Uveitis: 12-Month Outcomes from a Single Tertiary Centre.

Ocul Immunol Inflamm 2021 Jun 14:1-7. Epub 2021 Jun 14.

Manchester Royal Eye Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Aim: To present efficacy and safety of 0.19 mg fluocinolone acetonide insert (FAi) to treat chronic noninfectious uveitis (NIU) in a single referral center.

Methods: A retrospective observational clinical study of 11 eyes with NIU complicated by chronic cystoid macular edema (CMO).

Results: The main indication for treatment was chronic CMO in all 11 eyes. The mean central retinal thickness (CRT) at baseline was 435 μm ± 176, improving to 296 μm ± 67 at 12 months. Raised intraocular pressure (IOP) was the commonest adverse event. An IOP >21 mmHg was observed in three eyes, and >30 mmHg in one eye, managed with topical therapy. The mean best corrected visual acuity (BCVA) was stable at 12 months. There were no observed recurrences of uveitis. Two eyes received adjunctive treatment for worsening CRT.

Conclusions: Our results suggest FAi is an effective maintenance treatment for NIU with favorable functional and anatomical outcomes.
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http://dx.doi.org/10.1080/09273948.2021.1922707DOI Listing
June 2021

Evaluating the Safety, Efficacy and Patient Acceptability of Intravitreal Fluocinolone Acetonide (0.2mcg/Day) Implant in the Treatment of Non-Infectious Uveitis Affecting the Posterior Segment.

Clin Ophthalmol 2021 7;15:1433-1442. Epub 2021 Apr 7.

Ophthalmology Department, Centro Hospitalar Universitário Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal.

Long-acting, slow-release injectable fluocinolone intravitreal implants have been approved for the treatment of non-infectious uveitis affecting the posterior segment. We summarise the development of intravitreal fluocinolone implants and discuss the technology including pharmacokinetics. We conducted a systematic review of evidence for the efficacy, safety and patient acceptability of fluocinolone 0.18 mg and 0.19 mg injectable implants. We summarise evidence from the pivotal phase 3 studies that lead to the approval of these implants and evaluate real-world including disease-specific evidence. Safety including injection-related events and long-term adverse events is presented.
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http://dx.doi.org/10.2147/OPTH.S216912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039205PMC
April 2021

A Non-Infectious Uveitis Multidisciplinary Clinic in a Tertiary Referral Center: Clinical Impact and Added Value.

J Multidiscip Healthc 2021 22;14:695-704. Epub 2021 Mar 22.

Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal.

Non-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.
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http://dx.doi.org/10.2147/JMDH.S292981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997415PMC
March 2021

Why Should SARS-CoV-2 Post-Pandemic Recovery Funding Be Used to Foster a Physician-Scientist Program?

Acta Med Port 2020 Sep 15;33(9):628. Epub 2020 Jul 15.

Centro de Genética Médica Jacinto Magalhães. Centro Hospitalar Universitário do Porto. Porto. Unit for Multidisciplinary Research in Biomedicine. Instituto de Ciências Biomédicas Abel Salazar. Universidade do Porto. Porto. Portugal.

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http://dx.doi.org/10.20344/amp.14421DOI Listing
September 2020

Retinal Vascular Reactivity in Type 1 Diabetes Patients Without Retinopathy Using Optical Coherence Tomography Angiography.

Invest Ophthalmol Vis Sci 2020 06;61(6):49

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Purpose: 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.
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http://dx.doi.org/10.1167/iovs.61.6.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415313PMC
June 2020

Intraocular Pressure Reduction After Real-world Cataract Surgery.

J Glaucoma 2020 08;29(8):689-693

University of Bristol and Bristol Eye Hospital.

PRéCIS:: A large cohort undergoing cataract extraction was retrospectively analyzed to ascertain the degree of real-world intraocular pressure (IOP) reduction in normal eyes and those with glaucoma, and a predictive formula was developed.

Purpose: The purpose of this study was to define the real-world degree of IOP reduction after cataract extraction to guide its role as an isolated intervention for glaucoma.

Materials And Methods: A retrospective analysis was carried out of clinical data collected in 8 clinical sites in the United Kingdom from an electronic medical record system between January 2006 and May 2015. A total of 20,508 eyes without known pathology and 2251 eyes from patients with glaucoma undergoing phacoemulsification and intraocular lens insertion were included. Eyes with intraoperative complications, undergoing additional procedures, axial lengths outside 22 to 26.5 mm, preoperative IOP under 6 mm Hg or over 30 mm Hg, and copathology, except for amblyopia or glaucoma, were excluded. The main outcome measure was the change in preoperative IOP compared with the next recorded visit for up to 12 weeks.

Results: In eyes without pathology, the mean reduction in IOP was 1.40 mm Hg (±3.74) compared with 1.03 (±5.02), P-value <0.001, in eyes with a diagnosis of glaucoma. A multiple linear regression model identified preoperative IOP, a glaucoma diagnosis, preoperative corrected visual acuity, age, and axial length as determinants of IOP reduction. The model was validated against an independent cohort.

Conclusions: We quantify mean IOP reduction achieved in a real-world setting from cataract surgery alone. In glaucomatous eyes where angle closure is not differentiated, phacoemulsification alone yields only a modest reduction of IOP.
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http://dx.doi.org/10.1097/IJG.0000000000001527DOI Listing
August 2020

Complete ILM Peeling Versus Inverted Flap Technique for Macular Hole Surgery: A Meta-Analysis.

Ophthalmic Surg Lasers Imaging Retina 2020 03;51(3):187-A2

Background And Objective: To compare complete internal limiting membrane (ILM) peeling with the inverted flap technique for macular hole (MH) surgery.

Patients And Methods: An electronic database search on PubMed, CENTRAL, and ClinicalTrials.gov was performed. Inclusion criteria were comparative prospective/retrospective studies including patients with MH of any size with at least 6 months of follow-up. The primary outcome was MH closure rate. Secondary outcomes were best-corrected visual acuity improvement and surgery-related adverse events.

Results: Sixteen papers enrolling 1,403 eyes were included (733 ILM peeling, 670 inverted flap). MH mean minimum diameter and time of symptomatic evolution were higher in the inverted flap group (531.1 μm ± 188.8 μm vs. 602.8 μm ± 223.8 μm; 10.4 ± 20.2 months vs. 12.0 ± 18.4 months; P < .01). Overall, MH closure rate was superior with the inverted flap technique (risk-ratio [RR]: 1.25; 95% confidence interval [CI], 1.14-1.38; P < .0001), as well as in all subgroups: idiopathic large MH (n = 362; RR: 1.12; 95% CI, 1.05-1.20; P < .001), myopic MH without retinal detachment (n = 133; RR: 1.35; 95% CI, 1.14-1.59; P < .001), and MH retinal detachment (n = 198; RR: 1.89; 95% CI, 1.31-2.73; P < .001).

Conclusion: This meta-analysis suggests the inverted flap technique is more effective in achieving MH closure. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:187-195.].
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http://dx.doi.org/10.3928/23258160-20200228-08DOI Listing
March 2020

Intra and inter-rater agreement of inflammatory choroidal neovascular membrane measurements using optical coherence tomography angiography.

Graefes Arch Clin Exp Ophthalmol 2020 Mar 19;258(3):647-651. Epub 2019 Dec 19.

Manchester Royal Eye Hospital, Central Manchester Foundation Trust, Manchester, UK.

Purpose: Automated measurement algorithm software is not routinely available in optical coherence tomography angiography (OCTA) devices and manual measurement of choroidal neovascular membrane (CNVM) size is necessary. Our aim was to determine intra- and inter-rater agreement of inflammatory CNVM manual measurements obtained with OCTA.

Methods: OCTA (Triton® Topcon Corporation) images in patients with inflammatory CNVM were imported into ImageJ software v1.50 (NIH image). Two experienced observers performed manual area and perimeter measurements independently, and one of the observers performed the same measurements twice. Agreement was evaluated with intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC). Bland-Altman plots were plotted to graphically assess concordance. Statistical analysis was performed using STATA v13.0.

Results: Sixteen eyes of 16 subjects, with a mean age of 39.0 ± 16.6 years (range 13-71), were included. Mean CNVM area and perimeter was 124.83 ± 117.80 and 4.20 ± 2.00 mm, respectively. Intra-rater ICC for both area and perimeter measured was 0.99 (95% confidence interval (CI) 0.99-0.99). Inter-rater ICC for area and perimeter measured was 0.95 (95%CI 0.87-0.98) and 0.81 (95%CI 0.17-0.94), respectively. Intra-rater CCC for both area and perimeter measured was 0.99 (95%CI 0.99-0.99). Inter-rater CCC for both area and perimeter measured was 0.91 (95%CI 0.81-0.99) and 0.66 (95%CI 0.44-0.88), respectively.

Conclusions: Inflammatory CNVM manual measurement showed high intra-rater agreement and moderate inter-rater agreement. Repeatability and reproducibility studies are essential in manual analysis to establish thresholds that can distinguish measurements variation from true clinical change. An automatic algorithm may be helpful to accurately grade lesions and monitor disease activity and response to treatment.
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http://dx.doi.org/10.1007/s00417-019-04538-1DOI Listing
March 2020

Tubulointerstitial nephritis and uveitis (TINU) syndrome: a review.

Br J Ophthalmol 2020 06 12;104(6):742-747. Epub 2019 Nov 12.

Centro de Estudos das Ciências da Visão, Faculdade de Medicina de Lisboa, Lisboa, Portugal

Inflammation 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.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314926DOI Listing
June 2020

[Choosing Wisely Portugal: The View of Portuguese Doctors].

Acta Med Port 2019 Aug 1;32(7-8):559-560. Epub 2019 Aug 1.

Centro de Estudos de Medicina Baseada na Evidência. Faculdade de Medicina. Universidade de Lisboa. Centro Académico de Medicina de Lisboa. Lisboa. Cochrane Portugal. Lisboa. Portugal.

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http://dx.doi.org/10.20344/amp.12448DOI Listing
August 2019

Optical coherence tomography angiography study of the retinal vascular plexuses in type 1 diabetes without retinopathy.

Eye (Lond) 2020 02 4;34(2):307-311. Epub 2019 Jul 4.

Ophthalmology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Av. Professor Egas Moniz, 1649-035, Lisboa, Portugal.

Aim: 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.
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http://dx.doi.org/10.1038/s41433-019-0513-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002748PMC
February 2020

A Protocol to Evaluate Retinal Vascular Response Using Optical Coherence Tomography Angiography.

Front Neurosci 2019 12;13:566. Epub 2019 Jun 12.

Ophthalmology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.

Introduction: 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 angiograms. Statistical analysis was performed using STATA v14.1 and < 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 ( < 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 ( < 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, < 0.001) and deep (60.2 ± 1.8 to 56.7 ± 2.8, < 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.
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http://dx.doi.org/10.3389/fnins.2019.00566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582622PMC
June 2019

Anti-TNF Drugs for Chronic Uveitis in Adults-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Front Med (Lausanne) 2019 24;6:104. Epub 2019 May 24.

Department of Rheumatology, Hospital de Santa Maria, Lisbon, Portugal.

We aimed to assess efficacy and safety of anti-tumor necrosis factor (TNF) drugs for adult chronic non-infectious uveitis (NIU). 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. 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, = 217), whereas the etanercept group did not (RR 0.81, 95%CI 0.57 to 1.14, = 20). In inactive NIU, adalimumab was associated with increased likelihood of VA preservation (RR 1.31, 95%CI 1.12 to 1.53, = 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, = 410). 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.
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http://dx.doi.org/10.3389/fmed.2019.00104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543521PMC
May 2019

Prescription pattern of ocular hypotensive drugs in Portugal and its comparison with the European guidelines - PEM Study.

Acta Ophthalmol 2019 Nov 27;97(7):e1030-e1031. Epub 2019 Mar 27.

Vision Sciences Study Centre, CECV, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.

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http://dx.doi.org/10.1111/aos.14103DOI Listing
November 2019

Surgical treatment of neovascular glaucoma: a systematic review and meta-analysis.

Graefes Arch Clin Exp Ophthalmol 2019 Jun 6;257(6):1079-1089. Epub 2019 Feb 6.

Department of Ophthalmology, Hospital Santa Maria, Av Prof. Dr. Egas Moniz, 1649-035, Lisbon, Portugal.

Purpose: This literature review and meta-analysis aims to compare intraocular pressure (IOP) lowering efficacy, failure rates and loss of light perception (LP) rates 6 months after an IOP-lowering surgical procedure in neovascular glaucoma (NVG) eyes.

Methods: MEDLINE and EMBASE were used as data sources. Only studies including NVG patients who underwent two different surgical approaches were considered. The treatment effect measures were (i) weighted mean difference (WMD) for IOP reduction, (ii) risk ratio (RR) for failure rates and (iii) risk difference (RD) for loss of LP. Outcome measures were reported with a 95% confidence interval (CI) and P < 0.05 was considered statistically significant. Analysis was performed using RevMan v5.0.

Results: No RCT were retrieved. Seven comparative non-randomised studies were eligible. In glaucoma drainage devices (GDDs) vs cyclophotocoagulation arm, there was no statistical difference in IOP-lowering efficacy (WMD = - 3.63; CI [- 8.69, 1.43], P = 0.16), although failure rates and loss of LP were lower in the GDDs group (RR = 0.64, CI [0.41, 0.99], P = 0.05; and RD = - 0.15, CI [- 0.25, - 0.05], P = 0.004, respectively). In the Ahmed glaucoma valve (AGV) vs trabeculectomy arm, there was no statistical difference in IOP-lowering efficacy and loss of LP (WMD = 0.78, CI [- 2.29, 3.85], P = 0.62 and RD of 0.04, CI [- 0.05, 0.14], P = 0.34, respectively), but failure rates were lower in trabeculectomy group (RR of 2.25, CI [1.14, 3.71], P = 0.02).

Conclusions: There is lack of high-quality evidence on the subject as no RCT were retrieved comparing two different IOP-lowering procedures in NVG patients. Our findings are based, therefore, on non-RCT studies and should be interpreted with caution. There appears to be no difference in IOP-lowering efficacy between GDDs and cyclophotocoagulation, although GDDs appear to be safer. AGV and trabeculectomy also seem to provide similar IOP-lowering results with trabeculectomy showing lower failure rates.
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http://dx.doi.org/10.1007/s00417-019-04256-8DOI Listing
June 2019

Automated gonioscopy photography for iridocorneal angle grading.

Eur J Ophthalmol 2020 Jan 26;30(1):112-118. Epub 2018 Oct 26.

Department of Ophthalmology, Hospital de Santa Maria, Lisbon, Portugal.

Purpose: The aim of this study is to assess the agreement between manual and automated gonioscopy for iridocorneal angle opening.

Methods: The research is a cross-sectional observational study. Manual and automated gonioscopy were performed to consecutive patients in a glaucoma clinic. Iridocorneal angle opening grading was performed according to Shaffer's classification. Automated gonioscopy was performed with NGS-1 automated gonioscope (NIDEK Co., Gamagori, Japan). The automated gonio-photos were graded by two independent observers. Agreement between automated and manual gonioscopy and also among raters was ascertained by Fleiss' kappa statistic and comparison of area under curve.

Results: In total, 88 eyes of 47 subjects were analysed. Mean age was 63 ± 10 years. Twenty eyes (22.7%) were excluded from grading due to poor quality images. Angle closure was detected in 23.4% with dynamic gonioscopy in comparison with 4.3% using automated image grading. The agreement for angle closure diagnosis between dynamic and automated gonioscopy was low (κ = 0.09 ± 0.10; p = 0.18). The area under curve for detecting eyes with angle closure showed poor accuracy between automated and manual methods (area under curve: 0.53 ± 0.05, 95% confidence interval: 0.44-0.62). There was modest inter-rater agreement for angle opening assessment of automated images with Fleiss' kappa of 0.17 (95% confidence interval: 0.035-0.238).

Conclusion: Manual and automated gonioscopy showed only slight agreement for the assessment of iridocorneal angle opening status. Further improvements of the NGS-1 automated gonioscopy and technique are desired for widespread use in a real-life setting.
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http://dx.doi.org/10.1177/1120672118806436DOI Listing
January 2020

Association Between Alcohol Intake and Cardiac Remodeling.

J Am Coll Cardiol 2018 09;72(13):1452-1462

Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: Alcohol-induced cardiotoxicity is incompletely understood. Specifically, the long-term impact of alcohol use on ventricular remodeling or dysfunction, its modulators, and effect thresholds among young adults remain controversial.

Objectives: The authors sought to evaluate a potential relationship between alcohol intake and cardiac remodeling, assessed by echocardiography, over 20 years of follow-up.

Methods: Among the CARDIA (Coronary Artery Risk Development in Young Adults) study cohort, the authors studied all subjects without baseline heart disorders who provided adequate information on their drinking habits and underwent echocardiographic evaluation at years 5 and 25 of the study. The echocardiographic outcomes were left ventricular (LV) ejection fraction, indexed LV end-diastolic volume and LV mass, and left atrial diameter. Participants were grouped according to their weighted-average weekly drinking habits. An additional analysis used the estimated cumulative alcohol consumption. Regression models and multivariable fractional polynomials were used to evaluate the association between alcohol consumption and the outcomes.

Results: Among the 2,368 participants, alcohol consumption was an independent predictor of higher indexed LV mass (p = 0.014) and indexed LV end-diastolic volume (p = 0.037), regardless of sex. No significant relationship between alcohol intake and LV ejection fraction was found. Drinking predominantly wine was associated with less cardiac remodeling and there was a nonsignificant trend for a harmful effect of binge drinking.

Conclusions: After 20 years of follow-up, alcohol intake was associated with adverse cardiac remodeling, although it was not related with LV systolic dysfunction in this initially healthy young cohort. Our results also suggest that drinking predominantly wine associates with less deleterious findings in cardiac structure.
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http://dx.doi.org/10.1016/j.jacc.2018.07.050DOI Listing
September 2018

Steroid-induced protracted severe ocular hypertension in a 14-year-old girl.

BMJ Case Rep 2018 Jun 27;2018. Epub 2018 Jun 27.

Ophthalmology Department, Hospital de Santa Maria, Lisboa, Portugal.

Steroid-induced ocular hypertension (SIOH) is a challenging entity in paediatric age, with many being refractory to medical therapy. Literature is scarce about surgical options in these cases. A 14-year-old girl with bilateral uveitis and macular oedema had received an intravitreal and subconjunctival triamcinolone injection in the right (OD) and left (OS) eye, respectively. While the steroid was effective in resolving the oedema, intraocular pressure (IOP) increased to about 40 mm Hg OD and 34 mm Hg OS, despite being under maximal IOP-lowering therapy. An initial conservative approach was preferred due to the young patient age and given that most cases of SIOH are transient. However, progressive structural changes were documented, and bilateral sequential minimally invasive glaucoma surgery (MIGS: XEN gel stent) was taken. With a follow-up of 6 months, the patient is drug-free with IOP around 14 mm Hg. This report discusses the role and efficacy of MIGS in a paediatric case of SIOH.
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http://dx.doi.org/10.1136/bcr-2018-225244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020893PMC
June 2018

Tubulointerstitial nephritis and uveitis syndrome in children: report of three cases.

J Bras Nefrol 2018 Jul-Sep;40(3):296-300. Epub 2018 Jun 18.

Unidade de Nefrologia e Transplantação Renal, Serviço de Pediatria Médica, Departamento de Pediatria, Hospital de Santa Maria, Centro Académico de Medicina, Universidade de Lisboa, Lisboa, Portugal.

Tubulointerstitial nephritis and uveitis syndrome is a rare and probably underdiagnosed condition. Renal and ocular manifestations may not occur simultaneously, making the diagnosis more difficult. Nephritis may be asymptomatic; therefore, renal function evaluation is essential for diagnosis. Urinary β2-microglobulin levels may be particularly useful. Uveitis, mostly anterior, nongranulomatous and bilateral, occurs usually after the onset of nephritis. Treatment includes corticosteroids and, eventually, other immunosuppressant agents. Renal disease is usually benign and resolves spontaneously or after treatment with systemic corticosteroids. Uveitis, however, may be chronic or recurrent. The authors described the cases of three pediatric patients diagnosed with tubulointerstitial nephritis and uveitis syndrome. The goal of this paper was to warn the medical community over the need to screen patients with uveitis for renal disease.
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http://dx.doi.org/10.1590/2175-8239-jbn-2018-0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533956PMC
June 2019

[Analysis of the Cochrane Review: Cortisteroid Implants for Chronic Non-Infectious Uveitis. Cochrane Database Syst Rev. 2016;2:CD010469].

Acta Med Port 2018 May 30;31(5):243-246. Epub 2018 May 30.

Centro de Estudos de Medicina Baseada na Evidência. Faculdade de Medicina. Universidade de Lisboa. Lisboa; Centro Colaborador Português da Rede Cochrane Iberoamericana. Faculdade de Medicina. Universidade de Lisboa. Lisboa. Portugal.

Non-infectious uveitis is a heterogeneous collection of inflammatory eye diseases and is one of the most important causes of blindness among active adults in developed countries. Inflammation control is crucial in the prevention of ocular structural and functional damage. Regarding acute inflammatory control, corticosteroids are the mainstay of treatment. Several types of intra-ocular corticosteroids have been used with the aim of enhanced efficacy compared to their topical or peri-ocular administration, while minimizing its adverse effects associated with the systemic administration. The purpose of this Cochrane review was to synthetize the available evidence regarding the efficacy and safety of corticosteroid implants in comparison with standard treatment. Due to the heterogeneity in the design of the studies and outcome measures assessed, authors could not conclude that implants are superior to traditional systemic therapy in Non-infectious uveitis. The safety analysis suggested increased risks of post-implant surgery for cataract and high intraocular pressure compared with standard-of-care therapy.
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http://dx.doi.org/10.20344/amp.10660DOI Listing
May 2018

Efficacy and safety of intravitreal anti-tumour necrosis factor drugs in adults with non-infectious uveitis - a systematic review.

Acta Ophthalmol 2018 Sep 25;96(6):e665-e675. Epub 2018 Mar 25.

Department of Rheumatology, Hospital de Santa Maria-CHLN, Lisbon Academic Medical Centre, Lisbon, Portugal.

Anti-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.
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http://dx.doi.org/10.1111/aos.13699DOI Listing
September 2018

XEN Gel Stent Obstruction: Test for Patency.

Ophthalmol Glaucoma 2018 Jul - Aug;1(1):81. Epub 2018 Aug 13.

Visual Sciences Study Center, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; Ophthalmology Department, Hospital Santa Maria, Lisbon, Portugal.

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http://dx.doi.org/10.1016/j.ogla.2018.04.001DOI Listing
August 2021

Ophthalmoparesis and unilateral finger flexor muscle weakness in seronegative myasthenia gravis.

Can J Ophthalmol 2017 12 28;52(6):e213-e216. Epub 2017 Jun 28.

Department of Ophthalmology, Hospital de Santa Maria, 1649-035, Lisbon, Portugal; Centro de Estudos Ciências da Visão, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal.

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http://dx.doi.org/10.1016/j.jcjo.2017.04.012DOI Listing
December 2017

Hypoxia challenge test and retinal circulation changes - a study using ocular coherence tomography angiography.

Acta Ophthalmol 2018 May 21;96(3):e315-e319. Epub 2017 Nov 21.

Ophthalmology Department, Hospital de Santa Maria, Lisbon, Portugal.

Purpose: Previous studies report that the response of retinal vessels to a decrease in oxygen (hypoxia) is vasodilation, thus increasing blood flow. We aimed to characterize the changes in retinal microvasculature induced by a mild hypoxia stress test in a healthy population, using ocular coherence tomography angiography (OCT-A) technology.

Methods: Interventional repeated-measures study. The standardized hypoxia challenge test (HCT) was performed to all volunteers, according to the British Thoracic Society protocol. Ocular coherence tomography angiography (OCT-A) was performed at three time-points (baseline, during HCT and 30' posthypoxia). Macular and peripapillary vessel densities were assessed using the built-in software. To minimize bias, analysis was performed separately in right (OD) and left (OS) eyes. Repeated-measures anova and mean comparison analysis were used as statistical tests (stata v13).

Results: Studied population included 30 healthy subjects (14 women), with a mean age of 28.8 ± 4.2 [range 22-37] years. Baseline vessel density increased in hypoxic conditions and subsequently decreased to near-baseline values in posthypoxia conditions. This pattern was observed for both eyes in both parafovea (OD: 55.3 ± 2.3 to 56.7 ± 1.9 to 55.8 ± 1.9, p < 0.05; OS: 56.9 ± 2.1 to 57.9 ± 1.9 to 57.3 ± 1.7, p < 0.05) and peripapillary (OD: 60.5 ± 0.5 to 62.6 ± 0.5 to 60.1 ± 0.4, p < 0.05; OS: 60.4 ± 0.4 to 62.3 ± 0.5 to 60.7 ± 0.4, p < 0.05) areas.

Conclusion: To our knowledge, there are no published data specifically addressing mild hypoxia conditions and retinal microvasculature changes, using OCT-A. This pilot study may pave way to better understand vascular responses in disease setting.
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http://dx.doi.org/10.1111/aos.13622DOI Listing
May 2018

[Analysis of the Cochrane Review: Anti-vascular Endothelial Growth Factor for Prevention of Postoperative Vitreous Cavity Hemorrhage after Vitrectomy for Proliferative Diabetic Retinopathy. Cochrane Database Syst Rev. 2015;8:CD008214.]

Acta Med Port 2017 Aug 31;30(7-8):513-516. Epub 2017 Aug 31.

Centro de Estudos de Medicina Baseada na Evidência. Faculdade de Medicina. Universidade de Lisboa. Lisboa. Portugal; Cochrane Portugal. Lisboa. Portugal.

Postoperative vitreous hemorrhage is a complication following vitrectomy for proliferative diabetic retinopathy, delaying visual recovery and making fundus examination and disease follow-up more difficult. Anti-vascular endothelial growth factor drugs such as bevacizumab, when injected in the vitreous cavity, reduce vascular proliferation and their use has been proposed to reduce the incidence of postoperative vitreous hemorrhage. The authors of this Cochrane systematic review evaluated all randomized controlled trials on the pre- or intraoperative use of anti-vascular endothelial growth factor to reduce postoperative vitreous hemorrhage occurrence after vitrectomy in patients with proliferative diabetic retinopathy. The results suggested that the use of intravitreal bevacizumab was effective in reducing early postoperative vitreous hemorrhage (i.e. at four weeks) occurrence, with a good safety profile. This work aims to summarize and discuss the findings and clinical implications of this Cochrane systematic review.
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http://dx.doi.org/10.20344/amp.9437DOI Listing
August 2017

Sympathetic ophthalmia related to conjunctival invasive squamous-cell carcinoma.

Indian J Ophthalmol 2017 08;65(8):741-743

Department of Ophthalmology, Hospital de Santa Maria; Visual Sciences Study Center, CECV, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

Sympathetic ophthalmia (SO) is a rare, diffuse, bilateral, and granulomatous nonnecrotizing panuveitis that may follow intraocular penetrating trauma. Our aim is to report a rare case of SO following orbital exenteration. Orbital exenteration was performed on a 48-year-old african female due to conjunctival keratinizing squamous cell carcinoma with intraocular involvement of the left eye. Five days after the uneventful procedure, the patient presented signs and symptoms compatible with SO. Key differential diagnoses were excluded, and prompt and aggressive immunosuppression was started with a favourable but slow clinical response. This case highlights the fact that SO can also be induced by a neoplasm with intraocular invasion or by aggressive nonpenetrating surgery. While the underlying pathogenesis of SO is still not fully elucidated, we hereby contribute with a novel potential mechanism leading to its development.
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http://dx.doi.org/10.4103/ijo.IJO_983_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598188PMC
August 2017

Photocatalytic ozonation using doped TiO catalysts for the removal of parabens in water.

Sci Total Environ 2017 Dec 25;609:329-340. Epub 2017 Jul 25.

CIEPQPF - Chemical Engineering Processes and Forest Products Research Center, Department of Chemical Engineering, Faculty of Sciences and Technology, University of Coimbra, Rua Sílvio Lima, 3030-790 Coimbra, Portugal.

Conventional wastewater treatments are inefficient for the removal of parabens. The aim of this study was finding a suitable solution using ozone and UVA irradiation combined with TiO catalysts doped with different noble metals (Ag, Pt, Pd, Au). Photocatalytic ozonation required lower amounts of ozone for higher efficiency on the removal of parabens, chemical oxygen demand (COD) and total organic carbon (TOC). The best catalyst for the initial contaminants degradation was 0.5% Ag-TiO leading to total parabens removal using 46mgO/L. Due to the relative low mineralization achieved, the toxicity of the treated solutions was still compared with the initial one over several species (Vibrio fischeri, Lepidium sativum and Corbicula fluminea). All the treatments applied led to a clear decrease on the toxicity compared with initial mixture of parabens. From an economical point of view, it was concluded that the presence of UVA irradiation increased the energy consumption compared with catalytic ozonation with these catalysts but it can decrease the time of reaction. From the by-products analysis, it was concluded that hydroxylation appears to be the most significant reaction pathway and the main responsible for parabens degradation.
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http://dx.doi.org/10.1016/j.scitotenv.2017.07.180DOI Listing
December 2017

Use of Ocular Hypotensive Medications in Portugal: PEM Study: A Cross-sectional Nationwide Analysis.

J Glaucoma 2017 Jun;26(6):571-576

*Department of Ophthalmology, Hospital Santa Maria †Visual Sciences Study Center, Faculdade de Medicina, Universidade de Lisboa, PT ‡Shared Services of the Ministry of Health, EPE, Lisboa, PT §Tays Eye Centre, Tampere University Hospital, Tampere, FI.

Purpose: There is scarcity of European data about intraocular pressure (IOP)-lowering prescribing patterns. We aimed to describe and discuss the nationwide prescription of these medications in Portugal.

Materials And Methods: This was a cross-sectional study including all patients who were prescribed at least 1 IOP-lowering medication in 2015 in Portugal. All ocular hypotensive drug prescriptions were gathered from the common electronic drug prescription system used by all hospitals and clinics in Portugal. Demographic data, medications prescribed (number and formulation), physician specialty, and costs of medications were provided in an encrypted and anonymous form. Statistical analyses were performed using STATA.

Results: A total of 231,634 participants (57% women) were prescribed IOP-lowering medications in 2015, representing 4.0% of the population older than 40 years of age and 2.2% of the Portuguese total population. Mean age was 72±13 years. Topical IOP-lowering therapy accounted for a total of 26 million euros (M&OV0556;) in costs, shared between patients and the national health system. General practitioners (GPs) accounted for 52% of all prescriptions. The most prescribed drugs were latanoprost (28%), timolol/dorzolamide (19%), and brimonidine (14%). Among all, 72% of patients were on monotherapy. Compared with ophthalmologists, GPs presented qualitative differences in their prescription pattern, such as a lower proportion of unit dose prescription.

Conclusion: A significant percentage of the Portuguese population is currently treated with IOP-lowering medications, and the majority of them are on monotherapy. Although GPs are responsible for most prescriptions, their prescription pattern is different from that of ophthalmologists. This nationwide study revealed prescription patterns and disclosed the burden of the disease in terms of its medical management.
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http://dx.doi.org/10.1097/IJG.0000000000000668DOI Listing
June 2017
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