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- Application of Optical Coherence Tomography Angiography for Microvascular Changes in Patients Treated with Hydroxychloroquine: a Systematic Review and Meta-AnalysisPublication . Ferreira, A; Anjos, R; José-Vieira, R; Afonso, M; Abreu, AC; Monteiro, S; Macedo, M; Andrade, J; Furtado, MJ; Lume, MBackground: Retinal toxicity with long-term hydroxychloroquine (HCQ) treatment is a major concern. This systematic review aims to assess the application of optical coherence tomography angiography (OCTA) to detect microvascular alterations in patients under HCQ. Methods: PubMed, Scopus, Web of Science, and Cochrane Library databases were systematically searched until January 14, 2023. Studies using OCTA as a primary diagnostic method to evaluate the macular microvasculature of HCQ users were included. Primary outcomes were macular vessel density (VD) and foveal avascular zone (FAZ) at the superficial (SCP) and deep (DCP) capillary plexus. Meta-analysis was performed using a random-effects model. Results: Of 211 screened abstracts, 13 were found eligible, enrolling 989 eyes from 778 patients. High-risk patients due to longer duration of treatment presented lower VD in the retinal microvasculature than those with low-risk in SCP (P = 0.02 in fovea; P = 0.004 in parafovea) and in DCP (P = 0.007 in fovea; P = 0.01 in parafovea). When compared with healthy controls, HCQ users had lower VD in both plexus-no quantitative synthesis was presented. Conclusions: Microvascular changes were found in autoimmune patients under HCQ treatment without any documented retinopathy. However, the evidence produced so far does not allow to draw conclusion concerning the effect of drug as studies were not controlled for disease duration.
- Cost Comparison Between Defocus Spectacle Lens and Compound Atropine in Myopia Treatment in the Portuguese SettingPublication . Barros da Silva, P; Ludovico, I; Basilio, AL; Guimarães, SINTRODUCTION: The rising prevalence of myopia poses a substantial global concern. Low concentration atropine and defocus spectacle lens (DSL) are the most widely used myopia prevention treatment in Portugal. Atropine drops must be compounded in pharmacies, because there is still no commercial low concentration atropine approved in Portugal. There are no studies with enough evidence to prefer one treatment over the other, so cost might be a decisive factor. Our purpose was to compare the costs between DSL and compound atropine for myopia progression prevention in Portugal. METHODS: We collected data on compound atropine from different pharmacies in Portugal, monofocal (MF) lenses prices from the four most common brands in Portugal and DSL price from brand representatives. Cost estimates were done per year of four consecutive years of myopia prevention treatment, considering different scenarios according to the need of spectacle lens exchange. We compared costs of low dose compound atropine plus MF lens versus DSL in the different scenarios. RESULTS: Atropine treatment proved more cost-effective than DSL treatment only when there was a requirement for lens exchange every 6 months or less (609.25€ for atropine versus 780.00€ for DSL per year of treatment). When myopia progression prevention is more effectiveand the need of lens exchange is equal or greater than 12 months, DSL treatment showed to be less expensive than mean values of atropine treatment plus MF lens (390.00€ for DSL vs 464.59€ for atropine, per year of treatment). CONCLUSION: DSL take a cost advantage in prevention of myopia progression, in situations when there is a need of lens exchange within once a year or less frequently. However, atropine plus MF lenses might be a less expensive in cases whenever there is a need of lens exchange every 6 months or more frequently. It is essential to conduct further studies focusing on the costeffectiveness of different treatment options for preventing myopia progression
- The 2021 Portuguese Society of Ophthalmology Joint Guidelines with Paediatric Rheumatology on the Screening, Monitoring and Medical Treatment of Juvenile Idiopathic Arthritis-Associated UveitisPublication . Leal, I; Miranda, V; Fonseca, C; Barbosa-Breda, J; Cordeiro Sousa, D; Mesquita-Marques, P; Araújo, J; Silva, MI; Pedrosa, AC; Palmares, J; Furtado, MJ; Macedo, M; Lages, V; Fonseca, S; Gonçalves, R; Ruão, M; Gomes Rodrigues, F; Ribeiro, M; Proença, R; Almeida, M; Liverani, M; Morais Pina, S; Bernardo, M; Nogueira, V; Guerra Pinto, R; Pinto Ferreira, F; Pinto Proença, R; Domingues, I; Guedes, M; Cordeiro, M; Fragata, F; Berens, O; Gregório, T; Brito, I; Oliveira-Ramos, F; Fonseca, JE; Figueira, LAim: To develop the first Ophthalmology joint guidelines with Paediatric Rheumatology with recommendations on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis (JIA-U), endorsed by the Portuguese Society of Ophthalmology (SPO). Methods: A systematic literature review was conducted to include publications up to July 14th 2020, with no language restrictions, in order to include all the international position papers/guidelines concerning the medical management of JIA-U and randomised clinical trials assessing the efficacy and safety of medical treatment in this field. We searched through MEDLINE (PubMed), Scopus, Web of Science and Cochrane Library. The Delphi modified technique to generate consensus was used. Preliminary evidence statements were subject to an anonymous agreement assessment and discussion process using an online survey, followed by further discussion and update at a national meeting. A draft of the manuscript with all recommendations was then circulated among all participants and suggestions were incorporated. The final version was again circulated before publication. Results: Twenty-six recommendations were developed focusing on the following topics: general management (3), screening and follow-up of uveitis (4), treatment (17) and health education in JIA-U among patients and families (2). Conclusion: These guidelines were designed to support the shared medical management of patients with JIA-U and emphasize the need for a multidisciplinary approach between Ophthalmology and Paediatric Rheumatology regarding the comprehensive care of JIA-U. We acknowledge that updating these recommendations will be warranted in the future, as more evidence becomes available.
- Choroidal Vascular Impairment in Intermediate Age-Related Macular DegenerationPublication . Flores, R; Carneiro, A; Neri, G; Fradinho, A; Quenderra, B; Barata, MJ; Tenreiro, S; Seabra, MAge-related macular degeneration (AMD) is a multifactorial disease, whose complete pathogenesis is still unclear. Local hemodynamics may play a crucial role in its manifestation and progression. To evaluate choroidal and retinal vascular parameters, a total of 134 eyes were analyzed, 100 with intermediate AMD and 34 age matched healthy controls. 131 eyes of 104 patients were eligible for complete image assessment and 3 eyes were excluded for insufficient image quality: Group 1: intermediate AMD (n = 97) and Group 2: healthy controls (n = 34). Spectral domain optic coherence tomography (SD-OCT) with enhanced depth imaging (EDI) and optic coherence tomography angiography (OCT-A) were acquired using Spectralis (Heidelberg Engineering). Choroid and retinal capillary plexus were evaluated and image binarization was used to obtain quantitative data. Mean age was 77.67 years old (YO) and 67.2% were women. Total subfoveal choroidal area and luminal area were significantly reduced in Group 1 compared with Group 2 (0.88 mm2 and 0.40 mm2 vs. 1.24 mm2 and 0.55 mm2, respectively) (p < 0.05). Regarding choriocapillary flow density, AMD eyes recorded reduced values (34.83%) compared with controls (36.25%) (p < 0.05). Chorioretinal vasculature is impaired in intermediate AMD patients and vascular parameters could be attractive new prognostic biomarkers. Future therapeutic approaches may target this vascular dysfunction and delay disease progression.
- The Challenges of Setting Up a Clinical Study with the New European Union Medical Device RegulationPublication . Rêgo, S; Dutra-Medeiros, M; Nunes, F
- Lymphocyte Subpopulations in Sjögren’s Syndrome Are Distinct in Anti-SSA-Positive Patients and Related to Disease ActivityPublication . Barcelos, F; Martins, C; Madeira, N; Dias, M; Cardigos, J; Alves, N; Vaz-Patto, J; Cunha-Branco, J; Borrego, LMObjectives: Sjögren's syndrome (SjS) patients exhibit great phenotypical heterogeneity, reinforced by the positiveness of anti-SSA antibody. We aimed to evaluate lymphocyte subpopulations in SSA-positive (SSA+SjS) and SSA-negative (SSA-SjS) SjS patients, Sicca patients, and healthy controls (HC), and to investigate associations between lymphocyte subpopulations and disease activity in SjS. Methods: According to the fulfilment of the ACR/EULAR 2016 classification criteria, patients were included as SjS or as Sicca. HC were selected from the Ophthalmology outpatient clinic. Lymphocyte subpopulations were characterized by flow cytometry. Statistical analysis was performed with GraphPad PrismTM, with statistical significance concluded if p < 0.05. Results: We included 53 SjS patients (38 SSA+ and 15 SSA-), 72 Sicca, and 24 HC. SSA+SjS patients presented increased IL-21+CD4+ and CD8+ T cells compared to Sicca and HC, whereas compared to SSA-SjS patients, only IL-21+CD4+ T cell percentages were increased and Tfh17 percentages and numbers were decreased. Compared to Sicca and HC, SSA+SjS patients had higher levels of CD24HiCD38Hi B cells, naïve B cells, and IgM-/+CD38++ plasmablasts, and lower levels of memory B cells, including CD24HiCD27+ B cells. SSA+SjS patients with clinically active disease had positive correlations between ESSDAI and IL-21+CD4+ (p = 0.038, r = 0.456) and IL-21+CD8+ T cells (p = 0.046, r = 0.451). Conclusions: In SjS, a distinct lymphocyte subset distribution profile seems to be associated with positive anti-SSA. Moreover, the association between ESSDAI and IL-21+CD4+ and IL-21+CD8+ (follicular) T cells in SSA+SjS patients suggests the involvement of these cells in disease pathogenesis and activity, and possibly their utility for the prognosis and assessment of response to therapy. Key Points • SSA+SjS patients have a pronounced naïve/memory B cell imbalance. • SSA+SjS patients have more active disease associated with IL-21+CD4+ and IL-21+CD8+ follicular T cell expansion. • IL-21+CD4+ and IL-21+CD8+ T cell quantification may be useful for the prognosis and assessment of response to therapy.
- Added Value of Lymphocyte Subpopulations in the Classification of Sjögren's SyndromePublication . Barcelos, F; Brás-Geraldes, C; Martins, C; Papoila, AL; Monteiro, R; Cardigos, J; Madeira, N; Alves, N; Vaz-Patto, J; Cunha-Branco, J; Borrego, LMSjögren's Syndrome (SjS) is a chronic systemic immune-mediated inflammatory disease characterized by lymphocytic infiltration and consequent lesion of exocrine glands. SjS diagnosis and classification remains a challenge, especially at SjS onset, when patients may have milder phenotypes of the disease or uncommon presentations. New biomarkers are needed for the classification of SjS, thus, we aimed to evaluate the added-value of lymphocyte subpopulations in discriminating SjS and non-Sjögren Sicca patients. Lymphocyte subsets from 62 SjS and 63 Sicca patients were characterized by flow cytometry. The 2002 AECG and the 2016 ACR/EULAR SjS classification criteria were compared with clinical diagnosis. The added discriminative ability of joining lymphocytic populations to classification criteria was assessed by the area under the Receiver-Operating-Characteristic Curve (AUC). Considering clinical diagnosis as the gold-standard, we obtained an AUC = 0.952 (95% CI: 0.916-0.989) for AECG and an AUC = 0.921 (95% CI: 0.875-0.966) for ACR/EULAR criteria. Adding Tfh and Bm1 subsets to AECG criteria, performance increased, attaining an AUC = 0.985 (95% CI: 0.968-1.000) (p = 0.021). Th1/Breg-like CD24hiCD27+ and switched-memory B-cells maximized the AUC of ACR/EULAR criteria to 0.953 (95% CI: 0.916-0.990) (p = 0.043). Our exploratory study supports the potential use of lymphocyte subpopulations, such as unswitched memory B cells, to improve the performance of classification criteria, since their discriminative ability increases when specific subsets are added to the criteria.
- Screening for Diabetic Retinopathy Using an Automated Diagnostic System Based on Deep Learning: Diagnostic Accuracy AssessmentPublication . Rêgo, S; Dutra-Medeiros, M; Soares, F; Monteiro-Soares, MPurpose: To evaluate the diagnostic accuracy of a diagnostic system software for the automated screening of diabetic retinopathy (DR) on digital colour fundus photographs, the 2019 Convolutional Neural Network (CNN) model with Inception-V3. Methods: In this cross-sectional study, 295 fundus images were analysed by the CNN model and compared to a panel of ophthalmologists. Images were obtained from a dataset acquired within a screening programme. Diagnostic accuracy measures and respective 95% CI were calculated. Results: The sensitivity and specificity of the CNN model in diagnosing referable DR was 81% (95% CI 66-90%) and 97% (95% CI 95-99%), respectively. Positive predictive value was 86% (95% CI 72-94%) and negative predictive value 96% (95% CI 93-98%). The positive likelihood ratio was 33 (95% CI 15-75) and the negative was 0.20 (95% CI 0.11-0.35). Its clinical impact is demonstrated by the change observed in the pre-test probability of referable DR (assuming a prevalence of 16%) to a post-test probability for a positive test result of 86% and for a negative test result of 4%. Conclusion: A CNN model negative test result safely excludes DR, and its use may significantly reduce the burden of ophthalmologists at reading centres.
- Association Between Memory B-Cells and Clinical and Immunological Features of Primary Sjögren’s Syndrome and Sicca PatientsPublication . Barcelos, F; Martins, C; Papoila, A; Geraldes, C; Cardigos, J; Nunes, G; Lopes, T; Alves, N; Vaz-Patto, J; Branco, J; Borrego, LMB-cells play a pivotal role in primary Sjögren's syndrome (pSS) pathogenesis. We aim to (1) evaluate the distribution of B-lymphocyte subpopulations in pSS and Sicca patients, (2) establish cut-off points that discriminate pSS from controls, (3) evaluate the association between memory B-cells and phenotypic features in pSS. We included 57 pSS patients, 68 Sicca and 24 healthy controls. Circulating B-cells were characterized by flow cytometry as naïve and memory subsets and classified from Bm1 to Bm5. Compared to controls, pSS patients had lower percentages (29.5 vs 44.4%) and absolute numbers (47 vs 106 cells/µl) of memory B-cells. Through ROC curves, a cut-off of ≤ 58 total memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.60 for pSS, and was met by 59.6% of pSS patients, 38.8% of Sicca and 12.5% of controls. A cut-off of < 23.5 Switched-memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.54 and was met by 54.4% of pSS patients, 37.3% of Sicca and 12.5% of controls. In pSS, lower total memory B-cells count was associated with longer disease duration (14.3 vs 8.1 years, p = 0.006) and more active disease profile, as evaluated by the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) (3.1 vs 1.4, p = 0.043). Decreased numbers of memory B-cells clearly discriminated pSS from controls and can also have prognostic value. It remains to be clarified whether Sicca patients with decreased memory B-cells represent pSS and if B-cell profiling could help in the diagnosis of pSS.
- Orbital Metastasis from an Occult Breast Carcinoma (T0, N1, M1)Publication . Pinto Proença, R; Fernandes, J; Burnier, M; Proença, RThe authors report a case of an orbital metastasis from an occult breast carcinoma. A 66-year-old woman presented with a growing left orbital tumour. Orbital CT scan was consistent with lymphoma. However, ocular pathology revealed small neoplastic cells showing an 'indian file pattern' suggestive of metastatic carcinoma and immunohistochemistry was positive for CK7, CK CAM5.2 and oestrogen receptor. A systemic evaluation was then performed with mammogram, breast ultrasound and MRI considered normal. An exhaustive systemic evaluation revealed multiple bone lesions, a right axillary lymph node lesion, which presented the same pattern on pathology and immunohistochemistry, with no evidence of a primary tumour. A diagnosis of a metastatic lobular carcinoma of the breast (T0, N1, M1) was made and the patient was started on chemotherapy and adjuvant hormonal therapy.