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- The Paradigm Shift of Ophthalmology in the COVID-19 EraPublication . Campos, António; Oliveira, Nuno; Martins, Joana; Arruda, Henriques; Sousa, JoãoTo describe how a fixed regimen of intravitreal injections (IVI) was helpful to continue activity during the COVID-19 outbreak and lockdown and to address basic conditions to resume activity.
- The value of choroidal thickness in diabetic macular oedema is contradictoryPublication . Campos, António; Campos, Elisa J.; Martins, João; Ambrósio, António Francisco; Silva, Rufino
- Thrombophilic risk factors for retinal vein occlusionPublication . Vieira, Maria J.; Campos, António; Carmo, Anália; Arruda, Henrique; Martins, Joana; Sousa, João P.The aim is to study risk factors for retinal vein occlusion (RVO), such as thrombophilic and cardiovascular risk factors (CRF). A retrospective consecutive case series of 60 patients with RVO was made, tested for CRF, hyperhomocysteinemia, lupic anticoagulant, antiphospholipid antibody and 5 gene variants: factor V (FV) Leiden (G1691A), factor II (PT G20210A), 5,1-methylenetetra-hydrofolate reductase (MTHFR; 677 C > T and 1298 A > C), plasminogen activator inhibitor 1 (PAI-1; 4 G/5 G). More than 1 CRF were present in 36 patients (60%), which had a significantly higher mean age at diagnosis (66.7 ± 12.9 versus 59.5 ± 13.7 with ≤1 CRF, [t(57) = -2.05, p = 0.045, d = 0.54). Patients with thermolabile MTHFR forms with decreased enzyme activity (T677T or C677T/A1298C) had a significant lower mean age [57.6 ± 15.1; t (58) = 3.32; p = 0.002; d = 0.846] than patients with normal MTHFR enzyme activity (68.5 ± 10.2). Regarding CRF and thermolabile forms of MTHFR, the mean age at diagnosis could be significantly predicted [F(2,56) = 7.18; p = 0.002] by the equation: 64.8 - 10.3 × (thermolabile MTHFR) - 5.31 × ( ≤ 1CRF). Screening of MTHFR polymorphisms may be useful in younger RVO patients, particularly when multiple CRF are absent.
- Inflammatory cells proliferate in the choroid and retina without choroidal thickness change in early Type 1 diabetesPublication . Campos, António; Campos, Elisa J.; Martins, João; Rodrigues, Flávia S.C.; Silva, Rufino; Ambrósio, António FranciscoIncreasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal inflammatory changes in diabetes have been reported and in vivo choroidal thickness (CT) has been searched as a marker of retinopathy with contradictory results. We aimed to investigate the early stages in the retina and choroid in an animal model of Type 1 diabetes. Type 1 diabetes was induced in male Wistar rats via a single i.p. streptozotocin injection. At 8 weeks after disease onset, CT, choroidal vascular density, VEGF and VEGFR2 expression, microglial cell and pericyte distribution were evaluated. Diabetic rats showed no significant change in CT and choroidal vascular density. A widened pericyte-free gap between the retinal pigment epithelium and the choroid was observed in diabetic rats. The immunoreactivity of VEGFR2 was decreased in the retina of diabetic rats, despite no statistically significant difference in the immunoreactivity of VEGF. The density of microglial cells significantly increased in the choroid and retina of diabetic rats. Reactive microglial cells were found to be more abundant in the choroid of diabetic rats. Evidences of the interconnection between the superficial, intermediate, and deep plexuses of the retina were also observed. At early stages, Type 1 diabetes does not affect choroidal thickness and choroidal vascular density. Proliferation and reactivity of microglial cells occurs in the choroidal stroma and the retina. The expression of VEGFR2 decreases in the retina.
- Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetesPublication . Campos, António; Martins, João; Campos, Elisa J.; Silva, Rufino; Ambrósio, António FranciscoIncreasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal changes in diabetes have been reported and several attempts were made to validate in vivo choroidal thickness (CT) as a marker of retinopathy. We aimed to study choroidal and retinal changes associated with retinopathy in an animal model of spontaneous Type 2 diabetes, Goto-Kakizaki (GK) rats. Sclerochoroidal whole mounts and cryosections were prepared from 52-week-old GK and age-matched control Wistar Han rats. CT was measured by optical coherence tomography. Microglia reactivity, pericyte and endothelial cells distribution, and immunoreactivity of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) were evaluated by immunofluorescence. Choroidal vessels were visualized by direct perfusion with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Choroidal vascular density was evaluated by fluorescence microscopy. GK rats had increased CT (58.40 ± 1.15 μm versus 50.90 ± 1.58 μm, p < 0.001), reduced vascular density of the choriocapillaris (CC) (p = 0.045), increased Iba1+ cells density in the outer retina (p = 0.003) and increased VEGFR2 immunoreactivity in most retinal layers (p = 0.021 to 0.037). Choroidal microglial cells and pericytes showed polarity in their distribution, sparing the innermost choroid. This cell-free gap in the inner choroid was more pronounced in GK rats. In summary, GK rats have increased CT with decreased vascular density in the innermost choroid, increased VEGFR2 immunoreactivity in the retina and increased Iba1+ cells density in the outer retina.
- Emerging Trends in Nanomedicine for Improving Ocular Drug Delivery: Light-Responsive Nanoparticles, Mesoporous Silica Nanoparticles, and Contact LensesPublication . Rodrigues, Flávia S. C.; Campos, António; Martins, João; Ambrósio, António Francisco; Campos, Elisa J.Vision is the most dominant of our senses, and it is crucial in every stage of our lives. Ocular diseases, regardless of whether they cause vision impairment or not, lead to personal and financial hardships. The anatomy and physiology of the eye strongly limit the efficacy of current ocular drug delivery strategies. Nanotechnology has been the ground for the development of powerful strategies in several fields, namely in medicine. This review highlights emerging nanotechnology-based solutions for improving ocular drug delivery and thus the bioavailability and efficacy of drugs. We focus our review on ambitious but promising approaches currently emerging to leverage the efficacy of nanoparticle-based systems in ocular therapy: (i) light-responsive nanoparticles, which enable spatiotemporal control of drug release; (ii) mesoporous silica nanoparticles, which offer high surface area-to-volume ratio, simple surface modification, good biocompatibility, and improved bioavailability; and (iii) contact lenses, which serve as a compliant method of nanoparticles use and as drug delivery systems for the treatment of ocular diseases.
- Preserving visual acuity: a compelling 12-year case study of controlling neovascular age-related macular degenerationPublication . Tomás, Rita O.; Campos, António; Oliveira, Nuno; Soares, Pedro; Sousa, João P.Introduction: In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency decreases after the first year, while outcomes remain primarily related to the number of injections. To the best of our knowledge, there are no reports of maintaining the best corrected visual acuity (BCVA) for more than 7 years in extension studies. Objective To report a 12-year follow-up of a real-world case of nAMD where BCVA was preserved from declining. Case description A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. Examination showed a BCVA of 85 letters (L) in the right eye (RE) and 35 L in the LE. Fundus examination showed drusen in the macula of both eyes. Macular edema, loss of the macular lutein pigment, macular hypo/hyperpigmentation were observed in the LE. A diagnosis of Type 2 choroidal neovascular membrane (CNV) in the LE was established and within two months a Type 1 CNV developed in the RE. She undergone 9 injections of bevacizumab (six) and ranibizumab (three) within the first year of treatment in the LE and seven injections of ranibizumab within the first year in the RE. Results The LE had a mean of 5.2 injections per year, and the RE had a mean of 7.5 injections per year, from 2010 to 2022. RE’s BCVA dropped by 8L (85L to 77L) and central retinal thickness (CRT) increased by 16 μm (276 μm to 292 μm) while LE’s BCVA increased by 28L (35L to 63L) and CRT decreased by 369 μm (680 μm to 311 μm), at the twelfth year. Conclusions Although the final visual outcome depends on baseline BCVA and lesion type or size, the number of injections is paramount in preserving BCVA and achieving favorable functional outcomes in nAMD, even after 12 years of treatment.