Cristina Fonseca

Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity.

The main objective of this study was to develop a polymeric drug delivery system for paclitaxel, intended to be intravenously administered, capable of improving the therapeutic index of the drug and devoid of the adverse effects of Cremophor EL. To achieve this goal paclitaxel (Ptx)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Ptx-PLGA-Nps) were prepared by the interfacial deposition method. The influence of different experimental parameters on the incorporation efficiency of paclitaxel in the nanoparticles was evaluated. Our results demonstrate that the incorporation efficiency of paclitaxel in nanoparticles was mostly affected by the method of preparation of the organic phase and also by the organic phase/aqueous phase ratio. Our data indicate that the methodology of preparation allowed the formation of spherical nanometric (<200 nm), homogeneous and negatively charged particles which are suitable for intravenous administration. The release behaviour of paclitaxel from the developed Nps exhibited a biphasic pattern characterised by an initial fast release during the first 24 h, followed by a slower and continuous release. The in vitro anti-tumoral activity of Ptx-PLGA-Nps developed in this work was assessed using a human small cell lung cancer cell line (NCI-H69 SCLC) and compared to the in vitro anti-tumoral activity of the commercial formulation Taxol. The influence of Cremophor EL on cell viability was also investigated. Exposure of NCI-H69 cells to 25 microg/ml Taxol resulted in a steep decrease in cell viability. Our results demonstrate that incorporation of Ptx in nanoparticles strongly enhances the cytotoxic effect of the drug as compared to Taxol, this effect being more relevant for prolonged incubation times.

Influence of the Vitreoretinal Interface on the Treatment with Anti-VEGF for Exudative Age-Related Macular Degeneration

Purpose: To investigate the influence of the vitreoretinal interface on the outcomes of different ranibizumab regimens for exudative age-related macular degeneration. Methods: We conducted a retrospective subanalysis of 2 prospective clinical trials. Patients were treated with ranibizumab for 12 months according to 3 different regimens: pro-re-nata (PRN), treat and extend (T&E), and monthly. Vitreoretinal interface was assessed for absence (group ON) or presence (group OFF) of posterior vitreous detachment (PVD). Results: We included 64 eyes from 64 patients. Visual improvement was poorer for group ON (0.3 ± 10.7 letters) than for group OFF (9.2 ± 13.3; p = 0.007). A significant difference in letters of improvement between groups was observed in the PRN cohort (ON: –5.0 ± 12.9; OFF: 11.4 ± 11.9; p = 0.003), but not in the cohorts with monthly (ON: 5.7 ± 7.8; OFF: 7.9 ± 15.2; p = 0.735) or T&E (ON: 4.3 ± 4.3; OFF: 7.8 ± 11.1; p = 0.424) treatment. Conclusion: The negative impact of absence of PVD is regimen dependent, with monthly dosing providing similar outcomes to PVD patients. In the absence of PVD (group ON), PRN should be avoided, and T&E might be an alternative.

Bilateral giant macular holes: A rare manifestation of Alport syndrome

Purpose: Alport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations. Herein, we present a rare case of a patient diagnosed with Alport syndrome and bilateral giant macular holes. Case description: A 40-year-old woman with a previously unreported mutation in the COL4A4 gene suggestive of autosomal-recessive Alport syndrome presented at our department. The patient exhibited bilateral full-thickness macular holes measuring >1500 µm at their smallest diameters. The very large dimensions of both macular holes were indicative of a bad prognosis regarding hole closure, and a conservative approach was adopted. The patient was maintained on renal substitution therapy, and genetic counseling was offered to other family members. Conclusion: Ophthalmological findings associated to Alport syndrome commonly include anterior lenticonus and dot-and-fleck retinopathy, although giant macular holes can also be associated with this condition. A multidisciplinary approach is crucial in the management of these patients, as Alport syndrome is an inherited systemic basement membrane disease.

Central serous chorioretinopathy as a cause of vision loss in chronic relapsing inflammatory optic neuropathy

Purpose Chronic relapsing inflammatory optic neuropathy (CRION) is a type of idiopathic recurrent optic neuritis that responds to systemic corticosteroids and relapses on steroid withdrawal or dose reduction. Central serous chorioretinopathy (CSCR) is often associated with glucocorticoid therapy. This paper aims to highlight CSCR as a cause of visual loss in patients being treated with corticosteroids for optic neuritis. Observations We describe the case of a 42-year-old woman with a history of CRION in her left eye who presented with painful vision loss in the right eye and diffuse right optic disc edema. Steroid therapy was initiated, leading to visual and perimetric improvement. Two months later however, the patient returned with painless visual loss, now related to CSCR. Despite oral steroids being continued, there was spontaneous tomographic and visual recovery after four months. Conclusions and importance We believe this is the first report of CSCR causing vision loss in a patient with CRION treated with oral corticosteroids. CSCR should be suspected in patients with optic neuritis of any cause who develop vision loss while on treatment with steroids.

Dificuldades no cotidiano dos pacientes com glaucoma avançado - avaliação objetiva com registro em vídeo

Objective The purpose of this study was to perform an objective videotaped evaluation of the difficulties of eyedrop instillation and daily tasks in patients with advanced glaucoma with visual impairment Methods A prospective observational study was performed in advanced glaucoma patients with visual impairment, during 5 months. Patients completed a survey (with demographic questions, quality of life, compliance and eyedrop instillation) with interview and video recording in specific daily tasks (eyedrop instillation, climbing stairs, walking in a crowded room and in an irregular floor). Ophthalmologic evaluation was performed and its results registered in a form. Correlation was searched between limitation in quality of life, tasks’ performance and visual fields. Results 25 patients were included, corresponding to 12h of videotaping. All patients reported being capable of self-instilling eyedrops. 68% of them reported no difficulty instilling the eye drops at home, however 20% of the patients were unable to instill a drop in the eye in the objective evaluation. 72% of the patients stated never touching the eye with the bottle but 40% touched the ocular surface with the bottle. There was a moderate difficulty in the other tasks, with some patients exhibiting proprioceptive mechanisms of adaptation to impaired vision. There was a tendency of correlation between limitation in tasks and visual field defects, but no statistically significant. Conclusion Patients with advanced glaucoma and visual impairment have marked difficulty in eye drop instillation and daily tasks, with a poor awareness of their inabilities. Some patients have proprioceptive adaptations that allow them to perform better than expected in tasks.