André Luis Freire Portes

In vitro effects of bevacizumab treatment on newborn rat retinal cell proliferation, death, and differentiation.

PURPOSE Vascular endothelial growth factor (VEGF) is an important signal protein in vertebrate nervous development, promoting neurogenesis, neuronal patterning, and glial cell growth. Bevacizumab, an anti-VEGF agent, has been extensively used for controlling pathological retinal neovascularization in adult and newborn patients, although its effect on the developing retina remains largely unknown. The purpose of this study was to investigate the effect of bevacizumab on cell death, proliferation, and differentiation in newborn rat retina. METHODS Retinal explants of sixty 2-day-old Lister hooded rats were obtained after eye enucleation and maintained in culture media with or without bevacizumab for 2 days. Immunohistochemical staining was assessed against proliferating cell nuclear antigen (PCNA, to detect cell proliferation); caspase-3 and beclin-1 (to investigate cell death); and vimentin and glial fibrillary acidic protein (GFAP, markers of glial cells). Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. Results from treatment and control groups were compared. RESULTS No significant difference in the staining intensity (on immunohistochemistry) of PCNA, caspase-3, beclin-1, and GFAP, or in the levels of PCNA, caspase-3, beclin-1, and vimentin mRNA was observed between the groups. However, a significant increase in vimentin levels and a significant decrease in GFAP mRNA expression were observed in bevacizumab-treated retinal explants compared with controls. CONCLUSIONS Bevacizumab did not affect cell death or proliferation in early developing rat retina but appeared to interfere with glial cell maturation by increasing vimentin levels and downregulating GFAP gene expression. Thus, we suggest anti-VEGF agents be used with caution in developing retinal tissue.

Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after shortterm treatment with intravitreous bevacizumab

OBJECTIVE: Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits. METHODS: Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test. RESULTS: No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group. CONCLUSIONS: Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eyes.

Using Frequency-Doubling Perimetry to Detect Optic Neuropathy in Patients with Graves' Orbitopathy

Purposeto test the ability of frequency-doubling technology (FDT) perimetry to detect dysthyroid optic neuropathy (DON).MethodsFifteen eyes of 15 patients with DON and 15 healthy control eyes were studied. Eligible eyes had a diagnosis of DON based on visual field abnormalities on standard automated perimetry and had visual acuity better than 20/30. FDT testing was performed using both the C-20-5 screening test and the C-20 full-threshold test. Normal and DON eyes were compared with regard to FDT mean sensitivity.ResultsSensitivity ranges were 40.0%–86.7% for the screening test, and 53.3%–100.0% (total deviation) and 20.0–93.3 (pattern deviation) for the C-20 threshold test. The corresponding specificity ranges were 86.7–100.0, 33.3–93.3, and 26.7–100.0, respectively. The best sensitivity/specificity ratios were for one abnormal point depressed <5% in the screening test (86.7%/86.7%), one point depressed <1% in the total deviation analysis (80.0%/86.7%), and one point depressed <2% in the pattern deviation analysis (80.0%/86.7%). DON eyes presented significantly lower than normal average sensitivity in the central, pericentral, and peripheral areas.ConclusionsFDT perimetry is a useful screening tool for DON in eyes with normal or only slightly reduced visual acuity.

Hipertensão intracraniana idiopática de apresentação atípica com papiledema unilateral

Este trabalho descreve o caso de uma paciente de 56 anos que se apresentou com cefaleia, edema unilateral de papila e constricao do campo visual nasal. Os exames laboratoriais e de neuroimagem, o acompanhamento clinico e resposta ao tratamento permitiram o diagnostico de hipertensao intracraniana idiopatica. Chamamos a atencao que o papiledema unilateral pode ser uma forma de apresentacao incomum da sindrome e discutimos o seu diagnostico diferencial e tratamento.