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Objectives: To evaluate the success rate of the implants and the survival rate of the eyelid prosthesis, as well as the quality of the peri-implant soft tissue. Material and method: A retrospective study was conducted, after approval of the Ethics Committee, using the medical records of all cancer patients with orbital deformities, and who received implants for rehabilitation with eyelid prosthesis, between the period 2003 to 2015. Two outcome variables were considered for the study: the success rate of the implants and the survival rate of the eyelid prosthesis. Data were analysed using the Kaplan-Meier test. Results: A total of 33 extra-oral implants were installed in 14 patients. The success rate of the implants was 96.9%, and the survival rate of the eyelid prosthesis was 92.3% at 2 years. Conclusions: The rehabilitation of the orbital region with extra-oral implants is a safe, reliable and predictable technique to restore the facial aesthetics of the patient and improve their quality of life.

Purpose: Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesising the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardised, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina.Methods: We searched five online databases for the combined terms for outcome ("retina") and exposure ("cannabis"). Eligibility of studies were conducted by two independent reviewers, and risk of bias was assessed.Results: We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects.Conclusions: This review suggests that cannabinoids may have an important role in retinal processing and function.

To analyze contrast sensitivity of intravitreal bevacizumab injections with optimizing glycemic control versus optimizing glycemic control (in combination with sham injections) in eyes with Diabetic Macular Edema (DME).Prospective, interventional, masked, randomized controlled trial.Forty-one eyes of 34 patients with type 2 diabetes mellitus and DME with glycated hemoglobin (HbA1c) 11% received either intravitreal bevacizumab injection (Group 1) or sham injection (Group 2) at 0 and 6 weeks along with optimizing glycemic control. Mean change in best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT)-measured by central macular thickness (CMT) were compared and correlated at baseline, 2, 6 and 12 weeks.The study showed a mean CS improved in group 1 from 1.14 ± 0.36 logCS to 1.32 ± 0.24 logCS and also in group 2 from 1.11 ± 0.29 logCS to 1.18 ± 0.29 logCS at 12 weeks (P = 0.12). CS and CMT promptly decreased in group 1 compared to group 2 at 2 weeks (ΔCS = 0.15 ± 0.25 vs. 0.03 ± 0.15 logCS; P = 0.04; ΔCMT = 116 ± 115 vs. 17 ± 71 μm; P = 0.01). There was a mean reduction of approximately 0.5% in HbA1c levels in both groups at 12 weeks (P = 0.002).The use of bevacizumab in combination with optimizing glycemic control results in earlier improvement of contrast sensitivity in type 2 diabetes patients with DME. However, the optimizing glycemic control itself has shown also to be effective at 12 weeks. ClinicalTrials.gov Identifier: NCT02308644.

Background Prenatal exposure to Cannabis is a worldwide growing problem. Although retina is part of the central nervous system, the impact of maternal Cannabis use on the retinal development and its postnatal consequences remains unknown. As the prenatal period is potentially sensitive in the normal development of the retina, we hypothesized that recreational use of Cannabis during pregnancy may alter retina structure in the offspring. To test this, we developed a murine model that mimics human exposure in terms of dose and use. Methods Pregnant BalbC mice were exposed daily for 5 min to Cannabis smoke (0.2 g of Cannabis) or filtered air, from gestational day 5 to 18 (N = 10/group). After weaning period, pups were separated and examined weekly. On days 60, 120, 200, and 360 after birth, 10 pups from each group were randomly selected for Spectral Domain Optical Coherence Tomography (SD-OCT) analysis of the retina. All retina layers were measured and inner, outer, and total retina thickness were calculated. Other 37 mice from both groups were sacrificed on days 20, 60, and 360 for retinal stereology (total volume of the retina and volume fraction of each retinal layer) and light microscopy. Means and standard deviations were calculated and MANOVA was performed. Results The retina of animals which mother was exposed to Cannabis during gestation was 17% thinner on day 120 (young adult) than controls (P = 0.003) due to 21% thinning of the outer retina (P = 0.001). The offspring of mice from the exposed group presented thickening of the IS/OS in comparison to controls on day 200 (P Conclusion Gestational exposure to Cannabis smoke may cause structural changes in the retina of the offspring that return to normal on mice adulthood. These experimental evidences suggest that children and young adults whose mothers smoked Cannabis during pregnancy may require earlier and more frequent clinical care than the non-exposed population.

Pigmented and albino rabbits are commonly used in visual research; however, the lack of pigment in the eyes may affect retinal responses. Here, we compare and describe the differences of retinal function between pigmented (English Butterfly) and albino (New Zealand) rabbits. Electroretinograms were recorded in pigmented and albino rabbits in the dark-adapted eye, in the light-adapted eye and for four temporal frequencies in the light-adapted eye. The implicit time and amplitude of the a- and b-waves were analyzed, as well as the amplitude and phase of the first harmonic component of the photopic flicker response. Albino rabbits presented significantly larger amplitudes for both a- and b-waves at all intensities and frequencies. The intensity–response function of the scotopic b-wave also showed that the albino retina is more sensitive than the pigmented retina and the larger flicker amplitudes found in the albino group also revealed post-receptoral changes specifically related to cone pathways. The larger amplitude of albino receptoral and post-receptoral activities might be attributed to greater availability of light due to scatter and reflection at the retinal layer, and as the differences in response amplitudes between the groups increase with flicker frequency, we suggest that ON bipolar cells recover faster in the albino group, suggesting that this might be a mechanism to explain the higher temporal resolution for albinos compared to the pigmented group.

Purpose The purpose of this study was to characterize changes in the full-field flash electroretinogram (ERG) in association with psychophysical dark-adapted visual thresholds in patients with genetically characterized Duchenne muscular dystrophy (DMD) either lacking Dp427 (Up 30) or at least Dp260 in addition to Dp427 (Down 30). Methods Twenty-one patients with DMD and 27 age-similar controls participated in this study. Dark-adapted (0.01, 3.0, and 10 cd.s/m² flashes) and light-adapted (3.0 cd.s/m² flash) ERGs were recorded following International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. Visual detection thresholds to 625-nm (cone function) and 527-nm (rod function) light-emitting diode (LED) flashes (2 degree diameter) were measured during a dark adaptation period after a 1-minute exposure to a bleaching light (3000 cd/m²). Initially, 8 minutes of interleaved 625-nm and 527-nm thresholds were measured. After an additional 5 minutes of dark-adaptation, a second set of threshold measurements to 527-nm stimuli was performed during the subsequent 6 minutes. Results Dark-adapted b-wave amplitude was significantly reduced to all strengths of flash and a-wave in response to the strong flash stimulus was delayed (15.6 vs. 14.7 ms, P < 0.05) in patients with Down 30 compared with controls. Dark-adapted cone thresholds did not differ among the groups (−2.0, −1.8, and −1.7 log cd/m² for Down 30, Up 30, and controls, respectively, P = 0.21). In contrast, dark-adapted rod thresholds were elevated (F(2,36) = 8.537, P = 0.001) in patients with Down 30 (mean = −3.2 ± 1.1 log cd/m²) relative to controls (mean = −4.2 ± 0.3 log cd/m²). Dark-adapted b-wave amplitudes were correlated with dark-adapted rod sensitivity in patients with DMD (Spearman Rho = 0.943, P = 0.005). The changes were much smaller or absent in patients with intact Dp260. Conclusions Dp260 is particularly required for normal rod-system function in dark adaptation.

Purpose To follow the visual acuity development of children exposed to or infected with the Zika virus (ZIKV) during gestation and to relate potential visual acuity deficits to their clinical condition. Methods In this prospective study, visual acuity was measured via Teller Acuity Cards in three groups of children: (1) those with confirmed ZIKV exposure (ZE) through the mother only, (2) those with confirmed infection (ZI), and (3) unaffected controls. Visual acuity was measured 2-4 times in each child during the first 30 months of age. Results The study included 22 children in the ZE group, 11 in the ZI group, and 27 controls. Visual acuity developed normally in both patient groups, including infected patients (ZI) that did not manifest clinical symptoms. In a small subgroup of patients with characteristics consistent with congenital Zika syndrome (CZS), visual acuity was within normative values, with the exception of single child with chorioretinal atrophy. Conclusions In this southeastern Brazil study cohort, visual acuity development seemed to progress normally in infected children without CZS symptoms.

Purpose To evaluate visual acuity and visual acuity development in children from the state of Sao Paulo, Brazil, who were exposed to the Zika virus (ZIKV) gestationally. Methods Children who had been exposed to ZIKV during gestation and age-matched control subjects received visual acuity and funduscopic examination. ZIKV exposure was confirmed by maternal quantitative polymerase chain reaction testing or serology assay. The ZIKV group was divided into two subgroups: Zika - exposed (ZE), with only the mother having confirmed ZIKV-infection, and Zika-infected (ZI), with confirmed infection. Visual acuity development was compared with prior norms and quantified by measuring visual acuity correlation with age. Results A total of 110 children were included: 47 who had been exposed to ZIKV (ZE, 23; ZI, 24) and 63 controls. Abnormal visual acuity was found in 5 of 24 ZI children. Of the 4 children with microcephaly, only 2 had visual acuity loss (only 1 also had abnormal funduscopic findings). There was significant correlation between age and visual acuity in both the control group ( R 2 = 0.8; P R 2 = 0.6; P R 2 = 0.04; P = 0.38). Furthermore, the increment in octaves/month was much lower in the ZI subgroup. Conclusions Our data indicates that visual acuity losses only occur in infants who suffered gestational-infection, not simply exposure. Lack of correlation between age and visual acuity in the ZI subgroup suggests a slowing of visual development even in the absence of microcephaly. This result may have broad implications for the deleterious effects of ZIKV on the central nervous system.

To determine the half-life of mycophenolic acid (MPA) in the vitreous of New Zealand albino rabbits after intravitreal injection and the retinal toxicity of different doses of MPA.Ten micrograms of MPA (Roche Bioscience, Palo Alto, CA) was injected in the vitreous of 16 rabbits, animals were sacrificed at different time-points, and vitreous samples underwent high-performance liquid chromatography. For functional and morphological studies, 5 doses of MPA (0.05, 0.5, 2, 10, and 100 μg) were injected in the vitreous of 20 rabbits. As control, contralateral eyes were injected with aqueous vehicle. Electroretinograms (ERGs) were recorded before injection and at days 7, 15, and 30. Animals were sacrificed on day 30 and retinas were analyzed under light microscopy.MPA half-life in the vitreous was 5.0±0.3 days. ERG revealed photoreceptor functional impairment in eyes injected with 0.5 μg and higher on day 30, while eyes injected with 100 μg presented the same changes already from day 15. No morphological change was found.MPA vitreous half-life is 5.0 days. Intravitreal injection of 0.5 μg MPA and higher causes dose- and time-related photoreceptor sensitivity decrease in rabbits. The MPA dose of 0.05 μg may be safe for intravitreal use in rabbits.

PURPOSE The aims of this study were to determine the scleral attenuation of focused neodymium: yttrium-lanthanum-fluoride laser at 1,047 nm applied transsclerally and whether transscleral delivery can close the vascular supply at the base of experimental choroidal melanoma in rabbits. METHODS Fifty-two New Zealand albino rabbits were included. Scleral laser attenuation was measured across fresh sclera. B16F10 melanomas were established in the subchoroidal space of 49 rabbits. Twenty-one animals were killed immediately after transscleral treatment, 14 were followed for 2 weeks to 4 weeks, and 14 were followed without treatment. Ophthalmoscopy, fundus photographs, and fluorescein angiography were performed before treatment, immediately after, and weekly during the follow-up. Eyes were examined by light microscopy. RESULTS Sclera attenuated laser energy by 31% ± 7%. Immediately after treatment, angiography showed diffuse hypofluorescence in 71% (15 of 21 rabbits). Light microscopy showed vascular occlusion extending at least two thirds of the tumor thickness from the base. Seven of the 14 tumors followed for 15 days ± 8 days were eradicated. There was no correlation between tumor height and eradication. CONCLUSION Rabbit sclera attenuated 31% ± 7% of laser energy. A single transscleral treatment causes tumor vascular closure at the base and may serve as an adjuvant therapy to ensure destruction of deep and intrascleral tumor cells.

Mycophenolic acid (MPA) is an immunosuppressive agent that controls noninfectious uveitis. Intravitreal MPA delivery may be a potential adjuvant therapy in patients who have to discontinue steroid or immunosuppressive systemic therapy because of side effects. The aims of this study are to evaluate the in vitro effects of MPA over human retinal pigment epithelium (ARPE-19) and human Muller cells (MIO M-1).ARPE-19 cells and MIO M-1 cells were exposed to 25, 50, and 100 µg/mL of MPA (Roche Bioscience, Palo Alto, CA) for 24 hours. Toxicity was evaluated by trypan blue dye-exclusion cell viability assay, caspase-3/7 apoptosis-related assay, and JC-1 mitochondrial membrane potential assay.The MPA (25 µg/mL and 50 µg/mL) did not cause reduction in cell viability or significant change in caspase-3/7 activity in both cell lines tested. Mycophenolic acid (100 µg/mL) caused a significant decrease in cell viability (P0.01) and higher caspase-3/7 activity (P0.05) in both cell lines compared with untreated cells. The JC-1 mitochondrial membrane potential did not show statistically significant differences for both cell lines and all concentration tested when compared with untreated controls (P0.05).Intraocular delivery may be a potential alternative for the treatment of noninfectious uveitis, either by intravitreal injection or sustained-release drug-delivery systems, in doses of 50 µg/mL or lower.

OBJECTIVES: Chemical pleurodesis is an important therapeutic tool to control recurrent malignant pleural effusion. Among the various sclerosing agents, iodopovidone is considered effective and safe. However, in a recent study, ocular changes were described after iodopovidone was used in recurrent pneumothorax. The aim of the study was to evaluate the efficacy and morbidity of iodopovidone pleurodesis in an experimental model. METHODS: New Zealand rabbits were submitted to intrapleural injection of iodopovidone at concentrations of 2%, 4% and 10%. Biochemical (lactic dehydrogenase, proteins, triiodothyronine, free thyroxine, urea and creatinine) and immunological (Interleukin-8 [IL-8], VEGF and TGFβ) parameters were measured in the pleural fluid and blood. After 1, 3, 7, 14 and 28 days, groups of animals were euthanized, and macro- (pleura) and microscopic (pleura and retina) analyses were performed. RESULTS: An early pleural inflammatory response with low systemic repercussion was observed without corresponding changes in thyroid or renal function. The higher concentrations (4% and 10%) correlated with greater initial exudation, and maximum pleural thickening was observed after 28 days. No changes were observed in the retinal pigment epithelium of the rabbits. CONCLUSION: Iodopovidone is considered to be an effective and safe sclerosing agent in this animal model. However, its efficacy, tolerance and safety in humans should be further evaluated.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:46:41Z No. of bitstreams: 1 S0004-27492012000200016.pdf: 210572 bytes, checksum: 2dc842d6d0bc54b81cfcf6b7be23d602 (MD5) Made available in DSpace on 2013-08-22T18:46:41Z (GMT). No. of bitstreams: 1 S0004-27492012000200016.pdf: 210572 bytes, checksum: 2dc842d6d0bc54b81cfcf6b7be23d602 (MD5) Previous issue date: 2012-04-01 Made available in DSpace on 2013-09-30T19:36:03Z (GMT). No. of bitstreams: 2 S0004-27492012000200016.pdf: 210572 bytes, checksum: 2dc842d6d0bc54b81cfcf6b7be23d602 (MD5) S0004-27492012000200016.pdf.txt: 34788 bytes, checksum: 57b21b43117bf2009f5844473c90ac52 (MD5) Previous issue date: 2012-04-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:36:24Z No. of bitstreams: 2 S0004-27492012000200016.pdf: 210572 bytes, checksum: 2dc842d6d0bc54b81cfcf6b7be23d602 (MD5) S0004-27492012000200016.pdf.txt: 34788 bytes, checksum: 57b21b43117bf2009f5844473c90ac52 (MD5) Made available in DSpace on 2014-05-20T13:36:24Z (GMT). No. of bitstreams: 2 S0004-27492012000200016.pdf: 210572 bytes, checksum: 2dc842d6d0bc54b81cfcf6b7be23d602 (MD5) S0004-27492012000200016.pdf.txt: 34788 bytes, checksum: 57b21b43117bf2009f5844473c90ac52 (MD5) Previous issue date: 2012-04-01 A inflamação ocular é uma das principais causas de perda visual e cegueira. As uveítes constituem um grupo complexo e heterogêneo de doenças caracterizadas por inflamação dos tecidos intraoculares. O olho pode ser o único órgão envolvido ou a uveíte pode ser parte de uma doença sistêmica. A etiologia é desconhecida em um número significativo de casos, que são considerados idiopáticos. Modelos animais têm sido desenvolvidos para estudar a fisiopatogênese da uveíte autoimune devido às dificuldades na obtenção de tecidos de olhos humanos inflamados para experimentos. Na maioria desses modelos, que simulam as uveítes autoimunes em humanos, a uveíte é induzida com proteínas específicas de fotorreceptores (antígeno-S, proteína ligadora de retinoide do interfotoreceptor, rodopsina, recoverina e fosducina). Antígenos não retinianos, como proteínas associadas à melanina e proteína básica de mielina, são também bons indutores de uveíte em animais. Entender os mecanismos básicos e a patogênese dessas doenças oculares é essencial para o desenvolvimento de novas formas de tratamento das uveítes autoimunes e de novos agentes terapêuticos. Nesta revisão serão abordados os principais modelos experimentais utilizados para o estudo de doenças inflamatórias oculares autoimunes. Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin). Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases. Universidade de São Paulo Universidade Estadual Paulista Júlio de Mesquita Filho Escola Bahiana de Medicina e Saúde Pública Universidade Estadual Paulista Júlio de Mesquita Filho

Vogt-Koyanagi-Harada disease (VKH), a well-established multiorgan disorder affecting pigmented structures, is an autoimmune disorder of melanocyte proteins in genetically susceptible individuals. Several clinical and experimental data point to the importance of the effector role of CD4+ T cells and Th1 cytokines, the relevance of searching a target protein in the melanocyte, and the relevance of the HLA-DRB1*0405 in the pathogenesis of the disease. Vogt-Koyanagi-Harada disease has a benign course when early diagnosed and adequatey treated. Full-blown recurrences are rare after the acute stage of Vogt-Koyanagi-Harada disease is over. On the other hand, clinical findings, such as progressive tissue depigmentation (including sunset glow fundus) and uveitis recurrence, indicate that ocular inflammation may persist after the acute phase. Additionally, indocyanine green angiography findings suggest the presence of choroidal inflammation in eyes without clinically detectable inflammation. The aim of this paper is to review the latest research results on Vogt-Koyanagi-Harada disease pathogenesis and chronic/convalescent stages, which may help to better understand this potentially blinding disease and to improve its treatment.A doença de Vogt-Koyanagi-Harada (VKH) afeta vários órgãos que têm em comum a presença de pigmento. É doença autoimune que agride os melanócitos de indivíduos geneticamente susceptíveis. Inúmeras evidências clínicas e experimentais demonstram a importância de células T CD4+ como células efetoras da resposta imune celular, das citocinas pró-inflamatórias Th1, da procura da proteína-alvo dentro do melanócito, e da relevância do HLA-classe II DRB1*0405 na patogênese desta doença. A doença de Vogt-Koyanagi-Harada apresenta bom prognóstico visual desde que o diagnóstico seja precoce e o tratamento instituído seja adequado. Recidivas com acometimento do segmento posterior são raras após a fase aguda da doença. No entanto, achados clínicos como a progressiva despigmentação do fundo, incluindo o aspecto em por do sol, e as recidivas da uveíte indicam que a inflamação ocular pode persistir mesmo após a fase aguda da doença. Os achados da angiografia com indocianina verde também sugerem a presença de inflamação da coróide mesmo em olhos sem inflamação clinicamente detectável. O objetivo do presente trabalho é rever os mais recentes estudos sobre a patogênese da doença Vogt-Koyanagi-Harada e sobre os aspectos clínicos da fase crônica e/ou convalescente da doença, permitindo melhores conhecimentos sobre esta doença potencialmente mórbida e oferecendo terapias mais adequadas.

Angiogênese é o processo de formação de vasos sangüíneos a partir de vasos preexistentes, que ocorre em condições fisiológicas e patológicas. É fenômeno complexo no qual participam inúmeras moléculas que estimulam e inibem a formação dos neovasos. O aumento da permeabilidade vascular e a neovascularização sub-retiniana são as causas da perda visual nas doenças proliferativas da retina, como a degeneração macular relacionada à idade e a retinopatia diabética, e o fator de crescimento do endotélio vascular ("vascular endothelial growth factor", VEGF) desempenha um papel muito importante nesse processo. Existem quatro isoformas da molécula de VEGF biologicamente ativas em seres humanos, das quais o VEGF165 é a isoforma predominante no olho humano, e existem evidências de que seja a isoforma responsável pela neovascularização patogênica no olho. Além de ser potente mitógeno de células endoteliais, o VEGF aumenta a permeabilidade vascular, inibe a apoptose das células endoteliais e promove migração de precursores de células endoteliais. O VEGF não é a única molécula cuja expressão está aumentada na angiogênese patológica. O fator de crescimento de fibroblasto ("basic fibroblast growth factor", bFGF), as angiopoetinas, o fator derivado do epitélio pigmentado ("pigment epithelium-derived factor", PEDF) e os fatores de adesão relacionados à matriz extracelular também exercem papel importante no balanço entre fatores pró- e antiangiogênicos. Todo o conhecimento adquirido sobre o mecanismo da angiogênese ocular patológica tem possibilitado o desenvolvimento de vários inibidores desse processo. Atualmente existem dois anticorpos anti-VEGF para uso intravítreo e outras abordagens terapêuticas do bloqueio da angiogênese ocular estão em fase de desenvolvimento. As novas drogas deverão ser armas poderosas no tratamento das principais causas de cegueira legal irreversível em indivíduos com mais de 65 anos.Angiogenesis is the process involving the growth of new blood vessels from preexisting vessels which occurs in both physiologic and pathological settings. It is a complex process controlled by a large number of modulating factors, the pro-and antiangiogenic factors. The underlying cause of vision loss in proliferative retinal diseases, such as age-related macular degeneration and proliferative diabetic retinopathy, are increased vascular permeability and choroidal neovascularization, and vascular endothelial growth factor (VEGF) plays a central role in this process. VEGF is produced in the eye by retinal pigment epithelium (RPE) cells and is upregulated by hypoxia. There are four major biologically active human isoforms, of which VEGF165 is the predominant in the human eye and appears to be the responsible for pathological ocular neovascularization. Besides being a potent and specific mitogen for endothelial cells, VEGF increases vascular permeability, inhibits endothelial cells apoptosis, and is a chemoattractant for endothelial cell precursors. VEGF is not the only growth factor involved in ocular neovascularization. Basic fibroblast growth factor (bFGF), angiopoietins, pigment epithelium-derived factor (PEDF), and adhesion molecules also play a role in the pro- and antiangiogenic balance. Advances in the understanding of the bases of pathological ocular angiogenesis and identification of angiogenesis regulators have enabled the development of novel therapeutic agents. Anti-VEGF antibodies have been developed for intravitreal use, and other approaches are currently under investigation. These new drugs may be powerful tools for the treatment of the leading causes of irreversible blindness in people over age 65.

PURPOSE To evaluate the morphologic effects of intravitreal triamcinolone acetonide (TA) on rabbit retina. METHODS Intravitreal injections of 0.5 mg, 1 mg, 4 mg, 8 mg, and 20 mg of TA (Kenalog-40; Bristol-Myers Squibb, Princeton, NJ) in 0.1 mL were given to pigmented rabbits. For control, 0.1 mL of TA vehicle and saline were injected. Animals were killed on day 14, and retinas were analyzed by light as well as electron microscopy. RESULTS No ophthalmoscopic change was found. Eyes injected with 0.5 mg and 1 mg of TA did not have morphologic abnormality. Eyes injected with 4 mg, 8 mg, and 20 mg showed destruction of photoreceptor outer segments and migration of macrophage-like cells in the subretinal space. Eyes injected with 20 mg showed more extensive damage and increased pigment granules in the retinal pigment epithelium cells with large oil droplets in the cytoplasm. Electron microscopy also showed loss of photoreceptor/retinal pigment epithelium interdigitations. Eyes injected with vehicle or saline did not show morphologic changes. CONCLUSION Single intravitreal injection of 0.5 mg or 1 mg of TA did not produce morphologic retinal changes in pigmented rabbits. However, injections of 4 mg, 8 mg, and 20 mg of TA produced outer retina toxic effects. These findings suggest that long-term retinal toxicity studies should be carried out, using single and repeated injections before this therapy becomes more widely used.

Vogt-Koyanagi-Harada disease (VKH) is a multisystem autoimmune disorder principally affecting pigmented tissues in the ocular, auditory, integumentary and central nervous systems. Patients are typically 20 to 50 years old and have no history of either surgical or accidental ocular trauma. Pigmented races are more commonly affected. Depending on revised diagnostic criteria, the disease is classified as complete, incomplete or probable based on the presence of extraocular findings (neurological, auditory and integumentary). The clinical course of VKH is divided into four phases: prodromal (mimics a viral infection), uveitic (bilateral diffuse uveitis with papillitis and exudative retinal detachment), convalescent (tissue depigmentation), and chronic recurrent (recurrent uveitis and ocular complications). The pathogenesis of VKH is thought to be related to an aberrant T cell-mediated immune response directed against self-antigens found on melanocytes. VKH has been linked to human leukocyte antigen DR4 (HLA-DR4) and HLA-Dw53, with strongest associated risk for HLA-DRB1*0405 haplotype. The diagnosis of VKH is clinical, and differential includes sympathetic ophthalmia, sarcoidosis, primary intraocular B-cell lymphoma, posterior scleritis, and uveal effusion syndrome. Treatment is typically initiated with high-dose oral corticosteroids, but other immunomondulatory agents (most oftentimes cyclosporine) may be needed for non-responsive patients or when corticosteroid side-effects are not tolerated. Visual prognosis is generally good with prompt diagnosis and aggressive immunomodulatory treatment.

Purpose Visual information is processed in parallel pathways in the visual system. Parallel processing begins at the synapse between the photoreceptors and their postreceptoral neurons in the human retina. The integrity of this first neural connection is vital for normal visual processing downstream. Of the numerous elements necessary for proper functioning of this synaptic contact, dystrophin proteins in the eye play an important role. Deficiency of muscle dystrophin causes Duchenne muscular dystrophy (DMD), an X-linked disease that affects muscle function and leads to decreased life expectancy. In DMD patients, postreceptoral retinal mechanisms underlying scotopic and photopic vision and ON- and OFF-pathway responses are also altered. Methods In this study, we recorded the electroretinogram (ERG) while preferentially activating the (red-green) opponent or the luminance pathway, and compared data from healthy participants (n = 16) with those of DMD patients (n = 10). The stimuli were heterochromatic sinusoidal modulations at a mean luminance of 200 cd/m2. The recordings allowed us also to analyze ON and OFF cone-driven retinal responses. Results We found significant differences in 12-Hz response amplitudes and phases between controls and DMD patients, with conditions with large luminance content resulting in larger response amplitudes in DMD patients compared to controls, whereas responses of DMD patients were smaller when pure chromatic modulation was given. Conclusions The results suggest that dystrophin is required for the proper function of luminance and red-green cone opponent mechanisms in the human retina.

OBJECTIVES: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina. METHODS: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision. RESULTS: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes. CONCLUSIONS: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina.

Emerging treatments for dry age-related macular degeneration (AMD) and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS) formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

To compare the intravitreal pharmacokinetic profile of a triamcinolone acetonide formulation containing the preservative benzyl alcohol (TA-BA) versus a preservative-free triamcinolone acetonide formulation (TA-PF), and evaluate potential signs of toxicity to the retina.A total of 60 New Zealand male white rabbits, divided into two groups, were studied. In the TA-BA group, 30 rabbits received an intravitreal injection of TA-BA (4 mg/0.1 ml) into the right eye. In the TA-PF group, 30 rabbits received an intravitreal injection of TA-PF (4 mg/0.1 ml) into the right eye. The intravitreal drug levels were determined in 25 animals from each group by high-performance liquid chromatography (HPLC). The potential for toxicity associated with the intravitreal triamcinolone injections was evaluated in five randomly selected animals from each group by electroretinography (ERG) and by light microscopy.Median intravitreal concentrations of TA-BA (µg/ml) were 1903.1, 1213.0, 857.8, 442.0, 248.6 at 3, 7, 14, 21 and 28 days after injection. Intravitreal concentrations of TA-PF (µg/ml) were 1032.9, 570.1, 516.6, 347.9, 102.8 at 3, 7, 14, 21 and 28 days after injection. The median intravitreal triamcinolone concentration was significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection (p 0.05). There was no significant difference between the two groups in median triamcinolone concentration at the other time points evaluated. There was no evidence of toxic effects on the retina in either group based on ERG or histological analyses.Following a single intravitreal injection, the median concentration of triamcinolone acetonide is significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection. No toxic reactions in the retina were observed in either group.

To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira®) in the rabbit eye.Thirty New Zealand albino rabbits received intravitreous injections of 0.5 mg (6 eyes), 1.0 mg (6 eyes), 2.5 mg (6 eyes), 5 mg (6 eyes), and 10 mg (6 eyes) adalimumab. Slit lamp biomicroscopy and fundoscopy were carried out at baseline, day 7, and day 14 after intravitreous injection, whereas electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed.Slit lamp biomicroscopy and fundoscopy were normal in all eyes receiving doses up to 5 mg. In the 10 mg group, 3 of 6 eyes showed mild anterior chamber inflammatory reaction on day 7. Similarly, scotopic and photopic a- and b-wave ERG amplitudes at baseline and day 14 were similar in all groups up to 5 mg, but there was a significant decrease in the photopic-wave ERG response in the 10 mg group (P=0.046). Finally, histopathology demonstrated no differences among eyes receiving balanced salt solution, 0.5, 1.0, 2.5, 5.0, or 10 mg of adalimumab.Intravitreous adalimumab exhibited no associated ocular short-term toxicity in rabbit eyes up to the 5 mg dose. In the 10 mg group mild clinical findings and ERG amplitude reduction could reflect early toxicity.

PURPOSE To evaluate achromatic contrast sensitivity (CS) with magnocellular- (M) and parvocellular- (P) probing stimuli in type 2 diabetics, with (DR) or without (NDR) nonproliferative retinopathy. METHODS Inferred M- and P-dominated responses were assessed with a modified version of the steady-/pulsed-pedestal paradigm (SP/PP) applied in 26 NDR (11 male; mean age, 55 ± 9 years; disease duration, 5 ± 4 years); 19 DR (6 male; mean age, 58 ± 7 years; disease duration = 9 ± 6 years); and 18 controls (CTRL; 12 male; mean age, 55 ± 10 years). Thresholds were measured with pedestals at 7, 12, and 19 cd/m(2), and increment durations of 17 and 133 ms. The thresholds from the two stimulus durations were used to estimate critical durations (Tc) for each data set. RESULTS Both DR and NDR patients had significant reduction in CS in both SP and PP paradigms in relation to CTRL (Kruskal-Wallis, P < 0.01). Patients' critical duration estimates for either paradigm were not significantly different from CTRL. CONCLUSIONS The significant reduction of CS in both paradigms is consistent with losses of CS in both M and P pathways. The CS losses were not accompanied by losses in temporal processing speed in either diabetic group. Significant CS loss in the group without retinopathy reinforces the notion that neural changes associated with the cellular and functional visual loss may play an important role in the etiology of diabetic visual impairment. In addition, the results show that the SP/PP paradigm provides an additional tool for detection and characterization of the early functional damage due to diabetes.

Purpose To evalulate the applicability of the Revised Diagnostic Criteria for Vogt-Koyanagi-Harada (VKH) disease to Brazilian patients and to verify the association between different disease categories, clinical parameters, and the presence of HLA-DRB1*0405. Design A retrospective observational case series. Methods Medical charts of 67 patients (10 to 64 years in age; 12 men and 55 women), from the Uveitis Service, Hospital das Clinicas, University of Sao Paulo School of Medicine (HCFMUSP), Sao Paulo, Brazil were reviewed. Patients, previously diagnosed with VKH disease using criteria proposed by the American Uveitis Society, underwent retrospective classification based on the Revised Diagnostic Criteria. The degree of concordance was assessed. At presentation, 46 patients (69%) were in the early phase. In this group, the mean time from disease onset to treatment was 15 days (range, one to 30 days). Forty-eight patients (72%) were typed for HLA-DRB1*0405 by polymerase chain reaction-sequence specific primer and polymerase chain reaction-sequence-specific oligonucleotides primer. Disease categories, phase at initial presentation, and ocular complications were analyzed. Results There was a 100% of concordance between the two criteria. Disease was classified as complete in 10 patients (15%), incomplete in 37 patients (55%), and probable in 20 patients (30%). In each group, respectively, 90%, 76%, and 45% were in the early phase at presentation ( P = .017). There was no association between disease categories, the presence of HLA-DRB1*0405, and clinical parameters. Conclusion The Revised Diagnostic Criteria proved useful for diagnosis of VKH disease in Brazilian patients. The present retrospective study did not find any association between disease category and severity parameters. To better understand the relevance of disease categories, a minimum follow-up period to categorize patients should be included in future prospective studies.

Syphilis is a sexually transmitted, chronic, systemic infection caused by the spirochete Treponema pallidum. If left untreated, the disease progresses through four stages, with the potential to cause significant morbidity to any major organ of the body. Frequent syphilitic ocular manifestations, which can occur at any stage of the disease, include interstitial keratitis, anterior, intermediate, and posterior uveitis, chorioretinitis, retinitis, retinal vasculitis and cranial nerve and optic neuropathies. Diagnosis is centered around a high level of clinical suspicion and includes treponemal specific and non-treponemal serologic tests. All patients with newly diagnosed syphilis should be tested for co-infection with human immunodeficiency virus, as the risk factors are similar for both diseases. Additionally, all patients with ocular syphilis should be tested for neurosyphilis. The preferred treatment for all stages of syphilis remains parenteral penicillin G. With proper diagnosis and prompt antibiotic treatment, the majority of cases of syphilis can result in a cure.

Intermediate uveitis is an intraocular inflammation involving the anterior vitreous, peripheral retina and pars plana. It usually affects patients from 5 to 30 years old, without gender or racial preferences. The etiology is unknown but there are several associated diseases: multiple sclerosis, idiopathic optic neuritis, autoimmune corneal endotheliopathy, sarcoidosis, thyroid diseases and inflammatory bowel diseases. Symptoms are blurry vision, floaters and distortion of central vision. The syndrome is bilateral in 80% of the patients and chronic with periods of exacerbation and remission. Clinical presentation includes: mild to moderate anterior chamber inflammation, thin keratic precipitates in the inferior portion of the cornea, autoimmune endotheliopathy, vitreitis, vasculitis in the peripheral retina, intravitreal "snowballs," retinal "snowbanking," optic neuritis and cystoid macular edema. Cataract and glaucoma are frequent complications. Treatment of intermediate uveitis is based on periocular and oral corticosteroids. Cryotherapy or laser photocoagulation of the peripheral retina are options in patients with snowbanking when there is an insufficient response to periocular or systemic corticosteroids. Imunosuppression may also be used when other therapies fail, and Cyclosporin A is the first drug of choice. Pars plana vitrectomy is indicated in patients with chronic significant inflammation, non-responsive cystoid macular edema, non-clearing vitreous hemorrhage, tractional retinal detachment and epiretinal membranes. The long-term prognosis of intermediate uveitis is usually good, particularly with strict control of inflammation and with proper management of complications. Patients can often maintain a vision of 20/50 or better.

PURPOSE Vogt-Koyanagi-Harada disease (VKH), an autoimmune disease targeted against melanocytes, is associated with HLA-DRB1*0405. This study was undertaken to analyze T-cell recognition and the cytokine expression profile induced by melanocyte epitopes in HLA-DRB1*0405-positive and -negative patients with VKH uveitis. METHODS Peripheral blood mononuclear cells (PBMC) proliferation and Th1 (IFN-gamma) and Th2 (IL-4 and IL-5) cytokine production were analyzed in HLA-DRB1*0405-positive (n = 12) and -negative (n = 22) patients with VKH and HLA-DRB1*0405-positive (n = 9) and -negative (n = 8) control subjects in response to human melanoma cell line lysate (HMCLL) and 28 synthetic peptides derived from the human melanocyte differentiation proteins TYR, TRP1, TRP2, and Pmel17. The peptides were selected using the TEPITOPE algorithm, based on their predicted binding to HLA-DRB1*0405 and to the non-disease-related HLA-DRB1*15. RESULTS HMCLL was recognized exclusively by the patients' PBMC (44%) but not by those of the control subjects (P < 0.01). PBMC from patients with VKH recognized an increased breadth of melanocyte-derived peptides at lower peptide concentrations than in the control subjects (68% vs. 25%; P < 0.01, at 1 microM) and did not produce the Th2 cytokine IL-4 in response to disease-specific peptides (0% vs. 50%, P < 0.001). Five peptides were exclusively recognized in patients bearing HLA-DRB1*0405. Furthermore, HLA-DRB1*0405-bearing patients, but not those with HLA-DRB1*15, recognized an increased breadth of melanocyte epitopes in comparison to HLA-matched control subjects (60% vs. 28%; P < 0.05). CONCLUSIONS These data indicate that patients with VKH are sensitized to melanocyte epitopes and display a peptide-specific Th1 cytokine response. In addition, the data indicate that patients bearing HLA-DRB1*0405 recognize a broader melanocyte-derived peptide repertoire, reinforcing the importance of this allele in susceptibility to the development of VKH disease.

RESUMO Objetivo: Estudar a incidência de uveíte era pacientes com artrite reumatóide juvenil (ARJ) do Hospital das Clínicas da Faculdade de Medicina da USP bem como a freqüência da uveíte nos diferentes subtipos de ARJ e possíveis fatores de risco para desenvolvimento de uveíte. Métodos: Foi realizado exame oftalmológico completo em 160 crianças com idade inferior ou igual a 16 anos e diagnóstico de ARJ, sendo 52 cora a forma sistêmica, 35 com a forma poliarticular e 73 com a forma pauciarticular. Resultados: Na forma sistêmica observou-se fator anti-núcleo (FAN) positivo em 8,5% e fator reumatóide (FR) positivo em 2,2%; na forma poliarticular, FAN e FR foram positivos em 8,6%; e na forma pauciarticular encontrou-se FAN positivo em 25,8% e FR positivo em 0%. Na forma sistêmica não foi observado nenhum tipo de uveíte. Na forma poliarticular foi encontrada iridociclite bilateral em 5,7%, sendo que um deles evoluiu com catarata e ceratopatia em faixa em ambos os olhos. Na forma pauciarticular foi observada iridociclite em 6,8%, sendo um caso unilateral e quatro bilaterais, tendo um olho evoluído com catarata. Conclusões: A incidência de uveíte foi de 4,4%, acometendo principalmente os portadores da forma pauciarticular. FAN positivo e idade do início da artrite foram fatores de risco para o desenvolvimento da uveíte.

RESUMO Introdução: Os pacientes portadores de tumores oculares podem ter pior prognóstico visual e sistêmico na ocorrência de atraso diagnóstico e terapêutico. Os estudos que avaliaram as causas desse atraso no nosso meioforam retrospectivos e relacionados a doença específica. Objetivos: Elucidar a trajetória rumo ao diagnóstico e tratamento empreendida por esses pacientes e descrever as características demográficas e clínicas dos mesmos. Material e métodos: Entrevista com pacientes portadores de tumores oculares de diagnóstico recente atendidos em hospital universitário no período de maio/95 a maio/96. Resultados: Foram avaliados 37 pacientes. Os tumores malignos encontrados com maior freqüência foram retinoblastoma, carcinoma epidermóide de conjuntiva e melanoma de coróide. A trajetória desde o início do quadro ocular até a terapêutica desenvolveu-se em quatro etapas principais, com problemas diferentes relatados em cada uma delas. As etapas de 1 a 3, relacionadas principalmente à motivação dos pacientes e ao acesso aos serviços de saúde, contribuiram igualmente, cada uma aumentando de um a três meses o tempo de evolução da doença. A etapa 4, de realização dos exames complementares, foi a mais breve, durando menos de 30 dias para a maioria dos pacientes. Conclusão: Sugere-se que os programas de saúde ocular levem em conta o padrão das dificuldades existentes na população para poderem atuar de forma eficiente.

The study investigated possible asymmetric dysfunction of the ON and OFF visual mechanisms in DMD (Duchenne muscular dystrophy) patients associated with specific genetic alterations.nineteen DMD patients and 7 heterozygous dmd carriers were tested, as well as 19 age-matched controls.Full-field ergs were recorded using mesopic (1 cd/m(2)) and photopic (250 cd/m(2)) sawtooth luminance modulations as stimuli: rapid increase and ramping decrease (to isolate ON responses) or rapid decrease and ramping increase (for OFF responses). In addition, a psychophysical study comprised contrast sensitivity tests using two checkerboard stimuli at either higher (ON) or lower (OFF) luminance relative to the background: 0.3 cycles per degree (cpd) presented for 33 ms (low spatial frequency, short duration) and 2 cpd presented for 1500 ms (high spatial frequency, long duration).A significant ERG amplitude reduction, relative to controls, was detected in the DMD patients in the mesopic positive peaks for both ON and OFF stimuli, as well as for the photopic ON stimulus (P0.05). Contrast sensitivity was significantly lower in the DMD patients (P0.05) relative to controls for the ON stimuli. Neither the ERG nor the contrast sensitivities were altered in the carriers.This study suggests that there are ON and OFF ERG alterations when both rods and cones contribute to the ERG responses in DMD patients. When only cones are activated there is an asymmetrical ERG alteration, also revealed by the contrast sensitivity measurements.

Objective : to determine the functional and morphological effects at rabbits retina of PS80 concentration used in the preparation of intravitreal drugs. Methods: eleven New Zealand rabbits received a intravitreal injection of 0.1ml of PS80. As control, the contralateral eye of each rabbit received the same volume of saline. Electroretinography was performed according to a modified protocol, as well as biomicroscopy and retina mapping before injection and seven and ten days after. Animals were euthanized in the 30th day and the retinas were analyzed by light microscopy. Results: eyes injected with PS80 did not present clinical signs of intraocular inflammation. Electroretinography did not show any alteration of extent and implicit time of a and b waves at scotopic and photopic conditions. There were no morphological alterations of retinas at light microscopy. Conclusion: intravitreal injection of PS80 in the used concentration for intravitreal drug preparations do not cause any functional or morphological alterations of rabbit retinas. These results suggest that PS80 is not toxic to rabbit retinas and may be safely used in the preparation of new lipophilic drugs for intravitreal injection.

OBJETIVOS: Avaliar a segurança e eficácia da associação de implante de segmentos de anéis corneanos intraestromais (ICRS) seguido de ceratectomia fotorrefrativa (PRK) para tratamento de alto astigmatismo pós-ceratoplastia penetrante. MÉTODOS: Trata-se de estudo prospectivo e não comparativo que incluiu pacientes com astigmatismo corneano acima de 6,0 dioptrias (D) secundário à ceratoplastia penetrante. Todos os pacientes foram submetidos ao implante de ICRS através de laser de femtossegundo. Três meses depois realizou-se tomografia de coerência óptica (OCT) de segmento anterior para definir a segurança e viabilidade do tratamento subsequente com PRK. Os parâmetros avaliados foram refração, acuidade visual para longe sem correção (AVLsc) e com correção (AVLcc), acuidade visual para perto sem correção (AVPsc) e com correção (AVPcc), valores ceratométricos [ceratometria central média (KMéd) e maior valor de ceratometria do mapa topográfico (Kmáx)], paquimetria do ponto mais fino (PMF), densitometria corneana (DC) e densidade de células endoteliais (DEnd). As avaliações foram realizadas no pré-operatório, 3 meses após implante de ICRS, assim como 6 e 12 meses após a PRK. Ao fim do estudo foi realizada análise vetorial da mudança de astigmatismo. RESULTADOS: Foram incluídos 30 olhos de 29 pacientes. Os dois procedimentos foram realizados em 27 olhos, uma vez que o PRK foi contraindicada em três casos. Vinte e seis casos seguiram até o fim do estudo. Resumo Houve melhora de AVLsc e AVLcc em todos os casos, exceto em um. Suas médias variaram de 1,16 ± 0,37 LogMAR a 0,34 ± 0,29 LogMAR (p

Objetivos: Comparar estereopsia, aniseiconia, e sintomas associados, em pacientes pseudofácicos bilaterais, com e sem anisometropia. Métodos: Foi realizado estudo clínico transversal em população de portadores de catarata senil, submetidos previamente à facoemulsificação com implante de LIO monofocal em ambos os olhos. Os pseudofácicos foram divididos em dois grupos: Grupo Controle (n=69) - diferença na refração pós-cirúrgica interocular pelo EE

Introdução: A artroplastia total de joelho (ATJ) é uma cirurgia de alta complexidade amplamente realizada devido à sua eficácia no tratamento da osteoartrite. O sangramento perioperatório na ATJ é uma importante complicação, pois eleva a chance de hemotransfusão, implicando, assim, maior risco de infecção, sobrecarga cardiovascular, prolongamento no tempo de internação e aumento do custo hospitalar e da mortalidade. O uso do garrote pneumático visa à diminuição do sangramento no intraoperatório, porém, além de agravar o risco de sangramento no pós-operatório (PO), também está associado ao desenvolvimento de trombose venosa profunda (TVP). A isquemia distal ao garrote gera um desequilíbrio entre oferta e demanda metabólica, causando hipóxia tecidual e metabolismo anaeróbio. Na reperfusão, entretanto, ocorre a produção de citocinas e radicais livres, conhecidos como espécies reativas de oxigênio (O2), que desencadeiam uma resposta inflamatória local e sistêmica. O pré-condicionamento anestésico (PCA) com sevoflurano (SEVO) é um recurso utilizado para minimizar os efeitos deletérios da síndrome de isquemia-reperfusão (SIR), incluindo o sangramento no PO. Objetivo: avaliar os efeitos do PCA com SEVO sobre o sangramento pósoperatório em pacientes submetidos à ATJ. Métodos: 30 pacientes foram divididos em dois grupos, assim definidos: grupo SEVO (com PCA com sevoflurano 2% por 15 minutos antes do garroteamento) e grupo CONT. (controle, sem PCA). Exames laboratoriais foram colhidos em quatro momentos: LAB PRÉ (venóclise na sala cirúrgica), LAB PÓS (imediatamente após a soltura do garrote), LAB 2 HORAS (2 horas após a soltura do garrote), LAB 12 HORAS (12 horas após a soltura do garrote) e LAB 24 HORAS (24 horas após a soltura do garrote), e o volume do dreno de sucção foi mensurado nos seguintes momentos: 1, 2, 12 e 24 horas após o término da cirurgia. A necessidade de hemotransfusão no período perioperatório também foi considerada. A nenhum dos grupos foi administrado antifibrinolíticos. Resultados: não houve diferença estatisticamente significativa entre os dois grupos no que concerne às variáveis relacionadas ao sangramento: volume drenado, medidas de hemoglobina e hematócrito. O volume drenado registrado mostrou aumento no período analisado e as medidas de hemoglobina e hematócrito reduziram-se entre os tempos estudados, sendo que essas variações foram mais intensas entre os momentos pré e pós e entre os momentos 2 horas e 12 horas. Conclusão Este estudo demonstrou que o uso do sevoflurano na concentração de 2%, durante 15 minutos, como modelo de pré-condicionamento anestésico em artroplastia total de joelho não foi eficaz na redução do sangramento pós-operatório em procedimentos com mais de duas horas de garroteamento Introduction: Total knee arthroplasty (TKA) is a complex surgery performed largely because of its effectiveness in the treatment of osteoarthritis. The perioperative bleeding in the TKA is an important complication because it increases the chance of hemotransfusion, thus implying an increased risk of infection, cardiovascular overload, length of hospital stays, increased hospital costs and mortality. The use of the tourniquet aims at reducing intraoperative bleeding. However, besides increasing the risk of postoperative bleeding (PO), it is also associated with the development of deep venous thrombosis. Ischemia distal to the tourniquet generates an imbalance between supply and metabolic demand, causing tissue hypoxia and anaerobic metabolism. But it is during the reperfusion that occurs the production of cytokines and free radicals, known as reactive oxygen species, that trigger a local and systemic inflammatory response. The anesthetic preconditioning (APC) with sevoflurane is a resource used to minimize the deleterious effects of ischemia-reperfusion syndrome (IRS), including bleeding in the post op period. Objective: To evaluate the effects of APC with SEVO on perioperative bleeding in patients submitted to TKA. Methods: 30 patients were divided into two groups, defined as follows: SEVO group (with APC with sevoflurane 2% for 15 minutes before the garrote) and CONTROL group (control, without APC). Laboratory tests were collected in four moments: LAB PRE (in the operating room), LAB POST (immediately after loosening of the club), LAB 2 HOURS (2 hours after loosening of the club), LAB 12 HOURS (12 hours after loosening of the tourniquet), and LAB 24 HOURS and the volume of the suction drain measured at the following moments: 1, 2, 12 and 24 hours after the end of the surgery. The need for blood transfusion in the peri-operative period was also considered. Neither of the groups received antifibrinolytics. Results: There was no statistically significant difference between the two groups regarding bleeding related variables: drained volume, hemoglobin, and hematocrit measurements. The recorded drainage volume showed an increase in the analyzed period and the hemoglobin and hematocrit measurements were reduced between the studied times, being these variations more intense between the Pre and Post moments and between the moments 2 hours and 12 hours. Conclusion: This study demonstrated the use of sevoflurane at a concentration of 2% for 15 minutes as a model of anesthetic preconditioning in total knee arthroplasty was not effective in reducing postoperative bleeding in procedures with more than two hours of tourniquet

OBJETIVO: Avaliar a evolução da inflamação ocular mediante análise multimodal e da função visual em pacientes com doença de Vogt-Koyanagi-Harada (DVKH), acompanhados desde a fase aguda e tratados com imunossupressão precoce associada à corticoterapia em altas doses, em um período de 24 meses de seguimento. MÉTODOS: Estudo prospectivo e longitudinal, incluindo pacientes com diagnóstico da DVKH desde a fase aguda, tratados com pulsoterapia de metilprednisolona seguida de prednisona 1mg/kg/dia com redução lenta, associada precocemente (em até 2 meses) à azatioprina. As avaliações sistemáticas consistiram em: exame clínico oftalmológico, retinografia, angiografias com fluoresceína sódica (AGF) e indocianina verde (ICGA), tomografia de coerência óptica (OCT) e com profundidade de imagem aprimorada (OCT EDI) e eletrorretinograma de campo total (ERGct). RESULTADOS: Foram incluídos 15 pacientes (14 mulheres), com idade mediana de 34 anos e tempo mediano de início do tratamento de 21 dias. No primeiro mês, 76,6% dos olhos apresentaram acuidade visual >= 20/40; houve redução da espessura de coroide (EC) subfoveal em 100% dos olhos e melhora do escore de dark dots (DD) em 80% dos olhos (comparando-se o mês 12 com o mês 1). Após os 6 meses de início da doença, foram observados sinais de inflamação clínica: 12 olhos (40%) com persistência/recorrência da celularidade de câmara anterior e cinco olhos (16,7%) com edema macular. Quanto aos sinais sugestivos de inflamação do segmento posterior, foram observados: flutuação no escore dos DD em 24 olhos (80%); aumento da EC em 13 olhos (43,3%); extravasamento perivascular em 17 olhos (56,7%) e dobras de coroide em seis olhos (20%). Os olhos foram agrupados de acordo com a presença ou não de redução >= 30% de qualquer um dos parâmetros da fase escotópica do ERGct entre os 12 e 24 meses de seguimento. Desse modo, 11 olhos (36,7%) foram classificados no grupo de piora e 19 olhos (63,3%) no grupo estável. Aos 24 meses, 23 olhos (76,7%) apresentavam ERGct subnormal em pelo menos um parâmetro. O grupo de piora apresentou uma maior média do escore de DD no mês 24 (p=0,047) e mais flutuações no escore de DD (90,9% dos olhos) (p=0,032). O grupo estável apresentou 52,6% dos olhos com flutuação da EC (p=0,002). A dose de prednisona = 20/40 em 90% dos olhos e controlando a inflamação clínica em 60% dos olhos. Entretanto, não foi capaz de suprimir os sinais subclínicos, sendo que 36,7% dos olhos evoluíram com piora dos parâmetros escotópicos do ERGct. Estes resultados sugerem a necessidade de um tratamento individualizado em uma parcela pequena de pacientes com evolução mais grave. OBJECTIVE: To evaluate ocular inflammation behavior through multimodal analysis and visual function of patients with Vogt-Koyanagi-Harada disease (VKHD) followed from the acute phase and treated with early immunosuppression (IMT) associated with high-dose corticosteroid therapy for a minimum period of 24 months. METHODS: A prospective and longitudinal study, in which patients diagnosed with VKHD from the acute phase were included. These subjects received initial treatment with methylprednisolone pulse therapy followed by prednisone 1 mg/kg/day with slowly regressive doses associated with early immunosuppression (within two months) with azathioprine. Systematic evaluations consisted of: ophthalmological clinical examination; retinography; fluorescein (FA) and indocyanine green (ICGA) angiographies; optical coherence tomography (OCT) also with enhanced depth imaging (EDI OCT) and full-field electroretinogram (ffERG). RESULTS: 15 patients (14 female) were included, with a median age of 34 years and median time of treatment onset of 21 days. In the first month, 76.6% of the eyes had best corrected visual acuity >= 20/40; subfoveal choroidal thickness (CT) reduced in 100% of the eyes, and dark dots (DD) score improved in 80% of the eyes (comparing month 12 with month 1). Six months after the onset of the disease, there were: 12 eyes (40%) with persistence or recurrence of anterior chamber cells and 5 eyes (16.7%) with macular edema. Regarding signs suggestive of posterior segment inflammation, the following were observed: DD score fluctuation in 24 eyes (80%); increase of CT in 13 eyes (43.3%); perivascular leakage in 17 eyes (56.7%) and choroidal folds in 6 eyes (20%). VKHD patients\' eyes were divided into stable and worsening groups, in the presence of any ffERG scotopic phase parameters reduction >= 30%, when 12- and 24-month exams were compared. Eleven eyes (36.7%) were classified into worsening group and 19 eyes (63.3%) into stable group. In the 24th month, 23 eyes (76.7%) presented subnormal ffERG in at least one parameter. The worsening group presented a higher mean DD score at month 24 (p=0.047) and more DD score fluctuations (90.9% of eyes) (p=0.032). 52.6% of the eyes of the stable group evolved with a fluctuation of CT (p=0.002). The dose of prednisone = 20/40 in 90% of the eyes and controlling clinical inflammation in 60% of the eyes. However, this therapy was not able to suppress subclinical inflammation and 36.7% of the eyes evolved with worsening of scotopic ffERG parameters. These results suggest the need for individualized treatment in a small portion of patients with more severe evolution

O vírus Zika é uma arbovirose emergente que é transmitida pelos mosquitos do género Aedes. A infecção, que se caracteriza clinicamente como uma síndrome febril aguda, muito inespecífico parecido ao dengue, está associada com alterações no sistema nervoso, bem como microcefalias no recém-nascido. O desenvolvimento infantil é um processo contínuo e muito dinâmico que inclui entre outras muitas funções, a visão. A evolução da visão inicia-se na vida intrauterina e continua após o nascimento. O período intra-útero e essencialmente importante para o futuro desenvolvimento visual da criança. Assim, as alterações causadas pela infecção pelo Zika têm demostrado repercutir no futuro desenvolvimento da criança. Uma forma de avaliar o sistema visual humano é avaliando a função de sensibilidade ao contraste. A FSC descreve o desempenho do sistema visual em níveis diferentes de contrastes. Neste trabalho de pesquisa está se avaliando a função de sensibilidade ao contraste em bebês cujas mães apresentaram Zika vírus na gestação. Foram feitos testes em 77 crianças com faixa etária de 2 a 24 meses, mais da metade destas crianças formará parte do grupo de controle. A função de sensibilidade ao contraste foi avaliada por meio do Programa de Psicofísica Psykinematix. Foi realizado teste descritivo completo para cada grupo e faixa etária. Análises comparativas entre os grupos foram realizadas com bases nas diferenças entre os valores individuais dos grupos controle e exposto, por meio de Análise de Variância de 1 Via. Correlações entre idade e sensibilidade ao contraste foram realizadas pelo teste de Spearman Rank Order para cada grupo e frequências espaciais. Comparando o grupo exposto e o grupo infectado não encontramos diferença estatística para nenhuma das frequências espaciais. Realizamos correlação entre idade e valor de sensibilidade ao contrate para as frequências testadas. Os dados preliminares mostraram haver uma correlação moderada significativa entre a idade e os valores de sensibilidade ao contrate para a frequência 0,6 cpg (r = 0,45; p< 0,05) para o grupo exposto. Nosso método se mostrou como uma ferramenta eficaz para estudos de sensibilidade ao contraste espacial de luminância nesta população. O desenvolvimento de métodos de medida de funções visuais em bebês e crianças não verbais é de grande importância, pois há pouca disponibilidade de metodologia comportamental para esta faixa etária. O desenvolvimento deste programa de medida permitiu que realizássemos avaliações de sensibilidade ao contraste em bebês e crianças com Zika vírus, discutidos na próxima sessão desta discussão. Outro resultado que mostra a robustez de nosso estudo está no fato dos resultados de nossas medidas estarem similares às medidas realizadas em bebês desta idade por outros pesquisadores para as mesmas frequências espaciais. Concluímos que as medidas de sensibilidade ao contraste em bebês com exposição ao Zika vírus não apresentaram redução da sensibilidade ao contraste em comparação com bebês não expostos The Zika virus is an emerging arbovirus that is transmitted by mosquitoes of the genus Aedes. The infection, which is clinically characterized as an acute, very nonspecific febrile syndrome similar to dengue, is associated with changes in the nervous system as well as microcephaly in the newborn. Child development is a continuous and very dynamic process that includes many functions as vision. The evolution of vision begins in intrauterine life and continues after birth. The intra-uterus period is essentially important for the child\'s future visual development. Thus, the changes caused by the infection by Zika have been shown to have an impact on the child\'s future development. One way of assessing the human visual system is by evaluating the contrast sensitivity function. FSC describes the performance of the visual system at different levels of contrasts. In this research, the contrast sensitivity function is evaluated in infants whose mothers presented Zika virus during pregnancy. Were tested 77 children aged 2 to 24 months, half of these children will be part of the control group. The contrast sensitivity function was evaluated through Psykinematix Psychophysics Program. A complete descriptive test was performed for each group and age group. Comparative analyzes between the groups were performed based on the differences between the individual values of the control and exposed groups, using one-way analysis of variance. Correlations between age and contrast sensitivity were performed by Spearman Rank Order test for each group and spatial frequencies. Comparing the exposed group and the infected group we found no statistical difference for any of the spatial frequencies. We performed a correlation between age and value of sensitivity to the contrast for the frequencies tested. Preliminary data showed a moderate significant correlation between age and contrast sensitivity values for the 0.6 cpg (r = 0.45, p

Distrofia muscular de Duchenne (DMD) e distrofia muscular de Becker (BMD) são distúrbios neuromusculares ligados a mutações no gene Dmd localizado no braço curto do cromossomo X. O gene Dmd, localizado na região Xp21, é responsável pela produção da proteína distrofina. Essa proteína é uma das proteínas que formam o complexo glicoproteico necessário para a integridade da fibra muscular e sua disfunção causa a DMD e a BMD. Além disso, a distrofina é necessária para a fisiologia da retina e, portanto, para o processamento da informação visual para funções com visão de cores e de contrastes. OBJETIVO: Avaliar o impacto de diferentes tipos de alteração genética do gene Dmd na visão de cores e de contrastes dos pacientes com DMD e BMD. METODOLOGIA: O estudo compreendeu a avaliação visual de três grupos de sujeitos: i) pacientes com DMD (n = 87); pacientes com BMD (n = 10) e voluntários saudáveis (n = 41) com o uso de dois novos testes psicofísicos adaptados ao tablet - Tablet Color Vision Test (CVT), para discriminação cromática e Tablet Contrast Sensitivity Test (CST) para medir sensibilidade ao contraste espacial de luminância. O tablet CVT utiliza mosaicos de pequenos pontos nos quais o alvo (estímulo) e o fundo apresentam apenas diferenças cromáticas sem bordas e com uma variação da luminância para os eixos protan, deutan e tritan; enquanto, o tablet CST utiliza estímulos acromáticos estáticos (preto e branco) para as frequências espacias: 0,8; 1,4; 2,0; 4,0; 10,0 e 16,0 ciclos por grau. RESULTADOS: Foram encontradas diferenças estatísticas significantes (p

A Degeneração Macular Relacionada à Idade (DMRI) é a principal causa de cegueira e perda de visão central em pessoas acima dos 50 anos nos países desenvolvidos. O diagnóstico da DMRI é geralmente realizado em consulta de rotina na qual, através da biomicroscopia de fundo, é detectada a presença de drusas, exsudatos subrretinianos ou atrofias geográficas na retina. Embora o diagnóstico seja razoavelmente simples, sua fisiopatologia é complexa, não está totalmente elucidada e envolve os sistemas antioxidante, imune e vascular, afetando principalmente a mácula, área responsável pela acuidade visual e visão de cores. Assim, nosso objetivo foi avaliar a atividade dos fotorreceptores em pacientes com DMRI através de testes psicofísicos e eletrofisiológicos. Para isto, foram incluídos 49 participantes, 19 no grupo controle (71,6 ± 4,8 anos) e 30 no grupo com DMRI seca (69,2 ± 7,7 anos). Os participantes foram submetidos a teste de visão de cores (Cambridge Colour Test - CCT), a pupilometria cromática para verificar a integridade da retina externa e interna e eletrorretinografia (ERG) com flicker heterocromático. Os resultados obtidos no CCT apresentaram uma pior discriminação de cores nos eixos Protan, Deutan e Tritan dos sujeitos portadores de DMRI comparados com os controles. Na pupilometria cromática, constatamos integridade da retina externa, mas houve redução da amplitude da resposta do estímulo às células ipRGC da retina interna. No ERG, não foram observadas diferenças nas respostas correspondentes a atividade das vias magno- e parvocelular. Estes resultados indicam que há preservação de função das vias magno- e parvocelulares na DMRI inicial, assim como das respostas pupilares mediadas pelos fotorreceptores, e que a discriminação de cores pode ser um instrumento sensível para revelar alterações iniciais na DMRI Age Related Macular Degeneration (AMD) is the leading cause of blindness and loss of central vision in people over 50 in developed countries. The AMD diagnosis is usually performed in a routine examination in which the presence of drusen, subretinal exudates or geographic atrophy in the retina is detected through background biomicroscopy. Although the diagnosis is simple, its pathophysiology is complex, not fully elucidated and involves the antioxidant, immune and vascular systems, mainly affecting the macula, region responsible for visual acuity and color vision. Thus, our objective was to evaluate the photoreceptor activity in patients with AMD through psychophysical and electrophysiological tests. For this, 49 participants were included, 19 in the control group (71.6 ± 4.8 years) and 30 in the dry AMD group (69.2 ± 7.7 years). Participants underwent color vision test (Cambridge Colour Test - CCT), chromatic pupilometry to verify the integrity of the external and internal retina, and electroretinography (ERG) with heterochromatic flicker. The results in the CCT showed worse color discrimination in the Protan, Deutan and Tritan axes of subjects with AMD compared to controls. The Tritan results is positively correlated to alteration on EPR-Bruchs membrane. In chromatic pupilometry, we observed external retinal integrity, but there was a reduction in the response amplitude of the stimulus to ipRGC cells of the internal retina. On ERG, no differences were observed between the groups in the activity of the magno- and parvocellular pathways. These results indicate preservation of magno- and parvocellular pathways function in initial AMD, as well as photoreceptors-mediated pupillary responses, and that color discrimination might a sensitive instrument to reveal initial changes in AMD

Objetivos: Estudos epidemiológicos recentes mostram que o uso de Cannabis sativa (maconha) durante a gravidez é cada vez mais frequente. Estudos experimentais evidenciam que o uso da maconha durante a gestação afeta o desenvolvimento fetal, peso ao nascer e o desenvolvimento infantil. Os receptores canabinoides estão presentes na retina de camundongos desde o nascimento. Os efeitos da exposição de gestantes à droga sobre a saúde fetal, especialmente sobre a retina em desenvolvimento, ainda não são bem compreendidos. Considerando que o período pré-natal é potencialmente sensível no desenvolvimento normal da retina, o objetivo deste estudo foi avaliar se os camundongos nascidos de mães expostas à fumaça da queima da Cannabis inalada durante a gestação apresentaram alterações morfológicas na retina ao longo da vida em comparação aos camundongos cujas mães não foram expostas à fumaça da queima da Cannabis. Métodos: Parâmetros biométricos fetais foram avaliados por ultrassonografia, dopplervelocimetria e testes comportamentais em neonatos e jovens adultos. A exposição das gestantes foi realizada através de um aparato para geração e inalação de fumaça capaz de mimetizar o uso recreacional de Cannabis em humanos. Dez fêmeas grávidas de camundongos BALB/c foram expostas à fumaça da queima de cigarros de Cannabis sativa a partir do 5,5° dia gestacional (DG) (fase pós implantacional) até o 17,5° DG (grupo Cannabis, CAN) e dez fêmeas foram expostas à inalação de ar filtrado (grupo controle, AF). Para avaliar as alterações estruturais in vivo da retina da prole, foram realizadas tomografia de coerência óptica de domínio espectral (Heildelberg Engineering, Alemanha) em 20 animais no 60º dia (camundongo adulto jovem), 120º, 200º e 360º dias pós-natal (DPN) (camundongo idoso) sob sedação. Trinta e sete camundongos de ambos os grupos foram sacrificados nos 20º, 60º ou 360º DPN para estereologia da retina (cálculo do volume fracionário das camadas da retina, volume de cada camada retiniana e volume total da retina) e microscopia de luz. Resultados: Os dados tomográficos mostraram que os animais do grupo CAN apresentaram diminuição de 17% na espessura total da retina no 120º DPN (p=0,005) quando comparados aos animais do grupo AF e essa diferença foi devida à redução de 21% na espessura na retina externa (p < 0,001). Na análise de cada camada da retina, os animais do grupo CAN apresentaram aumento na espessura da camada de segmentos internos e externos dos fotorreceptores em comparação ao grupo AF (p < 0,001). Na análise volumétrica pela estereologia da retina, os animais do grupo CAN apresentaram aumento de 89% do volume da camada de segmentos internos e externos dos fotorreceptores em relação ao grupo AF (p=0,001) e normalização no 360º DPN (p=0,001). Na análise da retina sob microscopia de luz, os animais do grupo CAN apresentaram espessamento de 64% na camada de segmentos internos e externos dos fotorreceptores no 360º DPN em relação ao grupo AF (p=0,041). Conclusão: A exposição materna durante a gestação à fumaça da queima da Cannabis sativa altera o desenvolvimento normal da retina da prole e esse efeito se mantém mesmo na fase adulta dos camundongos. Essas alterações são evidências experimentais de que os indivíduos cujas mães usaram maconha durante a gestação devem ser acompanhados por oftalmologista mais precoce e mais regularmente que os indivíduos cujas mães não usaram maconha Objectives: Recent epidemiologic studies have shown that the use of Cannabis sativa (marijuana) during pregnancy is increasing. Research into the impact of marijuana use during pregnancy has focused primarily on brain development and cognitive outcomes in the offspring. Cannabinoid receptors are present in the retina in mice since birth. Little is known about the impacts of maternal cannabis use on the retinal development and its potential postnatal consequences. Considering that the pre-natal period is potentially sensitive in the normal development of the retina, the aim of this study is to evaluate if the offspring of pregnant mice exposed to the smoke of Cannabis during pregnancy presents morphologic retinal changes from birth on in comparison to the offspring of pregnant mice that were not exposed to the smoke of the Cannabis during pregnancy. Methods: Fetal biometric parameters were evaluated by ultrasonography, dopplervelocimetry and behavioral tests in neonates and young adults. Twenty pregnant BALB/c mice were exposed (nose-only) daily to either marijuana smoke (10 animals, CAN group) or filtered air (10 animals, FA group) from gestational day 5 to 18. Exposure occurred in a smoke-generating and inhalation apparatus capable of mimicking the use of Cannabis in humans according to dose and exposure. In vivo retinal thickness was assessed by spectral domain optical coherence tomography (SD-OCT; Spectralis, Heidelberg Engineering, Germany) on days 60 (adult young mice), 120, 200, and 360 (old mice) under anesthesia. Fifty seven mice of both groups were sacrificed on days 20, 60, and 360 for stereology of the retina (fractionary volume of the retinal layers, volume of each retinal layer, and of the total volume of retina) and light microscopy. Results: SD-OCT findings showed that the animals of CAN group presented 17% decrease in the total thickness of the retina on day 120 (p=0.005) when compared to animals of FA group and it was secondary to the 21% thinning of the external retina (p=0.001). The analysis of each retinal layer showed that mice of the CAN group presented thickening of the internal and external segments of the photoreceptors in comparison to animals from the FA group (p < 0.001). In the volumetric analyses by retinal stereology, the CAN group presented an 89% increase of the internal and external segments of the photoreceptors on day 60 compared to the FA group (p=0.001) and normalization on day 360 (p=0.001). Light microscopy showed that animals of the CAN group presented 64% thickening of the internal and external segments of the photoreceptors on day 360 compared to group FA (p=0,041). Conclusion: Maternal exposure to the smoke of Cannabis sativa during pregnancy causes structural changes in the retina of the offspring that continue even with the aging of the mouse. These are experimental evidences that suggest that children and young adults born from mothers who used to smoke marijuana during pregnancy may require clinical care earlier and more frequent than the non-exposed population

Objetivo: Avaliação funcional (acuidade visual e sensibilidade ao contraste) e morfológica da retina de pacientes com edema macular diabético (EMD) tratados com bevacizumabe intravítreo e controle glicêmico optimizado durante 24 semanas de acompanhamento. Projeto: Estudo prospectivo intervencionista, randomizado e controlado. Métodos: Quarenta e um olhos de 34 pacientes com diabetes mellitus tipo 2 e EMD com Hemoglobina glicada (HbA1c)

A retina é formada por camadas de células que a estrutura, os contatos sinápticos e as características fisiológicas são específicas para cada tipo de célula. O processamento da informação visual, após a ativação dos fotorreceptores pela luz, ocorre em mecanismos pós-receptorais que formam diferentes circuitos de processamento, entre eles as vias ON, OFF, de luminância e de oponência cromática. As doenças que afetam a retina podem estar relacionadas com alterações específicas de um determinado circuito, como acontece com a distrofia muscular de Duchenne (DMD) que na alteração do gene dmd da retina afeta a comunicação entre os fotorreceptores e as células bipolares, e na diabetes Mellitus (DM) o dano celular ocorre principalmente na camada mais interna da retina. O objetivo deste estudo foi avaliar os efeitos da DMD e da diabetes Mellitus Tipo 1 (DM1) em diferentes mecanismos visuais. A amostra deste trabalho contou com três grupos: controle com 18 participantes (13,5, ±7,6), DMD com 9 participantes (16, ±5,9) e DM1 com 12 partcipantes (13,8, ±2,5). Os testes eletrorretinográficos foram aplicados nas condições mesópica, fotópica com estímulos que enfatizam respostas ON ou OFF, e flicker heterocromático (verde-vermelho) em 12Hz (para enfatizar a atividade da via de oponência cromática) e 36Hz (para enfatizar a atividade da via de luminância), e testes psicofísicos com estímulos que enfatizam os mecanismos ON e OFF com contraste de luminância e a via de oponência cromática por um estímulo com contraste cromático (isoluminante) verde-vermelho. O grupo DMD apresentou alteração no tempo de resposta e redução na amplitude da onda-a e onda-b nas condições mesópicas ON e OFF, redução da amplitude da onda-b na condição fotópica ON e alteração da via cromática. Enquanto o grupo DM1 apresentou aumento na amplitude e tempo da ond-a e onda-b das via ON e OFF na condição mesópica, mudança na fase da resposta na via cromática e na via de luminância. Os resultados estão de acordo com diversos estudos anteriores que mostram que as duas doenças causam alterações funcionais na retina, mas cada doença com características específicas. O presente estudo demonstrou que as duas doenças afetam as vias visuais ON e OFF independente do prejuízo neural ocorrer principalmente nas camadas mais externas ou nas camadas mais internas da retina. A possibilidade de identificar prejuízos funcionais em pacientes sem alteração clínica é uma valiosa ferramenta para o acompanhamento de doenças e para avaliar a eficácia de tratamentos. O presente estudo poderá contribuir para o estabelecimento de novos protocolos mais sensíveis e capazes de identificar alterações assimétricas no caso da DMD ou alterações que precedem o diagnóstico clínico no caso da DM1 The retina is formed by layers of cells that the structure, synaptic contact and physiology characters are specific for each type of this cells. The processing of visual information, after the photoreceptor activation by light is separate by post-receptor mechanisms that constitute the ON, OFF, luminance and chromatic pathways. The retina diseases have specific alteration in this tissue, thus it happens with the Duchenne muscular dystrophy (DMD), that have communication problems among photoreceptors and bipolar cells because of damage in dmd gene, and the Diabetes Mellitus (DM) that has cells damage mainly in the inner layer of retina. The purpose of this study was to evaluate the effects of DMD and Type 1 diabetes Mellitus (DM1) on different visual mechanisms. The sample had three grups: control with 18 subjects (13.5, ±7.6), DMD with 9 subjects (16, ±5.9) and DM1 with 12 subjects (13,8, ±2,5). The ERG recordings were applied in of the mesopic and photopic conditions with stimuli that laid emphasis on ON and OFF responses and heterochromatic (red-green) flicker modulation in 12Hz (laid emphasis on chromatic pathway) and 36Hz (laid emphasis on luminance pathway), and psychophysical tests laid emphasis on ON and OFF mechanisms with luminance contrast and the chromatic opponent pathway by stimulus with red-green chromatic contrast (isoluminance). As a result the DMD group presented alteration in the response time and reduction in the amplitude of the a- and b-wave in ON and OFF mesopic conditions, reduction of the amplitude of the a- and b-wave in ON photopic condition and alteration of the chromatic pathway. While the DM1 group showed an increase in the amplitude and time of the a- and b-wave in ON and OFF pathways of the mesopic condition, change in phase of the chromatic pathway and luminance pathway. These results were in agreement with previous studies that showed the two diseases present functional changes in the retina, but each disease with specific characteristics. The present study showed that two diseases affect the ON and OFF pathways regardless of the neural damage occur mainly in outer layer or inner layer of the retina. The possibility identify functional damage in patients without clinic injuries is the valuable tool for the following the dieses and evaluated treatment efficiency. The present study may contribute to establishment of the new sensitive and able protocols to identify asymmetric changes in DMD or changes that precede the clinical diagnosis in DM1

Introdução: A Retinose Pigmentar (RP) é uma doença hereditária da retina, caracterizada por perda da função visual, principalmente devido à degeneração dos fotorreceptores (bastonetes e cones). Objetivo: Avaliar os efeitos de uma única injeção intravítrea de fração mononuclear de células da medula óssea (FMMO) CD34+ em pacientes portadores de RP. Métodos: Ensaio clínico aberto, não randomizado, prospectivo, observador mascarado, no qual 20 pacientes, portadores de RP, com boa fixação ao exame de campo visual, foram incluídos. Única injeção intravítrea (IIV) de FMMO foi aplicada em apenas um dos olhos de cada paciente, enquanto que os olhos contralaterais serviram como controle e foram submetidos à injeção simulada. As avaliações incluíram: melhor acuidade visual corrigida (MAVC); campo visual estático - estratégia 30-2 (Octopus 900); microperimetria (MAIA - Center Vue) para avaliar estabilidade de fixação e sensibilidade macular; eletrorretinografia de campo total (ERG) e multifocal (mfERG) - padrão da ISCEV usando aparelho Espion E2 (Diagnosys LLC) e tomografia de coerência óptica (OCT). Os exames foram realizados antes da injeção e 4, 16, 32 e 48 semanas após. Resultados: Não houve diferença significativa na MAVC durante o seguimento. A diferença entre MAVC medida após 48 semanas e a basal foi de -0,04 ? 0,02 logMAR nos olhos tratados frente a -0,03 ? 0,01 logMAR nos controles (p=0,3898). A melhora da sensibilidade macular foi discretamente maior nos olhos com FMMO: 1,0 ? 0,5 dB do que nos olhos contralaterais: 0,2 ? 0,5 dB, mas sem significância estatística (p=0,0569). Não se observou mudança na estabilidade de fixação. A perda de desvio médio (MD) do campo visual dos olhos tratados (0,33 ? 0,70 dB) foi discretamente menor do que nos olhos controle (1,12 ? 0,58 dB) (p=0,0761). Nenhuma diferença significativa foi observada nas amplitudes e latências das respostas eletrorretinográficas durante o período avaliado. Não se verificou nenhuma complicação e nem efeito colateral após a injeção. Conclusão: A aplicação intravítrea de FMMO contendo células CD34+ mostrou-se segura em pacientes com RP. Observou-se, ainda, discreta melhora na sensibilidade macular, mas esta não foi significativa estatisticamente. Estudos futuros são necessários para esclarecer o potencial uso dessas células em distrofias retinianas. Introduction: Retinitis pigmentosa (RP) is a hereditary disease of the retina, characterized by loss of visual function, mainly due to degeneration of the photoreceptors (rods and cones). Objective: To evaluate the effects of a single intravitreal injection of bone marrow mononuclear fraction (BMMF) containing CD34+ cells in patients with RP. Methods: Open trial, non-randomized, prospective, masked observer, in which 20 patients with RP with good fixation in visual field examination were included. Single intravitreal injection of BMMF was performed in only one eye of each patient, while the contralateral eyes served as control and underwent shaw injection. Evaluations included: best corrected visual acuity (BCVA); static visual field - strategy 30-2 (Octopus 900); microperimetry (MAIA - Center Vue) to evaluate fixation stability and macular sensitivity; full-field (ERG) and multifocal (mfERG) electroretinograms according to the ISCEV using Espion E2 (Diagnosys LLC) and optical coherence tomography (OCT). The exams were performed before the injection and 4, 16, 32 and 48 weeks after. Results: There was no significant difference in BCVA during follow-up. The difference measured in BCVA between 48 weeks and baseline was 0.04 ? 0.02 logMAR in treated eyes versus -0.03 ? 0.01 logMAR in controls (p=0.3898). The improvement in macular sensitivity was slightly higher in BMMF eyes: 1.0 ? 0.5 dB than in contralateral eyes: 0.2 ? 0.5 dB, but without statistical significance (p=0.0569). No change in fixation stability was observed. The mean deviation loss (MD) of the visual field in treated eyes (0.33 ? 0.70 dB) was slightly lower than in the control eyes (1.12 ? 0.58 dB) (p=0.0761). No significant difference was observed evaluating amplitudes and latencies of ERG and mfERG responses during the follow-up. No complications or side effects were observed after the injection. Conclusion: The intravitreal injection of BMMF containing CD34 + cells was shown to be safe in patients with RP. There was still a slight improvement in macular sensitivity, but this was not statistically significant. Future studies are needed to clarify the potential use of these cells in retinal dystrophies.

Objetivos: Avaliar o potencial terapêutico e a segurança do uso intravítreo de (FMMO) contendo células CD34+ em pacientes portadores de degeneração macular relacionada com a idade na forma atrófica. Casuística e Métodos: Foram avaliados 10 pacientes com degeneração macular relacionada à idade (DMRI) seca e acuidade visual no pior olho

INTRODUÇÃO: A administração de aciclovir por via sistêmica é o tratamento de escolha para a necrose aguda de retina. Entretanto, por ser uma doença rapidamente progressiva, a injeção intravítrea de aciclovir ao diagnóstico pode ser utilizada como terapia adjuvante, enquanto o aciclovir sistêmico ainda não alcançou níveis terapêuticos na retina. Os objetivos deste estudo experimental foram determinar a meia-vida do aciclovir no vítreo após injeção intravítrea e determinar os efeitos funcionais e morfológicos do aciclovir na retina de coelhos saudáveis após injeção intravítrea do medicamento em diferentes doses. MÉTODOS: Foram utilizados 32 coelhos albinos da raça New Zealand (estudo farmacológico) e 86 coelhos pigmentados da raça Dutch Belted (30 no estudo eletrofisiológico, 36 no estudo morfológico com microscopia de luz e 20 no estudo morfológico com imuno-histoquímica). Para a determinação da meia-vida do aciclovir no vítreo, os 32 coelhos albinos receberam injeção intravítrea de aciclovir 1 mg e foram sacrificados nos dias 2, 9, 14 e 28. Para a avaliação funcional e microscopia de luz, os 66 coelhos pigmentados receberam três doses intravítreas de aciclovir (0,1; 1 ou 10 mg) no olho direito e soro fisiológico no olho esquerdo. Destes, 30 animais foram submetidos ao eletrorretinograma (ERG) antes da injeção e nos dias 2, 7 e 15 após a injeção. Para a análise histológica (microscopia de luz), 36 animais foram sacrificados 2, 7 e 15 dias após a injeção. Para imuno-histoquímica (apoptose, GFAP, DAPI e vimentina), os 20 coelhos pigmentados receberam injeção intravítrea de 1 e 10 mg de aciclovir e foram sacrificados após cinco dias. RESULTADOS: No estudo da meia-vida do aciclovir no vítreo, as concentrações médias de aciclovir no vítreo foram 0,25, 0,09, 0,06 e 0,08 ?g/ml, respectivamente 2, 9, 14 e 28 dias depois da injeção. Nos estudos eletrofisiológico e de microscopia de luz, os olhos que receberam injeção intravítrea de 0,1 mg de aciclovir não apresentaram alterações funcionais ou histológicas. Os olhos injetados com 1 mg de aciclovir apresentaram redução significativa da amplitude das ondas a e b no ERG e desalinhamento dos fotorreceptores na microscopia de luz. Estes achados regrediram no 15º dia. Os olhos que receberam injeção intravítrea de 10 mg de aciclovir apresentaram as mesmas alterações funcionais, mas que não regrediram após o 15º dia. À microscopia de luz, esses olhos apresentaram destruição da camada de fotorreceptores e desorganização de toda a retina. Na camada de células ganglionares houve áreas com ausência de células da retina interna. A imuno-histoquímica mostrou lesão das células de Müller e apoptose de fotorreceptores apenas nos animais injetados com 10 mg. CONCLUSÕES: A meia-vida do aciclovir no vítreo após injeção intravítrea é muito curta para a sua detecção em dias. Os resultados funcionais e morfológicos sugerem que a injeção intravítrea de aciclovir em coelhos causa alterações tóxicas dose e tempo dependentes nos fotorreceptores e nos neurônios pós-receptorais da retina. A dose de 0,1 mg de aciclovir parece ser segura para injeção intravítrea em coelhos e pode ser utilizada em modelos experimentais de uveíte ou retinite viral OBJECTIVE: The gold standard for the treatment of acute retinal necrosis is the use of systemic intravenous acyclovir. Nevertheless, as a rapidly progressive disease, use of intravitreal acyclovir injection at the time of diagnosis may be a second therapy until the systemic acyclovir reaches therapeutic levels in the retina. The aim of this experimental study was to determine pharmacological levels of the drug in the vitreous within days and to determine the functional and morphologic effects of acyclovir in the retina of healthy rabbits, after intravitreal injections in different dosages. METHODS: We have used 32 albino New Zealand rabbits for the pharmacologic experiments and 86 pigmented Dutch Belted animals for electrophysiology, immunochemistry and morphology. Thirty rabbits were used for the electrophysiological study, 36 were used for the light microscopy morphology and 20 animals were used for immunochemistry morphology. For the half-life study, the 32 albino rabbits received a 1mg acyclovir intravitreal injection and they were euthanized at 2, 9, 14 and 28 days. For functional and morphologic evaluations, the 66 pigmented animals received one of 3 intravitreal dosages of acyclovir (0,1; 1 or 10 mg) in the right eye and saline in the left eye. For the functional evaluation, 30 pigmented animals underwent electroretinography before the injection and on days 2, 7 and 15 after the procedure. For the histology with light microscopy, 36 animals were euthanized on days 2, 7 and 15 after the injection. Twenty rabbits that received 1 and 10mg of acyclovir were euthanized on day 5 were used for the immunohistochemistry to evaluate apoptosis, with GFAP, DAPI and vimentin. RESULTS: For the pharmacology study, the mean acyclovir concentrations when 1?g/ml was injected into the vitreous were respectively 0,25; 0,09; 0,06 e 0,08?g/ml on days 2, 9, 14 and 28 after injected. The eyes that received 0,1 mg acyclovir showed no functional or histological alterations. The eyes injected with 1 mg acyclovir had significant reduction on a and b waves amplitude and photoreceptor misalignment, which regressed on day 15. The 10mg injected eyes, showed the same electrophysiology changes. The retinas of those animals had photoreceptor layer destruction and total retina disorganization. In the ganglion cell layer, there were areas of absence of internal retinal cells. The immunohistochemistry showed Müller cells lesion and photoreceptor apoptosis in the 10mg animals. CONCLUSIONS: Acyclovir half-life is too short for its detection within days. The functional and morphological results suggest that the intravitreal acyclovir injection in rabbits cause toxic changes that are dose and time dependent on photoreceptors and post-receptor neurons in the retina. The 0,1 mg acyclovir dosage seems to be safe for intravitreal use in rabbits and may be studied in experimental models of viral uveitis or retinitis