Eduardo Buchele Rodrigues

Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy

The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

Comparative analysis of the nuclear lens opalescence by the Lens Opacities Classification System III with nuclear density values provided by Oculus Pentacam: a cross-section study using Pentacam Nucleus Staging software

PURPOSE To compare the clinical classification of cataract using the Lens Opacities Classification System (LOCS) III with the mean values of lens density provided by the Pentacam Scheimpflug System in nuclear cataracts. METHODS One hundred and one eyes from 101 patients with age-related nuclear cataract were submitted to clinical examination for lens grading score using LOCS III. According to LOCS III, nuclear opalescence was divided in six groups. Patients were evaluated by the Pentacam Scheimpflug System for the mean lens density using the Pentacam lens densitometry program (PLDP), the Pentacam Nucleus Staging (PNS) mean value and the PNS cataract grading score. RESULTS A positive correlation between the mean values of lens density and LOCS III classification, considering groups 1 to 5, could be noticed with PLDP and PNS mean value. The mean values between the groups were similar using the PLDP and the PNS mean value. However, when the PNS cataract grading score was evaluated, there was low correspondence with LOCS III classification. CONCLUSION Pentacam Scheimpflug device offers an objective measure of the lens nuclear density on nuclear cataracts. PLDP and the PNS mean value were both useful to evaluate age-related nuclear cataract up to LOCS III group 5.

Subretinal Brilliant Blue G migration during internal limiting membrane peeling

We read with interest the article by Schumann et al ,1 who have reported the ultrastructural analyses of internal limiting membrane (ILM) specimens after staining with new dye Brilliant Blue G (BBG). In their study, morphological analyses failed to reveal any adverse effects possibly related to BBG. However, they stated that ultrastructural analyses alone may not be sufficient to allow definite conclusions on the safety of a vital dye used for macular surgery. Here we report the effects of accidental subretinal migration of BBG for ILM identification during vitrectomy for epiretinal membrane (ERM). A 56-year-old man had decreased visual acuity and metamorphopsia. He had an idiopathic ERM, and the best-corrected visual acuity (BCVA) measured by the Early Treatment Diabetic Retinopathy Study chart was 1.0 logMAR (Snellen equivalent 6/60). Pars plana vitrectomy and ERM peeling …

Fusion proteins for treatment of retinal diseases: aflibercept, ziv -aflibercept, and conbercept

AbstractIn the last few years, monoclonal antibodies have revolutionized the treatment of retinal neovascular diseases. More recently, a different class of drugs, fusion proteins, has provided an alternative treatment strategy with pharmacological differences. In addition to commercially available aflibercept, two other drugs, ziv-aflibercept and conbercept, have been studied in antiangiogenic treatment of ocular diseases. In this scenario, a critical review of the currently available data regarding fusion proteins in ophthalmic diseases may be a timely and important contribution. Aflibercept, previously known as VEGF Trap Eye, is a fusion protein of VEGF receptors 1 and 2 and a treatment for several retinal diseases related to angiogenesis. It has firmly joined ranibizumab and bevacizumab as an important therapeutic option in the management of neovascular AMD-, DME- and RVO-associated macular edema. Ziv-aflibercept, a systemic chemotherapeutic agent approved for the treatment of metastatic colorectal cancer, has recently drawn attention because of its potential for intravitreal administration, since it was not associated with ERG-related signs of toxicity in an experimental study and in human case reports. Conbercept is a soluble receptor decoy that blocks all isoforms of VEGF-A, VEGF-B, VEGF-C, and PlGF, which has a high binding affinity for VEGF and a long half-life in vitreous. It has been studied in a phase three clinical trial and has shown efficacy and safety. This review discusses three fusion proteins that have been studied in ophthalmology, aflibercept, ziv-aflibercept and conbercept, with emphasis on their clinical application for the treatment of retinal diseases.

Técnica para injeção intravítrea de drogas no tratamento de doenças vítreorretinianas

Intravitreal injections are the standard technique applied in the treatment of some vitreoretinal diseases. In this paper the technique and complications of intravitreal injections are presented. In summary, the procedure involves various consecutive steps. Initially, days before the treatment topical antibiotics and acetazolamide may be prescribed for reduction of the ocular flora and intraocular pressure. Before the injection, the pupil should be dilated and topical anesthesia should be achieved. Injection shall be performed in the operating room under sterile conditions, the surgeon should wear surgical gloves and mask. The eye is then exposed with sterile blepharostat and sterile-drape thereby providing protection of the needle against the contact with contaminated lashes and lids. Injection is done 3.5 mm from the limbus through the pars plana. The needle should be inserted up to 6 mm into the vitreous cavity. Immediately after injection the patient must be examined by indirect ophthalmoscopy to verify central artery perfusion and complications as vitreous hemorrhage. Visual acuity better than light perception should be detected right after injection. If persistent central retinal artery occlusion is diagnosed, anterior chamber paracentesis should be performed. The patient may be discharged with an occlusive patch. Examination at the first postoperative day should exclude various complications such as endophthalmitis, and topical steroid and antibiotics should be prescribed for 7 days. Some complications encountered after intravitreal injections include retinal detachment, vitreous hemorrhage, cataract, uveitis, ocular hypertension, or endophthalmitis.

Diabetes induces changes in neuroretina before retinal vessels: a spectral-domain optical coherence tomography study

PurposeTo investigate retinal changes prior to vascular signs in patients with type 2 diabetes without diabetic retinopathy or with mild non proliferative diabetic retinopathy.MethodsA cross-sectional study was performed in three groups: patients without diabetes, patients with type 2 diabetes without diabetic retinopathy, and patients with diabetes with mild diabetic retinopathy. Analysis of retinal layers was performed objectively with the Cirrus Review Software 6.0 (Carl Zeiss Meditec, Dublin, CA, USA). Macular cube scans were analyzed with regard to: the ganglion cell layer + inner plexiform layer analysis, retinal nerve fiber layer thickness, central subfoveal retinal thickness and average macular thickness.ResultsIn total, 102 patients were included in this study, of which 28 (27.4%) were classified into control group, 46 (45.0%) classified as diabetic patients with no diabetic retinopathy and 28 (27.4%) classified as mild diabetic retinopathy. Quantitative analysis with the Cirrus software showed that the mean ganglion cell layer and mean retinal nerve fiber layer were thinner in diabetes without diabetic retinopathy group when compared to controls. ANOVA with Bonferroni post test indicated a statistically significant reduction in average retinal thickness in mild diabetic retinopathy group (P = 0.032) compared to control and reduction in ganglion cell layer in diabetes with no diabetic retinopathy (P = 0.039) and mild diabetic retinopathy (P = 0.003). Also indicated reduction in retinal nerve fiber layer in diabetic without diabetic retinopathy and eyes with mild diabetic retinopathy (P < 0.001), compared to controls.ConclusionsOur study found reduction in thickness of ganglion cell layer and retinal nerve fiber layer in patients with diabetes without diabetic retinopathy, which suggests neuroretinal changes before vascular signs of diabetic retinopathy.

Arboviruses and the eye

Arthropod-borne viruses, or arboviruses, are viruses that are transmitted through the bites of mosquitoes and ticks. There are numerous arboviruses throughout the world capable of causing human disease spanning different viral families and genera. Recently, dengue, chikungunya, and zika viruses have emerged as increasingly important arboviruses that can cause human disease, however no specific treatment or vaccine is available for them. In addition, ocular manifestations of these diseases have become more prevalent over the past few years. This review highlights the current understanding on the pathogenesis, systemic changes and ocular findings, emphasizing the retinal manifestations related to dengue, chikungunya, and zika viruses.

Survey: technique of performing intravitreal injection among members of the Brazilian Retina and Vitreous Society (SBRV)

PURPOSE To evaluate and describe the precautions involved in the technique of intravitreal injection of antiangiogenic drugs adopted by the ophthalmologists who are members of the Brazilian Society of Retina and Vitreous (SBRV). METHODS A questionnaire containing 22 questions related to precautions taken before, during, and after intravitreal injection was sent electronically to 920 members of SBRV between November 15, 2013 and April 31, 2014. RESULTS 352 responses (38%) were obtained. There was a predominance of men (76%) from the southwest region of Brazil (51%). The professional experience varied between 6 and 15 years after medical specialization (50%). Most professionals (76%) performed an average of 1 to 10 intravitreal injections a week, and 88% of the procedures were performed in the operating room using povidone iodine (99%), sterile gloves, and blepharostat (94%). For inducing topical anesthesia, usage of anesthetic eye drops was the most used technique (65%). Ranibizumab (Lucentis®) was the most common drug (55%), and age-related macular degeneration (AMD) was the most treated disease (57%). Regarding the complications treated, 6% of the ophthalmologists had treated at least one case of retinal detachment, 20% had treated cases of endophthalmitis, 9% had treated cases of vitreous hemorrhage, and 12% had encountered cases of crystalline lens touch. CONCLUSION Intravitreal injection is a procedure routinely performed by retina specialists and has a low incidence of complications. Performing the procedure in the operating room using an aseptic technique was preferred by most of the respondents. Ranibizumab was the most used drug, and AMD was the most treated disease.

Oclusão de ramo venoso da retina associado ao uso de infliximabe: relato de caso

A case of a 53 year-old female patient who developed branch retinal vein occlusion after six 3 mg/kg Infliximab infusions for rheumatoid arthritis treatment is reported. Hematological disorders, cardiopathy and chronic systemic hypertension evaluation were negative. The relationship between the infliximab therapy and the development of retinal vein occlusion raises awareness of the possibility of a potential side effect of this medication.

Vital Dyes in Ophthalmology: a Chemical Perspective

Abstract Vital dyes have advanced diagnosis and surgical technique in various specialties, including oncology, gastroenterology and ophthalmology. Intra-operative and diagnostic dyes are finding uses in all areas of ophthalmology, including cornea, cataract, retina, glaucoma, orbit and conjunctiva. We provide a summary of current knowledge of the chemical concepts of vital dyes in ophthalmology. We review the properties of dyes, techniques of application, indications and complications in ocular surgery. Vital dyes represent an expanding area of research, and novel dyes deserve further investigation.