Rodrigo Jorge

Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study).

Objective: To evaluate the short-term fluorescein angiographic and visual acuity effects of a single intravitreal injection of bevacizumab (Avastin) for the management of persistent new vessels (NV) associated with diabetic retinopathy. Methods: A prospective, nonrandomized open-label study of diabetic patients with actively leaking NV refractory to laser treatment and best-corrected Early Treatment Diabetic Retinopathy Study visual acuity (BCVA) worse than 20/40. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 6, and 12 (±1) following intravitreal injection of 1.5 mg of bevacizumab. Main outcome measures include changes in total area of fluorescein leakage from active NV and BCVA. Results: Fifteen consecutive patients (men, 9 [60%]; women, 6 [40%]) were included and all completed the 12-week follow-up period of the study. The mean ± SD age of participants was 60.08 ± 7.75 years (median, 59.5; range, 49–73 years). At baseline, mean ± standard error of the mean (SEM) NV leakage area was 27.79 ± 6.29 mm2. The mean ± SEM area of active leaking NV decreased significantly to 5.43 ± 2.18 mm2 and 5.50 ± 1.24 mm2 (P < 0.05, Tukey multiple comparisons post-test) at 1 and 12 weeks postinjection, respectively; at week 6 no leakage was observed. The mean ± SEM logMAR (Snellen equivalent) BCVA improved significantly from 0.90 (20/160) ± 0.11 at baseline to 0.76 (20/125+2) ± 0.12, 0.77 (20/125+2) ± 0.11, and 0.77 (20/125+2) ± 0.12 at weeks 1, 6, and 12, respectively (P < 0.05, Tukey multiple comparisons post-test). No major adverse events were observed. Conclusions: Intravitreal injection of bevacizumab achieved short-term reduction of fluorescein leakage from persistent active NV without loss of vision in patients with diabetic retinopathy. Further studies to investigate the role of anti-VEGF therapy with bevacizumab for the management of diabetic retinopathy refractory to laser treatment are warranted.

Intravitreal bevacizumab (avastin) for central and hemicentral retinal vein occlusions: IBeVO study.

Purpose: To evaluate the safety, visual acuity changes, and morphologic effects associated with intravitreal bevacizumab injections for the management of macular edema due to ischemic central or hemicentral retinal vein occlusion (RVO). Methods: In this prospective, open-label study, 7 consecutive patients (7 eyes) with macular edema associated with ischemic central or hemicentral RVO were treated with intravitreal injections of 2.0 mg (0.08 mL) of bevacizumab at 12-week intervals. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 6, and 12 after each injection. Clinical evidence of toxicity and complications as well as changes in logarithm of minimum angle of resolution Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), central macular thickness (CMT) and total macular volume (TMV) shown by optical coherence tomography (OCT), and dye leakage shown by fluorescein angiography were evaluated. Results: The median age of the 7 patients was 65 years (range, 58–74 years), and the median duration of symptoms before injection was 7 months (range, 2.5–16 months). At baseline, mean BCVA was 1.21 (Snellen equivalent, ≈20/320) in the affected eye. Mean baseline CMT and TMV were 730.1 &mgr;m and 17.1 mm3, respectively. Fluorescein leakage was observed in the macula and affected retinal quadrants in all seven eyes. Six patients completed the 25-week follow-up examination with reinjections performed at weeks 12 and 24. The most common adverse events were conjunctival hyperemia and subconjunctival hemorrhage at the injection site. At the last follow-up, mean BCVA in the affected eye was 0.68 (Snellen equivalent, 20/100+1). No patient had a decrease in BCVA. Mean CMT and TMV at the 25-week follow-up were 260.3 &mgr;m and 9.0 mm3, respectively; fluorescein leakage within the macula and affected retinal quadrants as compared with baseline was markedly reduced in all patients. Coupled with fluorescein angiographic findings, OCT data suggest a trend of macular edema recurrence between 6 weeks and 12 weeks after injection. Conclusions: Intravitreal bevacizumab injections of 2.0 mg at 12-week intervals were well tolerated and were associated with short-term BCVA stabilization or improvement and favorable macular changes in all patients with ischemic RVO and associated macular edema.

Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study)

Background/aims: The aim of this study was to compare the morphological and visual acuity outcomes associated with a single intravitreal injection of triamcinolone acetonide versus bevacizumab for the treatment of refractory diffuse diabetic macular oedema. Methods: Twenty-eight patients were randomly assigned to receive a single intravitreal injection of either 4 mg/0.1 ml triamcinolone acetonide or 1.5 mg/0.06 ml bevacizumab. Comprehensive ophthalmic evaluation was performed at baseline and at weeks 1, 4, 8 (±1), 12 (±2) and 24 (±2) after treatment. Main outcome measures included central macular thickness measured with optical coherence tomography (OCT) and best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. Results: Twenty-six patients (26 eyes) completed all study visits (two patients missed two consecutive study visits). Central macular thickness was significantly reduced in the intravitreal triamcinolone group compared with the bevacizumab group at weeks 4, 8, 12 and 24 (p<0.05). Logarithm of the minimum angle of resolution (LogMAR) best-corrected visual acuity was significantly higher at weeks 8 (0.69; ∼20/100+1) and 12 (0.74; 20/100−2) in the intravitreal triamcinolone group compared with the bevacizumab group (weeks 8 (0.83; ∼20/125−1) and 12 (0.86; 20/160+2)) (p<0.05). Significant change from baseline in mean intraocular pressure (mmHg) was seen at week 4 (+2.25) only in the intravitreal triamcinolone group (p<0.0001). No patient had observed cataract progression during the study. Conclusions: One single intravitreal injection of triamcinolone may offer certain advantages over bevacizumab in the short-term management of refractory diabetic macular oedema, specifically with regard to changes in central macular thickness. The actual clinical relevance of our preliminary findings, however, remains to be determined in future larger studies.

Ticks (Acari: Ixodida) on wild carnivores in Brazil

The present study reports field data of ticks infesting wild carnivores captured from July 1998 to September 2004 in Brazil. Additional data were obtained from one tick collection and from previous published data of ticks on carnivores in Brazil. During field work, a total of 3437 ticks were collected from 89 Cerdocyon thous (crab-eating-fox), 58 Chrysocyon brachyurus (maned-wolf), 30 Puma concolor (puma), 26 Panthera onca (jaguar), 12 Procyon cancrivorus (crab-eating-raccoon), 4 Speothos venaticus (bush-dog), 6 Pseudalopex vetulus (hoary-fox), 6 Nasua nasua (coati), 6 Leopardus pardalis (ocelot), 2 Leopardus tigrinus (oncilla), 1 Leopardus wiedii (margay), 1 Herpailurus yagouaroundi (jaguarundi), 1 Oncifelis colocolo (pampas-cat), 1 Eira barbara (tayara), 1 Galictis vittata (grison), 1 Lontra longicaudis (neotropical-otter), and 1 Potus flavus (kinkajou). Data obtained from the Acari Collection IBSP included a total of 381 tick specimens collected on 13 C. thous, 8 C. brachyurus, 3 P. concolor, 10 P. onca, 3 P. cancrivorus, 4 N. nasua, 1 L. pardalis, 1 L. wiedii, 4 H. yagouaroundi, 1 Galictis cuja (lesser grison), and 1 L. longicaudis. The only tick infested-carnivore species previously reported in Brazil, for which we do not present any field data are Pseudalopex gymnocercus (pampas fox), Conepatus chinga (Molina’s hog-nosed skunk), and Conepatus semistriatus (striped hog-nosed skunk). We report the first tick records in Brazil on two Felidae species (O. colocolo, H. yagouaroundi), two Canidae species (P. vetulus, S. venaticus), one Procyonidae species (P. flavus) and one Mustelidae (E. barbara). Tick infestation remains unreported for 5 of the 26 Carnivora species native in Brazil: Oncifelis geoffroyi (Geoffroy’s cat), Atelocynus microtis (short-eared dog), Pteronura brasiliensis (giant otter), Mustela africana (Amazon weasel), and Bassaricyon gabbii (olingo). Our field data comprise 16 tick species represented by the genera Amblyomma (12 species), Ixodes (1 species), Dermacentor (1 species), Rhipicephalus (1 species), and Boophilus (1 species). Additional 5 tick species (3 Amblyomma species and 1 species from each of the genera Ixodes and Ornithodoros) were reported in the literature. The most common ticks on Carnivora hosts were Amblyomma ovale (found on 14 host species), Amblyomma cajennense (10 species), Amblyomma aureolatum (10 species), Amblyomma tigrinum (7 species), Amblyomma parvum (7 species), and Boophilus microplus (7 species).

Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy (IBeHi study)

Purpose:  To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab on best corrected visual acuity (BCVA) and total area of fluorescein leakage from active new vessels (NVs) in patients with high‐risk proliferative diabetic retinopathy (PDR).

Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial.

Purpose: To evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa or cone-rod dystrophy. Methods: A prospective, Phase I, nonrandomized, open-label study including 3 patients with retinitis pigmentosa and 2 patients with cone-rod dystrophy and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/200 or worse. Evaluations including best-corrected visual acuity, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography, and optical coherence tomography were performed at baseline and 1, 7, 13, 18, 22, and 40 weeks after intravitreal injection of 10 × 106 autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient. Results: No adverse event associated with the injection was observed. A 1-line improvement in best-corrected visual acuity was measured in 4 patients 1 week after injection and was maintained throughout follow-up. Three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave amplitude approximately 35 μV), which remained recordable throughout follow-up, and 1 patient showed a small response (a wave amplitude approximately 20 μV) recordable only at Weeks 7, 13, 22, and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on optical coherence tomography or fluorescein and indocyanine green angiograms. Conclusion: Intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced retinitis pigmentosa or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. Further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies.

Intraoperative Bleeding during Vitrectomy for Diabetic Tractional Retinal Detachment With versus Without Preoperative Intravitreal Bevacizumab (IBeTra Study)

Aims: To compare the amount of intraoperative intraocular bleeding in patients with diabetes with macula-involving tractional retinal detachment (TRD) undergoing pars plana vitrectomy (PPV) with and without preoperative intravitreal bevacizumab (IVB) injection. Methods: An institutional study was carried out with consecutive patients with diabetic retinopathy and macula-involving TRD of recent (3 months) onset who were randomly assigned to PPV only (PPV group) or PPV combined with one IVB (1.5 mg/0.06 ml) injection 2 weeks prior to surgery (bevacizumab (BEV)/PPV group). All patients underwent 23-gauge PPV 3 weeks after baseline. The main outcome measure was erythrocyte count in the fluid retrieved from the vitrectomy cassette using a Neubauer counting chamber. Results: The study included 20 patients. The mean erythrocyte count was 14 865×103 (SD 19 332×103; median 4500×103) cells in the BEV/PPV group, and 176 240×103 (SD 108 375×103; median 166 600×103) cells in the PPV group. The mean erythrocyte count was significantly lower in the BEV/PPV group than in the PPV group (p<0.0001). No major adverse events were identified. Conclusion: Preoperative IVB injection was associated with reduced intraocular bleeding during 23-gauge PPV for diabetic macula-involving TRD. Further studies are needed to confirm our preliminary findings. Trial registration number: NCT00690768.

A prospective randomized trial of intravitreal bevacizumab versus ranibizumab for the management of diabetic macular edema.

PURPOSE To compare visual acuity and spectral-domain optical coherence tomography (SDOCT) outcomes associated with intravitreal (IV) bevacizumab vs IV ranibizumab for the management of diabetic macular edema (DME). DESIGN Prospective randomized trial. METHODS Forty-eight patients (63 eyes) with center-involved DME were randomly assigned to receive 1.5 mg (0.06 cc) IV bevacizumab or 0.5 mg (0.05 cc) IV ranibizumab at baseline and monthly if central subfield thickness was greater than 275 μm. RESULTS Forty-five patients (60 eyes) completed 48 weeks of follow-up. At baseline, mean ± standard error best-corrected visual acuity (BCVA) (logMAR) was 0.60 (20/80) ± 0.05 in the IV bevacizumab group and 0.63 (20/85) ± 0.05 in the IV ranibizumab group. A significant improvement in mean BCVA was observed in both groups at all study visits (P < .05); this improvement was significantly greater in the IV ranibizumab group compared with the IV bevacizumab group at weeks 8 (P = .032) and 32 (P = .042). A significant reduction in mean central subfield thickness was observed in both groups at all study visits compared with baseline (P < .05), with no significant difference in the magnitude of macular thickness reduction between groups. The mean number of injections was significantly higher (P = .005) in the IV bevacizumab group (9.84) than in the IV ranibizumab group (7.67). CONCLUSIONS IV bevacizumab and IV ranibizumab are associated with similar effects on central subfield thickness in patients with DME through 1 year of follow-up. IV ranibizumab is associated with greater improvement in BCVA at some study visits, and the mean number of injections is higher in the IV bevacizumab group.

Multimodal fundus imaging in Best vitelliform macular dystrophy.

BackgroundBest vitelliform macular dystrophy (BVMD) is a rare autosomal dominant retinal disease of highly variable phenotypic expression. Interpretations of disease mechanisms based on histopathology, electrophysiology, genetic analysis, and retinal imaging are somewhat discordant in fundamental issues such as the location and extension of primary retinal changes. Herein we describe the morphological macular features in patients with BVMD undergoing simultaneous multimodal fundus imaging and compare to those of normal age-matched subjects.MethodsComparative study including seven patients with BVMD (14 eyes) and seven age-matched healthy subjects (14 eyes). All participants were submitted to complete ophthalmological examination, fundus photography, and standardized multimodal fundus imaging protocol including Fourier-domain optical coherence tomography (Fd-OCT) combined with near-infrared reflectance and blue-light fundus autofluorescence (FAF).ResultsIn two eyes in the “subclinical” stage, Fd-OCT revealed thickening of the middle highly reflective layer (HRL) localized between the photoreceptors’ inner/outer segments junction (inner-HRL) and RPE/Bruch’s membrane reflective complex (outer-HRL) throughout the macula. In one eye in the “vitelliform” stage, a homogeneous hyper-reflective material on Fd-OCT was observed between the middle-HRL and outer-HRL; this material presented increased fluorescence on FAF. The outer nuclear layer (ONL) was thinned in the central macula and subretinal fluid was not identified in these earlier disease stages. In patients of “pseudohypopyon” (two eyes), “vitelliruptive” (eight eyes) and “atrophic” (one eye) stages, Fd-OCT revealed a variety of changes in the middle- and inner-HRLs and thinning of ONL. These changes were found to be associated with the level of visual acuity observed. Thickening of the middle-HRL was observed beyond the limits of the clinically evident macular lesion in all eyes.ConclusionsMultimodal fundus imaging demonstrated thickening of the reflective layer corresponding to the photoreceptors’ outer segments throughout the macula with no subretinal fluid accumulation as the earliest detectable feature in BVMD. Changes detected in the photoreceptors’ reflective layers (middle- and inner- HRLs) and ONL thinning seemed to be progressive with direct implications for the level of visual acuity impairment observed among the different stages of the disease.

Intravitreal injection of dispase causes retinal hemorrhages in rabbit and human eyes

Purpose. To check the effects of intravitreally injected dispase in the vitreo-retinal region. Methods. Dispase, 0.05 to 2.5 units dissolved in 100µl of phosphate-buffered saline, was injected into the midvitreous of rabbits which were killed from 15 to 120 min afterwards. The enzyme was also injected into four human eyes of patients with orbital tumors 15 min before enucleation during orbital exenteration surgery. The eyes were examined in vivo as well as by light and electron microscopy. Results. Hemorrhages were detected by fundus observations and confirmed by microscopical analysis in nearly all rabbits and in half of the human eyes. The red blood cells were observed in the vitreous and retina. Breaches in the inner limiting membrane were visualized in human eyes and ruptures of small blood vessels in rabbit eyes. In spite of that, vitreous detachment was not verified. In fact, the cortical-vitreous collagen-fibril network was conspicuous on scanning electron micrographs. Conclusions. Retinal hemorrhages were evident as early as 11 min after injection. It is suggested that this enzyme degraded selectively basement membrane components without affecting other proteins involved in the vitreous-retinal junction.