Eduardo Büchele Rodrigues

Pathogenesis and classification of proliferative diabetic vitreoretinopathy

Purpose: To review the current knowledge regarding the pathogenesis of proliferative diabetic vitreoretinopathy (PDVR) and to present recommendations for its clinical staging. Design: Focused literature review and authors’ clinical experience. Results: Although several biochemical mediators may be responsible for the pathogenesis of PDVR, no common biochemical pathway exists. Of those mediators, vascular endothelial growth factor is the one most studied so far. However, since in proliferative diabetic retinopathy (PDR) the thickened posterior vitreous cortex is one of the main factors in the development of proliferations, a consequent shrinkage of the posterior vitreous cortex leads to hemorrhages and tractive retinal detachments. Therefore, PDR should be called PDVR. In consequence, the authors present a new morphological classification of PDVR. Conclusions: There is no consensus about the biochemical pathway responsible for the progression of PDVR. Although several classifications are described in the literature, the classification suggested here is important in the judgment of, the communication about and the therapy of diabetic retinopathy. Furthermore, it is the only reliable classification for predicting the surgical outcome in diabetics.

Primary vitrectomy in complicated rhegmatogenous retinal detachment--a survey of 205 eyes.

Introduction: In a few types of rhegmatogenous retinal detachment (RRD), scleral buckling (SB) has a lower success, and, here, pars plana vitrectomy (PPV) is a good alternative option. This survey reviews the indications and the surgical outcome of primary PPV with internal tamponade. Patients and Methods: We reviewed 205 eyes operated by primary PPV for RRD at the Department of Ophthalmology of the Philipps University Marburg between the years 1990 and 1997. The indications of PPV were: holes greater than 90°; holes posterior to the equator; proliferative vitreoretinopathy grade C; pseudophakic status. Results: A complete reattachment of the retina after absorption of the gas or after silicone oil removal was achieved by 1 operation in 146 eyes (71.2%) and in 195 eyes (95.2%) by a second intervention. Conclusion: Although SB is the standard procedure for the treatment of RRD, complicated cases can be treated successfully with primary PPV.

INTRAVITREAL INJECTIONS OF ZIV-AFLIBERCEPT FOR DIABETIC MACULAR EDEMA: A Pilot Study.

Purpose: Diabetic macular edema is the leading cause of blindness in young adults in developed countries. Beyond metabolic control, several therapies have been studied such as laser treatment and intravitreal injections of corticosteroids or anti–vascular endothelial growth factor drugs. In terms of public health the long-term treatment with the current available drugs is very expensive and new therapies with the same or better effect should be investigated. This study sought to evaluate the efficacy and safety of intravitreal injections of ziv-aflibercept for the treatment of diabetic macular edema. Methods: Seven consecutive patients with diabetic macular edema were enrolled. A complete examination, including full-field electroretinography, visual acuity, central retinal thickness, and evaluation of systemic and ocular complications, was performed before and at 24 weeks after intravitreal injections of ziv-aflibercept. The seven patients were submitted to six consecutive intravitreal injections of ziv-aflibercept with a 4-week interval. Results: No significant differences were found in the amplitude or implicit time of any electroretinography component after intravitreal injections of ziv-aflibercept, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at 24 weeks (P < 0.05). The central retinal thickness significantly decreased during the course of 24 weeks. Conclusion: Intravitreal injections of ziv-aflibercept seem to be a safe and effective treatment option for diabetic macular edema.

Intravitreal Injection of Ziv-Aflibercept in Patient With Refractory Age-Related Macular Degeneration

The results of a patient with exudative age-related macular degeneration who received an intravitreal injection of ziv-aflibercept (Zaltrap; Sanofi-Aventis, Paris, France) in the right eye are described. A complete ocular examination as well as color fundus photography, optical coherence tomography, fluorescein angiography, microperimetry, full-field electroretinography, and multifocal electroretinography were performed and repeated 1 month later. The patient experienced subjective and objective improvement of visual acuity with a decrease in intraretinal and subretinal fluid. Microperimetric improvement also occurred. Electroretinographic changes were noted from baseline to the 30-day follow-up. No adverse events were observed at any time point. Ziv-aflibercept demonstrated short-term safety and efficacy after intravitreal administration for neovascular macular degeneration.

Preclinical investigations of intravitreal ziv-aflibercept.

BACKGROUND AND OBJECTIVE To investigate the retinal safety of intravitreal (IVT) ziv-aflibercept in rabbits. MATERIALS AND METHODS Eighteen rabbits were given an IVT injection of ziv-aflibercept (25 mg/mL) or aflibercept (40 mg/mL) and examined by funduscopy, electroretinography (ERG), optical coherence tomography (OCT), light microscopy, and transmission electron microscopy (TEM). Serum, aqueous, and vitreous were obtained afterward for osmolarity analysis. The effect of ziv-aflibercept on human retinal cultured cells (ARPE-19) was assessed by the MTT cell viability assay. RESULTS All eyes showed normal funduscopy, OCT, and ERG findings at baseline and 24 hours or 7 days after the procedure. Median baseline serum, vitreous, and aqueous osmolarity remained unchanged. Histology and TEM showed no major anatomic signs of toxicity. No cytotoxic effect was observed in ARPE-19 cells exposed to ziv-aflibercept. CONCLUSION IVT injection ziv-aflibercept at a concentration of 25 mg/mL proved to be safe for the rabbit retina.

Posterior hyaloid detachment and internal limiting membrane peeling assisted by anthocyanins from acai fruit (Euterpe oleracea) and 10 other natural vital dyes: experimental study in cadaveric eyes.

Purpose: The purpose of this study was to determine whether natural dyes facilitate posterior hyaloid detachment (posterior vitreous detachment [PVD]) and retinal internal limiting membrane (ILM) peeling in human eyes. Methods: Open-sky vitrectomy with posterior hyaloid and ILM removal was performed in 86 human cadaveric eyes. After core vitrectomy, 11 different dyes were injected into the vitreous cavity to aid hyaloid detachment and ILM removal. The dyes were allowed to settle on the macula for 5 minutes after PVD and were removed by mechanical aspiration. Intraocular forceps were used for ILM peeling, which was confirmed by light microscopy of the peeled tissue. Acai fruit (Euterpe oleracea) extract and 10 additional dyes from plants or animal sources were tested: pomegranate (Punica granatum), logwood (Haematoxylum campechianum), chlorophyll extract from alfalfa (Medicago sativa), cochineal (Dactylopius coccus), hibiscus (Hibiscus rosa-sinensis), indigo (Indigofera tinctoria), paprika (Capiscum annuum), turmeric (Curcuma longa), old fustic (Maclura tinctoria), and grape (Vitis vinifera). Results: The dyes facilitated PVD and ILM peeling. Acai fruit (E. oleracea) extract, logwood (H. campechianum), cochineal (D. coccus), and old fustic (M. tinctoria) facilitated PVD in all cases; dye-assisted PVD was compared with triamcinolone-assisted PVD performed previously in a comparative model. Acai fruit (E. oleracea) extract, cochineal (D. coccus), and chlorophyll extract from alfalfa (M. sativa) showed the best capability for ILM staining; dye-assisted ILM removal was compared with the ILM peeling guided by indocyanine green staining performed previously in a comparative model. Light microscopy confirmed the ILM removal in all cases. Conclusion: Anthocyanin dye of the acai fruit (E. oleracea) and the dyes from cochineal (D. coccus) and chlorophyll extract from alfalfa (M. sativa) resulted in the best capability for posterior hyaloid and ILM staining in human cadaveric eyes and may be a useful tool for vitreoretinal surgery.

Prevalência de retinopatia diabética na população portadora de diabetes mellitus tipo 2 do município de Luzerna - SC

PURPOSE To evaluate the prevalence of diabetic retinopathy in patients affected by type 2 diabetes mellitus in the city of Luzerna (SC). METHODS Cross-sectional study including all individuals with type 2 diabetes mellitus, all ages, both genders, residents in the city of Luzerna. The work analyzed database of 5,350 people from two Family Health Programs, where all city residents are registered. A total of 136 people with type 2 diabetes mellitus were encountered and 120 completed data gathering to the end, resulting in an inclusion rate of 89%. All patients underwent ophthalmologic examination for diagnosis of retinopathy and visual acuity examination. Patients underwent a household questionnaire to evaluate the demographic profile, duration of disease and type of treatment performed. The presence of risk factors for diabetic retinopathy: hypercholesterolemia, fasting plasma glucose, glycosylated hemoglobin and hypertension were also assessed. RESULTS The prevalence of diabetic retinopathy was 38.4% in the studied population. Moreover, a direct relationship was established between diabetic retinopathy and diabetes mellitus evolution time (p<0.0001), renal damage (p<0.0001), insulin use (p<0.0001) and glycosylated hemoglobin change (p=0.003). There was no correlation between diabetic retinopathy and hypertension (p=0.184), hypercholesterolemia (LDL p=0.745, TGC=0.163, CT=0.528), gender (p=0.299) and origin (p=0.889). CONCLUSION The prevalence of diabetic retinopathy found among the patients with type 2 diabetes mellitus was of 38.4%. This result confirms the need for greater attention by public services in prevention and counseling patients with type 2 diabetes, in order to achieve early diagnosis and disease prevention.

Clinical And Electrophysiological Evaluation After Intravitreal Ziv-aflibercept For Exudative Age-related Macular Degeneration

Purpose: To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. Methods: Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. Results: Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P < 0.0001) from 9.51 ± 1.36 mm3 to 8.08 ± 1.34 mm3, and the a-wave implicit time increased, with no differences in the other full-field electroretinography parameters. The average multifocal electroretinography macular responses within the first central 15° showed significantly (P < 0.05) increased P1 amplitudes at 26 weeks. No systemic or ocular complications developed. Conclusion: Intravitreal ziv-aflibercept significantly improved the best-corrected visual acuity, multifocal electroretinography amplitudes, central retinal thickness, and total macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.

Is membrane extraction in cases of exudative age-related macular degeneration still up-to-date? A 4-year résumé

Background: Age-related macular degeneration (AMD) is a frequent cause of an irreversible loss of the ability to read. The non-exudative form of AMD has not been therapeutically approached in the past in contrast to the exudative form with choroidal neovascularizations (CNVs). Parafoveal laser coagulation can be applied, and in cases of subfoveal location a pars plana vitrectomy with subretinal resection of the CNV is possible. Material and Methods: Since 1995, we have operated 46 eyes of 45 patients with CNV developing from AMD. Patient ages ranged from 63 to 85 years (mean 71.8 years). Pre- and postoperatively we performed vision tests, fluorescence angiographies with sodium fluorescein and indocyanine green. Follow-up times ranged from 3 to 28 months (mean 12.3 months). Results: Pre-operative vision was 0.10 (range: hand movements to 0.4). Postoperative vision at the end of the follow-up period was 0.12 (range: hand movements to 0.4). Vision at the end of the follow-up was lower in 41%, unchanged in 20% and improved in 39%. In 43 eyes, a non-exudative form of AMD developed. Two eyes had a recurrent CNV, which was removed successfully with a second pars plana vitrectomy. Three patients developed a retinal detachment, which was successfully treated by pars plana vitrectomy, encircling buckle and gas tamponade. Conclusions: We still have to wait for the results of the photodynamic study trials and a randomized study of macular dislocation. Subretinal removal of the CNV by pars plana vitrectomy allows a stabilization of the visual function in most of our cases of AMD. This method inhibits the development of large pseudotumour-like scars. Postoperatively remaining pigment epithelial defects with choroidal atrophies however limit a visual rehabilitation so that reading vision can only be achieved in cases with good pre-operative vision. Long-term results of photodynamic therapy are still lacking and have to show its effectiveness over greater time spans.

Correlation Between Choroidal Thickness and Ciliary Artery Blood Flow Velocity in Normal Subjects

BACKGROUND AND OBJECTIVE To study the correlation between the choroidal thickness (CT) measured by spectral-domain optical coherence tomography (SD-OCT) and retrobulbar blood flow measured by color Doppler flowmetry (CD) in normal subjects. PATIENTS AND METHODS Healthy subjects underwent enhanced-depth imaging SD-OCT and CD using a linear 6 MHz to 18 MHz transducer. The maximal peak systolic velocity and resistance index (RI) were obtained for the ophthalmic artery (OA), short posterior ciliary artery (SPCA), and central retinal artery (CRA) and correlated with the subfoveal CT measured by SD-OCT. RESULTS Twenty-seven eyes of 27 healthy patients were enrolled (mean age: 40.6 ± 12.4 years; range: 27-68 years). An inverse proportional relationship (P = .0496) was identified between the RI of the SPCA (mean, 0.6117 ± 0.07911) and the subfoveal CT (319.9 µm ± 83.79 µm) but not between the RI and the OA (mean: 0.7019 µm ± 0.07317 µm) or the CRA (mean: 0.68843 µm ± 0.08994 µm). CONCLUSION The results of this study suggested there is an inverse proportional relationship between the RI of the SPCA and the subfoveal CT. The data also suggested a correlation between a decrease in the CT and increased RI in the retrobulbar arteries. Therefore, lower choroidal blood flow may explain the thinner CT in normal subjects.