Ângela Carneiro

Vascular endothelial growth factor plasma levels before and after treatment of neovascular age-related macular degeneration with bevacizumab or ranibizumab

Purpose: To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of ranibizumab or bevacizumab in patients with exudative age‐related macular degeneration (AMD).

Intravitreal ranibizumab for myopic choroidal neovascularization: 12-month results

Purpose: The purpose of this study was to evaluate the safety and efficacy of intravitreal ranibizumab after 12 months in the treatment of choroidal neovascularization secondary to pathologic myopia. Methods: This was a prospective, multicenter, consecutive, nonrandomized, interventional case series. The study included 34 eyes of 32 patients with choroidal neovascularization secondary to pathologic myopia; 13 eyes had previous photodynamic therapy, and 21 eyes had no previous treatment. The patients were followed for ≥12 months. Best-corrected visual acuity, optical coherence tomography, and the presence of metamorphopsia were assessed monthly. Results: Mean visual acuity improved 8 letters from baseline to 12-month follow-up, and the difference was statistically significant (P < 0.001): 100% of the eyes lost <3 lines on the Early Treatment Diabetic Retinopathy Study chart, 24% of the eyes improved ≥3 lines, 44% improved ≥2 lines, 65% improved ≥1 line, and 79% improved ≥0 lines. Central retinal thickness decreased significantly from baseline to the 12-month follow-up (P < 0.01). A mean of 3.6 treatments were performed during the 12-month follow-up, and no systemic or ocular side effects were registered during that time. Conclusion: One-year results of intravitreal ranibizumab for myopic choroidal neovascularization are very promising. Additional prospective studies are necessary to better determine long-term efficacy and safety.

Arterial Thromboembolic Events in Patients with Exudative Age-Related Macular Degeneration Treated with Intravitreal Bevacizumab or Ranibizumab

Background/Aims: To compare retrospectively the incidence of arterial thromboembolic events (ATEs) in patients treated with bevacizumab or ranibizumab for exudative age-related macular degeneration. Methods: Charts of 378 patients treated with at least 1 intravitreal injection of ranibizumab or bevacizumab were reviewed to calculate the incidence of ATEs. Only patients under monotherapy were analyzed. Results: ATEs occurred in 15 patients: 12 (12/97) with bevacizumab (12.4%) and 3 (3/219) with ranibizumab (1.4%) – odds ratio 10.16; 95% confidence interval 2.80–36.93; p < 0.0001. ATEs in the bevacizumab and ranibizumab cohorts included stroke, myocardial infarction, angina pectoris, peripheral thromboembolic disease, transient ischemic attack, sudden death and lethal stroke. Conclusion: In this series, bevacizumab raised the risk of ATEs when compared to ranibizumab. In an elderly population with multiple cardiovascular risk factors, the new ATEs may not be attributed exclusively to the intravitreal bevacizumab administration. These findings raise an issue that must be confirmed in randomized clinical trials.

Comparative effects of bevacizumab, ranibizumab and pegaptanib at intravitreal dose range on endothelial cells.

Anti-VEGF therapy proved to be useful against several ocular pathological situations, including choroidal neovascularization and proliferative retinopathies. Ranibizumab (Ran), Pegaptanib (Peg) and Bevacizumab (Bev) are the pharmacological agents more frequently used in clinical practice by intravitreal injection. However, their exact effects on the angiogenic process have not been accurately established in a comparative study. The aim of the present study was to elucidate the precise effects of Ran, Peg and Bev on the multiple steps of the angiogenic process. Human umbilical vein endothelial cells (HUVEC) were incubated with each agent within the clinically established concentration range, or identical amounts of the excipients; cell cytotoxicity, proliferation, apoptosis, migration and vessel assembly were assessed. No cytotoxic effects were found for any of the agents studied at any concentration tested. At the clinical dose, cell proliferation was significantly reduced by Bev and Ran, whereas no difference was observed after Peg treatment. In addition, HUVEC apoptosis was effectively increased by Bev and Ran. Cell migration was reduced after incubation with every agent analyzed, though only reaching statistical significance upon Ran intravitreal dose. At clinical doses, capillary assembly was only affected by Bev. In agreement with these data, the active form of VEGF receptor-2 expression was decreased after incubation with Bev (to 66% of control values), Ran (78%) and Peg (86%) relative to controls. These findings indicate that these three agents display distinct effects on endothelial cells.

Combination of Intravitreal Ranibizumab and Laser Photocoagulation for Aggressive Posterior Retinopathy of Prematurity

Purpose: To report on 2 cases of aggressive posterior retinopathy of prematurity (ROP) treated with intravitreal ranibizumab (Lucentis®) and laser photocoagulation. Methods: Two premature females, born at 25 and 26 weeks’ gestation with a birth weight of 530 and 550 g, respectively, with aggressive posterior ROP received combined treatment with laser photocoagulation and intravitreal ranibizumab (0.3 mg [30 µl]) to each eye. Structural outcomes were evaluated by indirect ophthalmoscopy and documented by retinography. Results: An intravitreal injection was made at 34 weeks of postmenstrual age in the first case, followed by laser photocoagulation 1 week later. There was a partial regression of ROP with treatment. Five weeks later, neovascularization regrowth with bleeding in both eyes (intraretinal and subhyaloid) occurred and retreatment with combined therapy was performed. In the second case, single therapy with laser photocoagulation was made at 34 weeks of postmenstrual age. In spite of the confluent photocoagulation in the avascular area, progression to 4A ROP stage occurred 1 week later. Both eyes were retreated 1 week later with intravitreal ranibizumab and laser photocoagulation. Treatment resulted in ROP regression in both cases. There were no signs of systemic or ocular adverse side effects. Conclusion: The cases presented show that combination therapy of indirect laser photocoagulation and intravitreal ranibizumab can be effective in the management of aggressive posterior ROP. Further investigation on anti-VEGF safety in premature infants is necessary . Additional studies are needed to define the role of anti-VEGF in ROP treatment.

Spectral-Domain Optical Coherence Tomography Features of Acute Syphilitic Posterior Placoid Chorioretinitis: The Role of Autoimmune Response in Pathogenesis

Purpose: Syphilis is an infectious disease that can cause a wide variety of ocular signs. One of the rarest manifestations of ocular syphilis is acute syphilitic posterior placoid chorioretinitis (ASPPC). We report on the spectral-domain optical coherence tomography (SD-OCT) features of a case diagnosed with unilateral ASPPC. Methods: A 64-year-old man presented with a sudden loss of visual acuity (VA) in the right eye. His only clinical sign was a large, geographic, yellow-white lesion centered on the right fovea. Our patient was studied with SD-OCT on presentation and during follow-up, as well as with fluorescein and indocyanine green angiography, electrophysiological study, and serologic and autoimmune screening. Results: Laboratory workup revealed positive serology for active syphilis and elevated anti-beta2 glycoprotein I antibodies. SD-OCT showed a marked distortion of both the choroidal and outer retinal architecture. After treatment, best-corrected VA improved to 20/25. Pattern electroretinography displayed a severe reduction of P50 amplitude, which improved in late follow-up. Six months after presentation, VA was 20/25 and anti-beta2 glycoprotein I antibodies returned to normal levels. Conclusions: Our findings are compatible with immunologically mediated temporary physiological impairment of the neuroretina, since the changes seen by SD-OCT could not have normalized if they were due to anatomical injury. The results of our study provide clues to understanding the pathogenesis of this disease and allow us to define a characteristic temporal sequence of events in ASPPC.

Switch to Aflibercept in the Treatment of Neovascular AMD: One-Year Results in Clinical Practice

Purpose: To report the clinical outcomes of intravitreal aflibercept therapy in eyes with refractory and recurrent neovascular age-related macular degeneration (AMD) switched from intravitreal bevacizumab or ranibizumab. Methods: This is a retrospective review of eyes with neovascular AMD switched to intravitreal aflibercept with at least 1 year of follow-up after the switch. All patients had had a minimum of 3 injections of bevacizumab or ranibizumab before the switch. Aflibercept was used in patients considered refractory to bevacizumab (group 1) and in recurrent patients on therapy with ranibizumab due to an institutional policy decision (group 2). Changes in best-corrected visual acuity, fluid on optical coherence tomography (OCT), central retinal thickness (CRT) and the frequency of injections were compared. Results: Eighty-five eyes of 69 patients were analyzed, 39 eyes in group 1 and 46 in group 2. The mean follow-up time was 31.6 months prior to the switch and 14.7 months on treatment with aflibercept. One year after the switch, there was a nonsignificant mean decrease of 2 letters in visual acuity in both groups (group 1: from 58.2 to 55.8 letters, p = 0.086; group 2: from 56.4 to 54.5 letters, p = 0.168), but the mean number of injections per month was significantly lower (from 0.76 to 0.57, p < 0.001). With the switch, 90.6% of the patients showed anatomic improvement with a reduction of fluid on OCT, and both groups presented significant improvement in CRT (group 1: 65.3 µm, p = 0.051; group 2: 91.0 µm, p < 0.001). Conclusion: Aflibercept appears to be a valuable tool for the management of patients with poor responses to other anti-vascular endothelial growth factor drugs. These patients could have anatomic improvement, and the injection intervals could be extended.

Anti-VEGF Therapy in Myopic Choroidal Neovascularization: Long-Term Results

Purpose: To evaluate the medium- and long-term efficacy of anti-VEGF agents in the treatment of choroidal neovascularization secondary to pathologic myopia (mCNV). Methods: We performed a retrospective analysis of patients with mCNV who had been treated with intravitreous anti-VEGF for at least 2 years. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared before and after the treatment. The number of injections per year was also assessed. Results: The results were analysed at 2 years for 67 eyes, at 3 years for 52 eyes, at 4 years for 28 eyes and at 5 years for 13 eyes. The mean change from baseline BCVA was significant at 2 years (+8.6 letters; p < 0.001) and this gain remained significantly stable for a period of 5 years. The mean CRT showed a significant decrease over time, with a nadir at 2 years (-104.0 μm; p < 0.001). The mean number of injections performed during the first year was 5.2, being lower in subsequent years (p < 0.001). Conclusion: In this subset of patients with mCNV, an intravitreous therapy with anti-VEGF agents proved to have effective results over 5 years, with a sustained increase in BCVA.

Isolated Foveal Hypoplasia: Tomographic, Angiographic and Autofluorescence Patterns

Purpose. To report clinical aspects, tomographic, angiographic, and autofluorescence patterns of two cases of isolated foveal hypoplasia. Methods. Foveal hypoplasia was found in a 23-year-old male patient and in a 64-year-old woman with impaired visual acuity of unknown etiology that remained unchanged for years. Results. In the first case, spectral-domain optical coherence tomography (SD-OCT) showed reduced foveal pit and continuity of inner retinal layers in the fovea. Photoreceptor layer had a normal thickness centrally. The foveal avascular zone (FAZ) was absent in the flourescein angiogram (FA). Fundus autofluorescence showed reduced foveal attenuation of autofluorescence. In the second patient, there was the same pattern in SD-OCT, with normal aspect in FA and only a slightly reduced foveal attenuation of autofluorescence. Conclusion. OCT, as a noninvasive and quick method, is helpful in the diagnosis of foveal hypoplasia. FA and fundus autofluorescence were less sensitive.

Multimodal Image Analysis in Acquired Vitelliform Lesions and Adult-Onset Foveomacular Vitelliform Dystrophy

Purpose. To characterize vitelliform lesions (VLs) in adult-onset foveomacular vitelliform dystrophy (AOFVD) and acquired vitelliform (AVL) patients using multimodal image analysis. Methods. Retrospective study of twenty-eight eyes from nineteen patients diagnosed with AVL or AOFVD. They were evaluated by color fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA), and spectral-domain optical coherence tomography (SD-OCT). Results. Bilateral VLs were associated with AOFVD (p = 0.013). Regular and centered VLs were associated with AOFVD (p = 0.004 and p = 0.016), whereas irregular and noncentered lesions were more frequent in AVL patients. Visual acuity, greatest linear dimension (GLD), lesion height (LH), and pseudohypopyon were similar between groups. Whereas median LH and GLD in AVL group diminished significantly during follow-up (p = 0.009 and p = 0.001), AOFVD lesions tended to become larger and thicker. Conclusions. When consulting a patient presenting a VL with unknown age of onset, familial history, or previous retinal diseases, some aspects of multimodal imaging assessment may lead the ophthalmologist to a correct diagnosis.