Carlos Eduardo Veloso

Homozygosity for the +674C>T polymorphism on VEGF gene is associated with age-related macular degeneration in a Brazilian cohort

PurposeTo investigate the association between VEGF gene polymorphism and age-related macular degeneration (AMD) in a Brazilian cohort.MethodsWe examined 160 affected individuals and 140 sex- and age-matched controls recruited at the Vision Institute and the Retina Department, São Geraldo Hospital, Minas Gerais Federal University, Brazil, between 2007 and 2011. Genotyping for the VEGF rs1413711 single nucleotide polymorphism (SNP) (+674C>T) was performed. The incidence rate ratios and 95% confidence interval (CI) for AMD for this genotype was calculated. The odds ratio (OR) was also assessed by using logistic regression, controlling for CFH and LOC387715 risk genotype.ResultsWe observed a prevalence of homozygosity (TT genotype) of 18.1% for rs1413711 among AMD cases compared with 5.8% among controls (P < 0.002). The ORs for this polymorphism were 3.6 (95%CI 1.6–8.2) for homozygous subjects and 1.5 (95%CI 1.1–2.1, P < 0.01) if the subject had at least one risk allele. When we studied separately exudative and dry AMD groups, this polymorphism was statistically significant for both groups. Controlling for CFH and LOC387715 risk genotype the OR was 3.0 for VEGF homozygous, and the OR increases if the patient is homozygous for the three genes.ConclusionThe present data suggests that VEGF TT genotype is associated with AMD among Brazilian patients.

Vitreomacular Interface after Anti–Vascular Endothelial Growth Factor Injections in Neovascular Age-Related Macular Degeneration

PURPOSE To evaluate the incidence of posterior vitreous detachment (PVD) induced by intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents in cases of neovascular age-related macular degeneration (AMD). DESIGN Cohort study conducted at a single tertiary referral vitreoretinal practice. PARTICIPANTS A total of 396 eyes of 295 patients were diagnosed with neovascular AMD between 2009 and 2014. A total of 125 eyes of 112 patients met the inclusion criteria and were evaluated in this study. METHODS This study included patients with neovascular AMD who presented vitreomacular adhesion (VMA) detected by spectral-domain optical coherence tomography (OCT) at baseline. Eyes with VMA were classified according to the diameter of vitreous attachment to the macular surface measured by OCT, with attachment of ≤1500 μm defined as focal and attachment of >1500 μm defined as broad. All patients received at least 3 monthly intravitreal injections of anti-VEGF agents. Follow-up visits were performed 1 month after each intravitreal injection and included OCT analysis to evaluate the incidence of PVD. MAIN OUTCOME MEASURES Posterior vitreous detachment induced by anti-VEGF injections. RESULTS The mean follow-up period was 21.3 months (range, 3-59 months). The mean number of intravitreal injections was 8.3 (range, 3-29 injections). Intravitreal drugs used in the study were ranibizumab (51.5%), bevacizumab (33.5%), and aflibercept (15.0%). Seven eyes (5.6%) developed PVD after intravitreal drug injection (3 eyes after the first intravitreal injection: bevacizumab in 1 and ranibizumab in 2; 2 eyes after the second injection: ranibizumab in 1 and bevacizumab in 1; 1 eye after the fourth injection: ranibizumab; and 1 eye after the sixth injection: aflibercept). A total of 118 eyes remained with persistent VMA. All 7 eyes that developed PVD were classified as having focal VMA, with the diameter of vitreous attachment ranging from 210 to 1146 μm (mean, 600 μm). CONCLUSIONS Intravitreal injections of commonly used anti-VEGF intravitreal drugs rarely induce PVD in patients with neovascular AMD. Eyes with focal VMA have a greater chance to develop PVD than eyes with a broad area of VMA.

VEGF Gene Polymorphism and Response to Intravitreal Ranibizumab in Neovascular Age-Related Macular Degeneration

Background/Aims: To investigate the association between VEGF gene polymorphism and response to ranibizumab in neovascular age-related macular degeneration (AMD). Methods: A total of 92 patients were genotyped for the VEGF rs1413711 single nucleotide polymorphism. Patients with neovascular AMD initially received 3 monthly ranibizumab intravitreal injections and were retreated as needed. Visual acuity (VA) and central retinal thickness (CRT) were measured before and 1, 3, 6 and 12 months after treatment. Results: For patients with TT and CT genotypes, paired comparisons of mean VA showed improvement when the data obtained at all visits were compared with baseline values, in contrast to patients with the CC genotype. CRT statistically improved at all visits for all genotypes. Conclusion: Patients with the CC genotype showed poorer long-term functional and anatomical response to anti-VEGF therapy.

Optical Coherence Tomography Angiography Imaging of Quiescent Choroidal Neovascularization in Age-Related Macular Degeneration.

A 67-year-old asymptomatic man presented with bilateral drusen. Spectral-domain optical coherence tomography (OCT) showed no signs of choroidal neovascularization (CNV) and no intraretinal or subretinal fluid. OCT angiography (OCTA) revealed the presence of a type 1 CNV in the right eye. Management options were discussed with the patient, who opted for a clinical follow-up. This is the first description demonstrating the OCTA characteristics of a quiescent CNV secondary to age-related macular degeneration.

Characteristics of Neovascular Age-Related Macular Degeneration in Brazilian Patients

Purpose: To report features of neovascular age-related macular degeneration (AMD) in Brazilian patients. Procedures: Data were prospectively collected from patients diagnosed with neovascular AMD. Eyes were classified as having typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), or retinal angiomatous proliferation (RAP). Results: In total, 265 eyes of 207 patients of predominantly Caucasian ancestry were included; 166 (62.6%) eyes had typical neovascular AMD, 65 (24.5%) eyes had PCV, and 34 (12.8%) eyes had RAP. RAP demonstrated a higher percentage of bilateral cases (p = 0.015). The mean foveal subfield thickness was significantly lower in eyes with PCV (p < 0.001). Cases with typical neovascular AMD had a higher percentage of predominantly classic and minimally classic lesions on fluorescein angiography (FA; p = 0.005). Conclusions: In Brazilian patients, PCV and RAP represented 24.5 and 12.8% of neovascular AMD cases. Neovascular AMD subtypes differ in relation to clinical features, mean foveal subfield thickness and FA presentation.

Choroidal neovascularization induced by immunogenic alteration of the retinal pigment epithelium in dengue Fever.

Purpose: To report the first case of choroidal neovascularization (CNV) secondary to dengue fever. Case Report: A 54-year-old female was referred to our department with blurred vision and metamorphopsia in her left eye. Two weeks earlier, she had presented all of the classic symptoms of dengue fever including a positive serology. Her best-corrected visual acuity (BCVA) was 20/150 in the left eye. She underwent a fundus examination, fluorescein angiography (FA) and spectral domain optical coherence tomography. Results: All findings were consistent with CNV secondary to dengue fever. FA revealed a classic CNV associated with focal retinal pigment epithelium (RPE) destruction and detachment. Three consecutive monthly injections of intravitreal ranibizumab resulted in functional and anatomical improvement for as long as 6 months with a BCVA of 20/25. However, CNV recurred 2 years later, again with an improvement after ranibizumab therapy, but with persistence of a fibrovascular RPE detachment, highlighting the pathomechanism of a classic CNV formation. Conclusions: Maculopathy in dengue fever may be followed by CNV as a result of the immunologic alteration of the RPE. Physicians should be aware of this manifestation to be able to initiate adequate treatment with excellent functional and anatomical results.

Importance of genetic polymorphisms in the response to age-related macular degeneration treatment

Age-related macular degeneration (AMD) is a degenerative disorder that affects the central retina and involves the Bruchs membrane, the retinal pigment epithelium and the photoreceptors. Recent studies have shown that polymorphisms of the CFH, LOC387715 and VEGF genes are associated with AMD. Herein, we review the literature to analyze the association between the main genetic polymorphisms and the response to the existing therapeutic modalities. Patients with CFH high-risk alleles show a poorer response to preventive treatment of AMD with antioxidants and zinc.The association between genetic polymorphisms and response to photodynamic therapy and antiangiogenic drugs, however, is controversial until now.

CFH Y402H polymorphism and response to intravitreal ranibizumab in Brazilian patients with neovascular age-related macular degeneration.

OBJECTIVE To investigate the association between CFH gene polymorphism and response to ranibizumab in Brazilian patients with neovascular age-related macular degeneration (AMD). METHODS 95 patients were genotyped for the CFH rs1061170 (Y402H) single nucleotide polymorphism. Patients with neovascular AMD initially received intravitreal ranibizumab injections for three months and were retreated as needed. Visual acuity (VA) and central retinal thickness (CRT) were measured before treatment and at 1, 3, 6, and 12 months post-treatment. RESULTS For patients with the TT and TC genotypes, paired comparisons of VA showed a statistically significant improvement when the data obtained at all visits were compared with baseline. Patients homozygous for the risk genotype (CC) did not show a statistically significant improvement when VA obtained at visits 1, 3, 6 and 12 were compared with baseline. For all genotypes, paired comparisons of CRT showed a statistically significant improvement when the data obtained at visits 1, 3, 6 and 12 were compared with baseline. CONCLUSION Patients with the CC genotype showed poorer long-term functional response to intravitreal ranibizumab.

Intravitreal Bevacizumab for Type 2 Idiopathic Macular Telangiectasia

Background/Aims: The aim of this paper is to report the treatment of type 2 nonproliferative idiopathic macular telangiectasia (IMT) with intravitreal bevacizumab (IVB). Methods: Retrospective case series of 10 eyes of 5 patients with type 2 IMT. All patients received 3 monthly IVB injections. Visual acuity (VA), fluorescein angiography (FA) and optical coherence tomography (OCT) were performed at baseline and 4 weeks after each injection. Results: Four weeks after the third IVB injection, VA remained stable for all patients. All eyes showed some decrease in fluorescein leakage, and there was a mild decrease in central macular thickness. One year later, VA, OCT and FA findings returned to the baseline levels. Conclusion: IVB did not improve VA in cases of type 2 IMT.

Quantitative analysis of external limiting membrane, ellipsoid zone and interdigitation zone defects in patients with macular holes

PurposeTo investigate the correlation between the length of external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) defects and visual prognosis in patients undergoing macular hole (MH) surgery, using spectral-domain optical coherence tomography (SD-OCT).MethodsThis is a retrospective, consecutive, observational case series study. Fifty-two eyes of 52 patients with primary MH were evaluated. A quantitative analysis of ELM, EZ and IZ defects was performed preoperatively and at 3 and 6 months postoperatively using SD-OCT. The correlation between pre- and postoperative ELM, EZ and IZ defects and the best-corrected visual acuity (BCVA) was investigated.ResultsThe lengths of ELM, EZ and IZ defects correlated significantly with BCVA in each study period (P < 0.001). Preoperative measures of these band defects were also associated with visual outcomes 3 and 6 months after surgery (P < 0.05). Considering all preoperative parameters, the length of the ELM defect was the factor most strongly correlated with BCVA at 6 months (β = 0.643, P < 0.012). The integrity of the ELM was the only factor significantly associated with BCVA at 6 months (β = 0.427; P = 0.004).ConclusionsThe preoperative length of the ELM defect is the strongest predictor of visual acuity after MH surgery. Postoperative integrity of the ELM is significantly associated with visual restoration after surgical treatment of MH.