Evaluation of contrast sensitivity in non-high-risk proliferative diabetic retinopathy treated with panretinal photocoagulation with and without intravitreal injections of ranibizumab / Avaliação da sensibilidade ao contraste em retinopatia diabética proliferativa de não alto risco tratada com panfotocoagulação retiniana com ou sem injeções intravítrea de ranibizumabe

ABSTRACT Purpose: To evaluate contrast sensitivity in non-high-risk, treatment-naïve proliferative diabetic retinopathy patients treated with panretinal photocoagulation and intravitreal injections of ranibizumab) versus panretinal photocoagulation alone. Methods: Sixty eyes of 30 patients with bilateral proliferative diabetic retinopathy were randomized into two groups: one received panretinal photocoagulation and ranibizumab injections (study group), while the other received panretinal photocoagulation alone (control group). All eyes were treated with panretinal photocoagulation in three sessions according to the Early Treatment Diabetic Retinopathy Study guidelines. Contrast sensitivity measurements were performed under photopic conditions (85 cd/m2) with the Visual Contrast Test Sensitivity 6500 chart, allowing for the evaluation of five spatial frequencies with sine wave grating charts: 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). Outcomes were measured in contrast sensitivity threshold scores among and within groups, from baseline to 1, 3, and 6 months. Results: Fifty-eight eyes (28 in the study group and 30 in the control group) reached the study endpoint. A comparative analysis of changes in contrast sensitivity between the groups showed significant differences mainly in low frequencies as follows: at month 1 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.04); at month 3 in 1.5 cpd (p=0.016), and at month 6 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.026) in favor of the study group. Conclusions: In eyes of patients with non-high-risk proliferative diabetic retinopathy, panretinal photocoagulation treatment with ranibizumab appears to cause less damage to contrast sensitivity compared with panretinal photocoagulation treatment alone. Thus, our evaluation of contrast sensitivity may support the use of ranabizumab as an adjuvant to panretinal photocoagulation for the treatment of proliferative diabetic retinopathy.

RESUMO Objetivos: Avaliar a sensibilidade ao contraste em pacientes virgens de tratamento com retinopatia diabética proliferativa de não alto risco, submetidos a panfotocoagulação retiniana com injeções intravítreas de ranibizumabe versus pan­fotocoagulação isolada. Métodos: Sessenta olhos de 30 pa­cientes foram randomizados em dois grupos: um submetido a panfotocoagulação com injeções de ranibizumabe (grupo estudo), e o outro submetimedo a panfotocoagulação isolada (grupo controle). Todos olhos foram tratados em 3 sessões de laser, seguindo recomendação do Early Treatment Diabetic Retinopathy Study (ETDRS). Avaliação da sensibilidade ao contraste foi realizada sob condições fotópicas (85 cd/m2) com tabela Visual Contrast Test Sensitivity 6500, permitindo avaliação de cinco frequências espaciais medidas com redes senoidais: 1.5, 3.0, 6.0, 12.0 e 18.0 ciclos por grau de ângulo visual (cpd). Foram realizadas medidas dos limiares de sensibilidade ao contraste intra e entre grupos na visita inicial, no 1º, 3º, e 6º mês de seguimento. Resultados: Cinquenta e oito olhos, 28 do grupo estudo e 30 do grupo controle, atingiram o término do estudo. Análise comparativa da SC entre os grupos mostrou diferença estatisticamente significante, nas baixas frequências espaciais, no 1º mês em 1.5 cpd (p=0,001) e 3.0 cpd (p=0,04), no 3º mês em 1.5 cpd (p=0,016) e no 6º mês em 3.0 cpd (p=0,026) a favor do grupo estudo. Conclusão: O tratamento com panfotocoagulação associada a injeção de ranibizumabe parece causar menos danos a sensibilidade ao contraste quando comparada com panfotocoagulação isolada em olhos com retinopatia diabética proliferativa de não alto risco. Dessa forma, os resultados apresentados podem justificar a associação do ranibizumabe à panfotocoagulação nestes pacientes.

Evaluation of contrast sensitivity in non-high-risk proliferative diabetic retinopathy treated with panretinal photocoagulation with and without intravitreal injections of ranibizumab.

PURPOSE: To evaluate contrast sensitivity in non-high-risk, treatment-naïve proliferative diabetic retinopathy patients treated with panretinal photocoagulation and intravitreal injections of ranibizumab) versus panretinal photocoagulation alone. METHODS: Sixty eyes of 30 patients with bilateral proliferative diabetic retinopathy were randomized into two groups: one received panretinal photocoagulation and ranibizumab injections (study group), while the other received panretinal photocoagulation alone (control group). All eyes were treated with panretinal photocoagulation in three sessions according to the Early Treatment Diabetic Retinopathy Study guidelines. Contrast sensitivity measurements were performed under photopic conditions (85 cd/m2) with the Visual Contrast Test Sensitivity 6500 chart, allowing for the evaluation of five spatial frequencies with sine wave grating charts: 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). Outcomes were measured in contrast sensitivity threshold scores among and within groups, from baseline to 1, 3, and 6 months. RESULTS: Fifty-eight eyes (28 in the study group and 30 in the control group) reached the study endpoint. A comparative analysis of changes in contrast sensitivity between the groups showed significant differences mainly in low frequencies as follows: at month 1 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.04); at month 3 in 1.5 cpd (p=0.016), and at month 6 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.026) in favor of the study group. CONCLUSIONS: In eyes of patients with non-high-risk proliferative diabetic retinopathy, panretinal photocoagulation treatment with ranibizumab appears to cause less damage to contrast sensitivity compared with panretinal photocoagulation treatment alone. Thus, our evaluation of contrast sensitivity may support the use of ranabizumab as an adjuvant to panretinal photocoagulation for the treatment of proliferative diabetic retinopathy.

Short-term effects of intravitreal bevacizumab in contrast sensitivity of patients with diabetic macular edema and optimizing glycemic control.

AIMS: To analyze contrast sensitivity of intravitreal bevacizumab injections with optimizing glycemic control versus optimizing glycemic control (in combination with sham injections) in eyes with Diabetic Macular Edema (DME). DESIGN: Prospective, interventional, masked, randomized controlled trial. METHODS: Forty-one eyes of 34 patients with type 2 diabetes mellitus and DME with glycated hemoglobin (HbA1c) < 11% received either intravitreal bevacizumab injection (Group 1) or sham injection (Group 2) at 0 and 6 weeks along with optimizing glycemic control. Mean change in best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT)-measured by central macular thickness (CMT) were compared and correlated at baseline, 2, 6 and 12 weeks. RESULTS: The study showed a mean CS improved in group 1 from 1.14 ±â€¯0.36 logCS to 1.32 ±â€¯0.24 logCS and also in group 2 from 1.11 ±â€¯0.29 logCS to 1.18 ±â€¯0.29 logCS at 12 weeks (P = 0.12). CS and CMT promptly decreased in group 1 compared to group 2 at 2 weeks (ΔCS = 0.15 ±â€¯0.25 vs. 0.03 ±â€¯0.15 logCS; P = 0.04; ΔCMT = 116 ±â€¯115 vs. 17 ±â€¯71 µm; P = 0.01). There was a mean reduction of approximately 0.5% in HbA1c levels in both groups at 12 weeks (P = 0.002). CONCLUSION: The use of bevacizumab in combination with optimizing glycemic control results in earlier improvement of contrast sensitivity in type 2 diabetes patients with DME. However, the optimizing glycemic control itself has shown also to be effective at 12 weeks. ClinicalTrials.gov Identifier: NCT02308644.

Association of the CFH Y402H Polymorphism with the 1-Year Response of Exudative AMD to Intravitreal Anti-VEGF Treatment in the Brazilian Population.

AIM: Evidence of the relationship between the polymorphism of the complement factor H (CFH) gene at position 402 (Y402H) and the response to the treatment of wet AMD is controversial. The aim of this study was to compare the functional and morphological 1-year evolution of patients with exudative AMD treated with antivascular endothelial growth factor (VEGF) drugs with the CFH Y402H polymorphism in the Brazilian population. METHODS: Forty-six patients treated for wet AMD with bevacizumab or ranibizumab in a pro re nata regimen were included. The evolution of best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and the number of injections over 1 year of follow-up were correlated with CFH genotypes. RESULTS: The analysis of variance for the difference between the BCVA denoted as logMAR (logarithm of the minimum angle of resolution) values showed an improvement at 1 year when compared to baseline (p = 0.039). Profile contrast analysis showed that this difference was significant only in the group without the C allele (p = 0.049), without significance in patients presenting with the risk allele (p = 0.241). CRT showed a mean reduction at 1 year compared to baseline (p < 0.001). Significant differences in the profile contrast test were found in the group without the C allele (p < 0.001) and in patients with the risk allele (p = 0.002). No difference was found in the number of injections among the different groups (p = 0.787). CONCLUSIONS: The presence of the risk allele of the Y402H polymorphism in the CFH gene was related to a less favorable evolution over 1 year in this sample of the Brazilian population with exudative AMD who were being treated with anti-VEGF drugs. In agreement with similar previous studies, this study concludes that the CFH risk genotypes may affect the disease response to treatment.

Pharmacogenetic Effect of Complement Factor H Gene Polymorphism in Response to the Initial Intravitreal Injection of Bevacizumab for Wet Age-Related Macular Degeneration.

PURPOSE: To compare the functional and morphological response to the initial intravitreal (IVT) injection of bevacizumab in exudative age-related macular degeneration (AMD) patients with the complement factor H (CFH) gene polymorphism T1277C in the Brazilian population. METHODS: Twenty-five unrelated patients with treatment-naive exudative AMD underwent an IVT injection of 1.25 mg bevacizumab at the initial presentation (D0) and were reexamined 7 days (D7) and 28 days (D28) later. The time and extent of visual acuity (VA) and central retinal thickness (CRT) changes were evaluated according to the presence of the T1277C polymorphism. RESULTS: In the homozygous risk group (CC), VA improvement was detected mostly from D7 to D28, while in the heterozygous (CT) and homozygous for the wild-type allele (TT) groups, functional response occurred earlier, from D0 to D7. Morphological response to the first IVT injection of bevacizumab was significant in the CT and TT groups, while the CC group presented no significant change in CRT up to D28. CONCLUSION: The CC variant of the CFH gene polymorphism T1277C is related to delayed functional and limited morphological response to the initial IVT injection of bevacizumab in exudative AMD patients in a sample of the Brazilian population.

A randomized controlled trial of panretinal photocoagulation with and without intravitreal ranibizumab in treatment-naive eyes with non-high-risk proliferative diabetic retinopathy.

PURPOSE: To compare the efficacy of panretinal photocoagulation (PRP) and intravitreal ranibizumab injection with PRP alone in patients with treatment-naive bilateral non-high-risk proliferative diabetic retinopathy. METHODS: Sixty eyes of 30 patients were randomized either to the study group (SG) receiving PRP plus 2 ranibizumab injections or to the control group (CG) receiving PRP alone. Mean change in best-corrected visual acuity and in optical coherence tomography were compared at baseline and 1, 3, and 6 months. RESULTS: Best-corrected visual acuity was significantly better at 6 months in the SG; however, there was decrease in best-corrected visual acuity in the CG. Central macula thickness decreased significantly at 6 months in SG when compared with baseline (-47.6 µm, P < 0.001) and did not reveal significant difference in the CG. In eyes with diabetic macular edema, best-corrected visual acuity increased by 3.6 letters (P = 0.06) in the SG and decreased by 4.4 letters in the CG (P = 0.003). Central macula thickness decreased by 69.3 µm (P = 0.001) in the SG and decreased by 45.5 µm (P = 0.11) in the CG. CONCLUSION: Intravitreal ranibizumab in combination with PRP can be an effective treatment in eyes with non-high-risk proliferative diabetic retinopathy and diabetic macular edema.

Single intravitreal bevacizumab injection effects on contrast sensitivity in macular edema from branch retinal vein occlusion.

PURPOSE: To evaluate the effect of a single intravitreal bevacizumab injection on visual acuity, contrast sensitivity and optical coherence tomography-measured central macular thickness in eyes with macular edema from branch retinal vein occlusion. METHODS: Seventeen eyes of 17 patients with macular edema from unilateral branch retinal vein occlusion were treated with a single bevacizumab injection. Patients were submitted to a complete evaluation including best corrected visual acuity, contrast sensitivity and optical coherence tomography measurements before treatment and one and three months after injection. Visual acuity, contrast sensitivity and optical coherence tomography measurements were compared to baseline values. RESULTS: Mean visual acuity measurement improved from 0.77 logMAR at baseline to 0.613 logMAR one month after injection (P=0.0001) but worsened to 0.75 logMAR after three months. Contrast sensitivity test demonstrated significant improvement at spatial frequencies of 3, 6, 12 and 18 cycles/degree one month after injection and at the spatial frequency of 12 cycles/degree three months after treatment. Mean ± standard deviation baseline central macular thickness (552 ± 150 µm) reduced significantly one month (322 ± 127 µm, P=0.0001) and three months (439 ± 179 µm, P=0.01) after treatment. CONCLUSIONS: Bevacizumab injection improves visual acuity and contrast sensitivity and reduces central macular thickness one month after treatment. Visual acuity returns to baseline levels at the 3-month follow-up, but some beneficial effect of the treatment is still present at that time, as evidenced by optical coherence tomography-measured central macular thickness and contrast sensitivity measurements.

Single intravitreal bevacizumab injection effects on contrast sensitivity in macular edema from branch retinal vein occlusion / Efeito de uma única injeção intravítrea de bevacizumabe sobre a sensibilidade ao contraste no edema macular causado por oclusão de ramo venoso da retina

PURPOSE: To evaluate the effect of a single intravitreal bevacizumab injection on visual acuity, contrast sensitivity and optical coherence tomography-measured central macular thickness in eyes with macular edema from branch retinal vein occlusion. METHODS: Seventeen eyes of 17 patients with macular edema from unilateral branch retinal vein occlusion were treated with a single bevacizumab injection. Patients were submitted to a complete evaluation including best corrected visual acuity, contrast sensitivity and optical coherence tomography measurements before treatment and one and three months after injection. Visual acuity, contrast sensitivity and optical coherence tomography measurements were compared to baseline values. RESULTS: Mean visual acuity measurement improved from 0.77 logMAR at baseline to 0.613 logMAR one month after injection (P=0.0001) but worsened to 0.75 logMAR after three months. Contrast sensitivity test demonstrated significant improvement at spatial frequencies of 3, 6, 12 and 18 cycles/degree one month after injection and at the spatial frequency of 12 cycles/degree three months after treatment. Mean ± standard deviation baseline central macular thickness (552 ± 150 µm) reduced significantly one month (322 ± 127 µm, P=0.0001) and three months (439 ± 179 µm, P=0.01) after treatment. CONCLUSIONS: Bevacizumab injection improves visual acuity and contrast sensitivity and reduces central macular thickness one month after treatment. Visual acuity returns to baseline levels at the 3-month follow-up, but some beneficial effect of the treatment is still present at that time, as evidenced by optical coherence tomography-measured central macular thickness and contrast sensitivity measurements.

OBJETIVO: Avaliar o efeito de uma única injeção intravítrea de bevacizumabe na função visual, sensibilidade ao contraste, em olhos com edema macular causado por oclusão de ramo venoso retiniano. MÉTODOS: Dezessete olhos de 17 pacientes com edema macular unilateral causado por oclusão de ramo venoso retiniano foram tratados com uma única injeção intravítrea de bevacizumabe. Pacientes previamente foram submetidos a exame ocular completo, sensibilidade ao contraste, variável de maior interesse, melhor acuidade visual corrigida e tomografia de coerência óptica e foram reavaliados no 1º e 3º mês de seguimento. RESULTADOS: O teste de sensibilidade ao contraste demonstrou melhora significante nas frequências espaciais 3, 6, 12 e 18 ciclos/grau (c/g) no primeiro mês de seguimento e na frequência espacial 12 c/g após o 3º mês de tratamento. A média da acuidade visual melhorou de 0,77 no pré-tratamento para 0,61 logMAR no 1º mês de seguimento (P=0,0001), com piora ao final do 3º mês, 0,75 logMAR. A média da espessura foveal central (552 ± 150 µm) reduziu significantemente no 1º (322 ± 127 µm, P=0,0001) e 3º (439 ± 179 µm, P=0,01) mês de seguimento. CONCLUSÃO: No edema macular causado por oclusão de ramo venoso retiniano, uma única injeção intravítrea de bevacizumabe melhora a sensibilidade ao contraste, acuidade visual e reduz a espessura foveal central após 1 mês de tratamento. Após 3 meses de seguimento, ainda é possível observar benefício com o tratamento, como foi evidenciado pela sensibilidade ao contraste e a medida da espessura foveal central à tomografia de coerência óptica.

Relationship between diabetic retinopathy severity and the timespan between the endocrinopathy diagnosis and the first ophthalmic examination.

PURPOSE: To investigate whether the time interval between type 2 diabetes mellitus (DM) diagnosis and the first fundoscopic examination is related with the presence and the severity of diabetic retinopathy (DR) observed. METHODS: A survey of 105 type 2 DM patients referred to ophthalmologic evaluation in the "Hospital das Clinicas" (HC), University of São Paulo Medical School (USPMS). RESULTS: Regarding classification of DR in the 105 patients, 15 (14.28%) did not show signs of DR, and 90 (85.72%) exhibited them on fundoscopy. Sixty patients underwent laser therapy, and 46.66% reported poor control of DM. Only 15.23% of DM patients were adequately screened for DR on the first year of their DM diagnosis. Among the 36 patients (34.30%) examined within five years of DM diagnosis, 58.33% did not present or demonstrate signs of mild DR and 22.20% of proliferative DR; 30 patients underwent an ophthalmologic examination after more than eleven years of DM diagnosis, 21.62% did not exhibit signs of DR and 59.46% were classified as proliferative DR. CONCLUSION: This study showed a statistically significant relationship between the time interval from the diagnosis of type 2 DM and the first fundoscopic examination with the severity of DR.

Relationship between diabetic retinopathy severity and the timespan between the endocrinopathy diagnosis and the first ophthalmic examination / Relação entre a gravidade da retinopatia diabética e o tempo decorrido entre o diagnóstico da endocrinopatia e o primeiro exame oftalmológico

Purpose: To investigate whether the time interval between type 2 diabetes mellitus (DM) diagnosis and the first fundoscopic examination is related with the presence and the severity of diabetic retinopathy (DR) observed. Methods: A survey of 105 type 2 DM patients referred to ophthalmologic evaluation in the "Hospital das Clinicas" (HC), University of São Paulo Medical School (USPMS). Results: Regarding classification of DR in the 105 patients, 15 (14.28 percent) did not show signs of DR, and 90 (85.72 percent) exhibited them on fundoscopy. Sixty patients underwent laser therapy, and 46.66 percent reported poor control of DM. Only 15.23 percent of DM patients were adequately screened for DR on the first year of their DM diagnosis. Among the 36 patients (34.30 percent) examined within five years of DM diagnosis, 58.33 percent did not present or demonstrate signs of mild DR and 22.20 percent of proliferative DR; 30 patients underwent an ophthalmologic examination after more than eleven years of DM diagnosis, 21.62 percent did not exhibit signs of DR and 59.46 percent were classified as proliferative DR. Conclusion: This study showed a statistically significant relationship between the time interval from the diagnosis of type 2 DM and the first fundoscopic examination with the severity of DR.

Objetivo: Avaliar se o tempo de intervalo entre o diagnóstico do diabetes mellitus (DM) tipo 2 e o primeiro exame de fundo de olho está relacionado com a gravidade da retinopatia diabética (RD). Métodos: Inquérito realizado em 105 pacientes portadores de DM tipo 2 que foram referenciados para avaliação oftalmológica no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Resultados: Quanto à classificação da RD, dos 105 pacientes, 15 (14,28 por cento) não apresentavam sinais de RD e 90 (85,72 por cento) demonstraram presença de sinais de RD ao exame de fundo de olho. Somente 15,23 por cento dos pacientes avaliados foram examinados no primeiro ano do diagnóstico de DM. Sessenta pacientes foram submetidos à laserterapia, 46,66 por cento relataram mal controle do DM. Quando examinados em até 5 anos de diagnóstico de DM, 36 (34,30 por cento), pacientes, 58,33 por cento não apresentaram sinais ou demonstravam sinais de RD grau leve e 22,20 por cento RD proliferativa. Trinta pacientes receberam exame oftalmológico superior a 11 anos do diagnóstico de DM, 21,62 por cento não apresentavam sinais de RD e 59,46 por cento classificados com RD proliferativa. Conclusão: Este estudo demonstrou significância estatística na relação entre o intervalo de tempo do diagnóstico do DM tipo 2 e o primeiro exame de fundo de olho com a gravidade de RD.