RESUMEN
OBJECTIVES: To assess whether insulin therapy impacts the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) injection for the treatment of diabetic macular edema (DME) in type 2 diabetes mellitus. METHODS: This was a retrospective multi-center analysis. The best-corrected visual acuity (BCVA) at 12 months, BCVA change, central macular thickness (CMT), CMT change, and cumulative injection number were compared between the insulin and the oral hypoglycemic agent (OHA) groups. RESULTS: The mean final BCVA and CMT improved in both the insulin (N = 137; p < 0.001; p < 0.001, respectively) and the OHA group (N = 61; p = 0.199; p < 0.001, respectively). The two treatment groups were comparable for final BCVA (p = 0.263), BCVA change (p = 0.184), final CMT (p = 0.741), CMT change (p = 0.458), and the cumulative injections received (p = 0.594). The results were comparable between the two groups when stratified by baseline vision (p > 0.05) and baseline HbA1c (p > 0.05). CONCLUSION: Insulin therapy does not alter treatment outcomes for anti-VEGF therapy in DME.
Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Edema Macular , Inhibidores de la Angiogénesis/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Retinopatía Diabética/complicaciones , Retinopatía Diabética/tratamiento farmacológico , Humanos , Insulina/uso terapéutico , Inyecciones Intravítreas , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza VisualRESUMEN
Intraocular anti-vascular endothelial growth factor (VEGF) therapies are the front-line treatment for diabetic macular edema (DME); however, treatment response varies widely. This study aimed to identify genetic determinants associated with anti-VEGF treatment response in DME. We performed a genome-wide association study on 220 Australian patients with DME treated with anti-VEGF therapy, genotyped on the Illumina Global Screening Array, and imputed to the Haplotype Reference Consortium panel. The primary outcome measures were changes in central macular thickness (CMT in microns) and best-corrected visual acuity (BCVA in ETDRS letters) after 12 months. Association between single nucleotide polymorphism (SNP) genotypes and DME outcomes were evaluated by linear regression, adjusting for the first three principal components, age, baseline CMT/BCVA, duration of diabetic retinopathy, and HbA1c. Two loci reached genome-wide significance (p < 5 × 10−8) for association with increased CMT: a single SNP on chromosome 6 near CASC15 (rs78466540, p = 1.16 × 10−9) and a locus on chromosome 12 near RP11-116D17.1 (top SNP rs11614480, p = 2.69 × 10−8). Four loci were significantly associated with reduction in BCVA: two loci on chromosome 11, downstream of NTM (top SNP rs148980760, p = 5.30 × 10−9) and intronic in RP11-744N12.3 (top SNP rs57801753, p = 1.71 × 10−8); one near PGAM1P1 on chromosome 5 (rs187876551, p = 1.52 × 10−8); and one near TBC1D32 on chromosome 6 (rs118074968, p = 4.94 × 10−8). In silico investigations of each locus identified multiple expression quantitative trait loci and potentially relevant candidate genes warranting further analysis. Thus, we identified multiple genetic loci predicting treatment outcomes for anti-VEGF therapies in DME. This work may potentially lead to managing DME using personalized treatment approaches.
Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Proteínas Adaptadoras Transductoras de Señales , Inhibidores de la Angiogénesis/uso terapéutico , Australia , Diabetes Mellitus/tratamiento farmacológico , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/genética , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Inyecciones Intravítreas , Edema Macular/tratamiento farmacológico , Edema Macular/genética , Ranibizumab/uso terapéutico , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Factores de Crecimiento Endotelial Vascular , Agudeza VisualRESUMEN
Diabetic retinopathy (DR) is the most common microvascular complication related to diabetes. There is evidence that genetics play an important role in DR pathogenesis, but the complexity of the disease makes genetic studies a challenge. This chapter is a practical overview of the basic steps for genome-wide association studies with respect to DR and its associated traits. Also described are approaches that can be adopted in future DR studies. This is intended to serve as a guide for beginners and to provide a framework for further in-depth analysis.
Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Humanos , Diabetes Mellitus Tipo 2/genética , Retinopatía Diabética/genética , Estudio de Asociación del Genoma Completo/métodos , FenotipoRESUMEN
BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the standard of care for diabetic macular edema (DME), a common complication of diabetes. This study aimed to identify factors influencing DME intravitreal anti-VEGF treatment outcomes in real-world practice. METHODS: This was a multi-center retrospective observational study using medical chart review of participants receiving anti-VEGF injections for DME (N = 248). Demographic and clinical variables were assessed for association with best corrected visual acuity (BCVA) and central macular thickness (CMT) outcomes using regression models. RESULTS: There was a significant improvement in BCVA (p < 0.001) and CMT (p < 0.001) after 12 months of treatment, although 21% of participants had decreased BCVA, and 41% had a < 10% CMT reduction at 12 months. Higher baseline BCVA (p = 0.022, OR=-0.024, 95% CI=-0.046,-0.004) and longer duration of diabetic retinopathy (p = 0.048, OR=-0.064, 95% CI=-0.129,-0.001) were negative predictors for BCVA response, whereas Aflibercept treatment (p = 0.017, OR = 1.107, 95% CI = 0.220,2.051) compared with other drugs and a positive "early functional response" (p < 0.001, OR=-1.393, 95% CI=-1.946,-0.857) were positive predictors. A higher baseline CMT (p < 0.001, OR = 0.019, 95% CI = 0.012,0.0261) and an "early anatomical response", (p < 0.001, OR=-1.677, 95% CI=-2.456, -0.943) were predictors for greater reduction in CMT. Overall, the variables could predict only 23% of BCVA and 52% of CMT response. CONCLUSIONS: The study shows a significant proportion of DME patients do not respond to anti-VEGF therapy and identifies several clinical predictors for treatment outcomes. TRIAL REGISTRATION: The study was approved through the Human Research Ethics Committee, University of Tasmania (approval number H0012902), and the Southern Adelaide Clinical Human Research Ethics Committee (approval number 86 - 067).
RESUMEN
OBJECTIVE: To compare the visual outcomes of intravitreal antivascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in a real-world setting. METHODS AND ANALYSIS: Retrospective analysis of data from the Tasmanian Ophthalmic Biobank database. The median change in best-corrected visual acuity (BCVA) between baseline and 12 months post initiating intravitreal anti-VEGF treatment were compared between the three diseases. Final BCVA, central macular thickness (CMT), cumulative number of injections and overall predictors of change in BCVA and CMT were also determined. RESULTS: At 12 months, change in BCVA was significantly different between nAMD, DMO and RVO cohorts (p=0.032), with lower median change for DMO (2 letters, range -5 to 20) than for RVO (11 letters, range -20 to 35). Likewise, CMT change was significantly different between the three cohorts (p=0.022), with a smaller reduction in CMT in DMO (-54 µm, range -482 to 50) than RVO patients (-137 µm, range -478 to 43; p=0.033). Total number of injections received (p=0.028) and final BCVA score (p=0.024) were also significantly different between the groups. Baseline BCVA was a negative predictor (p=0.042) and baseline CMT a positive predictor (p<0.001) of outcome. After adjusting for baseline BCVA and CMT, diagnosis of nAMD or RVO was a predictor of visual improvement compared with the DMO. CONCLUSIONS: At the end of 12 months, nAMD and RVO cohorts had the greatest improvement in BCVA, however the final BCVA for DMO was significantly better than for nAMD.
RESUMEN
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). DR is complex and the term encompasses several clinical subtypes of diabetic eye disease, including diabetic macular edema (DME), the most frequent cause of central vision loss in DR patients. Both genetic and environmental factors contribute to the pathophysiology of DR and its subtypes. While numerous studies have identified several susceptibility genes for DR, few have investigated the impact of genetics on DME susceptibility. This review will focus on the current literature surrounding genetic risk factors associated with DME. We will also highlight the small number of studies investigating the genetics of response to antivascular endothelial growth factor (anti-VEGF) injection, which is used to treat DME.
Asunto(s)
Retinopatía Diabética/genética , Edema Macular/genética , Aldehído Reductasa/genética , Inhibidores de la Angiogénesis/uso terapéutico , Apolipoproteínas E/genética , Bevacizumab/uso terapéutico , Retinopatía Diabética/tratamiento farmacológico , Eritropoyetina/genética , Proteínas del Ojo/genética , Predisposición Genética a la Enfermedad , Humanos , Edema Macular/tratamiento farmacológico , MicroARNs/genética , Factores de Crecimiento Nervioso/genética , Óxido Nítrico Sintasa/genética , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Serpinas/genética , Superóxido Dismutasa/genética , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/genética , Factor C de Crecimiento Endotelial Vascular/genéticaRESUMEN
Valsalva retinopathy is a common condition but retinal holes secondary to Valsalva retinopathy are rarely reported. The author believes this to be the first report to describe multiple retinal holes after hyaloidotomy for Valsalva retinopathy.
RESUMEN
PURPOSE: Valsalva hemorrhagic retinopathy is a form of preretinal hemorrhage that develops after a valsalva maneuver, leading to rupture of the superficial retinal capillaries. Here, we report a case of valsalva retinopathy secondary to blowing a conch, the first case report of its kind. The patient blew conch, which was part of his daily ritual to pray to God as he was a Hindu priest. OBSERVATIONS: A 58-year-man developed an acute decrease in vision to 5/60 in his right eye after blowing the conch while performing "Puja," which is the act of praying to God in Hindu culture. Ophthalmoscopy showed a fresh preretinal hemorrhage over the macula in his right eye. YAG laser membranotomy was performed, and his vision returned to 6/6. CONCLUSIONS AND IMPORTANCE: Conch "Shankha" is a religious instrument used routinely in Hindu culture. Its mechanism is very much similar to that of a wind instrument. This is the first case report of valsalva retinopathy caused by conch blowing.