RESUMO

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

RESUMO

PURPOSE: To evaluate the short-term effects (hours-days) of intravitreal dexamethasone implant (IDI) in eyes with diabetic macular edema (DME) refractory to anti-vascular endothelial growth factor (VEGF) injections. METHODS: This was a prospective, single-arm, interventional clinical series. Eyes with DME and 3-9 injections of ranibizumab without a good response were included. Patients underwent a single IDI. Best-corrected visual acuity (BCVA) measurement, complete ophthalmic evaluation, and spectral-domain optical coherence tomography (SD-OCT) were performed at baseline, 2 h, 3 h, 24 h, 7 days, and 1 month. The main outcomes were change in central retinal thickness (CRT) on SD-OCT and BCVA. RESULTS: Fifteen eyes of 15 patients were included. Mean CRT decreased after treatment from 515.87 µm ± 220.00 µm at baseline to 489.60 µm ± 176.53 µm after 2 h (p = 0.126), and 450.13 µm ± 163.43 at 24 h (p = 0.006). Change in BCVA was from 0.85 ± 0.44 logMAR baseline to 0.58 ± 0.37 log MAR at 1 month (p = 0.003). CONCLUSIONS: Eyes treated with IDI showed significant decrease in CRT detectable 1 day after injection. In some patients, the effect could be observed 3 h post-implantation. TRIAL REGISTRATION: Clinicaltrials.gov NCT05736081 . Registered 20 February 2023, Retrospectively registered.

Assuntos

Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Dexametasona , Glucocorticoides , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Estudos Prospectivos , Injeções Intravítreas , Implantes de Medicamento , Tomografia de Coerência Óptica

RESUMO

Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.

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PURPOSE: To report the use of intravitreal triamcinolone to treat macular edema associated with isolated perifoveal exudative vascular anomalous complex (PVAC) and resembling lesion (PVAC-RL). METHODS: In this case series, three diabetic patients (3 eyes) with PVAC-RLs and one healthy patient (1 eye) with PVAC lesion associated with cystic spaces underwent three intravitreal injections of aflibercept before switching to one intravitreal triamcinolone injection in each patient. RESULTS: Macular edema improved from 297.5 ± 8.10 µm, at baseline, to 269.2 ± 8.89 µm, after triamcinolone; whereas visual acuity improved from 20/38 to 20/26 (ETDRS). CONCLUSION: PVAC and PVAC-RL are rare and often misdiagnosed lesions that may be associated with decreased vision. Our outcomes suggest that intravitreal injection of triamcinolone may be an effective and affordable treatment for PVAC and PVAC-RL with intraretinal fluid.

Assuntos

Retinopatia Diabética , Edema Macular , Humanos , Triancinolona , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Glucocorticoides , Injeções Intravítreas , Triancinolona Acetonida

RESUMO

Objectives: To identify risk factors for loss to follow-up in periodic intravitreal anti-vascular endothelial growth factor injections for the treatment patients with diabetic macular edema, subretinal neovascularization, age-related macular degeneration, and retinal vein occlusion in a single eye center in São Paulo, Brazil. Methods: This was a retrospective longitudinal study that gathered information from 992 patients who required intravitreal anti-vascular endothelial growth factor drugs over 6 months. The authors included age, eye disease, laterality, monthly income, distance, and payment mode as risk factors. Results: Two hundred and seventy patients (29.93%) were lost to follow-up. Multivariate analysis showed age, monthly income, eye involvement, and type of medical assistance independently associated with loss to follow-up. The odds of loss to follow-up were greater among older patients than those less than 50 years (reference), p < 0.001. The odds of loss to follow-up were greater among patients who received unilateral treatment than those who received bilateral injections (p = 0.013). Concerning gross monthly income, there were no differences in the odds of the four salary strata; the data also indicate an absence of difference in the three strata of patients' distance to the clinic. Considering the diagnosis, only age-related macular degeneration showed greater odds of loss to follow-up (p = 0.016). Finally, the data suggest greater odds of loss to follow-up in private patients than in those on a health care plan (p < 0.001). Conclusion: Loss to follow-up is paramount because many patients may remain unassisted concerning their eye diseases. Identifying the risk factors is crucial to enforcing measures to increase adherence and the long-term success of the treatment.

RESUMO

INTRODUCTION: Diabetic macular edema (DME) is one of the leading causes of vision impairment. The relationship between DME and estimated glomerular filtration rate (eGFR) has not been clearly evaluated in Hispanic or Latino populations. The objective of this study was to evaluate the eGFR in a Latino population with DME. METHODS: A cross-sectional, observational, and descriptive study was carried out on the basis of a multicenter phase III clinical trial. RESULTS: A total of 82 subjects diagnosed with DME (36 women and 46 men) were included in the study. The mean age was 61.93 ± 6.71 years. Mean values of the blood chemistry parameters glycated hemoglobin and eGFR were 7.20 ± 0.95% and 74.42 ± 26.82 mL/min/1.73 m2, respectively. The time elapsed since diagnosis of diabetes mellitus was 15.30 ± 7.35 years, while the duration of DME was 1.41 ± 1.75 years. Mean values for central macular thickness (CMT) and total macular volume (TMV) were 440.99 ± 132.22 µm and 11.97 ± 2.11 mm3, respectively. DME duration had a negative correlation with TMV (Rho - 0.26, p < 0.05) and a positive correlation with mean arterial pressure (Rho 0.26, p < 0.05). CMT was correlated with TMV (Rho 0.43, p < 0.0001) and visual acuity (Rho 0.26, p < 0.05). No significant correlations were observed between eGFR and CMT, TMV, or any demographic variable (p > 0.05). Chronic kidney disease (CKD) was associated with hypertension (OR 9.32, p = 0.035), elevated intraocular pressure (IOP) (OR 0.03, p = 0.011), and advanced age (OR 0.45, p = 0.011). CMT was significantly associated with TMV (ß = 27.69, p < 0.0001). CONCLUSIONS: We did not find a correlation between eGFR and DME. Our findings suggest that the presence of hypertension is associated with a decrease in the GFR < 60 mL/min/1.73 m2, and CKD may be associated with advanced age and elevated IOP which may increase the risk for the development of glaucoma. TRIAL REGISTRATION: NCT05217680 (clinicaltrials.gov).

RESUMO

INTRODUCTION: Diabetic retinopathy is a major cause of visual loss worldwide. The most important clinical findings include diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). AREAS COVERED: PubMed was used for our literature review. Articles from 1995 to 2023 were included. Pharmacologic treatment of diabetic retinopathy generally involves the use of intravitreal anti-vascular endothelial growth factor (VEGF) therapy for DME and PDR. Corticosteroids remain important second-line therapies for patients with DME. Most emerging therapies focus on newly identified inflammatory mediators and biochemical signaling pathways involved in disease pathogenesis. EXPERT OPINION: Emerging anti-VEGF modalities, integrin antagonists, and anti-inflammatory agents have the potential to improve outcomes with reduced treatment burdens.

Assuntos

Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/complicações , Inibidores da Angiogênese , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Fator A de Crescimento do Endotélio Vascular , Glucocorticoides/uso terapêutico , Injeções Intravítreas , Diabetes Mellitus/tratamento farmacológico

RESUMO

BACKGROUND: Data on visual impairment (VI) in patients with diabetes are necessary in order to guide economic and human resources for reducing its prevalence. OBJECTIVE: To estimate the prevalence of diabetic retinopathy-related VI in patients with type 2 diabetes in a hospital-based setting. MATERIAL AND METHODS: Cross-sectional study carried out from 2014 to 2019 in an ophthalmology outpatient clinic. Any VI was defined as corrected pin-hole visual acuity in the better eye of ≥ 0.24 logMAR. The presence of diabetic retinopathy (DR), diabetic macular edema (DME) and cataract was evaluated. RESULTS: A total of 840 patients were included; median diabetes duration was 15 years. The prevalence of VI was 30%. DR was found in 62% of patients (30% had sight-threatening DR [STDR]), 17% had referable DME, and 3%, cataracts. The odds ratio for moderate or worse VI was 9.02 for STDR (p < 0.001), 5.89 for referable DME (p = 0.001), and 2.51 for cataract (p = 0.006). CONCLUSION: Thirty percent of participants had some degree of VI. Moderate or worse VI showed a strong association with STDR and referable DME.

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ANTECEDENTES: Los datos sobre discapacidad visual (DV) en pacientes con diabetes son necesarios para orientar los recursos económicos y humanos que disminuyan su prevalencia. OBJETIVO: Estimar la prevalencia de DV relacionada con retinopatía diabética en pacientes con diabetes tipo 2 en un entorno hospitalario. MATERIAL Y MÉTODOS: Estudio transversal realizado de 2014 a 2019 en una consulta externa de oftalmología. Cualquier DV se definió como agudeza visual corregida con agujero estenopeico en el ojo con mejor visión (≥ 0.24 logMAR). Se evaluó la presencia de retinopatía diabética, edema macular diabético (EMD) y cataratas. RESULTADOS: Se incluyeron 840 pacientes; la mediana de duración de la diabetes fue de 15 años. La prevalencia de DV fue de 30 %. Se encontró retinopatía diabética en 62 % (30 % tenía retinopatía diabética que amenazaba la visión [RDAV]); 17 %, EMD y 3 %, cataratas. La razón de momios para DV moderada o de mayor gravedad fue de 9.02 para RDAV (p < 0.001), 5.89 para EMD referible (p = 0.001) y 2.51 para catarata (p = 0.006). CONCLUSIÓN: Treinta por ciento de los participantes tenía algún grado de DV. La DV moderada o de mayor gravedad mostró una fuerte asociación con RDAV y EMD referible.

Assuntos

Catarata , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Edema Macular , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Edema Macular/epidemiologia , Edema Macular/etiologia , Estudos Transversais , Hospitais , Catarata/complicações , Catarata/epidemiologia , Transtornos da Visão/etiologia , Transtornos da Visão/complicações

RESUMO

Resumen Antecedentes: Los datos sobre discapacidad visual (DV) en pacientes con diabetes son necesarios para orientar los recursos económicos y humanos que disminuyan su prevalencia. Objetivo: Estimar la prevalencia de DV relacionada con retinopatía diabética en pacientes con diabetes tipo 2 en un entorno hospitalario. Material y métodos: Estudio transversal realizado de 2014 a 2019 en una consulta externa de oftalmología. Cualquier DV se definió como agudeza visual corregida con agujero estenopeico en el ojo con mejor visión (≥ 0.24 logMAR). Se evaluó la presencia de retinopatía diabética, edema macular diabético (EMD) y cataratas. Resultados: Se incluyeron 840 pacientes; la mediana de duración de la diabetes fue de 15 años. La prevalencia de DV fue de 30 %. Se encontró retinopatía diabética en 62 % (30 % tenía retinopatía diabética que amenazaba la visión [RDAV]); 17 %, EMD y 3 %, cataratas. La razón de momios para DV moderada o de mayor gravedad fue de 9.02 para RDAV (p < 0.001), 5.89 para EMD referible (p = 0.001) y 2.51 para catarata (p = 0.006). Conclusión: Treinta por ciento de los participantes tenía algún grado de DV. La DV moderada o de mayor gravedad mostró una fuerte asociación con RDAV y EMD referible.

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Abstract Background: Data on visual impairment (VI) in patients with diabetes are necessary in order to guide economic and human resources for reducing its prevalence. Objective: To estimate the prevalence of diabetic retinopathy-related VI in patients with type 2 diabetes in a hospital-based setting. Material and methods: Cross-sectional study carried out from 2014 to 2019 in an ophthalmology outpatient clinic. Any VI was defined as corrected pin-hole visual acuity in the better eye of ≥ 0.24 logMAR. The presence of diabetic retinopathy (DR), diabetic macular edema (DME) and cataract was evaluated. Results: A total of 840 patients were included; median diabetes duration was 15 years. The prevalence of VI was 30 %. DR was found in 62 % of patients (30 % had sight-threatening DR [STDR]), 17 % had referable DME, and 3 %, cataracts. The odds ratio for moderate or worse VI was 9.02 for STDR (p < 0.001), 5.89 for referable DME (p = 0.001), and 2.51 for cataract (p = 0.006). Conclusion: Thirty percent of participants had some degree of VI. Moderate or worse VI showed a strong association with STDR and referable DME.

RESUMO

PURPOSE: The aim of this study is to investigate the safety of combined intravitreal injection of dexamethasone aqueous-solution (IVD) and bevacizumab (IVB) in patients with refractory diabetic macular edema (DME) and its effect on intraocular pressure (IOP), best-corrected visual acuity (BCVA) and central subfield thickness (CSFT). METHODS: This prospective study included 10 patients (10 eyes) with DME refractory to laser photocoagulation and/or anti-vascular endothelial growth factor (anti-VEGF) therapy. A complete ophthalmological examination was performed at baseline, during the first week of treatment, and monthly through week 24. Therapy consisted of monthly injections of combined IVD and IVB "pro re nata" (PRN) if CST > 300 µm. We investigated the impact of the injections on intraocular pressure (IOP), cataract development, Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA), and central sub-foveal thickness (CSFT) measured by spectral-domain optical coherence tomography (OCT). RESULTS: Eight patients (80%) completed 24 weeks of follow-up. Compared to baseline, mean IOP increased significantly (p < 0.05) and anti-glaucomatous eye drops were necessary for 50% of the patients, CSFT was significantly reduced at all follow-up visits (p < 0.05), although mean BCVA showed no significant improvement. One patient developed dense cataract progression and another showed vitreoretinal traction at week 24. No inflammation or endophthalmitis was observed. CONCLUSION: Treatment of DME refractory to laser and/or anti-VEGF therapy with combined PRN IV dexamethasone aqueous solution and bevacizumab was associated with adverse effects related to the use of corticosteroids. However, there was a significant improvement in CSFT meantime best-correct visual acuity remained stable or improved in 50% of patients.

RESUMO

Objetivo: determinar los cambios en el espesor macular establecido por Tomografía de Coherencia Óptica (OCT) posterior al tratamiento con Bevacizumab intravítreo en pacientes con Edema Macular Diabético, diagnosticados en el Hospital Otorrino Oftalmológico. Material y Métodos: es un estudio de serie de casos. Se realizo un muestreo por conveniencia de pacientes con edema macular diabético, la muestra obtenida fue de 106 casos de un universo de 146 pacientes con una confiabilidad del 95%, pero según criterios de inclusión y exclusión, la muestra se redujo a 24 pacientes. Resultados: disminución del espesor macular inicial de 493,8 µm a 287,6 µm. La agudeza visual mejora después del tratamiento con Bevacizumab en 79,2% de los pacientes, de los cuales el 62,5% mejoro hasta la 3era dosis de inyección intravítrea y en relación con la HbA1c (Hemoglobina Glicosilada) valores < a 7% da una frecuencia relativa de 66,7% y > a 7% un 33,3%. Existió mayor representatividad de edad entre un rango de 51 a 60 años en 9 pacientes 37,5%. Conclusiones: el tratamiento del edema macular diabético con Bevacizumab intravítreo produce mejorías significativas tanto anatómicas como funcionales. Los valores de HbA1Ac es influyente tanto para la mejora anatómica como funcional.

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Objective: to determine the changes in macular thickness established by Optical Coherence Tomography (OCT) after treatment with intravitreal bevacizumab in patients with Diabetic Macular Edema, diagnosed at the Otorrino Ophthalmological Hospital. Material and Methods: it is a case series study. A convenience sampling of patients with diabetic macular edema was performed, the sample obtained was 106 cases from a universe of 146 patients with a reliability of 95%, but according to inclusion and exclusion criteria, the sample was reduced to 24 patients. Results: decrease in initial macular thickness from 493.8 µm to 287.6 µm. Visual acuity improved after treatment with bevacizumab in 79.2% of patients, of whom 62.5% improved to the 3rd dose of intravitreal injection and in relation to HbA1c (Glycosylated Hemoglobin) values < to 7% gives a relative frequency of 66.7% and > to 7% 33.3%. There was a greater representation of age between a range of 51 to 60 years in 9 patients, 37.5%. Conclusions: the treatment of diabetic macular edema with intravitreal bevacizumab produces significant anatomical and functional improvements. HbA1Ac values are influential for both anatomical and functional improvement.

Assuntos

Humanos

RESUMO

Diabetic retinopathies are important disabling conditions. Micro-RNAs (miRNAs) are regulators of gene expression and diseases can change their expression. Our aim was to analyze the expression of miRNAs in serum and vitreous samples from patients with diabetic retinopathies. The following groups and number of individuals were included: proliferative diabetic retinopathy (PDR) (n = 16), diabetic macular edema (DME) (n = 17), and idiopathic epiretinal membrane (IEM) as non-diabetic controls (n = 23). The initial miRNA expression was explored using TaqMan low-density arrays (TLDAs) with subsequent validation through a quantitative polymerase chain reaction (qPCR). Target genes were identified through bioinformatic tools for enrichment analysis. The TLDAs revealed the following miRNAs with differential expression in terms of PDR vs. IEM: miR-320a-3p, miR-92a-3p, and miR-375-3p in the serum, with miR-541-5p and miR-223-5p in the vitreous samples. DME vs IEM: miR-486-5p, miR-145-5p, miR-197-3p, and miR-125b-5p in the serum, and miR-212-3p in vitreous samples. PDR vs. DME: miR-486-5p, miR-100-5p, miR-328-3p, miR-660-5p, and miR-145 in the serum and none in the vitreous samples. Validation was confirmed only for miR-145, miR-92a, and miR-375 in the serum. The relevant enriched pathways for these three validated miRNAs, miR-145, miR-92a, and miR-375 were the vascular endothelial growth factor and its receptor, hepatocyte growth factor receptor, epidermal growth factor, focal adhesion, and phosphoinositide 3-kinase. Our results support the involvement of miRNAs in the pathophysiology of diabetic retinopathies and reinforce their potential as biomarkers or therapeutic resources.

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BACKGROUND: Diabetic macular edema (DME) is the main cause of visual loss in diabetic patients. Despite the use of anti-VEGF therapy as first-line treatment, there are many patients whose response to treatment is poor or transient at best. Sophisticated laser techniques have emerged aiming at low-intensity retinal damage, avoiding excessive heat that causes tissue necrosis and related collateral effects. OBJECTIVE: To evaluate the effect of combined sublethal laser modalities from short-pulse duration (SPD) with endpoint management (EpM) subthreshold laser [named the "sandwich technique" (SWiT)] on central subfield thickness (CST) and best-corrected visual acuity (BCVA) in patients with DME. MATERIAL AND METHODS: In this consecutive retrospective study, 37 patients (37 eyes) with center-involved (CI) DME were treated with SWiT laser therapy from April 2017 to June 2021. The technique consisted of a mean number of 200 (range number 50-400) SPD laser burns OCT-guided thickened area performed on the juxta- and perifoveal area 500 µm away from the foveal center, overlapping with a mean number of 1000 (range number 800-1200) EpM laser burns focused on 6 mm macular diameter area but saving 300 µm toward the foveal center. All patients underwent ophthalmological evaluations, including BCVA and CST measurement by spectral-domain optical coherence tomography (SD-OCT), before and after SWiT laser therapy. The mean follow-up time was 19.2 months (range 2-60 months). RESULTS: Thirty-five out of 37 cases showed an improvement in CST and BCVA following treatment. At baseline, mean CST (µm) ± standard error (SE) and mean BCVA (logMAR) ± SE was 456.95 ± 37.00 and 0.71 ± 0.29, respectively. After a mean follow-up of 19.2 months, mean CST (µm) ± SE and BCVA (logMAR) ± SE were 272.09 ± 9.10 (p < 0.0001) and 0.54 ± 0.26 (p = 0.003), respectively. A statistically significant reduction in CST and improvement in BCVA was noted after laser therapy application. The anti-VEGF injection frequency was reduced during the mean 19.2 months of the study period. CONCLUSIONS: The novel "sandwich" laser therapy aid reduced CST and improved BCVA in this retrospective case series. Further prospective studies are warranted.

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Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide. Multiple treatment options have been used over time to attempt to modify the natural progression of the disease in both proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). These two retinal complications are the result of microvascular occlusions and vascular hyperpermeability and are considered one of the leading causes of irreversible blindness in patients of working age. It is now well demonstrated that PDR and DME are associated with increased levels of inflammatory and pro-angiogenic factors in the ocular compartment. To date, laser photocoagulation, vascular endothelial growth factor (VEGF) inhibitors, and corticosteroids have demonstrated efficacy in their treatment in large randomized controlled trials and in real-life observational studies. This manuscript aims to provide a comprehensive review of current treatments, including the main drugs used in diabetic pathologic manifestations, as well as new therapeutic alternatives, such as extended-release intraocular devices.

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PURPOSE: To evaluate the occurrence of transient central retinal artery occlusion following intravitreal anti-vascular endothelial growth factor injection. METHODS: Prospective, observational study of 807 patients (807 eyes) who were given intravitreal injections of ranibizumab or aflibercept to treat any cause of retinal vascular diseases between 1 January 2017 and 30 November 2018 at the Federal Fluminense University Hospital in Niteroi, and a private facility in Rio de Janeiro, Brazil. Patients who did not present transient central retinal artery occlusion were excluded. RESULTS: Among 4069 injections, only 18 patients (0.44%) presented transient central retinal artery occlusion, 14 mild cases (77.7%), and 4 severe cases (22.3%). The clinical factors associated with more severe cases of transient central retinal artery occlusion were the duration of the transient central retinal artery occlusion (p = 0.001), number of prior injections (p = 0.01), and a positive carotid Doppler test (p = 0.01). Twelve cases (66.6%) had positive carotid artery obstruction (atheroma plaque size ≥70%) while 6 cases (33.3%) had negative carotid artery obstruction (atheroma plaque size <70%). The age group >60 years old (p = 0.06), cup/disc ratio >0.6 (p = 0.06), and pseudophakic lens status were also factors with association with transient central retinal artery occlusion, although did not meet criteria for statistical significance. The only patient who experienced a recurrent episode of transient central retinal artery occlusion had diabetic macular edema, positive carotid Doppler test, and cup/optic disc ratio >0.6. CONCLUSION: Transient central retinal artery occlusion is a rare adverse event that can appear in patients with retinal vascular disease receiving anti-vascular endothelial growth factor therapy. The atheroma plaque size and the number of prior injections can be associated with the severity of the event.

Assuntos

Retinopatia Diabética , Edema Macular , Placa Aterosclerótica , Oclusão da Artéria Retiniana , Oclusão da Veia Retiniana , Inibidores da Angiogênese/efeitos adversos , Artérias , Bevacizumab/uso terapêutico , Brasil , Retinopatia Diabética/tratamento farmacológico , Fatores de Crescimento Endotelial/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Pessoa de Meia-Idade , Placa Aterosclerótica/induzido quimicamente , Placa Aterosclerótica/complicações , Placa Aterosclerótica/tratamento farmacológico , Estudos Prospectivos , Ranibizumab/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/efeitos adversos , Retina , Oclusão da Artéria Retiniana/induzido quimicamente , Oclusão da Artéria Retiniana/complicações , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual

RESUMO

RESUMO: O edema macular diabético é uma das principais causas de baixa visual no mundo e a indicação mais frequente de injeções intravítreas no Hospital de Clínicas de Porto Alegre. O tratamento com injeção intra-vítrea de medicamentos anti-vascular endothelial growth factor, incluindo o bevacizumaberevolucionou o desfecho visual destes pacientes às custas de múltiplas aplicações mensais. Assim como em outros centros, discrepâncias entre condutas da equipe assistencial e dificuldades logísticas acabam comprometendo a efetividade do tratamento. Portanto, desenvolvemos um protocolo de tratamento para a doença embasado na literatura, estabelecendo critérios de inclusão, exclusão, regime de tratamento e seguimento do paciente. Com isto, esperamos otimizar a efetividade e assistência do paciente com edema macular diabético.

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ABSTRACT: Diabetic macular edema is one of the leading causes of visual impairment worldwide and the most common indication for intravitreal injections at the Hospital de Clínicas de Porto Alegre. Treatment with intravitreal injection of anti-vascular endothelial growth factor drugs, including bevacizumab, has revolutionized patient outcome at the expense of multiple monthly injections. As in other hospitals, discrepancies in health team conduct and logistical difficulties compromise treatment effectiveness. Therefore, we developed a literature-based treatment protocol for diabetic macular edema, in which we established criteria for patient inclusion and exclusion, treatment regimen, and patient follow-up. We expect the treatment protocol to optimize patient care effectiveness in diabetic macular edema.

Assuntos

Humanos , Edema Macular/tratamento farmacológico , Retinopatia Diabética/complicações , Injeções Intravítreas/métodos , Protocolos Clínicos , Resultado do Tratamento , Bevacizumab/administração & dosagem

RESUMO

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic eyes, and due to the rapid rise in the number of diabetic patients, the treatment burden has increased exponentially. The introduction of antivascular endothelial growth factor (anti-VEGF) therapy has been a major breakthrough in the management of center-involving DME, replacing laser photocoagulation as the first-line treatment. Despite the improvement in DME treatment with anti-VEGF therapy, persistent DME remains a challenge due to the extremely complex pathogenesis and the involvement of several different biochemical pathways. This review focuses on therapeutic options for persistent DME, which include corticosteroids, laser, and surgery. Novel agents for DME control such as new anti-VEGF, interleukin inhibitor, Rho-kinase inhibitor, and neuroprotective agents that are being investigated are reviewed as well. Future treatment perspectives include an individualized DME management.

Assuntos

Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Humanos , Inibidores de Interleucina , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia

RESUMO

INTRODUCTION: Diabetic macular edema is a frequent pathology that causes gradual deterioration of visual acuity, which does not have a standardized treatment. The anti-vascular endothelial growth factor (anti-VEGF) drugs and corticosteroids are widely used, especially aflibercept and dexamethasone, respectively, but it is unclear which one is best. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: No evidence that compared the interventions directly in the population of interest was found, so systematic reviews that provide an estimate of the effect indirectly using network meta-analysis were selected. We identified two systematic reviews that together included four primary studies, all randomized trials. We concluded that we are uncertain whether aflibercept compared to dexamethasone improves visual acuity or is safer, as the certainty of the evidence has been assessed as very low.

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INTRODUCCIÓN: El edema macular diabético es una patología frecuente, causante de deterioro gradual de la agudeza visual, que no tiene un tratamiento estandarizado. Los fármacos anti factor del crecimiento vascular endotelial (anti-VEGF) y los corticoides se encuentran entre los tratamientos más ampliamente utilizados, destacando aflibercept y dexametasona, respectivamente, sin haber una clara superioridad entre ambas terapias. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: No se encontró evidencia que compare las intervenciones directamente en la población de interés, por lo que se seleccionaron revisiones sistemáticas que entregan una estimación del efecto de manera indirecta, mediante la técnica de metanálisis de comparaciones múltiples (metanálisis en red). Identificamos dos revisiones sistemáticas que en conjunto incluyeron cuatro estudios primarios, todos ensayos aleatorizados. Concluimos que no es posible establecer con claridad si usar aflibercept comparado con dexametasona aumenta la agudeza visual o es más seguro, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.

Assuntos

Inibidores da Angiogênese , Dexametasona , Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Inibidores da Angiogênese/uso terapêutico , Bases de Dados Factuais , Dexametasona/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Humanos , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Ranibizumab , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Revisões Sistemáticas como Assunto , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular

RESUMO

Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA-loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled on the ocular surface. To evaluate the safety, tolerability, and biological activity of TALF, an animal study and a phase I clinical assay were performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biological activity of the formulation. No inflammation, lens opacity, swelling, or increase in intraocular pressure were recorded after the instillation of TALF in any of the animal or clinical studies. Mainly, mild and transient adverse events such as dry eye and burning were reported. TALF significantly improves visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biological activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroid IVTs and their associated hazards.

RESUMO

BACKGROUND: Diabetic macular edema (DME) is a major cause of visual impairment and its treatment is a public health challenge. Even though anti-angiogenic drugs are the gold-standard treatment, they are not ideal and subthreshold laser (SL) remains a viable and promising therapy in selected cases. The aim of this study was to evaluate its efficacy in a real-life setting. METHODS: Retrospective case series of 56 eyes of 36 patients with center-involving DME treated with SL monotherapy. Treatment was performed in a single session with the EasyRet® photocoagulator with the following parameters: 5% duty cycle, 200-ms pulse duration, 160-µm spot size and 50% power of the barely visible threshold. A high-density pattern was then applied to the whole edematous area, using multispot mode. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) data were obtained at baseline and around 3 months after treatment. RESULTS: Fifty-six eyes of 36 patients were included (39% women, mean age 64.8 years old); mean time between treatment day and follow-up visit was 14 ± 6 weeks. BCVA (Snellen converted to logMAR) was 0.59 ± 0.32 and 0.43 ± 0.25 at baseline and follow-up, respectively (p = 0.002). Thirty-two percent had prior panretinal photocoagulation (p = 0.011). Mean laser power was 555 ± 150 mW and number of spots was 1,109 ± 580. Intraretinal and subretinal fluid (SRF) was seen in 96 and 41% of eyes at baseline and improved in 35 and 74% of those after treatment, respectively. Quantitative analysis of central macular thickness (CMT) change was performed in a subset of 23 eyes, 43% of which exhibited > 10% CMT reduction post-treatment. CONCLUSIONS: Subthreshold laser therapy is known to have RPE function as its main target, modulating the activation of heat-shock proteins and normalizing cytokine expression. In the present study, the DME cases associated with SRF had the best anatomical response, while intraretinal edema responded poorly to laser monotherapy. BCVA and macular thickness exhibited a mild response, suggesting the need for combined treatment in most patients. Given the effect on SRF reabsorption, subthreshold laser therapy could be a viable treatment option in selected cases.