Asociación entre biomarcadores en tomografía de coherencia óptica y agudeza visual en pacientes con edema macular diabético tratados con antiangiogénicos

Objetivos Evaluar la asociación entre los principales biomarcadores del Edema Macular Diabético (EMD) y la Agudeza Visual (AV), y determinar su importancia como herramienta pronóstica a la hora de iniciar un tratamiento antiangiogénico en cada paciente. Métodos Estudio de cohorte retrospectivo, observacional y longitudinal. Se analizaron 25 escaneos de OCT de 23 pacientes con edema macular diabético (EMD) y se registró la Agudeza Visual Mejor Corregida (AVMC) al inicio, y a los 3, 6 y 9 meses de tratamiento. Las imágenes basales se evaluaron para el tipo predominante de edema macular (Cistoide, espongiforme, con desprendimiento seroso subfoveal o con compromiso traccional); presencia de daño en la retina externa (considerado como cualquier discontinuidad en la Membrana Limitante Externa, Zona Elipsoide y/o Zona de Interdigitación); presencia de desorganización de las Capas Internas de la Retina (DRIL) y cantidad de Puntos Hiperreflectivos (PH) así como del Espesor Macular Central (EMC). Las correlaciones entre cada biomarcador y la ganancia de Agudeza Visual se analizaron utilizando modelos longitudinales de efectos mixtos. Resultados Se incluyeron veinticinco ojos con EMD NAIVE de tratamiento. La AVMC basal se encontraba entre 0,3 y 1,3 en un logaritmo del gráfico visual de ángulo mínimo de resolución (LogMAR). El tipo de edema macular, la presencia de DRIL y el EMC presentaron un efecto estadísticamente significativo sobre la modificación de la AV a lo largo del tiempo (p< 0,001 en todos los casos). Los pacientes con DRIL mostraron menor ganancia de AV en términos LogMAR a los 9 meses que los pacientes sin DRIL, siendo la diferencia estadísticamente significativa (p=0,026), y mostraron menor mejoría en la AV a lo largo de los nueve meses de tratamiento (efecto de interacción p=0,007). Los subtipos de edema con desprendimiento seroso subfoveal, y con componente traccional por otro lado, ganaron menos visión que los pacientes que sólo presentaban edema macular de tipo cistoide. No hubo diferencias estadísticamente significativas entre la presencia de PH y la alteración de las capas retinianas externas con la AV a lo largo del tiempo de tratamiento. Conclusión Es de gran utilidad evaluar el EMC inicial, aunque no de manera aislada, así como es primordial evaluar y considerar la presencia de DRIL como biomarcador pronóstico, que en el presente estudio resultó ser el aquel con mayor potencial como predictor de respuesta clínica en términos de AV.Purpose To evaluate the association between the main biomarkers of Diabetic Macular Edema (DME) and the Visual Acuity (VA), and determine its importance as a prognostic tool at time to start an antiangiogenic treatment in each patient. Methods Retrospective, observational and longitudinal cohort study. 25 OCT scans of 23 patients with diabetic macular edema (DME) were analyzed, and the Best Corrected Visual Acuity (BCVA) at baseline and at 3, 6 and 9 months of treatment was registered. Baseline images were evaluated for predominant type of macular edema (cystoid, spongiform, with subfoveal serous detachment, or tractional compromise); presence of outer retinal damage (ORD, considered as any discontinuity in Limiting Extern Membrane, Ellipsoid Zone, and/or Interdigitation Zone); presence of disorganization of the Inner Retinal Layers (DRIL), and Hyperreflective Focis (HF) quantity, as well as Central Macular Thickness (CMT). Correlations between each OCT biomarker and visual acuity gain were analyzed using longitudinal mixed-effects models. Results Twentyfive eyes with NAIVE DME were included. Baseline best-corrected visual acuity (BCVA) was between 0.3 and 1.3 on a logarithm of minimum angle of resolution visual chart (logMAR). Type of macular edema, DRIL presence, and CMT presented a statistically significant effect on the VA modification along the time (p<0,001 in all cases). Patients with DRIL showed worse VA in logMAR terms at 9 months than patients without DRIL, being the difference statistically different (p=0,026), and showed less improvement in VA along the nine months treatment (interaction effect p=0,007). Eyes with subfoveal serous detachment and eyes with tractional component gained less vision than patients with only cystoid macular edema. There were no statistically significant differences between presence of hyperreflective focis, extern retinal layers alteration and VA along the treatment time. Conclusion This study showed that it is useful to assess the initial CMT but not in isolation, and above all the presence of DRIL, which proved to be the tomographic biomarker with the greatest potential as a predictor of clinical response in terms of VA.Fil: Dorrego, Camila Iris. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Pellice, Silvana. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Carauni, Ana Lisa. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Chiapella, Luciana Carla. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Dapena, Gimena. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Chamartin, Pablo. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Rocco, Franco Daniel. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Alezzandrini, Arturo Alberto. Universidad de Buenos Aires; Argentin

Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy

Anatomical and functional outcomes of symptomatic idiopathic vitreomacular traction

Purpose: To describe the natural history of eyes with symptomatic idiopathic vitreomacular traction (VMT). Methods: Retrospective multicenter study of 168 eyes with spectral-domain optical coherence tomography (SD-OCT) findings consistent with idiopathic VMT. All eyes were graded according to SD-OCT findings. Grade 1 was defined as incomplete cortical vitreous separation with foveal attachment. Grade 2 was defined as Grade 1 plus intraretinal cysts or clefts. Grade 3 was defined as Grade 2 plus a foveal detachment. All patients were followed for at least 6 months. Results: There were 168 patients (51 men) with a mean age of 68.8 ± 10.7 years. Patients were followed for a mean of 22.7 ± 20.1 months. The mean duration of symptoms before the initial presentation was 3.65 ± 5.42 months. At baseline, 72 eyes had Grade 1, 74 eyes had Grade 2, and 22 eyes had Grade 3 SD-OCT findings. Over the follow-up period, 36 eyes (21.4%) had spontaneous resolution of the VMT with normalization of the foveal anatomy. The mean time to resolution was 12.3 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of the eyes, with 6 eyes developing a lamellar macular hole and 7 eyes developing a full-thickness macular hole. This occurred at a mean of 10.3 ± 10.7 months after the presentation. Subgroup analysis based on baseline SD-OCT grade showed that 4.1% (3 of 73) of Grade 1 eyes compared with 6.8% (5 of 74) of Grade 2 eyes, and 23.8% (5 of 21) of Grade 3 eyes developed a full-thickness macular hole or lamellar macular hole (P 0.0109, chi-square test). In the remaining 119 eyes, at the last follow-up, 65 eyes had Grade 1, 42 eyes had Grade 2, and 12 eyes had Grade 3 VMT. On average, the best-corrected visual acuity improved from 0.40 ± 0.35 logarithm of the minimum angle of resolution (Snellen, 20/50) at baseline to 0.35 ± 0.36 logarithm of the minimum angle of resolution (Snellen, 20/45; P 0.0372), and the mean central macular thickness improved from 350 ± 132 m to 323 ± 121 m. Conclusion: Spontaneous resolution of VMT occurred in 21.4% (36 of 168) of eyes after a mean follow-up of 11.4 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of eyes. The baseline SD-OCT grade may predict the progression to full-thickness macular hole

Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma

Abordaje quirúrgico temporal en vitrectomía transconjuntival microincisional: una orientación diferente mejora el acceso a patologías superiores

Microincisional vitrectomy, performed with 23-, 25-, or 27-gauge instrumentation, offers many advantages when compared with conventional 20-gauge vitrectomy. Among the advantages is the possibility of creating small, self-sealing transconjunctival wounds that lead to less postoperative inflammation and patient discomfort and more rapid recovery of visual acuity compared with sutured 20-gauge wounds.1-7 In conventional surgery, the infusion cannula is placed in the inferotemporal quadrant, and 2 sclerotomies are performed in the upper quadrants. In microincisional surgeries, however, interchangeable microcannulas are used, so it is easier to change the position of the infusion cannula to one of the other accesses to the vitreous cavity. This allows the surgeon to perform vitrectomy with a temporal orientation— an approach that can be used regardless of whether it was planned prior to surgery

New treatment modalities for neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is considered one of the main causes of severe vision loss in older adults. The neovascular form (nAMD) is an advanced stage, which is responsible for the most severe vision loss. Vascular endothelial growth factor (VEGF) is at present the main factor that leads to the development of a neovascular membrane and the increased leakage from the membrane to the retina. At present, anti-VEGF therapy is the only treatment that achieves vision gains in many patients and halts progression in most of them. VEGF blockade can be achieved with several molecules and various treatment regimens, which have been studied with excellent results. Unfortunately, real-world data has shown to be far less efficacious than clinical trials. This gap between clinical trials and real-world results is an unmet medical need that supports the necessity of new treatment modalities for nAMD. Of the various treatments being studied, anti-VEGFs of higher efficacy and longer durability are those more advanced in their development. Brolucizumab and abicipar pegol are 2 new anti-VEGF drugs that had positive results in phase 2 studies and are being tested in phase 3 trials at present. Other promising therapies are antiangiopoietin 2 molecules, which are in phase 2 development. At earlier stages of development but with promising results are squalamine, anti-VEGF-C and -D, and gene therapy. The future will give retina specialists a broad armamentarium with which patients may achieve high visual gains for the long term with a low treatment burden. Copyright © 2017 by Asia Pacific Academy of Ophthalmology

New treatment modalities for neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is considered one of the main causes of severe vision loss in older adults. The neovascular form (nAMD) is an advanced stage, which is responsible for the most severe vision loss. Vascular endothelial growth factor (VEGF) is at present the main factor that leads to the development of a neovascular membrane and the increased leakage from the membrane to the retina. At present, anti-VEGF therapy is the only treatment that achieves vision gains in many patients and halts progression in most of them. VEGF blockade can be achieved with several molecules and various treatment regimens, which have been studied with excellent results. Unfortunately, real-world data has shown to be far less efficacious than clinical trials. This gap between clinical trials and real-world results is an unmet medical need that supports the necessity of new treatment modalities for nAMD. Of the various treatments being studied, anti-VEGFs of higher efficacy and longer durability are those more advanced in their development. Brolucizumab and abicipar pegol are 2 new anti-VEGF drugs that had positive results in phase 2 studies and are being tested in phase 3 trials at present. Other promising therapies are antiangiopoietin 2 molecules, which are in phase 2 development. At earlier stages of development but with promising results are squalamine, anti-VEGF-C and -D, and gene therapy. The future will give retina specialists a broad armamentarium with which patients may achieve high visual gains for the long term with a low treatment burden. Copyright © 2017 by Asia Pacific Academy of Ophthalmology