Evaluación preclínica de la toxicidad retiniana en la administración intravítrea de ácido docosahexaenoico en modelo experimental de conejo

Objetivo: Evaluar la toxicidad retiniana a corto plazo de la administración intravítrea de una dosis única de ácido docosahexaenoico (DHA) en un modelo experimental de conejo. Material y métodos: Dieciséis conejos albinos Nueva Zelanda fueron seleccionados para este estudio toxicológico preclínico. Se prepararon seis concentraciones de DHA (Brudy Laboratorios, Barcelona, España): 10mg/50μl, 5mg/50μl, 2'5mg/50μl, 50μg/50μl, 25μg/50μl, 5μg/50μl. Cada concentración fue inyectada por vía pars plana en inyección intravítrea en el ojo derecho de dos conejos. La solución vehículo se inyectó en el ojo derecho de cuatro animales que se consideraron el grupo control. Se evaluó la seguridad retiniana de cada concentración de DHA mediante la exploración clínica oftalmológica y la realización del electrorretinograma. Los animales fueron eutanasiados y sus ojos fueron enucleados y procesados para el estudio histológico mediante microscopía óptica. Al mismo tiempo se tomaron muestras de humor acuoso y vítreo 1 Rosa Dolz Marco Resumen para la cuantificación de ácidos grasos por cromatografía de gases. El análisis estadístico se realizó con el programa SPSS 21.0. Resultados: El examen clínico reveló una gran reacción inflamatoria en el segmento anterior en los conejos a los que se administró las concentraciones mas altas (10mg/50μl, 5mg/50μl, 2'5mg/50μl). Las concentraciones inferiores de DHA no produjeron respuesta inflamatoria. Los parámetros estudiados en el electrorretinograma y el examen histológico morfológico y morfométrico no mostraron diferencias estadísticamente significativas entre los conejos de los grupos control y aquellos en los que se administró una inyección intravítrea de DHA, salvo para la dosis de 50μg/50μl. Conclusión: Nuestros resultados indican que el DHA administrado por vía intravítrea es un agente farmacológico seguro en el modelo de conejo albino con una dosis máxima tolerada de 25μg/50μl. Este estudio deberá completarse con nuevos estudios que permitan evaluar el efecto de la administración intravítrea de DHA como tratamiento, per se o en combinación con otros fármacos, de diferentes enfermedades de la retina.Purpose: to evaluate the retinal toxicity of a unit dose of intravítrea pure docosahexaenoico acid (DHA) in rabbit eyes over a short-term period. Methods: Sixteen New Zealand albino rabbits were selected for this toxicology pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelone, Spain) were prepared: 10mg/50 μL, 5mg/50 μL, 2’5mg/50 μL, 50μg/50 μL, 25μg/50 μL, and 5μg/50 μL. Each concentration was injected intravitreally in one eye of two rabbits. As a control, the vehicle solution was injected into one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intreavitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histologic examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis were performed by SPSS 21.0 3 Rosa Dolz Marco Abstract Results: Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10mg/50μl, 5mg/50μl, 2'5mg/50μ) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected results at any of the concentrations except for the group injected with 50μg/50. Conclusions: Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25μg/50 μL. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination of different retinal diseases

Pattern Dystrophy of the Macula in a Case of Steinert Disease

IntroductionMyotonic dystrophies are typically associated with ocular complications like ptosis, weakness of the ocular muscle and cataracts, but also with less recognized retinal changes.Case ReportA 41-year-old female with type 1 myotonic dystrophy complained of progressive vision loss. Slit lamp examination revealed the presence of typical bilateral polychromatic cataract with posterior subcapsular component. Dilated fundus examination was remarkable for bilateral macular depigmented changes. Multimodal imaging analysis of the macula suggested the presence of a butterfly-shaped pattern dystrophy.DiscussionIn cases of myotonic dystrophies it is of great relevance to analyze the presence of retinal changes that might limit the visual improvement following cataract extraction

Adult Coats’ Disease Successfully Managed with the Dexamethasone Intravitreal Implant (Ozurdex®) Combined with Retinal Photocoagulation

Purpose: To report a case of Coats’ disease managed with the dexamethasone intravitreal implant Ozurdex® (Allergan, Inc., Irvine, Calif., USA) combined with retinal photocoagulation. Methods: A 46-year-old female with 20/200 visual acuity was diagnosed with Coats’ disease with secondary retinal vasoproliferative tumor. An initial approach was performed with an intravitreal injection of the sustained-release dexamethasone implant Ozurdex. After reattachment of the retina, the telangiectatic vessels were treated with laser photocoagulation. Results: The patient’s visual acuity improved to 20/25 after the intravitreal Ozurdex. No further recurrences of exudation were evident through the 12-month follow-up. Conclusions: Ozurdex may be an effective initial therapeutic approach for Coats’ disease with immediate anatomical response and visual improvement

Pachychoroid Diseases of the Macula

Advances in optical coherence tomography have enabled a better appreciation of the role of pathologic choroidal changes in a variety of retinal disease. A “pachychoroid†(pachy-[prefix]: thick) is defined as an abnormal and permanent increase in choroidal thickness often showing dilated choroidal vessels and other structural alterations of the normal choroidal architecture. Central serous chorioretinopathy is just one of several pachychoroid-related macular disorders. This review summarizes the current state of knowledge of the pachycoroid spectrum and the hallmark features seen with multimodal imaging analysis of these entitie

Pachychoroid Diseases of the Macula

Advances in optical coherence tomography have enabled a better appreciation of the role of pathologic choroidal changes in a variety of retinal disease. A “pachychoroid” (pachy-[prefix]: thick) is defined as an abnormal and permanent increase in choroidal thickness often showing dilated choroidal vessels and other structural alterations of the normal choroidal architecture. Central serous chorioretinopathy is just one of several pachychoroid-related macular disorders. This review summarizes the current state of knowledge of the pachycoroid spectrum and the hallmark features seen with multimodal imaging analysis of these entitie

Intravitreal docosahexaenoic acid in a rabbit model: preclinical safety assessment

Purpose The purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA) in rabbit eyes over a short-term period. Methods Sixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain) were prepared: 10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis was performed by SPSS 21.0. Results Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µ) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 µg/50 µl. Conclusions Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/50 µl. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination, of different retinal diseases

Serous Macular Detachment Associated with Dome-Shaped Macula and Tilted Disc

Introduction: An entirely new type of staphyloma has been recently described as dome-shaped macula (DSM). It is characterized by an abnormal convex macular contour within the concavity of a posterior staphyloma. We found DSM associated with serous macular detachment (SMD) and tilted disc in two consecutive cases. Case Reports: Case 1: A 37-year-old female presented to our department because of sudden onset blurred vision in her right eye (OD). The best-corrected visual acuity (BCVA) was 0.5 in both eyes. Funduscopy evidenced bilateral tilted disc associated with posterior staphyloma. Optical coherence tomography (OCT) demonstrated a DSM with SMD in her OD. After 15 months of follow-up, BCVA of her OD remained stable with chronic SMD. Case 2: A 32-year-old female presented to our department because of blurred vision in her OD. The BCVA was 0.4 in the OD and 1.0 in the left eye (OS). Bilateral tilted disc and posterior staphyloma were evidenced in the funduscopy. OCT demonstrated a bilateral DSM with SMD in her OD. After 45 months of follow-up, two further episodes of transient SMD were observed in her OD and seven in her OS. The final BCVA was 0.63 in the OD and 0.8 in the OS. Discussion: SMD associated with tilted disc constitutes a potential cause of subretinal fluid accumulation in myopic patients. OCT is essential for the detection of both SMD and DSM

Evaluación de signos tomográficos no exudativos en casos de degeneración macular asociada a la edad de tipo exudativo

Producción CientíficaABSTRACT. OBJECTIVE: To analyze the prevalence of non-exudative tomographic signs (onion sign, pseudoswelling, external retinal tubulation, pseudocysts, subretinal clefts and macular atrophy) in patients with neovascular age-related macular degeneration. MATERIAL AND METHODS: A total of 174 eyes of patients with neovascular age-related macular degeneration who had not received previous treatment were included in the study. Visual acuity, neovascularization activity, and the appearance or not of the different signs under study were assessed at times 0 (initial visit), 4 months, one year, year and a half, and at 2 and 3 years of follow-up. The following were also evaluated: age, sex, affected eye and type of neovascularization (1, 2, 3, polypoid or mixed). The analysis were performed using the statistical software R (version 3.3.2) and the glmmADMB package (version 0.8.3.3). RESULTS: The presence of pseudocysts and external retinal tubulation increases throughout the follow-up. The onion sign begins with an ascending frequency up to 12 months, then decreases at 18 months and increases again at 24 months. Regarding pseudowelling, it maintains an increase until 18 months to finally decrease. Subretinal clefts is the rarest sign, presenting in 1.1% on the first visit. Finally, macular atrophy, present in 12.6% of the eyes initially, is found in 25% after 2 years. CONCLUSION: Pseudocysts, external retinal tubulation and macular atrophy were the most prevalent signs, while subretinal clefts were the most infrequent

Fluid as a critical biomarker in neovascular age-related macular degeneration management: literature review and consensus recommendations.

Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAMD. However, few guidelines distinguished between types of fluid when providing recommendations. A total of 52 publications reported primary evidence from clinical trials, studies, and chart reviews. Observations from these were sometimes inconsistent, but trends were observed with regard to features reported as being predictive of visual outcomes. Based on these findings, diagnostic recommendations and a treatment algorithm based on a treat-and-extend (T&E) regimen were developed. These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the T&E regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity