Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: sterile vs. infectious.

The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. Those drugs are associated to a higher rate of inflammatory adverse events compared to classic drugs. In this context it is essential to differentiate between sterile and infectious cases for a fast and effective treatment. The clinical similarities between infectious and sterile cases, the high rate of culture negative patients and the heterogeneity in the terminology used are obstacles for a correct diagnosis and report of these complications. Sterile cases appear early after the injection, before 48 h; or 20 days after in brolucizumab-related vasculitis cases. Infectious cases show up around the third day after injection and up to a week after it. A severe visual impairment, severe pain, severe hyperemia, hypopyon and a more severe intraocular inflammatory process are signs of a likely infectious origin. If the cause of the inflammation is uncertain we must follow up the patient closely or "tap and inject" antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation.

Evaluation of non-exudative tomographic signs in cases of exudative age-related macular degeneration.

OBJECTIVE: To analyse 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.

Incidence and clinical outcomes of the different neovascular forms of age-related macular degeneration in Valencia (Spain). / Incidencia y resultados clínicos de las distintas formas neovasculares de degeneración macular asociada a la edad en Valencia (España).

OBJECTIVE: To analyse the incidence and outcomes of the different neovascular subtypes in age-related macular degeneration (AMD). MATERIAL AND METHODS: A retrospective review was carried out on patients with neovascular AMD treated in the University and Polytechnic Hospital la Fe in Valencia by the same retinal physician (RGP) between December 2012 and July 2015. The anatomic classification of the neovascular lesions was recorded, as well as the number of intravitreal treatments administered and the change in visual acuity (VA) obtained throughout the follow-up. RESULTS: A total number of 174 eyes of 156 patients (mean age: 79.9years) with a minimum follow-up of 4 months were included. The anatomic classification of choroidal neovascularisation (CNV) showed the presence of type1 lesions in 40,8%, type2 lesions in 12%, type3 lesions in 31%, and mixed lesions in 14.4%, with 1.7% showing polypoidal choroidal vasculopathy features. Overall, the mean baseline VA was 0,32, improving to 0,38 at 24months, after having received a mean of 9.3 injections. Type2, 3, and mixed forms showed a visual result significantly lower than type1, but there was no significant difference in the polypoidal vasculopathy. CONCLUSIONS: Type 1 CNV was the most common finding, and was associated with a better visual prognosis, compared to the other neovascular lesions.

Geographic atrophy: Etiopathogenesis and current therapies. / Atrofia geográfica: etiopatogenia y terapias actuales.

Geographic atrophy is characterized by severe visual deficit whose etiology and pathophysiology are yet to be elucidated. As a working hypothesis, oxidative damage could trigger a chronic inflammation in Bruch's membrane-RPE-choriocapillaris complex, mostly due to complement pathway overactivation. Some individuals with mutations in the complement system and other factors have diminished capacity in the modulation of the inflammatory response, which results in cell damage and waste accumulation. This accumulation of intracellular and extracellular waste products manifests as drusen and pigmentary changes that precede the atrophy of photoreceptors, RPE, choriocapillaris with an ischemic process with decreased choroid flow. All these processes can be detected as tomographic findings and autofluorescence signals that are useful in the evaluation of patients with atrophic AMD, which helps to establish an individualized prognosis. Anti-inflammatory, antioxidant and therapies that decrease the accumulation of toxins for the preservation of the RPE cells and photoreceptors are being investigated in order to slow down the progression of this disease.

Cardiovascular involvement in patients with diabetic macular oedema treated with intravitreal ranibizumab in routine clinical practice. / Afectación cardiovascular en pacientes con edema macular diabético tratados con ranibizumab intravítreo en la práctica clínica habitual.

OBJECTIVE: To determine the cardiovascular events in naïve patients with diabetic macular oedema, before and after being treated with intravitreal ranibizumab. MATERIAL AND METHODS: A retrospective and descriptive study was conducted on patients with diabetic macular oedema and foveal involvement, who started treatment with intravitreal ranibizumab in 2014 in the Hospital Universitario Nuestra Señora de Candelaria and the Hospital Universitario y Politécnico La Fe. During the follow-up until August 2015, a record was made of parameters, including the prevalence and incidence of stroke and myocardial infarction. RESULTS: Among the 1,324 intravitreal ranibizumab injections administered in 2014, only 159 of them corresponded to treatment initiation in 99 patients, with more than half requiring treatment of both eyes. The study patients included 58.4% males, in the 6th decade of life (Mean=65.93±11.24 years), non-smokers (86.7%), type 2 diabetes (91.9%), hypertension (70.7%), and with dyslipidaemia (65.7%). Prior to treatment initiation, it was found that 6 patients (6.1%) suffered from an acute myocardial infarction, and 8 (8.1%) from stroke, and only one (1%) with post-stroke (P=.039). CONCLUSION: In our experience it seems that the intravitreal ranibizumab in diabetic macular oedema could be a safe alternative in patients with a history of stroke and myocardial infarction.

Implications of the anatomical classification of the neovascular form of age-related macular degeneration. / Implicaciones de la clasificación anatómica de la forma neovascular de la degeneración macular asociada a la edad.

OBJECTIVE: To present the clinical relevance of the anatomical classification of the neovascular form of Age-Related Macular Degeneration (AMD). METHODS: Critical analysis of the current situation in the management of patients with neovascular AMD, by reviewing the available scientific evidence with regards to the classification of the types of neovascular lesion by angiography and optical coherence tomography (OCT). RESULTS: The classification of the neovascular lesion type secondary to AMD by OCT in type 1 lesions (under the pigment epithelium), type 2 (subretinal), and type 3 (retinal angiomatous proliferation), provides an added value in allowing to establish a long-term visual prognosis, an estimate of the number of treatments that a certain case may require, and a stratification of the risk for secondary geographic atrophy. CONCLUSIONS: Incorporating OCT to the initial qualitative analysis of cases with neovascular AMD offers an added value superior to that provided by the angiography, with the relevant clinical implications.

Functional impact of treatment with ranibizumab under a reactive strategy in patients with neovascular age-related macular degeneration. / Impacto funcional del tratamiento con ranibizumab bajo una estrategia reactiva en pacientes con degeneración macular asociada a la edad exudativa neovascular.

OBJECTIVE: To analyse the functional recovery using a pro re nata (PRN) dosing strategy with intravitreal injections of ranibizumab for patients with neovascular age-related macular degeneration (AMD). MATERIAL AND METHODS: An observational, retrospective, single-centre study, was conducted on patients with neovascular AMD managed with a PRN strategy with ranibizumab, and were followed-up for a minimum of 18 months. Sociodemographic and clinical data were collected from medical records. The percentage of visual acuity (VA) recovered after losing 5 or more letters was calculated taking into account the previous visit, as well as considering the best VA recorded prior to the retreament. RESULTS: The analysis included 128 patients. The mean (SD) follow-up period was 18.9 (2.3) months. The mean (SD) elapsed days between onset of symptoms and diagnosis, and between prescription and administration of treatment was 50.2 (57.4) and 10.9 (16.0), respectively. Only 108 patients were prescribed ranibizumab after losing 5 or more letters of VA. The mean (SD) VA recovery compared to the previous VA was 70.3% (114.4). On the other hand, the mean (SD) VA recovery when considering the best VA registered before the retreatment was 43.5% (112.9), with 59.4% of re-treatments having a VA recovery below 75%, and with 11.7% not presenting any VA recovery. CONCLUSIONS: A PRN dosing strategy with intravitreal ranibizumab for neovascular AMD may not be efficient in preserving and/or recovering VA in the long-term, due to a cumulative irreversible VA loss.

Intravitreal therapies for non-neovascular age-related macular degeneration with intraretinal or subretinal fluid. / Terapias intravítreas en degeneración macular asociada a la edad no neovascular con fluido intrarretiniano o subretiniano.

OBJECTIVE: To evaluate the efficacy of intravitreal therapies in cases of atrophic age-related macular degeneration (AMD) with subretinal or intraretinal fluid. METHODS: A retrospective review was made of the clinical charts of patients diagnosed with atrophic AMD with subretinal or intraretinal fluid. Fundus photographs and spectral-domain optical coherence tomography images were examined, and an analysis was made on the presence of fluid and its density. Neovascularisation was ruled out by fluorescein and/or indocyanine green angiography. RESULTS: The study included 14 eyes from 13 patients with a mean age of 72.64 years and a mean follow-up of 80.5 weeks. Intraretinal fluid was observed in 6 eyes (42.9%), while subretinal fluid was shown in 8 eyes (57.1%), with high density in 4 eyes (28.5%), and low density in 4 eyes (28.5%). Snellen best-corrected visual acuity improved from 0.37 at baseline to 0.56 at the final visit (P=.002). Central subfield thickness (microns) significantly decreased (P<.001) from 291.0 at baseline to 228.9 at the final visit. Eight eyes received ranibizumab, 5eyes received bevacizumab, and one case received triamcinolone. CONCLUSIONS: Cases of atrophic AMD may present with subretinal or intraretinal fluid in the absence Neovascularisation. Further studies are required to analyse the value of this finding as a risk factor of developing advanced forms of AMD, as well as the efficacy of intravitreal therapies.

Systematic study of retinal vein occlusion in young patients. Case report and review of the literature.

PURPOSE: To report the case of a young woman with retinal vein occlusion and prothrombin heterozygous mutation, and to review the current evidence on the systematic study in cases of retinal vein occlusion (RVO) in young patients. METHODS: Eligible articles were identified using a comprehensive literature search of PubMed. CONCLUSION: RVO risk factors may have different relevance depending on each age group. In the systematic study of cases in young patients, it is recommended to look for "emerging" risk factors, bilateral involvement, or absence of "classic" risk factors.

Genetic systems for a new approach to risk of progression of diabetic retinopathy. / Sistemas genéticos para un nuevo abordaje del riesgo de progresión de la retinopatía diabética.

OBJECTIVE: To evaluate the risk of progression of diabetic retinopathy (DR) using new strategies to obtain genetic information in type 2 diabetes (T2D) based on interfering ribonucleic acid (RNA). MATERIAL AND METHODS: A prospective multicentre case-control study of 132 participants was distributed into: T2D with (+DR) or without (-DR) (T2DG; n=77), and a control group (CG; n=55). After an eye examination and personal interview, tears were collected for molecular analysis (expression of microRNAs [miRNAs] (miRCURY ™ ARN Isolation Kit, Qiagen)]. Libraries, 137 vs. 140bp (GeneMapper, Applied Biosystems), were obtained in 18 samples (T2DG+DR=6; T2DG-DR=6; CG=6) by performing next-generation sequencing (NGS). SPSS 15.0 statistical program was used to perform data analysis. RESULTS: The mean age was 67±12 years in the T2DG vs. 55±21 years in the CG. Distribution men/women: 25/30 in T2DG vs. 51/28 in CG. A family history of DM, diet compliance, smoking, drinking and exercise, showed significant differences between groups (P<.001). A 20-25 microlitre sample of tears contained a mean of 9.42±3.30 ng/mL of purified ARN, with significant differences between T2DG/CG (P=.002) and T2DG+RD/CG (P=.004). Tear expression of miARNs in T2DG directly correlated with age/obesity/T2D duration (P<.05), and indirectly with visual acuity (P<.05). A total of 14 miRNAs related to the presence, pathogenic mechanisms and risk factors for the progression of diabetic retinopathy, were identified. CONCLUSIONS: We propose to use tears as a source of genetic information for DM. Specific miRNAs involved in DR development and/or progression can be used as molecular biomarkers, and based on these, for developing future biotherapies.

[Goldmann-Witmer, definitive diagnosis in unifocal helicoid choroiditis]. / Goldmann-Witmer, diagnóstico de certeza en coroiditis unifocal helioide.

CASE REPORT: A 20 year-old healthy patient consulted due to acute loss vision in his left eye. A fundus examination showed a macular alteration compatible with unifocal helioid choroiditis, characterized by being an atypical inflammatory yellow-white, round, single lesion of approximately an optic disc in diameter. The etiology study detected low Antitoxoplasma gondii Ig G (immunoglobulin) titers. DISCUSSION: The non-specificity of the serology and the atypical characteristics of the lesion is a limitation in the diagnosis. The Goldmann-Witmer coefficient may be useful in the diagnosis of atypical lesions, by comparing the concentration of IgG from the serum and aqueous humor.

Aflibercept in exudative age related macular degeneration refractory to ranibizumab.

PURPOSE: The aim of this study is to determine the effectiveness, safety and cost of aflibercept in the treatment of wet age-related macular degeneration (ARMD) refractory to ranibizumab. METHODS: Retrospective observational study was conducted on patients diagnosed with wet ARMD, and previously treated with ranibizumab. Efficacy variables assessed were changes in visual acuity (BCVA) and anatomical improvements in the most affected eye. Factors associated with improvement of BCVA with aflibercept were also studied. Adverse events related to the aflibercept administration were recorded. Cost analysis data were collected from the hospital perspective, and only taking the direct medical costs into account. Cost-effectiveness analysis was calculated using the aflibercept treatment cost, and effectiveness calculated as BCVA gained. RESULTS: A total of 50 eyes corresponding to 46 patients were included. The median follow-up period was 4.6 months (range: 1.0-6.0). Improvement in visual acuity after the first 2 doses and at the end of the follow-up period was observed in 32.0 and 28.0% of treated eyes, respectively. None of the variables studied was associated with an improvement in the BCVA after treatment. No significant differences were found in the average monthly cost between treatments. CONCLUSIONS: Aflibercept is shown to be an effective treatment in a significant number of patients resistant to treatment with ranibizumab, presenting a cost similar to that generated during the final stages of treatment with ranibizumab.

Diagnóstico diferencial de las reacciones inflamatorias tras uso de medicación intravítrea en degeneración macular asociada a la edad: estéril vs. infeccioso / Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: Sterile vs. infectious

El interés por las complicaciones inflamatorias tras la inyección intravítrea de fármacos antiangiogénicos ha aumentado tras la comercialización de brolucizumab y el desarrollo de nuevas moléculas como el abicipar pegol. Dichos fármacos se asocian a una tasa de complicaciones inflamatorias mayor a los antiangiogénicos clásicos. En este contexto resulta clave el diferenciar procesos infecciosos y estériles para realizar un tratamiento efectivo y precoz. El solapamiento del cuadro clínico entre procesos infecciosos y estériles, la baja tasa de positividad en los cultivos y la heterogeneidad en la terminología son barreras para el correcto diagnóstico y reporte de las complicaciones inflamatorias tras la inyección de medicación antiangiogénica intravítrea. Los cuadros estériles comienzan de forma precoz tras la inyección, dentro de las primeras 48 h, o alrededor de 20 días después en los casos de vasculitis asociada a brolucizumab. Los procesos infecciosos comienzan como promedio en el tercer día tras la inyección, y hasta una semana después de la misma. La disminución grave de la agudeza visual, el dolor severo, la hiperemia severa, el hipopion y un mayor grado de inflamación intraocular deben orientar hacia procesos infecciosos. En los casos en que exista duda sobre la etiología de la inflamación, debe procederse a un control muy estrecho del paciente o al tratamiento antimicrobiano empírico junto con la toma de muestra para evitar complicaciones derivadas de una endoftalmitis infecciosa. Por el contrario, los fenómenos estériles deben ser tratados con observación en los casos más leves o corticoterapia adaptada a la gravedad de inflamación en los casos más graves (AU)

The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. Those drugs are associated to a higher rate of inflammatory adverse events compared to classic drugs. In this context it is essential to differentiate between sterile and infectious cases for a fast and effective treatment. The clinical similarities between infectious and sterile cases, the high rate of culture negative patients and the heterogeneity in the terminology used are obstacles for a correct diagnosis and report of these complications. Sterile cases appear early after the injection, before 48h; or 20 days after in brolucizumab-related vasculitis cases. Infectious cases show up around the third day after injection and up to a week after it. A severe visual impairment, severe pain, severe hyperemia, hypopyon and a more severe intraocular inflammatory process are signs of a likely infectious origin. If the cause of the inflammation is uncertain we must follow up the patient closely or “tap and inject” antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation (AU)

Evaluación de signos tomográficos no exudativos en casos de degeneración macular asociada a la edad de tipo exudativo / Evaluation of non-exudative tomographic signs in cases of exudative age-related macular degeneration

Objetivo Analizar la prevalencia de signos tomográficos no exudativos (signo de cebolla, seudoedema, tubulación de la retina externa, seudoquistes, hendiduras subretinianas y atrofia macular) en pacientes con degeneración macular asociada a la edad neovascular. Material y métodos Un total de 174 ojos de pacientes con degeneración macular asociada a la edad neovascular que no habían recibido tratamiento previo fueron incluidos en el estudio. Se valoró la agudeza visual, la actividad de la neovascularización y la aparición o no de los distintos signos objeto de estudio en los tiempos 0 (visita inicial), 4 meses, un año, año y medio y a los 2 y 3 años de seguimiento. Se evaluaron también: la edad, el sexo, el ojo afecto y el tipo de neovascularización (1, 2, 3, polipoidea o mixta). Los análisis se han realizado mediante el software estadístico R (versión 3.3.2) y el paquete glmmADMB (versión 0.8.3.3). Resultados La presencia de seudoquistes y tubulación de la retina externa va en aumento a lo largo del seguimiento. El signo de cebolla comienza con una frecuencia ascendente hasta los 12 meses, posteriormente desciende a los 18 meses y vuelve a incrementarse a los 24 meses. En cuanto al seudoedema, mantiene un incremento hasta los 18 meses para finalmente descender. Las hendiduras subretinianas son el signo más raro, presentándose en el 1,1% en la primera visita. Finalmente, la atrofia macular, presente en el 12,6% de los ojos inicialmente, se encuentra en el 25% a los 2 años. Conclusión Los seudoquistes, la tubulación de la retina externa y la atrofia macular fueron los signos más prevalentes, mientras que las hendiduras subretinianas fueron los más infrecuentes (AU)

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 (AU)

[Towards the new spectral-domain optical coherence tomography based classification of age-related macular degeneration]. / Hacia la nueva clasificación de la degeneración macular asociada a la edad basada en la tomografía de coherencia óptica de dominio espectral.

INTRODUCTION: Age-related macular degeneration (AMD) is major social and health problem in industrialised societies. The contribution of the new diagnostic techniques, mainly spectral-domain optical coherence tomography (SD-OCT), has led to a better understanding of this disease. AIM: To review the current clinical classification of AMD, to describe the new tomographic classification of wet AMD, and to review the new topographical findings in dry AMD. DEVELOPMENT: There are two classically described forms of AMD: dry and wet; there are also three progressive stages of severity: early, intermediate and advanced. This purely clinical stratification does not take into account any criteria based on SD-OCT. On the other hand, a new SD-OCT based classification has been proposed for choroidal neovascularisations secondary to AMD: types 1 (equivalent to occult), 2 (equivalent to classic), and 3 (equivalent to retinal angiomatous proliferation). Finally, SD-OCT offers exclusive and valuable information on the evaluation of dry AMD as regards subretinal drusenoid deposits, drusenoid pigment epithelium detachments, drusen coalescence, or the appearance of subretinal fluid in absence of choroidal neovascularisation. CONCLUSIONS: Dry AMD exhibits a range of tomographical signs that also have their own relative risk of progression to advance stages of the disease. We need an international consensus in order to follow-up and treat in the best way all those patients with AMD, not only with the wet but also with the dry form.