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.

Guidance on brolucizumab management recommendations.

PURPOSE: Brolucizumab, a new generation anti-VEGF, has demonstrated efficacy and safety in AMD in the pivotal HAWK and HARRIER trials. Post-marketing, previously undetected adverse events related to intraocular inflammation have been reported. An independent post hoc review of the pivotal trials puts the rate of IOI at 4.6%. The aim of this paper is to propose a set of recommendations for implementing the management of brolucizumab in clinical practice. METHODS: The recommendations made by the authors are based on their clinical experience, critical review of (i) the pivotal trials, the post-hoc analysis of the Safety Review Committee, (ii), and (iii) the published literature. RESULTS: In the pivotal trials, brolucizumab showed sustained functional gains, superior anatomical outcomes with potentially longer intervals between injections and a well-tolerated overall safety profile. Adverse events reported post-marketing include retinal vasculitis and retinal vascular occlusion. Based on the available information, experts recommend (i) ruling out non-recommended patient profiles (prior history of ORI), (ii) screening the patient prior to each injection to rule out active ORI, (iii) monitoring the patient for early warning signs, and (iv) treating immediately should any adverse events develop. CONCLUSIONS: The adverse events reported are rare, but may be associated with severe and irreversible loss of visual acuity. The recommendations made are intended to facilitate the management of brolucizumab in the routine practice of retinologists, to ensure patient safety and, should any adverse events occur, to minimise their impact on vision.

Vogt-Koyanagi-Harada: treatment of recurrence after administration of 3 intravenous bolus of 1 g of corticosteroids and mycophenolate mofetil.

The case is presented on a young Honduran female with no medical history of note, who presented with multiple areas of exudative retinal detachment (RD), and a best-corrected visual acuity of 1.3 logMAR in both eyes. She was diagnosed with incomplete Vogt-Koyanagi-Harada syndrome, and treated early with a combination of intravenous therapy with 1 g of prednisolone per day for 3 days, as recommended by published evidence, as well as mycophenolate mofetil (2 g per day). During the corticosteroids tapering, there was a recurrence of exudative retinal detachments, and megadoses of 1 g of intravenous corticosteroids per day were reintroduced for 6 days until the complete resolution of the fluid of the exudative RD, and cyclosporine (100 mg per day), subtenon triamcinolone (40 mg/mL), and intravitreal ranibizumab once a month in the both eyes were added to the treatment, with a great control of choroidal inflammation that resulted in the remission of symptoms and signs.

Vogt-Koyanagi-Harada: treatment of recurrence after administration of 3 intravenous bolus of 1g of corticosteroids and mycophenolate mofetil. / Vogt-Koyanagi-Harada: tratamiento de la recurrencia tras la administración de 3 bolos intravenosos de 1g de corticoides y micofenolato de mofetilo.

The case is presented on a young Honduran female with no medical history of note, who presented with multiple areas of exudative retinal detachment (RD), and a best-corrected visual acuity of 1.3logMAR in both eyes. She was diagnosed with incomplete Vogt-Koyanagi-Harada syndrome, and treated early with a combination of intravenous therapy with 1g of prednisolone per day for 3 days, as recommended by published evidence, as well as mycophenolate mofetil (2g per day). During the corticosteroids tapering, there was a recurrence of exudative retinal detachments, and megadoses of 1g of intravenous corticosteroids per day were reintroduced for 6 days until the complete resolution of the fluid of the exudative RD, and cyclosporine (100mg per day), subtenon triamcinolone (40mg/mL), and intravitreal ranibizumab once a month in the both eyes were added to the treatment, with a great control of choroidal inflammation that resulted in the remission of symptoms and signs.

Retinal pigment epithelial tears.

A retinal pigment epithelial (RPE) tear is a well-known complication of retinal pigment epithelial detachments (PED) and may cause a significant visual impairment. The most common cause is a vascularized PED in patients with exudative age-related macular degeneration (AMD). The development of diagnostic imaging techniques brings us closer to the etiology and pathophysiological mechanisms of this entity, offering us new strategies for treatment and follow-up. The advent of intravitreal antiangiogenic treatment (anti-VEGF) has led to an increase in the number of reported cases of RPE tears, which are an important vision-limiting factor during treatment. However, RPE tears may occur spontaneously or as a consequence of thermal laser treatment, photodynamic therapy or anti-VEGF therapy. It is accepted that the mechanism of RPE tears is multifactorial. The optimization of the functional outcome of this complication has been described with continuous treatment with antiangiogenic drugs. The goal of the present review is to evaluate the incidence, risk factors and treatment of RPE tears.

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.

Idiopathic macular telangiectasia type 2: Prevalence and a morphometric and phenotypic study. / Telangiectasias maculares idiopáticas de tipo 2: prevalencia en nuestra área y estudio morfométrico y fenotípico.

OBJECTIVE: Type 2 idiopathic macular telangiectasia (MacTel2) is a rare retinal disease that has still not been well-defined. The aim of the present manuscript is to describe the clinical features by multimodal retinal imaging, to present the functional characteristics, and to estimate the prevalence of the disease. METHODS: A retrospective study was conducted on the 12 eyes of 6 patients with MacTel2. Fundus colour photographs, fundus autofluorescence, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography were performed and subsequently analysed. Visual acuity (VA) was prospectively recorded. The prevalence was established based on the patients referred to a specialised macular diseases unit. Minimum follow-up period was 18 months. RESULTS: Prevalence of MacTel 2 in our study was 0.12%. Clinical features were presented using multimodal retinal imaging. VA remained stable during follow-up. Three patients developed choroidal neovascularisation (CNV), requiring intravitreal treatment with antiangiogenic agents. CONCLUSIONS: The prevalence of the disease found was 0.12%. The study using multimodal imaging allows a more accurate diagnosis and follow-up of this pathology. The VA is maintained during the 18-month follow-up (P=.492). Patients who develop CNV and are treated with antiangiogenic agents appear to respond adequately to them. More studies are needed to establish these conclusions.

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.