Clinical features, management and outcomes of patients with sterile endophthalmitis associated with intravitreal injection of antivascular endothelial growth factor. / Características clínicas, manejo y resultados de los pacientes con endoftalmitis estéril asociados con la inyección intravítrea de factores de crecimiento endotelial antivascular.

PURPOSE: Analyze clinical features, management and outcomes of patients with sterile endophthalmitis associated with intravitreal antivascular endothelial growth factor. METHODS: Observational retrospective case series of patients with sterile endophthalmitis following anti-VEGF intravitreal injections. Clinical data of patients treated with intravitreal anti-VEGFs during one year have been revised. Those who have presented an episode of sterile endophthalmitis are analyzed and their causality and management are studied. RESULTS: Seven patients have had a sterile endophthalmitis onset within 4days after intravitreal injection (aflibercept n=5 and ranibizumab n=2). These patients have some active neovascular condition: age related macular degeneration (n=4), myopic choroidal neovascularization (n=1) or macular edema: diabetic macular edema (n=1), branch retinal vein occlusion (n=1). Shared signs and symptoms included painless vision loss, anterior chamber and vitreous cell and lack of hypopyon. In all patients, visual acuity returned to within one line of baseline acuity. CONCLUSION: Differentiating cases of sterile from infectious endophthalmitis may be challenging. It is crucial to differentiate both entities as a good diagnosis determines the visual prognosis. We should be aware of minimal inflammation after repeated intravitreal injections in order to establish the adequate treatment.

Longitudinal study of retinal nerve fiber layer thickness changes in a multiple sclerosis patients cohort: A long term 5 year follow-up.

PURPOSE: To analyze the changes in retinal nerve fiber layer (RNFL) in eyes with and without prior history of optic neuritis (ON) of patients with multiple sclerosis (MS) after a 5-year time period (2010-2015) using optical coherence tomography. METHODS: The RNFL thickness of 114 eyes of 57 MS patients and 40 eyes of 20 healthy subjects were measured in year 2010 and year 2015. Measurements were made separately in twelve sectors around the optic nerve head. Statistical comparisons were made with the obtained data. RESULTS: Progressive RNFL thinning occurs with time in both MS patients (regardless the eye had history of ON or not) and in normal subjects. The baseline mean RNFL thickness in ON eyes of MS patients (year 2010) was 74.2 ± 15.7µm and five years later was 68.7 ± 12.2µm. The baseline mean RNFL thickness in eyes without ON of MS patients was 90.0 ± 11.1µm and 84.7 ± 10.3µm five years later. The median RNFL thickness reduction was 3.5µm for ON eyes, 4.7µm for eyes without ON, and 2.2µm for control eyes. The RNFL thickness reduction rate was similar in eyes with history of ON that in those with no history of ON. On the contrary, the MS group had a significantly higher rate of reduction than the control group. CONCLUSIONS: MS patients have thinner RNFL than normal controls, regardless their eyes had past episodes of ON or not. Eyes of MS patients lose their axons in a similar fashion regardless they had history of ON or not. Although ON causes RNFL loss, once resolved it does not influence the rate of RNFL loss in MS patients.

[Intravitreal bevacizumab in the treatment of idiopathic juxtafoveal telangiectasis type I]. / Bevacizumab intravítreo como tratamiento de las telangiectasias yuxtafoveales idiopáticas tipo i.

CLINICAL CASE: We report a case of a 42 year-old male with a macular edema due to idiopathic juxtafoveal retinal telangiectasis type i, treated with 3 sequential injections of intravitreal bevacizumab (1.25 mg in 0.05 ml). Anatomical improvements were observed after one year of follow up. DISCUSSION: There is currently no general consensus regarding the treatment of unilateral idiopathic juxtafoveal telangiectasis. The therapeutic options are, grid laser photocoagulation, intravitreal triamcinolone, verteporfin photodynamic therapy, or anti-VEGF. Visual acuity and anatomical improvements were observed in this case after intravitreal bevacizumab. Thus, intravitreal bevacizumab seems to be effective to treat macular edema in idiopathic juxtafoveal telangiectasis type i.

Fundus autofluorescence: applications and perspectives.

PURPOSE: To describe the findings of the study of autofluorescence of the different retinal diseases included in the study. To determine in which diseases autofluorescence may be more, or just as, useful as fluorescein angiography (FAG) in terms of diagnostic information. MATERIAL AND METHODS: We studied the retinal autofluorescence of 123 eyes of 93 patients, including various diseases of the eye fundus. In all cases we explored the fundus, retinal autofluorescence, and, if indicated, FAG was performed. Analysis of the autofluorescence was performed using the Heidelberg Retina angiography Angiograph 2 (HRA2) Heidelberg Engineering (Germany). RESULTS: The autofluorescence information provided was equal or better (than FAG) in: 68.18% of cases of macular edema, 50% of pigment epithelium detachments, 100% of pigment epithelium atrophies, 100% of central serous chorioretinopathy; 55.55% of choroidal neovascularization, 100% of retinal dystrophies with deposition of lipofuscin, 100% of hard exudates and pre-retinal hemorrhages. CONCLUSIONS: Autofluorescence is a quick and non-invasive examination method, comfortable for both patient and examiner, and with a very short learning curve. It provides diagnostic information about many eye fundus diseases. While more studies and more experience with its use are needed, its interest lies in the possibility of avoiding the performing of angiography in patients with these diseases, and in the additional information autofluorescence provides about the functional situation of cells and retinal pigments.

Triamcinolone and bevacizumab as adjunctive therapies to panretinal photocoagulation for proliferative diabetic retinopathy.

Purpose. To evaluate efficacy of intravitreal triamcinolone (IVT) and bevacizumab (IVB) as adjunctive treatments to panretinal photocoagulation (PRP) in proliferative diabetic retinopathy (PDR). Methods. In 60 eyes of 45 patients with PDR, PRP (PRP group), PRP with IVT (IVT group), or PRP with IVB (IVB group) was performed. Regression of new vessels (NV), changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and contrast sensitivity at 1,2, and 6 months were evaluated. Results. Initial mean numbers of active NV and BCVA were 3.45 and 67.35 in the PRP group, 4.35 and 76.65 in the IVT group, and 4.79 and 75.53 in the IVB group. At the 6-month follow-up, numbers of active NV were 2.5 (P = 0.064), 1.11 (P = 0.000), and 1.11 (P = 0.002), and there was a mean loss of 2,6 (P = 0.055), 3.9 (P = 0.011), and 0.9 letters (P = 0.628) in the PRP, IVT, and IVB groups, respectively. Changes in CMT in the PRP and IVT groups were not significant, but significantly increased in the IVB group (P = 0.032). Contrast sensitivity remained stable in PRP and IVB groups and slightly decreased in IVT group. Conclusions. Adjunctive use of both triamcinolone and bevacizumab with PRP lead to a greater reduction of active NV than PRP alone in PDR, although no differences were seen between the two of them.

[From scientific evidence to clinical practice: treatment regimens for macular edema secondary to retinal vein occlusion]. / De la evidencia cientifica a la practica clinica: pautas de tratamiento del edema macular secundario a oclusion venosa retiniana.

Retinal vein occlusion (RVO) is the second most common cause of retinal vascular disease after diabetic retinopathy. Despite the existence of several possible treatment options, none was entirely satisfactory and many patients suffered irreversible visual loss. As a result of the BRAVO, CRUISE and GENEVA trials, ranibizumab and the intravitreal biodegradable implants of dexamethasone has recently been approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of RVO secondary edema. In this paper we begin by describing the current treatment options for RVO associated macular edema and continue with the description of the treatment regimen with ranibizumab.

Development and validation of a computer-aided diagnostic tool to screen for age-related macular degeneration by optical coherence tomography.

BACKGROUND: To develop and assess the technical validity of new computer-aided diagnostic software (CAD) for automated analyses of optical coherence tomography (OCT) images for the purpose of screening for neovascular age-related macular degeneration. METHODS: Artificial visual techniques were used to develop the CAD in two steps: normalisation and feature vector extraction from OCT images; and training and classification by means of decision trees. Technical validation was performed by a retrospective study design based on OCT images randomly extracted from clinical charts. Images were classified as normal or abnormal to serve for screening purposes. Sensitivity, specificity, positive predictive values and negative predictive values were obtained. RESULTS: The CAD was able to quantify image information by working in the perceptually uniform hue-saturation-value colour space. Particle swarm optimisation with Haar-like features is suitable to reveal structural features in normal and abnormal OCT images. Decision trees were useful to characterise normal and abnormal images using feature vectors obtained from descriptive statistics of detected structures. The sensitivity of the CAD was 96% and the specificity 92%. CONCLUSIONS: This new CAD for automated analysis of OCT images offers adequate sensitivity and specificity to distinguish normal OCT images from those showing potential neovascular age-related macular degeneration. These results will enable its clinical validation and a subsequent cost-effectiveness assessment to be made before recommendations are made for population-screening purposes.

[SERV clinical practice guidelines: management of retinal vein occlusion. Sociedad Española de Retina y Vitreo]. / Guías de práctica clínica de la SERV: manejo de las oclusiones venosas de la retina. Sociedad Española de Retina y Vitreo.

PURPOSE: A guidelines for the management of retinal vein occlusion is presented. This is necessary because at this moment several therapeutic alternatives have been developed although their role is not yet sufficiently defined. METHODS: Review of the literature for evidence published up to date. Relevant literature was identified and the level of evidence graded. Evidence was then assessed for consistency, applicability and clinical impact. The information was contrasted with those guides published in other countries. RESULTS: Taking into account the different options of treatment that are currently used, several modes of action are suggested. The role of the various complementary examinations are discussed and it is recommended that criteria for the treatment are based on clinical, angiographic, and tomographic findings. CONCLUSIONS: Although there is no overall consensus, these guidelines promote a good standard of clinical practise and provide an update of the management of retinal vein occlusion.

Sirius: a web-based system for retinal image analysis.

PURPOSE: Retinal image analysis can lead to early detection of several pathologies such as hypertension or diabetes. Screening processes require the evaluation of a high amount of visual data and, usually, the collaboration between different experts and different health care centers. These usual routines demand new fast and automatic solutions to deal with these situations. This work introduces Sirius (System for the Integration of Retinal Images Understanding Services), a web-based system for image analysis in the retinal imaging field. METHODS: Sirius provides a framework for ophthalmologists or other experts in the field to collaboratively work using retinal image-based applications in a distributed, fast and reliable environment. Sirius consists of three main components: the web client that users interact with, the web application server that processes all client requests and the service module that performs the image processing tasks. In this work, we present a service for the analysis of retinal microcirculation using a semi-automatic methodology for the computation of the arteriolar-to-venular ratio (AVR). RESULTS: Sirius has been evaluated in different real environments, involving health care systems, to test its performance. First, the AVR service was validated in terms of precision and efficiency and then, the framework was evaluated in different real scenarios of medical centers. CONCLUSIONS: Sirius is a web-based application providing a fast and reliable work environment for retinal experts. The system allows the sharing of images and processed results between remote computers and provides automated methods to diminish inter-expert variability in the analysis of the images.

[Management of intravitreal injections]. / Manejo de las inyecciones intravítreas.

PURPOSE: The intravitreal injection is a minimally invasive technique which has been proved to be an effective therapy in the management of numerous vitreoretinal diseases. Its use has been rapidly increased in the last few years due to new medications and indications. However, non-standardized performance of this procedure might cause severe complications, being of special concern intraocular infection. The aim of this Guide is to give ophthalmologists, with the information we have up to date, the guidelines needed to make this procedure safe. METHODS: 1. Reviewing the literature regarding evidence published up to date. 2. Consulting with experienced surgeons their common practice in this technique. 3. Contrasting the information from this Guide with those guides published in other countries. RESULTS: Although there is no complete consensus regarding the intravitreal injection procedure technique, the recommendations in this Guide are, up to date from our point of view, the most appropriate to prevent complications, specially infection. Of most importance are antisepsis with povidone iodine, the use of sterile material and gloves and an adequate injection technique. CONCLUSIONS: Large series published of intravitreal injections which took place in clinic settings applying a procedure technique as recommended in this Guide, presented a very low incidence of complications, specially endophthalmitis.

Intravitreal bevacizumab to treat subfoveal choroidal neovascularisation in highly myopic eyes: 1-year outcome.

AIMS: The aim of the study was to examine the changes in visual acuity, fluorescein angiography (FA) and optical coherence tomography (OCT) macular thickness of subfoveal, and juxtafoveal choroidal neovascularisation (CNV) in highly myopic eyes treated by intravitreal bevacizumab. METHODS: The study was a prospective, non-randomised, multicentre, interventional case series. Twenty-nine highly myopic eyes from 28 patients with subfoveal and juxtafoveal CNV were treated by three monthly intravitreal injections of 1.25 mg bevacizumab. Patients were evaluated for best-corrected visual acuity (BCVA) and OCT at baseline and then monthly for 1 year. FA was performed at baseline, after 3 months, and whenever CNV activity was suspected. RESULTS: The average age was 50 (SD 15, range 29-82) years. The mean LogMAR BCVA at baseline was 0.55 (SD 0.25, range 0.2-1.0) and 0.38 (SD 0.32, range 0.0-1.2) at 1 year. Sixteen eyes were naïve for treatment and 13 eyes had been previously treated by photodynamic therapy (average 2.5 sessions). Leakage from CNV had ceased in all eyes at month 3. OCT central foveal thickness decreased significantly from 282 (SD 68) mum at baseline to 224 (SD 46) mum at month 12 (p = 0.008, Student t test for paired data). Six eyes needed one re-injection during follow-up at month 4 (one eye), month 6 (four eyes) and month 12 (one eye). Neither ocular nor systemic adverse reactions appeared during follow-up. CONCLUSIONS: The results of this case series suggest that intravitreal bevacizumab seems to be an effective therapeutic procedure to treat subfoveal and juxtafoveal CNV in highly myopic eyes at 1-year follow-up. Further studies are required to verify the efficacy and usefulness of this therapy compared with established treatments for this condition.

Intravitreous bevacizumab to treat subfoveal choroidal neovascularization in highly myopic eyes: short-term results.

AIM: To describe the anatomical and visual outcome of subfoveal and juxtafoveal choroidal neovascularization (CNV) in highly myopic eyes treated by intravitreal bevacizumab. METHODS: Prospective, nonrandomized, multicentric, interventional pilot study. Twenty-six highly myopic eyes from 25 patients with subfoveal and juxtafoveal CNV were treated by three monthly intravitreal injections with 1.25 mg bevacizumab. Patients were evaluated for best-corrected visual acuity (BCVA) and optical coherence tomography at baseline and then monthly. Fluorescein angiography was performed at baseline and at month 3. RESULTS: Patients averaged 49.5 years of age (SD 16.0, range 29-82). Five patients were male and 20 were female. BCVA at baseline averaged 20/62 (range 20/200-20/32) and 20/38 (range 20/160-20/20) at month 6. Average central foveal thickness was 282.4 microm (SD 68.3, range 168-447) at baseline and 224.0 microm (SD 46, range 132-294) at month 6. Fifteen eyes were naïve for treatment and 11 eyes had been previously treated by photodynamic therapy (PDT) (average 2.5 PDT sessions). Leakage from CNV had ceased in all eyes at month 3 and CNV was still closed at month 6. Neither ocular nor systemic safety issues appeared during the follow-up. CONCLUSIONS: Intravitreal bevacizumab seems to be an effective and safe therapeutic procedure to treat subfoveal and juxtafoveal CNV in highly myopic eyes. Further studies are required to verify the efficacy and usefulness of this therapy compared with established treatments for this condition.

[Urgent retinal detachment management by the National Health System of Spain. Project Retina 2]. / Manejo de los desprendimientos de retina regmatógenos urgentes en el Sistema Nacional de Salud de España. Proyecto Retina 2.

OBJECTIVE: To identify problems in the urgent management of retinal detachments (RD) in hospitals of the Spanish National Health System (NHS). METHODS: A questionnaire was submitted confidentially to the heads of Ophthalmic Departments of 217 hospitals of the NHS to obtain information on the management of urgent RD during the last year. Data was stored in a Microsoft Access database and statistically analyzed by Excel and Statgraphics. Qualitative variables were analyzed by Chi-Square and Fisher exact tests and quantitative variables by the Kruskall-Wallis test. RESULTS: A global response rate of 54.8% was achieved with higher participation of the Teaching Hospitals (TH). District Hospital and non-Teaching Hospital responses were similar and grouped as non-TH. Eighteen percent of centers, mostly non-TH, had no ophthalmologist on duty. Thirty-six percent had a vitreoretinal specialist on call. Eighty percent of centres admitted to have problems handling urgent RD during weekends. Twenty-four had no ophthalmic surgical theatre available. Fifty percent referred to have problems having an anaesthesiologist available and only 22% had ophthalmic trained personnel (nurses) available. Sixty-four percent of centres performed pars plana vitrectomy (PPV) and 77% of those were able to perform an urgent PPV. Ninety percent admitted that a patient with a macula-threatening RD occurring at the beginning of the week-end would not be treated until at least 24 hours had elapsed, although 84% considered this to be inadequate. CONCLUSION: Despite the methodological problems and bias of this questionnaire, we did identify several important problems in the management of urgent RD by NHS hospitals. The data obtained provides useful information to enable the quality of the NHS care of RD to be improved, particularly that available at the week-end.

[National survey on vitreo-retinal surgery and the management of rhegmatogenous retinal detachments in Spain. Project retina 2]. / Encuesta nacional sobre la cirugía vítreo-retiniana y la atención de los desprendimientos de retina regmatógenos en España. Proyecto retina 2.

PURPOSE: To obtain information throughout Spain on the current management of vitreo-retinal surgical diseases, the number of ophthalmologists involved in retinal surgical diseases care, and the urgent management of retinal detachments. METHODS: A 30 item questionnaire was sent by mail, on two separate occasions, to the heads of Ophthalmology Departments of 276 centers in Spain. RESULTS: A total response rate of 48.2% was achieved, however the answers from private centers represented only 9.4% of the total so these were excluded from the analysis. The centers most likely to respond were those in Teaching Hospitals (TH) (52.3%). Of these, 64% of hospitals responded that, in the last year, they performed pars plana vitrectomies (PPV) and 70% performed more than 100 PPVs in the year. In all, 77% of the centers that performed PPVs had also performed them urgently. A total of 75% of hospitals indicated that they had ophthalmologists mainly dedicated to retinal diseases care, with a median of 2 specialists per center, with this representing 23% of their total staff. Retinal surgery was performed by general ophthalmologists in 11.5% of centres. Only 40.3% of hospitals audit their results (37.5% TH). CONCLUSIONS: Despite the existence of a relatively low response rate, as well as some biases and methodological problems, data on the management of retinal surgical disease has been obtained for the first time at a national level. This data will facilitate later studies and must be taken into consideration in improving the planning and adequate management of these diseases in Spain.

Comparison of different techniques for purification of triamcinolone acetonide suspension for intravitreal use.

BACKGROUND: Intravitreal triamcinolone has increasingly been used for the treatment of oedematous and neovascular diseases and purification of triamcinolone suspension may be important in order to avoid the potential toxic effects of the vehicle. The aim was to evaluate different techniques used to reduce the solvent agent benzyl alcohol (9.9 mg/ml) from a commercially prepared triamcinolone acetonide suspension. METHODS: Different techniques were used to reduce the solvent agent benzyl alcohol: filter techniques using 0.22 mum or 5 mum pore size, and non-filter techniques using sedimentation or centrifugation. Quantification of triamcinolone acetonide and benzyl alcohol was performed by high pressure liquid chromatography (HPLC). RESULTS: Benzyl alcohol concentration was decreased significantly in all the techniques used compared with the original commercial suspension (p<0.05), with no significant differences among them. The reduction was approximately one tenth of its original concentration. However, triamcinolone acetonide concentration differed significantly depending on the method used. Centrifugation method showed no differences versus the original commercial solution; sedimentation technique reduced the expected dose only 25%; the filter technique using a 5 mum pore size membrane reduced the expected dose to one fourth, while the filter technique using a 0.22 mum pore size membrane reduced the expected dose to 45%. CONCLUSIONS: All the different techniques employed effectively reduced the concentration of benzyl alcohol. However, the final concentration of triamcinolone was much lower than expected using the filter techniques. The pore size membrane inversely influenced the final concentration, with part of the triamcinolone crystals probably being entrapped in the filter. Centrifugation is recommended as the best way of administering the drug.

Reproducibility of optic nerve head measurements obtained by optical coherence tomography.

PURPOSE: To evaluate reproducibility of optic nerve head (ONH) morphometry measurements obtained by optical coherence tomography (the fast optical disk protocol of the -Zeiss model 3000 OCT system) in normal and glaucomatous eyes. METHODS: Prospective instrument-evaluation study. ONH measurements for 20 eyes were obtained in eight scan sessions taken during two visits to an ophthalmology clinic (10 normal patients, 10 glaucoma patients, one eye per subject). At every one of the eight sessions for each eye, estimates of eight ONH morphometry variables (see Main outcome measures) were obtained. The first two sessions were performed by two operators, followed by a 30-minute break. The same operators then completed a third and fourth session. This sequence was duplicated on a second visit. Intrasession, intersession, intervisit, and interoperator reproducibility of the eight variables were calculated by the use of a components variance model. Intraclass correlation coefficients (ICC) were used to assess reliability. RESULTS: Vertical integrated rim area, horizontal integrated rim area, disk area, cup area, rim area, cup/disk area ratio, cup/disk horizontal ratio, cup/disk vertical ratio. With the exception of the horizontal integrated rim area and rim area in normal subjects, the factor subject was the most important source of variance for all variables. Reliability values as measured by ICC for normal eyes were above 81%, with the exception of measurements of the horizontal integrated rim area (23.1%), rim area (33.3%), and disk area (64.7%). For glaucomatous eyes all values were above 85%, with the exception of the disk area (68.1%). CONCLUSIONS: ONH measurements obtained using the fast optical disk protocol of the Zeiss 3000 OCT system show good reproducibility, for both normal and glaucomatous eyes.