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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 4 days 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.

Optical Coherence Tomography (OCT) imaging has revolutionized the daily clinical practice, especially in the field of ophthalmology. Diabetic Macular Edema (DME) is one of the most important complications of diabetes and a leading cause of preventable blindness in the developed countries. In this way, a precise identification and analysis of DME biomarkers allow the clinical specialists to make a more accurate diagnosis and treatment of this relevant ocular disease.

Diabetic macular edema is a relevant ocular disease associated with diabetes mellitus that constitutes a concerning global health issue. This disease is one of the main causes of reversible blindness in industrialized countries, despite the availability of effective health interventions. This macular disorder is a consequence of the appearance of abnormal fluid regions within the main tissues of the retina that significantly decrease the patient's visual acuity. These fluid accumulations are also known as macular edemas (MEs). In this chapter, we present a computational methodology for the identification and clinical classification of ME using optical coherence tomography (OCT) scans, following the clinical classification of reference in the ophthalmological field. The presented system was tested with a dataset composed of 170 OCT scans retrieved from different patients that were labeled by a clinical expert. The presented system obtained satisfactory results in the localization of the area affected by each type of ME, even when they are combined in the same region of the retina. This fully automatic tool has demonstrated to be very useful not only for patients (helping in the early diagnosis of diseases that, consequently, improve their quality of life and well-being), but also in clinical systems by reducing costs.

Combined central retinal artery and vein occlusion is an uncommon vascular pathology that can cause severe and permanent visual impairment. Optical coherence tomography angiography (OCTA) is a newly available, noninvasive imaging technique that can potentially improve understanding of the structural and vascular implications and prognosis of this infrequent pathology. The present report describes the principal clinical findings in a case of combined central retinal artery and vein occlusion, as detected by the different imaging modalities available in a tertiary referral hospital. OCTA wide-field montage images identified an extensive area of nonperfusion on the macula with involvement of the entire retina at nearly 360°. We observed the most severe nonperfusion in the deep capillary plexus, while perfusion of the choriocapillaris was unaffected. Meanwhile, fluorescein angiography (FA) findings revealed a delay in perfusion rate with marked nonperfusion areas in the peripheral retina at 360°. We identified that the wide-field OCTA montage permitted visualization of a similar or wider peripheral retinal area compared with FA. Therefore, OCTA is potentially useful for assessment of the global retinal nonperfusion status at baseline and during follow-up, with the added advantage of being a noninvasive technique This work was supported in part by the Mutua Madrileña project (Ref. 2017/365) SI

A formulation of aflibercept for intravitreal injection (Eylea) is approved for the treatment of patients with exudative age-related macular degeneration (AMD). Aflibercept has a significantly higher affinity for Vascular endothelial growth factor (VEGF)-A compared with other monoclonal anti-VEGF antibodies. In addition to binding all VEGF-A isoforms, aflibercept also blocks other proangiogenic factors such as VEGF-B and placental growth factor. The VIEW 1 and 2 trials showed this drug achieves improved results in patients with exudative AMD similar to those obtained with monthly ranibizumab, using a bimonthly treatment regimen after a loading dose of three intravitreal injections, which translates to less use of healthcare resources. There is a subgroup of patients that present with persistent fluid after the loading dose that could benefit from monthly injections or personalized proactive treatment after the first year. In the second year of treatment, the Treat and Extend patterns can permit even more lengthening of the time between injections. More data are needed to confirm the optimal monitoring and retreatment dosing, to maintain long-term efficacy. Other preliminary data suggest that patients that do not respond to other anti-angiogenics and patients with special pathologies such as polypoidal choroidopathy or retinal angiomatous proliferation can improve upon switching to aflibercept. To date, the safety profile of aflibercept is excellent and is comparable to other anti-angiogenic treatments.

Objectives. To evaluate efficacy and safety of an aflibercept treat-and-extend (TAE) regimen in patients with macular oedema (MO) secondary to central retinal vein occlusion (CRVO). Design, Setting, and Patients. Phase IV, prospective, open-label, single-arm trial in 11 Spanish hospitals. Treatment-naïve patients with Intervention. Intravitreal aflibercept 2 mg monthly (3 months) followed by proactive individualized dosing. Main Outcomes. Mean change in BCVA after 12 months. Results. 24 eyes (24 patients) were included; mean (SD) age: 62.8 (15.0) years; 54.2% male; median (IQR) time since diagnosis: 7.6 (3.0, 15.2) days. Mean BCVA scores significantly improved between baseline (56.0 (16.5)) and Month 12 (74.1 (17.6)); mean (95% CI) change: 14.8 (8.2, 21.4); P=0.0001. Twelve (50.0%) patients gained ≥15 ETDRS letters. Foveal thickness improved between baseline (mean: 569.4 (216.8) µm) and Month 12 (mean 257.4 (48.4) µm); P<0.0001. At Month 12, 8.3% patients had MO. The mean (SD) number of injections: 8.3 (3.0). No treatment-related AEs were reported. Five (20.8%) patients experienced ocular AEs. Two nonocular serious AEs were reported. Conclusions. An aflibercept TAE regimen improves visual acuity in patients with MO secondary to CRVO over 12 months with good tolerability.

We performed a systematic review and meta-analysis to determine whether the use of local antibiotics is a beneficial prophylactic treatment for endophthalmitis in patients treated with anti-VEGF agents. We searched the MEDLINE and EMBASE databases, and the Cochrane Library over the period January 2007 to December 2016. The search terms used included “Endophthalmitis”, “Antibiotic” and “Intravitreal injection”. Studies in which the patients were treated exclusively with intravitreal injections of anti-VEGF were selected. Eight studies fit the inclusion criteria, which included a total of 276,774 injections; 109,178 (39.45%) were associated with the use of antibiotics and 114,821 (60.55%) were not associated with the use of antibiotics. Our meta-analysis indicated a significant risk for endophthalmitis that was 1.70 times greater with the use of antibiotics than that without antibiotics, with a confidence interval of 1.08 to 2.66 (p = 0.02). A meta-regression indicated that the location (operating rooms versus outpatient clinics) of injection did not have a significant effect on the incidence of endophthalmitis. The prophylactic use of antibiotics when administering anti-VEGF intravitreal injections may contribute to a greater incidence of endophthalmitis. This finding, in addition to reducing costs, would eliminate a treatment that has been shown to be unnecessary and even harmful to patients.

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 ± 15.7 µm and five years later was 68.7 ± 12.2 µm. The baseline mean RNFL thickness in eyes without ON of MS patients was 90.0 ± 11.1 µm and 84.7 ± 10.3 µm five years later. The median RNFL thickness reduction was 3.5 µm for ON eyes, 4.7 µm for eyes without ON, and 2.2 µm 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.

This work aimed at describing the time course of vitreous clearance through the use of positron emission tomography (PET) as a noninvasive tool for pharmacokinetic studies of intravitreal injection.The pharmacokinetic profile of intravitreal injections of molecules labeled with 18Fluorine (18F) was evaluated in adult Sprague Dawley rats by using a dedicated small-animal PET/computed tomography scanner. Different conditions were studied: three molecules radiolabeled with 18F (18F-FDG, 18F-NaF, and 18F-Choline), three volumes of intravitreal injections (7, 4, and 2 μL), and absence or presence of eye inflammation (uveitis).Our results showed that there are significant pharmacokinetic differences among the radiolabeled molecules studied but not among the injected volumes. The presence or absence of uveitis was an important factor in vitreous clearance, since the elimination of the drug was clearly increased when this condition is present.Intravitreal pharmacokinetic studies based on the use of dedicated PET imaging can be of potential interest as noninvasive tools in ophthalmic drug development in small animals.

The foveal avascular zone (FAZ) is the capillary-free area in the central macula with high photoreceptor density and metabolic activity. In the present study we measured the superficial and deep macular foveal avascular zone (sFAZ, dFAZ) in the eyes of healthy adults of both sexes of various ages ranging from 10 to 69 years using optical coherence tomography angiography (OCT-A) in order to evaluate the influence of gender and age on FAZ size. A cross-sectional study was carried out in 240 eyes of 120 healthy subjects, OCT-A was performed by means of a Topcon swept source OCT. sFAZ and dFAZ areas were measured using the IMAGEnet6 software package. Subjects were grouped by age (six groups) and gender. The mean ± sd age of the subjects was 39.2 ± 17.4 years (50% women, 50% men), ranging from 10 to 69 years. The overall mean sFAZ size in women (0.297 ± 0.110 mm2) was significantly larger (p = 0.002) than in men (0.254 ± 0.098 mm2). Similarly, the overall mean dFAZ in women (0.322 ± 0.111 mm2) was significantly larger (p In conclusion for both sFAZ and dFAZ, women have larger areas than men, but this occurs only in the young and old age groups. In men, age does not seem to influence the size of the FAZ, but in women, both sFAZ and dFAZ were significantly smaller in younger than in older ages. These results suggest that retinal changes in retinal structure caused by aging may be different in woman than in men, probably reflecting the more hormonal variations known to exist with age in women.

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.

Diabetic retinopathy is one of the leading causes of vision loss worldwide. Fluorescein angiogram still plays a primary role in its diagnosis but new non-invasive technologies as optical coherence tomography, fundus autofluorescence and microperimetry are gaining popularity in the last years. Anatomical changes found with these devices have been widely described but their correlation with visual function needs to be assessed and several features have been proposed as indicators of visual prognosis. The aim of this paper is to give a scope of the actual role of these techniques in the evaluation of retinal impairment secondary to diabetes.

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.

Although intravitreal administration of anti-infectives represents the standard treatment for infectious endophthalmitis, the knowledge about their pharmacokinetics is still limited. In this review, we aimed to summarise the factors influencing the pharmacokinetics of the anti-infective agents. We have conducted a comprehensive review of the preclinical pharmacokinetic parameters obtained in different studies of intravitreal injections of anti-infectives performed on animals, mainly rabbits. The two aspects with the biggest influence on pharmacokinetics are the distribution in the vitreous humour and the elimination through the posterior segment. The distribution can be affected by the molecular weight of the drug, the convection flow of the vitreous, the condition of the vitreous humour depending on the age of the patient, the possible interactions between the drug and the components of the vitreous, and the presence of vitrectomy. Meanwhile, the elimination includes the metabolism of the drug, the clearance via the anterior and posterior routes, and the possible inflammation of the eye resulting from the disease. Understanding the pharmacokinetics of the anti-infectives used in clinical practice is essential for a correct application. The information provided in this review could offer guidance for selecting the best therapeutic option according to the characteristics of the drugs.

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. © 2010 Published by Elsevier Espana, S.L.

PURPOSE. To evaluate the efficacy of intravitreal bevacizumab to treat retinal angiomatous proliferation (RAP) stages II and III. METHODS. A retrospective, interventional, nonrandomized multicentric study was performed. The files, optical coherence tomography (OCT) scans, indocyanine green, and fluorescein angiograms of patients with RAP stages II and III who had been treated by intravitreal bevacizumab were retrospectively examined. Final visual acuity, number of injections, and appearance of adverse events were considered as main outcome indicators. RESULTS. Twenty-six eyes from 24 patients (9 male and 15 female) were treated by intravitreal bevacizumab. Fourteen eyes presented RAP stage II and 12 eyes presented RAP stage III. Mean age was 76±9 and 79±6 years, respectively. Mean initial best-corrected visual acuity (BCVA) was logMAR 0.60±0.24 and 1.13±0.37, respectively. Mean BCVA was 0.62±0.26 and 1.06±0.37, respectively, at 6 months (p=0.96 and 0.10, respectively, Student t test for paired data) and 0.63±0.26 and 1.04±0.37, respectively, at 12 months (p=0.82 and p=0.06, respectively, Student t test for paired data). The average number of injections during the first year was 3.4 and 3.2, respectively. CONCLUSIONS. Intravitreal bevacizumab may stabilize visual acuity during the first year in RAP lesion stage II and III. Visual prognosis seems to be better in RAP II lesions. (Eur J Opjhthalmol 2009; 19: 448-51)

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 μm (SD 68.3, range 168-447) at baseline and 224.0 μm (SD 46, range 132-294) at month 6. Fifteen eyes were naive 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. © 2009 Macmillan Publishers Limited All rights reserved.

Ocriplasmin is a human plasmin fragment indicated for vitreomacular traction treatment. With its increasing use, several reported cases have suggested possible toxicity to the retina.We describe a case of a 55-year-old woman with symptomatic vitreomacular traction and a macular hole in the right eye who showed an acute decrease in visual acuity after an intravitreal ocriplasmin injection. Spectral-domain optical coherence tomography showed an alteration in the ellipsoid layer. Significant retinal vessel constriction was observed by angiography. The visual acuity improved to 20/100, and the electroretinogram progressively improved after the 1-year follow-up and following pars plana vitrectomy.A decrease in visual acuity and an enlargement of the macular hole were observed while studying this patient. This study shows the recovery of adverse effects caused by intravitreal injection of ocriplasmin for 1-year follow-up.

Purpose: To evaluate the efficacy of photodynamic therapy (PDT) in the treatment of idiopathic and inflammatory choroidal neovascularization (CNV). Methods: This study represents a non-randomized, multicentre, interventional case series. Sixteen eyes of 16 patients with classic or predominantly classic sub- and juxtafoveal idiopathic CNV and 26 eyes of 24 patients with classic or predominantly classic sub- and juxtafoveal CNV secondary to inflammatory conditions were treated with PDT with verteporfin. Best corrected visual acuity (BCVA) before and after PDT, the number of lines gained or lost and the number of PDT sessions were analysed. Results: The mean follow-up periods were 20 months (SD 11) and 16 months (SD 9) for the idiopathic and inflammatory groups, respectively. The mean BCVA in idiopathic CNV changed from 0.63 logMAR (SD 0.37) before treatment to 0.82 logMAR (SD 0.43) after treatment (p = 0.16; Student's t-test paired data). The number of treatments performed averaged 2.1 (range 1−4, SD 0.9). The mean BCVA in postinflammatory CNV changed from 0.60 logMAR (SD 0.4) before treatment to 0.57 logMAR (SD 0.6) after treatment (p = 0.79; Student's t-test paired data). The mean number of treatments was 2.6 (range 1−6, SD 1.2). Conclusions: Photodynamic therapy with verteporfin may be useful in stabilizing BCVA in patients with sub- and juxtafoveal postinflammatory CNV and subfoveal idiopathic CNV.

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.

Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that “treat and extend” and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.

OBJECTIVE—Detecting and grading of diabetic retinopathy (DR) by means of digital retinal images sent via the Internet. RESEARCH DESIGN AND METHODS—Four nonstereoscopic digital retinal images (45° field each) of 126 eye fundus images from 70 diabetic patients were obtained with a nonmydriatic camera at two peripheral units. The images were sent via the Internet using a web-based system to a reference center, where they were diagnosed and graded by one ophthalmologist. These results were compared with those obtained by two other ophthalmologists, one at each peripheral unit, after direct examination of the patients. A modified severity scale of Airlie House was used for grading DR in all cases. Agreement between observers was assessed using unweighted κ for categorical data and the intraclass correlation coefficient (ICC) for continuous data. RESULTS—Presence of DR was detected in 69 eyes (55%). All eyes with DR (69 of 69, 100%) were correctly identified (κ = 1) by inspecting the digital images. In 118 eyes (118 of 126, 94%), 57 with no DR and 61 with DR, there was an agreement between the gradation made after the direct examination and the gradation made after the inspection of the images (ICC = 0.92). In eight eyes with DR (8 of 126, 6%), there was disagreement in the grading made with both techniques. CONCLUSIONS—Inspection of digital retinal images sent via the Internet allowed diagnosis and grading of DR. The presence or absence of DR was correctly assessed by inspection of the images in all instances. We also found agreement, in most cases, between retinopathy gradation made from the images and the gradation made by direct examination of the eyes. These findings suggest that this technique is suitable for screening procedures.

We have evaluated a teleophthalmology service linking a primary health care centre and an eye clinic at a reference hospital. General practitioners at the primary care centre serving a population of 15,000 and ophthalmologists at the reference hospital participated in this study. Eye fundus digital images were taken from 278 eye fundi of 139 consecutive patients with clinical conditions that could potentially produce fundus alterations. Fundus images were obtained with a non-mydriatic fundus camera (Canon CR6-45M) and were electronically sent to a reference hospital where an ophthalmologist inspected the images and returned the diagnosis. In 18 patients (13%) the images did not have good enough quality to exclude eye fundus lesions. In 24 patients (17%) clear eye fundus alterations were found in at least one eye. In 14 patients (10%) there were image features suggesting retinal alterations that could not be confirmed by image inspection. Media opacity (13 eyes, 5%, seven patients, 5%) was the most common cause of poor image quality. The most difficult assessment was the evaluation of optic nerve head cupping. Retinal oedema was not observable in the digital images. In our experience teleopthalmology services seem to be an effective alternative for eye fundus diagnosis and patient follow-up.

Purpose The study was carried out to describe the indocyanine green angiographic findings in isolated primary retinal arterial macroaneurysms and their contribution to the diagnosis of this condition. Methods Fluorescein and indocyanine green angiography examination techniques were used to study isolated primary retinal arterial macroaneurysms in 8 consecutive patients with retinal or preretinal haemorrhage over a period of 12 months. Results The fluorescein angiography examination showed the macroaneurysm in four cases; pulsatility was not observed in any case. Indocyanine green angiography disclosed the macroaneurysm in six cases; pulsatility was observed in two cases. Conclusion Indocyanine green angiography allows better visualization of arterial macroaneurisms in the first examination and therefore facilitates the diagnosis, follow-up and laser treatment of this vascular abnormality.

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 .

This paper focuses on evaluating a method for measuring the retinal vessel widths in a recently publicly available database (REVIEW). The algorithm is based on deformable models and it constitutes an essential step in a methodology to compute the AVR automatically. This methodology is part of a web-based framework aimed to integrate diverse techniques in the field of retinal image analysis. The results achieved in the REVIEW database indicate the method is comparable or, in some cases, improves the accuracy of other techniques for measuring the vessel widths.

Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

Luis Arias,1–3 Francisco Gómez-Ulla,2–4 José M Ruiz-Moreno2,3,51Ophthalmology Department, Bellvitge University Hospital, C/Feixa Llarga, L’Hospitalet de Llobregat, Barcelona, 2Spanish Vitreoretinal Society (SERV), C/Xosé Chao Rego, Santiago de Compostela, 3RETICS OFTARED, Institute of Health Carlos III, C/Sinesio Delgado, Madrid, 4Gómez-Ulla Eye Institute, Santiago de Compostela, 5Department of Ophthalmology, Albacete University Hospital, Avenida de Almansa s/n, Albacete, Spain Purpose: To compare the effects of intravitreal ranibizumab in monotherapy (group A) and combined with photodynamic therapy (PDT) with verteporfin (group B) in retinal angiomatous proliferation (RAP) treatment.Methods: This was a multicentric, prospective, randomized clinical study conducted with parallel groups. The study eye in both groups received ranibizumab on days 1, 30, and 60 (loading dose); group B received PDT additionally on day 1. Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) testing and optical coherence tomography were performed monthly, and fluorescein angiography and indocyanine green angiography were performed quarterly. Retreatment criteria were leakage in fluorescein angiography or indocyanine green angiography, mean foveal thickness increase≥100 µm, or VA decrease ≥5 letters.Results: Twenty patients were recruited (ten patients in each group). Six eyes had previous treatment (three eyes in group A and three eyes in group B), so only 14 eyes were naïve. At 12-month follow-up, mean VA improved +1.5 letters in group A and +5.6 letters in group B (analysis of variance test; P>0.05). Two patients (20%) in both groups gained ≥15 letters (chi-square test; P>0.05). Mean changes in greatest linear dimension and in foveal thickness were not statistically significant between groups of treatment (analysis of variance test; P>0.05). Mean retreatments per patient were 1.8 (group A) and 0.9 (group B) (Mann–Whitney U-test; P>0.05). One patient died due to underlying disease not related to study medication.Conclusion: Intravitreal ranibizumab administered in monotherapy or combined with PDT was efficacious in terms of VA stabilization in patients with RAP.Keywords: age-related macular degeneration, intravitreal injection, photodynamic therapy, ranibizumab, retinal angiomatous proliferation, verteporfin

Purpose: To evaluate the efficacy and safety of standard photodynamic therapy with verteporfin at 48 months in patients with chronic central serous chorioretinopathy. Methods: A retrospective, multicenter, interventional case series analysis in patients with chronic central serous chorioretinopathy, treated with standard photodynamic therapy, and with ≥4 years of follow-up. Evaluations were performed every 3 months in the first year, every 6 months in the second year, and thereafter annually. Optical coherence tomography was performed in all visits. Fluorescein angiography and indocyanine green angiography were performed at baseline and thereafter as necessary. Retinal thickness on optical coherence tomography was measured manually, evaluating central macular thickness and neural retina thickness. Main outcomes included the evolution of best-corrected visual acuity, the resolution of subretinal fluid, documented with optical coherence tomography, the number of treatments, and the evaluation of neural retina thickness during the 48 months of follow-up. Results: The study included 46 eyes of 42 patients, 38 men (90.4%) and 4 women (9.5%), with mean age of 49.19 ± 9.9 years (range, 32-70 years), and the minimal follow-up period was 48 months (mean, 56.8 ±10.3 months). Subretinal fluid was observed in all the included eyes at baseline, and 10 eyes (21.7%) had intraretinal diffuse or cystoid fluid. Concerning the mean best-corrected visual acuity, a statistically significant improvement (P < 0.01, Student t-test) was registered from 58.8 ± 18.3 letters at baseline to 66.9 ± 18.6 letters at 48th month. A complete resolution of subretinal fluid was achieved in 93.4%, and resolution of intraretinal fluid occurred in all 10 cases at 48 months. Neural retina thickness remained stable during the 48 months of follow-up (163.8 ± 47 μm at baseline and 163.8 ± 46 μm at 48 months). The mean number of treatments was 1.08 ± 0.3. No systemic or ocular side effects were registered. Conclusion: Standard photodynamic therapy with verteporfin was effective and safe in chronic central serous chorioretinopathy treatment with a significant improvement in the long term, both anatomic and visual, without inducing additional retinal atrophy or systemic adverse effects.

The arteriovenous ratio is an objective way to assess the arteriolar narrowing related to several diseases such as hypertension. It is computed as the ratio between the artery and vein mean widths. However, its calculus is not straightforward since the experts do not use all the retinal vessels. This paper presents an automatic, precise and reproducible methodology for the AVR computation. We analyze the way the experts select the vessels in order to build a system which emulates them. The system was evaluated by two ophthalmologists in a data set of 86 images. The correlation results among the system and the experts are an indication of the reproducibility of the results.

The angiographic characteristics of central serous chorioretinopathy (CSC) were studied by analyzing digitalized angiograms with an IMAGEnet system. We determined the type of leak, its location, and its distance from the fovea and from the center of the detachment. Round leaks were located farther from the detachment center and farther from the fovea than smokestack leaks. Detachments tended to center on the fovea regardless of the leak to fovea distance. These findings suggest that for serous detachment of the sensory retina to develop and be maintained, there must be a diffuse dysfunctional area of retinal pigment epithelium and a focal leak.

Background: Bonemarrow transplantion (BMT) isthe treatment of choice for bothmalignant and nonmalignant disordersof the bone marrow. BMT retinopathy occurs aftera latent period of 6 months and usuallyrecovers after a few weeks.Methods: We present a case of BMTretinopathy (BMT) in a patient with a high-degreeof non-Hodgkin lymphoma. We analysed the funduscopic andangiographic findings, andthe evolution of the case.Results: and conclusions: After a period oftwo and a half years we observed thespontaneous complete resolution of the funduslesions and the recovery of visual acuityAll of this confirm the theory that BMTretinopathy does not progress beyond theischemic microvascular stage.

To report the changes during a 1-year follow-up in visual acuity and macular thickness in a series of highly myopic eyes with choroidal neovascularization treated with bevacizumab.Retrospective and multicenter study including 107 highly myopic eyes from 107 patients (mean age, 55 years) with subfoveal or juxtafoveal choroidal neovascularization. All cases were treated by one intravitreous injection of 1.25 mg bevacizumab. Best-corrected visual acuity and macular thickness with the optical coherence tomography were evaluated at baseline and then monthly during 1 year.Logarithm of the minimum angle of resolution best-corrected visual acuity at baseline averaged 0.72 (standard deviation [SD], 0.43) versus 0.53 (SD, 0.41) at 1 year after treatment (P0.001). Logarithm of the minimum angle of resolution best-corrected visual acuity was 0.30 or better in 49 of 107 eyes (45%) at 1 year. Thirty-three eyes (30%) gained at least 3 Early Treatment Diabetic Retinopathy Study lines (15 letters) during the follow-up. In 43 eyes (40%), reinjections were necessary because signs of choroidal neovascularization activity were still evident. The mean number of reinjections was 0.8 (SD, 1.3). Best-corrected visual acuity improvement was better in the younger group (younger than 50 years). No adverse reactions were reported.One intravitreal bevacizumab injection seems to be an effective therapeutic approach to treat choroidal neovascularization in highly myopic eyes. Careful monitoring is necessary to assess the need for reinjections.

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. © 2010 Elsevier Ireland Ltd.

Purpose: This study aimed to evaluate the efficacy of photodynamic therapy (PDT) in treating chronic central serous chorioretinopathy (CSC). Methods: We describe a non-randomized, multicentre, interventional case series. A total of 82 eyes of 72 patients with chronic CSC were treated by conventional PDT. LogMAR best corrected visual acuity (BCVA) (ETDRS charts) and central foveal thickness (CFT) measured by optical coherence tomography before and after PDT, number of PDT treatments and complications were used as outcome indicators. Results: Mean follow-up was 12 ± 10 months and mean age was 46 ± 10 years. Mean logMAR BCVA changed from 0.53 (standard deviation [SD] 0.43) before PDT to 0.38 (SD 0.41) at 3 months and 0.48 (SD 0.50) at 6 months (p < 0.0001 and p = 0.007, respectively, Student's t-test for paired data). Mean BCVA at the end of follow-up was 0.37 (SD 0.45; p < 0.0001 from baseline). Macular detachment was resolved and subretinal fluid (SRF) disappeared in all cases. Central foveal thickness decreased from 325 μm (SD 95), to 229 μm (SD 70) at 1 month after PDT, 206 μm (SD 68) at 3 months, and 202 μm (SD 76) at 6 months (all p < 0.0001, Student's t-test for paired data). No cases developed severe visual loss or complications derived from PDT. Reactive retinal pigment epithelium hypertrophy appeared in nine cases after PDT. Conclusions: Photodynamic therapy with verteporfin may be useful in chronic CSC for improving BCVA and reducing SRF and CFT. Randomized studies with longer follow-up are needed to assess the real role of this treatment in chronic CSC. © 2009 Acta Ophthalmol.

PURPOSE To assess efficacy and safety in the treatment of nonsubfoveal choroidal neovascularization secondary to age-related macular degeneration with intravitreal ranibizumab. METHODS Retrospective, multicentric, noncomparative, interventional case series. We included patients with naive extrafoveal and juxtafoveal choroidal neovascularization treated with intravitreal ranibizumab and a follow-up of 1 year. Patients were evaluated using visual acuity testing with Snellen charts, fluorescein angiography, and optical coherence tomography scans. RESULTS There were 15 patients with a mean age of 72.4 years (SD, 7.2). There were 11 juxtafoveal lesions (73.3%) and 4 extrafoveal lesions (26.6%). Eight lesions were predominantly classic (53.3%), 6 lesions were occult (40%), and 1 lesion was minimally classic (6.6%). The mean visual acuity improved from 20/60 (mean logarithm of the minimum angle of resolution = 0.47) at baseline to 20/40 (mean logarithm of the minimum angle of resolution = 0.34) at the 1-year follow-up visit (P = 0.03). The mean foveal thickness improved from 312 microm to 262 microm (P = 0.01), and the mean lesion size (disk areas) improved from 1.9 to 1.1 (P = 0.01). No cases progressed to a subfoveal location. The mean number of injections was 3.8. As complications, we had an endophthalmitis and a macular hole. CONCLUSION In our study, intravitreal ranibizumab showed efficacy for the treatment of nonsubfoveal choroidal neovascularization secondary to age-related macular degeneration mainly in terms of preventing subfoveal progression.

Early alterations in retinal microcirculation are observed in most hypertensive patients seen in daily practice and the European guidelines consider it is necessary an objective method to quantify these alterations. We have previously described a semi-automatic computerized system to evaluate the calibre of retinal blood vessels that has shown high sensitivity and specificity to calculate the arteriovenous ratio (AVR), though with limitations. We describe a method based on the snakes model to calculate the arteriovenous ratio.We had compared it with the previously reported lineal method, and we have analyzed 173 digital photographs from 96 hypertensive patients, most of them receiving treatment. Photos were made in two hospitals (A Coruña: 66 and Santiago de Compostela: 107), and were analysed by the same people in each Centre, by the lineal and snake method.We have observed that the arithmetic mean and the differences in AVR between both methods were minimal and showed a normal distribution. Cronbach statistics was 0.974 and intraclass correlation coefficient 0.949 (p0.001), for the images from Santiago and 0.923 with an intraclass correlation coefficient of 0.857 (p0.001) for the images from A Coruña.This semiautomatic method to calculate the AVR ratio has a high sensitivity and a greater specificity than previous method, and the correlation between the results obtained with both is excellent.

Diabetic macular edema is an important cause of visual loss in the developed world and may frequently lead to irreversible changes in visual acuity. The Early Treatment Diabetic Retinopathy Study showed a significant benefit in using focal laser photocoagulation for the treatment of macular edema, more specifically defined as clinically significant macular edema. However, some cases of diabetic macular edema are refractory to laser therapy and do not have a good prognosis with such treatment. Triamcinolone acetonide is glucocoticosteroid with antiangiogenic and antiedematous properties. Recently, some promising results, respect to the increases of visual acuity and decreases in foveal thickness, have been shown in different studies for the treatment of refractory diabetic macular edema with intravitreal triamcinolone acetonide.

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 naive 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) μm at baseline to 224 (SD 46) μm at month 12 (p = 0.008, Student t test for paired data). Six eyes needed one reinjection 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.

Diabetic macular edema is one of the leading causes of visual loss in first world countries and the first cause in diabetic retinopathy. The Early Treatment Diabetic Retinopathy Study showed a significant benefit in using focal laser photocoagulation for the treatment of macular edema, more specifically defined as clinically significant macular edema. Nevertheless, progressive visual loss is found in the 26% of patients with diabetic macular edema treated with photocoagulation. The failure of laser treatment and the destructive nature of the therapy has forced researchers to pursue new alternatives including vitrectomy with or without internal limiting membrane peels, the use of proteinkinase C inhibitors, intravitreal injections of antibodies that inhibit the vascular endothelial growth factor, somatostatin analog, or the intravitreal injection with corticosteroids. Triamcinolone acetonide is glucocoticosteroid with antiangiogenic and antiedematous properties. Publications evaluating the safety and efficacy of intravitreal injection of triamcinolone in the treatment of diabetic macular edema show varying outcomes with respect to the increases of visual acuity and decreases in foveal thickness. Despite this, intravitreal triamcinolone is a treatment that has evolved quickly and is considered increasingly useful.

espanolObjetivo: Establecer los problemas en el manejo de los desprendimientos de retina (DR) durante los fines de semana en el Sistema Nacional de Salud (SNS) espanol. Metodos: Se envio una encuesta confidencial al jefe de Servicio de 217 hospitales del SNS. Los datos fueron almacenados en una base de datos Microsoft Access y analizados estadisticamente con Excel y Statgraphics. Las variables cualitativas fueron analizadas con el test de Chi-cuadrado y el test exacto de Fisher, y las cuantitativas con el test no parametrico de Kruskall-Wallis. Resultados: Se obtuvo una tasa de respuesta del 54,8% con mayor participacion de hospitales docentes (HD). Los Comarcales (HC) se incluyeron en el grupo de los No Docentes (HnD) por su patron de respuestas similares. El 18% de centros no tiene oftalmologo de guardia. De los que si disponen, el 36% tiene especialistas de vitreo retina de guardia. Mas del 80% de los centros admite tener problemas para atender los DR urgentes. El 24% no tiene acceso a quirofano de oftalmologia; el 50% refiere problemas con Anestesia y el 22% dispone de enfermeras de Oftalmologia. El 64% realiza vitrectomias y de ellos, el 77% atiende urgencias. El 90% de los centros reconoce que un paciente con DR superior y macula no afectada tardaria mas de 24 horas en intervenirse, aunque el 84% lo considera una practica inadecuada. Conclusion: A pesar de los sesgos y cuestiones metodologicas, se han identificado problemas del SNS relacionadas al manejo de los DR urgentes. Esto proporciona importante informacion para organizar una cobertura mas eficiente. EnglishObjective: 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 refered 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.