Brachial artery peak velocity variation to predict fluid responsiveness in mechanically ventilated patients

INTRODUCTION Although several parameters have been proposed to predict the hemodynamic response to fluid expansion in critically ill patients, most of them are invasive or require the use of special monitoring devices. The aim of this study is to determine whether noninvasive evaluation of respiratory variation of brachial artery peak velocity flow measured using Doppler ultrasound could predict fluid responsiveness in mechanically ventilated patients. METHODS We conducted a prospective clinical research in a 17-bed multidisciplinary ICU and included 38 mechanically ventilated patients for whom fluid administration was planned due to the presence of acute circulatory failure. Volume expansion (VE) was performed with 500 mL of a synthetic colloid. Patients were classified as responders if stroke volume index (SVi) increased >or= 15% after VE. The respiratory variation in Vpeakbrach (DeltaVpeakbrach) was calculated as the difference between maximum and minimum values of Vpeakbrach over a single respiratory cycle, divided by the mean of the two values and expressed as a percentage. Radial arterial pressure variation (DeltaPPrad) and stroke volume variation measured using the FloTrac/Vigileo system (DeltaSVVigileo), were also calculated. RESULTS VE increased SVi by >or= 15% in 19 patients (responders). At baseline, DeltaVpeakbrach, DeltaPPrad and DeltaSVVigileo were significantly higher in responder than nonresponder patients [14 vs 8%; 18 vs. 5%; 13 vs 8%; P < 0.0001, respectively). A DeltaVpeakbrach value >10% predicted fluid responsiveness with a sensitivity of 74% and a specificity of 95%. A DeltaPPrad value >10% and a DeltaSVVigileo >11% predicted volume responsiveness with a sensitivity of 95% and 79%, and a specificity of 95% and 89%, respectively. CONCLUSIONS Respiratory variations in brachial artery peak velocity could be a feasible tool for the noninvasive assessment of fluid responsiveness in patients with mechanical ventilatory support and acute circulatory failure. TRIAL REGISTRATION ClinicalTrials.gov ID: NCT00890071.

Chromosomal number aberrations and transformation in adult mouse retinal stem cells in vitro.

PURPOSE: The potential of stem cells (SCs) as a source for cell-based therapy on a wide range of degenerative diseases and damaged tissues such as retinal degeneration has been recognized. Generation of a high number of retinal stem cells (RSCs) in vitro would thus be beneficial for transplantation in the retina. However, as cells in prolonged cultivation may be unstable and thus have a risk of transformation, it is important to assess the stability of these cells. METHODS: Chromosomal aberrations were analyzed in mouse RSC lines isolated from adult and from postnatal day (PN)1 mouse retinas. Moreover, selected cell lines were tested for anchorage-dependent proliferation, and SCs were transplanted into immunocompromised mice to assess the possibility of transformation. RESULTS: Marked aneuploidy occurred in all adult cell lines, albeit to different degrees, and neonatal RSCs were the most stable and displayed a normal karyotype until at least passage 9. Of interest, the level of aneuploidy of adult RSCs did not necessarily correlate with cell transformation. Only the adult RSC lines passaged for longer periods and with a higher dilution ratio underwent transformation. Furthermore, we identified several cell cycle proteins that might support the continuous proliferation and transformation of the cells. CONCLUSIONS: Adult RSCs rapidly accumulated severe chromosomal aberrations during cultivation, which led to cell transformation in some cell lines. The culture condition plays an important role in supporting the selection and growth of transformed cells.

Altered expression of beta-galactosidase-1-like protein 3 (Glb1l3) in the retinal pigment epithelium (RPE)-specific 65-kDa protein knockout mouse model of Leber's congenital amaurosis

Purpose: In this study, we investigated the expression of the gene encoding beta-galactosidase (Glb)-1-like protein 3 (Glb1l3), a member of the glycosyl hydrolase 35 family, during retinal degeneration in the retinal pigment epithelium (RPE)-specific 65-kDa protein knockout (Rpe65(-/-)) mouse model of Leber congenital amaurosis (LCA). Additionally, we assessed the expression of the other members of this protein family, including beta-galactosidase-1 (Glb1), beta-galactosidase-1-like (Glb1l), and beta-galactosidase-1-like protein 2 (Glb1l2).Methods: The structural features of Glb1l3 were assessed using bioinformatic tools. mRNA expression of Glb-related genes was investigated by oligonucleotide microarray, real-time PCR, and reverse transcription (RT) -PCR. The localized expression of Glb1l3 was assessed by combined in situ hybridization and immunohistochemistry.Results: Glb1l3 was the only Glb-related member strongly downregulated in Rpe65(-/-) retinas before the onset and during progression of the disease. Glb1l3 mRNA was only expressed in the retinal layers and the RPE/choroid. The other Glb-related genes were ubiquitously expressed in different ocular tissues, including the cornea and lens. In the healthy retina, expression of Glb1l3 was strongly induced during postnatal retinal development; age-related increased expression persisted during adulthood and aging.Conclusions: These data highlight early-onset downregulation of Glb1l3 in Rpe65-related disease. They further indicate that impaired expression of Glb1l3 is mostly due to the absence of the chromophore 11-cis retinal, suggesting that Rpe65 deficiency may have many metabolic consequences in the underlying neuroretina.

Perinatal Hypoxia Enhances Cyclic Adenosine Monophosphate-mediated BKCa Channel Activation in Adult Murine Pulmonary Artery.

Exposure to perinatal hypoxia results in alteration of the adult pulmonary circulation, which is linked among others to alterations in K channels in pulmonary artery (PA) smooth muscle cells. In particular, large conductance Ca-activated K (BKCa) channels protein expression and activity were increased in adult PA from mice born in hypoxia compared with controls. We evaluated long-term effects of perinatal hypoxia on the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway-mediated activation of BKCa channels, using isoproterenol, forskolin, and dibutyryl-cAMP. Whole-cell outward current was higher in pulmonary artery smooth muscle cells from mice born in hypoxia compared with controls. Spontaneous transient outward currents, representative of BKCa activity, were present in a greater proportion in pulmonary artery smooth muscle cells of mice born in hypoxia than in controls. Agonists induced a greater relaxation in PA of mice born in hypoxia compared with controls, and BKCa channels contributed more to the cAMP/PKA-mediated relaxation in case of perinatal hypoxia. In summary, perinatal hypoxia enhanced cAMP-mediated BKCa channels activation in adult murine PA, suggesting that this pathway could be a potential target for modulating adult pulmonary vascular tone after perinatal hypoxia.

On-pump beating heart coronary surgery for high risk patients requiring emergency multiple coronary artery bypass grafting.

BACKGROUND: Cardiopulmonary bypass (CPB) with aortic cross-clamping and cardioplegic arrest remains the method of choice for patients requiring standard myocardial revascularization. Therefore, very high-risk patients presenting with acute coronary syndrome, unstable angina, onset of cardiac decompensation and requiring emergency multiple myocardial revascularization, can have a poor outcome. The on-pump beating heart technique can reduce the mortality and the morbidity in such a selected group of patients and this report describes our clinical experience. METHODS: Out of 290 patients operated for CABG from January 2005 to January 2006, 25 (8.6%) selected high-risk patients suffering from life threatening coronary syndrome (mean age 69 +/- 7 years) and requiring emergency multiple myocardial revascularization, underwent on-pump beating heart surgery. The mean pre-operative left ventricle ejection fraction (LVEF) was 27 +/- 8%. The majority of them (88%) suffered of tri-vessel coronary disease and 6 (24%) had a left main stump disease. Nine patients (35%) were on severe cardiac failure and seven among them (28%) received a pre-operative intra-aortic balloon pump. The pre-operative EuroScore rate was equal or above 8 in 18 patients (73%). RESULTS: All patients underwent on-pump-beating heart coronary revascularization. The mean number of graft/patient was 2.9 +/- 0.6 and the internal mammary artery was used in 23 patients (92%). The mean CPB time was 84 +/- 19 minutes. Two patients died during the recovery stay in the intensive care unit, and there were no postoperative myocardial infarctions between the survivors. Eight patients suffered of transitorily renal failure and 1 patient developed a sternal wound infection. The mean hospital stay was 12 +/- 7 days. The follow-up was complete for all 23 patients survived at surgery and the mean follow-up time was 14 +/- 5 months. One patient died during the follow-up for cardiac arrest and 2 patients required an implantable cardiac defibrillator. One year after surgery they all had a standard trans-thoracic echocardiogram showing a mean LVEF rate of 36 +/- 11.8%. CONCLUSION: Standard on-pump arrested heart coronary surgery has higher mortality and morbidity in emergencies. The on-pump beating heart myocardial revascularization seems to be a valid alternative for the restricted and selected cohort of patients suffering from life threatening coronary syndrome and requiring multiple emergency CABG.

Vertebral artery occlusion after chemotherapy

We present a patient who experienced a stroke due to vertebral artery occlusion after chemotherapy

Prevalence of symptomatic and silent stress-induced perfusion defects in diabetic patients with suspected coronary artery disease referred for myocardial perfusion scintigraphy.

PURPOSE: Silent myocardial ischaemia--as evaluated by stress-induced perfusion defects on myocardial perfusion scintigraphy (MPS) in patients without a history of chest pain--is frequent in diabetes and is associated with increased rates of cardiovascular events. Its prevalence has been determined in asymptomatic diabetic patients, but remains largely unknown in diabetic patients with suspected coronary artery disease (CAD) in the clinical setting. In this study we therefore sought (a) to determine the prevalence of symptomatic and silent perfusion defects in diabetic patients with suspected CAD and (b) to characterise the eventual predictors of abnormal perfusion. METHODS: The patient population comprised 133 consecutive diabetic patients with suspected CAD who had been referred for MPS. Studies were performed with exercise (41%) or pharmacological stress testing (1-day protocol, (99m)Tc-sestamibi, 201Tl or both). We used semi-quantitative analysis (20-segment polar maps) to derive the summed stress score (SSS) and the summed difference score (SDS). RESULTS: Abnormal MPS (SSS> or =4) was observed in 49 (37%) patients (SSS=4.9+/-8.4, SDS=2.4+/-4.7), reversible perfusion defects (SDS> or =2) in 40 (30%) patients [SSS=13.3+/-10.9; SDS=8.0+/-5.6; 20% moderate to severe (SDS>4), 7% multivessel] and fixed defects in 21 (16%) patients. Results were comparable between patients with and patients without a history of chest pain. Of 75 patients without a history of chest pain, 23 (31%, 95% CI=21-42%) presented reversible defects (SSS=13.9+/-11.3; SDS=7.4+/-1.2), indicative of silent ischaemia. Reversible defects were associated with inducible ST segment depression during MPS stress [odds ratio (OR)=3.2, p<0.01). Fixed defects were associated with erectile dysfunction in males (OR=3.7, p=0.02) and lower aspirin use (OR=0.25, p=0.02). CONCLUSION: Silent stress-induced perfusion defects occurred in 31% of the patients, a rate similar to that in patients with a history of chest pain. MPS could identify these patients with a potentially increased risk of cardiovascular events.

Long-term prognostic value of single-photon emission computed tomography myocardial perfusion imaging in diabetic patients with and without coronary artery disease

Keywords Diabetes mellitus; coronary artery disease; myocardial ischemia; prognostic value; single-photon emission computed tomography myocardial perfusion imaging Summary Aim: To determine the long-term prognostic value of SPECT myocardial perfusion imaging (MPI) for the occurrence of cardiovascular events in diabetic patients. Methods: SPECT MPI of 210 consecutive Caucasian diabetic patients were analysed using Kaplan-Meier event-free survival curves and independent predictors were determined by Cox multivariate analyses. Results: Follow-up was complete in 200 (95%) patients with a median period of 3.0 years (0.8-5.0). The population was composed of 114 (57%) men, age 65±10 years, 181 (90.5%) type 2 diabetes mellitus, 50 (25%) with a history of coronary artery disease (CAD) and 98 (49%) presenting chest pain prior to MPI. The prevalence of abnormal MPI was 58%. Patients with a normal MPI had neither cardiac death, nor myocardial infarction, independently of a history of coronary artery disease or chest pain. Among the independent predictors of cardiac death and myocardial infarction, the strongest was abnormal MPI (p<.0001), followed by history of CAD (Hazard Ratio (HR)= t 5.9, p=0.0001), diabetic retinopathy (HR=10.0, p=0.001) and inability to exercise (HR=7.7, p=0.02). Patients with normal 1VIPI had a low revascularisation rate of 2.4% during the follow-up period. Compared to normal MPI, cardiovascular events increased 5.2 fold for reversible defects, 8.5 fold for fixed defects and 20.1 fold for the association of both defects. Conclusion: Diabetic patients with normal MPI had an excellent prognosis independently of history of CAD. On the opposite, an abnormal MPI led to a > 5 fold increase in cardiovascular events. This emphasizes the value of SPECT MPI in predicting and risk-stratifying cardiovascular events in diabetic patients. Mots-Clés Diabète; maladie coronarienne; ischémie myocardique; valeur pronostique; tomoscintigraphie myocardique de perfusion par émission monophotonique Résumé Objectifs: Déterminer la valeur pronostique à long terme de la tomoscintigraphie myocardique de perfusion (TSMP) chez les patients diabétiques pour prédire les événements cardiovasculaires (ECV). Méthodes: Etude de 210 diabétiques caucasiens consécutifs référés pour une TSMP. Les courbes de survie ont été déterminées par Kaplan-Meier et les facteurs prédictifs indépendants par analyses multivariées de type Cox. Résultats: Le suivi a été complet chez 200 (95%) patients avec une durée médiane de 3.0 ans (0.8-50). La population était composée de 114 (57%) hommes, âge moyen 65±10 ans, avec 181 (90.5%) diabète de type 2, 50 (25%) antécédents de maladie coronarienne (AMC) et 98 (49%) patients connus pour un angor avant la TSMP. La prévalence de TSMP anormales était de 58%. Aucun décès d'origine cardiaque ou infarctus du myocarde n'est survenu chez les patients avec une TSMP normale, ceci indépendamment de leurs AMC et des douleurs thoraciques. Les facteurs prédictifs indépendants pour les ECV sont une TSMP anormale (p<.0001), les AMC (Hazard Ratio (HR)=15.9, p-0.0001), suivi de la rétinopathie diabétique (HR-10.0, p=0.001) et de l'incapacité à effectuer un exercice (HR=7.7, p=0.02). Les patients avec une TSMP normale ont présenté un taux de revascularisations de 2.4%. La présence de défauts mixtes accroît le risque d'ECV de 20.1 fois, les défauts fixes de 8.5 fois et les défauts réversibles de 5.2 fois comparés aux sujets avec une TSMP normale. Conclusion: Les patients diabétiques, coronariens ou non, avec une tomoscintigraphie myocardique de perfusion normale ont un excellent pronostique. A l'opposé, une TSMP anormale est associée à une augmentation du risque d'ECV de plus de 5 fois. Ceci confirme l'utilité de la TSMP dans la stratification du risque chez les patients diabétiques.

Reproducibility of straylight measurement by C-Quant for assessment of retinal straylight using the compensation comparison method.

BACKGROUND: Straylight gives the appearance of a veil of light thrown over a person's retinal image when there is a strong light source present. We examined the reproducibility of the measurements by C-Quant, and assessed its correlation to characteristics of the eye and subjects' age. PARTICIPANTS AND METHODS: Five repeated straylight measurements were taken using the dominant eye of 45 healthy subjects (age 21-59) with a BCVA of 20/20: 14 emmetropic, 16 myopic, eight hyperopic and seven with astigmatism. We assessed the extent of reproducibility of straylight measures using the intraclass correlation coefficient. RESULTS: The mean straylight value of all measurements was 1.01 (SD 0.23, median 0.97, interquartile range 0.85-1.1). Per 10 years of age, straylight increased in average by 0.10 (95%CI 0.04 to 0.16, p < 0.01]. We found no independent association of refraction (range -5.25 dpt to +2 dpt) on straylight values (0.001; 95%CI -0.022 to 0.024, p = 0.92). Compared to emmetropic subjects, myopia reduced straylight (-.011; -0.024 to 0.02, p = 0.11), whereas higher straylight values (0.09; -0.01 to 0.20, p = 0.09) were observed in subjects with blue irises as compared to dark-colored irises when correcting for age. The intraclass correlation coefficient (ICC) of repeated measurements was 0.83 (95%CI 0.76 to 0.90). CONCLUSIONS: Our study showed that straylight measurements with the C-Quant had a high reproducibility, i.e. a lack of large intra-observer variability, making it appropriate to be applied in long-term follow-up studies assessing the long-term effect of surgical procedures on the quality of vision.

Intrinsically photosensitive retinal ganglion cell function in relation to age: a pupillometric study in humans with special reference to the age-related optic properties of the lens.

BACKGROUND: The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC. METHODS: Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0-10 s after light termination) and late (10-30 s after light termination). Lens transmission was measured with an ocular fluorometer. RESULTS: The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p=0.02, p=0.0014, respectively) for the blue light stimulus condition only.The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions.Lens transmission decreased linearly with age (p<0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m2 light (p=0.02). CONCLUSIONS: Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led to similar results, however, the effect of age was greater on these pupil responses than that of the lens transmission. Thus there must be other age related factors such as lens scatter and/or adaptive processes influencing the ipRGC mediated pupil response enhancement observed with advancing age.

Perfusion computed tomography-guided subacute endovascular reperfusion in a patient with carotid occlusion.

Most patients with symptomatic internal carotid artery occlusion have a single minor or major hemispheric stroke. A minority of patients have ipsilateral retinal ischemia, recurrent strokes, or transient ischemic attacks. Whereas spontaneous carotid recanalization is rare, acute surgical recanalization has been attempted, with mixed results. Recently, acute endovascular recanalization has been performed and described as feasible and relatively safe. We describe a patient with symptom recurrence related to hemodynamic factors after occlusion of the carotid artery who was successfully treated 14 days after symptom onset.

Intrinsically photosensitive retinal ganglion cells.

The recent discovery of melanopsin-expressing retinal ganglion cells that mediate the pupil light reflex has provided new insights into how the pupil responds to different properties of light. These ganglion cells are unique in their ability to transduce light into electrical energy. There are parallels between the electrophysiologic behavior of these cells in primates and the clinical pupil response to chromatic stimuli. Under photopic conditions, a red light stimulus produces a pupil constriction mediated predominantly by cone input via trans-synaptic activation of melanopsin-expressing retinal ganglion cells, whereas a blue light stimulus at high intensity produces a steady-state pupil constriction mediated primarily by direct intrinsic photoactivation of the melanopsin-expressing ganglion cells. Preliminary data in humans suggest that under photopic conditions, cones primarily drive the transient phase of the pupil light reflex, whereas intrinsic activation of the melanopsin-expressing ganglion cells contributes heavily to sustained pupil constriction. The use of chromatic light stimuli to elicit transient and sustained pupil light reflexes may become a clinical pupil test that allows differentiation between disorders affecting photoreceptors and those affecting retinal ganglion cells.

Chronic nitric oxide synthase inhibition and carotid artery distensibility in renal hypertensive rats.

The goal of the present study was to examine the viscoelastic properties of the carotid artery in genetically identical rats exposed to similar levels of blood pressure sustained by different mechanisms. Eight-week old male Wistar rats were examined 2 weeks after renal artery clipping (two-kidney, one clip [2K1C] Goldblatt rats, n = 53) or sham operation (n = 49). One half of the 2K1C and sham rats received the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 1.48 mmol/L) in their drinking water for 2 weeks after the surgical procedure. Mean blood pressure increased significantly in the 2K1C-water (182 mm Hg), 2K1C-L-NAME (197 mm Hg), and sham-L-NAME (170 mm Hg) rats compared with the sham-water rats (127 mm Hg). Plasma renin activity was not altered by L-NAME but significantly enhanced after renal artery clipping. A significant and similar increase in the cross-sectional area of the carotid artery was observed in L-NAME and vehicle-treated 2K1C rats. L-NAME per se did not modify cross-sectional area in the sham rats. There was a significant upward shift of the distensibility-pressure curve in the L-NAME- and vehicle-treated 2K1C rats compared with the sham-L-NAME rats. L-NAME treatment did not alter the distensibility-pressure curve in the 2K1C rats. These results demonstrate that the mechanisms responsible for artery wall hypertrophy in renovascular hypertension are accompanied by an increase in arterial distensibility that is not dependent on the synthesis of nitric oxide.

IROme, a New High-Throughput Molecular Tool for the Diagnosis of Inherited Retinal Dystrophies.

The molecular diagnosis of retinal dystrophies is difficult because of the very important number of genes implicated and is rarely helped by genotype-phenotype correlations. This prompted us to develop IROme, a custom designed in solution-based targeted exon capture assay (SeqCap EZ Choice library, Roche NimbleGen) for 60 retinitis pigmentosa-linked genes and three candidate genes (942 exons). Pyrosequencing was performed on a Roche 454 GS Junior benchtop high-throughput sequencing platform. In total, 23 patients affected by retinitis pigmentosa were analyzed. Per patient, 39.6 Mb were generated, and 1111 sequence variants were detected on average, at a median coverage of 17-fold. After data filtering and sequence variant prioritization, disease-causing mutations were identified in ABCA4, CNGB1, GUCY2D, PROM1, PRPF8, PRPF31, PRPH2, RHO, RP2, and TULP1 for twelve patients (55%), ten mutations having never been reported previously. Potential mutations were identified in 5 additional patients, and in only 6 patients no molecular diagnosis could be established (26%). In conclusion, targeted exon capture and next-generation sequencing are a valuable and efficient approach to identify disease-causing sequence variants in retinal dystrophies.

Anti-vascular endothelial growth factor acts on retinal microglia/macrophage activation in a rat model of ocular inflammation.

PURPOSE: To evaluate whether anti-vascular endothelial growth factor (VEGF) neutralizing antibodies injected in the vitreous of rat eyes influence retinal microglia and macrophage activation. To dissociate the effect of anti-VEGF on microglia and macrophages subsequent to its antiangiogenic effect, we chose a model of acute intraocular inflammation. METHODS: Lewis rats were challenged with systemic lipopolysaccharide (LPS) injection and concomitantly received 5 µl of rat anti-VEGF-neutralizing antibody (1.5 mg/ml) in the vitreous. Rat immunoglobulin G (IgG) isotype was used as the control. The effect of anti-VEGF was evaluated at 24 and 48 h clinically (uveitis scores), biologically (cytokine multiplex analysis in ocular media), and histologically (inflammatory cell counts on eye sections). Microglia and macrophages were immunodetected with ionized calcium-binding adaptor molecule 1 (IBA1) staining and counted based on their differential shapes (round amoeboid or ramified dendritiform) on sections and flatmounted retinas using confocal imaging and automatic quantification. Activation of microglia was also evaluated with inducible nitric oxide synthase (iNOS) and IBA1 coimmunostaining. Coimmunolocalization of VEGF receptor 1 and 2 (VEGF-R1 and R2) with IBA1 was performed on eye sections with or without anti-VEGF treatment. RESULTS: Neutralizing rat anti-VEGF antibodies significantly decreased ocular VEGF levels but did not decrease the endotoxin-induced uveitis (EIU) clinical score or the number of infiltrating cells and cytokines in ocular media (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α, and monocyte chemoattractant protein [MCP]-1). Eyes treated with anti-VEGF showed a significantly decreased number of activated microglia and macrophages in the retina and the choroid and decreased iNOS-positive microglia. IBA1-positive cells expressed VEGF-R1 and R2 in the inflamed retina. CONCLUSIONS: Microglia and macrophages expressed VEGF receptors, and intravitreous anti-VEGF influenced the microglia and macrophage activation state. Taking into account that anti-VEGF drugs are repeatedly injected in the vitreous of patients with retinal diseases, part of their effects could result from unsuspected modulation of the microglia activation state. This should be further studied in other ocular pathogenic conditions and human pathology.