The balance between controlling infection and limiting inflammation is particularly precarious in the brain because of its unique vulnerability to the toxic effects of inflammation. Astrocytes have been implicated as key regulators of neuroinflammation in CNS infections, including infection with Toxoplasma gondii, a protozoan parasite that naturally establishes a chronic CNS infection in mice and humans. In CNS toxoplasmosis, astrocytes are critical to controlling parasite growth. They secrete pro-inflammatory cytokines and physically encircle parasites. However, the molecular mechanisms used by astrocytes to limit neuroinflammation during toxoplasmic encephalitis have not yet been identified. Transforming growth factor beta (TGFβ) signaling in astrocytes is of particular interest because TGFβ is universally upregulated during CNS infection and serves master regulatory and primarily anti-inflammatory functions. We report here that TGFβ signaling is activated in astrocytes during toxoplasmic encephalitis, and that inhibition of astrocytic TGFβ signaling increases immune cell infiltration, uncouples pro-inflammatory and chemokine production from CNS parasite burden, and increases neuronal injury. Remarkably, we show that the effects of inhibiting astrocytic TGFβ signaling are independent of parasite burden and the ability of GFAP+ astrocytes to physically encircle parasites.

inner layers (DRIL) has demonstrated significant correlations with visual acuity (VA) in center-involved diabetic macular edema. In patients with retinal vein occlusion (RVO) and secondary macular edema, DRIL may be a useful biomarker in determining VA outcomes. OBJECTIVE To examine whether DRIL at baseline and after treatment is associated with VA in RVO. DESIGN, SETTING, AND PARTICIPANTSA retrospective review of records of 147 patients 18 years or older with treatment-naive branch RVO (BRVO), central RVO (CRVO), or hemispheric RVO (HRVO), with a minimum of 12 months of follow-up, who presented to a tertiary ophthalmic center from December 1, 2010, to January 1, 2016, was conducted. Data collection continued through January 2017. Exclusion criteria included active confounding retinal or ocular disease, history of pars plana vitrectomy, or prior intravitreal injections. Two masked graders calculated a DRIL score based on DRIL presence in 3 predefined regions on spectral-domain optical coherence tomography at baseline, 6 months, and 12 months. A third masked grader was used for discrepancies.EXPOSURES Anti-vascular endothelial growth factor (AVF) therapy (ranibizumab, aflibercept, or bevacizumab) determined by the treating physician. MAIN OUTCOMES AND MEASURESThe DRIL score at baseline for determining VA outcomes and correlation of VA with changes in DRIL burden in response to AVF therapy. RESULTSIn the 147 patients (mean [SD] age, 68.9 [13.1] years; 75 [51.0%] female), baseline DRIL was seen in 91 eyes (61.9%). In the BRVO group but not the CRVO group, baseline DRIL was associated with lower baseline Early Treatment Diabetic Retinopathy Study (ETDRS) score (score of 66.7 for no DRIL vs 54.6 for DRIL, P = .002). Absence of DRIL at baseline in the CRVO/HRVO group correlated with greater VA gains at 6 months, adjusting for baseline VA (score change of 19.50 for no DRIL vs 12.72 for DRIL; P = .04). During 12 months, continued DRIL presence in BRVO was associated with less VA gain up to 6 months (score change of 6.2 for the DRIL increase group vs 18.6 for the DRIL decrease group vs 2.9 for the DRIL stable group; P = .02). Increasing DRIL scores in CRVO/HRVO were associated with reduced VA improvement at 6 months (score change of -0.12 for the DRIL increase group vs 16.90 for the DRIL decrease group vs 8.45 for the DRIL stable group; P = .002) and 12 months (score change of -1.91 for the DRIL increase group vs 17.83 for the DRIL decrease group vs 6.97 for the DRIL stable group; P < .001). CONCLUSIONS AND RELEVANCEBaseline DRIL presence and DRIL burden changes with AVF therapy for macular edema secondary to RVO may be useful biomarkers of ETDRS score improvements.

IntroductionContrast sensitivity function (CSF) may better estimate a patient’s visual function compared with visual acuity (VA). Our study evaluates the quick CSF (qCSF) method to measure visual function in eyes with macular disease and good letter acuity.MethodsPatients with maculopathies (retinal vein occlusion, macula-off retinal detachment, dry age-related macular degeneration and wet age-related macular degeneration) and good letter acuity (VA ≥20/30) were included. The qCSF method uses an intelligent algorithm to measure CSF across multiple spatial frequencies. All maculopathy eyes combined and individual macular disease groups were compared with healthy control eyes. Main outcomes included area under the log CSF (AULCSF) and six CS thresholds ranging from 1 cycle per degree (cpd) to 18 cpd.Results151 eyes with maculopathy and 93 control eyes with VA ≥20/30 were included. The presence of a maculopathy was associated with significant reduction in AULCSF (β: −0.174; p<0.001) and CS thresholds at all spatial frequencies except for 18 cpd (β: −0.094 to −0.200 log CS, all p<0.01) compared with controls. Reductions in CS thresholds were most notable at low and intermediate spatial frequencies (1.5 cpd, 3 cpd and 6 cpd).ConclusionCSF measured with the qCSF active learning method was found to be significantly reduced in eyes affected by macular disease despite good VA compared with healthy control eyes. The qCSF method is a promising clinical tool to quantify subtle visual deficits that may otherwise go unrecognised by current testing methods.

For macular oedema secondary to retinal vein occlusion, anti-VEGF treatment can result in a greater improvement in average letters gained and in CST for those with poor initial VA compared with those with better initial VA.