Development of cystoid macular edema after uneventful cataract surgery in eyes with a history of vitrectomy using silicone oil versus gas tamponade.

BACKGROUND/OBJECTIVES: The purpose of this study is to investigate whether history of silicone oil tamponade may predispose to the development of cystoid macular edema (CMO) following uneventful post-vitrectomy cataract surgery. SUBJECTS/METHODS: This is a retrospective study that was conducted at a single academic institution. Records of patients who underwent pars plana vitrectomy (PPV) with or without silicone oil tamponade and subsequent cataract surgery between 2017-2020 were reviewed. Macular optical coherence tomography (OCT) findings up to 4 years after surgery were assessed. RESULTS: A total of 95 eyes were included. Forty-one eyes underwent cataract surgery and had a history of PPV with silicone oil tamponade (Group 1). Fifty-four eyes underwent cataract surgery by phacoemulsification and had a history of PPV with gas tamponade (Group 2). Average follow up time after cataract surgery was 41.1 months. In Group 1, the incidence of OCT-detected CMO was 39.0%, compared to 27.8% in Group 2 (p = 0.247). The incidence of clinically significant CMO in Group 1 was 22.0%, compared to 18.5% in Group 2 (p = 0.679). The duration of CMO was significantly longer in Group 1 (p = 0.041) and cases were less likely to resolve by the last follow up visit (p = 0.040). CONCLUSIONS: The incidence of OCT-detected or clinically significant pseudophakic CMO is not significantly different between eyes with prior PPV with gas tamponade versus silicone oil tamponade. However, CMO after uneventful cataract surgery may have a prolonged course if there is history of silicone oil tamponade, requiring longer treatment.

Modified Endolaser Instrument for Chandelier Scleral Buckling.

Purpose: To report a new modification of an illuminated endolaser to facilitate safe endophotocoagulation during chandelier-assisted scleral buckling surgery. Methods: This case series comprised phakic patients with rhegmatogenous retinal detachments (RRDs) who had primary scleral buckling with chandelier endoillumination, external drainage, and endophotocoagulation using the modified endolaser instrument. Results: All 6 patients had successful outcomes after primary scleral buckling for RD repair without significant intraoperative or postoperative complications. Conclusions: The new modified endolaser instrument can be safely used in a nonvitrectomized eye during chandelier scleral buckling.

Amniotic Membrane Patching to Assist Closure of Recalcitrant Macular Holes.

BACKGROUND AND OBJECTIVE: This study reports a case series of patients with persistent macular holes (MHs) who underwent human amniotic membrane subretinal placement to achieve successful anatomic MH closure. PATIENTS AND METHODS: This was a retrospective case series of patients with persistently open full-thickness MHs who underwent human amniotic membrane placement. Patients were observed up to 6 months postoperatively. RESULTS: Ten patients were included. The mean preoperative best-corrected visual acuity was 1.6 logMAR (20/800). Postoperatively, mean best-corrected visual acuity improved to 1.3 logMAR (20/400) at 1 month and 1.1 logMAR (20/250) by the 3- and 6-month visits. In all cases, the MH appeared closed at the 1-week visit and remained closed at their last follow-up. Optical coherence tomography showed closure in all cases. No adverse events were reported. CONCLUSIONS: Human amniotic membrane sub-retinal placement may serve as a useful surgical technique to assist in the closure of recalcitrant macular holes. [Ophthalmic Surg Lasers Imaging Retina 2023;54:218-222.].

Impact of prior pars plana vitrectomy on development of cystoid macular edema after uneventful cataract surgery.

PURPOSE: To investigate whether a history of prior pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) predisposes to the development of pseudophakic cystoid macular edema (CME). SETTING: New York Eye and Ear Infirmary of Mount Sinai, New York, New York. DESIGN: Retrospective cohort study. METHODS: Records of 365 subjects who underwent PPV for RRD and subsequent cataract surgery between 2017 and 2020 were reviewed. Patients with a history of diabetic retinopathy, inflammatory retinal vascular disease, uveitis, advanced age-related macular degeneration, intraocular infection, myopic maculopathy, or significant intraoperative complications precluding posterior chamber intraocular lens placement were excluded. Age-matched subjects who underwent routine cataract surgery served as controls. Clinical data and macular optical coherence tomography (OCT) findings up to 4 years postoperatively were obtained. RESULTS: 54 eyes underwent uneventful cataract surgery by phacoemulsification and had a history of PPV with gas tamponade. 55 eyes underwent uneventful cataract surgery only. The average follow-up time after cataract surgery was 39.1 months. In eyes with a history of PPV, the incidence of OCT-detected CME was 27.8% (15/54) compared with 3.8% (2/55) in the control group ( P < .001) and the incidence of clinically significant CME was 18.5% (10/54) compared with 1.8% (1/55) in the control group ( P = .004). 80% (12/15) of CME cases were treated with topical therapy, and none required intravitreal injection. CONCLUSIONS: Prior PPV for RRD is associated with an increased incidence of pseudophakic CME after uneventful cataract surgery. Prophylactic or prolonged postoperative anti-inflammatory topical therapy may be prudent to consider in these patients.

Navigated Retina Laser Therapy as a Novel Method for Laser Retinopexy of Retinal Tears.

BACKGROUND AND OBJECTIVE: To describe the use of a navigated laser system for the treatment of retinal tears. MATERIALS AND METHODS: A planned pattern laser retinopexy was performed using a navigated laser photocoagulator incorporating rapid panretinal photocoagulation technology with an individualized target overlay to produce a 3 × 3 square pattern surrounding a horseshoe tear. Institutional review board approval was not applicable for this case. RESULTS: Successful laser retinopexy 360° around the tear was achieved. CONCLUSION: In select cases, a navigated laser system may be utilized for the treatment of retinal tears. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e206-e209.].

Manual Removal of Primary Posterior Capsular Plaques Using Retinal End-Grasping Forceps.

INTRODUCTION: Primary posterior capsular plaques can be highly adherent to the posterior capsule leading to possible posterior capsular rupture during attempted removal. Here we describe a novel method for posterior capsular plaque removal using a technique inspired by the experience of retina surgeon in the peeling of membranes from the posterior pole. METHODS: Retinal end-grasping forceps were used to peel the plaque from the posterior capsule. RESULTS: We have performed this technique on 12 eyes with successful removal of the posterior capsular plaque in all instances without compromise of the posterior capsule in any case. CONCLUSIONS: We hope that the anterior segment surgeons will benefit by employing this useful technique during cataract surgeries in the eyes with adherent posterior plaques.

Current choice of treatments for neovascular AMD.

Age-related macular degeneration is the leading cause of irreversible blindness in developed countries with the neovascular form accounting for the majority of severe vision loss in the disease. The management of wet age-related macular degeneration has improved drastically in the past decade as anti-VEGF agents took its place at the forefront of treatment. As the choice of therapy is based on a number of factors, this review summarizes the pivotal studies that brought these agents to use and compares the different agents currently available. This review also briefly describes the promising new therapies that are in development.

Qualitative spectral OCT/SLO analysis of drusen change in dry age-related macular degeneration patients treated with Copaxone.

PURPOSE: High-resolution spectral domain OCT/SLO (SD-OCT) has become an increasingly useful tool for differentiating drusen morphologic parameters such as shape, internal reflectivity, homogeneity, and presence of overlying hyperreflective foci. Our purpose was to evaluate which types of drusen may respond to Copaxone (glatiramer acetate) treatment of dry age-related macular degeneration (AMD) patients by shrinking or disappearing. METHODS: A prospective and interventional clinical trial of patients with dry AMD who received subcutaneous treatment with Copaxone or sham injections was conducted. SD-OCT images were used for analysis of drusen ultrastructure. Morphologic characteristics for specific drusen within the macular region were assessed with serial studies. Pre- and posttreatment statuses of drusen were compared. Main outcome measure was a change of drusen morphologic parameters in Copaxone-treated and sham-treated dry AMD patients between baseline and 12 weeks of treatment. RESULTS: Three hundred eleven drusen from 26 eyes of 14 dry AMD patients were evaluated. One hundred seventy-two drusen from 14 eyes (7 patients) of Copaxone-treated and 139 drusen from 12 eyes sham-treated (7 patients) were included. Overall, between baseline and 12-week visit, the percentage of drusen that disappeared/shrank in the Copaxone-treated group was 19.2% versus 6.5% in the sham-treated group (P = 0.13). The percentage of convex drusen that shrank or disappeared after 12 weeks of treatment was significantly higher in the Copaxone-treated group (27.8%) in comparison with the sham-treated group (6.8%) (P = 0.008). The difference between the groups was found to be statistically significant for drusen with low and medium internal reflectivity (P = 0.019 and P = 0.036, respectively). CONCLUSIONS: Convex shape and low/medium internal reflectivity were found to be favorable parameters in prediction of drusen reduction in the Copaxone-treated patients. This study represents a preliminary attempt to identify SD-OCT features of drusen that may predict susceptibility to Copaxone treatment and therefore help clinicians decide which patients to treat.

Cilioretinal arteries in diabetic eyes are associated with increased retinal blood flow velocity and occurrence of diabetic macular edema.

PURPOSE: The main purpose was to investigate the relationship between occurrence of cilioretinal arteries and macular edema in diabetic eyes in terms of retinal blood flow characteristics revealed by the Retinal Function Imager (RFI). Other standard imaging techniques such as fundus photography, fluorescein angiography, and spectral-domain optical coherence tomography/scanning laser ophthalmoscopy were also used along with the RFI. The additional purpose was to look for the evidence of cilioretinal-retinal collaterals using the RFI. METHODS: Patients with a diagnosis of diabetic retinopathy were included. All patients underwent fundus photography, fluorescein angiography, spectral-domain optical coherence tomography, and imaging using RFI. The presence of cilioretinal artery (CilRA) was recognized using color/red-free fundus photographs, fluorescein angiography, and RFI. There were two groups according to the presence (CilRA group) or absence (NoCilRA group) of cilioretinal artery or arteries in the study eye. RESULTS: Thirty-nine eyes with diabetic retinopathy were included. Cilioretinal artery was identified in 15 eyes (38%). In the CilRA group, spectral-domain optical coherence tomography evidence of macular edema was observed in 13 of 15 eyes (87%), whereas in the NoCilRA group, macular edema was observed on spectral-domain optical coherence tomography in 7 of 24 eyes (29%). Mean blood flow velocities in retinal arteries and veins were significantly higher in diabetic eyes with cilioretinal artery (P = 0.04 and P = 0.005, respectively). Mean blood velocity in cilioretinal arteries was significantly higher in comparison with the mean arterial blood velocity (P = 0.03). In the CilRA group, cilioretinal-retinal collaterals, assessed by RFI, were detected in 4 of 15 eyes (27%) with cilioretinal arteries. In the NoCilRA group, mean blood velocity in retinal veins was significantly higher in eyes with macular edema in comparison with those without macular edema (P = 0.03). CONCLUSION: Using the RFI in conjunction with standard fundus imaging techniques, the presence of cilioretinal artery in diabetic eyes was found to be associated with increased retinal blood flow velocity and increased occurrence of diabetic macular edema. The occurrence of cilioretinal-retinal collaterals was also noted; however, the pathophysiologic significance of this finding requires further investigation.

Macular hole formation, progression, and surgical repair: case series of serial optical coherence tomography and time lapse morphing video study.

BACKGROUND: To use a new medium to dynamically visualize serial optical coherence tomography (OCT) scans in order to illustrate and elucidate the pathogenesis of idiopathic macular hole formation, progression, and surgical closure. CASE PRESENTATIONS: Two patients at the onset of symptoms with early stage macular holes and one patient following repair were followed with serial OCTs. Images centered at the fovea and at the same orientation were digitally exported and morphed into an Audiovisual Interleaving (avi) movie format. Morphing videos from serial OCTs allowed the OCTs to be viewed dynamically. The videos supported anterior-posterior vitreofoveal traction as the initial event in macular hole formation. Progression of the macular hole occurred with increased cystic thickening of the fovea without evidence of further vitreofoveal traction. During cyst formation, the macular hole enlarged as the edges of the hole became elevated from the retinal pigment epithelium (RPE) with an increase in subretinal fluid. Surgical repair of a macular hole revealed initial closure of the macular hole with subsequent reabsorption of the sub-retinal fluid and restoration of the foveal contour. CONCLUSIONS: Morphing videos from serial OCTs are a useful tool and helped illustrate and support anterior-posterior vitreofoveal traction with subsequent retinal hydration as the pathogenesis of idiopathic macular holes.

Acquired senile retinoschisis of the peripheral retina imaged by spectral domain optical coherence tomography: a case report.

PURPOSE: We report spectral domain optical coherence tomography findings of the peripheral retina in a patient with senile (acquired) retinoschisis. METHODS: This is an observational case report. Spectral domain optical coherence tomography was performed to image the peripheral retina at the area of retinoschisis in a 70-year-old man with bilateral inferonasal elevated peripheral retinal lesions. Since the lesions were not entirely transparent and smooth, and demonstrated a certain degree of mobility, the diagnosis of retinal detachment could not be excluded. RESULTS: Spectral domain optical coherence tomography scans obtained at the margin of the lesions demonstrated attached retina with a characteristic splitting of the neurosensory retina at the outer plexiform layer and cystic changes in the inner retina. CONCLUSIONS: Spectral domain optical coherence tomography can assist in the diagnosis of senile (acquired) retinoschisis, particularly in cases where retinal detachment cannot be excluded on clinical examination alone.

A new vascular pattern for idiopathic juxtafoveal telangiectasia revealed by the retinal function imager.

BACKGROUND AND OBJECTIVE: The Retinal Function Imager (RFI) (Optical Imaging, Rehovot, Israel) is a novel method for assessing retinal blood flow characteristics and demonstrating the dynamics of fine retinal vasculature. The authors report a new pattern of retinal blood flow in five patients with idiopathic juxtafoveal telangiectasia (IJT) type 2. PATIENTS AND METHODS: Retinal circulation is imaged using the RFI as a series of high-speed stroboscopically captured fundus photographs. Proprietary software aligns the images, allowing serial subtraction, and creates short video loops that show movement of red blood cells in the small and medium size retinal blood vessels. RESULTS: Ten eyes of five patients with IJT type 2 were examined. In all cases, the RFI demonstrated a common pattern of centripetal vascular flow in the region of telangiectasia. This pattern is unique in its configuration of vascular flow into the focus of the area of telangiectasia. This pattern could not be appreciated on fluorescein angiography. CONCLUSION: The RFI can detect the specific vascular pattern of the retinal blood flow in eyes of patients with IJT. The ability to characterize such blood flow patterns may aid in identification of ambiguous cases of IJT when the diagnosis is not straightforward.

Combined three-dimensional spectral OCT/SLO topography and Microperimetry: steps toward achieving functional spectral OCT/SLO.

AIMS: To investigate the combination of 3D optical coherence tomography (OCT) retinal thickness measurements and superimposed scanning laser ophthalmoscopy (SLO) microperimetry obtained using a Spectral OCT/SLO and to test the correlation between retinal thickness and retinal sensitivity in retinal diseases grouped according to anatomic locations. METHODS: Patients with various retinal diseases and subjects with normal fundi underwent microperimetry testing and imaging with the Spectral OCT/SLO. Based on the Spectral OCT/SLO findings, the participants were divided into 4 groups: patients with retinal thickening due to the outer retina pathology (group I); patients with retinal thickening due to the cystic changes observed in the inner retina (group II); patients with macular neurosensory retina thinning associated with geographic atrophy or underlying subretinal cicatricial changes (group III), and subjects with unremarkable fundus appearance and normal appearing retina on Spectral OCT/SLO (group IV). The primary outcome was the correlation coefficient (r) between Spectral OCT/SLO-measured macular thickness and microperimetry values. RESULTS: Correlations between retinal thickness and psychophysical thresholds were calculated for each patient, and these values were averaged within groups. The mean correlation values (Pearson product movement) were as follows: for group I (n = 21 eyes) r = 0.04; for group II (n = 24 eyes) r = -0.53; for group III (n = 16 eyes) r = 0.41, and for group IV (n = 15 eyes) r = 0.04. CONCLUSIONS: The combination of 3D OCT images and superimposed SLO microperimetry obtained by Spectral OCT/SLO demonstrated that thickening due to cystic changes of the inner retinal layers or thinning of the neurosensory retina on OCT correlated most significantly with decreases in psychophysical threshold sensitivities.

Comparative study of intravitreal bevacizumab (Avastin) versus ranibizumab (Lucentis) in the treatment of neovascular age-related macular degeneration.

AIMS: To compare the safety and efficacy of 2 anti-vascular-endothelial-growth-factor agents - bevacizumab (Avastin) versus ranibizumab (Lucentis) - in the treatment of patients with neovascular age-related macular degeneration (AMD). METHODS: Retrospective analysis of patients who received intravitreal injections of bevacizumab or ranibizumab for neovascular AMD. Primary outcome measures were best-corrected visual acuity (BCVA) and central foveal thickness (CFT) assessed by Spectral Domain scanning laser ophthalmoscope-optical coherence tomography (SD-OCT). A secondary outcome measure was the report of any adverse events in the 2 groups. RESULTS: The number of injections in the bevacizumab group was 184 (average of 4.7 per eye) compared to 187 in the ranibizumab group (average of 5.5 per eye). The mean logMAR equivalent of BCVA at 1 month after the injection improved by 0.18 in the bevacizumab group (p = 0.009) and by 0.13 in the ranibizumab group (p = 0.004). The average SD-OCT CFT decreased from 325 + or - 72 to 300 + or - 69 microm in the bevacizumab group (p = 0.016) and from 307 + or - 57 to 289 + or - 56 microm in the ranibizumab group (p = 0.017). In the bevacizumab group, there was 1 event of lower extremity pain (0.54%) and 1 event of increased arterial blood pressure (0.54%). In the ranibizumab group, there were 2 events of transiently increased intraocular pressure (1.1%) and 1 event (0.53%) of intraocular inflammation following injection. CONCLUSIONS: Bevacizumab and ranibizumab treatments resulted in similar gains in visual acuity and reduction in macular thickness, documented each month following injection. Intravitreal bevacizumab appears to be as safe and effective as intravitreal ranibizumab in the treatment of exudative AMD.

Correlation between spectral domain optical coherence tomography findings and fluorescein angiography patterns in diabetic macular edema.

OBJECTIVE: To study the relationship between spectral domain optical coherence tomography (SD-OCT) findings and fluorescein angiography (FA) patterns in patients with diabetic macular edema (DME). DESIGN: Retrospective, observational, cross-sectional study. PARTICIPANTS: We included 59 eyes from 59 patients with DME that had SD-OCT/scanning laser ophthalmoscope (SLO) and FA performed on the same day. Eyes with macular edema owing to other ocular diseases were excluded. METHODS: The relationship between SD-OCT and FA findings was evaluated by superimposing and aligning the SLO images onto the FA photos. The SLO image of the OPKO/OTI Spectral OCT/SLO (OPKO-OTI, Miami, FL) corresponds with the exact origin and orientation of the SD-OCT scan, which was then correlated with the FA image. Foveal and extrafoveal regions were studied separately. Leakage on FA and pathologic changes on OCT were graded by using standard photographs. Pathologic changes studied in the OCT images included edema and cystic spaces in the inner and outer retina, loss of retinal layers, and foveal cysts. MAIN OUTCOME MEASURES: Correlation between SD-OCT changes and corresponding FA patterns. RESULTS: The outer retina was the predominant location of fluid in DME. The severity of the outer retinal edema on OCT was positively correlated with the severity of leakage on FA (r = 0.735; P<0.001). Cystic changes in the inner and outer retina were also correlated with the severity of fluorescein leakage (r = 0.507 and P<0.001; r = 0.561 and P<0.001, respectively). Loss of inner retinal layers on OCT was highly correlated with capillary nonperfusion on FA (r = 0.953; P<0.001). Large foveal cysts on SD-OCT corresponded to cystoid leakage patterns on FA. CONCLUSIONS: Pathologic changes on SD-OCT correlated well with FA findings. Loss of inner retinal layers was specifically correlated with capillary nonperfusion and severe ischemia. Judgment of whether management of DME based on fine retinal structural changes influences clinical outcomes must be reserved pending further investigation with prospective trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Weekly vaccination with Copaxone (glatiramer acetate) as a potential therapy for dry age-related macular degeneration.

PURPOSE: Drusen formation in age-related macular degeneration (AMD) shares some similarities with Alzheimer's disease (AD), which is associated with amyloid deposits. Aggregated beta-amyloid induces microglia to become cytotoxic and block neurogenesis. Recent evidence showed that T cell-based vaccination with Copaxone in AD mice model resulted in modulation of microglia into neuroprotective phenotype and as a result in reduction of cognitive decline, elimination of plaque formation, and induction of neuronal survival and neurogenesis. The aim was to investigate whether the effect of Copaxone on drusen in dry AMD is similar to that on deposits of other age-related chronic neurodegenerative diseases such as Alzheimer disease (AD). MATERIALS AND METHODS: Patients over 50 years of age with intermediate dry AMD in both eyes were randomized to receive Copaxone or sham injections and were weekly treated by subcutaneous injections of Copaxone (dose of 20 mg) or sham injections for 12 weeks. At baseline, 6-week, and 12-week visits, visual acuity, contrast sensitivity, fundus examination and photography, fluorescein angiography, and ocular coherent tomography were performed. Main outcome measure was a change in total drusen area (TDA) measured by Image-Pro software and presented in arbitrary units (AU). RESULTS: Eight studied eyes of four treated patients showed a decrease in TDA from 48130 to 16205 AU at 12 weeks as compared to baseline. In contrast, four control eyes (two patients) demonstrated almost no change in TDA (from 32294 to 32781 AU). CONCLUSION: These preliminary results show that Copaxone reduces drusen area.

Outcome of posterior capsulotomy in late capsular block syndrome with posterior capsular opacification.

BACKGROUND: To examine the results of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser posterior capsulotomy in eyes with late or previously unrecognized capsular block syndrome (CBS) presenting with deterioration of vision owing to posterior capsular opacification (PCO). METHODS: Patients, who underwent uneventful phacoemulsification with intraocular implantation and were referred for Nd:YAG laser capsulotomy owing to PCO, were prospectively examined for the presence of CBS. When indicated, Nd:YAG laser posterior capsulotomy was carried out. Prospective follow-up examinations were performed for the next 6 months. The outcome measures were post-laser change in best corrected visual acuity, refraction, change in intraocular pressure, inflammation and complication rate. RESULTS: Of 655 patients referred for capsulotomy, eight had an associated CBS in that eye. These eight eyes comprised the study cases. The presence of CBS had not been recognized before the development of PCO. Best corrected visual acuity improved in all cases. In seven out of eight (87.5%) eyes refraction was unchanged throughout the follow up. Ocular hypertension, inflammation or other complications did not develop. CONCLUSION: Nd:YAG laser capsulotomy in eyes with PCO and late or previously unrecognized CBS is a safe procedure, resulting in improved visual acuity without refractive change.

Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1.

Alzheimer's disease (AD) is characterized by plaque formation, neuronal loss, and cognitive decline. The functions of the local and systemic immune response in this disease are still controversial. Using AD double-transgenic (APP/PS1) mice, we show that a T cell-based vaccination with glatiramer acetate, given according to a specific regimen, resulted in decreased plaque formation and induction of neurogenesis. It also reduced cognitive decline, assessed by performance in a Morris water maze. The vaccination apparently exerted its effect by causing a phenotype switch in brain microglia to dendritic-like (CD11c) cells producing insulin-like growth factor 1. In vitro findings showed that microglia activated by aggregated beta-amyloid, and characterized as CD11b(+)/CD11c(-)/MHC class II(-)/TNF-alpha(+) cells, impeded neurogenesis from adult neural stem/progenitor cells, whereas CD11b(+)/CD11c(+)/MHC class II(+)/TNF-alpha(-) microglia, a phenotype induced by IL-4, counteracted the adverse beta-amyloid-induced effect. These results suggest that dendritic-like microglia, by facilitating the necessary adjustment, might contribute significantly to the brain's resistance to AD and argue against the use of antiinflammatory drugs.

Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells.

Cell renewal in the adult central nervous system (CNS) is limited, and is blocked in inflammatory brain conditions. We show that both neurogenesis and oligodendrogenesis of adult neural progenitor cells in mice are blocked by inflammation-associated (endotoxin-activated) microglia, but induced by microglia activated by cytokines (IL-4 or low level of IFN-gamma) associated with T-helper cells. Blockage was correlated with up-regulation of microglial production of tumor necrosis factor-alpha. The effect induced by IL-4-activated microglia was mediated, at least in part, by insulin-like growth factor-I. The IL-4-activated microglia showed a bias towards oligodendrogenesis whereas the IFN-gamma-activated microglia showed a bias towards neurogenesis. It thus appears that microglial phenotype critically affects their ability to support or impair cell renewal from adult stem cell.