Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial.

BACKGROUND: We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. METHODS: A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. RESULTS: BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). CONCLUSIONS: We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. TRIAL REGISTRATION: The trail has been registered at Chinese Clinical Trail Registry( https://www.chictr.org.cn ) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.

Purpose: To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). Methods: This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. Results: The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). Conclusion: Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).

Comparison of 27-gauge beveled-tip and 25-gauge flat-tip microincision vitrectomy surgery in the treatment of proliferative diabetic retinopathy: a randomized controlled trial.

PURPOSE: To compare the effectiveness and safety of a 27-gauge (27G) beveled-tip microincision vitrectomy surgery (MIVS) with a 25-gauge (25G) flat-tip MIVS for the treatment of proliferative diabetic retinopathy (PDR). METHODS: A prospective, single-masked, randomized, controlled clinical trial included 52 eyes (52 patients) with PDR requiring proliferative membrane removal. They were randomly assigned in a 1:1 ratio to undergo the 27G beveled-tip and or 25G flat-tip MIVS (the 27G group and the 25G group, respectively). During surgery, the productivity of cutting the membrane, the number of vitrectomy probe (VP) exchanges to microforceps, total operation time, vitrectomy time and intraoperative complications were measured. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) and postoperative complications were also assessed to month 6. RESULTS: Forty-seven eyes (47 patients) completed the follow-up, including 25 in the 27G group and 22 in the 25G group. During surgery in the 27G group, cutting the membrane was more efficient (P = 0.001), and the number of VP exchanges to microforceps was lower (P = 0.026). The occurrences of intraoperative hemorrhages and electrocoagulation also decreased significantly (P = 0.004 and P = 0.022). There were no statistical differences in the total operation time or vitrectomy time between the two groups (P = 0.275 and P = 0.372), but the former was slightly lower in the 27G group. Additionally, the 27G group required fewer wound sutures (P = 0.044). All the follow-up results revealed no significant difference between the two groups. CONCLUSIONS: Compared with the 25G flat-tip MIVS, the 27G beveled-tip MIVS could be more efficient in removing the proliferative membrane while reducing the occurrence of intraoperative hemorrhages and electrocoagulation using appropriate surgical techniques and instrument parameters. Its vitreous removal performance was not inferior to that of the 25G MIVS and might offer potential advantages in total operation time. In terms of patient outcomes, advanced MIVS demonstrates equal effectiveness and safety to 25G flat-tip MIVS. TRIAL REGISTRATION: The clinical trial has been registered at Clinicaltrials.gov (NCT0544694) on 07/07/2022. And all patients in the article were enrolled after registration.

Association of metformin treatment with enhanced effect of anti-VEGF agents in diabetic macular edema patients.

PURPOSE: To investigate the effect of metformin combined with anti-VEGF agents in patients with diabetic macular edema (DME). METHODS: This study was a prospective, nonrandomized case-control study. Patients were included in with a diagnosis of DME who received anti-VEGF agents injection. Basic information, medical history, best-corrected visual acuity (BCVA), central macular thickness (CMT), the number of intravitreal injections, panretinal photocoagulation (PRP), and macular grid photocoagulation treatment during the 6-month follow-up, were recorded for each patient. RESULTS: A total of 50 DME patients were collected (24 patients with a history of oral metformin ≥ 6 months and 26 patients who had not taken metformin). The BCVA and the CMT were significantly improved after anti-VEGF treatment in two groups (F1 = 19.35, F2 = 26.78; F1 = 65.45, F2 = 76.23; P < 0.05). The BCVA in the metformin group was better than that in non-metformin group at every point after treatment (F = 34.45, P < 0.05). The CMT in metformin group decreased much more than that in non-metformin group during the follow-up period (F = 87.05, P < 0.05). The injection numbers decreased in the metformin group compared with the non-metformin group (t = 5.14, P < 0.05). However, there was no difference in PRP and macular grid photocoagulation therapy between the two groups during the 6-month follow-up. CONCLUSION: Metformin can enhance the therapeutic effect of anti-VEGF agents on DME patients to improve their visual acuity, improve the structure of the macular area, and reduce the number of intravitreal injections 90.

Clinical experience of using the NGENUITY three-dimensional surgery system in ophthalmic surgical procedures.

PURPOSE: To assess the clinical experience of using a three-dimensional (3D) system for ophthalmic surgical procedures. METHODS: We retrospectively analysed video recordings of patients who underwent 3D ophthalmic surgery, using the NGENUITY® 3D visualization system, or traditional microsurgery at our hospital, from August 2017 to February 2018. Patients underwent phacoemulsification or phacoemulsification combined with vitrectomy. Diagnoses, operation type, duration of continuous curvilinear capsulorhexis (CCC), number of forceps nips during CCC and capsulorhexis complications were recorded. Five surgeons and four assistants answered a 3D surgery questionnaire. RESULTS: Twenty-six of 46 patients who underwent 3D surgery, and 31 of 51 patients who underwent traditional microsurgery (control group) were enrolled. The mean CCC duration in the study and control groups was 31.2 ± 10.8 and 28.7 ± 13.2 seconds (p = 0.071), and the mean number of forceps nips was 5 ± 2 and 5 ± 2 (p = 0.634), respectively. The anterior capsular rupture rate of phacoemulsification under 3D and traditional conditions was 3.85% (1/26 cases) and 3.23% (1/31 cases), respectively. The complication rate was similar between the two groups (p > 0.999). Four of five surgeons and two of four assistants believed the clarity of 3D surgery was similar or better than that of traditional microsurgery. The occurrence of dizziness (p > 0.999), shoulder and neck pain (p = 0.262), backache (p = 0.471) and visual fatigue (p = 0.347) did not differ significantly between the two methods. CONCLUSION: The 3D surgical system facilitated similar operation speed and stability as the traditional microscope and provided reliable support for ophthalmic surgery.

Association of VEGF Gene Polymorphisms with Susceptibility to Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

The associations between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of type 2 diabetic retinopathy (DR) - proliferative diabetic retinopathy (PDR), and nonproliferative diabetic retinopathy (NPDR) - remain unclear. A systematic search and meta-analysis using odds ratio (OR) with 95% confidence interval (CI) was performed to evaluate the association. Our study concluded 26 studies containing 10 single nucleotide polymorphisms (SNPs). In Asian populations, rs3025039 polymorphism was associated with DR risk, while in overall populations and Caucasians, the DR risk was increased by association with rs2010963. There was a significant association between rs25648 and rs833061 and DR risk in Caucasians. DR risks were found to be significantly associated between rs3025021, rs13207351, and rs2146323 in either overall populations, Caucasians or Asians. Besides, in overall and Asian populations, rs699947 and rs3025039 were associated with PDR risk. rs1570360, rs3025039, and rs833061 played a key role in PDR etiology in Caucasians. rs2010963 was associated with increased risk of PDR in overall populations. A significant association between rs699947, rs3025039, and rs833061 and NPDR risk in overall populations and Asians was found. A significant association was observed between rs2010963 and increased NPDR risk in overall and Caucasian populations. This study provides a new insight into the parthenogenesis of diabetic retinopathy. Targeting VEGF SNPs may be a potential of therapeutic approach for the treatment of DR, PDR, and NPDR.

Comparison of adsorption properties for cadmium removal from aqueous solution by Enteromorpha prolifera biochar modified with different chemical reagents.

Using biochar to remove heavy metals from water is environmentally beneficial. In this study, three kinds of chemical reagents, including ZnCl2, H3PO4 and KMnO4, were introduced to modify the biochar derived from Enteromorpha prolifera. The performance of these modified biochar in removing Cadmium ions (Cd(II)) from water was investigated. The physicochemical properties of activated biochars were characterized by N2-sorption, thermal gravity and differential thermal gravity (TG/DTG), scanning electron microscopy (SEM), elemental analysis and Fourier transform infrared spectroscopy (FTIR). The results showed that the removal rate of Cd(II) from water by EP biochar modified with H3PO4 was significantly increased, and the maximum adsorption capacity of Cd(II) reached to 423 mg/g for PBC. Moreover, the adsorption of Cd(II) from water by phosphoric acid modified biochar was very fast, and the saturation adsorption of Cd(II) was reached within 1 h. Compared with pseudo first-order model, pseudo secondary-order model was much more suitable for analyzing the adsorption kinetics data of Cd(II) onto KBC or ZBC. The adsorption of Cd(II) onto PBC was analyzed by the intra-particle diffusion kinetic model, where the value of R2 was high as 0.98. The Langmuir model was fit for phosphoric acid modified biochar.

PF4 antagonizes retinal neovascularization via inhibiting PRAS40 phosphorylation in a mouse model of oxygen-induced retinopathy.

Retinal neovascularization (RNV) is a common pathology of blinding proliferative retinopathies. The current treatments to RNV, however, are hindered by limited efficacy, side effects, and drug resistance. A naturally-occurring cytokine in retina that is amicable to immune system and possesses robust anti-neovascular function would facilitate to overcome the hurdles. In this study, retinas from a mouse model of oxygen-induced retinopathy (OIR) underwent a protein array to screen the naturally-occurring cytokines that may antagonize RNV. Among the 62 angiogenesis-associated cytokines, platelet factor 4 (Pf4) stood out with the most prominent upregulation and statistical significance. Moreover, an intravitreal injection of mouse Pf4 demonstrated dramatic anti-vaso-obliteration and anti-neovascularization effects dose dependently in the OIR model; whereas human PF4 inhibited the proliferation, migration, and tubulogenesis of monkey retinal vascular endothelial cells treated with VEGF and TNF-α. These previously undescribed angiostatic effects of PF4 in OIR retinas and retinal vascular endothelial cells support translation of this naturally-occurring chemokine into a therapeutic modality to RNV supplementary to the anti-VEGFs. Mechanistically, a phosphorylation array and western blots indicated that downregulation of proline-rich Akt substrate of 40 kDa (Pras40) and its phosphorylation were necessary for Pf4's anti-neovascular effects in the OIR retinas. Indeed, overexpression of the wildtype Pras40 and the mutant version with deficient phosphorylation abolished and mimicked the Pf4's angiostatic effects in the OIR retinas, respectively. The similar effects were also observed in vitro. This study, for the first time, links PF4's anti-RNV function to an intracellular signaling molecule PRAS40 and its phosphorylation.

A Protective Effect of PPARα in Endothelial Progenitor Cells Through Regulating Metabolism.

Deficiency of endothelial progenitor cells, including endothelial colony-forming cells (ECFCs) and circulating angiogenic cells (CACs), plays an important role in retinal vascular degeneration in diabetic retinopathy (DR). Fenofibrate, an agonist of peroxisome proliferator-activated receptor α (PPARα), has shown therapeutic effects on DR in both patients and diabetic animal models. However, the function of PPARα in ECFC/CACs has not been defined. In this study, we determined the regulation of ECFC/CAC by PPARα. As shown by flow cytometry and Seahorse analysis, ECFC/CAC numbers and mitochondrial function were decreased in the bone marrow, circulation, and retina of db/db mice, correlating with PPARα downregulation. Activation of PPARα by fenofibrate normalized ECFC/CAC numbers and mitochondrial function in diabetes. In contrast, PPARα knockout exacerbated ECFC/CAC number decreases and mitochondrial dysfunction in diabetic mice. Primary ECFCs from PPARα -/- mice displayed impaired proliferation, migration, and tube formation. Furthermore, PPARα -/- ECFCs showed reduced mitochondrial oxidation and glycolysis compared with wild type, correlating with decreases of Akt phosphorylation and expression of its downstream genes regulating ECFC fate and metabolism. These findings suggest that PPARα is an endogenous regulator of ECFC/CAC metabolism and cell fate. Diabetes-induced downregulation of PPARα contributes to ECFC/CAC deficiency and retinal vascular degeneration in DR.

Effects of mesenchymal stem cells and their exosomes on the healing of large and refractory macular holes.

PURPOSE: To assess the efficacy of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) to promote the healing of large and refractory macular holes (MHs). METHODS: Seven patients (age 51-75 years old) with large and long-standing idiopathic MHs underwent vitrectomy, internal limiting membrane peeling, MSC (two patients) or MSC-Exo (five patients) intravitreal injection, and heavy silicon oil, air, 20% SF6, or 14% C3F8 tamponade. The MSCs were isolated from human umbilical cord tissue, and MSC-Exos were isolated from the supernatants of cultured MSCs using sequential ultracentrifugation. RESULTS: Five eyes underwent pars plana vitrectomy (PPV) only, while two underwent PPV combined with cataract surgery. Six MHs were closed, while one remained in a flat-open state. The best-corrected visual acuity (BCVA) was improved in five patients with MH closure and remained unchanged in one patient with MH closure who had a 4-year history of MH. A fibrotic membrane was observed on the surface of the retina in one patient who underwent MSC therapy. One patient who received a higher dose of MSC-Exos exhibited an inflammatory reaction. CONCLUSIONS: MSC and MSC-Exo therapy may promote functional and anatomic recovery from MH. MSC-Exo therapy may be a useful and safe method for improving the visual outcomes after surgery for refractory MHs.

Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration.

Choroidal neovascularization (CNV) in age-related macular degeneration usually causes blindness. We established a novel targeted inhibitor for CNV in age-related macular degeneration. The inhibitor CR2-sFlt 1 comprises a CR2-targeting fragment and an anti-vascular endothelial growth factor (VEGF) domain (sFlt 1). The targeting of CR2-sFlt 1 was studied using the transwell assay in vitro and frozen sections in vivo using green fluorescent labeling. Transwell assay results showed that CR2-sFlt 1 migrated to the interface of complement activation products and was present in the retinal tissue of the CR2-sFlt 1-treated CNV mice. Treatment effects were assessed by investigating the VEGF concentration in retinal pigmented epithelial cell medium and the thickness of the CNV complex in the mice treated with CR2-sFlt 1. CR2-sFlt 1 significantly reduced the VEGF secretion from retinal pigmented epithelial cells in vitro and retarded CNV progress in a mouse model. Expression analysis of VEGF and VEGFRs after CR2-sFlt 1 intervention indicated the existence of feedback mechanisms in exogenous CR2-sFlt 1, endogenous VEGF, and VEGFR interaction. In summary, we demonstrated for the first time that using CR2-sFlt 1 could inhibit CNV with clear targeting and high selectivity.

INTRAVITREAL CONBERCEPT (KH902) FOR SURGICAL TREATMENT OF SEVERE PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To evaluate the role, safety, and effectiveness of intravitreal conbercept (KH902) injections as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy. METHODS: A randomized controlled trial was performed on 36 eyes of 36 patients affected by vitreous hemorrhage and tractional retinal detachment, which occurred as a consequence of active proliferative diabetic retinopathy. The patients were randomly assigned to two groups. The patients in one of the groups received an intravitreal injection of conbercept in the inferior temporal sector 4 mm from the sclerocorneal limbus with a sterile technique 1 week before vitrectomy. RESULTS: In the group without conbercept, intraoperative bleeding occurred in 14 patients (77.8%), and in five of these cases, bleeding was significant. The use of endodiathermy was necessary in 8 patients (44.4%). In 3 patients (16.6%), iatrogenic retinal breaks occurred, and in 1 patient (5.5%), a relaxing retinotomy was performed. Endotamponade with silicone oil was performed in 12 patients (66.6%). In the group treated with conbercept, intraoperative bleeding occurred in 2 cases (11.1%). The use of endodiathermy was necessary in 1 patient (5.5%). No patients experienced iatrogenic breaks or relaxing retinotomy during the surgery. Endotamponade with silicone oil was performed in 2 patients (11.1%). CONCLUSION: Preoperative intravitreal injection of conbercept could reduce the chances of intraoperative bleeding, which are beneficial in the management of proliferative diabetic retinopathy.

Surgical induced astigmatism correlated with corneal pachymetry and intraocular pressure: transconjunctival sutureless 23-gauge versus 20-gauge sutured vitrectomy in diabetes mellitus.

AIM: To determine the difference of surgical induced astigmatism between conventional 20-gauge sutured vitrectomy and 23-gauge transconjunctival sutureless vitrectomy, and the influence of corneal pachymetry and intraocular pressure (IOP) on surgical induced astigmatism in diabetic patients. METHODS: This retrospective, consecutive case series consisted of 40 eyes of 38 diabetic subjects who underwent either 20-gauge or 23-gauge vitrectomy. The corneal curvature and thickness were measured with Scheimpflug imaging before surgery and 1wk; 1, 3mo after surgery. We compared the surgical induced astigmatism (SIA) on the true net power in 23-gauge group with that in 20-gauge group. We determined the correlation between corneal thickness change ratio, IOP and SIA measured by Pentacam. RESULTS: The mean SIAs were 1.082±0.085 D (mean±SEM), 0.689±0.070 D and 0.459±0.063 D at postoperative 1wk; 1, 3mo respectively in diabetic subjects. The vitrectomy induced astigmatisms were declined significantly with time (F 2,36=33.629, P=0.000) postoperatively. The 23-gauge surgery group induced significantly less astigmatism than 20-gauge surgery group (F -1,37=11.046, P=0.020). Corneal thickness in diabetes elevated after surgery (F 3,78=10.532, P=0.000). The linear regression analysis at postoperatively 1wk went as: SIA=-4.519+4.931 change ratio (Port3) +0.026 IOP (R(2)=0.46, P=0.000), whereas the rate of corneal thickness change and IOP showed no correlation with the change of astigmatism at postoperatively 1 and 3mo. CONCLUSION: There are significant serial changes in both 20-gauge and 23-gauge group in diabetic subjects. 23-gauge induce less astigmatism than 20-gauge and become stable more rapidly than 20-gauge. The elevation of corneal thickness and IOP was associated with increased astigmatim at the early postoperative stage both in 23-gauge and 20-gauge surgery group.

[Pathogenic mechanisms and therapeutic strategies of myopic traction maculopathy].

Myopic traction maculopathy is a group of ocular fundus diseases related to high myopia, which can severely impact on patients' visual function. It is well recognized that the abnormal of macular structure and function in the disease are resulted from various traction mechanisms, including the forces from posterior vitreous detachment, posterior vitreous cortex, and macular epiretinal membrane which acting on the inner retina, the force from posterior staphyloma which acting on the outer retina, and retinal intrinsic features such as the changes of inner limiting membrane and arterioles. The treatments are mainly based on surgery, including vitrectomy and scleral reinforcement surgery in order to relieve the retinal traction. The options of specific surgery procedures are still under debated. In this article, we reviewed the pathogenic mechanisms and therapeutic strategies of myopic traction maculopathy.

[Coverage on cataract surgery among adults aged 40 or above in a multiethnic rural district of high altitude area in Gongshan county, Yunnan province, China].

OBJECTIVE: To estimate the prevalence of cataract and its surgical coverage rate together with the burden related to bilateral cataract-blindness, among adults aged 40 or above in Gongshan county of Yunnan province and to evaluate the current cataract status and the efficacy of local cataract prevention program. METHODS: Cluster sampling was used. The protocol consisted of personal interview, pilot study, visual acuity checking, measuring the intraocular pressure; slit lamp microscopy and the fundus of the eye examination etc. Cataract was graded clinically using the Lens Opacity Classification System (LOCS) III. Bilateral cataract-blindness burden, bilateral cataract-blindness burden and cataract surgical coverage rate were calculated respectively, using two different criteria. Odds ratios (OR) were compared among different groups regarding age, gender, education, ethnic group and altitude of living area. RESULTS: Among the 1236 eligible residents, 1116 (90.3%) were enrolled in the present study. The prevalence of cataract was 23.8% among adults aged 40 or order. When the bilateral best refractive vision<3/60 was defined as the blindness criterion, the bilateral cataract-blindness burden showed as 1.3%, and cataract blindness surgical coverage rate was 50.0%. When the bilateral presenting vision<6/60 was defined as the blindness criterion, the bilateral cataract-blindness burden was 25.0%, and cataract blindness surgical coverage rate was 12.9%. The cataract surgical coverage rates were much lower and the bilateral cataract-blindness burden much higher in women, illiterates, living in high altitude areas and those who were aged 70 or above. CONCLUSION: Cataract blindness was a serious public health problem in aged individuals and illiteracy in the residents of the studied areas. Poor prevention programs on cataract called for urgent action to be taken.

Discovery and structure-activity relationship studies of indole derivatives as liver X receptor (LXR) agonists.

A structurally novel liver X receptor (LXR) agonist (1) was identified from internal compound collection utilizing the combination of structure-based virtual screening and high-throughput gene profiling. Compound 1 increased ABCA1 gene expression by eightfold and SREBP1c by threefold in differentiated THP-1 macrophage cell lines. Confirmation of its agonistic activity against LXR was obtained in the co-factor recruitment and reporter transactivation assays. Structure-activity relationship studies on compound 1 are described.