Long-Term Risk of Steroid-Induced Ocular Hypertension/Glaucoma With Topical Prednisolone Acetate 1% After Descemet Stripping Endothelial Keratoplasty.

PURPOSE: The aim of this study was to assess the long-term risk of steroid-induced ocular hypertension and the need for glaucoma treatment with long-term use of topical prednisolone acetate 1% in patients without preexisting glaucoma. METHODS: We retrospectively reviewed the charts of 211 patients without previous glaucoma, who underwent Descemet stripping endothelial keratoplasty (DSEK) and used topical prednisolone acetate long-term to prevent graft rejection. Dosing was 4 times daily for 4 months and tapered to once daily. The main outcomes were ocular hypertension (defined as intraocular pressure ≥24 mm Hg, or increase of ≥10 mm Hg over baseline) and initiation of glaucoma treatment. RESULTS: The median patient age was 70 years (range: 34-94 years). The indications for DSEK were Fuchs dystrophy (88%), pseudophakic corneal edema (7%), failed DSEK (3%), and failed penetrating keratoplasty (2%). The median follow-up period was 7 years (range, 1-17 years). At 1, 5, and 10 years, the cumulative risks of steroid-induced ocular hypertension were 29%, 41%, and 49%, respectively, and the risks of requiring glaucoma treatment were 11%, 17%, and 25%, respectively. Among 35 eyes treated for glaucoma, 28 (80%) were managed medically and 7 (20%) had filtration surgery. CONCLUSIONS: Long-term use of potent topical corticosteroids, such as prednisolone acetate 1%, entails substantial risk of developing steroid-induced ocular hypertension, so frequent monitoring of intraocular pressure is required. With corneal transplantation, the risk can be mitigated by using techniques with a low inherent risk of rejection, such as Descemet membrane endothelial keratoplasty, whenever possible, to allow earlier reduction of steroid potency.

Intracameral dexamethasone 9% vs prednisolone acetate 1% in controlling postoperative pain and inflammation in patients undergoing cataract surgery.

PURPOSE: To compare patient preferences of postoperative cataract surgery topical medication use between a 1-drop and a 3-drop regimen. SETTING: Two private cataract surgery centers. DESIGN: Open-label randomized self-controlled prospective study. METHODS: This study included 30 patients (60 eyes) undergoing routine cataract surgery in both eyes. In this contralateral eye study, 1 eye of each patient was randomized to the 1-drop regimen of intracameral delivery of moxifloxacin and dexamethasone suspension and topical bromfenac for 30 days. The other eye, randomized to the 3-drop regimen, received topical moxifloxacin 0.5% 4 times a day for 7 days and bromfenac 0.07% daily for 30 days postoperatively, along with prednisolone acetate 1% 4 times a day for 30 days. Patients reported their preferred regimen 2 weeks after the second surgery with a validated questionnaire. Secondary outcomes included subjective ocular pain, inflammation score, and out-of-pocket cost. Intraocular pressure (IOP) and macular thickness were also measured. RESULTS: Of the 29 patients, 28 (96.6%) significantly more preferred the eye treated with a 1-drop regimen. Self-reported pain, activity interference, and out-of-pocket cost were significantly less in the 1-drop group. Inflammation and 1-day uncorrected distance visual acuity were also significantly better in the 1-drop group. Macular thickness and mean IOP were similar between groups. CONCLUSIONS: Intracameral delivery of steroid and antibiotics was preferred by most of the patients undergoing cataract surgery. These eyes had significantly less pain, inflammation, activity interference, and out-of-pocket cost and significantly better uncorrected distance visual acuity at 1 day postoperatively. IOP and macular thickness were similar between groups.

Difluprednate 0.05% twice a day vs prednisolone acetate 1% 4 times a day for cataract postsurgical inflammation treatment: noninferiority trial.

PURPOSE: To establish whether difluprednate 0.05% nanoemulsion (DIFL) twice a day is as effective as prednisolone acetate 1% + phenylephrine hydrochloride 0.12% suspension (PRED) 4 times a day for postsurgical inflammation treatment. SETTING: 4 private Argentine ophthalmological centers. DESIGN: Noninferiority, prospective, multicenter, double-blind, randomized, parallel-group, comparative trial. METHODS: A total of 259 patients who underwent phacoemulsification randomly received DIFL or PRED, starting the day before surgery and continuing for 28 days. The primary endpoint was central corneal thickness. Noninferior anti-inflammatory efficacy was considered if the difference of corneal thickness between baseline and day 4 did not differ beyond 17 µm between treatments. Secondary endpoints were cell and flare, corrected distance visual acuity (CDVA), endothelial cell count, optical coherence tomography (OCT) central macular thickness, and intraocular pressure. All outcomes were evaluated at baseline and day 1, 4, and 28 postoperatively. RESULTS: 225 patients finished the study. The difference in corneal thickness at baseline and day 4 did not differ beyond 17 µm between treatments (95% CI -2.78 µm to 14.84 µm), with no statistically significant difference ( P = .523). No statistically significant differences were found between groups in total anterior chamber clearance at any study timepoint ( P > .05). Moreover, no statistically significant differences were reported between treatments in CDVA ( P = .455), endothelial cell count ( P = .811), OCT central macular thickness ( P = .869), and intraocular pressure outcome ( P = .316). CONCLUSIONS: Difluprednate administered twice a day was at least as effective as prednisolone acetate administered 4 times a day for inflammatory treatment after cataract surgery.

Development of a dual delivery of levofloxacin and prednisolone acetate via PLGA nanoparticles/ thermosensitive chitosan-based hydrogel for postoperative management: An in-vitro and ex-vivo study.

Post-operative endophthalmitis (POE) is one of the most dreadful complications after intraocular surgery. For cataract surgery patients, both commercially available topical 0.5% levofloxacin and 1% prednisolone acetate (PA) ophthalmic solution require at least 3 to 4 times application daily. In this study, we develop a dual drug delivery system composed of the thermosensitive chitosan/gelatin-based hydrogel containing PA and levofloxacin-loaded nanoparticles (LNPs). LNPs with negative surface charge show the monodisperse (polydispersity index ~0.045), nanosize (~154.7 nm) and sphere-like structure. The optimal concentration of LNPs and PA to corneal epithelial cells was 5 µg/mL and 50 µg/mL, respectively. The developed dual drug delivery system (PAgel-LNPs) could gel at 34 °C within 63 s. The osmolarity of PAgel-LNPs was 301.2 ± 1.5 mOsm/L. PAgel-LNPs showed a sustained-release profile for 7 days. Post-treatment of PAgel-LNPs in TNF-α-damaged corneal epithelial cells could decrease the inflammation (inflammatory genes (TNF-α, IL-6, MMP-3 andMMP-9) and IL-6 production) and cell death. In ex-vivo rabbit model of S. aureus keratitis, the anti-inflammation and anti-bacterial property have been demonstrated. These results suggest that thermosensitive PAgel-LNPs may have the potential to use for the prevention of POE.

Incidence and Outcomes of Cystoid Macular Edema after Descemet Membrane Endothelial Keratoplasty (DMEK) and DMEK Combined with Cataract Surgery.

PURPOSE: To investigate the incidence and outcomes of cystoid macular edema (CME) after Descemet membrane endothelial keratoplasty (DMEK) alone and DMEK combined with cataract surgery (DMEK triple). MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent DMEK and DMEK triple between January 2014 and March 2018 at two tertiary hospitals. Patients with minimum of 6 months of follow-up were included. Logistic regression analysis was used to identify potential risk factors for CME including gender, age, glaucoma, uveitis, epiretinal membrane, diabetes mellitus, iridotomy, and rebubbling. RESULTS: 09 eyes of 193 patients who underwent DMEK (124 eyes) and DMEK triple (85 eyes) were included. The 6-month incidence of CME was 3.8% (8/209) for all cases, 2.4% (2/85) for DMEK triple, and 4.8% (6/124) for DMEK alone. CME was treated with topical prednisolone acetate 1% and nepafenac four times daily, and/or periocular triamcinolone acetonide, with resolution in all cases. On average, CME was detected 8.9 ± 2.1 weeks postoperatively, with a mean time to resolution of 4.1 ± 1.7 months. The 6-month best-corrected distance visual acuity of eyes that developed CME was not significantly different compared to eyes that did not develop CME (0.17 ± 0.15 logMAR vs. 0.23 ± 0.27 logMAR; p = .76). On logistic regression analysis, no risk factors for developing CME were identified. CONCLUSIONS: The incidence of CME after DMEK was low and not associated with decreased long-term visual acuity. Most cases of CME occurred between 1 and 3 months postoperatively. Predictive factors for CME after DMEK require further study.

Exopolysaccharides from Lactobacillus plantarum YW11 improve immune response and ameliorate inflammatory bowel disease symptoms.

Exopolysaccharides (EPSs) possess many bioactivities such as immune regulation, antioxidant, anti-tumor and modulation of intestinal microbial balance but their direct effect on inflammatory bowel disease (IBD) response has not been studied. The purpose of this study was to evaluate the anti-inflammatory effect of EPS produced by L. plantarum YW11 administered at different dosages in IBD mouse model induced with 5% dextran sulphate sodium (DSS). The DSS-induced colitis, accompanied by body weight loss, reduction of colon coefficient and histological colon injury was considerably ameliorated in mice fed the EPS (10 mg/kg). The middle dose of the EPS (25 mg/kg) could effectively recover the intestinal microbial diversity and increase the abundance of Roseburia, Ruminococcus and Blautia with increased content of butyric acid. Moreover, EPS also reduced the production of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IFN-γ, IL-12 and IL-18) and enhanced the anti-inflammatory cytokine IL-10. This study showed that EPS might help in modulation of gut microbiota and improve the immunity of the host to reduce the risk of IBD symptoms.

MAD2B contributes to parietal epithelial cell activation and crescentic glomerulonephritis via Skp2.

Mitotic spindle assembly checkpoint protein 2 (MAD2B), a well-known anaphase-promoting complex/cyclosome (APC/C) inhibitor and a small subunit of DNA polymerase-ζ, is critical for mitotic control and DNA repair. Previously, we detected a strong increase of MAD2B in the glomeruli from patients with crescentic glomerulonephritis and anti-glomerular basement membrane (anti-GBM) rats, which predominantly originated from activated parietal epithelial cells (PECs). Consistently, in vitro MAD2B was increased in TNF-α-treated PECs, along with cell activation and proliferation, as well as extracellular matrix accumulation, which could be reversed by MAD2B genetic depletion. Furthermore, we found that expression of S phase kinase-associated protein 2 (Skp2), an APC/CCDH1 substrate, was increased in the glomeruli of anti-GBM rats, and TNF-α-stimulated PECs and could be suppressed by MAD2B depletion. Additionally, genetic deletion of Skp2 inhibited TNF-α-induced PEC activation and dysfunction. Finally, TNF-α blockade or glucocorticoid therapy administered to anti-GBM rats could ameliorate MAD2B and Skp2 accumulation as well as weaken PEC activation. Collectively, our data suggest that MAD2B has a pivotal role in the pathogenesis of glomerular PEC activation and crescent formation through induction of Skp2 expression.

Safety and Efficacy of 0.1% Nepafenac versus 1% Prednisolone Acetate Eye Drops after Laser Peripheral Iridotomy: A Prospective, Randomized Trial.

PURPOSE: To compare 0.1% nepafenac, a topical nonsteroidal anti-inflammatory drop, with 1% prednisolone acetate in controlling inflammation after neodymium:yttrium-aluminum-garnet laser peripheral iridotomy (LPI) in primary angle-closure suspects (PACS). DESIGN: Randomized controlled trial. PARTICIPANTS: One hundred fifty-two PACS undergoing bilateral LPI. METHODS: Patients were randomized to 0.1% nepafenac or 1% prednisolone acetate eye drops in both eyes. Medications were given 4 times daily for 7 days, then twice daily for additional 7 days. Investigators were masked to the type of medication. Right eyes in patients with bilateral PACS and the PACS eye in asymmetrical disease (primary angle closure in fellow eye) were analyzed. MAIN OUTCOME MEASURES: Noninferior control of inflammation, defined as absence of cell in the anterior chamber at 2 weeks and absence of rebound iritis with medication discontinuation, was the primary outcome, whereas difference in the rise in intraocular pressure (IOP) was a secondary outcome. RESULTS: Both groups were comparable in baseline characteristics, including IOP and total laser energy. Nepafenac was noninferior to prednisolone with regard to inflammation control, with 1 nepafenac-treated eye (1.3%) not meeting the primary end point because of 1+ anterior chamber cell at 2 weeks and 4 prednisolone-treated eyes (5.4%) failing to meet the primary end point because of rebound iritis (P < 0.001). A greater increase in IOP from baseline to 2 weeks was observed in the prednisolone group compared with the nepafenac group (+2.6 mmHg vs. +0.6 mmHg; P = 0.004), although at 4 weeks, IOP was not significantly different than baseline in either group (P > 0.05 for both). Two weeks after LPI, 3 nepafenac-treated eyes and 10 prednisolone-treated eyes demonstrated a 6- to 15-mmHg IOP elevation from baseline (P = 0.10), whereas 2 prednisolone-treated eyes and no nepafenac-treated eyes showed IOP elevation of more than 15 mmHg (P = 0.20). Four weeks after LPI, more prednisolone-treated eyes showed IOP elevation of 6 to 15 mmHg as compared with nepafenac-treated eyes (6 eyes vs. 1 eye; P = 0.04); no eyes showed IOP elevation of more than 15 mmHg. CONCLUSIONS: Nepafenac was noninferior to prednisolone in controlling inflammation after LPI in PACS.

Graft copolymerization of polyvinylpyrollidone onto Azadirachta indica gum polysaccharide in the presence of crosslinker to develop hydrogels for drug delivery applications.

In this work, graft-copolymerization of poly vinylpyrollidone onto Azadirachta indica gum polysaccharide in the presence of crosslinker has been carried out to prepare the hydrogel for use in drug delivery. The polymers were characterized by cryo-SEM, AFM, FTIR, and 13C NMR. The gel strength, cross-link density, mesh size, thrombogenicity, antioxidant and mucoadhesion properties of the gum-PVP hydrogels were determined along with the evaluation of drug release profile of methyl prednisolone, a colonic anti-inflammatory agent, from the drug loaded hydrogels. Cryo SEM images showed the porous crosslinked structure of the polymer network. The drug release from the polymer followed non-Fickian diffusion mechanism. The polymers showed 71.47 ±â€¯4.63% haemo-compatibility and 05.52 ±â€¯0.59 Nmm gel strength. The value of DPPH radical scavenging assay (73.16 ±â€¯04.85%) indicated that the gum-PVP polymers are antioxidant. The results of biocompatibility, antioxidant activity, mucoadhesion and drug release properties of the polymers inferred the use of this drug carrier for colonic drug delivery.

Loteprednol etabonate gel 0.5% vs prednisolone acetate suspension 1% for the treatment of inflammation after cataract surgery in children.

PURPOSE: To compare loteprednol etabonate (LE) gel 0.5% with prednisolone acetate suspension (PA) 1% for the treatment of inflammation after cataract surgery in children. SETTING: Eleven sites in the United States. DESIGN: Randomized, double-masked, parallel-group, noninferiority study. METHODS: Eligible patients were aged 11 years or younger and candidates for routine, uncomplicated cataract surgery. Patients were randomized to a 4-week postsurgical regimen with LE gel 0.5% or PA 1%, twice on the day of surgery, 4 times daily for 2 weeks, twice daily for 1 week, and once daily for 1 week. Assessments included anterior chamber (AC) cells/flare, anterior chamber inflammation (ACI), synechiae, precipitates on the intraocular lens/cornea, visual acuity, and intraocular pressure. RESULTS: The intent-to-treat population comprised 105 patients (LE gel, n = 53; PA 1%, n = 52) including 52 patients aged 3 years or younger. Patients achieved a similar mean ACI grade on postoperative day 14 (primary efficacy endpoint) whether treated with LE gel 0.5% or PA 1% (difference = 0.006, 2-sided 95% CI, -0.281 to 0.292). Similar ACI outcomes additionally were observed in patients aged 3 years or younger. LE gel 0.5% and PA 1% also appeared equally effective in resolving inflammation at all visits (days 7, 14, and 28 postsurgery), based on categorical distributions of ACI, AC cells, and AC flare scores/grades (P ≥ .06). Synechiae and corneal/IOL precipitates occurred infrequently with no significant differences between groups. No safety or tolerability concerns were identified, including no treatment-related IOP increases. CONCLUSIONS: LE gel 0.5% was safe and effective in treating pediatric postcataract surgical inflammation, with similar outcomes as PA 1%.

Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment.

Regardless of recent progress, melanoma is very difficult to treat, mainly due to the drug resistance modulated by tumor cells as well as by the tumor microenvironment (TME). Among the immune cells recruited at the tumor site, tumor associated macrophages (TAMs) are the most abundant, promoting important tumorigenic processes: angiogenesis, inflammation and invasiveness. Furthermore, it has been shown that TAMs are involved in mediating the drug resistance of melanoma cells. Thus, in the present study, we used liposomal formulation of prednisolone disodium phosphate (LCL-PLP) to inhibit the protumor function of TAMs with the aim to sensitize the melanoma cells to the cytotoxic drug doxorubicin (DOX) to which human melanoma has intrinsic resistance. Consequently, we evaluated the in vivo effects of the concomitant administration of LCL-PLP and liposomal formulation of DOX (LCL-DOX) on B16.F10 melanoma growth and on the production of key molecular markers for tumor development. Our results demonstrated that the concomitant administration of LCL-PLP and LCL-DOX induced a strong inhibition of tumor growth, primarily by inhibiting TAMs-mediated angiogenesis as well as the tumor production of MMP-2 and AP-1. Moreover, our data suggested that the combined therapy also affected TME as the number of infiltrated macrophages in melanoma microenvironment was reduced significantly.

Comparative study on the efficacy of non-steroidal, steroid and non-use of anti-inflammatory in the treatment of acute epidemic conjunctivitis.

PURPOSE: To evaluate the effects of prednisolone against sodium diclofenac both with ciprofloxacin compared to artificial tears on the symptoms and signs of acute viral conjunctivitis. METHODS: Study included 37 patients diagnosed with acute conjunctivitis and distributed by three groups: A (1% prednisolone acetate + ciprofloxacin (0.3%); B (Sodium diclofenac (0.1%) + ciprofloxacin (0.3%) and C (artificial tears + ciprofloxacin (0.3%). Patients received medication 6/6 hours daily. Signs and symptoms (e.g. lacrimation, burning, photophobia, etc.) were scored at baseline and on the first, third, fifth and seventh days and in the end of treatment using a standardized questionnaire and slit lamp anterior segment examination. RESULTS: All three groups demonstrated an improvement in the signs and symptoms of conjunctivitis in their follow-up visits. There was no significant difference in symptom and sign scores between Group A and B and B and C in the study visits ( p >0.05). However, the comparison between groups A and C showed a clinical trend (p=0.05) on third evaluation suggesting better clinical action using the corticosteroids. CONCLUSION: The prednisolone acetate was not superior to the use of sodium diclofenac or artificial tears in relieving the signs and symptoms of viral conjunctivitis.

Anti-inflammatory Medication of Cataract Surgery in Pseudoexfoliation Syndrome - NSAID Is Needed.

BACKGROUND: To optimize the anti-inflammatory treatment of cataract surgery in pseudoexfoliation syndrome (PXF) eyes. METHODS: A prospective randomized double-masked trial. Sixty eyes of 60 patients with PXF undergoing routine cataract surgery were randomized for potent topical postoperative anti-inflammatory medication either with prednisolone acetate (10mg/ml), nepafenac (1mg/ml) or their combination. Clinical outcome parameters were recorded at 28 days and 3 months. Recovery from surgery was recorded by a structured home questionnaire. RESULTS: Patient age and gender distribution, and all baseline ophthalmic and surgical parameters were comparable between the study groups. At 28 days, change in central subfield macular thickness was +11.4 ± 11.9 µm in prednisolone acetate group compared to +1.7 ± 16.8 µm in nepafenac (P = .017), and -0.3 ± 8.7 µm in combination therapy (P = .010) groups. At 3 months, the values were +11.8 ± 18.1 µm, +1.8 ± 17.5 µm (P = .055), and -1.3 ± 6.4 µm (P = .055), respectively. Pseudophakic cystoid macular edema (PCME) was reported in two eyes, both with prednisolone acetate monotherapy. After surgery, conjunctival injection lasted 6.5 ± 5.0 days and irritation of the eye 9.5 ± 8.5 days in prednisolone acetate group compared with nepafenac (2.6 ± 2.2 days; P = .037 and 4.3 ± 5.2 days; P = NS, respectively) and combination therapy (3.3 ± 1.9 days; P = NS and 3.0 ± 4.0 days; P = .025, respectively). CONCLUSIONS: Routine cataract surgery of PXF eyes with nonsteroidal anti-inflammatory drugs (NSAID) alone, or in combination with steroids resulted in faster recovery from surgery and avoidance of PCME compared to steroids alone. ABBREVIATIONS: BAB: blood-aqueous barrier; CDVA: corrected distance visual acuity; CDE: cumulative dissipated energy; CSMT: central subfield macular thickness; HRQoL: Health-related quality of life; IOP: intraocular pressure; logMAR: log of the minimum angle of resolution; NSAID: nonsteroidal anti-inflammatory drug; PCME: pseudophakic cystoid macular edema; PXF: pseudoexfoliation syndrome; OCT: optical coherence tomography; t.i.d.: three times a day; VA: visual acuity.

AggreRATE-Pred: a mathematical model for the prediction of change in aggregation rate upon point mutation.

MOTIVATION: Protein aggregation is a major unsolved problem in biochemistry with implications for several human diseases, biotechnology and biomaterial sciences. A majority of sequence-structural properties known for their mechanistic roles in protein aggregation do not correlate well with the aggregation kinetics. This limits the practical utility of predictive algorithms. RESULTS: We analyzed experimental data on 183 unique single point mutations that lead to change in aggregation rates for 23 polypeptides and proteins. Our initial mathematical model obtained a correlation coefficient of 0.43 between predicted and experimental change in aggregation rate upon mutation (P-value <0.0001). However, when the dataset was classified based on protein length and conformation at the mutation sites, the average correlation coefficient almost doubled to 0.82 (range: 0.74-0.87; P-value <0.0001). We observed that distinct sequence and structure-based properties determine protein aggregation kinetics in each class. In conclusion, the protein aggregation kinetics are impacted by local factors and not by global ones, such as overall three-dimensional protein fold, or mechanistic factors such as the presence of aggregation-prone regions. AVAILABILITY AND IMPLEMENTATION: The web server is available at http://www.iitm.ac.in/bioinfo/aggrerate-pred/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

AntiHIV-Pred: web-resource for in silico prediction of anti-HIV/AIDS activity.

MOTIVATION: Identification of new molecules promising for treatment of HIV-infection and HIV-associated disorders remains an important task in order to provide safer and more effective therapies. Utilization of prior knowledge by application of computer-aided drug discovery approaches reduces time and financial expenses and increases the chances of positive results in anti-HIV R&D. To provide the scientific community with a tool that allows estimating of potential agents for treatment of HIV-infection and its comorbidities, we have created a freely-available web-resource for prediction of relevant biological activities based on the structural formulae of drug-like molecules. RESULTS: Over 50 000 experimental records for anti-retroviral agents from ChEMBL database were extracted for creating the training sets. After careful examination, about seven thousand molecules inhibiting five HIV-1 proteins were used to develop regression and classification models with the GUSAR software. The average values of R2 = 0.95 and Q2 = 0.72 in validation procedure demonstrated the reasonable accuracy and predictivity of the obtained (Q)SAR models. Prediction of 81 biological activities associated with the treatment of HIV-associated comorbidities with 92% mean accuracy was realized using the PASS program. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://www.way2drug.com/hiv/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The value of prednisolone acetate provocative test before intravitreal triamcinolone acetonide injections.

PURPOSE: The aim of this study was to investigate the diagnostic value of a topical prednisolone acetate 1% provocative test for steroid-induced ocular hypertension before intravitreal triamcinolone acetonide injection. METHODS: This is a prospective, single-center, randomized controlled study at Kasr El Aini Hospital, Cairo University. Patients scheduled for intravitreal triamcinolone acetonide were enrolled and randomly allocated in a ratio 2:1 to either Group A: received prednisolone acetate provocative test and those who did not develop SIOH proceeded with intravitreal triamcinolone acetonide or Group B: did not receive prednisolone acetate provocative test and proceeded directly to intravitreal triamcinolone acetonide. Intraocular pressures were measured weekly for 4 weeks following intravitreal triamcinolone acetonide. Steroid-induced ocular hypertension is defined as intraocular pressure increase of 5 mmHg or more from baseline after prednisolone acetate provocative test or intravitreal triamcinolone acetonide. RESULTS: A total of 66 eyes (66 patients) were included. Of which, 10 eyes (23.8%) showed prednisolone acetate provocative test steroid-induced ocular hypertension during the 4-week period. Intravitreal triamcinolone acetonide steroid-induced ocular hypertension was less likely to develop in Group A (prednisolone acetate provocative test non-steroid-induced ocular hypertension, n = 32, 31.25%) than in group B (n = 24, 54.2%) (p = 0.006, odds ratio: 0.178, 95% CI: 0.53-0.596). Our test achieved a negative predictive value of 68.75%. CONCLUSION: The topical prednisolone acetate provocative test may be a useful method to predict a steroid-induced ocular hypertension following intravitreal triamcinolone acetonide.

Difluprednate versus Prednisolone Acetate after Cataract Surgery: a Systematic Review and Meta-Analysis.

OBJECTIVE: Topical steroids are the cornerstone in controlling the inflammation after cataract surgery. Prednisolone acetate and difluprednate are the two main products for this purpose. However, it is unclear which one should be used in terms of effectiveness and safety. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline via PubMed, Cochrane Central Register of Controlled Trials, Web of science and clinicaltrials.gov were searched through 10 January 2018, and updated on 20 July 2019, in addition to researching the references' lists of the relevant articles. ELIGIBILITY CRITERIA: Randomised-controlled trials (RCTs) comparing difluprednate and prednisolone acetate regardless of the dosing regimen used. DATA EXTRACTION AND SYNTHESIS: Two independent authors assessed the included RCTs regarding the risk of bias using the Cochrane tool. Relevant data were extracted, and meta-analysis was conducted using a random-effects model. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to appraise the evidence quality. RESULTS: We included six RCTs with 883 patients: 441 received difluprednate and 442 received prednisolone acetate. The evidence quality was graded as moderate for corneal oedema and intraocular pressure and low for anterior chamber (AC) clearance. After small incision cataract surgery, difluprednate was superior in clearing AC cells at 1 week (OR=2.5, p>0.00001) and at 2 weeks (OR=2.5, p=0.04), as well as clearing the AC flare at 2 weeks (OR=6.7, p=0.04). After phacoemulsification, difluprednate was superior in terms of corneal clarity at 1 day (OR=2.6, p=0.02) and 1 week after surgery (OR=1.96, p=0.0007). No statistically significant difference was detected between both agents at 1 month in effectiveness. Also, both agents were safe, evaluated by the ocular hypertension (OR=1.23, p=0.8). CONCLUSION: With low-to-moderate certainty, difluprednate and prednisolone acetate are safe agents for controlling the inflammation after cataract surgery. Difluprednate showed significant superiority in terms of AC cells and AC flare at 2 weeks postoperatively.

The prednisolone phosphate­induced suppression of the angiogenic function of tumor­associated macrophages enhances the antitumor effects of doxorubicin on B16.F10 murine melanoma cells in vitro.

Several lines of evidence have clearly demonstrated the role of the tumor microenvironment in favoring the drug resistance of melanoma cells, as well as the progression of this cancer type. Since our previous studies proved that the accumulation of prednisolone disodium phosphate (PLP) in melanoma tissue inhibited tumor growth by exerting anti­angiogenic effects on the most abundant cells of the tumor microenvironment, tumor­associated macrophages (TAMs), the present study investigated whether PLP could enhance the cytotoxic effects of doxorubicin (DOX) on B16.F10 murine melanoma cells. To assess the antitumor efficacy of the combined therapeutic approach based on PLP and DOX, we used a co­culture system composed of bone marrow­derived macrophages (BMDMs) and B16.F10 murine melanoma cells at a cell density ratio that approximates the melanoma microenvironment in vivo, ensuring the polarization of the BMDMs into TAMs. Thus, we assessed the combined therapeutic effects of PLP and DOX on melanoma cell proliferation and apoptosis, as well as on supportive processes for tumor growth, such as oxidative stress as well as the angiogenic and inflammatory capacity of the cell co­culture. Our data demonstrated that the cytotoxicity of DOX was potentiated mainly via the anti­angiogenic activity of PLP in the melanoma microenvironment in vitro. Moreover, the amplitude of the cytotoxicity of the combined treatments may be linked to the degree of the suppression of the pro­angiogenic function of TAMs. Thus, the potent decrease in the expression of the majority of the angiogenic and inflammatory proteins in TAMs following the concomitant administration of PLP and DOX may be associated with their anti­proliferative, as well as pro­apoptotic effects on B16.F10 melanoma cells. However, the combination therapy tested did not affect the immunosuppressive phenotype of the TAMs, as the levels of two important markers of the M2­like phenotype of macrophages (IL­10 and Arg­1) were not reduced or even increased following these treatments. On the whole, the findings of this study indicated that PLP improved the therapeutic outcome of DOX in the melanoma microenvironment via the inhibition of the pro­angiogenic function of TAMs.