Search

Aim: To describe the effectiveness and side-effect profile of adding difluprednate therapy to patients with anterior scleritis being treated systemically., Methods: Retrospective chart review. Charts from all patients with anterior scleritis who were treated with topical difluprednate in addition to systemic therapy from 1 January 2018 to 1 January 2020 were reviewed. Data collected included: demographics, scleritis type, systemic diagnosis, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops used, type of systemic treatment used, best-corrected visual acuity (BCVA) and lens status. The primary outcome was clinical resolution of scleritis. Secondary outcomes included BCVA loss ≥2 lines, change in lens status or cataract surgery and IOP ≥24 mm Hg., Results: Thirty-two patients (44 eyes) were analysed. The median age was 57 years (IQR 52, 72); 59% were female; 72% were Caucasian. An associated systemic disease was present in 59%. Systemic therapies used when difluprednate was added were: 65% immunosuppressive agents, 43% prednisone and 25% non-steroidal anti-inflammatory drugs. The addition of difluprednate resulted in clinical resolution in 79.6% of the treated eyes. Median time to inactivity was 9 weeks (IQR 5, 20). Eyes initially using 2-4 drops per day had a higher response rate (89%, p=0.005). Over a median follow-up of 34 weeks (IQR 21, 74), 11 eyes had IOP elevation; 6 eyes lost ≥2 lines of BCVA, 5 eyes had cataract progression., Conclusion: Most eyes treated with difluprednate achieved inactivity. The addition of difluprednate to systemic therapies provides an alternative to achieve control of inflammation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report the outcomes of secondary full-thickness macular holes (FTMHs) treated with topical therapy., Design: Retrospective case series., Participants: Patients with secondary FTHMs initially treated with topical therapy in a referral-based retina practice., Methods: Patients evaluated between April 14, 2016, and February 22, 2019, for secondary FTMHs who underwent topical therapy were included. Patient demographics, ocular history, type of drops used, duration of therapy, and duration of follow-up as well as anatomic features on OCT, including hole diameter and presence of vitreomacular traction, epiretinal membrane (ERM), and cystoid macular edema (CME), were analyzed., Main Outcome Measures: Closure rate of FTMHs and change in visual acuity., Results: A total of 123 FTMHs were seen during the study, of which 12 were secondary macular holes. Topical therapy was attempted in 9 eyes (8 patients). Six of these 9 FTMHs were associated with prior retinal detachment (RD). Previous pars plana vitrectomy (PPV) had been performed in 3 eyes (1 for RD, 2 for ERM). One eye had vitreomacular traction and a remote history of blunt trauma. Average initial hole diameter was 79.6 μm (range, 44-132 μm). Average follow-up was 53 weeks (range, 5-153 weeks). All FTMHs had some element of ERM and CME. All patients received difluprednate with the addition of a topical carbonic anhydrase inhibitor in 6 eyes and nonsteroidal anti-inflammatory drug (NSAID) drops in 2 eyes. Eight eyes (89%) achieved successful hole closure and resolution of CME with concurrent improvement in visual acuity after an average of 6 weeks of therapy (range, 2-19 weeks). Average vision among all 9 eyes improved from 0.69 to 0.37 logarithm of the minimum angle of resolution (Snellen equivalent from approximately 20/100 to approximately 20/50). No episodes of corneal melts or ulcers occurred. One patient showed mild keratopathy and elevation of intraocular pressure with topical NSAID and steroid therapy that resolved when the topical NSAID was stopped and difluprednate was tapered down to once weekly., Conclusions: Topical therapy achieved high closure rates in secondary FTMH and can be considered as an initial treatment option especially in those with small holes and CME., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate outcomes of difluprednate treatment in penetrating keratoplasty (PK) graft rejection DESIGN: Retrospective, interventional case series., Participants: Patients treated with difluprednate for acute endothelial rejection after PK., Methods: Data were collected on resolution of rejection, treatment regimen used, best spectacle-corrected visual acuity (BSCVA), intraocular pressure (IOP), and side effects., Main Outcome Measure: rate of rejection resolution., Secondary Outcome Measures: BSCVA change and side-effect rates., Results: Thirty-three eyes of 33 patients aged 56.7 ± 17.9 years were included. Twenty-four grafts (72.7%) were high-risk grafts. Complete treatment success was achieved in 19 of 33 grafts (57.6%) over 1.8 ± 1.4 months. Non-high-risk grafts had 100% treatment success rate (9 of 9 grafts). All treatment failures occurred in high-risk grafts, which had a significantly lower treatment success rate of 41.7% (10 of 24 grafts) compared with non-high-risk grafts (p = 0.004). Mean BSCVA in the treatment-success group improved from 1.07 ± 0.74 logMAR at the time of rejection to 0.44 ± 0.33 logMAR after treatment (p = 0.003). High-dose difluprednate (every 1-3 hours while awake) was used in 93.9% of eyes. IOP elevation and toxic epitheliopathy were each seen in 21.2% of patients. IOP elevation was managed successfully with topical medication and/or difluprednate discontinuation. Epitheliopathy resolved in all cases after completion of difluprednate treatment, except for one case complicated by an infected ulcer., Conclusions: High-dose difluprednate was effective in treating PK graft rejection, especially in non-high-risk grafts. Adjunct treatment may be required in high-risk grafts. Monitoring for IOP elevation and for toxic epitheliopathy is recommended., (Copyright © 2019. Published by Elsevier Inc.)

Purpose of Review: This review aims to cover the preoperative planning, intraoperative considerations, and postoperative management that aids in successful outcomes of patients with cataract and uveitis. Disease-specific management and pediatric management will also be addressed., Recent Findings: Dexamethasone implants appear to be a safe and effective addition to standard steroid treatment in decreasing the incidence of postoperative cystoid macular edema (CME). Intravitreal steroids and topical difluprednate have shown utility in CME treatment., Summary: Cataract surgery in eyes with uveitis is generally safe and effective if inflammation is well controlled; however, complication rates are still higher than in eyes without uveitis. Future investigations should delineate outcomes for eyes with different etiologies of uveitis, and further research is needed to adequately control inflammation and avoid postoperative complications.

Establishing bioequivalence (BE) of ophthalmic emulsions in the absence of in vivo data is challenging. In these emulsions, drug release is a complex process due to drug distribution among various phases which are difficult to characterize. The objective of this study is to investigate the process of drug distribution and mechanism of drug release in the context of formulation-associated variables. A previously reported kinetic method for determining drug partitioning was used to quantitatively evaluate the drug distribution within a simplified biphasic (emulsion) system employing cyclosporine and difluprednate as model drugs. The impacts of formulation variables, such as the amount of polysorbate 80, glycerin, and carbomer copolymer as well as the area of oil-water interface were investigated. Polysorbate 80 was found to have the greatest influence on the drug distribution. It enhanced both the rate and extent of the drug distribution from oil to aqueous phase. Glycerin was found to slightly reduce the rate and extent of drug distribution of cyclosporine into the aqueous phase, probably by suppressing the solubilization capability of the micelles. Carbomer slowed down the diffusion of drug into the oil phase and shifted the equilibrium drug distribution towards the aqueous phase. Furthermore, increase in the interfacial area significantly increased the rate of drug diffusion across the oil-aqueous interface but had negligible effect on the extent of drug distribution. It is noteworthy that the experimental setup utilized a planar interface rather than an interface with curvature, which may have slightly underestimated the influence of globule size on equilibrium drug distribution. The findings of this study give insight into the drug distribution and diffusion in complex ophthalmic emulsions and assist with formulation design as well as development of in vitro methods to support BE assessment of ophthalmic emulsions., (Published by Elsevier B.V.)

Purpose : To analyse pooled data from 2 similar phase 3 noninferiority studies comparing difluprednate 0.05% versus prednisolone acetate 1% in patients with endogenous anterior uveitis. Methods : Patients received difluprednate alternating with vehicle or prednisolone acetate for 14 days (8 drops/day in both groups), followed by tapering from day 14 to 28. All patients were observed until day 42. Results : More patients on difluprednate than on prednisolone acetate were cleared of anterior chamber cells on day twenty one (71.3% vs 54.7%; p  = 0.02); results were similar at the other time points. Treatment withdrawals were higher with prednisolone acetate than difluprednate (19.8% vs 7.4%; log-rank p  = 0.02). Study discontinuation due to lack of efficacy was also higher with prednisolone acetate than difluprednate (14.0% vs 0%; p  = 0.0002 [pre-specified exploratory analysis]). Conclusions : More difluprednate-treated eyes were quiet following 21 days of treatment, and difluprednate-treated patients were much less likely to be withdrawn from the study because of treatment failure.

Implantable collamer lenses (ICL) have gained popularity for correction of myopia where kerato-refractive procedures are not indicated as in cases of high myopic refractive errors. Toxic anterior segment syndrome (TASS) is a very uncommonly reported postoperative complication following ICL implantation. A young patient developed severe corneal oedema and anterior segment inflammation on the first day after ICL implantation. Analysing retrospectively, possible idiosyncratic response to intracameral pilocarpine was considered as a cause for TASS. Prompt and intensive therapy with oral and topical potent steroids was visually rewarding. TASS, though a sterile inflammation can have catastrophic sequelae such as corneal decompensation and secondary glaucoma. Hence, timely identification and management is important., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

OBJECTIVE To compare the effects of 3 equimolar concentrations of methylprednisolone acetate (MPA), triamcinolone acetonide (TA), and isoflupredone acetate (IPA) on equine articular tissue cocultures in an inflammatory environment. SAMPLE Synovial and osteochondral explants from the femoropatellar joints of 6 equine cadavers (age, 2 to 11 years) without evidence of musculoskeletal disease. PROCEDURES From each cadaver, synovial and osteochondral explants were harvested from 1 femoropatellar joint to create cocultures. Cocultures were incubated for 96 hours with (positive control) or without (negative control) interleukin (IL)-1β (10 ng/mL) or with IL-1β and MPA, TA, or IPA at a concentration of 10 -4 , 10 -7 , or 10 -10 M. Culture medium samples were collected from each coculture after 48 and 96 hours of incubation. Concentrations of prostaglandin E 2 , matrix metalloproteinase-13, lactate dehydrogenase, and glycosaminoglycan were determined and compared among treatments at each time. RESULTS In general, low concentrations (10 -7 and 10 -10 M) of MPA, TA, and IPA mitigated the inflammatory and catabolic (as determined by prostaglandin E 2 and matrix metalloproteinase-13 quantification, respectively) effects of IL-1β in cocultures to a greater extent than the high (10 -4 M) concentration. Mean culture medium lactate dehydrogenase concentration for the 10 -4 M IPA treatment was significantly greater than that for the positive control at both times, which was suggestive of cytotoxicosis. Mean culture medium glycosaminoglycan concentration did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the in vitro effects of IPA and MPA were similar to those of TA at clinically relevant concentrations (10 -7 and 10 -10 M).

Purpose: To describe clinical outcomes associated with the use of topical difluprednate in treating uveitic cystoid macular edema., Design: Retrospective, interventional case series., Methods: Setting: Medical record review in a tertiary care uveitis center., Patient Population: Fifty-eight patients (72 eyes) with uveitic cystoid macular edema (CME) treated with difluprednate 0.05% ophthalmic solution between June 2012 and May 2016., Main Outcome Measures: Macular central subfield thickness (CST) determined by optical coherence tomography, improvement of CME (≥20% reduction in CST or resolution), and resolution of CME (CST ≤ 320 μm with no cysts) at 30 days after starting treatment. Outcomes were assessed up to 90 days., Results: CST on average decreased by 17% (95% CI: -33%, -7%) for eyes using only difluprednate (n = 43) and by 6% (95% CI: -17%, -2%) for eyes in patients using concomitant systemic immunosuppressive therapy (n = 29) at 30 days, a 12% difference between groups (95% CI: 2%, 21%, P = .02). Of eyes on difluprednate alone, 76% had improvement and 48% had resolution of CME. In patients using systemic therapy, 37% of eyes had improvement and 17% had resolution. Eight eyes (11%) had an intraocular pressure (IOP) > 24 mm Hg within the first 30 days. By 90 days, CME had improved in 69% of all eyes and resolved in 43% of eyes, with only 9 patients starting or increasing systemic immunosuppressive medications and 2 patients receiving periocular corticosteroid injections., Conclusions: Difluprednate was associated with an improvement in uveitic CME and could be a reasonable first-line therapy. IOP should be closely monitored., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: We aimed to evaluate the effect of the topical application of a strong corticosteroid, difluprednate, on the levels of inflammatory and angiogenic cytokine in the vitreous and aqueous humor after laser photocoagulation., Methods: Pigmented rabbits were treated with retinal laser photocoagulation and divided into 4 groups, namely control (no additional treatment), topical application of difluprednate 0.05%, betamethasone sodium phosphate 0.1%, and sub-Tenon injection of triamcinolone acetonide (STTA). Samples of vitreous and aqueous humor were collected on posttreatment days 0, 1, 7, and 14. The levels of intraocular vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1) were measured using an immunoassay. Intraocular pressure (IOP) was monitored in each group., Results: VEGF, IL-6, ICAM-1, and MCP-1 were significantly elevated on day 1 and were reduced in both the vitreous and aqueous humor following topical application of difluprednate and STTA. Topical betamethasone reduced their levels in the aqueous humor but not in the vitreous. A significant increase of IOP induced by difluprednate returned to control levels after withdrawal of administration., Conclusion: Although the elevation of IOP was an expected, manageable side effect, topical application of difluprednate was more effective than STTA and betamethasone for reducing inflammatory cytokine levels after laser treatment.

Purpose: Topical corticosteroids are widely used in the treatment of inflammation and pain after ocular surgery, but they possess several shortcomings, including frequent dosing and low patient adherence. We evaluated the efficacy and pharmacokinetics of ENV905 (difluprednate or DFBA) Ophthalmic Implant, a single-dose drug delivery system, compared with 0.05% Durezol., Methods: PRINT ® technology was used to fabricate ENV905 implants for either intracameral (IC) or subconjunctival (SCJ) delivery of extended-release DFBA. A postoperative inflammation model and ocular pharmacokinetics studies of ENV905 or Durezol were conducted in albino rabbits for a maximum of 12 weeks., Results: Suppression of ocular inflammation was marked for both IC and SJC ENV905 compared with placebo, and it was superior or equivalent to that observed with QID Durezol. Concentrations of desacetyl difluprednate (DFB, active metabolite) peaked on day 1 and tapered over time for ENV905, with IC ENV905 delivering DFB to the target tissue at the time of greatest inflammation, whereas SJC produced a longer duration of exposure. Durezol eyes demonstrated consistent exposure over time with maximal exposure in the cornea. Although the pharmacokinetic profile differed for the two routes, efficacy was similar., Conclusion: ENV905 was well tolerated and demonstrated a robust reduction in ocular inflammation with targeted drug delivery. The results from these studies show that ENV905 provides a sustained therapeutic effect after a single dose. By resolving low patient compliance and eliminating the peaks and troughs in drug concentration, sustained drug delivery via ENV905 may further improve the overall control of postoperative inflammation and pain.

Purpose: To evaluate the short-term safety and efficacy of topical difluprednate (0.05%) for the treatment of noninfectious uveitic cystoid macular edema., Methods: Twenty-seven patients (35 eyes) undergoing treatment with difluprednate 4 times daily for 3 weeks for noninfectious uveitic cystoid macular edema were reviewed for visual acuity, intraocular pressure, optical coherence tomography, and fluorescein angiography results. A mixed model analysis was fit with each measure as the outcome, visit as the primary predictor, and patient and eye as random effects., Results: Mean central foveal thickness decreased by 117 μm (P < 0.001) at 30 ± 15 days, 124 μm (P < 0.001) at 60 ± 15 days, and 152 μm (P < 0.001) at 180 ± 30 days. Complete resolution of intraretinal fluid was observed in 15 of 34 (44%) eyes at 30 ± 15 days, 11 of 21 (52%) eyes at 60 ± 15 days, and 9 of 12 (75%) eyes at 180 ± 30 days. Improvement in fluorescein leakage was noted in 7 of 8 eyes (88%). Visual acuity improved by a mean of 5 letters (P = 0.001) at 30 ± 15 days, 5.5 letters (P = 0.007) at 60 ± 15 days, and 7 letters (P = 0.032) at 180 ± 30 days. Mean increase in intraocular pressure was 1.48 mmHg at 30 ± 15 days (P = 0.080), 1.92 mmHg at 60 ± 15 days (P = 0.110), and 6.18 mmHg (P = 0.001) at 180 ± 30 days., Conclusion: Topical difluprednate is a well-tolerated and effective treatment for noninfectious uveitic cystoid macular edema with decreased central foveal thickness, mild improvement in visual acuity, and elevation of intraocular pressure observed in a few patients.

Introduction: Cataract is any opacification in lens or its capsule, which accounts for about 50% of treatable blindness worldwide. The prevalence of cataract in India is about 62.6%. The incidence of post operative endophthalmitis ranges from 0.05% - 0.14% and so the use of post-operative antibiotics and steroids is necessary to control infection and prevent inflammation. Fixed drug combinations not only cut the cost but also the dosage and improve the compliance of patients in the immediate post operative period. In this regard, the present study was conducted with the aim of studying the efficacy of using fixed drug combination (Difluprednate and Moxifloxacin) in reducing ocular inflammation and pain in post-operative patients undergoing cataract surgery., Methodology: Study design: Prospective interventional study, in which 749 eyes underwent SICS with IOL. All of them were treated with Difluprednate and Moxifloxacin, combination eye drops postoperatively 4 times a day, and reviewed on day 1, 5 and once in two weeks up to 6 weeks., Results: Out of 749 eyes, 730 were normal, 10 eyes had minimal raise in IOP in the range of 21 mmHg-31mmHg (considering 21mmHg as baseline) which decreased without any intervention within 3 weeks and only 9 eyes had raise in IOP of more than 31mmHg, which did not decrease in spite of discontinuing the drops and needed anti-glaucoma treatment., Conclusion: Our study clearly shows that fixed drug combination of antibiotic and steroid does not cause raised IOP in about 97% of cases of SICS in the post-operative period and also improves the compliance of the patients., (© NEPjOPH.)

Patients with bilateral serous retinal detachments and panuveitis related to Vogt-Koyanagi-Harada disease are commonly managed with oral corticosteroids, immunosuppressive agents, and/or intravitreal injections. We present the case of a 56-year-old Hispanic man with Harada disease whose bilateral serous retinal detachments and panuveitis were treated with topical corticosteroid difluprednate alone. Functional and anatomical recoveries were assessed by fluorescein angiograms and optical coherence tomography studies over a period of 9 months. The patient's serous retinal detachments resolved, and his vision and panuveitis improved dramatically over a period of 2 weeks, after which he was placed on a drop taper and maintenance therapy for the remainder of the 9 months.

To evaluate the efficacy and safety of treatment of diabetic macular edema (persistent type) with difluprednate ophthalmic emulsion 0.05 % (off label use). 20 patients with persistent diabetic macular edema were enrolled. In all subjects, more than 4 months had passed since prior treatment. All patients were treated with difluprednate ophthalmic emulsion 0.05 % three times daily for 3 months. At the end of 3 months the visual acuity had increased by two lines to a mean value of 0.61 ± 0.18 on logMAR from a baseline value of 0.885 ± 0.20 and the central retinal thickness had decreased from 423 ± 72.04 microns to 345 ± 68.7 microns. Hence, there was a total of 18.4 % decrease in retinal thickness on difluprednate. Major side effects included raised intraocular pressure in 20 %. Difluprednate is a potent and strong steroid which causes a rapid decrease in persistent diabetic macular edema. However, the potential side effect of raised intraocular pressure limits its use as an adjuvant therapy in non-steroid responders.

Current treatment of glaucoma relies on administration of daily drops or eye surgery. A gene therapy approach to treat steroid-induced glaucoma would bring a resolution to millions of people worldwide who depend on glucocorticoid therapy for a myriad of inflammatory disorders. Previously, we had characterized a short-term Adh.GRE.MMP1 gene vector for the production of steroid-induced MMP1 in the trabecular meshwork and tested reduction of elevated intraocular pressure (IOP) in a sheep model. Here we conducted a trial transferring the same transgene cassette to a clinically safe vector (scAAV2), and extended the therapeutic outcome to longer periods of times. No evidence of ocular and/or systemic toxicity was observed. Viral genome distributions showed potential reinducible vector DNAs in the trabecular meshwork (0.4 v.g. per cell) and negligible copies in six major internal organs (0.00002-0.005 v.g. per cell). Histological sections confirmed successful transduction of scAAV2.GFP to the trabecular meshwork. Optimization of the sheep steroid-induced hypertensive model revealed that topical ophthalmic drug difluprednate 0.05% (durezol) induced the highest IOP elevation in the shortest time. This is the first efficacy/toxicity study of a feasible gene therapy treatment of steroid-induced hypertension using clinically accepted self-complementary adeno-associated vectors (scAAV) vectors in a large animal model.

Purpose: Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition., Methods: This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogenous AU to receive difluprednate 0.05% (n = 56) four times daily, alternating with vehicle four times daily, or prednisolone acetate 1% (n = 54) eight times daily. The 14-day treatment period was followed by a 14-day dose-tapering period and a 14-day observation period. The primary efficacy end point was change in anterior chamber cell grade (range, 0 for ≤1 cell to 4 for >50 cells) from baseline to day 14., Results: At day 14, the mean change in anterior chamber cell grade with difluprednate was noninferior to that with prednisolone acetate (-2.2 vs. -2.0, P = 0.16). The proportions of difluprednate-treated patients versus prednisolone acetate-treated patients demonstrating complete clearing of anterior chamber cells at day 3 were 13.0% vs. 2.1% (P = 0.046) and at day 21 were 73.9% vs. 63.8% (P = 0.013). A significant between-group difference in the mean IOP increase was seen at day 3 (2.5 mm Hg for difluprednate-treated patients and 0.1 mm Hg for prednisolone acetate-treated patients, P = 0.0013) but not at other time points. The mean IOP values in both groups remained less than 21 mm Hg throughout the study., Conclusions: Difluprednate 0.05% four times daily is well tolerated and is noninferior to prednisolone acetate 1% eight times daily for the treatment of endogenous AU. (ClinicalTrials.gov number, NCT01201798.).

Hypokalemia occurs commonly in lactating dairy cows. The objectives of this study were to determine (1) whether a 24-h oral KCl dose of 0.4 g/kg of body weight (BW) was effective and safe in hypokalemic cattle; (2) whether potassium was best administered as 2 large doses or multiple smaller doses over a 24-h period; and (3) the effect of oral KCl administration on plasma Mg concentration and urine Mg excretion in fasted lactating dairy cattle. Plasma K and Cl concentrations were decreased, and blood pH increased, in 15 lactating Holstein-Friesian cows by administering 2 intramuscular (i.m.) 10-mg injections of isoflupredone acetate 24h apart followed by 2 i.m. injections of furosemide (1mg/kg of BW) 8h apart and by decreasing feed intake. Cows were randomly assigned to 1 of 3 treatment groups with 5 cows/group: untreated control (group C); oral administration of KCl at 0.05 g/kg of BW 8 times at 3-h intervals (group K3); and oral administration of KCl at 0.2g/kg of BW twice at 12-h intervals (group K12). A 24-h KCl dose rate of 0.4 g/kg of BW increased plasma and milk K concentration and plasma Cl concentration, and corrected the metabolic alkalosis and alkalemia, with no clinically significant difference between 2 large doses (group K12) or multiple small doses (group K3) of KCl over 24 h. Oral KCl administration decreased peripheral fat mobilization in cattle with experimentally induced hypokalemia, as measured by changes in plasma nonesterified fatty acid concentration, and slightly augmented the fasting-induced decrease in plasma Mg concentration. Our findings support recommendations for a 24-h oral KCl dose of 0.4 g/kg of BW for treating moderately hypokalemic cattle. Additional Mg may need to be administered to inappetant lactating dairy cattle being treated with oral KCl to minimize K-induced decreases in magnesium absorption., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the clinical effect of topical difluprednate in pediatric patients for treatment of noninfectious uveitis., Design: Retrospective, observational case series., Methods: Twenty-six eyes of 14 pediatric patients with noninfectious uveitis who were treated with topical difluprednate were evaluated. Anterior and posterior cell grade, visual acuity, intraocular pressure (IOP), and cystoid macular edema (CME) were recorded at each visit. Main outcome measures were changes in anterior segment cell, CME, visual acuity, and IOP and development of a visually significant cataract., Results: A significant (≥ 2-grade decrease or decrease to 0 in anterior segment cell) reduction in anterior segment inflammation was observed during treatment with topical difluprednate in 88% of eyes (22/25) when used as an adjuvant to systemic immunomodulatory therapy. In addition, improvement in CME associated with uveitis was seen in response to topical therapy with difluprednate in 78% of eyes with CME (7/9). A significant IOP response (IOP increase of ≥ 10 mm Hg from baseline and IOP ≥ 24 mm Hg) was seen in 50% of eyes (13/26) and in 50% of patients (7/14); 3 eyes of 2 patients required glaucoma surgery. Cataract formation or progression was observed in 39% of eyes (10/26) and in 43% of patients (6/14); 5 eyes of 3 patients required cataract surgery., Conclusions: Difluprednate is an effective agent for both control of anterior segment inflammation and reduction of CME in pediatric patients with uveitis when used as an adjuvant to systemic immunomodulatory therapy. A high rate of steroid-induced IOP elevation and cataract formation is seen in this population. Close monitoring of pediatric patients receiving difluprednate is recommended., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effects of graft rejection episodes after Descemet's stripping automated endothelial keratoplasty surgery (DSAEK) on long-term endothelial cell density (ECD) decline and graft survival., Design: Retrospective, comparative analysis of an interventional case series., Participants: We included 615 eyes of 415 Fuchs' dystrophy patients at a single institution with ≥ 6 months follow-up and without comorbidities known to influence postoperative ECD. All patients were enrolled as part of an ongoing, institutional review board-approved clinical protocol for a long-term, prospective study of endothelial keratoplasty in patients with endothelial dysfunction., Methods: Preoperative specular microscopy of donor corneal tissue was performed. Postoperative specular microscopy measurements were recorded at 6 and 12 months, and yearly thereafter. The percentages of endothelial cell loss recorded at 1, 2, 3, and 4 years were compared with the Mann-Whitney U test., Main Outcome Measures: Percentage ECD declines were calculated at each time point from the results of the preoperative and postoperative specular microscopy. Patients with graft rejection episodes and late endothelial failure were identified. Graft rejection was defined as findings of keratic precipitates with or without corneal edema, or anterior chamber cell and flare with or without corneal edema after the initial resolution of perioperative inflammation., Results: We identified 45 cases of graft rejection. The greatest number of rejections occurred between postoperative months 12 and 18. Eyes with a graft rejection episode had a higher median percentage decline in ECD at all time points compared with eyes without graft rejection episodes. This was statistically significant at 2 and 3 years postoperatively., Conclusions: There is a trend toward a greater percentage of ECD loss with time in eyes experiencing graft rejection after DSAEK surgery., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the effects of 2 corticosteroids on corneal thickness and visual acuity after cataract surgery., Design: Multicenter, randomized, contralateral-eye, double-masked trial., Methods: Fifty-two patients (104 eyes) underwent bilateral phacoemulsification. The first eye randomly received difluprednate 0.05% or prednisolone acetate 1%; the fellow eye received the alternative. Before surgery, 7 doses were administered over 2 hours; 3 additional doses were given after surgery, before discharge. For the remainder of the day, corticosteroids were administered every 2 hours, then 4 times daily during week 1 and twice daily during week 2. Corneal pachymetry, visual acuity, and corneal edema were evaluated before surgery and at days 1, 15, and 30 after surgery. Endothelial cell counts were evaluated before surgery and at 30 days after surgery. Retinal thickness was evaluated before surgery and at 15 and 30 days after surgery., Results: Corneal thickness at day 1 was 33 μm less in difluprednate-treated eyes (P = .026). More eyes were without corneal edema in the difluprednate group than in the prednisolone group at day 1 (62% vs 38%, respectively; P = .019). Uncorrected and best-corrected visual acuity at day 1 were significantly better with difluprednate than prednisolone by 0.093 logMAR lines (P = .041) and 0.134 logMAR lines (P < .001), respectively. Endothelial cell density was 195.52 cells/mm(2) higher in difluprednate-treated eyes at day 30 (P < .001). Retinal thickness at day 15 was 7.74 μm less in difluprednate-treated eyes (P = .011)., Conclusions: In this high-dose pulsed-therapy regimen, difluprednate reduced inflammation more effectively than prednisolone acetate, resulting in more rapid return of vision. Difluprednate was superior at protecting the cornea and reducing macular thickening after cataract surgery., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Difluprednate (6α,9-difluoro-11β,17,21-trihydroxy-1,4-pregnadiene-3,20-dione 21-acetate 17-butyrate, DFBA) has long been used as an anti-inflammatory dermatological agent. The main objectives of the current study were to evaluate the pharmacokinetic and pharmacodynamic features of DFBA when used as an ophthalmic agent, and to compare these features with those of other common ophthalmic agents, to determine which has the highest activity., Methods: A glucocorticoid (GC) receptor-binding test was performed to evaluate GC receptor-binding activity (GCRBA, the index of pharmacological effect). Using this information, we calculated dose-response curves, IC(50) values, and K(d) values to evaluate each drug's K(i) value. Finally, we performed studies in live rabbits to compare the activity of 4 formulations [0.002%, 0.01%, or 0.05% DFBA, or an ophthalmic solution of 0.1% betamethasone sodium phosphate (BMP)] at 4 time points (0.5, 1, 2, 4  h). At each time point, blood and eye samples were taken so that C(max) (the maximum equivalent concentration of the active DFBA metabolite, DFB), T(max) (the time at which C(max) was measured), and the area under the concentration-time curve could be compared across the 4 formulations., Results: BMP had the highest K(i) value (8.4 × 10(-8) nmol/L), whereas DFB had the lowest (6.1 × 10(-11) nmol/L). The GCRBA of DFBA was intermediate to these 2 values (7.8 × 10(-10) nmol/L). Instillation of the DFBA ophthalmic emulsion in the eyes of rabbits led to dose-dependent increases in GCRBA, which was mostly attributable to the activity of DFB. The 0.05% DFBA ophthalmic emulsion elicited the greatest response in both aqueous humor and iris/ciliary body tissues, though there were no significant dose-dependent differences in GCRBA in plasma samples., Conclusions: The 0.05% DFBA ophthalmic emulsion appears to be an effective and safe anti-inflammatory treatment in ocular tissues. It is comparable, and possibly even superior, to the 0.1% BMP solution, and may be particularly useful in cases of severe disease where treatment with BMP solution alone is insufficient.

Purpose: To evaluate ocular distribution and excretion of tritium-labeled difluprednate ((3)H-DFBA) ophthalmic emulsion 0.05% after a single or repeated instillation to pigmented rabbit eyes., Methods: (3)H-DFBA ophthalmic emulsion 0.05% was instilled in the right eyes of pigmented rabbits, in either a single or repeated quater in die (QID) for 3 days or 7 days) dose of 25  μg/50  μL. The radioactivity in right and left ocular tissues, urine, blood, plasma, and feces were measured with a liquid scintillation counter. Additionally, the distribution of radioactivity around ocular tissues was investigated with autoradiography., Results: After a single instillation, the highest maximum radioactive concentrations were found in the cornea (2,081  ng eq./g), followed by the iris/ciliary body (926  ng eq./g), conjunctiva (330  ng eq./g), anterior retina/choroid (273  ng eq./g), sclera (222  ng eq./g), and aqueous humor (144  ng eq./mL) of treated eyes. The maximum radioactivity concentration of the posterior retina/choroid was 59  ng eq./g, and difluprednate delivered as a topical ophthalmic emulsion reached the back of the eye. However, radioactivity in untreated eyes was very low. Total radioactivity excreted in urine and feces 168  h after a single instillation was 99.5% of the total dose. Radioactivity concentration levels measured 24  h after 28 instillations were no more than twice those measured 24  h after 12 instillations. Radioactive concentrations in ocular and periocular tissues were highest at 0.5 or 1  h after a single instillation, and were mostly eliminated from these tissues by the end of the study. Radioactivity was barely detectable in the blood, with very little accumulation even after multiple doses., Conclusions: After instillation of (3)H-DFBA ophthalmic emulsion 0.05% in rabbit eyes, radioactivity was distributed at the anterior segment and cleared rapidly. Some radioactivity was detected in the posterior retina/choroid, suggesting that difluprednate and its metabolites reach these tissues. These results suggest that difluprednate delivered as a topical ophthalmic emulsion reached the anterior and posterior segments of the eye quickly and may be a potential treatment for ocular inflammation in these areas.

Purpose: To report the effects of twice-daily difluprednate in a child with pars planitis (PP)., Design/methods: Case report., Results: PP was controlled with topical difluprednate for 1 year. Then an atypical pattern of steroid response--delayed, relatively sudden onset of recalcitrant ocular hypertension (OHT)--and posterior subcapsular cataract (PSC) formation necessitated alternative treatment., Conclusion: Although not a standard treatment, in select cases of PP topical difluprednate therapy could be a useful short-term treatment option while alternative treatments are considered or immunosuppressive agents build to therapeutic levels. Ophthalmologists must be aware of the potential for delayed onset of serious complications when using difluprednate.

Purpose: The aim of this study was to evaluate the efficacy and safety of difluprednate ophthalmic solution 0.05% (Durezol; Alcon Laboratories, Fort Worth, TX) compared with prednisolone acetate ophthalmic suspension 1% (Pred Forte; Allergan, Inc., Irvine, CA) for endogenous anterior uveitis., Methods: In this phase 3, multicenter, randomized, noninferiority trial, 90 patients with endogenous anterior uveitis [>10 anterior chamber (AC) cells and an AC flare score of ≥2 in at least 1 eye] received either difluprednate 4x /day (QID) (n=50) or prednisolone 8x/day (n=40) for 14 days, followed by a 2-week tapering regimen. The main outcome measure was change from baseline in AC cell grade on day 14., Results: At day 14, mean AC cell grade improvement for difluprednate-treated patients was similar to prednisolone-treated patients (2.1 vs. 1.9, respectively), proving noninferiority. At day 14, 68.8% of difluprednate patients had AC cell clearing (grade 0:≥ 1cell) compared with 61.5% of prednisolone patients. In the prednisolone-treated group, 12.5% of patients were withdrawn because of investigator-determined lack of efficacy; no difluprednate-treated patients were withdrawn for this reason (P=0.01). Clinically significant intraocular pressure elevation occurred in 3 difluprednate-treated patients (6.0%) and 2 prednisolone-treated patients (5.0%)., Conclusions: Difluprednate administered QID is at least as effective as prednisolone administered 8x/day in resolving the inflammation and pain associated with endogenous anterior uveitis. Difluprednate provides effective treatment for anterior uveitis and requires less frequent dosing than prednisolone acetate., Clinical Trial Registration: Trial NCT00501579 was registered at the National Institutes of Health Registry in July 2007 ( http://clinicaltrials.gov/ct2/show/NCT00501579?term=sirion&rank=4 ).

Purpose: To assess the efficacy and safety of difluprednate ophthalmic emulsion 0.05% (Durezol) 2 or 4 times a day compared with those of a placebo in the treatment of inflammation and pain associated with ocular surgery., Setting: Twenty-six clinics in the United States., Methods: One day after unilateral ocular surgery, patients who had an anterior chamber cell grade of 2 or higher (>10 cells) were treated with 1 drop of difluprednate 2 times or 4 times a day or with a placebo (vehicle) 2 times or 4 times a day in the study eye for 14 days. This was followed by a 14-day tapering period and a 7-day safety evaluation. Outcome measures included cleared anterior chamber inflammation (grade 0, or=10 mm Hg and >or=21 mm Hg from baseline, respectively) versus 1% in the placebo group., Conclusions: Difluprednate given 2 or 4 times a day cleared postoperative inflammation and reduced pain rapidly and effectively. There were no serious ocular adverse events. Fewer adverse events were reported in the difluprednate-treated groups than in the placebo group.

Glucocorticoids are commonly used to treat cows with clinical ketosis and fatty liver disease, but their use is controversial. The objectives of the present study were to investigate the effects of isoflupredone acetate alone or with insulin on the energy metabolism of dairy cows in early lactation in a large double-blind, randomized clinical trial. A total of 1,162 Holstein cows and first-lactation heifers were randomly assigned to receive 1 of 3 treatments between the day of parturition and 8 DIM: group A, 20-mg i.m. injection of isoflupredone and 100 units of insulin; group B, 20-mg i.m. injection of isoflupredone; group C (control group), 10-mL i.m. injection of sterile water. Treatments were randomized across 24 dairy farms located near Guelph, Ontario, Canada. Serum samples obtained at the time of treatment and at wk 1 and 2 following treatment were analyzed for beta-hydroxybutyrate, nonesterified fatty acids, glucose, calcium, potassium, sodium, and chloride. Cows were assigned a body condition score at the time of enrollment. Data were analyzed using a repeated-measures mixed model that accounted for the effects of parity and body condition score, and the random effects of cow and farm. Cows that received isoflupredone with insulin and isoflupredone alone had higher beta-hydroxybutyrate and nonesterified fatty acid concentrations 1 wk after treatment compared with control cows. Cows that received isoflupredone acetate plus insulin had lower glucose concentrations at 1 wk after treatment. Calcium concentrations 1 wk after treatment were lower for cows that received isoflupredone and insulin or isoflupredone only compared with control cows. Serum sodium, potassium, and chloride concentrations were not influenced by treatment. The effect of treatment on the proportion of cows with subclinical ketosis was evaluated with a logistic regression model. Over the 2 wk following treatment, a significant increase in the prevalence of subclinical ketosis was observed in the isoflupredone plus insulin group relative to the control group. Among 972 cows that were not ketotic at enrollment, cows that received isoflupredone acetate plus insulin or isoflupredone acetate only were, respectively, 1.72 and 1.59 times more likely than control cows to develop subclinical ketosis 1 wk after treatment. There were no treatment effects on test-day milk production, milk fat and protein percentages, or the intervals from calving to first insemination or pregnancy.

Objective: To determine whether administration of isoflupredone acetate (ISO) to healthy cows increases the frequency of severe hypokalemia and whether dexamethasone (DEX) has detectable mineralocorticoid properties., Animals: 33 cows at 20 to 25 days of lactation., Procedures: Cows were randomly allocated to 5 treatment groups and received 2 IM injections (on days 0 and 2) of sterile saline (0.9% NaCl) solution (10 mL each), an injection of ISO (20 mg) or DEX (20 mg) followed by 10 mL of saline solution, or 2 injections of ISO or DEX. Milk production was measured, physical examinations were performed, and blood and urine samples were collected daily on days 0 through 7., Results: Physical examination parameters did not differ among groups; however, 1 cow developed atrial fibrillation on day 4. Both corticosteroids significantly increased plasma glucose concentrations, and ISO significantly decreased plasma potassium concentrations and increased total carbon dioxide concentrations with time. One dose of ISO decreased mean plasma potassium concentration by 25% on day 2, compared with day 0, and severe hypokalemia (serum potassium concentration < 2.3 mEq/L) developed in 1 of 6 cows. Mean plasma potassium concentration was 46% lower on day 3 than on day 0 in cows receiving 2 doses of ISO, and 5 of 7 cows became severely hypokalemic. Mean urinary fractional excretion of potassium significantly increased from that on day 0 in cows receiving 2 doses of ISO., Conclusions and Clinical Relevance: Both corticosteroids had glucocorticoid activity; however, only ISO had mineralocorticoid activity. Compared with saline solution, administration of 2 doses of ISO significantly increased the frequency of severe hypokalemia.

Preparation of oil-in-water (o/w) type lipid emulsion is one of the approaches to formulate drugs that are poorly water-soluble but can be dissolved in the oil phase of the emulsions. A synthetic glucocorticoid medicine, difluprednate (DFBA), is a water-insoluble compound. We formulated DFBA (0.05%, w/v) ophthalmic lipid emulsion containing 5.0% (w/v) caster oil and 4.0% (w/v) polysorbate 80. The appearance of the emulsion was blue and translucent lipid emulsion, and the median particle size of the lipid emulsion was 104.4 nm. Neither separation nor change in particle size was observed after 6 months at 40 degrees C. Furthermore, when compared with DFBA (0.05%, w/v) ophthalmic suspension, the lipid emulsion showed 5.7-fold higher concentration of DFB that was an active metabolite of DFBA in aqueous humor at 1h after instillation. Ophthalmic lipid emulsion enhances the intraocular penetration of drugs, and it is useful as a delivery system for the ophthalmic preparations of lipophilic drugs.

Three commercial trials were conducted to evaluate the use of dexamethasone (Dex) and/ or isoflupredone (Predef) in improving preweaning growth performance of neonatal pigs. The objectives of the commercial trials were threefold: 1) to evaluate Predef in comparison with Dex; 2) to address the sexual dimorphic growth response observed in a previous commercial trial; and 3) to determine whether there is any benefit of providing Dex treatment to pigs being fed supplemental milk. In Exp. 1, 276 pigs (Triumph 4 x PIC Camborough 22) were assigned according to birth weight and sex to three treatments. Treatments included saline (Control), Dex (2 mg/kg BW i.m. injection of Dex), or Predef (2 mg/kg BW i.m. injection of Predef 2X) within 24 h after birth. A treatment effect was observed for BW at weaning (P < 0.001), with pigs injected with Predef being 0.51 kg lighter than Control and Dex-treated pigs. The lower BW of Predef-treated pigs at weaning were a result of a lower ADG (P < 0.001) during the preweaning period compared with Control and Dex pigs. In Exp. 2, 703 pigs (Triumph 4 x PIC Camborough 22) were assigned according to birth weight and sex to three treatments. Treatments included either an i.m. injection of saline (Control), Dexl (1 mg/kg BW of Dex), or Dex2 (2 mg/kg BW of Dex) within 24 h after birth. No treatment effects were observed for BW at weaning (P = 0.24) or ADG (P = 0.19). In Exp. 3, 342 pigs (Genetiporc) were assigned according to birth weight and sex to two treatments. Treatments included either an i.m. injection of saline or Dex (2 mg/kg BW) within 24 h after birth. All pigs were provided supplemental milk from the time of treatment until weaning age. No treatment effects were observed for BW at weaning (P = 0.13) or ADG (P = 0.11). The negative response to Predef was similar to the growth-suppressive effects observed by others using chronic glucocorticoid treatment. In contrast to our previous findings, Dex did not improve preweaning growth performance regardless of dose or supplemental milk.

Terms of re-epithelialization, severity of the painful syndrome, intensity of corneal "crepe" (opacity) are assessed in myopic patients treated by maxitrol, eubetal, colbiocin ointments and maxitrol eyedrops in the early postoperative period after photorefraction keratectomy. The crepe intensity was assessed routinely according to a clinical score: 0) transparent cornea, 1) trace crepe; 2) moderate crepe; and 3) intensive crepe. Biomicroscopy on day 4 after photorefraction keratectomy showed complete epithelialization in 91.7% patients after colbiocin ointment, in 91.% after maxitrol eyedrops, 87% after eubetal ointment, and 82.6% after maxitrol ointment. The least corneal opacity (0 and 0-1) was observed after eubetal ointment and maxitrol eyedrops. The mean score for pain was virtually the same in all groups; in the colbiocin ointment group more patients complained of pain for more than 24 h in comparison with other groups.

We performed this prospective, randomised, investigator-masked, parallel-group study to compare Fluorometholone-Gentamicin eye drops with Maxitrol (dexamethasone, neomycin, polymyxin B) eye drops in the reduction of ocular bacterial flora and control of ocular inflammation after cataract surgery. One hundred and twelve (FML-Genta 54, Maxitrol 58) patients of both sexes undergoing cataract and posterior chamber lens implant surgery for visually disabling cataract were enrolled in the study and examined pre-operatively and post-operatively on days 1, 6-8 and 24-34. The baseline parameters were similar in the two study groups. The conjunctival bacterial colony count on day 6-8 post-operatively was significantly less on FML-Genta compared with Maxitrol (p = 0.033). There was no statistically significant difference between the two treatments in the degree of intra-ocular inflammation as assessed by flare and cells in the anterior chamber. Both treatments were judged to be equal in the global assessment of the success of therapy and local tolerance by the study patients and doctors. Fluorometholone-gentamicin eye drops were more effective than Maxitrol eye drops in the reduction of ocular bacterial flora while being as well-tolerated and as effective as Maxitrol in the control of ocular inflammation after cataract surgery.

The effects of four days' treatment with topical Maxitrol (neomycin sulphate 3500 IU/mL, polymyxin-B sulphate 6000 IU/mL with dexamethasone 0.1%) were compared with those of Maxidex (dexamethasone 0.1% alone) in a double-masked study in 111 patients with bacterial blepharitis or conjunctivitis, 95 of whom were evaluable for efficacy. The majority of patients (N = 80) had chronic blepharitis. Maxitrol treatment resulted in a significantly greater reduction (90%) in bacterial counts and bacterial eradication (50%) compared with Maxidex (34% and 17% respectively). Maxitrol treatment also produced a significantly greater reduction in conjunctival discharge than did Maxidex, while the treatments were equally effective in alleviating other ocular signs and symptoms. It was concluded that use of a fixed dose combination steroid-antibiotic product was more effective for bacterial control and therapeutic efficacy in the treatment of chronic blepharitis and conjunctivitis patients than treatment with steroid alone. However, in the long-term treatment of chronic blepharitis the well-known toxic problems of neomycin sulphate have to be taken into account.

Background and Objective: Following silicone intubation, most surgeons prescribe either an antibiotic or an antibiotic-steroid combination medication. No known controlled study has been performed to determine whether steroids in addition to antibiotics improve the postoperative outcome., Patients and Methods: The author performed a prospective randomized study of 108 patients (118 eyes) who underwent silicone intubation over a period of 4 1/2 years. Sixty-seven patients received a combination of neomycin, polymyxin B, and dexamethasone and 41 patients received gentamicin for 2 weeks after surgery. A standardized surgical technique and instruments were used. Follow-up ranged from 8 to 44 months (average 19 months)., Results: No statistically significant difference was found in the failure rates when patients treated with an antibiotic-steroid combination were compared with those treated with antibiotic alone., Conclusion: Following silicone intubation, there appears to be no additional benefit of an antibiotic-steroid combination medication over an antibiotic alone.

OBJECTIVE--To document plasma, urine, and synovial fluid disposition of 2 common intra-articularly administered steroid preparations, methylprednisolone acetate (MPA) and isoflupredone acetate (IPA). DESIGN--Descriptive investigation. SAMPLE POPULATION--100 mg of MPA or 4 mg of IPA was administered to 2 groups of 4 healthy sound radiographically normal female horses. PROCEDURE--Blood samples were collected at time 0 (before) and 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after administration of the designated steroid. Complete urine collection for measurement of designated steroid was accomplished by use of occluding 28-F balloon catheters. Synovial fluid samples were aseptically aspirated from the injected and contralateral uninjected tarsocrural joint at time 0 and 8, 24, 48, 240, and 672 hours after administration of the designated steroid. All samples were screened by ELISA to detect parent drug or metabolite equivalent, with a sensitivity of 2.5 ng/ml for MPA and 0.1 ng/ml for IPA. If drug was detected by ELISA in the plasma or synovial fluid, the samples were further quantified and specified, using HPLC with a lower limit of quantification (10 ng/ml). RESULTS--Between 2 and 12 hours after administration, plasma contained < 10 ng of MPA or IPA/ml (parent drug or metabolite equivalent), as intermittently detected by ELISA. Parent drug or metabolite equivalent was detected in the urine for 24 and 72 hours after injection of IPA and MPA, respectively. Synovial fluid from the contralateral joint contained no detectable MPA or IPA at any sample collection time. Median half-life for MPA, as detected by HPLC, was 10.3 hours (range, 6.1 to 10.6) in the synovial space. Median half-life for methylprednisolone, as detected by HPLC, was 10.4 (range, 9.9 to 32.1) hours. CONCLUSIONS--Both steroids appeared to be rapidly hydrolyzed to their respective ester forms, as detected by HPLC. The ELISA appeared to be a useful screening tool for detection of corticosteroids in this variety of body fluids.

Purpose: The aim of this study was the assessment of possible changes in corneal metabolism and epithelial barrier function after an extracapsular lens extraction with artificial lens implantation., Methods: Ten patients without any eye medication were selected out of 140 patients attending for extracapsular lens extraction with lens implantation at the university hospital. Corneal metabolism was evaluated by fluorophotometric measurement of corneal autofluorescence. The corneal fluorescence values were corrected for interference by the fluorescence of the ocular lens. Corneal epithelial barrier function was evaluated by determination of corneal epithelial permeability. The permeability was calculated from the fluorescein penetration into the cornea after application of an eye bath containing fluorescein. Operated and fellow eyes were investigated 1 week before and 3-4 weeks after the operation., Results: The corneal autofluorescence of the operated eye decreased significantly after surgery (mean decrease: 14%, Wilcoxon paired-sample test: P = 0.038). The corneal epithelial permeability of both eyes increased after surgery above the normal range of healthy controls (mean increase operated eye: 34%, P = 0.015, fellow eye: 32%, P = 0.15). Both corneal autofluorescence and epithelial permeability returned to normal values after one year., Conclusions: The lower corneal autofluorescence in the operated eye after surgery indicates a lower corneal metabolism which may be due to surgery. The increased epithelial permeability of both eyes implies a temporary impairment of the corneal barrier function. The interaction with the fellow eye indicates a consensual reaction which may attributed to damage to the neural system by the surgery.

In order to evaluate the long-term-safety of halopredone acetate (THS-201: 17 alpha, 21-diacetoxy-2-bromo-6 beta, 9 alpha-difluoro-11 beta-hydroxy-1, 4-pregnadiene-3, 20-dione), a 52-week chronic toxicity study was performed on the basis of its local accumulation in dogs. In doses of 0.1, 0.5 and 2.5 mg/kg, THS-201 was injected into the right knee joint in both sexes of dogs every 2 weeks for 39 weeks and withdrawn for 13 weeks. In this study, the below slight local changes were observed in both sexes of dogs treated with 2.5 mg/kg/2 weeks of THS-201: focal loss of hair of the injection site, lesser stain in cartilage matrix of articular cartilage and meniscus in light microscopic examinations, and irregular thickness and elongation of collagen fibers, roughness of fibrous density and decrement of proteoglycans in electron microscopic examinations. In conclusion, systemic adverse effects were not observed in any dogs treated with THS-201.

Since halopredone acetate (THS-201), a synthetic corticosteroid, is expected to be used clinically for intra-articular injections because of its long-lasting activity in the synovial bursa, its acute toxicity was compared with that of triamsinolone acetonide (TA) and methylprednisolone acetate (MPA). The test animals were Jcl: ICR mice and Jcl: Wistar rats, and drugs were administered orally, intraperitoneally and subcutaneously. The LD50 values of THS-201 both in mice and rats were estimated more than 5000 mg/kg at each route, and these are for above larger than those of TA or MPA. Moreover, in oral and subcutaneous administration of THS-201, no severe toxic signs were observed either in mice or in rats. In intraperitoneal injection, a few of mice and rats died after showing several clinical signs and suppression of body weight gain, and their autopsy revealed atrophy of thymus, spleen and adrenal, induction of infection and hemorrhage in digestive tract. On the other hand, the mice and rats administered TA or MPA revealed the severe toxic signs such as loss of hair gloss, marked emaciation, decrease in spontaneous movement, anemia, bloated face, decrease or suppression of body weight gain, atrophy of thymus, spleen and adrenal, severe induction of infection and lesions in digestive tracts. Accordingly, it is concluded that the acute toxicity of THS-201 in mice and rats was lower than that of TA or MPA.

Among the various syndromes caused by excess mineralocorticoids, the factitious syndrome produced by excessive 9-alpha-fluorprednisolone inhalations is more common than might be expected, especially in places where the drug is easily obtained without a doctor's prescription. A fairly typical case of addiction to a nasal spray containing ephedrine hydrochloride and an imidazoline compound as well as the steroid is described. The diagnosis of the case is analysed with details of certain differences from similar cases reported in the literature and the modifications to clinical and instrumental parameters achieved after over two months' treatment with spironolactone are described.

A patient is reported who presented with severe arterial hypertension and pronounced hypokalemic metabolic alkalosis along with suppression of 17-hydroxicorticoids, plasma renin activity and urinary aldosterone excretion, in relation to topical application of 9-alpha-fluoroprednisolone, 300 mg weekly. The clinical picture changed after discontinuation of the steroid preparation. Whenever topical steroids are prescribed for extensive chronic skin the development of systemic side-effects must be watched. Depending on the type of steroid employed, Cushing's syndrome or a hypermineralcorticism state may appear. The differential diagnosis of a hypermineralcorticism syndrome without aldosteronism should include the possible topical application of fluorated steroids.