Effectiveness of Difluprednate for the Treatment of Anterior Scleritis.

PURPOSE: To describe the effectiveness and side effect profile of difluprednate therapy in a series of patients with anterior scleritis. DESIGN: Retrospective, interventional case series. METHODS: Data collected from all patients with anterior scleritis who used difluprednate as a single treatment agent from January 1, 2018, to January 1, 2020, including demographics, scleritis type, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops 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: Twenty-five patients (35 eyes) were analyzed. The median age was 60 years (range 13-78); 60% were female; 64% were White. Forty percent had bilateral disease, and 44% of patients had an associated systemic disease. The majority of eyes (66%) had diffuse anterior scleritis. Eighty-three percent of eyes achieved resolution of scleritis, with a median time of resolution of 6 weeks. Eyes treated with an initial dose of ≥4 times daily were more likely to achieve disease resolution (hazard ratio [HR] = 3.43, 95% confidence interval [CI] 1.19, 9.88, P = .02). Nine eyes had IOP elevation. Four eyes lost ≥2 lines of BCVA, and 1 due to cataract progression. One eye underwent cataract surgery. CONCLUSIONS: Difluprednate alone may effectively treat non-infectious anterior scleritis with a tolerable side effect profile.

Localized alopecia and suppression of hypothalamic-pituitary-adrenal (HPA) axis in dogs following treatment with difluprednate 0.05% ophthalmic emulsion (Durezol®).

BACKGROUND: Despite the common use of topical ophthalmic corticosteroids in dogs, detailed reports on systemic and dermatologic adverse effects are limited. RESULTS: Nine purpose-bred research Beagles were treated with difluprednate 0.05% ophthalmic emulsion in one or both eyes 2-3 times daily. Some difluprednate treated dogs developed mild to severe alopecia of the periocular region, face, and distal pinna (5/9). The median duration of treatment prior to onset of dermatologic signs for difluprednate treated dogs was 550 days (453-1160 days). Diagnostic testing included complete blood count (CBC) and serum biochemistry, adrenocorticotropic hormone (ACTH) stimulation testing combined with endogenous ACTH measurement, and skin biopsy. The CBC and chemistry were within normal limits for all dogs. There were varying degrees of suppression of the hypothalamic-pituitary-adrenocortical (HPA) axis with difluprednate treatment. Dogs with the most profound alopecic changes had less pronounced HPA axis suppression compared to dogs with no integumentary changes. Skin biopsies demonstrated follicular atrophy and follicular keratosis. When topical difluprednate was reduced to unilateral therapy, the hair regrew on the untreated side of the face. In addition to the affected research dogs, a 7-year old female spayed Chihuahua that was being treated as a clinical patient with long-term difluprednate 0.05% ophthalmic emulsion developed generalized hypotrichosis on the head and body and a potbellied appearance. ACTH stimulation testing revealed suppression of the HPA axis with a mild increase in serum alkaline phosphatase (ALP) activity and a urine specific gravity of 1.016. The combination of clinical signs and laboratory abnormalities was supportive of iatrogenic hyperadrenocorticism. CONCLUSIONS: In dogs long-term use of difluprednate ophthalmic emulsion results in HPA axis suppression and in some cases iatrogenic hyperadrenocorticism. A novel pattern of localized alopecia is suspected to be related to dermal absorption and local action due to superior potency and penetration compared to other commonly utilized ophthalmic corticosteroids.

Comparison of early posttreatment effects of two steroidal anti-inflammatory ophthalmic drugs on the ocular inflammatory response induced by paracentesis in healthy canine eyes.

OBJECTIVE: We investigated the early posttreatment effects of two steroidal anti-inflammatory ophthalmic drugs on blood-aqueous barrier (BAB) breakdown by paracentesis in dogs. ANIMAL STUDIES: We studied 21 healthy beagles with normal eyes. PROCEDURES: Controlled anterior chamber paracentesis (0.5 mL) was performed in one eye of each dog. Control group dogs (n = 7) received no medication, whereas those in the treatment groups received a topical anti-inflammatory medication (difluprednate [DFBA] ophthalmic emulsion 0.05% [n = 7] or betamethasone [BMZ] sodium phosphate ophthalmic solution 0.1% [n = 7]) at 0, 15, 30, and 45 minutes after initial paracentesis in the paracentesed eyes. Secondary aqueous humor (AH) was collected 60 minutes after initial paracentesis. Protein and prostaglandin E2 (PGE2 ) concentrations in AH were determined using the bicinchoninic acid assay and commercially available immunoassay kit, respectively. All mean values in the three groups were compared using analysis of variance followed by Tukey's post hoc test. RESULTS: Aqueous protein and PGE2 concentrations were markedly increased at 60 minutes following paracentesis. Both concentrations in the secondary AH of the DFBA group were significantly lower than those of the control group; however, treatment with BMZ had no significant effects. CONCLUSIONS: Early postparacentesis treatment with DFBA was more effective than that with BMZ for reducing aqueous protein and PGE2 contents in dogs with paracentesis-induced BAB breakdown. DFBA may be an appropriate treatment during the early stage of anterior uveitis caused by intraocular surgery in dogs.

Toxic anterior segment syndrome following phakic posterior chamber IOL: a rarity.

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.

Comparison of Efficacy of Difluprednate 0.05% and Loteprednol Gel 0.5% After Cataract Surgery.

PURPOSE: To compare the outcomes and complications of topical difluprednate 0.05% and loteprednol gel 0.5% after routine cataract surgery. METHODS: Subjects received either difluprednate emulsion 0.05% (n=30 eyes) or loteprednol gel 0.5% (n=30 eyes) after routine cataract surgery. Topical steroid drops were initiated 3 days before cataract surgery and continued for 2 weeks postoperatively. Anterior chamber (AC) cell grade, corneal edema, corneal pachymetry, visual acuity, ocular surface quality (Oxford scale), and intraocular pressure (IOP) were evaluated at 1 day, 1 week, and 1 month postoperatively. RESULTS: Patients treated with difluprednate or loteprednol had statistically similar resolution of their AC cell grade and corneal edema at 1 day, 1 week, and 1 month postoperatively (P>0.05 at each study visit). Difluprednate-treated and loteprednol-treated eyes achieved a mean best-corrected visual acuity of at least 20/25 by 1 week postoperatively (0.055 and 0.061 logarithm of the minimum angle of resolution, respectively; P=0.82). The nasal ocular surface quality at 1 week had improved in loteprednol-treated eyes compared with difluprednate-treated eyes (1.0 vs. 1.9 Oxford score, respectively; P<0.001), but similar at all other visits. There was no statistical difference between IOP levels between both treatment groups (P>0.05). In the difluprednate-treated group, one patient developed rebound inflammation and two patients developed cystoid macular edema at their 1-month postoperative visit. CONCLUSIONS: The anti-inflammatory effect, visual recovery, and IOP of patients using topical difluprednate or loteprednol gel after cataract surgery are equivalent. There may be an additional short-term benefit of loteprednol gel in protecting the ocular surface after cataract surgery.

Nonclinical Development of ENV905 (Difluprednate) Ophthalmic Implant for the Treatment of Inflammation and Pain Associated with Ocular Surgery.

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.

Comparison of prednisolone acetate 1.0% and difluprednate ophthalmic emulsion 0.05% after cataract surgery: Incidence of postoperative steroid-induced ocular hypertension.

PURPOSE: To compare intraocular pressure (IOP) outcomes between 2 common, commercially available corticosteroid drops: difluprednate ophthalmic emulsion 0.05% and prednisolone acetate 1.0%. SETTING: TLC Eyecare and Laser Centers, Jackson, Michigan, USA. DESIGN: Retrospective chart review. METHODS: The outcomes of consecutive patients who had uneventful cataract surgery from April 2013 to September 2013 and used prednisolone acetate postoperatively were compared with the outcomes of consecutive patients who had uneventful cataract surgery from June 2014 to October 2014 and used difluprednate postoperatively. RESULTS: The study included 224 eyes treated with prednisolone acetate 4 times daily for 30 days and 225 eyes treated with difluprednate 2 times daily for 30 days. There was no significant difference between the 2 groups in age, sex, or race. In addition, the mean IOP did not differ significantly between the prednisolone acetate group and the difluprednate group at the preoperative measurement or 1 month after surgery, nor was there a difference in the 1-month change in IOP between groups. No association was found between the incidence of a 6 mm Hg or higher increase in IOP 1 month after surgery and steroid treatment. One month postoperatively, 4 eyes in the prednisolone acetate group and 5 eyes in the difluprednate group had an IOP higher than 21 mm Hg. CONCLUSIONS: There was no significant difference in the mean IOP or percentages showing IOP elevation between eyes treated with difluprednate and eyes treated with prednisolone acetate after cataract surgery. This was likely the result of low-frequency dosing and short duration of steroid use.

Difluprednate versus prednisolone acetate for inflammation following cataract surgery in pediatric patients: a randomized safety and efficacy study.

PurposeTo evaluate safety and efficacy of difluprednate 0.05% ophthalmic emulsion for treatment of postoperative inflammation after cataract surgery in pediatric patients.MethodsThis was a phase 3B, multicentre, randomized, double-masked, active-controlled study of patients aged 0-3 years who underwent uncomplicated cataract surgery in one eye, with/without intraocular lens implantation. Patients were randomized to receive difluprednate 0.05% four times daily or prednisolone acetate 1% for 14 days post surgery, followed by tapering for 14 days. Safety included evaluation of adverse events. Primary efficacy was the proportion of patients with an anterior cell grade of 0 (no cells) at day 14; secondary efficacy was a global inflammation score.ResultsForty patients were randomized to each treatment group. Adverse drug reactions included corneal oedema (difluprednate 0.5%, n=1; prednisolone acetate 1%, n=0) and increased intraocular pressure or ocular hypertension (n=2/group). Mean intraocular pressure values during treatment were 2-3 mm Hg higher with difluprednate 0.05% compared with prednisolone acetate 1%; mean values were similar between groups by the first week after treatment cessation. At 2 weeks post surgery, the incidence of complete clearing of anterior chamber cells was similar between groups (difluprednate 0.05%, n=30 (78.9%); prednisolone acetate 1%, n=31 (77.5%). Compared with prednisolone acetate 1%, approximately twice as many difluprednate 0.05%-treated patients had a global inflammation assessment score indicating no inflammation on day 1 (n=12 (30.8%) vs n=7 (17.5%) and day 8 (n=18 (48.7%) vs n=10 (25.0%).ConclusionsDifluprednate 0.05% four times daily showed safety and efficacy profiles similar to prednisolone acetate 1% four times daily in children 0-3 years undergoing cataract surgery.

Topical difluprednate monotherapy for uveitic macular edema.

OBJECTIVE: To describe the use of topical difluprednate for the treatment of uveitic macular edema. DESIGN: Retrospective review of 3 consecutive cases of uveitic macular edema. METHODS: Patients were treated with topical difluprednate monotherapy. RESULTS: All patients experienced complete resolution of uveitic macular edema within 2-4 weeks. We observed a statistically significant improvement in central subfield macular thickness (p = 0.04). There was an overall improvement in visual acuity, but this result was not statistically significant (p = 0.33). CONCLUSIONS: Topical difluprednate can be effective for uveitic macular edema. Further investigation of this therapy in prospective randomized controlled trials is warranted.

Inflammatory Papillitis in Uveitis: Response to Treatment and Use of Optic Nerve Optical Coherence Tomography for Monitoring.

PURPOSE: To describe the clinical course of uveitis-associated inflammatory papillitis and evaluate the utility and reproducibility of optic nerve spectral domain optical coherence tomography (SD-OCT). METHODS: Data on 22 eyes of 14 patients with uveitis-related papillitis and optic nerve imaging were reviewed. SD-OCT measure reproducibility was determined and parameters were compared in active vs. inactive uveitis. RESULTS: Papillitis resolution lagged behind uveitis resolution in three patients. For SD-OCT measures, the intraclass correlation coefficients were 99.1-100% and 86.9-100% for intraobserver and interobserver reproducibility, respectively. All SD-OCT optic nerve measures except inferior and nasal peripapillary retinal thicknesses were significantly higher in active vs. inactive uveitis after correction for multiple hypotheses testing. Mean optic nerve central thickness decreased from 545.1 to 362.9 µm (p = 0.01). CONCLUSIONS: Resolution of inflammatory papillitis can lag behind resolution of uveitis. SD-OCT assessment of papillitis is reproducible and correlates with presence vs. resolution of uveitis.

A case of bilateral uveitis and papillitis in a patient treated with pembrolizumab.

PURPOSE: Drug-induced uveitis is a well-known effect of ocular inflammation that has been reported with many medications. Pembrolizumab is a newer generation of the anti-programmed cell death-1 monoclonal antibodies that was recently approved by the Food and Drug Administration for the treatment of advanced melanoma. Immune-mediated adverse events involving different organs have been reported in recent literature in association with this drug. We present the first reported case of uveitis in association with pembrolizumab therapy. CASE REPORT: An 82-year-old man with stage IV melanoma was started on pembrolizumab infusion treatment every 3 weeks. Two months after initiating therapy, he presented with bilateral severe anterior uveitis and papillitis with fast and complete recovery after withholding further pembrolizumab infusions and treatment with topical steroid. Uveitis recurred after restarting pembrolizumab therapy. CONCLUSIONS: In current clinical practice, many new drugs are being approved, requiring better characterization of the prevalence, onset, and nature of adverse events in order to aid development of effective management strategies. Ophthalmologists should keep in mind that drugs are always a possible cause of ocular inflammation in patients presenting with uveitis.

Lamotrigine-induced tubulointerstitial nephritis and uveitis-atypical Cogan syndrome.

PURPOSE: To report a case of lamotrigine-induced tubulointerstitial nephritis and uveitis (TINU)-atypical Cogan syndrome. METHODS: Case report. RESULTS: A 16-year-old boy with traumatic brain injury and seizures presented to the emergency department with facial swelling, rash, and back pain several days after increasing lamotrigine dose secondary to a breakthrough seizure. Creatinine, urine ß2 microglobulin, and eosinophils were elevated. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme, and complement were normal. Renal biopsy showed acute granulomatous tubulointerstitial nephritis. Lamotrigine was discontinued, intravenous steroids were initiated, and the patient was discharged on Ativan and prednisone. Subsequently, he was diagnosed with bilateral anterior uveitis (vision 20/30 bilaterally) and started on prednisolone and cyclopentolate. Two months later, he developed a branch retinal artery occlusion in the right eye (vision 20/70) and bilateral ocular hypertension for which timolol-brimonidine and dorzolamide were added. Neuroimaging and hypercoagulability workup was unremarkable. Vision and intraocular pressure improved, while uveitis remained recalcitrant. Several months later, the patient developed central serous retinopathy in the right eye (vision 20/30). Prednisone was stopped but restarted due to methotrexate intolerance. A month later, he reported dizziness and was diagnosed with severe bilateral sensorineural hearing loss. Brain magnetic resonance imaging showed foci of perivascular, subcortical, and cochlear enhancement. Transtympanic Decadron injections and infliximab infusions were initiated. At the final visit, vision remained at 20/30 with trace anterior chamber reaction bilaterally while on timolol-brimonidine, dorzolamide, and prednisolone. CONCLUSIONS: An idiosyncratic drug reaction should be considered in the differential diagnosis of TINU-atypical Cogan syndrome.

Malignant catarrhal fever in a Red Angus cow.

A 3-year-old cow was presented with bilateral corneal edema, increased respiratory effort, nasal discharge, and pyrexia. Ovine herpesvirus-2 was detected, confirming malignant catarrhal fever (MCF). The findings from this case suggest that MCF should be included in the differential diagnosis of mature cattle with ocular and nasal lesions, especially when sheep are present on the farm.

Fièvre herpétique maligne chez une vache Red Angus. Une vache âgée de trois ans a été présentée avec un œdème cornéen bilatéral, un effort respiratoire accru, un écoulement nasal et de la pyrexie. L'herpèsvirus ovin de type 2 a été détecté, confirmant une fièvre herpétique maligne (FHM). Les constatations de ce cas suggèrent que la FHM devrait être incluse dans le diagnostic différentiel chez le bétail adulte atteint de lésions oculaires et nasales, particulièrement lorsque des moutons sont présents à la ferme.(Traduit par Isabelle Vallières).