Best practices in the treatment of melasma with a focus on patients with skin of color.

BACKGROUND: Melasma is a chronic hypermelanosis of the skin that affects approximately 1% of the global population, predominantly affects women, and is more prevalent in skin of color. Melasma is a common driver for patients with skin of color to seek out a dermatologist for treatment, and ensuring the right approach for these patients is important because some treatments may be associated with adverse side effects. Because of the chronicity of the disease and established psychosocial and emotional impacts, there is a large need to ensure care follows the best available evidence on the treatment of patients with melasma. OBJECTIVE: Here, we summarized current available topical treatments for melasma with considerations dermatologists should have for their patients with skin of color. METHODS: Steering committee consensus on clinical best practices. RESULTS: We describe a flexible and focused treatment algorithm that reflects both treatment and maintenance periods that is a consensus of our extensive clinical experience. LIMITATIONS: Use of real-world evidence and potential for individual practice bias. CONCLUSION: Melasma can be challenging to treat, particularly in patients with skin of color, and our recommendations for best practices for patients in the United States are an important step toward standardizing care.

Hypotony Maculopathy Associated With Extruded Fluocinolone Acetonide Intravitreal Implant.

This case report discusses a diagnosis of hypotony maculopathy associated with extrusion of a fluocinolone intravitreal implant in a patient who presented with painless, decreased vision in the right eye.

PSEUDOMONAS ENDOPHTHALMITIS AFTER 0.59 MG FLUOCINOLONE ACETONIDE SURGICAL IMPLANT IN A PATIENT WITH A LONG-STANDING CRAWFORD TUBE.

PURPOSE: The purpose of this study was to report a case of Pseudomonas aeruginosa endophthalmitis after surgical 0.59 mg fluocinolone acetonide implant in a patient with a long-standing Crawford tube. METHODS: This was a retrospective case review. RESULTS: A 52-year-old woman with a history of bilateral sarcoid-associated panuveitis and nasolacrimal duct obstructions treated with dacryocystorhinostomies and long-standing Crawford tubes underwent placement of a surgical fluocinolone acetonide implant. The Crawford tube was visible throughout the surgery and notably exhibited small amounts of rotation and prolapse with manipulation of the eye. On postoperative Day 4, the patient presented urgently with pain and decreased visual acuity. Endophthalmitis was suspected, and a vitreous tap and intravitreal injections of vancomycin and amikacin were performed. Cultures grew P. aeruginosa. Initially she responded to treatment with no evidence of intraocular infection or inflammation by postoperative Week 3. However, at postoperative Week 4, the patient returned with a yellow purulent subconjunctival nodule and surrounding scleral injection. A second nodule appeared 2 weeks later. The patient was treated with topical and systemic antibiotics. The nodules responded well to treatment showing notable consolidation and revealing an area of scleral thinning as they regressed. CONCLUSION: We present a case of P. aeruginosa endophthalmitis and presumed scleritis after the surgical fluocinolone acetonide implant placement in an eye with a Crawford nasolacrimal tube effectively treated with topical, intravitreal, and systemic antibiotics. Long-standing nasolacrimal duct hardware may allow reflux of nasopharyngeal and nasolacrimal bacteria, contaminating the ocular surface during surgery.

Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy.

Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is a debilitating health condition which is a result of degeneration of peripheral nerves found in extremities. Currently, there are no established treatment methods that can prevent or protect from PIPN. Fluocinolone acetonide (FA) has been recently identified as a potential candidate for protection from PIPN. However, the fundamental mechanism of action is still unknown. In this study, we showed that enhanced anterograde mitochondrial movement in dorsal root ganglion (DRG) cells has a major role in FA-mediated neuroprotection in PIPN. In this study, cells were treated with PTX or FA along with their combination followed by mitochondrial fluorescence staining. Somal (proximal) and axonal (distal) mitochondria were selectively stained using a microfluidic compartmentalized chamber with different MitoTrackers blue and red, respectively, which we termed, the two-color staining approach. Results revealed that axons were protected from degeneration by the PTX effect when treated along with FA. PTX exposure alone resulted in low mitochondrial mobility in DRG cells. However, cotreatment with PTX and FA showed significant enhancement of anterograde trafficking of somal (proximal) mitochondria to distal axons. Similarly, cotreatment with FA restored mitochondrial mobility significantly. Overall, this study affirms that increasing mitochondrial recruitment into the axon by cotreatment with FA can be a worthwhile strategy to protect or prevent PIPN. The proposed two-color staining approach can be extended to study trafficking for other neuron-specific subcellular organelles.

Perspectives of topical formulations for melasma.

Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.

Elevated Intraocular Pressure Associated With Anterior Chamber Migration of Fluocinolone Acetonide Implant 1 Year After Administration.

This case report describes the migration of a fluocinolone acetonide implant to the anterior chamber 1 year after it was placed.

Use of fluocinolone acetonide intravitreal implant to manage chronic panuveitis for long-term inflammatory control without interfering with systemic immunity.

We report 2 patients with chronic panuveitis who were treated with fluocinolone acetonide intravitreal implant (Yutiq, EyePoint Pharmaceuticals Inc, Watertown, MA) intended to control ocular inflammation long term without interfering with systemic immunity. The first case was a man in his 50s referred for ocular complaints in the setting of ongoing immunotherapy for the treatment of metastatic melanoma. He was diagnosed with bilateral drug-induced panuveitis. Treatment objectives were outlined as reduction of inflammation, prevention of uveitis recurrence, and continuation of systemic immunomodulatory therapy in order to maintain malignancy remission; the patient was treated with fluocinolone acetonide intravitreal implant bilaterally and at 18 months' follow-up had 20/20 bilateral visual acuity and no inflammation. In case 2, a woman in her 70s, presented with a 2-month history of worsening floaters and blurry vision. She was phakic, with bilateral nuclear sclerotic cataracts, 1+ vitreous cells and 2+ haze, diffuse vasculitis, and central leakage around the optic nerve and posterior pole. She was diagnosed with bilateral idiopathic panuveitis with retinal vasculitis. The patient continued to do well at 1 year following intravitreal implantation with fluocinolone acetonide.

Comparative Efficacy Of 35% Glycolic Acid Peel vs. Jessner Peel as an Adjuvant to Topical Triple Combination (2% Hydroquinone, 0.025% Tretinoin, 0.01% Fluocinolone Acetonide) Therapy in Melasma Females Cases.

Melasma is a common, acquired, circumscribed hypermelanosis of sun-exposed skin. It presents as symmetric, hyperpigmented macules having irregular, serrated, and geographic borders. Compare the efficacy of 35% gycolic acid (GA) peel vs. Jessner peel (JP) as an adjuvant to topical triple combination (2% Hydroquinone, 0.025% tretinoin, 0.01% Fluocinolone acetonide) therapy in Melasma in females. Sixty cases of Melasma attending Skin-VD OPD, Baroda Medical College from September 1, 2016 to July 30,/2017 were enrolled. Among them, 12% cases had history of menstrual irregularity, 5% cases had past history of oral contraceptive (OC) pill intake, and 10% cases had history of working outdoors. Most common pattern of melasma was centrofacial 32 cases (53%) which was followed by malar pattern in 27 cases (47%) and mandibular pattern in one case (2%). Fifty cases who completed study were evaluated for comparative efficacy of GA peel versus JP as an adjuvant to topical triple combination therapy. Average reduction in Melasma Area and Severity Index (MASI) score in cases treated with GA peel group was 58.56% with Jessner peel group was 59.12%. In GA peel group, 84% cases had moderate to good improvement, whereas in JP group 92% cases had moderate to good improvement. According to present study, safety and efficacy profile of 35% GA peel vs. JP was almost same. Both can be used as an adjuvant to topical triple combination therapy of 2% hydroquinone, 0.025% tretinoin, and 0.01% fluocinolone acetonide in females suffering from melasma. We recommend that it will be safer for the pregnant women to get the GA peel rather than the treatment containing hydroquinone and tretinoin since the activity/performance is very similar.

Study of oral tranexamic acid, topical tranexamic acid, and modified Kligman's regimen in treatment of melasma.

BACKGROUND: Melasma is a pigmentary disorder affecting mainly face . Various treatment modalities available as topicals, superficial chemical peels and lasers but none till date gives promising results, until date quest for the best treatment modality is on. AIM: To study the effect of oral and topical Tranexamic acid (TXA) and modified Kligman's regimen in treatment of melasma. METHOD: Patients having melasma were enrolled after consent for voluntary participation. A detailed history and clinical examination was done. Total 60 patients were enrolled and randomized in three groups, 20 received oral TXA 250 mg twice daily, 20 topical TXA and 20 received modified Kligman's regimen for 8 weeks along with sunscreen MASI(Melasma area severity index) was calculated at baseline, at end of 4 & 8 weeks. MASI score was compared with that at the end of the study. Based on reduction in mean MASI the therapeutic response was graded. Pre and post treatment photographs was also compared. Statistical analysis done by using student square T test , ANOVA And TUKEY test. RESULTS: Reduction in MASI score was observed in all the groups but greater reduction in MASI score with modified Kligman's regimen by 30% followed with oral TXA by 25% reduction and least with topical TXA by 5%. CONCLUSION: Although modified Kligman's regimen is comparatively more efficient but due to its side effects in long term usage oral tranexamic acid could be a promising therapeutic approach for melasma.

Topical metformin in the treatment of melasma: A preliminary clinical trial.

BACKGROUND: Melasma is a common acquired pigmentary disorder characterized by symmetric hyperpigmented macules on the face. Triple combination cream (TCC) remains the gold standard treatment but its prolonged use often causes adverse effects. Recently, studies have shown that topical metformin has melanopenic action. AIMS: To evaluate the safety and efficacy of topical metformin in the treatment of melasma and to compare its efficacy with TCC (hydroquinone 2% + tretinoin 0.025% + fluocinolone acetonide 0.01%). METHODS: This was a randomized controlled study conducted on 40 patients with melasma aged more than 18 years. Patients in group 1 (n = 20) were treated with 30% metformin lotion, whereas group 2 patients (n = 20) were treated with TCC for 8 weeks. Pigmentation was assessed using Melasma Area and Severity Index (MASI) at baseline and after 8 weeks. Outcome measures included global improvement scale (grades 1-4) and patient satisfaction. Safety was assessed according to adverse events and patch testing. RESULTS: All 40 patients completed the study. Out of 20 patients in group 1, 11 showed grade 1 improvement (1% to <25%) and grade 2 (25%-50%) and grade 3 (>50%-75%) improvements were seen in one patient each. In group 2, grades 1, 2, 3, and 4 improvements were seen in 14, 2, 1, and 1 patients, respectively. However, the difference was not statistically significant. Adverse events were noted in three patients in group 2 and none in group 1. CONCLUSION: Topical metformin is a novel, safe, and almost as effective modality as TCC to treat melasma.

Indicators of Post-Operative Intraocular Pressure Elevation after Naïve Fluocinolone Acetonide Surgical Implantation.

PURPOSE: To determine factors conferring an increased risk of developing ocular hypertension secondary to the fluocinolone acetonide (FA) sustained-release surgical implant (Retisert). DESIGN: Retrospective, observational case series. METHODS: Patients with a history of chronic noninfectious posterior uveitis undergoing naïve surgical FA implantation from 2007 to 2018 at the University of Colorado were studied. Patient demographics and multiple clinical measures were noted one year before and after FA implantation. RESULTS: Twenty-nine eyes of 21 patients were studied. The median age experiencing an IOP rise vs median age experiencing no IOP rise post-FA implantation was 27.0 and 54.0 years old, respectively (p = .01). A pre-FA implant risk factor of needing future glaucoma surgery after FA implantation is prior to maximum IOP (p = .02). CONCLUSIONS: A risk factor of elevated post-FA implantation IOP includes younger age. A potential risk factor for glaucoma surgery after FA implantation was higher maximum IOP before FA implantation.

Treatment of Acute Zonal Occult Outer Retinopathy With Intravitreal Steroids.

BACKGROUND AND OBJECTIVE: To report on the use of intravitreal steroids in the management of acute zonal occult outer retinopathy (AZOOR), a rare disorder affecting the outer retina. PATIENTS AND METHODS: Retrospective case series of nine eyes of five patients with AZOOR who received intravitreal triamcinolone acetonide (IVTA), dexamethasone intravitreal implant, and/or fluocinolone acetonide implant. Treatment response was determined by reported symptoms and multimodal imaging findings. Patients were observed for at least 1 year following intravitreal steroid treatment (range: 14 months to 63 months). RESULTS: Seven eyes received IVTA, six eyes received the dexamethasone intravitreal implant, and one eye received the fluocinolone acetonide implant. All patients experienced disease stability or improvement based on symptomatic response and multimodal imaging findings after intravitreal steroids. One eye developed central serous retinopathy, and another eye a choroidal neovascular membrane. Five of nine eyes experienced ocular hypertension. All phakic eyes developed cataracts. CONCLUSION: Intravitreal steroids effectively achieved disease stability in patients with AZOOR. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:504-509.].

ILUVIEN® technology in the treatment of center-involving diabetic macular edema: a review of the literature.

Diabetic macular edema (DME) is one of the major causes of blindness, caused primarily by hyperglycemia and results from multiple pathological processes mostly secondary to increased levels of VEGF and other inflammatory cytokines. DME management includes control of systemic risk factors together with laser photocoagulation, frequent intraocular injections of anti-VEGF agents and steroids implants. Recent adoption of novel alternative drug delivery options has led to the development of sustained release ocular implants with longer duration of action with less injection frequency. This article will review the pharmacology and clinical data in terms of efficacy, safety and benefits of the sustained release steroid implants in treatment of DME with special emphasis on the fluocinolone acetonide ILUVIEN® implant.

Fluocinolone acetonide for the treatment of diabetic macular edema.

INTRODUCTION: Fluocinolone acetonide intravitreal implant is a non-erodible implant approved for the treatment of diabetic macular edema (DME) insufficiently responsive to available therapies. Areas covered: The injectable intravitreal implant releases fluocinolone acetonide at an average rate of 0.2 µg/day for at least 36 months. The two pooled pivotal FAME trials showed that, in patients with DME previously treated with laser photocoagulation, fluocinolone acetonide intravitreal implant was more beneficial than sham injection when looking at the proportion of patients with an improvement from baseline in visual acuity of more than 15 letters at 24 months and at 36 months. Cataract (82%) and intraocular pressure (IOP) elevation (37%) were the most common adverse events. Raised IOP was mostly treated with IOP-lowering medications, with <5% of eyes requiring incisional IOP-lowering surgery. FAME trial program results are confirmed by a series of real-world studies in eyes with chronic/recalcitrant DME. Expert opinion: data indicate that fluocinolone acetonide intravitreal implant is a useful second-line option for the treatment of DME.

Association Between Long-Lasting Intravitreous Fluocinolone Acetonide Implant vs Systemic Anti-inflammatory Therapy and Visual Acuity at 7 Years Among Patients With Intermediate, Posterior, or Panuveitis.

IMPORTANCE: A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known. OBJECTIVE: To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis. DESIGN, SETTING, AND PARTICIPANTS: Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016). INTERVENTIONS: Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated. MAIN OUTCOMES AND MEASURES: Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death. RESULTS: Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%). CONCLUSIONS AND RELEVANCE: In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00132691.

A Nonrandomized, Open-Label, Multicenter, Phase 4 Pilot Study on the Effect and Safety of ILUVIEN® in Chronic Diabetic Macular Edema Patients Considered Insufficiently Responsive to Available Therapies (RESPOND).

PURPOSE: The aim of this study was to assess the effectiveness and safety of ILUVIEN® in patients with chronic diabetic macular edema (DME) who were insufficiently responsive to prior therapies. METHODS: This is a prospective, nonrandomized, multicenter, open-label, phase 4 pilot study assessing the effectiveness and safety of ILUVIEN® involving 12 patients insufficiently responsive to available therapies. Assessments were performed at screening, baseline, week 1, and months 1, 3, 6, 9, and 12. Demographics, medical/ophthalmic history, prior laser, anti-VEGF, and steroid treatments, and lab tests were recorded at screening. A complete ophthalmic examination and SD-OCT were performed at screening and at all follow-up visits. RESULTS: The patients showed improvements in best-corrected visual acuity (+3.7 letters), with greater improvement among pseudophakic patients (+6.8 letters) compared with phakic patients (-2.5 letters) 12 months after ILUVIEN®. The mean central subfield thickness decrease from baseline to month 12 was statistically significant, with a rapid reduction in the first week. Regarding safety, only 2 patients showed an intraocular pressure (IOP) increase over 25 mm Hg during the study, and the rise in IOP was well managed with eye drops only. CONCLUSIONS: This prospective and pilot study suggests that ILUVIEN® is safe and may be considered effective for chronic DME patients insufficiently responsive to other available therapies as it showed a rapid and sustained improvement of macular edema obtained after treatment with ILUVIEN®.

Report of 12-months efficacy and safety of intravitreal fluocinolone acetonide implant for the treatment of chronic diabetic macular oedema: a real-world result in the United Kingdom.

PurposeTo report the 12-months visual and anatomical outcomes of chronic diabetic macular oedema (DMO) treated with ILUVIEN in a real-world clinical practice in a single tertiary referral centre.MethodRetrospective data collection and analysis of consecutive 28 eyes of 23 diabetic patients received ILUVIEN implant for refractory DMO. Standard assessment included visual acuity (VA), central retinal thickness (CRT), slit-lamp biomicroscopy, and Goldmann tonometry for intraocular pressure (IOP) at 1, 6, and 12 months.ResultsBaseline mean VA was 47 (SD 18) letters improved to 55 (SD 17) letters (P=0.004) at 12 months. VA was improved in 16 eyes (57%), stabilised in 9 eyes (32%), and decreased in 3 eyes (11%). Seven eyes (25%) gained ≥15 letters, and 10 eyes (36%) gained >10 letters from baseline. The percentage of eyes achieved driving vision (≥70 Early Treatment Diabetic Retinopathy Study letters) was doubled from baseline 18 to 36% at 6 months and 32% at 12 months. Mean CRT decreased by 198 µm from baseline 494 µm (SD 191) to 296 µm (SD 121) at 12 months (P<0.001). Two eyes received additional anti-vascular endothelial growth factor injections after 10 months. COMPLICATIONS: Raised IOP in three eyes (11%) controlled with IOP-lowering drops, vitreous haemorrhage in one eye and one endophthalmitis (1 year vision improved to 6/24).ConclusionOur real-world results show that the visual and the anatomical improvements achieved by a single ILUVIEN implant injection were maintained up to 12 months with minimal adjunctive therapy. IOP monitoring remains essential in ILUVIEN patients, although our study shows a relatively low risk of IOP elevation post ILUVIEN injection, even in existing controlled ocular hypertension. Our results demonstrate that ILUVIEN is an effective long-term option in treating chronic refractory DMO.