Comparative Study of Combination of Oral Tranexamic Acid with Modified Kligman’s Formula Versus Oral Tranexamic Acid with Azelaic Acid 15% in the Treatment of Melasma

Background: Melasma refers to acquired hyper-pigmentary condition effecting skin. Owing to its multifactorial causation and chronicity, there is an increased need for new multimodality therapies to treat melasma more effectively and to prevent the side effects seen with the conventional modalities of treatment. Objectives: Compare efficacy of combining oral Tranexamic Acid and Azelaic Acid 15% with that of Oral Tranexamic Acid (TA) and Modified Kligman’s Formula. Also, to record any adverse effects of combining these agents. Methods: Patients having Melasma who will be coming to Dermatology OPD, AVBRH, Sawangi, Wardha, will be enrolled after considering the various inclusion and exclusion criteria. A detailed history will be asked, which will be followed by a cutaneous examination that includes the calculation of MASI (Melasma Area and Severity Index). One Group (A) - participants will receive - Oral 500 mg Tranexamic acid OD plus Modified Kligman’s Formula (fluocinolone acetonide 0.01%, tretinoin 0.05%, and hydroquinone 2%) cream one time at night only. Second Group (B)- participants will receive - Oral 500 mg Tranexamic Acid OD plus Azelaic Acid 15% gel once daily at night only. Both groups will also receive Broad-spectrum sunscreen SPF-30 daily (3 hourly). Patients will be called for regular follow up at 4 weeks and 8 weeks (for early results). Clinical photos will be clicked at every follow-up visit and MASI score shall be doocumented. Expected Results: To analyze efficacy of combining Oral TA along with Azelaic Acid 15% and if it provides better results, we can avoid the undesirable side effects that are seen on prescribing the Modified Klingman’s Formula, in Melasma patients. Conclusion: This study will help us in analyzing efficacy of combining Oral TA with Azelaic Acid 15%, therefore will provide a newer treatment modality with lesser side effects and maybe better results than the gold standard- Modified Klingman’s Formula.

Intravitreal fluocinolone acetonide implant for the treatment of persistent post-surgical cystoid macular edema in vitrectomized eyes

Cystoid macular edema (CME) is the most common cause of decreased visual acuity after both vitrectomy and cataract surgery. Various strategies have been used for its treatment, such as intravitreal corticosteroids. The intravitreal fluocinolone acetonide implant (Iluvien®) is approved for the treatment of persisting diabetic macular edema and for the prevention of recurrence of non-infectious uveitis affecting the posterior segment. There are very few reports about its off-label use for post-surgical CME. We present four clinical cases of post-surgical CME (three following vitrectomy and one following cataract surgery in a vitrectomized eye 2 years ago). All of them had been previously treated with an average of four injections of intravitreal dexamethasone implant (Ozurdex®), with repeated recurrence of CME. After treatment with Iluvien, three cases showed improvement of both visual acuity and macular anatomy, with resolution of the macular edema. One patient required additional treatment with Ozurdex during follow-up, further improving CME. Two of the cases required topical pressure lowering treatment, and none required filtering surgery. Iluvien could be an effective therapeutic option for persistent non-diabetic macular edema after vitrectomy or cataract surgery refractory to other intravitreal therapies, with the benefit of being able to provide longer recurrence-free periods.

Clinical Outcome and Drug Expenses of Intravitreal Therapy for Diabetic Macular Edema: A Retrospective Study in Sardinia, Italy

Background: Diabetic macular edema (DME) is a leading cause of visual loss in working-age adults. The purpose of this retrospective study was to perform an epidemiological analysis on DME patients treated with intravitreal drugs in a tertiary hospital. The clinical outcome, adverse drug reactions (ADRs), and intravitreal drug expenses were assessed. Methods: All DME patients treated with Ranibizumab, Aflibercept, Dexamethasone implant, and Fluocinolone Acetonide implant at the Sassari University Hospital, Italy, between January 2017 and June 2020 were included. Central macular thickness (CMT) and best corrected visual acuity (BCVA) were measured. ADRs and drug expenses were analyzed. Results: Two-hundred thirty-one DME patients (mean age: 65 years) received intravitreal agents. Mean CMT and BCVA were 380 μm and 0.5 LogMAR at baseline, 298 μm and 0.44 logMAR after one year (p = 0.04), and 295 μm and 0.4 logMAR at the end of the follow-up period. A total of 1501 intravitreal injections were given; no major ADRs were reported. Treatment cost was €915,000 (€261,429/year). Twenty non-responders to Ranibizumab or Aflibercept were switched to a Dexamethasone implant. In these patients, mean CMT and BCVA were 468 µm and 0.5 LogMar at the time of switching and 362 µm and 0.3 LogMar at the end of the follow-up (p = 0.00014 and p = 0.08, respectively). Conclusion: Results confirm that Ranibizumab, Aflibercept, and Dexamethasone implant are effective and safe in DME treatment. A switch to Dexamethasone implant for patients receiving Aflibercept or Ranibizumab with minimal/no clinical benefit should be considered.

Fluocinolone Implant for Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis Syndrome: A Case Report

Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is a rare and progressive disorder that predominantly affects both the eyes of young female individuals and can threaten visual function. Peripheral ischemia and macular exudation are common findings in patients. The treatment options include panretinal photocoagulation (PRP), systemic immunosuppression, and intravitreal antiangiogenic and corticosteroid therapy. Fluocinolone acetonide intravitreal implant is approved for the treatment of nonanterior noninfectious uveitis and diabetic macular edema (ME), with an estimated therapeutic duration of 3 years. We describe a case of IRVAN syndrome in a child with ME who had been previously treated with PRP, antiangiogenic therapy, and several dexamethasone intravitreal implants and received a fluocinolone acetonide intravitreal implant in her right eye. The patient showed stabilization of the visual acuity and a marked reduction of the macular thickness 1 month after the treatment. At 12-month follow-up, the patient required perifoveal focal photocoagulation due to a rebound of the ME. After 2 years of follow-up, visual acuity remains stable and macular retinal thickening under control. Local long-standing steroid therapy has proved to be quite efficient in controlling the progression of the disease in our patient.

Two Validated Chromatographic Methods for Determination of Ciprofloxacin HCl, One of its Specified Impurities and Fluocinolone Acetonide in Newly Approved Otic Solution

Two sensitive, selective and precise chromatographic methods have been established for concomitant quantification of ciprofloxacin HCl (CIP), fluocinolone acetonide (FLU) along with ciprofloxacin impurity A (CIP-imp A). The first method was thin-layer chromatography (TLC-densitometry) where separation was accomplished using TLC silica plates 60 G.F254 as a stationary phase and chloroform–methanol–33%ammonia (4.6:4.4:1, by volume) as a developing system. The obtained plates were scanned at 260 nm over concentration ranges of 1.0–40.0, 0.6–20.0 and 1.0–40.0 μg band−1 for CIP, FLU and CIP-imp A, respectively. The second method was based on high-performance liquid chromatography using a Zorbax ODS column (5 μm, 150 × 4.6 mm i.d.) where adequate separation was achieved through a mobile phase composed of phosphate buffer pH 3.6–acetonitrile (45:55, v/v) at flow rate 1.0 mL min−1 with ultraviolet detection at 254 nm. Linear regressions were obtained in the range of 1.0–40.0 μg mL−1 for CIP, 0.6–20.0 μg mL−1 for FLU and 1.0–40.0 μg mL−1 for CIP-imp A. The suggested methods were validated in compliance with the International Conference on Harmonization guidelines and were successfully applied for determination of CIP and FLU in bulk powder and newly marketed otic solution.

A Novel Approach to Assess the Potency of Topical Corticosteroids

The potencies of topical corticosteroid products have mainly been classified using clinical data but in some instances, the US Food and Drug Administration’s (FDA’s) vasoconstrictor assay (VCA) to assess the skin blanching response has also been used. However, the reported skin blanching response data were often based on a single visual reading and lack information on the dose (amount/quantity) or dose duration. Although several lists classifying potencies of various topical corticosteroid products have been published, the inherent potencies of topical corticosteroid raw materials used as active pharmaceutical ingredients (APIs) have not been investigated. The objective was to rank the inherent potencies of topical corticosteroid APIs and to standardize dosing such that the relevant compounds could be compared on a normalized molar basis. The potencies of clobetasol propionate, halcinonide, mometasone furoate, and fluocinolone acetonide were compared using the resulting Emax data following the fitting of the relevant response data to the Emax model where mometasone furoate > fluocinolone acetonide = clobetasol propionate > halcinonide. This ranking lists the respective inherent potencies of the APIs, which will facilitate the choice of a suitable candidate for incorporation into an appropriate topical corticosteroid product for a specific clinical indication.

Intravitreal 0.19 mg Fluocinolone Acetonide Implant in Non-Infectious Uveitis

The efficacy of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN) in the treatment of non-infectious uveitic macular edema (UME) was assessed on twenty-six patients (34 eyes) with non-infectious UME between 2013 and 2020, in a mean follow-up of 18 ± 19.3 (mean ± SD) months. Macular edema was resolved in 24 (70.6%) cases. Five of these eyes had a relapse after 23.2 ± 14 months. Three FAc reinjections were performed and a drying of the macula was observed. After FAc implantation, 24 eyes (70.6%) were completely dry; central retinal thickness (CRT) decreased in 6 eyes (17.6%), but residual intraretinal fluid was still evident. In 20 eyes (58.5%), visual acuity (VA) improved (from +1 to +5 lines) and remained stable in 9 eyes (26.5%). Thirty eyes (88.2%) were pseudophakic at baseline and four were phakic. Three of these eyes had a cataract prior to therapy and the other developed a cataract 2.5 years after the FAc implant was administered. There was an overall increase in intraocular pressure (IOP; +4.4 ± 3.7 mmHg) and eye drops were required in three eyes. The FAc implant led to long-term improvements in mean CRT and VA, and that the side-effect profile was manageable in a clinical setting in patients with non-infectious UME.