Multiple Topical Treatments Research Articles

Systematic review of ocular surface treatments in the setting of thyroid eye disease.

Approximately 85% of patients with thyroid eye disease experience ocular surface symptoms. Although corneal exposure plays a role in inducing inflammatory changes to the ocular surface, multiple studies reveal more complexity to the abnormal tear film composition and parameters in thyroid eye disease patients including those who do not have proptosis or increased corneal exposure. Currently, a majority of cases of thyroid associated dry eye symptoms are given treatments intended for ocular surface disease arising from different etiologies. Medline via Ovid, Cochrane CENTRAL, PubMed, and Google Scholar were systematically searched for articles evaluating the efficacy of treatments for dry eye symptoms in patients with thyroid eye disease. Articles were from all geographic regions and dates ranged from inception until October 2023. Seven papers ultimately met inclusion criteria and were included in this review. These papers revealed that multiple topical and non-topical treatment modalities address dry eye symptoms in thyroid eye disease and improve subjective and objective ocular surface parameters. However, due to the few studies that exist and due to disparities in sample size and study design, no overwhelming best practices were identified that could influence clinical practice. This systematic review identifies the current treatments that exist and highlights the clear unmet need for a large population suffering with dry eye symptoms. Ideally, further well-designed investigations into this area would target topical, non-invasive modalities to develop first line options for thyroid eye disease patients.

Topical treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials

BackgroundAtopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. ObjectivesWe systematically synthesized the benefits and harms of AD prescription topical treatments. MethodsFor the 2023 AAAAI/ACAAI JTFPP AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT to September 5, 2022 for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-quality of life, flares, and harms. The GRADE approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using seven classes—group 1 being most potent. OSF: https://osf.io/q5m6s. Results219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty, pimecrolimus improved six of seven outcomes—among the best for two; high-dose tacrolimus (0.1%) improved five—among the best for two; low-dose tacrolimus (0.03%) improved five—among the best for one. With moderate-to-high certainty, group 5 TCS improved six—among the best for three; group 4 TCS and delgocitinib improved four—among the best for two; ruxolitinib improved four—among the best for one; group 1 TCS improved three—among the best for two. These interventions did not increase harms. Crisaborole and difamilast were intermediately effective, but uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. ConclusionsFor individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.

Tolerance ofBiopronil Spot on® after repeated single- ormultiple-dose topical treatments indogs.

Avariety oftoxic effects offipronil (FIP), the active substance ofBiopronil Spot on®, onanimals and humans has been reported and raises the need toinvestigate the FIP toxic effects. The objectives ofthe study were the evaluation ofthe local and systemic tolerance ofBiopronil Spot on® and the assessment ofits influence onhaematological and biochemical blood parameters after single and multiple topical treatment indogs. Thirty-two mixed breed dogs were included inthe study assessing the local and general tolerance ofBiopronil Spot on® following single, triple and fivefold dose after spot-on multiple applications indogs (on days0, +28 and +56) atadosage 134mg for adog weighing 10-20kg and 268mg for adog weighing 21-40kg. Aphysical examination and biochemical and haematological analyses were performed onthe days ofthe study asfollows: -14, -5, +3, +31, +59, +70. Novisible pathological changes onthe skin were observed. The biochemical and haematological indicators rarely exceeded the reference values. Noinfluence ofBiopronil Spot on® administered insingle, triple and fivefold repeated doses onthe assessed clinical, haematological and biochemical parameters indogs was found under the conditions described inthe study.

Characterization and Potential Mitigation of Corneal Effects in Nonclinical Toxicology Studies in Animals Administered Depatuxizumab Mafodotin.

Purpose: To characterize the ocular toxicity of an antibody-drug conjugate (ADC), depatuxizumab mafodotin (Depatux-m), in nonclinical species and to evaluate the effects of drug-antibody ratios (DARs), variations of the ADC construct, and potential methods for mitigation of the corneal toxicity. Depatux-m contains the potent cytotoxic agent monomethyl auristatin F as the ADC payload. Methods: Depatux-m was administered intravenously to cynomolgus monkeys at doses up to 30 mg/kg and to mice up to 100 mg/kg. Ocular toxicity was evaluated by clinical ophthalmic examinations and histopathology. Potential mitigation was tested through agents to block target engagement and multiple topical ophthalmic treatments (antioxidant, vasoconstrictor, tear stimulant). Results: Effects primarily involved corneal epithelium and were dose-dependent with respect to onset, severity, and time to reversal in both monkeys and mice. On slit lamp biomicroscopy, the initial effect in monkeys was superficial multifocal punctate opacities (granularity), which migrated axially and were followed by pigmentation and multifocal punctate fluorescein staining. Microscopically, findings were characterized by single-cell necrosis, pigmentation, disordered basilar layer, and thinning of the corneal epithelium. Increased toxicity was associated with a higher DAR or more stably attached linker. Treatment with agents to block target engagement did not affect toxicity, and none of the topical treatments was successful. Conclusions: The corneal findings observed were similar to the effects described in clinical trials with Depatux-m and other ADCs. Collectively, these studies and available literature support the hypothesis that ADC-mediated toxicity is driven primarily by mechanism of action of the payload.

Contact allergy mimicking trench foot infection: a case study

Hard-to-heal wounds are a major cause of morbidity and/or mortality. Multiple aetiologies can be identified and wounds can be treated according to their aetiology and macroscopic appearance. However, evidence behind the wide range of locally applied treatments is weak, without clear guidelines available to treat a variety of wound aetiologies. We present the case of a 63-year-old male with hard-to-heal wounds not responding to standard topical treatment. No clear underlying aetiology could be found. Extensive contact allergies were diagnosed after multiple topical and systemic treatments had been applied. A full recovery was observed after stopping topical agents and treating the wounds with an alternative treatment based on epicutaneous test results.

The management of neurotrophic keratitis.

The management of neurotrophic keratitis (NK) has evolved in the last decade. The present article reviews updated management guidelines of this entity, as well as future innovations in the field. The advent of confocal microscopy has allowed for the first time to image corneal nerves. In addition, multiple novel topical treatments such as nerve growth factor have improved the prognosis of this disease, with many other in the pipeline. Finally, corneal nerve restoration is now possible with corneal neurotization procedures. Many novel treatments based on agents that stimulate nerve regrowth are now available to treat NK. Improvement in neurotization procedures could also address advanced stages of this disease with surgery.

A European field assessment of the efficacy of fluralaner (Bravecto\xae) chewable and spot-on formulations for treatment of dogs with generalized demodicosis

BackgroundRecent reports indicate that the isoxazoline compounds have the potential to provide safe and effective treatment of canine generalized demodicosis, a condition that has been traditionally difficult to cure. Controlled field studies are needed to confirm this potential. A study was therefore initiated to investigate the efficacy of a single oral or spot-on treatment with fluralaner, an isoxazoline, compared with multiple topical treatments with imidacloprid-moxidectin, in dogs naturally affected by generalized demodicosis.MethodsVeterinary clinics in 5 European countries enrolled 134 dogs diagnosed with generalized demodicosis. Dogs were randomized to treatment with either fluralaner chewables, fluralaner spot-on, or topical imidacloprid-moxidectin in a 2:2:1 ratio. Both fluralaner formulations were administered once, at the approved dose rate, on Day 0. Imidacloprid-moxidectin was administered per label on Day 0, and every 4 weeks, more frequently if necessary. At each visit (Days 0, 28, 56, 84), dogs were monitored for demodectic mites using deep skin scrapings and observed for health and for severity of skin lesions. Treatment was considered efficacious if more than 90% of the dogs were free of live mites at both Days 56 and 84.ResultsOf 124 dogs completing the study, 57 were diagnosed with juvenile-onset demodicosis and 67 with the adult-onset form. A single treatment with oral or spot-on fluralaner was efficacious, each eliminating mites from at least 98.0% of treated dogs on Days 56 and 84. Against juvenile-onset demodicosis, efficacy of the oral and spot-on formulations was 96.0% and 100%, respectively, and against adult-onset demodicosis 100% and 96.7%. Multiple administrations of imidacloprid-moxidectin were not efficacious, eliminating mites from 87.5% of dogs (92.0% with juvenile-onset demodicosis cured; 81.8% with adult-onset demodicosis). All groups showed a marked reduction in skin lesions by Day 28, with continuing clinical improvement at each subsequent visit through Day 84. There were no treatment-related adverse events.ConclusionsA single administration of fluralaner chewables or fluralaner spot-on is highly effective against with juvenile-onset and adult-onset forms of generalized canine demodicosis. Topically applied imidacloprid-moxidectin at weekly to monthly intervals over the 84-day study did not achieve the proportion of mite-free dogs required to demonstrate efficacy.

Correction

[This corrects the article DOI: 10.7759/cureus.7419.].

Hormonal modulation of reproduction in Polistes fuscatus social wasps: Dual functions in both ovary development and sexual receptivity

Hormones are often major regulators of complex behaviors, such as mating and reproduction. In insects, juvenile hormone (JH) is integral to many components of reproductive physiology and behavior, but its role in female sexual receptivity is not well understood. To investigate the influence of JH on receptivity, we utilized the social wasp Polistes fuscatus. In Polistes, mating behavior is temporally separated from other components of reproduction, which allows for examination of the physiology and behavior of mating, disentangled from fertilization and egg-laying. We reared virgin gynes (reproductive females) in the lab and divided them into four groups, in which gynes received multiple topical treatments of either 20 μg, 10 μg, 5 μg, or 0 μg of the JH analog methoprene. Gynes were then placed in petri dishes with 2 unrelated males and we recorded attempted and successful mating. Additionally, we measured gyne ovarian development and survival in each group. We found that methoprene increased both sexual receptivity and ovarian development, but was associated with a decrease in long-term survival. Receptivity increased linearly as methoprene treatment increased, but the effect of methoprene on ovarian development was independent of dose. These results demonstrate the importance of JH in sexual receptivity and mating behavior. We argue that the relatively understudied Polistes gyne has potential as a model for mating and reproduction, and for the internal and external regulation of this complex behavior.

Treatment of elephantiasis nostras verrucosa with CO2laser

Elephantiasis nostras verrucosa (ENV) is the most severe form of chronic non-filarial lymphedema that leads to disfiguration of body parts. Multiple topical and surgical treatments have been typically used with high relapse rates and local complications. In this context, CO2 laser emerges as a new well-tolerated and effective treatment option. We report two cases of long-term evolution of elephantiasis nostras verrucosa recalcitrant to topical therapy and successfully treated with CO2 laser. Both of them were septuagenarians with personal history of obesity and suffered from lower extremities edema due to heart failure in one case, and due to chronic venous insufficiency in the other. We describe the procedure, the results and the advisable maintenance for preventing recurrence in this difficult to treat and chronic condition.

An extracellular matrix graft (Oasis® wound matrix) for treating full-thickness pressure ulcers: A randomized clinical trial

AimThe purpose of the study was to evaluate clinical safety and effectiveness of Oasis® Wound Matrix as a treatment for full-thickness pressure ulcers and compare it to Standard Care. MethodsA total of 130 adults with Stage III or Stage IV pressure ulcers were randomly assigned, received either multiple topical treatments of SIS plus standard care (n = 67), or standard care alone (n = 63), and were subsequently evaluated. Ulcer size was determined at enrollment and weekly throughout treatment. Healing was assessed at each visit for a period of up to 12 weeks, with incidence of complete healing and 90% reduction in ulcer area being the primary outcome measures. ResultsThe proportion of complete healing in the SIS group was 40% as compared to 29% in the standard of care group (p = 0.111); the percentage of patients having a 90% reduction in ulcer surface area was 55% in the SIS group versus 38% in the standard of care group (p = 0.037). ConclusionsThe results of this study suggest that within the setting of a comprehensive wound care program, weekly treatment of chronic pressure ulcers with SIS wound matrix increases the incidence of 90% reduction in wound size versus standard of care alone.

Treatment of Uremic Pruritus: A Systematic Review

Uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by patients. The optimal treatments for uremic pruritus are not well defined. Systematic review. Adult patients with advanced CKD (stage≥ 3) or receiving any form of dialysis. PubMed, CINAHL, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and ClinicalTrials.gov from their inception to March 6, 2017, were systematically searched for randomized controlled trials (RCTs) of uremic pruritus treatments in patients with advanced CKD (stage≥ 3) or receiving any form of dialysis. 2 reviewers extracted data independently. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. Any intervention for the treatment of uremic pruritus was included. A quantitative change in pruritus intensity on a visual analogue, verbal rating, or numerical rating scale. 44 RCTs examining 39 different treatments were included in the review. These treatments included gabapentin, pregabalin, mast cell stabilizers, phototherapy, hemodialysis modifications, and multiple other systemic and topical treatments. The largest body of evidence was found for the effectiveness of gabapentin. Due to the limited number of trials for the other treatments included, we are unable to comment on their efficacy. Risk of bias in most studies was high. Heterogeneity in design, treatments, and outcome measures rendered comparisons difficult and precluded meta-analysis. Despite the acknowledged importance of uremic pruritus to patients, with the exception of gabapentin, the current evidence for treatments is weak. Large, simple, rigorous, multiarm RCTs of promising therapies are urgently needed.

Endophthalmitis Prophylaxis Using a Single Drop of Thermoresponsive Controlled-Release Microspheres Loaded with Moxifloxacin in a Rabbit Model.

PurposePostsurgical endophthalmitis is a sight-threatening problem. We introduce a simple approach by using a single application of thermoresponsive controlled-release microspheres, loaded with moxifloxacin, to prevent bacterial endophthalmitis in a rabbit endophthalmitis prevention model.MethodsWe separated 24 rabbits into 3 treatment groups in which topical drop treatment was placed onto the conjunctival cul-de-sac: (1) a single drop of controlled-release microspheres containing moxifloxacin, (2) a single drop of controlled-release microspheres without moxifloxacin, and (3) multiple topical treatment with moxifloxacin alone every 15 minutes for 1 hour. All rabbits were challenged, 1 hour after microspheres drop placement and immediately after the fifth topical dose of moxifloxacin, with anterior chamber injections of Staphylococcus aureus. Rabbits in the topical moxifloxacin group also were treated after challenge and four additional times over the next 24 hours. After 24 hours, the rabbits were clinically evaluated for endophthalmitis and the animals were euthanized to culture for intraocular S. aureus. The treatment groups were compared statistically for bacterial endophthalmitis.ResultsNo eyes had endophthalmitis, based on clinical presentation and/or positive culture, in the groups with controlled-release microspheres loaded with moxifloxacin (0/8, 0%) or multiple drops of topical moxifloxacin (0/8, 0%). In contrast, 8 of 8 eyes (100%; P = 0.0001), had endophthalmitis among eyes treated with controlled-release microspheres drops without moxifloxacin.ConclusionA single drop of controlled-release microspheres loaded with moxifloxacin was successful in preventing endophthalmitis. Further clinical studies will be required to confirm the full potential of controlled-release anti-infective loaded microspheres to prevent endophthalmitis.Translational RelevanceThis study presents a simple method of prophylaxis to prevent postsurgical endophthalmitis.

Paecilomyces Keratitis: Cases in Korea and Literature Review

Purpose: To analyze the Paecilomyces keratitis cases in Korea and compare cases from foreign literature. Methods: The records of 3 patients diagnosed with Paecilomyces keratitis at our hospital and other reported cases in Korea were evaluated to examine the predisposing factors, clinical aspects, antifungal therapy, therapeutic surgery, and visual outcome and compared with previously reported foreign cases. Results: In Korea, 1 patient was female, 4 patients were male and had predisposing factors including prior corneal trauma or surgery, except 1 spontaneous occurrence. All 5 eyes of 5 patients had poor initial visual acuity, less than finger count, and deep corneal infiltration. The patients were treated with multiple topical and systemic antifungal treatments such as intracameral or intrastromal voriconazole injections and required evisceration and penetrating keratoplasty. However, the final outcomes were unsatisfactory. Previously reported cases from foreign literature also had predisposing factors such as corneal surgery, trauma, and soft contact lens use. They were resistant to antifungal therapy and eventually led to surgeries such as penetrating keratoplasty and the final outcomes were poor. Conclusions: Frequently, Paecilomyces keratitis has direct risk factors and is resistant to many topical and systemic antifungal agents. In the majority of cases, therapeutic surgery was required and the final visual outcomes were poor. When Paecilomyces keratitis is suspected, we suggest aggressive therapy including intracameral and intravitreal injections of voriconazole in the initial treatment. J Korean Ophthalmol Soc 2016;57(3):390-398

Therapeutic sectorial full-thickness sclero-keratoplasty for recurrent fungal keratitis

ObjectiveTo report the management of a severe and recurrent fungal keratitis that required repeated penetrating keratoplasties. Despite multiple topical, intraocular and systemic antifungal treatments, superotemporal hyphal infiltration repeatedly penetrated the corneal transplant causing continuous recurrences. Cultures collected before and during surgery isolated the same organism, Fusarium spp. ConclusionCorneal infection extending to the sclera and internal angle structures is the main cause of recurrence of fungal keratitis after corneal transplantation. Sectorial full-thickness sclero-keratoplasty combined with a central penetrating keratoplasty should be a surgical technique to be considered in cases where these locations are suspected to be the source of recurrence. It enables a definitive elimination of the infection, with excellent final visual acuities. No postoperative complications were reported in this case.

Escleroqueratoplastia terapéutica sectorial de grosor completo en queratitis fúngica recurrente

ObjectiveTo report the management of a severe and recurrent fungal keratitis that required repeated penetrating keratoplasties. Despite multiple topical, intraocular and systemic antifungal treatments, superotemporal hyphal infiltration repeatedly penetrated the corneal transplant causing continuous recurrences. Cultures collected before and during surgery isolated the same organism, Fusarium spp. ConclusionCorneal infection extending to the sclera and internal angle structures is the main cause of recurrence of fungal keratitis after corneal transplantation. Sectorial full-thickness sclero-keratoplasty combined with a central penetrating keratoplasty should be a surgical technique to be considered in cases where these locations are suspected to be the source of recurrence. It enables a definitive elimination of the infection, with excellent final visual acuities. No postoperative complications were reported in this case.

Multiple Effective Treatments for AD

There are multiple topical and systemic treatments, as well as phototherapy, available to effectively treat and reduce relapse of atopic dermatitis (AD). This article discusses adherence to treatment regimens in patients with AD, current topical treatment options, systemic treatment options, strategies to treat pruritus, as well as the role of phototherapy in AD.

Effect of Nitric Oxide on Anterior Segment Physiology in Monkeys

To determine the effect of the nitric oxide donor, sodium nitroprusside (SNP), and the nitric oxide synthase (NOS) inhibitor, L-nitro-arginine-methylester (L-NAME), on IOP, mean arterial pressure (MAP), pupil diameter (PD), refraction (Rfx), aqueous humor formation (AHF), and outflow facility (OF) in monkeys. Monkeys were treated with single or multiple topical treatments of 500 μg SNP or L-NAME to one eye. IOP was determined by Goldmann applanation tonometry, PD with vernier calipers in room light, Rfx by Hartinger coincidence refractometry, AHF by fluorophotometry, and MAP with a blood pressure monitor. OF was determined by two-level constant pressure perfusion following anterior chamber exchange. Following four topical treatments with 500 μg SNP, 30 minutes apart, IOP was significantly decreased from 2 to 6 hours compared with the contralateral control with the maximum IOP reduction of 20% at 3 hours (P < 0.001). PD, Rfx, and AHF were unchanged. Effects on MAP were variable. OF after SNP exchange was significantly increased by 77% (P < 0.05) at 10(-3) M. Topical L-NAME had no effect on IOP, PD, Rfx, or MAP. Enhancement of nitric oxide concentration at targeted tissues in the anterior segment may be a useful approach for IOP reduction for glaucoma therapy. Additional studies are warranted before conclusions can be made regarding the effect of NOS inhibition on ocular physiology in nonhuman primates.

Carcinoma oculto de vulva en neoplasia vulvar intraepitelial diferenciada

We present the case of a 74-year-old woman with a 2-year history of a vulvar lesion associated with pruritus. The patient was treated with multiple topical treatments but, due to the persistence of the lesion and symptoms, she was referred to our clinic. The results of biopsy of the lesion corresponded to differentiated vulvar intraepithelial neoplasia. The initial treatment was wide local excision, with the pathological finding of occult differentiated squamous carcinoma of the vulva. The lesion was treated surgically through radical vulvectomy with sentinel node biopsy, which confirmed the diagnosis of stage iB squamous vulvar carcinoma.

A 12-Year-Old Boy with Foot Lesions

CME EDUCATIONAL OBJECTIVES: 1.Identify the clinical presentation of granuloma annulare.2.Describe the differential diagnosis for granuloma annulare.3.Discuss the appropriate management for granuloma annulare. A 12-year-old healthy male presented to the dermatology clinic for evaluation of lesions on his feet. The lesions were bilateral and had been present for at least 6 months. Multiple topical treatments had been prescribed in the past, including miconazole nitrate 2% cream, oxiconazole 1% cream and alclometasone dipropionate 0.05% ointment. Each had been used for several weeks without improvement. Because of this, the referring doctor prescribed griseofulvin microsize 250 mg twice daily for 4 weeks and referred the patient to dermatology. The patient denied pruritus or pain. Review of systems, medical history, and family history were unremarkable.