Diagnosis and management of allergic conjunctivitis in pediatric patients.

BACKGROUND: Allergic conjunctivitis (AC), although one of the most common ocular disorders in pediatric patients, is frequently overlooked, misdiagnosed, and undertreated in children. OBJECTIVE: To guide pediatric health care professionals in the optimal diagnosis and management of AC in pediatric patients. METHODS: To identify any existing best practice guidelines for the diagnosis and treatment of AC in pediatric patients, a review of the literature published between 2004 and January 2015 was conducted. Diagnosis and treatment algorithms and guidelines for pediatric patient referrals were then developed. RESULTS: A literature search to identify best practice guidelines for the treatment of AC in pediatric patients failed to return any relevant articles, which highlighted the need for best practice recommendations. Based on publications on adult AC and clinical experience, this review provides step-by-step guidance for pediatric health care professionals, including recognizing clinical features of AC, establishing a comprehensive medical history, and performing a thorough physical examination to ensure a correct diagnosis and the optimal treatment or referral to an eye care specialist or allergist when required. In addition to established drug treatments, the role of subcutaneous and sublingual immunotherapy is discussed to inform pediatric health care professionals about alternative treatment options for patients who do not tolerate pharmacotherapy or who do not respond sufficiently. CONCLUSION: The diagnostic and treatment algorithms and guidelines provided in this review help address the current literature and educational gap and may lead to improvements in diagnosis and management of pediatric AC.

Safety, adherence and discontinuation in varenicline solution nasal spray clinical trials for dry eye disease.

Aim: Herein, we report safety outcomes for varenicline solution nasal spray (VNS) within the context of clinical trial discontinuation, contrasting those with discontinuation outcomes from topical cyclosporine and lifitegrast clinical trials. Materials & methods: 1061 subjects were randomized across three clinical trials to receive either VNS 0.06 mg, VNS 0.03 mg, VNS 0.006 mg or vehicle control. Subjects who discontinued from treatment were noted and assigned to their appropriate categories. Results: Despite treatment emergent adverse events, 93.5% of subjects receiving VNS completed the treatment period. By comparison, only 80% of subjects in the integrated clinical trials for cyclosporine ophthalmic emulsion and 91% of subjects in the integrated trials for lifitegrast ophthalmic solution completed the full treatment period, respectively. Conclusion: In clinical trials, VNS demonstrated improvements in dry eye disease signs and symptoms, was well-tolerated, and had an overall completion rate >93%. Conventional dry eye treatments (e.g., cyclosporine and lifitegrast) noted considerably higher discontinuation rates in their clinical trials.

Does Menopausal Status Affect Dry Eye Disease Treatment Outcomes with OC-01 (Varenicline Solution) Nasal Spray? A Post Hoc Analysis of ONSET-1 and ONSET-2 Clinical Trials.

INTRODUCTION: This study sought to compare the efficacy of OC-01 (varenicline solution) nasal spray for treatment of dry eye disease (DED) in postmenopausal women (PM+) versus women who were not postmenopausal (PM-). METHODS: This was a post hoc subgroup analysis of data integrated from two prior randomized controlled clinical trials, ONSET-1 and ONSET-2. Women randomized to treatment with OC-01 (varenicline solution) nasal spray 0.03 mg or vehicle control (VC) whose self-reported menopausal status (PM+ versus PM-) was known were included. Outcomes included the treatment difference (the OC-01 [varenicline solution] nasal spray change from baseline [CFB] minus VC CFB) in Schirmer test score (STS, mm) with anesthesia and the eye dryness score (EDS) measured on a 100-mm visual analog scale (0 = no discomfort, 100 = maximal discomfort). Least-squares mean treatment differences were derived from analysis of covariance (ANCOVA) models. RESULTS: Overall, 449 female participants in the ONSET-1 and ONSET-2 trials randomized to the OC-01 (varenicline solution) nasal spray 0.03 mg or VC groups were included in this analysis. The treatment-menopausal status interaction terms in the STS and EDS ANCOVA and logistic regression models were not statistically significant (p > 0.05), indicating consistency of treatment effect between the PM- and PM+ groups. The treatment difference in STS was similar in the PM- and PM+ groups (6.7 and 5.5 mm, respectively). The treatment difference in EDS was similar in the PM- and PM+ groups (- 5.5 and - 4.1, respectively). CONCLUSIONS: OC-01 (varenicline solution) nasal spray demonstrated similar efficacy in promoting natural tear production and improving symptoms in both PM- and PM+ groups. As menopausal-related hormonal changes may be associated with more severe DED, these results may support OC-01 (varenicline solution) nasal spray as an effective treatment for DED in women regardless of presenting menopausal status. TRIAL REGISTRATION: Post hoc subgroup analysis of data integrated from ONSET-1 (ClinicalTrials.gov identifier NCT03636061) and ONSET-2 (ClinicalTrials.gov identifier NCT04036292).

OC-01 (Varenicline Solution) Nasal Spray Demonstrates Consistency of Effect Regardless of Age, Race, Ethnicity, and Artificial Tear Use.

Purpose: To evaluate OC-01 [varenicline solution nasal spray (VNS)] tear production and symptom outcomes in patients with dry eye disease by age, gender, race, ethnicity, and artificial tear use status. Patients and Methods: Adults ≥22 years of age diagnosed with dry eye disease, with Ocular Surface Disease Index score ≥23, corneal fluorescein staining score ≥2 in ≥1 region or ≥4 for all regions, and baseline Schirmer Test Score (STS) ≤10 mm, with no restrictions on eye dryness score (EDS). Efficacy was assessed using integrated data from ONSET-1 and ONSET-2 [vehicle control (VC), n=294; OC-01 VNS 0.03 mg, n=308]. Subgroups included age (≤55, 56-65, >65 years), gender (male, female), race (White, Black or African American), ethnicity (Hispanic or Latino, Not Hispanic or Latino), and artificial tear use (yes, no). Analysis of covariance models, with the covariates treatment, study site, and baseline severity measures, were used to calculate treatment-VC differences. Consistency of effect among subgroups was evaluated by conducting interaction tests. Results: Consistency of treatment effect across subgroups was observed for all endpoints, with P value for all treatment-subgroup interaction terms >0.05. For % of patients with ≥10mm improvement in STS and least squares (LS) mean change from baseline in STS and EDS, there was improvement in tear production across demographic group categories. Artificial tear use did not change STS or EDS outcomes with OC-01 VNS. Conclusion: OC-01 VNS improved tear production and patient-reported symptom outcomes across a broad range of patients by age, gender, race, and ethnicity, and regardless of artificial tear use status at baseline. OC-01 VNS demonstrated a consistent benefit across an extensive range of patients with dry eye disease.

Bilateral Effect of OC-01 (Varenicline Solution) Nasal Spray for Treatment of Signs and Symptoms in Individuals with Mild, Moderate, and Severe Dry Eye Disease.

PURPOSE: This study compares outcomes of therapy with OC-01 (varenicline solution) for dry eye disease in study eyes and nonstudy fellow eyes of participants in 2 pivotal clinical trials. METHODS: All 891 patients randomized to receive OC-01 (varenicline solution) 0.03 mg, OC-01 (varenicline solution) 0.06 mg, or vehicle control (VC) in each nostril twice daily for 28 days in the Phase IIb ONSET-1 (Evaluation of the Efficacy of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease) and Phase III ONSET-2 trials were included in this post hoc analysis. One eye was designated as the study eye. The mean change from baseline in anesthetized Schirmer test score (STS) and the percentage of eyes achieving a ≥10-mm STS improvement were compared between treatments in study and fellow eyes overall and by baseline Eye Dryness Score. FINDINGS: In the study eyes, the mean STS improvement from baseline to day 28 was 10.4 mm, 10.5 mm, and 4.9 mm in the 0.03 mg, 0.06 mg, and VC groups, respectively; comparable values in nonstudy fellow eyes were 8.7 mm, 8.8 mm, and 2.7 mm, respectively. The percentages of study eyes achieving a ≥10-mm STS improvement were 48.1%, 48.4%, and 25.9%, respectively, whereas the comparable values in nonstudy eyes were 42.9%, 43.9%, and 19.7%, respectively. No significant treatment-subgroup interactions were observed in study or fellow eye STS outcomes by baseline Eye Dryness Scores <40 and ≥40 (p > 0.05 for all). IMPLICATIONS: OC-01 (varenicline solution) nasal spray had significant tear film production improvements compared with VC in both study and fellow eyes. These findings suggest efficacy across a broad spectrum of presenting disease severity.

Lenticular neovascularization subsequent to traumatic cataract formation.

PURPOSE: To report a series of cases involving neovascularization within the human crystalline lens-a normally avascular structure-after ocular trauma. This is a retrospective, consecutive observational case series with review of the prevailing literature. METHODS: Four individuals with a history of ocular trauma and subsequent cataract development were examined between May 2004 and April 2007. All had hypermature cataracts and intraocular inflammation, presumably secondary to phacolysis; two of the four had concurrent hyphema and ocular hypertension in the involved eye. RESULTS: All subjects in this series were found to display a discrete network of blood vessels within the structure of the crystalline lens, just beneath the anterior lens capsule. CONCLUSIONS: Neovascularization of the crystalline lens has received little attention in the ophthalmic literature, having been described only rarely in individual case reports. This manuscript details the first known case series involving lenticular neovascularization, and offers insight into its possible developmental mechanism.

Managing Dry Eye Disease and Facilitating Realistic Patient Expectations: A Review and Appraisal of Current Therapies.

Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by loss of homeostasis of the tear film and accompanied by ocular signs and symptoms such as corneal and conjunctival damage, patient discomfort, and visual disturbance. The prevalence of DED ranges from 5%-33%. Patients with DED may have a reduced quality of life due to their discomfort and visual disturbances. The multifactorial nature of DED requires a multi-targeted treatment approach to address the signs and symptoms. Treatment for DED should follow a step-wise approach beginning with education, dietary modification, and lid and lash hygiene, and progressing to pharmacologic and nonpharmacologic interventions. Ocular lubricants, a mainstay of DED therapy, provide temporary symptomatic relief for the patient, but do not address the underlying pathophysiology. Some currently available pharmacologic treatments that address the underlying pathophysiology of DED may have a delay of 3-6 months in the onset of therapeutic effect; however, these treatment options may also have tolerability issues. These challenges highlight the need for newer pharmacologic treatments with an earlier onset of observable clinical effect and the potential for improved tolerability profile. Patient education is vital to DED management and should convey the complex and chronic nature of DED. It is important for the eye care practitioner to set realistic expectations with the patient when managing DED to help improve treatment success. This helps the patient understand the need for ongoing treatment and that results will likely not be seen immediately. This review covers the current management of DED, focusing on pharmacologic management, and offers recommendations for the practitioner to help facilitate realistic patient expectations for the treatment of DED.

In vitro demodicidal activity of commercial lid hygiene products.

PURPOSE: Demodex folliculorum is a ubiquitous mite that can infest the eyelash follicles. Two commercial lid hygiene products have asserted their effectiveness in killing Demodex mites, yet there has never been a comparative trial between these two products. This study evaluated the demodicidal activity of 0.01% hypochlorous acid (HOCl) solution (Avenova; NovaBay Pharmaceuticals; Emeryville, CA) and 4% terpinen-4-ol (T4O) solution (Cliradex, Bio-Tissue; Miami, FL) in comparison to mineral oil (MO), a negative control. METHODS: Live Demodex mites were obtained from volunteers. Samples were immersed in 1-2 drops of test solution: 0.01% HOCl, 4% T4O, or 100% MO. Samples were observed under the microscope every 10 mins for up to 90 mins. Kill time was defined as the elapsed time between the addition of test solution and all cessation of movement of the body, legs, mouth and pedipalps for a minimum of 60 seconds. RESULTS: T4O demonstrated a mean kill time of 40±0.0 mins. HOCl had a mean kill time of 87.86±4.23 mins, with 79% of samples surviving the full 90 mins. In the MO group, all samples survived through the 90 min mark. Kill time was statistically significant in favor of T4O as compared to HOCl (p=0.0005). There was no statistically significant difference in kill time between HOCl and MO (p=0.25). CONCLUSION: 4% T4O effectively killed all adult mite samples within 40 mins of exposure. In contrast, the demodicidal activity of 0.01% HOCl was minimal, and comparatively similar to 100% MO.

Accuracy, speed and repeatability of the voice assisted subjective refractor (VASR).

PURPOSE: To compare the accuracy, speed and repeatability of the voice assisted subjective refractor (VASR) to traditional refractive methods. METHODS: Fifty healthy adult subjects were examined by autorefractor, followed by subjective phoropter refinement. Subjects were then evaluated using the VASR (Vmax Vision) to obtain an objective and subjective result. Three total assessments were performed for each subject using each of the methods described. Corrected visual acuity was recorded for each eye after each procedure. The total time was measured for both the traditional and VASR refraction. RESULTS: A comparison of the results obtained by traditional refraction and VASR revealed no statistically significant difference from the mean in equivalent sphere measurements (P=0.1383), and the datasets were highly correlated (r=0.993). The data comparisons for cylinder power and axis were similar (cylinder: P=0.6377, r=0.864) (axis: P=0.6991, r=0.738). VASR, on average, required 71 additional seconds to complete when compared to traditional phoropter refraction. In terms of repeatability, the average difference noted upon repeat of equivalent sphere power was 0.01 D for the phoropter (P=0.98) and 0.10 D for the VASR (P=0.23). For sphere power, the average difference was 0.02 D for the phoropter (P=0.55) and 0.07 D for the VASR (P=0.58). For cylinder power, the average difference was 0.02 D for the phoropter (P=0.11) and 0.03 D for the VASR (P=0.39). For all refractive methods, the differences between measurements amounted to ≤0.10 diopters, which is neither clinically nor statistically significant. CONCLUSION: Refractive error results obtained with the VASR were not statistically different from those achieved using traditional phoropter methods. Time elapsed for the VASR was slightly longer than a more traditional refractive sequence. The VASR demonstrated clinically and statistically significant repeatability of measurement, consistent with traditional refraction.

Ocular distribution, bactericidal activity and settling characteristics of TobraDex ST ophthalmic suspension compared with TobraDex ophthalmic suspension.

INTRODUCTION: TobraDex ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container. METHODS: A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose. RESULTS: Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST. CONCLUSION: TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.

Therapeutic options for the management of early neurotrophic keratopathy: a case report and review.

BACKGROUND: Neurotrophic keratopathy is caused by the loss of corneal sensation secondary to impaired trigeminal nerve function. Timely and appropriate action is required in the management of this condition to prevent serious complications such as corneal ulceration, perforation, and loss of vision. The role of immunomodulating agents such as cyclosporine as a therapeutic option and a review of several future treatment modalities are discussed. CASE REPORT: A 46-year-old black woman with a noted history of recurrent herpes simplex virus-1 keratitis and secondary neurotrophic keratopathy in the left eye was examined. She reported that another physician had treated her for this condition over the last 6 months. Her treatment regimen consisted of a bandage contact lens, antibiotic solution, and artificial tears. Best-corrected visual acuities were 20/20 in the right eye and 20/25 in the left eye. Biomicroscopy evaluation found punctate keratitis in both eyes and neurotrophic keratopathy with an area of pinpoint epithelial defect in the left eye. Restasis (0.05% cyclosporine ophthalmic emulsion; Allergan, Irvine, California) bid was added to her medical regimen. Within 4 weeks of starting Restasis therapy, the epithelial defect had resolved, and she was advised to discontinue both the bandage lens and antibiotic solution. She was ultimately discharged on a continued regimen of Restasis twice a day and lubricating drops as needed with scheduled follow-up every 3 months. CONCLUSION: Management of neurotrophic keratopathy requires decisive action. Early treatment intervention is important to help avoid severe complications. The use of immunomodulating agents (topical cyclosporine) in the early stage of management should be considered.

Retinal capillary angioma managed with trans-pupillary thermotherapy.

Retinal capillary angioma is a tumour-like nodule of the retina and was first described in 1904 by von Hippel. This disease is characterised among the congenital syndromes known as the phakomatoses. It is the only known phakomatosis that does not exhibit skin lesions. A patient with retinal capillary angioma with leakage and haemorrhage is described and the differential diagnosis discussed. In addition, this patient was treated with trans-pupillary thermotherapy and the available therapies are summarised.