Relief Of Ocular Symptoms Research Articles

Eye amputation following lifitegrast treatment for ocular graft-versus-host disease: First case report

Graft-versus-host disease (GVHD) is a common complication in patients undergoing allogeneic stem cell transplantation for acute myeloblastic leukemia that could be very difficult to treat. Lifitegrast 5% (Xiidra@, Novartis), a new immunosuppressive eye drop, was recently approved by the FDA for the treatment of severe dry eye and is currently under review by the European Medicines Agency. In France, lifitegrast has been approved by the French authorities for temporary use in refractory dry eye syndrome resistant to tear substitutes and topical cyclosporine. To date, serious complications have been reported only exceptionally. In this article, we report the case of a 65-year-old patient with a medical history of acute myeloid leukemia (AML) diagnosed in 2015 who received a first matched related donor transplant. In 2019, this patient developed chronic GVH involving the skin, oral mucosa and eye. Despite taking topical and systemic medications for 3 months, the patient did not report relief of ocular symptoms. Therefore, lifitegrast was prescribed. To our knowledge, we report the first case of corneal perforation in which evisceration was required following treatment with topical lifitegrast for chronic GVH. In the case presented here, it can be assumed that the underlying mechanisms leading to corneal perforation are multifactorial. Using drug accountability criteria, lifitegrast appears to be strongly associated with the development of bacterial keratitis and corneal perforation.

Disease etiology‐based design of multifunctional trehalose emulsion eye drops for moderate or severe dry eye: a randomised, quadruple‐masked and active‐controlled clinical trial

AbstractPurposeTo assess the safety and efficacy of multi‐ingredient trehalose emulsion eye drops (TEED) designed to target (1) tear film instability, (2) tear hyperosmolarity, and (3) ocular surface damage and inflammation in moderate or severe dry eye.MethodsThis randomised, quadruple‐masked, active‐controlled parallel study in 64 adult patients comprised three parts. Part 1 (n = 3): One eye was treated with TEED for one day. Part 2 (n = 9): Randomised eyes were treated with TEED and 0.2% hyaluronic acid (HA) control eye drops 3 times a day for 10 days. Part 3 (n = 26 + 26): Randomised treatment was applied on both eyes 3 times a day for 30 days. Ocular assessments were performed at baseline and after the last dose.ResultsBoth treatments were well tolerated without adverse device effects. Tear film break‐up time (p = 0.0025) and ocular protection index (p = 0.0026; change vs. HA, p = 0.047) increased significantly with TEED after 30 days. Tear osmolarity decreased more in TEED than in HA group and significantly with both eye drops in hyperosmolar subgroups. Corneal (p = 0.014) and nasal conjunctival staining (p = 0.043) were reduced with TEED in per‐protocol patients (n = 24). Conjunctival (p = 0.001) and lid redness (p = 0.012) decreased with TEED in all patients (n = 26). Symptoms decreased by about 25 OSDI units with both treatments (p < 0.0001).ConclusionsTEED proved safe and efficacious in improving each etiologic factor for dry eye. Hyperosmolar stress dominating blink cycles must be disrupted by biophysical protection of the ocular surface to facilitate resolution of cellular damage and inflammation, and relief of ocular symptoms.

Disease aetiology-based design of multifunctional microemulsion eye drops for moderate or severe dry eye: a randomized, quadruple-masked and active-controlled clinical trial.

PurposeTo assess the safety and efficacy of multi‐ingredient sacha inchi microemulsion (SIME) eye drops designed to target (1) tear film instability, (2) tear hyperosmolarity, and (3) ocular surface damage and inflammation in moderate or severe dry eye.MethodsThis randomized, quadruple‐masked, active‐controlled parallel study in 64 adult patients comprised three parts. Part 1 (n = 3): one eye was treated with SIME for one day. Part 2 (n = 9): randomized eyes were treated with SIME and 0.2% hyaluronic acid (HA) control eye drops 3 times a day for 10 days. Part 3 (n = 26 + 26): randomized treatment was applied on both eyes 3 times a day for 30 days. OSDI change was tested for superiority of SIME over HA. Ocular assessments were performed at baseline and after the last dose.ResultsBoth treatments were well tolerated without adverse device effects. Tear film break‐up time (p = 0.0025) and ocular protection index (p = 0.0026; change vs. HA, p = 0.047) increased significantly with SIME after 30 days. Tear osmolarity decreased more in SIME than in the HA group and significantly with both eye drops in hyperosmolar subgroups. Corneal (p = 0.014) and nasal conjunctival staining (p = 0.043) were reduced with SIME in per‐protocol patients (n = 24). Conjunctival (p = 0.001) and lid redness (p = 0.012) decreased with SIME in all patients (n = 26). Symptoms decreased by about 25 OSDI units with both treatments (p < 0.0001) and with nonsignificant difference between treatments.ConclusionsSacha inchi microemulsion (SIME) proved safe and efficacious in improving each aetiologic factor for dry eye as revealed through objective tests. Hyperosmolar stress dominating blink cycles must be disrupted by biophysical protection of the ocular surface to facilitate resolution of cellular damage and inflammation, and relief of ocular symptoms.

Rapid Nasal Symptom Onset of Action and Ocular Symptom Relief With Olopatadine/Mometasone Combination Nasal Spray in Patients with Seasonal Allergic Rhinitis: A Pooled Analysis

Rapid Nasal Symptom Onset of Action and Ocular Symptom Relief With Olopatadine/Mometasone Combination Nasal Spray in Patients with Seasonal Allergic Rhinitis: A Pooled Analysis

Rapid Onset of Action on Nasal Symptoms and Ocular Symptom Relief With Olopatadine/Mometasone Combination Nasal Spray in a Ragweed Environmental Exposure Chamber

Rapid Onset of Action on Nasal Symptoms and Ocular Symptom Relief With Olopatadine/Mometasone Combination Nasal Spray in a Ragweed Environmental Exposure Chamber

Onset of action for loratadine tablets for the symptomatic control of seasonal allergic rhinitis in adults challenged with ragweed pollen in the Environmental Exposure Unit: a post hoc analysis of total symptom score

BackgroundLoratadine is a second-generation, non-sedating antihistamine used for the relief of allergic rhinitis symptoms. Previous studies reported that when loratadine was encapsulated, the onset of action for symptom relief was 180 min. However, unmodified loratadine tablets were not evaluated at that time. Using data from a previously published Environmental Exposure Unit (EEU) study comparing azelastine nasal spray with loratadine tablets, cetirizine tablets, and placebo, this post hoc analysis determines the onset of action of loratadine tablets (i.e. unmodified) by analyzing the total symptom score for the relief of nasal and ocular seasonal allergic rhinitis (SAR) symptoms.MethodsA Phase IV, randomized, single-center, double-blind, placebo-controlled, double-dummy, four-way crossover study was conducted in the EEU. Seventy participants were randomized sequentially into one of the four treatments during ragweed pollen exposure. Nasal and ocular symptom scores were self-reported by the participants and recorded. The original study analysis was carried out by evaluating the nasal symptom scores only. For this post hoc analysis, both nasal and ocular data from the loratadine and placebo treatment arms were analyzed. The primary endpoint for this analysis was the onset of action of loratadine as measured by the change in total symptom score (TSS) from baseline in comparison to placebo. The onset of ocular symptom relief using the total ocular symptom score (TOSS) was also reported.ResultsLoratadine tablets demonstrated a significant and durable improvement in both TSS (P = .005) and TOSS (P = .013) at 75 min post-treatment administration compared to placebo. The mean proportion of participants reporting none or mild for all component symptoms of TSS and TOSS at 75 min and thereafter was significantly higher in the loratadine (TSS, P = .0005; TOSS, P ≤ .0001) vs. placebo treatment arm.ConclusionsThe onset of action of loratadine tablets was 75 min for the relief of nasal and ocular symptoms in adults with SAR. These results suggest a faster onset of action for loratadine tablets (75 min) compared to previously reported studies which were conducted with modified (i.e. gelatin-encapsulated) loratadine tablets (180 min).Trial registration Clinicaltrials.gov identifier NCT00561717

ASCIA‐P56: BURDEN OF ALLERGIC RHINITS IN AUSTRALIA

Allergic rhinitis (AR) affects approximately 500 million individuals around the world and is increasing in prevalence. Often trivialised as a ‘nuisance disease’, its burden has been systematically under-estimated. The aim of this survey was to understand the burden of AR in Australia, both from an individual and societal perspective. 1151 adults with a self-reported diagnosis of AR were recruited across Australia via a patient panel to complete an online survey in August 2015. The survey included questions on type of AR and its severity, medication utilisation, GP services, absenteeism and presenteeism. Descriptive statistics were used to summarise results. Most Australian AR patients have seasonal AR, either alone (n = 376; 32.7%) or in combination with perennial AR (n = 616; 53.5%), and rate their disease as either moderate (n = 455, 39.5%) or severe (n = 495, 43.0%), predominantly. Patients visited their GP due to AR symptoms on average 2.9 times/year, with 1.1 visits due to dissatisfaction with current treatment. The majority had also seen a specialist for their AR (n = 771, 67.0%). Of respondents who used medication (n = 1016, 83.3%), 79.7% (n = 810) co-medicated, usually with intranasal corticosteroids and oral anti-histamines ± eye drops. This co-medication behaviour was driven by the need for better and faster nasal and ocular symptom relief (67.0% and 43.8% of patients, respectively), but only 16.9% of patients (n = 137) were completely satisfied with their multi-therapy regimen. Patients continued to experience high nasal (rTNSS 9.4/12) and ocular (rTOSS: 6.4/9) symptom burden, reported an AR-specific absenteeism rate of 3.9 days/year, with productivity negatively impacted on 31.3 days/year. Indeed 62.0% of patients reported a ≥50% reduction in productivity when symptomatic. Clearly, more effective AR treatments are needed to both reduce the symptomatic burden of AR for patients and costs to the Australian economy.

A new allergic rhinitis therapy (MP29‐02*) provides nasal and ocular symptom relief days faster than current firstline monotherapies

Methods Six hundred and ten moderate-to-severe SAR patients (≥12 yrs) were randomized into a double-blind, PLAcontrolled, 14-day, parallel-group, trial (NCT00660517) to MP29-02*, AZE, FP or PLA nasal sprays (1 spray/ nostril bd; daily dose: AZE=548μg; FP=200μg) [1]. Change from baseline (CFB) in reflective total of 7 symptom scores (rT7SS; AM + PM, max=42) was assessed post-hoc. CFB in rT7SS and each nasal (congestion, itching, rhinorrhea, sneezing) and ocular symptom (itching, redness, watering; max=6 each) was assessed over time.

The hidden burden of adult allergic rhinitis: UK healthcare resource utilisation survey.

BackgroundThe affliction of allergic rhinitis (AR) has been trivialised in the past. Recent initiatives by the European Academy of Allergy & Clinical Immunology and by the EU parliament seek to rectify that situation. The aim of this study was to provide a comprehensive picture of the burden and unmet need of AR patients.MethodsThis was a cross-sectional, online, questionnaire-based study (June–July 2011) including symptomatic seasonal AR (SAR) patients (≥18 years) from a panel. SAR episode pattern, severity, medication/co-medication usage, residual symptoms on treatment, number of healthcare visits, absenteeism and presenteeism were collected.ResultsOne thousand patients were recruited (mild: n = 254; moderate/severe: n = 746). Patients with moderate/severe disease had significantly more symptomatic episodes/year (8.0 vs 6.0/year; p = 0.025) with longer episode-duration (12.5 vs 9.8 days; p = 0.0041) and more commonly used ≥2 AR therapies (70.5 vs 56.1 %; OR 1.87; p = 0.0001), looking for better and faster nasal and ocular symptom relief. The reported symptom burden was high irrespective of treatment, and significantly (p < 0.0001) higher in the moderate/severe group. Patients with moderate/severe AR were more likely to visit their GP (1.61 vs 1.19 times/year; OR: 1.49; p = 0.0061); due to dissatisfaction with therapy in 35.4 % of cases. Patients reported SAR-related absenteeism from work on 4.1 days/year (total cost to UK: £1.25 billion/year) and noted presenteeism for a mean of 37.7 days/year (vs 21.0 days/year; OR 1.71; p = 0.0048). Asthma co-morbid patients reported the need to increase their reliever- (1 in 2 patients) and controller-medication (1 in 5 patients) if they did not take their rhinitis medication.ConclusionsThis study differentiated between patients with mild and moderate/severe AR, demonstrating a burden of poorly controlled symptoms and high co-medication use. The deficiency in obtaining symptom control with what are currently considered firstline treatments suggests the need for a novel therapeutic approach.Electronic supplementary materialThe online version of this article (doi:10.1186/s13601-015-0083-6) contains supplementary material, which is available to authorized users.

The journey from unmet need in allergic rhinitis to rationale for, and clinical development of, a new treatment option, MP29-02

The aim of allergic rhinitis treatment is to control symptoms, but currently considered first-line therapy provides suboptimal symptom relief for many patients. MP29-02 is a new treatment for allergic rhinitis, developed to fill this unmet need. Moderate/severe seasonal allergic rhinitis patients treated with MP29-02 experienced twice the nasal and ocular symptom relief as those treated with azelastine or fluticasone propionate. The effect was consistent across seasons, symptoms and by severity. MP29-02 delivered substantial and complete response in more patients and many days faster than fluticasone propionate or azelastine. Its efficacy advantage over fluticasone propionate extended beyond 14 days, up to 1 year, in chronic rhinitis patients. MP29-02 was well tolerated, both short and long term, and may change the way allergic rhinitis is managed, for the better.

Clinical developmentof an advanced intranasal delivery sistem of azelastine hydrochloride and fluticasone propionate

There is no shortage of pharmacologic treatments available for the management of allergic rhinitis (AR), but none regularly provide full relief from all symptoms. MP29-02 (Dymista®) is a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP), benefiting from an enhanced formulation and improved device characteristics compared to marketed intranasal corticosteroid (INS) formulations. Results from large, randomized, double-blind, placebo-controlled, head-to-head trials versus first-line therapies, confirmed MP29-02 as the evidence-based drug-of-choice for AR treatment. MP29-02 was twice as effective as AZE or FP for nasal and ocular symptom relief in moderate to severe seasonal AR patients, with superiority documented regardless of season, and in more severe patients. More MP29-02-treated patients experienced clinically relevant responses (i.e., halving of nasal symptom burden and complete/near-to-complete relief) days faster than those on INS or intranasal antihistamine monotherapy. MP29-02's efficacy was sustained long-term versus FP (up to 52 weeks) in chronic rhinitis patients (perennial AR or nonallergic rhinitis), with 7 out of 10 patients first becoming symptom-free following 1 month's treatment with MP29-02, and days faster than with the INS. These results confirm MP29-02's superiority over the historical gold-standard therapy for AR (i.e., INS), and position it now as first-line treatment for moderate to severe AR patients, the majority of whom are uncontrolled on existing medications.

Preventative Effect of a Flavonoid, Enzymatically Modified Isoquercitrin on Ocular Symptoms of Japanese Cedar Pollinosis

Flavonoids are nutrients that exert anti-allergic effects. We investigated the preventative effect of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve the symptoms of Japanese cedar pollinosis. In a parallel-group, double-blind placebo-controlled study design, 24 subjects with Japanese cedar pollinosis took 100mg EMIQ or a placebo for 8 weeks, starting 4 weeks prior to the onset of pollen release. Subjective symptoms, ADL scores and the usage of drugs were recorded daily, and the QOL score was obtained every 4 weeks. Blood sampling was performed before and after the study to measure serum levels of IgE and flavonoids. During the entire study period, ocular symptom + medication score for the EMIQ group was significantly lower (p < 0.05) than that of the placebo group. When limited to the period, ocular symptom scores (p < 0.05, weeks 5-6), and ocular congestion scores (p < 0.05, weeks 5-6) for the EMIQ group was significantly lower than that for the placebo group while other scores for the EMIQ group, such as ocular itching scores (p = 0.09, weeks 4-5), lacrimation scores (p = 0.07, weeks 5-6), and ocular congestion scores (p = 0.06, weeks 4-5), all tended to be lower. However no significant differences were found in nasal symptoms between the two groups. Serum concentrations of IgE were not significantly downregulated but the serum concentrations of quercetin and its derivatives were elevated significantly by the intake of EMIQ. Intake of the quercetin glycoside EMIQ proved to be effective for the relief of ocular symptoms caused by Japanese cedar pollinosis.

Medial Upper Eyelid Shortening to Correct Medial Eyelid Laxity in Floppy Eyelid Syndrome: A New Surgical Approach

To describe and present the results of a new surgical technique for patients with floppy eyelid syndrome, based on the medial upper eyelid stretching encountered in this condition. A case series of 24 patients with floppy eyelid syndrome who where found to have symptomatic predominately medial upper eyelid laxity was analyzed. The history, clinical features, histopathology, and outcome were reviewed after patients underwent medial upper eyelid shortening with or without upper eyelid skin reduction as the first surgical procedure. Of the 24 patients, 18 were men (75%) with a mean age at referral of 56 years, having ocular discomfort and conjunctival irritation/papillary conjunctivitis as the main complaints at presentation. Obesity was present in 96% of cases, with lower eyelid laxity/ectropion (50%) and upper eyelid eyelash ptosis (29%) in conjunction with the upper eyelid laxity. The affected side was related to sleeping habits or recurrent mechanical eyelid trauma. Histologic studies showed a nonspecific inflammatory cell infiltrate and loss of elastin with loose dermal connective tissue. After surgery, complete relief of ocular symptoms and good functional and cosmetic results were present in all cases after 18 months of follow-up. This new surgical approach is based on the presence of predominately medial upper laxity in patients with floppy eyelid syndrome. The excision of this stretched area stabilized the upper eyelid in an anatomic fashion, providing a good and stable long-term result. The possible mechanisms involved in the medial upper eyelid stretching are discussed.

Role of antihistamines in ocular allergy

Although H 1 antihistamines are commonly used to treat allergic disorders and have demonstrated efficacy in allergic rhinoconjunctivitis, data on the effects of these agents specifically on ocular symptoms are limited. Oral H 1 antihistamines inhibit some symptoms of pruritus and erythema in laboratory models and have been shown to be superior to placebo for relief of symptoms in clinical trials. Eye drops typically provide faster relief of ocular symptoms than oral agents, and combination therapy with a topical agent and an oral agent has been found to be superior to the oral agent alone. In general, oral H 1 antihistamines have been considered superior to intranasal corticosteroids for relief of ocular symptoms, but some studies have shown equal efficacy for these agents, or even superior efficacy for intranasal corticosteroids.

Topical ocular administration of cromolyn sodium for treatment in seasonal ragweed conjunctivitis

We studied topical ocular administration of a 4% solution of cromolyn sodium (CS)for treatment of 112 patients with ragweed conjunctivitis in two 8-wk, double-blind, matched-pair studies. During the 1977 and 1978 ragweed seasons, patients instilled a daily total of 12.8 or 19.2 mg CS into each eye, control patients received placebo drops. Treatment efficacy was assessed by daily symptom score diaries, ophthalmic examinations, and a subjective report by the patient at the end of the trials. In the 1977 trial, CS pair members whose preseasonal immunoglobulin E antibody level was <99 ng/ml showed a significant reduction in eye itching (p < 0.01), eye irritation (p < 0.02), visual blurring (p < 0.025), and nasal congestion (p < 0.025) and required less supplemental medication (p < 0.02) during the peak pollen period. In the 1978 trial all patients had IgE antibody levels >100 ng/ml. CS pair members showed a significant reduction in rhinorrhea (p < 0.004) and nasal congestion (p < 0.007) only; no significant reduction in eye symptoms was noted. Transient eye burning was noted by a total of 38 CS and 39 placebo patients from both studies; ophthalmic examinations were unremarkable; and no other side effects were noted. The 4% CS ophthalmic solution provided significant relief of nasal symptoms in both the 1977 and 1978 trials, but significant relief of ocular symptoms was noted only in the 1977 trial and only in those patients with lower preseasonal IgE ragweed antibody levels.

Knowledge, awareness and practice of CVS in digital device users

Aim: The aim was to study the knowledge, awareness, and practice of computer vision syndrome (CVS) in digital device users. Materials and Methods: This was an observational study conducted on 504 healthy students of a medical college. The students underwent an interview in the form of a preset questionnaire. Results: The present study comprised a total of 188 (37.3%) males and 316 (62.7%) females with the mean age of 21.98 ± 4.61 years. Awareness about CVS was poor, i.e., only 32% had ever heard of the term CVS of which around 65% could correctly define it. It was noted that more than half of the participants resorted to incorrect methods for relief of ocular symptoms. Social media was the largest source of information (15.1%). The association of age with awareness, knowledge with respect to definition, blink rate, and source of information was highly significant (P = 0.003, 0.001, 0.001, and 0.01, respectively). The association of profession of the participant with knowledge about blink rate and practice of taking a break was found to be highly significant (P = 0.002 and 0.01, respectively). Awareness about the blink rate and practice of closing eyes was significantly associated with the sex of the participant (P = 0.03 and 0.01, respectively). Conclusion: This study shows that the younger generation has significant knowledge about CVS, but there is a gap in practice. A program studying and addressing the barriers to practice needs to be developed for younger generation.