Multicenter Study of a Novel Topical Interleukin-1 Receptor Inhibitor, Isunakinra, in Subjects With Moderate to Severe Dry Eye Disease.

OBJECTIVES: Isunakinra, formerly known as EBI-005, is a novel interleukin (IL)-1 receptor inhibitor developed for topical treatment of patients with dry eye disease (DED). This phase 1b/2a multicenter, double-masked, randomized, vehicle controlled environmental trial assessed the safety and biological activity of isunakinra in patients with moderate to severe DED. METHODS: Subjects (N=74) were randomized to vehicle (placebo) or isunakinra (5 or 20 mg/mL) 3×/daily for 6 weeks. Evaluations included safety, tolerability, biological activity for signs (corneal fluorescein staining [CFS]), symptoms (pain or sore eyes and total Ocular Surface Disease Index [OSDI]), and reduction in rescue artificial tear use. RESULTS: Topical administration of isunakinra (5 and 20 mg/mL) was safe and well tolerated and resulted in clinically relevant improvements in symptoms (OSDI score, painful/sore eye component of OSDI) and signs (total CFS) compared with baseline with no dose response. OSDI scores improved from baseline by 38% (18.9 points) at 6 weeks and CFS scores improved by 33% (3 points) in the isunakinra groups. These changes were not statistically significant compared with the vehicle. Use of artificial rescue tears was significantly reduced in the isunakinra treatment groups (mean=9 vials) compared with vehicle (mean=31 vials). The differences between isunakinra and vehicle treatments were more pronounced in subjects with OSDI scores less than 50 at baseline. CONCLUSIONS: Isunakinra was safe, well tolerated and showed clinically meaningful improvements in signs and symptoms of DED. These results encouraged the design of an adequately powered study to characterize the safety and efficacy of isunakinra in ocular surface diseases.

Perception and quality of life associated with the use of olopatadine 0.2% (Pataday) in patients with active allergic conjunctivitis.

This 28-d, open-label, multicenter, single-arm clinical study was designed to evaluate perceptions of olopatadine 0.2% in patients with active ocular allergic signs and symptoms. The study enrolled 330 patients, 5 to 94 y of age, who had previously used olopatadine 0.1% for active allergic conjunctivitis. Most patients were white (n=230; 70.1%) and female (n=239; 72.9%). Of all enrolled patients, 328 were evaluable for analysis. Throughout the study, patients instilled 1 drop of olopatadine 0.2% into each eye once daily; adverse events were documented and ocular evaluations were conducted to ensure patient safety. Direct evaluations of efficacy were not performed. On days 1 and 7, patients completed the Rhinoconjunctivitis Quality of Life Questionnaire, recorded their perceptions of olopatadine 0.1% (day 1) or 0.2% (day 7), and had their ocular allergies assessed globally. On each of the first 6 d of treatment, patients also completed a telephone-based perception questionnaire. On day 28, patients returned to the study center, reported their treatment perceptions, had their ocular allergies assessed, and exited the trial. Overall, patients had a positive perception of olopatadine 0.2%. Patients were more satisfied with olopatadine 0.2% than they remembered being with olopatadine 0.1% (289 vs 257 patients; 87.6% vs 77.8%; P<.05). The majority of the 48 patients who wore contact lenses (n=42; 88%) believed that they could wear their contacts as desired. Significant improvement was noted in all categories of the Rhinoconjunctivitis Quality of Life Questionnaire (P<.0001). No unexpected safety findings were reported. Patients perceived olopatadine 0.2% to be effective and well tolerated.

Tear concentrations of levofloxacin following topical administration of a single dose of 0.5% levofloxacin ophthalmic solution in healthy volunteers.

BACKGROUND: Several fluorinated carboxyquinolones are used to treat ocular infectious disease. Levofloxacin, in particular, has demonstrated activity against both gram-negative and gram-positive bacteria. OBJECTIVES: An open-label study was undertaken to assess the pharmacokinetics and ocular bioavailability of levofloxacin in human tears, and to determine the tear concentration of levofloxacin in healthy volunteers, following topical administration of a single-dose of 0.5% levofloxacin ophthalmic solution. METHODS: Volunteers received 1 drop of 0.5% levofloxacin in each eye and were assigned sequentially to 1 of 5 groups for tear sampling. Tear samples were collected on Schirmer test strips at 9 predetermined time points ranging from 5 minutes to 24 hours after administration. Six tear samples were collected at each time point (1 eye each from 6 volunteers), except the 24-hour time point, at which 12 samples were collected (both eyes of 6 volunteers). No eye had > 1 tear sample taken during the study. Levofloxacin concentrations were measured using reverse-phase high-performance liquid chromatography. RESULTS: Thirty volunteers were enrolled, with 6 assigned to each of the 5 sampling groups. At 5 minutes after administration of a single topical dose of levofloxacin, the mean tear concentration was 49.19 +/- 26.73 microg/mL. The mean peak concentration of levofloxacin in the tear film, 221.06 +/- 256.68 microg/mL, was reached at 15 minutes after administration. At 4 hours after administration, the mean tear concentration of levofloxacin was 17.04 +/- 15.13 microg/mL. At 6 hours after administration, the mean concentration of levofloxacin was 6.57 +/- 5.26 microg/mL. At 24 hours after administration, levofloxacin concentrations > 2 microg/mL were measured in 2 of 6 (33%) subjects. CONCLUSIONS: Levofloxacin concentrations in the tear fluid after a single topical dose (1 drop) reached high levels quickly and remained above the minimum inhibitory concentration for most suspected ophthalmic pathogens (< or = 2 microg/mL) for at least 6 hours in most healthy volunteers, and for up to 24 hours in some volunteers.

Psychosomatic pain: new insights and management strategies.

At least 40 to 60 percent of women and at least 20 percent of men with chronic pain disorders report a history of being abused during childhood and/or adulthood. This incidence of abuse is two to four times higher than in the general population. Patients with more severe or frequent abuse, usually during childhood and worse if sexual in nature. often develop specific syndromes or combinations of syndromes. These syndromes include posttraumatic stress disorder, fibromyalgia, and other conditions characterized by repression, somatization, and increased utilization of medical care. Psychosomatic symptoms and dysfunctional behaviors may emerge as these patients seek attention and validation of their suffering, while paradoxically repressing painful memories of trauma. Behavioral observations and key features of the physical examination may greatly help the clinician identify both the presence and severity of psychosomatic disease. In addition, it is very interesting that various studies document physiologic changes in the brains of patients with a history of abuse and in patients with a diagnosis of fibromyalgia. These studies suggest that abuse may physiologically and developmentally increase a person's susceptibility to pain and that some organic changes may be associated with psychogenic disease. Diagnosis and treatment of even the most challenging patients with chronic pain is much more effective if it includes (a) careful inquiry about any history of past or present abuse or other severe trauma, (b) empathy and constructive validation of disease and suffering, (c) recognition of dysfunctional pain behaviors and personality traits, (d) documentation of nonanatomic as well as anatomic features on examination, (e) multidisciplinary treatments including psychotherapy whenever indicated, and (f) noninvasive procedures and alternatives to potentially habit-forming medications whenever possible and appropriate. Furthermore, it has been shown that helping patients gain insight about the relationship between abuse and their current symptoms leads to decreased health care utilization. Practical guidelines are provided for identifying psychopathology, communicating effectively, and achieving better treatment outcomes for these unfortunate patients.