Pinto‐Fraga 2016.
| Study characteristics | ||
| Methods |
00. Study design: randomized controlled trial, parallel group 01. Calendar time when the study enrolled the first participant (YYYY/MM): 2014/03 (ClinicalTrials.gov: 2014/02) 02. Calendar time when the study completed follow‐up (YYYY/MM): 2014/11 (ClinicalTrials.gov: 2014/12) 03. Unit of randomization (participant or eye): participant 04. Masking of participants, treatment allocator, outcome assessor, or data analyzer: participants, treatment allocators, and outcome assessors (examiners) 05. Study visits and the corresponding time points: Day 0 (Visit 1), Day 21 (Visit 2 and Visit 3), Day 22 (Visit 4) 06. Instruments and the scales used for documenting patient‐reported symptoms or quality of life: OSDI, SANDE version I 07. Assessment for safety outcomes: the safety of both treatments was assessed by recording the nature, severity, and duration of all adverse events and their relationship to the study medication. 4 additional safety endpoints were included in the trial (Table 1): changes in BCVA, fundus evaluation and optic cup‐to‐disc ratio, anterior segment anomalies (especially corneal epithelial problems or signs of infection), and IOP. 08. Planned follow‐up duration: 22 days 09. Actual follow‐up duration: 22 days 10. Planned treatment duration (of the intervention steroid): 21 days 11. How missing data were handled: "because 1 patient dropped from the study because of work‐related issues, 1 more individual was recruited, and thus a total of 41 patients eventually were included in the study, but data from only 40 patients were analyzed" 12. Description on power and sample size calculation: the sample size was estimated to detect a 1‐point difference (Oxford scale) in the main efficacy variable (corneal fluorescein staining), at a significance level of 0.05, with a statistical power of 0.9, and with an estimate of a 10% loss of the sample size |
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| Participants |
Country: Spain Setting: single medical center Interventions:
Age, mean (95% CI): 59.0 (55.2 to 62.7) Female, n (%): 17 (81%) Etiology, n (%): NR Participants (eyes) randomized: 21 Participants (eyes) analyzed for primary study outcomes: 21 Participants (eyes) analyzed for safety outcomes: 21
Age, mean (95% CI): 60.3 (56.0 to 64.7) Female, n (%): 17 (89%) Etiology, n (%): NR Participants (eyes) randomized: 19 Participants (eyes) analyzed for primary study outcomes: 19 Participants (eyes) analyzed for safety outcomes: 19
Age, mean (95% CI): 59.6 (58.9 to 60.3) Female, n (%): 34 (85%) Etiology, n (%): NR Participants (eyes) randomized: 40 Participants (eyes) analyzed for primary study outcomes: 40 Participants (eyes) analyzed for safety outcomes: 40 Inclusion criteria: Corneal fluorescein staining score of 1 or more (Oxford scale) in both eyes, a TBUT of 7 seconds or less in both eyes, unanesthetized Schirmer test results of 10 mm/5 min or less in both eyes, and an OSDI score of 12 points or more. Importantly, the patient had to express a worsening of DED‐related symptoms when exposed to adverse environmental conditions during their daily life and the use of artificial tears before beginning the study. Patients were accepted into the study if they were taking other topical or systemic treatment if it was begun at least 3 months before inclusion, and the dosage was to be maintained throughout the entire study. Finally, patients had to have a BCVA of 1.0 logarithm of the minimum angle of resolution or less in each eye. Exclusion criteria: Patients were excluded if they had a known sensitivity or intolerance to any of the treatments used in the study; a history of ocular infection or severe ocular inflammation (other than DED related) 6 months before inclusion in the study; any active ocular disease (different from DED); any uncontrolled severe systemic disease that may affect the eye (except Sjögren syndrome); any ocular surgery or trauma that could affect corneal sensitivity, normal tear distribution in the 6 previous months, any ocular or systemic surgery or procedure planned during the study duration that could affect outcomes, or a combination thereof; occlusion of the lacrimal puncta either surgically or with plugs within 3 months before study; contact lenses wear within 3 months or during the study; or use of any topical medication except for DED. Other exclusion criteria included initiation, discontinuation, or change of dosage of antihistaminic, cholinergic agents, beta‐blocking agents, antidepressants, or any systemic medication with possible effects over the tear film; history of glaucoma or IOP of more than 22 mmHg in any measurements 2 months before baseline; optic cup‐to‐disc ratio of more than 0.6 mm; pregnancy; lactation; or inadequate contraception. Also, patients were excluded if undergoing topical cyclosporine A eye drops within 3 months before study inclusion, topical corticosteroid eye drops within 1 month before inclusion, or both. Baseline comparison: for baseline clinical characteristics, there were no statistical differences (P = 0.06) between groups in corneal and conjunctival staining, hyperemia, TBUT, unanesthetized Schirmer test results, BCVA, tear osmolarity, or IOP (Table 4) |
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| Interventions |
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| Outcomes |
Time points of primary outcome data collected: between Visits 2 and 3, i.e. before and after 2 hours of desiccating stress in participants treated for 21 days Primary outcomes of the study:
Other outcomes of the study: All other evaluations were considered as secondary variables measuring efficacy, except those included as safety measures (Table 1); these included OSDI scores, BCVA (high and low contrast), tear osmolarity, treatment satisfaction, TBUT, Lissamine green conjunctival staining, biomicroscopy with slit lamp, Schirmer test (unanesthetized), IOP, fundus evaluation, and optic cup‐to‐disc ratio. These were evaluated between Visits 1 and 2, 2 and 3, and 3 and 4. |
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| Study Identification |
Sponsorship source: the study was sponsored by and conducted at Instituto Universitario de Oftalmobiología Aplicada, University of Valladolid, Valladolid, Spain (in the text). According to the footnotes of the article, the study was supported by the Spanish Ministry of Economy and Competitiveness (grant no.: SAF2010‐15361); European Social Funds, Operative Program for Castilla y León, Castilla y León Council, Spain (grant no.: EDU/346/2013); and the Inflammation Research Program, Allergan Inc (Irvine, CA, USA) (contributed extra funding for environmental chamber use). Ethics approval: "This clinical trial was approved by the University Hospital Ethics Committee (Valladolid, Spain) and by the Spanish Regulatory Agency (Spanish Drugs and Health Products Administration; www.aemps.gob.es/en/home.htm) with EUDRA (European Union Drug Regulating Authorities) number 2013‐002183‐63" Correspondence author's name: Margarita Calonge, MD, PhD; Institution: Instituto Universitario de Oftalmobiología Aplicada, Universidad de Valladolid Additional information:
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| Notes | ||