Skip to main content
. 2022 Oct 21;2022(10):CD015070. doi: 10.1002/14651858.CD015070.pub2

Sheppard 2014.

Study characteristics
Methods 00. Study design: randomized controlled trial, parallel group
01. Calendar time when the study enrolled the first participant (YYYY/MM): 2006/11 (ClinicalTrials.gov)
02. Calendar time when the study completed follow‐up (YYYY/MM): 2007/09 (ClinicalTrials.gov)
03. Unit of randomization (participant or eye): participant
04. Masking of participants, treatment allocator, outcome assessor, or data analyzer: double (participant, investigator)
05. Study visits and the corresponding time points: study visits occurred on day 1 (screening and baseline, Visit 1), 14 ± 2 days (Visit 2), 30 ± 3 days (Visit 3), and 60 ± 5 days (Visit 4)
06. Instruments and the scales used for documenting patient‐reported symptoms or quality of life: OSDI: a global assessment of their perceptions about their dry eye condition and how it had impacted their vision and daily activities at Visits 2, 3, and 4 and also rated the tolerability of the topical CsA drops since the previous study visit at the third and fourth study visits
07. Assessment for safety outcomes: safety outcomes included ocular and systemic adverse events, IOP, and ophthalmoscopic examination findings
08. Planned follow‐up duration: 60 days
09. Actual follow‐up duration: 60 ± 5 days
10. Planned treatment duration (of the intervention steroid): 60 days
11. How missing data were handled: complete‐case analysis
12. Description on power and sample size calculation: the calculations were based on a power of 80% with an alpha of 0.05 (2‐tailed) and also used published data to estimate standard deviations for individual parameters of the study, which included OSDI, Lissamine staining (NEI scale), central fluorescein staining (NEI scale), and Schirmer test
Participants Country: USA
Setting: multicenter
Interventions:

  • Loteprednol etabonate (LE) 0.5% plus cyclosporine A 0.05% (CsA, Restasis)


Age, mean/SD (range): 59.6/12.1 (27 to 80)
Female, n (%): 44 (77%)
Etiology, n (%): NR
Participants (eyes) randomized: NR
Participants (eyes) analyzed for primary study outcomes: 57
Participants (eyes) analyzed for safety outcomes: 57

  • Artificial tears (AT) plus cyclosporine A  0.05% (CsA, Restasis)


Age, mean/SD (range): 57.9/1038 (36 to 79)
Female, n (%): 43 (78%)
Etiology, n (%): NR
Participants (eyes) randomized: NR
Participants (eyes) analyzed for primary study outcomes: 55
Participants (eyes) analyzed for safety outcomes: 55

  • Overall


Age, mean/SD (range): 58.7/11.4 (24 to 80)
Female, n (%): 87 (78%)
Etiology, n (%): NR
Participants (eyes) randomized: 116
Participants (eyes) analyzed for primary study outcomes: 112
Participants (eyes) analyzed for safety outcomes: 112
Inclusion criteria:

  1. Between 30 and 80 years of age 

  2. Has not worn contact lenses for at least 1 month before the study and agrees to not wear contact lenses during the study 

  3. Oral medications stable 1 month before study 

  4. Oral medications anticipated to be stable during 60 days study 

  5. Patient is in generally good and stable overall health 

  6. Corneal stain, conjunctival stain, OSDI, or using regular AT at least on average twice a day 

  7. Informed consent signed


Exclusion criteria: 

  1. History of Stevens–Johnson syndrome or ocular pemphigoid 

  2. Punctal plugs inserted or punctual cautery in the past 3 month

  3. Intraocular surgery within 3 months

  4. History of liver disease 

  5. Pregnant or lactating women 

  6. Severe clinical vitamin deficiencies or history of vitamin overdose 

  7. Highly variable vitamin intake 

  8. Unstable use of systemic or topical medications known to create dry eye 

  9. Corneal pathology that could cause an ocular surface disorder 

  10. Use of glaucoma medications, topical or oral 

  11. Unstable diabetes mellitus 

  12. Allergy or sensitivity to Lotemax, Restasis, or the OTC tear supplement 

  13. Use of topical steroids or Restasis within the past 1 month

  14. Use of other topical ocular agents other than tear replacements within the past 1 week


Baseline comparison: there were no statistically significant differences in baseline characteristics within and between treatment groups (Table 2)
Interventions  

  • Loteprednol etabonate (LE) plus cyclosporine A  0.05% (CsA, Restasis), LE 4 times daily for 2 weeks, then CsA 2 times a day was added for day 15 to day 60

    • LE run‐in for 2 weeks before adding CsA

  • Artificial tears (AT) plus cyclosporine A  0.05% (CsA, Restasis), AT 4 times daily for 2 weeks, then CsA 2 times a day was added for day 15 to day 60


 
Outcomes Time points of primary outcome data collected: day 14, 30, and 60
Primary outcomes of the study: 
The primary efficacy outcomes included:

  1. a 12‐item OSDI questionnaire;

  2. Likert scale using standardized facial expressions;

  3. Lissamine green staining (NEI scale);

  4. fluorescein staining (NEI scale);

  5. Schirmer tear test.


Other outcomes of the study: frequency of adjunctive tear use (> 6/d, 3 to 6/d, 1 to 2/d, none)
Study Identification Sponsorship source: Supported by an unrestricted research grant from Bausch & Lomb Inc, Rochester, NY, USA, and the Virginia Eye Foundation, Norfolk, VA, USA
Ethics approval: NR
Correspondence author's name: John D Sheppard; Institution: Virginia Eye Consultants, Norfolk, VA, USA
Additional information:

  1. Trial registration no.: NCT00407043

  2. Trial registration website: ClinicalTrials.gov

  3. Financial disclosure or conflicts of interest statement from authors: the authors have no other conflicts of interest or funding to declare
Notes  

  • 77% of the study participants were white

  • Presented at the American Academy of Ophthalmology Annual Meeting, New Orleans, LA, November 2007; the Royal Hawaiian Eye Meeting, Wailea, Hawaii, January 2008; and the Association for Research in Vision and Ophthalmology Meeting, Ft Lauderdale, FL, April 2008