Efficacy of Zylet vs. Lotemax for the Treatment of Ocular Surface Inflammation/MGD/Blepharitis (ZvL)

• Change in the Presence of Corneal Inflammatory Cells [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  Change in the presence of corneal inflammatory cells from baseline to week 8, as seen by in-vivo confocal microscopy.
• Change in Ocular Surface Disease Index (OSDI) [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
  Change in Ocular Surface Disease Index (OSDI) from baseline to week 8.
• Change in Symptom Assessment iN Dry Eye (SANDE) [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
  Questionnaire given to patients to assess both the frequency and severity of dry eye symptoms. Change is quantified from baseline to week 8.
• Change in Corneal Fluorescein Staining Score [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
  Change in corneal fluorescein staining (NEI grading scheme) from baseline to week 8.
• Change in Bulbar Hyperemia [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
  Change in bulbar hyperemia from baseline to week 8.
• Meibomian Gland Disease (MGD) Score [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
  Change in Meibomian Gland Disease (MGD) Score from baseline to week 8.

This is a Phase IV, single site, randomized, double masked, parallel control clinical trial of 60 subjects to investigate the variance of efficacy between Lotemax® and Zylet® for treatment of ocular surface inflammation due to meibomian gland dysfunction (MGD). Efficacy will be measured by in-vivo confocal microscopy, corneal fluorescein staining, grading of meibomian gland dysfunction and validated ocular symptom assessment questionnaire.

Posterior blepharitis is a common chronic eyelid condition that is described as generalized inflammation of the posterior lid margin and associated with inflammation of the ocular surface and with symptoms of burning, irritation, and discomfort. Posterior blepharitis is associated with various disorders of the meibomian glands, known collectively as meibomian gland dysfunction (MGD). It is associated either with obstruction and inflammation of the meibomian glands or, less commonly, atrophy of the meibomian glands.

Clinically, MGD often presents with inspissated meibomian glands, oily tear film, as well as inflammation and vascularization of the meibomian gland orifices. Papillary hypertrophy of the tarsal conjunctiva and corneal punctate epitheliopathy are often present, and there are prominent associations with dermatoses, such as acne rosacea, seborrhoeic dermatitis, and atopic dermatitis. Evidence from several sources suggests that MGD of sufficient extent and degree is associated with a deficient tear lipid layer, an increase in tear evaporation, and the occurrence of an evaporative dry eye. In fact MGD is considered to be the most common cause of evaporative dry eye. Individuals with MGD often complain of significant discomfort, including burning, itching, irritation, and photophobia. They may also have other associated symptoms of dry eye and may be plagued by blurred vision, gradual contact lens intolerance. Furthermore, these patients may become functionally handicapped by the negative impact of dry eye on their crucial daily activities such as working, reading, using computer, and driving.

Despite the high incidence of posterior blepharitis, there is currently no consistently effective treatment for this condition and it still remains a therapeutic challenge. Posterior blepharitis has traditionally been managed with eyelid hygiene, topical antibiotics (erythromycin or bacitracin ointments), oral tetracyclines (tetracycline, doxycycline, or minocycline) and corticosteroids which are often time consuming, frustrating, and frequently ineffective or variably effective.

The purpose of this study is to compare the effectiveness of topical loteprednol (corticosteroid) vs. the combination of loteprednol and tobramycin (corticosteroid and antibiotic) against an artificial tear. It is critical to determine to what extent the addition of an antibiotic to a topical steroid can enhance the therapeutic efficacy of the treatment.

• Meibomian Gland Dysfunction
• Posterior Blepharitis

• Drug: Loteprednol/tobramycin
  Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks.
  Other Name: Zylet
• Drug: Loteprednol
  Eye drops, 1 drop twice a day for 4 weeks
  Other Name: Lotemax
• Drug: Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops
  Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), 1 drop twice a day for 4 weeks.

• Active Comparator: Zylet
  Subject randomized to this arm will be treated with Zylet, twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation (swelling). Tobramycin is an antibiotic.
  Intervention: Drug: Loteprednol/tobramycin
• Active Comparator: Lotemax
  Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation (swelling).
  Intervention: Drug: Loteprednol
• Placebo Comparator: Bausch & Lomb Lubricant Drops
  Subject randomized to this arm will be treated with artificial tears, twice a day, for 4 weeks.
  Intervention: Drug: Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops

Inclusion Criteria:

• Male or female
• At least 18 years of age
• Has not worn contact lenses, except for bandage contact lens or rigid gas permeable lens, for at least 2 weeks prior to the study and agrees to not wear contact lenses during study
• Patient is in generally good & stable overall health
• Minimum corneal fluorescein staining of 1+ in at least one eye
• OSDI score >30
• The patient must have a diagnosis of posterior blepharitis
• A negative urine pregnancy test result for women of childbearing potential
• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.
• Normal lid position and closure
• Ability to understand and provide informed consent to participate in this study
• Willingness to follow study instructions and likely to complete all required visits

Exclusion Criteria:

• History of Stevens-Johnson syndrome or ocular pemphigoid
• On systemic immunosuppressive regimen
• History of eyelid surgery
• Intra-ocular surgery or ocular laser surgery within 3 months
• History of microbial keratitis, including herpes
• Active ocular allergies
• Corneal epithelial defect > 1mm2
• Use of topical anti-inflammatories, such as steroids, Restasis, or NSAID within the past 2 weeks
• Any change in dosage of tetracycline compounds (tetracycline, doxycycline, and minocycline) within the last month
• Use of isotretinoin (Accutane) within the past 6 months
• Pregnant or lactating women
• Signs of current infection, including fever and current treatment with antibiotics
• Active liver, renal, or hematologic disease
• The use of any other investigational drug
• Individuals with a known history of glaucoma, individuals with IOP >22 Hg in either eye and individuals with a known family history of glaucoma in primary (first degree) relatives (ie. mother, father, sibling or child)