Anti-inflammatory Effects and Clinical Efficacy of Topical Thealoz Total Eye Drops in Patients With Chronic Dry Eye Disease and Associated Ocular Surface Inflammation

Medical University of Vienna30 enrolled

Overview

Dry eye disease (DED) is a highly prevalent ocular condition and induces a significant burden to the affected patients. Regardless of the underlying etiology, DED is associated with increased inflammation of the entire ocular surface including the adnexa, conjunctiva and cornea. As such, there is evidence from in vitro, animal and clinical studies that this inflammatory response of the ocular surface plays a pathophysiological key role in the development of DED. The Dry Eye Workshop 2007 (DEWS) therefore suggests beside of restoring the tear film by administering topical lubricants, breaking the vicious circle of inflammation is an important mainstay of therapy in patients with DED. Recently, a new medical device (Thealoz Total® eye drops) has been introduced for the treatment DED. Thealoz Total® eye drops are based on hyaluronic acid and exert their main action by lubricating the ocular surface. Further, this new formulation offers several advantages that make them potentially interesting to reduce DED related symptoms. First, the formulation is preservative-free, which is of special importance in patients with DED, since it has been shown that preservatives are detrimental for the ocular surface. thereby reducing signs and symptoms related to DED. Secondly, in addition to the lubricating effect of hyaluronic acid, Thealoz Total eye drops also contain trehalose, which exerts osmoprotetive effects and N-Acetyl Aspartyl Glutamic Acid (NAAGA). NAAGA is an amino conjugated dipeptide with anti-inflammatory properties. Thus, it is reasonable to hypothesize that Thealoz total eye drops are also capable of reducing ocular surface inflammation. The aim of the present study is to investigate whether topical administration with Thealoz Total® improves ocular surface inflammation as well as clinical signs and symptoms associated with DED.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years * Normal ophthalmic findings except dry eye disease * Chronic dry eye defined as longer than six months since diagnosis * OSDI ≥ 22 * Conjunctival Hyperemia≥ Grade 3 (Efron Scale) * Current use of topical lubricants since at least 3 months Exclusion Criteria: Ophthalmic exclusion criteria \- Best far corrected visual acuity \< 1/10 Severe Dry Eye associated with: * Eyelid malposition * Stevens Johnson Syndrome * Corneal dystrophy * Ocular neoplasia * Filamentous keratitis * Corneal neovascularisation * Orbital radiotherapy * Dry eye related to GVHD History of any of the following within last 3 months: * Systemic treatment of dry eye * Systemic treatment of MGD * Isotretinoïde, * Cyclosporine, * Tacrolimus, Siromilus, Pimecrolimus * Punctual plugs History of any of the following within previous six months: * ocular trauma * ocular infection, Ocular allergy History of any of the following within last 12 months: * inflammatory corneal ulcer * Herpetic eye infection or uveitis * Ocular surgery Systemic / non ophthalmic exclusion criteria: \- Known hypersensitivity to any of the components of the medical device under investigation or other study medication Specific exclusion criteria for women: * Pregnant or breast-feeding woman. * Woman of childbearing potential (neither menopausal, nor hysterectomized, nor sterilized) not using effective contraception (i.e. hormonal contraceptives, intra-uterine device, contraceptive implant or condoms) Exclusion criteria related to general conditions \- Inability of patient to understand the investigation procedures and thus inability to give valid, informed consent.

Outcomes

Primary Outcomes

Patient satisfaction assessed by a VAS

Patient satisfaction assessed by a Visual Analogue Scale (VAS) (min 0 - max 100) The VAS consists of a 10cm line, with two end points representing 0 ('no symptoms') and 100 ('max symptoms')

Time frame: week 12

Conjunctival hyperemia grading with Photographs (Efron) scale at week 12

Conjunctival hyperemia grading with Photographs (Efron) scale at week 12 The Efron Scale is a clinical grading scale used to assess conjunctival hyperemia. It provides a standardized visual grading from 0 to 4 Grade 0 = normal Grade 1 = trace / very mild Grade 2 = mild to moderate Grade 3 = moderate to severe Grade 4 = severe

Time frame: week 12

Secondary Outcomes

Changes from baseline in conjunctival hyperemia grading with photographs (Efron) scale

Changes from baseline in conjunctival hyperemia grading with photographs (Efron) scale The Efron Scale is a clinical grading scale used to assess conjunctival hyperemia. It provides a standardized visual grading from 0 to 4 Grade 0 = normal Grade 1 = trace / very mild Grade 2 = mild to moderate Grade 3 = moderate to severe Grade 4 = severe

Time frame: week 6 and 12

Changes from baseline in corneal fluorescein staining according to the Oxford Scale

Changes from baseline in corneal fluorescein staining according to the Oxford Scale The Oxford Scale is a standardized grading system corneal staining after fluorescein dye application. It indicates the level of epithelial damage or ocular surface compromise. The grading runs from 0 to 5, based on a set of reference panels with dots representing staining patterns. Grade 0 = none (no staining) Grade 1 = trace (minimal staining, very few punctate dots) Grade 2 = mild (slightly more numerous dots) Grade 3 = moderate (obvious punctate staining, more confluent areas) Grade 4 = marked (extensive staining, coalescent areas) Grade 5 = severe (dense, widespread staining, severe epithelial damage)

Time frame: week 6 and 12

Changes from baseline in Tear Break Up Time (BUT) with Minims- Fluorescein Sodium 2,0%

Time frame: week 6 and 12

Changes from baseline in Schirmer I test using Schirmer paper strips

Time frame: week 6 and 12

Changes from baseline in conjunctival hyperaemia assessment using Mc Monnies photographic scale

Changes from baseline in conjunctival hyperaemia assessment using Mc Monnies photographic scale The McMonnies Photographic Scale is a clinical grading system for bulbar conjunctival hyperemia. It uses a series of standardized photographs of eyes with increasing levels of redness. Clinicians compare the patient's eye to these photographs and assign a grade. The scale typically ranges from 0 to 5: 0 = none (normal, no redness) 1. = trace (very mild hyperemia) 2. = mild 3. = moderate 4. = marked 5. = severe (intense hyperemia with engorged vessels)

Time frame: week 6 and 12

Changes from baseline in symptoms using the OSDI questionnaire

Changes from baseline in symptoms using the Ocular Surface Disease Index (OSDI) questionnaire It contains 12 questions, divided into three domains, every qestion has 0-4 points: * Ocular symptoms * Vision-related function * Environmental triggers Interpretation of scores: 0-12 = normal 13-22 = mild dry eye 23-32 = moderate dry eye 33-100 = severe dry eye Not every patient will necessarily answer all 12 questions. To account for this, the OSDI uses a normalization formula: 1. Add together all the scores from the answered questions. 2. Multiply this sum by 25 (this scales the score to a 0-100 range). 3. Divide the result by the number of questions answered.

Time frame: week 6 and 12

Changes from baseline in symptoms within the last 48 hours

Changes from baseline in symptoms within the last 48 hours Patient will be asked: "How do you judge the severity of your following ocular symptoms within the last 48 hours?" The severity of the following ocular symptoms will be assessed at each visit: burning/irritation, stinging/eye pain, light sensitivity, itching/pruritus, eye dryness feeling, tearing, foreign body sensation as follows: 0 = Absent 1. = Mild, present but not disturbing 2. = Moderate, disturbing, but not limiting with daily activities 3. = Severe, very distressing and interfering with daily activities The ocular symptoms will be assessed in global for both eyes at each visit. The value at Visit 1 will be the baseline value. Questions are: Burning/irritation Burning/pain Light sensitivity (photophobia) Itching Sensation of dryness in the eyes Tearing (watery eyes) Foreign body sensation

Time frame: week 6 and 12

Changes from baseline in tear proteomics and lipidomics

Changes from baseline in tear proteomics and lipidomics Tear film samples will be collected on week 1 and week 12 by Schirmer-I-Test. Samples will be extracted and and measured in an untargeted fashion. Samples will be stored at -80°C until time of analysis and will be discarded after analysis.

Time frame: week 12

Patient satisfaction assessed by a VAS

Patient satisfaction assessed by a Visual Analogue Scale (VAS) The VAS consists of a 10cm line, with two end points representing 0 ('minimum') and 100 ('maximum')

Time frame: week 12

Anti-inflammatory Effects and Clinical Efficacy of Topical Thealoz Total Eye Drops in Patients With Chronic Dry Eye Disease and Associated Ocular Surface Inflammation

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes