Cross-linked Hyaluronic Acid and Coenzyme Q10 in the Treatment of Dry Eye
Condition: Dry Eye Syndrome
MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca
Study type: Interventional

Summary: 
      Background: Dry eye disease (DED) is a common condition causing burden on visual function and
      reducing quality of life. Corticosteroids and/or cyclosporine eye drops are able to improve
      DED symptoms, however, side effects of immune suppression and cost lead patients often to
      suspend treatment. Consequently, is important to identify therapies alleviating DED symptoms.
      A randomized, controlled, single masked study, was performed in 40 patients affected by mild
      to moderate DED, to evaluate efficacy and safety of a collyrium based on cross-linked
      hyaluronic acid (XLHA) added with Coenzyme Q10 (CoQ10) in comparison to an eye drop
      considered a gold standard for tear substitutes, based on hyaluronic acid (HA) 0.15%.

      Methods: eye drops were administered four times a day for 90 days to enrolled subjects
      divided in two groups: group A treated with XLHA+CoQ10, group B treated with HA. Ocular
      Surface Disease Index (OSDI) questionnaire, visual acuity, intraocular pressure (IOP), fundus
      exam, tear break-up time (TBUT), corneal and conjunctival fluorescein staining, corneal
      esthesiometry, corneal confocal microscopy, were performed at different visits until the 90th
      day.
    

Detailed description: 
      Introduction:

      Dry eye disease (DED) is a common eye condition causing burden on visual function and
      reducing quality of life and work productivity. DED is a tear film disorder resulting in
      hyperosmolarity of tear film and inflammation of ocular surface that results in symptoms of
      discomfort, visual disturbance, and tear film instability with potential damage to the ocular
      surface. This condition provokes traumatisms caused by the movement of the eyelids on the
      ocular surface and an insufficient cleansing of the same by microbial agents and/or foreign
      bodies.

      Prevalence of DED increases with age and women are particularly susceptible, especially those
      receiving estrogens. The pathogenesis is not fully understood; however, it has been
      recognized that inflammation has a prominent role .

      The most common symptoms of DED are: burning, foreign body sensation in the eye, difficulty
      in opening the eyelids on awakening, blurred vision and, in severe cases, pain and
      photophobia. DED is accompanied by increased tear film osmolarity and inflammation of ocular
      surface.

      There is no gold standard treatment for DED, but corticosteroids and/or cyclosporine eye
      drops improve the symptoms. However, given the side effects of immune suppression and the
      cost of pharmaceutical preparations, patients often suspend treatment before the
      effectiveness of therapy can be verified.

      Artificial tears are considered a mainstay in dry eye treatment. Hyaluronic acid (HA), a
      natural glycosaminoglycan, is a component of tear film. It increases tear film viscosity and
      hydrates and lubricates the ocular surface. HA possesses intrinsic water retention
      properties, viscoelasticity and favours the healing of corneal and conjunctival epithelium.
      Safety and efficacy of HA for the treatment of DED has been demonstrated. Eye-drops
      containing HA determine a reduction of ocular surface inflammation, with consequent
      improvement of quality of corneal and conjunctival epithelium. Our previous clinical study
      showed HA beneficial effects on the conjunctival epithelium of dry eye patients. Results of
      another clinical trial, confirm beneficial effects of HA and show that in combination with
      tamarind seed polysaccharide it can be effective in improving dry eye symptoms, opening new
      scenarios in the treatment of this disease by combining different molecules.

      Coenzyme Q10 (CoQ10) is an endogenous, lipid soluble molecule, also known as ubiquinone.
      CoQ10 plays a key role in oxidative metabolism supporting the adenosine triphosphate (ATP) in
      the mitochondria and, in its reduced form, acts as a lipid antioxidant. In almost all tissues
      of the human body, CoQ10 levels decline with age and ocular function is sensitive to
      variations of concentration of CoQ10 .

      A randomized, controlled, single masked study, was performed in mild to moderate dry eye
      patients, to evaluate the efficacy and the safety of a collyrium based on cross-linked HA
      (XLHA) added with CoQ10 in comparison to an eye drop formulation, commonly used in clinical
      practice and considered a gold standard for tear substitutes, in the treatment of dry eye,
      based on 0.15% linear HA.

      Methods This randomised, single-masked, parallel-group comparative study investigated the
      efficacy and safety, in treatment of dry eye patients, of an ophthalmic solution containing
      XLHA added with CoQ10 (VisuXL®, Visufarma, Rome, Italy) in comparison with a formulation
      containing hyaluronic acid 0.15% (HA). The study screened 46 patients and 40 were enrolled
      [(13 male, 17 female, with an age range 40-79 years; mean age 62 ± 12.8 (SD) years)]
      suffering from mild to moderate dry eye attending to the Eye Clinic, Department of Biomedical
      Sciences, Regional Referral Center for the Ocular Surface Diseases, University of Messina,
      Messina, Italy. Enrolled subjects were divided into two treatment groups (Group A receiving
      the study formulation based on XLHA+CoQ10 and Group B receiving the comparator formulation
      based on 0.15% HA) according to a randomization scheme, corresponding to allocation codes
      generated for the two treatments using the permuted block method. The two eye-drops
      compositions used for the study were the following: group A formulation (XLHA+CoQ10): 100 ml
      containing Cross-Linked HA sodium salt 100 mg, Coenzyme Q10 100 mg, with Vitamin E tocopheryl
      polyethylene glycol succinate (TPGS) 500 mg (as a solubilizing agent for the lipid soluble
      CoQ10), Isotonic buffered solution q.s. to 100 ml; group B formulation: HA sodium salt 100
      mg; isotonic buffered solution q.s. to 100 ml. Both formulations were unpreserved.

      All patients included were treated for a run-in period of 7 days with one eye drop of saline
      four times daily. At the end of this period (time 0 of the study) the subjects were randomly
      divided into the two groups and assigned to a treatment.

      The visits were carried out in a blind fashion by investigators. Eye drops were administered
      four times a day for 12 weeks and subjects enrolled in the study underwent grading of
      subjective symptoms and clinical examination at time 0 and after 15, 30, and 90 days. The
      patients were allowed to know the brand name of the eye drops they were using.

      Outcomes The Ocular Surface Disease Index (OSDI) questionnaire, visual acuity, intraocular
      pressure (IOP), and fundus exam, tear break-up time (TBUT), corneal and conjunctival
      fluorescein staining, esthesiometry, corneal confocal microscopy. Adverse events were
      monitored.

      OSDI is one of the most widely used questionnaires. The 12-item OSDI questionnaire scores
      range from 0 to 100, high scores represent higher disability. The scale showed good
      sensitivity in discriminating normal people from subjects affected by dry eye and to
      correlate well with disease severity.

      The ocular surface fluorescein stain score was assessed 3 minutes after the instillation of
      fluorescein; a modified Oxford score was used: cornea and conjunctiva were scored separately
      from 0 to 5 (from 0 = none to 5 = extended areas of confluent stain), for the conjunctiva a
      mean for the scores from the nasal and temporal regions was used. The ocular surface was
      observed through a cobalt blue light and a Wratten #12 yellow filter.The difference among the
      scores obtained in each visit was calculated.

      Corneal sensitivity was measured by Cochet-Bonnet aesthesiometer to evaluate the activity of
      the ophthalmic branch of fifth cranial nerve (trigeminal). It was measured by the evaluating
      the length of the filament able to evoke a tactile sensation (mm of filament).

      In vivo confocal microscopy was performed, after the topical instillation of a drop of
      unpreserved 0.4% oxybuprocaine, using the 40x contact objective and the additional Z-Ring
      probe, to allow a precise positioning of the probe over the central corneal area.

      For statistical analysis, only the results of right eyes were considered. Student's t-test
      and Mann-Whitney U-test were used as appropriate. Values of P≤0.05 were considered
      statistically significant.
    

Intervention name(s): XLHA+CoQ10; Hyaluronic acid (HA)
Intervention type(s): Device; Device
Intervention description(s): XLHA+CoQ10 for four times a day for 12 weeks.; Hyaluronic acid (HA) for four times a day for 12 weeks.
Other intervention name(s): VisuXL®
Intervention MeSH terms: Hyaluronic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomised, single-masked, parallel-group comparative study.
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Dry Eye Syndrome; artificial tear; CoQ10; Hyaluronic acid