Clinical Study Of Nearsightedness; TReatment With Orthokeratology Lenses (CONTROL)
Condition: Myopia
MeSH terms: Myopia
Study type: Interventional

Summary: 
      Myopia is a common disease of the eye with increasing prevalence in the Western World as well
      as in South East Asia where 60-90% of the children are affected. High myopia is associated
      with an increasing risk of sight threatening complications such as retinal detachment,
      glaucoma, macular choroidal degeneration and myopic choroidal neovascularization. In myopia
      the eye is elongated compared to an emmetropic eye. If the elongation of the eye can be
      controlled the progression of myopia can be controlled. Asian studies have shown reduction in
      axial length growth by 36-46% in children using orthokeratology contact lenses (OKL). OKL are
      custom fit, form stable lenses. During sleep the cornea is reshaped creating an emmetropic
      vision during the day, so no glasses or contact lenses are needed. Twin and family studies
      have shown a high heritability for the development of myopia, and more than 40 genetic loci
      have been identified indicating that the effect of OKL in Asian children might not be the
      same in North European children which is why we want to execute a similar study on North
      European children.

      Purpose:

        1. Investigate if nightly wear of OKL reduces the progression of childhood myopia (change
           in axial length) in Danish children when compared to a control group using monofocal
           glasses.

        2. Investigate the safety (Efron score) of OKL.

        3. Investigate children's quality of life impact of refractive correction (questionnaire)
           using OKL compared to glasses.

        4. Identify possible predictors for progression of myopia (AC/A ratio, peripheral defocus
           and higher order aberrations).

      Method:

      A randomized controlled 18 months prospective 1:1 study of a group of Danish children. 60
      children will be included; 30 in each group. The participants will undergo several
      measurements reflecting the anatomy and function of the eye at baseline, 6, 12 and 18 month
      to evaluate the effect.
    

Detailed description: 
      Myopia is a common disease of the eye with increasing prevalence in the Western World as well
      as in South East Asia where 60-90% of the children are affected. A Danish study found that
      early debut of myopia is associated with a higher degree of myopia later on in life. Myopia
      may be corrected with spectacles, contact lenses or surgically, but despite this
      socio-economic burden, high myopia is associated with an increasing risk of sight threatening
      complications such as retinal detachment, glaucoma, macular choroidal degeneration and myopic
      choroidal neovascularization.

      Myopia is a complex disease with a multi-factorial etiology. Twin studies and family studies
      have shown a high heritability for development of myopia, and more than 40 genetic loci have
      been identified. Outdoor activity seems to reduce the myopia progression. The shape of the
      eye may be of importance; axial growth makes the eye ellipsoidal which increase the
      peripheral defocus on the retina. Peripheral defocus has been suggested to induce further
      axial growth of the eyeball.

      Accommodation is a significant covariant of near work and reading. A cross section study has
      shown a reduced precision in accommodation (A) on a near object combined with increased
      convergence (C) in myopic eyes. This increased AC/A ratio (dynamic) may be a predictor for
      myopia progression.

      Interventions for reducing myopia progression have been many. The effects of progressive
      additional lenses, multifocal lenses and bifocal lenses have been limited. Anticholinergic
      eyedrops (Atropin 0.01%) significantly reduce the progression of myopia in Asian children by
      approximately 50% over a period of two years with limited side effects. Almost similar
      results have been found in Asian children using orthokeratology contact lenses (OKL) for
      reducing myopia progression.

      OKL are custom fit, form stable lenses used during sleep. The lenses induce a temporal
      flattening of the cornea, which modify or eliminate refractive errors, leaving no need for
      glasses or contact lenses during daytime. OKL were introduced in the 1960 ́s, but with
      limited success due the lens material (PMMA) which was not gas-permeable. Decentration was
      also a problem making the effect variable and unpredictable. With new gas- permeable lens
      materials and computer assisted topographic measurements of the cornea, fitting of the lenses
      has been improved significantly, so that nightly wear is now standard treatment.

      A clear-cut reduction in axial length growth in Asian children using OKL compared to
      single-vision spectacles (SVS) has been proofed in several studies. In these studies, which
      are very heterogeneous regarding design, reductions of 36-46% in axial length growth were
      found compared to a matched control group. Two European prospective cohort studies have
      investigated the effect of OKL compared to SVS in Spanish children. A reduction in axial
      growth of 32 % and 38% respectively was found. Side effects of OKL have been evaluated; in a
      meta-analysis from 2015, including 8 Asian and one of the European studies. Odds Ratio for
      side effects were 8.87 for the OK group compared to the control group, however all side
      effects were mild and disappeared after termination of the treatment.

      Thus, a reduction in childhood myopia using OKL has been proofed in Asian children; however,
      weather similar result can be achieved in a group of children from Northern Europe is
      unknown. The influence of OKL on quality of life impact of refractive correction has never
      been investigated in a randomized trail. How OKL reduce the axial growth of the eye is
      unknown. The lenses induce multifocality and higher order aberrations in the cornea, which
      might change the peripheral defocus. A change in defocus has been suggested as a mechanism
      for controlling axial length growth.

      Primary goals:

      In a randomized 18 months prospective 1:1 study of a group of Danish children to:

        1. Investigate if nightly wear of OKL (DreamliteR, Procornea, Nederlands) may reduce the
           progression of childhood myopia (change in axial length) when compared to a control
           group using SVS.

        2. Investigate safety (Efron score) in the use of OKL.

        3. Compare children's quality of life impact of refractive correction (questionnaire) using
           OKL and glasses.

        4. Identify possible predictors for progression of myopia (AC/A ratio, peripheral defocus
           and higher order aberrations).

      Hypothesis:

        -  Nightly wear of OKL reduces the progression of childhood myopia in Danish children.

        -  Use of OKL is safe, with no sight threatening complications during 18 months of nightly
           treatment.

        -  Children using OKL experience a higher quality of life impact of refractive correction
           compared to children wearing SVS.

        -  Response AC/A ratio is positively correlated to progression of childhood myopia.

        -  Use of OKL induce changes in corneal topography resulting in (1) decreased peripheral
           defocus (2) increased number of higher order aberrations. Progression in childhood
           myopia is associated to changes in peripheral defocus and higher order aberrations.

      Design:

      A 18-month randomized prospective 1:1 study of progression of myopia in a group of Danish
      children wearing OKL nightly (n=30) compared to a control group wearing SVS (n=30).

      Children randomized to OKL will be examined at BL and day 3 and 7 as well as month 1, 3, 6,
      9, 12, 15, and 18 after the start of treatment with OKL (T0).

      Children randomized to SVS will be examined at BL and month 6, 12 and 18 after receiving new
      glasses with optimal prescription (T0).

      Examination:

        -  Best corrected (using "push plus" refraction principle) ETDRS visual acuity: The OKL
           group (2-4 hours after lens removal) at BL and day 3 and 7 as well as month 1, 3, 6, 9,
           12, 15, and 18 after T0. The SVS group at BL and month 6, 12 and 18 after T0.

        -  Grading contact lens complications (Efron Grading Scale for Contact Lens Complications)
           for the OKL group at day 3 and 7 as well as month 1, 3, 6, 9,12, 15, and 18 after T0.

        -  Dynamic auto-refraction (Shin-Nippon SRW-5000, Kagawa, Japan) for both groups at a
           distance of 40 cm in primary gaze as well as 5, 10, 20 and 30 degrees eccentric to the
           nasal and temporal retina in the horizontal meridian at BL and month 6, 12 and 18 after
           T0.

        -  Measurements of convergence for both groups at a distance of 40 cm and 6 meter using the
           Eye-Link 1000 (SR Research, Ontario, Canada) at BL and month 6, 12 and 18 after T0.

        -  Cycloplegic auto-refraction at BL, 6, 12, and 18 months (Topcon KR-800, Topcon Europe
           Medical, Capelle aan den Ijss, Nederlands).

        -  Axial length measurements (Lensstar, LS900, Carl Zeiss, Haag-Streit, Koeniz,
           Switzerland) at BL, 6, 12 and 18 months after T0 for both patients groups.

        -  Pentacam (Oculus, Wetzlar, Germany) for the OKL group at BL, T0, day 3, 7 as well as
           month 1, 3, 6, 9, 12, 15, and 18 after T0 (measurements obtained 2-4 hours after lens
           removal). For the group wearing SVS at BL, and month 6, 12 and 18 after T0.

        -  Pediatric Refractive Error Profile 2 (questionnaire) will be performed at 12 month for
           both patient groups.
    

Intervention name(s): Orthokeratology lenses; Single-vision spectacles
Intervention type(s): Device; Device
Intervention description(s): Rigid gas permeable contact lenses; Regular single vision spectacles
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized controled clinical interventional trial
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Contact lenses; Children; Myopia