The DIOXXACT Trial(Diurnal IOP and OBF Xalatan vs Xalatan And Cosopt Trial)
Condition: Eye Disease
MeSH terms: Eye Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      Diurnal and intervisit fluctuations in IOP are strongly associated with progression of open
      angle glaucoma and therefore need to be minimized. Control of diurnal fluctuations of IOP
      with different ocular hypotensive medications has been studied in some detail. But how do IOP
      changes contribute to progressive glaucomatous optic nerve damage? It is reasonable to assume
      that there are two principal effects of IOP changes. First, IOP fluctuations result in
      changes in the stresses and strains on the ONH which in turn result in morphological changes
      to the ONH. These morphological changes could in turn result in stretching and damage to
      axons of the ONH. Secondly, IOP fluctuations results in changes to the forces acting on the
      ONH vasculature, leading to changes in ONH vascular perfusion. These changes to perfusion
      could in turn result in relative ischemia of the ONH and consequent ONH damage.

      The investigators propose to monitor diurnal fluctuations in IOP and choroidal blood flow
      (Pulsatile Ocular Blood Flow,POBF), and intervisit ONH topographical and blood flow
      changes-ie to monitor the direct ONH consequences of IOP . Open angle glaucoma patients are
      commonly prescribed topical latanoprost as first line therapy. The EXACCT study, for which I
      was the principal investigator and which is now submitted for publication, demonstrated that
      COSOPT was an efficacious choice as second line therapy for patients not controlled on
      latanoprost monotherapy. The investigators will therefore recruit 20 OAG patients on
      latanoprost monotherapy, perform diurnal curves of IOP, as well as a.m. ONH morphology and
      ONH blood flow. Cosopt will then be added and at the next visit the same measurements will be
      repeated.

      The investigators expect that when Cosopt is added the investigators will demonstrate
      improved IOP, morphology and blood flow compared to the latanoprost baseline. Furthermore the
      investigators expect the the diurnal fluctuation of IOP and choroidal blood flow will be
      stabilized on Cosopt therapy. The implications are that adding Cosopt to latanoprost can
      stabilize not only the IOP but also the damaging consequences of IOP to the optic nerve head.
    

Detailed description: 
      Twenty patients with open angle glaucoma or ocular hypertension currently on latanoprost
      immunotherapy will be recruited.

      A complete routine ophthalmic examination including biomicroscopy, gonioscopy and fundus
      ophthalmoscopy will be performed. The eye with better visual acuity is selected for fundus
      flowmetry.

      All patients will undergo a complete diurnal workup including IOP, as well as 10am Confocal
      scanning laser ophthalmoscopy (Heidelberg Retina Tomography-3) of ONH topography. Optic nerve
      head, nasal and temporal peripapillary retinal blood flow are measured with scanning laser
      Doppler flowmetry (SLDF; Heidelberg Retinal Flowmeter/Tomograph, SLDF analysis software v3.3,
      Heidelberg Engineering, Germany Goldmann IOP will be measured at 8am, 10am 2pm and 4pm. Pulse
      amplitude, similar to Pulsatility Ocular Blood Flow (POBF) will be measured using the Pascal
      Dynamic Contour Tonometer (DCT) at 8am, 10am, 2pm, and 4 pm.

      All procedures will conform to the Declaration of Helsinki and the study will be approved by
      the Ethics Committee and each patient will sign an informed consent form.

      Following visit one, Cosopt will be added to the patients therapy (bid). Following 6 weeks of
      therapy patients will return for visit two. Cosopt will be applied by the investigator at 8am
      on visit 2.

      We expect that this blood flow will be improved with COSOPT therapy and that the diurnal
      fluctuation of this parameter will be improved as well. It is evidently of great interest to
      examine diurnal changes in ocular blood flow with and without COSOPT and the measurement of
      POBF can be performed without great cost and is well tolerated by the patient.

      Changes in IOP, ONH Topography, and ONH blood flow will be analysed using appropriate
      statistical approaches
    

Intervention name(s): Dorzolamide 20 mg and Timolol 5 mg
Intervention type(s): Drug
Intervention description(s): Twice daily in the affected eye(s)
Other intervention name(s): Cosopt
Intervention MeSH terms: Timolol; Dorzolamide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Ocular Hypertension; Open Angle Glaucoma