Assessment of the Ability to Distinguish Odors in Glaucoma Patients
Condition: Glaucoma
MeSH terms: Glaucoma
Study type: Observational

Summary: 
      Glaucoma is one of the leading causes of blindness worldwide. The key feature of glaucoma is
      damage to the optic nerve head with loss of retinal ganglion cells and local tissue
      remodeling. Neuronal cell death in glaucoma occurs by apoptotic mechanisms1. Apoptosis of
      neurons also plays a major role in neurodegenerative diseases, such as Alzheimer's or
      Parkinson's disease. An association between glaucoma and these disorders has been described
      2-4. Furthermore, it has been reported that the olfactory function is disturbed in these
      neurodegenerative diseases5-6. We hypothesize that similar olfactory alterations may occur in
      glaucoma which is in fact a local neurodegenerative disease.
    

Detailed description: 
      1. Introduction

             1. Background and rationale of the study Glaucoma is one of the leading causes of
                blindness worldwide. The key feature of glaucoma is damage to the optic nerve head
                with loss of retinal ganglion cells and local tissue remodeling. Neuronal cell
                death in glaucoma occurs by apoptotic mechanisms1. Apoptosis of neurons also plays
                a major role in neurodegenerative diseases, such as Alzheimer's or Parkinson's
                disease. An association between glaucoma and these disorders has been described
                2-4. Furthermore, it has been reported that the olfactory function is disturbed in
                these neurodegenerative diseases5-6. We hypothesize that similar olfactory
                alterations may occur in glaucoma which is in fact a local neurodegenerative
                disease.

             2. Study objectives Primary Objective: To test the olfactory function in glaucoma
                patients.

             3. Investigational plan Chronic glaucoma patients will be assessed regarding
                inclusion/exclusion criteria and clinical criteria. A basic otorhinolaryngological
                examination addressing the possible exclusion criteria will be performed prior to
                the Sniffing Sticks test battery. A simple questionnaire regarding an olfactory
                status of the patient will be filled out. The olfactory performance of glaucoma
                patients will be compared to the existing age-matched normative database.

             4. Design Single center cohort study, normative database as control.

             5. Selection of study population

                I. Number of subjects Thirty consecutive glaucoma patients, age 18 - 70, will be
                recruited from the glaucoma consultation at the University Eye Clinic Basel.

                II. Prestudy screening A detailed medical and ophthalmic history will be recorded
                and all patients will complete an ophthalmologic examination (best corrected visual
                acuity, intraocular pressure measurements, slit-lamp examination, indirect
                fundoscopy) as well as an otorhinolaryngological examination.

                III. Inclusion criteria Diagnosis of chronic open-angle glaucoma will be based on
                the presence of typical glaucomatous disc damage and visual field defects. Only
                patients with a recent gonioscopic examination and at least two visual field
                examinations will be recruited.

                IV. Exclusion criteria Occludable iridocorneal angles, a history of current,
                chronic or recurrent inflammatory eye disease, a history of retinal or
                neuroophthalmologic disease that could result in visual field defects, need for any
                concomitant medications that may interfere with the evaluation of olfactory
                function, a history of past or active alcohol or drug abuse, smoking, a history of
                olfactory disturbance related to identifiable local factors, and any local
                condition that could lead to hyposmia/anosmia or interfere with the olfactory
                function, such as polyps, chronic sinus infection, sub(acute) viral or bacterial
                infection, history of sinus surgery, will be considered as an exclusion criterion.

                V. Study medication NA

             6. Study protocol I. General restrictions on subjects NA

                II. Dietary restriction NA.

                III. Description of study days On the experimental day a detailed history will be
                taken and a complete ophthalmologic examination including best corrected visual
                acuity, slit-lamp examination, indirect fundoscopy, and intraocular pressure
                measurement will be performed (KG). Based on these examinations and chart data, the
                patient shall be classified as glaucoma patient. A basic otorhinolaryngological
                screening examination will follow, the patient will fill an olfactory questionnaire
                and the Sniffing Sticks test battery will be performed (AWL).

             7. Efficacy variables I. Outcome variables Odor threshold score (0-16), odor
                discrimination task score (0-16), Odor identification score (0-16), composite score
                (sum of the three above).

           II. Follow-up safety investigations NA

        2. Methods of evaluation

           a. Sniffing Sticks test battery7 Commercially available felt-tip pens, 14 cm long and
           with an inner diameter of 1.3 cm, are filled with 4 mL of liquid odorants or odorants
           dissolved in propylene glycol. For odor presentation the cap is removed by the
           experimenter for approximately 3 seconds and the pen's tip is placed 2 cm in front of
           the examined nostril. Three tests are performed. Odor threshold for n-butanol is
           assessed using a single-staircase, triple-forced choice procedure. Sixteen dilutions are
           prepared. Three pens are presented at randomized order, with two containing only the
           solvent. The patient's task is to identify the odor-containing pen. The score ranges
           from 0 to 16. In the odor-discrimination test, the patient has to determine which of the
           three presented pens smell differently. A total of 16 triplets is presented to the
           patient, and thus the score ranges from 0 to 16. Odor identification is assessed by
           means of 16 common odors, using a multiple choice technique with a list of four
           descriptors. The score ranges also from 0 to 16. The composite score is the sum of three
           scores.

        3. Statistical procedures

             1. Biometric methods Mann-Whitney U-test, p<0.05 being considered significant.

             2. Statistical model Olfactory scores of glaucoma patients will be compared to the
                age-matched normative database by means of Mann-Whitney U-test.

             3. Study power No power calculations were performed, as there are no prior pilot
                studies.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        glaucoma patients
      
Keywords: Glaucoma; Olfactory functions; Sniffing Sticks Test