The Response of Intraocular Pressure to Systemic Hypercapnia and Hyperoxia

• Intraocular pressure [ Time Frame: Intraocular pressure will be measured during the study visit, ten minutes into each of the seven inhaled gas provocation stages ] [ Designated as safety issue: No ]
  Intraocular pressure will be measured using Goldmann applanation tonometry.
  
  

• Retinal blood flow [ Time Frame: Retinal blood flow will be measured during the second (optional) study visit, ten minutes into each of the seven inhaled gas provocation stages ] [ Designated as safety issue: No ]
  Retinal blood flow will be measured using the Canon Laser Blood Flowmeter in a subset of participants asked to return for a second visit. This will demonstrate that retinal blood flow behaves as the study claims that it does.
  
  

Device: RespirAct

Participants will breathe through a mask connected to a sequential rebreathing circuit and gas blender. The following seven gas stages will be targeted for about 10 minutes each:

1. Baseline, measured in eye A (PETCO2=38mmHg and PETO2=100mmHg)
2. 10% hypercapnic increase, measured in eye A (PETCO2=42mmHg and PETO2=100mmHg)
3. 20% hypercapnic increase, measured in eye A (PETCO2=46mmHg and PETO2=100mmHg)
4. Baseline, measured in both eyes (PETCO2=38mmHg and PETO2=100mmHg)
5. 250% hyperoxic increase, measured in eye B (PETCO2=38mmHg and PETO2=250mmHg)
6. 500% hyperoxic increase, measured in eye B (PETCO2=38mmHg and PETO2=500mmHg)
7. Baseline, measured in eye B (PETCO2=38mmHg and PETO2=100mmHg)
Other Name: Inhaled gas provocations

In response to changes in the composition of inhaled gases, blood vessels will dilate or constrict. As a result, hypercapnia or hyperoxia may affect the production and drainage of aqueous humour in the anterior chamber of the eye. The balance between the production and drainage of the aqueous humour determines the intraocular pressure. As this system is hydrodynamic, it is expected that any increase or decrease in the production of aqueous humour due to dilation or constriction of the capillaries within the ciliary body will be compensated by increased or decreased drainage at the trabecular meshwork. Therefore intraocular pressure is not expected to show a response to hypercapnia or hyperoxia, but this supposition needs to be tested in a stably controlled manner of inducing inhaled gas provocations. This study will measure the intraocular pressure at varying levels of hypercapnia and hyperoxia using a sequential rebreathing circuit and automated gas blender. This will allow the precise targeting and stable control of end-tidal partial pressure values of carbon dioxide and oxygen.

In this study, intraocular pressure will be measured at seven different inhaled gas stages. The seven stages are as follows:

1. Baseline, measured in eye A (PETCO2=38mmHg and PETO2=100mmHg)
2. 10% hypercapnic increase, measured in eye A (PETCO2=42mmHg and PETO2=100mmHg)
3. 20% hypercapnic increase, measured in eye A (PETCO2=46mmHg and PETO2=100mmHg)
4. Baseline, measured in both eyes (PETCO2=38mmHg and PETO2=100mmHg)
5. 250% hyperoxic increase, measured in eye B (PETCO2=38mmHg and PETO2=250mmHg)
6. 500% hyperoxic increase, measured in eye B (PETCO2=38mmHg and PETO2=500mmHg)
7. Baseline, measured in eye B (PETCO2=38mmHg and PETO2=100mmHg)