Choroidal Blood Flow Changes During Dark/Light Transitions in Patients With Insulin-dependent Diabetes Mellitus (IDDM)

Study Overview
=================
Brief Summary
-----------------
There is evidence from a variety of animal studies that choroidal blood flow is under neural control. Recent results in humans indicate that a light/dark transition is associated with a short lasting reduction in choroidal blood flow. Several observations indicate that the changes in choroidal perfusion are triggered at least in part by neural mechanisms. Particularly, we have shown that during unilateral dark/light transition both eyes react with choroidal vasoconstriction strongly indicating a neural mechanism for blood flow regulation. Investigation of changes in choroidal blood flow during light/dark transition may represent an interesting approach to study neural dysregulation at the level of the eye in patients with IDDM. Accordingly, the hypothesis of reduced choroidal blood flow responses to a light/dark transition in patient with IDDM will be tested. This response in choroidal blood flow will be correlated to parameters of diabetic neuropathy and diabetic retinopathy.

Official Title
-----------------
Choroidal Blood Flow Changes During Dark/Light Transitions in Patients With IDDM

Conditions
-----------------
Diabetes Mellitus, Type 1, Diabetic Retinopathy

Intervention / Treatment
-----------------
* Procedure: Light will be switched from 0.5µW/cm2/sr to 115µW/cm2/sr.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: For healthy control subjects: Men and women aged over 18 years, matched in regard to age, sex and smoking status Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant Normal ophthalmic findings, Ametropia < 3 dpt for healthy control subjects For patients with IDDM: Men and women aged over 18 years Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant Long standing IDDM > 10 years Mild or moderate to severe non-proliferative diabetic retinopathy (defined according to the MAHC) Ametropia < 3 dpt Exclusion Criteria: Any of the following will exclude a healthy subject from the study: Regular use of vasoactive medication with may interfere with the study procedure, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study Symptoms of a clinically relevant illness in the 3 weeks before the first study day Blood donation during the previous 3 weeks Any of the following will exclude a patient with IDDM from the study: Evidence of any relevant retinal or choroidal disease (Glaucoma, age related macula degeneration, cataract, history of central retinal artery obstruction or central retinal vein thrombosis) Ophthalmological surgery (history of photo laser coagulation, including argon laser trabeculoplasty (ALT), trabeculectomy, deep sclerectomy) History of intravitreal injection with anti-proliferative therapy Need for dialysis Non-treated systemic hypertension (SPB>150, DBP>95) Evidence of coronary heart disease, cardiomyopathy, stenocardia, congestive heart failure, peripheral occlusive vascular disease, cardiac autonomic neuropathy Symptoms of a clinically relevant illness in the 3 weeks before the first study day Blood donation during the previous 3 weeks

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>Patients with long standing IDDM (>10 years) and no diabetic retinopathy | Procedure: Light will be switched from 0.5µW/cm2/sr to 115µW/cm2/sr.<br>* Light will be switched from 0.5µW/cm2/sr to 115µW/cm2/sr.<br>|
| Other: 2<br>Patients with long standing IDDM (>10 years) and mild non-proliferative diabetic retinopathy | Procedure: Light will be switched from 0.5µW/cm2/sr to 115µW/cm2/sr.<br>* Light will be switched from 0.5µW/cm2/sr to 115µW/cm2/sr.<br>|
| Other: 3<br>Patients with long standing IDDM (>10 years) and moderate to severe non-proliferative diabetic retinopathy | Procedure: Light will be switched from 0.5µW/cm2/sr to 115µW/cm2/sr.<br>* Light will be switched from 0.5µW/cm2/sr to 115µW/cm2/sr.<br>|
| Other: 4<br>healthy volunteers, matched for age and sex | Procedure: Light will be switched from 0.5µW/cm2/sr to 115µW/cm2/sr.<br>* Light will be switched from 0.5µW/cm2/sr to 115µW/cm2/sr.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fundus pulsation amplitude |  | 3 hours | 
| choroidal blood flow |  | 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nerve conduction velocity |  | measured before intervention | 
| Pupil diameter during infra-red pupillometry |  | measured before intervention | 
| heart rate variability |  | measured before intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Choroidal blood flow, Laser Doppler flowmetry, Diabetic Retinopathy, Diabetic Neuropathy