Repeatability of Static & Dynamic Composite Confocal Microscopy for Assessment of the Corneal Nerve Fiber Plexus in Early Diabetic Polyneuropathy

Study Overview
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Brief Summary
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This prospective study was was divided into 2 parts and carried out at 2 sites in Germany. Part 1 assessed Repeatability in healthy, non-diabetic population (Group control). Part 2 collected data to evaluate the diagnostic and prognostic value of using Heidelberg Engineering Retina Tomograph (HRT) 3 with the Rostock Cornea Module EyeGuidance functional module (HRT RCM-E) in subjects with early to moderate DPN (Groupsnone and mild, respectively).

Detailed Description
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Part 1 aimed to evaluate the diagnostic and prognostic value of the optimized dynamic composite corneal nerve plexus image acquisitions done with HRT RCM-E compared to standard static composite image acquisition with Heidelberg Engineering Retina Tomograph (HRT) 3 with the Rostock Cornea Module (HRT RCM). The part 2 (research part) evaluated changes in corneal nerve plexus parameters in diabetes patients without or with early to moderate Diabetic Peripheral Neuropathy (DPN) and correlated the observed changes with progression of early DPN.

Official Title
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Repeatability of Static & Dynamic Composite Confocal Microscopy for Assessment of the Corneal Nerve Fiber Plexus in Early Diabetic Polyneuropathy

Conditions
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Normal Eyes of Subjects Without Diabetes Mellitus, Subjects With Diabetes Mellitus Type 2 Without Coexisting DPN, Subjects With Diabetes Mellitus Type 2 With Coexisting Early to Moderate DPN

Intervention / Treatment
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* Device: HRT RCM
* Device: HRT RCM-E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All Able and willing to undergo the test procedures, give consent, and to follow instructions. Signed informed consent. ≥18 years. Part 1, Site 1 Normal eyes of patients without Diabetes Mellitus Fasting blood glucose < 100 mg/dl HbA1c ≤ 6.5% Part 2, Site 2 Diabetes Mellitus Type 2 without coexisting DPN (NSS score ≤2 and / or NDS score ≤2) Diabetes Mellitus Type 2 with coexisting early to moderate DPN. (NSS score 3-4 and / or NDS score 3-5) 6.5% < HbA1c ≤ 9.5% Exclusion Criteria: Vulnerable subjects (Such as: individuals with lack of or loss of autonomy due to immaturity or through mental disability, persons in nursing homes, children, impoverished persons, subjects in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent. Other vulnerable subjects include, for example, members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel (if linked to CI site), employees of the sponsor, members of the armed forces (if linked to CI site or sponsor), and persons kept in detention.) Subjects unable to read or write Contact lens wearers (soft and rigid) Patients with symptomatic dry eye Patients with conjunctivitis at the time of inclusion Patients with history of corneal surgery Patients with diabetic retinopathy Patients with history of neuronal diseases that according to the expertise of the investigator might have an influence on corneal nerve fiber plexus

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal Eyes of Subjects without DM<br>Study Part 1 conducted at only site 1 . Single measurement made on 3 separate visits at site 1 (total 3 images acquired) with HRT RCM and HRT RCM-E functional module (investigational). | Device: HRT RCM<br>* Imaging with HRT RCM done only at site 1 (on normal eyes of subjects without DM).<br>* Other names: Heidelberg Engineering Retina Tomograph HRT 3 with the Rostock Cornea Module (HRT RCM);Device: HRT RCM-E<br>* imaging done on eyes of all enrolled subjects at site 1 and site 2.<br>* Other names: Heidelberg Engineering Retina Tomograph HRT 3 with the Rostock Cornea Module EyeGuidance functional module (HRT RCM-E);|
| Experimental: Eyes of DM Type 2 subjects without coexisting DPN<br>Study part 2 conducted at site 2. 1 image acquired with HRT RCM-E functional module (investigational). | Device: HRT RCM-E<br>* imaging done on eyes of all enrolled subjects at site 1 and site 2.<br>* Other names: Heidelberg Engineering Retina Tomograph HRT 3 with the Rostock Cornea Module EyeGuidance functional module (HRT RCM-E);|
| Experimental: Eyes of DM Type 2 subjects with coexisting early to moderate DPN<br>Study part 2 conducted at site 2. 1 image acquired with HRT RCM-E functional module (investigational). | Device: HRT RCM-E<br>* imaging done on eyes of all enrolled subjects at site 1 and site 2.<br>* Other names: Heidelberg Engineering Retina Tomograph HRT 3 with the Rostock Cornea Module EyeGuidance functional module (HRT RCM-E);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| corneal nerve fiber length (CNFL) | Acquired image processed to obtain parameters required to calculate nerve fibre metrics | Through study completion, an average of 1 day to upto 3 days | 
| corneal nerve fiber density (CNFD) | Acquired image processed to obtain parameters required to calculate nerve fibre metrics | Through study completion, an average of 1 day to upto 3 days | 
| average corneal nerve single fiber length (CNSFL) | Acquired image processed to obtain parameters required to calculate nerve fibre metrics | Through study completion, an average of 1 day to upto 3 days | 
| average weighted corneal nerve fiber tortuosity (CNFTo) | Acquired image processed to obtain parameters required to calculate nerve fibre metrics | Through study completion, an average of 1 day to upto 3 days | 
| corneal nerve branch density (CNBD) | Acquired image processed to obtain parameters required to calculate nerve fibre metrics | Through study completion, an average of 1 day to upto 3 days | 
| corneal nerve connecting points (CNCP) | Acquired image processed to obtain parameters required to calculate nerve fibre metrics | Through study completion, an average of 1 day to upto 3 days | 
| average weighted corneal nerve fiber thickness (CNFTh) | Acquired image processed to obtain parameters required to calculate nerve fibre metrics | Through study completion, an average of 1 day to upto 3 days |