JCHR

Title

Vitreous Proteomics in Eyes with a Macular Hole

Précis

The proteomics of vitreous samples from eyes with full-thickness macular holes undergoing vitrectomy and from control eyes undergoing vitrectomy (eyes with no retinal disease) with vitreous opacities causing floaters will be analyzed in two phases: the discovery phase will determine which proteins are up- and down-regulated, and the validation phase will target the most promising proteins found in the discovery phase. 

The vitreous samples may be a combination of retrospectively collected samples and prospectively collected samples. 

Objectives

The main objective of this protocol is to (1) verify and characterize abnormally expressed vitreous proteins in adults with macular holes, and (2) to identify biological pathways involved in the pathogenesis of macular hole formation and potential targets for therapeutic intervention.

Study Design

Observational

Number of Sites

~20 sites

Endpoint

Primary Outcomes:

·         Presence/absence of proteins in vitreous of cases vs. controls

·         Degree of upregulation and downregulation of these proteins

Key Secondary Outcomes:

·         Analyses in affected subgroups (e.g., women vs men, different ethnic groups, myopes vs. non-myopes, etc.)

Population

Key Inclusion Criteria

·         Age =18 years

·         Eyes undergoing standard of care vitrectomy to repair full-thickness macular hole, as confirmed on OCT, (cases) or to remove vitreous opacities (controls)

Key Exclusion Criteria

·         Type 1 or type 2 diabetes

Key Study Eye Exclusion Criteria

·         Previous vitrectomy

·         Aphakia

·         Endophthalmitis

·         Uveitis or history of uveitis

·         History of any intravitreal injection (anti-VEGF, steroid, gas)

·         History of laser vitreolysis

·         History of any retinal tear, retinal laser treatment, or cryopexy

·         History of ocriplasmin administration

·         History of recent trauma

·         Vitreous hemorrhage

·         History of vein occlusion

·         Age-related macular degeneration (note: small drusen are allowed)

·         Any history of secondary macular edema

·         History of retinal detachment

·         High level of myopia (including history of high myopia and evidence of high myopia on clinical exam)

·         Any retinal abnormalities (cases will have macular hole and may also have ERM or VMT)

Sample Size

Participants will be enrolled until a sufficient number of eligible samples are collected to achieve the following:

Discovery Phase: 60

·         30 cases (macular hole)

·         30 controls (vitreous opacities)

Validation Phase: 100

·         50 cases (macular hole)

·         50 controls (vitreous opacities)

Participant Duration

Participants completing prospective sample collection will have one baseline visit to collect data prior to standard care surgery. 

There will be no participant follow-up research visits. 

Protocol Overview/Synopsis

Participants completing prospective sample collection:

·  Informed consent will be obtained for screening. 

·  Eligibility will be assessed. 

·  Standard clinic VA, eye exam and OCT data will be collected for eligible eyes and do not need to be repeated for the study provided eligibly can be confirmed from the standard images

·  A central reading center will confirm eligibility criteria on OCT (cases will have full-thickness macular hole and no other retinal abnormalities; controls will have no retinal abnormalities).

·   Eyes will undergo standard of care vitrectomy.  The vitrectomy is not part of the research.  At the time of vitrectomy, vitreous samples will be obtained as standard care, provided to the researchers instead of discarded, and shipped on dry ice to a central lab.

·  The central lab will aliquot and store the samples at -80 degrees C until time for shipment to the lab for analysis.

Samples obtained retrospectively will undergo the following:

·  Eligibility will be assessed from existing data; including sending the OCT to the central reading center.

·  Eligible samples will be shipped to the lab for analysis

The following will be completed on all samples:

·  Discovery phase analyses (from time of last sample collection): ~ 6 months

o    Tandem Mass Tag (TMT) labeling

o    Process the samples

o    Bioinformatics

·  Validation phase analyses (from time of last sample collection): ~3 months

o    Selected Reaction Monitoring (SRM) to synthesize peptides

o    Process the samples

o    Bioinformatics