A Partnership for Maculopathy Research

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A Partnership for Maculopathy Research

• Christine A. Curcio, PhD
• Department of Ophthalmology
• University of Alabama
• School of Medicine

Firmon E Hardenbergh, MD, FACS, CEBT Director of
Technical Services Alabama Eye Bank
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Human Eyes in Age-related Maculopathy Research

• A logical starting point for laboratory studies
  using other model systems
• Standard against which animal models of disease
  are judged
• New questions arising from animal models will
  need answers from human tissue

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Our Approach

• New hypotheses about ARM pathobiology should be
  based on high-quality information about Bruchs
  membrane, drusen, and basal deposits in human
  eyes
• Human eyes with ARM are not routinely available
  through eye pathology labs
• Population-based eye pathology (eye bank
  mining)
• Obtain many eyes within fixed post-mortem
  interval (3-6 h)
• Screen post-mortem fundus for evidence of ARM
• To see more ARM cases, screen more eyes
• Use death-to-preservation interval as
  flow-control device
• Longer interval, more eyes
• Current criteria
• 6 hr death-to-preservation / exclude diabetics

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Tissue Quality Actually Matters

• In our work (3-6 hr post-mortem)
• Quantitative photoreceptor GC topography
• Ultrastructure of Bruchs membrane lipid deposits
• Non-abundant proteins and mRNA
• Need independent marker of post-mortem quality
  (time may not be accurate)
• Discard tissue that does not meet criteria --
  inherently inefficient process

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Strategies for Finding ARM Eyes
Registry sign up donors, wait for them to
die Clearinghouse matches donors, investigators
in different cities Mining screen eyes within a
post-mortem interval at local eye bank
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History

• 1984-1990 Tissues from Lions Eye Bank at UW
  gratis
• 1991- Tissues from AEB, fee per globe
• 1995- Systematic screening for ARM
• 1997-2001 Shared Ocular Tissues Module of UAB
  Vision Science Research Center
• Share donor tissue with other UAB researchers
• 2001- ARM Histopathology Laboratory
• Share donor tissues with researchers interested
  in ARM

Research Tissues in Curcio Lab, UAB, 1991-2002
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Donor Demographics, 1995-2002
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ALARMGS Finding ARM Eyes
Post-mortem fundus
Histopathologic evaluation
Pre-mortem fundus
Eyes from 60-90 donors/ yr, lt 4 hrs post-mortem
Contact donor families, MD/ OD for eye health
history Clinical information reviewed by retina
specialist Detailed gross and histopathologic
exam Mean age 71 yr 15 have ARM Curcio et
al., 1998, IOVS 39 1085
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ARM in Post-Mortem Fundus

• Most preserved eyes with grossly visible drusen
  and pigmentary change in fovea were photographed
• Stereo, color, epi- and trans-illumination,
  retina on
• Photographs were mounted with grids and graded by
  ALARMGS

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ARM Histopathology Laboratory

• Funded by International Retinal Research
  Foundation (2001-2003)
• Mission obtain 20 ARM donors per year
• Eyes/ Genomic DNA/ Clinical records
• Method screen 100 pairs of donor eyes
• Preserve one eye - diagnosis/ microscopic studies
• Freeze one eye - biochemistry, molecular biology

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Staffing

• Tissue Coordinator (50 FTE, AEB)
• Program Coordinator I (40 FTE,UAB)
• Correspond with families and eye doctors to
  obtain eye health histories
• Maintain public education program about eye
  donation for research
• Research Technician (100 FTE, UAB)
• Dissect and disburse eyes
• Prepare tissue for gross and microscopic
  pathologic characterization

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Financial Arrangements UAB

• Foundation grants support services
• Tissue collecting sharing service (eyes,
  personnel)
• International Retinal Research Foundation
• Donor program (pre- and post-donation activities)
• EyeSight Foundation of Alabama
• NEI-funded projects are users of the service
• Long-term goal
• Independently financed and staffed service and
  research laboratories
• Service lab combine surgery-based
  population-based eye pathology

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Local Eye Bank Practices Affect Research Tissue
Availability

• Medical examiner law
• Many young adult donors are ME cases due to cause
  of death
• Whole eye enucleation is not allowable for ME
  cases
• Little market for sclera
• Easier cheaper for eye bank to perform in situ
  excision
• Whole eye enucleation formerly done state-wide,
  now 2 counties in Birmingham area
• Eye health history required by EBAA is not
  adequate for ARM research
• We are responsible for obtaining records
• We maintain our own referral network

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Eye health history

• Use
• General level of pre-mortem vision
• Exclude non-ARM chorioretinal pathology
• Identify pre-mortem imaging
• Contact family in writing for consent for access
  to records
• 71 response rate
• Contact ophthalmologists and optometrists
• Obtain history from 40 of donors
• Records reviewed abstracted by retina
  specialist (paid consultant)
• Database entry

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Working with Local Eye Bank Tips

• Stay out of their way, so that they will get more
  eyes
• Be aware of factors that impact on eyes
  harvested
• Personnel, organizational changes
• Financial regulatory climate
• Relationship with organ procurement organization
• Provide regular training, follow-up for technical
  staff
• Keep protocols simple
• Discuss costs before grant applications
• Get cost commitment in writing
• Share the credit in publications presentations

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AEB Annual Statistics

• Procurements since 1995
• 2400 eyes/ year
• Top 10 for transplantable tissues since 1984
• Distributions since 1995
• 1500 for transplant (71)
• 500 for research (24)
• 100 for education (5)

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Reimbursements for Transplantable Tissues

• Full reimbursement for 70 of recipients
• 60 decrease in no reimbursement cases over
  last 4 yr
• Increase in partial reimbursement cases

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Caveat

• The concept of FREE tissue
• must encompass
• the concept of WORTHLESS tissue!

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Reimbursement for Research Eyes

• Must be determined by specific
  circumstances in each situation and
• specific eye bank-researcher relationship

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Researcher - Eye Bank Relationships

• Mutually rewarding
• Require mutual understanding and mutual
  accommodation

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Alabama Eye Bank Mission Statement

• To relieve suffering through the procurement,
  processing and delivery of the highest quality
  human eye tissue for transplant, research and
  teaching throughout Alabama and the world, while
  maintaining a viable financial base.