Eye Banking: biovigilance

diego.ponzin@fbov.it

The Veneto Eye Bank Foundation, Venice

Workshop on Quality Systems in Ocular Tissue Banking, TAIEX 50564.

Zagreb, Croatia, 30-31 January 2013

A set of surveillance procedures covering the entire transplantation chain (from the donation to the follow-up of recipients), intended to:

collect and assess information on unexpected or undesirable effects, and errors, resulting from the therapeutic use of blood products, organs, tissues, and cellular therapies;

prevent the occurrence or recurrence of such incidents;

improve clinical outcomes. A permanent assessment of the risk / benefit ratio

Biovigilance

The best opportunity to learn!

Biovigilance

The best opportunity to listen!

We have one mouth and two ears: in our dealing with others is enough to respect the ratio (… listen twice as much as you speak) Epictetus quotes (Greek, Stoic philosopher, born AD 55

The perfect murder is one that isn’t actually discovered

Rabl Walter. European Hospital 2013;21(6)12:1-2

The best opportunity to investigate

The perfect murder is one that isn’t actually discovered

Rabl Walter. European Hospital 2013;21(6)12:1-2

Curvature Transparency

LK: replacing only the diseased layers of the cornea

Tan DTH, Dart JKG, Holland EJ, Kinoshita S. Corneal transplantation. Lancet 2012;379:1749-61

Safer surgery, faster visual recovery, better and more predictable visual outcome

DSAEK: refractive-neutral procedure, most common EK

EK: the eye bank work station

Microkeratome

Artificial anterior chamber

Positive: outcomes expected and pursued benefitNegative: outcomes unexpected and unwanted risk Tissue-related (adverse event, reaction)

o Serious Adverse Event: something wrong during the process could cause harm to a patient

o Serious Adverse Reaction: something wrong in a donor or in a patient could have been caused by the tissues/cells

Non-tissue related (complication, failure)

Indicators (structure, process, outcome, efficiency, efficacy)

Directive 2004/23/EC: standards of quality and safety…Directive 2006/17/EC: technical requirements…

Directive 2006/86/EC: traceability requirements, notification of serious adverse reactions and events…

Tissue-related, negative indicators in corneal transplantation

Any communicable or other disease transmissible by, and attributable to, transplantation of donor eye tissue, including: Infections: systemic diseases, endophthalmitis (six months) keratitis (six weeks)

Eye Bank Association of America, Medical Standards, 2012

Biologic dysfunctions: immediate donor endothelial failure, donor corneal dystrophy, donor refractive surgery

PK: biologic dysfunctions

Immediate donor endothelial failure Presence of a diffusely edematous penetrating corneal graft on the first postoperative day

Failure of the cloudy graft to clear at any time postoperatively

Lack of an identifiable cause of corneal graft failure

FBOV risk: 0.2%

Wilhelmus KR. Arch Ophtalmol 1995;113:1497-502

Donor corneal dystrophy FBOV risk: <0.1%

Endothelial rejection

Cystoid macular edema

Graft dislocation Graft failureLK: biologic dysfunctions, complications

Risk of local transmission ofbacteria, fungi, viruses

Pathology: keratitis, endophthalmitis, uveitis

Risk: <0.1% (bacteria, fungi), occasional (virus)

Prevention: donor screening, asepsis conditions, microbiological screening of tissues

FBOV risk:

0.05% (bacteria, fungi)

0.005% (virus)

Herpetic keratouveitis after PK

Positive indicators for the evaluation of clinical outcomes of corneal transplantation

Graft survival Visual acuity (BCVA) Anthalgic effect Reconstruction Health related quality of life (SF-36,

SF-12) Visual function (VF14) Surgeon’s satisfaction Patient’s expectation and satisfaction

Delbosc et al, J Fr Ophthalmol, 2003. Fasolo A et al. Cornea 2006. Williams KA et al Eye, 1995. Vail A et al Ophthalmol, 1996. Bourne WM Ophthalmol, 1998. Claesson M et al BJO, 2002. KA Williams et al Ophthalmol 1991. Uiters E et al Cornea 2001; Fasolo A et al. J Ophthalmol 2012.

Biovigilance

The Agreement The Procedures The Reasons

Triennial agreement for the provision of services and tissues for ocular surgery

SOP - Standard Operating Procedures Forms

The procedures

SOP

K1.000Tissue distribution

SOP

K1.400Returned tissues

SOP

L1.000

Documentation to accompany

donor tissues

SOP

L2.000

Packaging, sealing and packing

for transport

SOP

M1.500Recipient follow-up information

SOP

M1.550

Monitoring and management of severe adverse reactions and events

Cornea/Lenticule Request Form

Non-Surgical Tissues Request / Utilization Forms

Cornea/Lenticule Evaluation Form

Cornea/Lenticule Utilization Form

Monitoring of adverse events / reactions

Questionnaire of satisfaction

The statistical report

Reporting: the reasons

200 surgeons involved

Reporting: the reasons

Active monitoring Cooperation with surgeons

Transparency Rare events more likely to occur in high-volumes TE

Multidisciplinary approach Dec 2009: thanksgiving letter sent to the eye bank by patient A (!)

Donor-to-host transmission of Acanthamoeba from an asymptomatic cornea donor

Rate of reporting by FBOV cooperating surgeons: Short term: 98% (within three months post op) Long term: 44% (SAE /SAR monitoring), 37% (satisfaction) Current risk: Systemic diseases: theoretical Endophthalmitis, keratitis: <0.1% (bacteria, fungi), <0.005%

(virus)

Biologic dysfunctions: <0.2% Current benefit:Fasolo A et al. The CORTES study: corneal transplant indications and graft survival in an Italian cohort of patients. Cornea 2006; 25:507-15.

Fasolo A et al. Risk factors for graft failure after penetrating keratoplasty: 5 year follow-up from the Corneal Transplant Epidemiological Study. Cornea 2011,30:1328–35.

Fasolo A et al. Health status and patient satisfaction after corneal graft: results from the Corneal Transplant Epidemiological Study. J Ophthalmol 2012; Vol 2012, Art. ID 230641.

Results (2012)

Fasolo A et al. The CORTES study: corneal transplant indications and graft survival in an Italian cohort of patients. Cornea 2006; 25:507-15.

Fasolo A et al. Risk factors for graft failure after penetrating keratoplasty: 5 year follow-up from the Corneal Transplant Epidemiological Study. Cornea 2011,30:1328–35.

Results

Overall Kaplan–Meier probability of 5-year survival: 83.0%

Fasolo A et al. Health status and patient satisfaction after corneal graft: results from the Corneal Transplant Epidemiological Study. J Ophthalmol 2012; Vol 2012, Article ID 230641.

Results

Leape LL. Reporting of adverse events. NEJM 2002;347(20):1633-8

A take-home message

Tissue Establishment, Surgeon, Competent Authority, Transplant Coordinators: an alliance to realize and improvement of patient’s care

Fundamental role of reporting is to enhance patient safety by learning from failures of the healthcare system

Individuals who report incidents must not be punished or suffer other ill-effects from reporting

Reporting: reliable if based on positive arguments (clinicians involved) only of value if it leads to a constructive response must be personally, professionally, institutionally rewarding

Conclusions

Ponzin D et al. Eye banking at the Fondazione Banca degli Occhi del Veneto: present and perspectives. Organs and Tissues 2003; (2)111-9Ferrari S et al. Advances in corneal surgery and cell therapy: challenges and perspectives for the eye banks. Expert Review of Ophthalmology 2009; 4(3):317-29