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Prevention of posterior capsule opacification by photodynamic therapy with localized benzoporphyrin derivative monoacid ring A (BPD-MA) in a rabbit surgical model

Posterior capsule opacification (PCO) is a major component of secondary cataract, a
complication of current cataract surgery practice. This iatrogenic condition occurs in
virtually all pediatric cases and to a lesser extent in adults. PCO correlates with the
development in the latter half of the 20th Century of extracapsular cataract extraction
(ECCE). In these surgeries, the lens capsule is left intact.
During ECCE surgery a circular capsulotomy opening is created in the anterior lens
capsule, and the cataractous, proteinaceous lens is removed, often via ultrasonic lens
liquefaction i.e. phacoemulsification. The posterior, equatorial and remaining anterior
portions of the sac-like capsule are left intact, permitting the insertion of an artificial lens
into the emptied capsule. However, cells from the monolayer of epithelium on the inner
surface of the capsule often begin to proliferate and migrate onto the normally cell-free
inner surface of the posterior capsule, and may obscure the central axis of vision.
Subsequently, a second surgery is necessary to create a small capsulotomy in the centre of
the posterior capsule, usually employing an Nd:YAG laser. However, up to 5% of patients
who have capsulotomies may then develop further serious, vision-threatening
complications such as macular edema and retinal detachments.
This thesis reports the photodynamic therapy (PDT) conditions required to prevent
lens epithelial (LE) cell de novo proliferation and migration onto posterior lens capsules in
a euthanized rabbit surgical model in order to predict parameters required to prevent PCO in
humans. Experiments with primary in vitro cultures of human LE cells have shown rapid
delivery of the photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA) and
efficient killing with low light doses of 690 nm red light. Additional studies have shown
the efficacy of various viscous agents in protecting the comeal endothelium. During model
phacoemulsification ECCE surgeries, the use of hyaluronate viscoelastic carriers addressed
the need for containment necessary for localized delivery of photosensitizer in the emptied
capsule. Long-term monitoring of PDT-treated rabbit lens capsules in vitro has demonstrated a phototoxic effect including complete cell kill in this surgical model
employing the prophylactic use of PDT.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU.2429/4176
Date11 1900
CreatorsMeadows, Howard Earl
PublisherUniversity of British Columbia
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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