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Abstract #21439 Published in IGR 10-3
Studies on clinical pathophysiology of pseudophakic/aphakic eyes - a journey of 4 decades
Miyake KNippon Ganka Gakkai Zasshi 2008; 112: 214-245
My prime years as an ophthalmologist began as intraocular lenses (IOLs) were just entering into the developmental stage, and I took on as my mission to contribute to perfecting safe and reproducible cataract/IOL implantation surgery. Identifying surgical and/or IOL-related complications consumed time; however, these complications soon became predictable and even preventable with the use of sensitive biological parameters and preclinical evaluation. This was a simple goal for me to pursue my studies on cataract/IOL implantation surgery. I discuss in this review article, based on my previous research, clinico-pathophysiological problems of these intra- and postoperative eyes. The early phase of cataract/IOL implantation surgery development began with a debate as to which is physiologically superior: intracapsular cataract extraction (ICCE) or extracapsular cataract extraction (ECCE). From the perspective of transporting substances from intraocular fluids to extraocular space, which we studied using a nonphysiological substance, fluorescein, ECCE was confirmed to be physiologically superior to ICCE. The transport mechanism of both physiological and nonphysiological substances from intraocular fluids (such as vitreous and aqueous humor) is believed to be related to the pathogenesis of various ocular disorders. Following the fluorescein study, I next focused my attention on biosynthesis and active transport of prostaglandin (PG), which are inflammatory mediators. My studies revealed that PG were more likely to accumulate in ICCE eyes than in ECCE eyes; higher intraocular concentration of PG was also confirmed in eyes with persistent aphakic or pseudophakic cystoid macular edema (CME). While conducting the above studies and having made some observations, I postulated another hypothesis on the pathogenesis of aphakic or pseudophakic CME as follows: topical application of nonsteroidal antiinflammatory drugs (NSAIDs) to eyes with PG, which are biosynthesized intra- and postoperatively during the healing process of uveal tissues and lens epithelial cells, prevents CME. Based on this hypothesis experimental studies were then started, and in 1977 I became the first in the world to prove that topical application of indomethacin, one of the NSAIDs, controls the incidence of CME in ICCE eyes. Thereafter, some 40 follow-up studies have been conducted worldwide, and recent meta-analysis has established the efficacy of indomethacin. Macular edema and CME are recently of significant interest as complications in various ocular disorders. Compared to other forms of CME, the pathophysiology of CME associated with aphakic/ pseudophakic eyes is relatively simple, its natural history is well understood and its reproducibility is high. It is possible that the other forms of macular edema or CME having more complicated pathogenesis may be interpreted by understanding the formation mechanism of aphakia/pseudophakic CME. Our studies have shown how chemical mediators (PG) are systematically involved in the development of aphakic/pseudophakic CME, and that they concurrently cause blood-aqueous barrier disruption and CME, decrease oscillatory potential of the full field ERG, and decrease choroidal blood flow at an early postoperative period, and this has recently been proven. All these phenomena, however, can be effectively prevented by topical application of NSAIDs. I believe these findings provide significant information when considering the pathogenesis and treatment of CME associated with other ocular disorders. Using the primitive method of an early phase, I discovered that anti-PG eye drops can treat disrupted blood-aqueous barrier, and confirmed that the blood-aqueous barrier function is indeed a very sensitive function. I next applied fluorophotometry and laser flaremetry. Using blood-aqueous barrier function as a parameter, the following were evaluated: consensual reaction of blood-aqueous barrier disruption, method of IOL fixation, racial differences in disruption of the aqueous barrier function, drugs used perioperatively, biocompatibility of IOL materials, and effects of preservative agents. Research on preservative agents disclosed that the preservative agent in anti-glaucoma drops more strong by induced pseudophakic CME than the anti-glaucoma agent itself. Thus, this introduced a new concept called Our desire to closely observe the endosurface of the iris, ciliary processes and anterior vitreous face, all of which are closely related to phacoemulsification techniques, posterior chamber lens fixation, and active transport of PG, led me to the development of 'Posterior video technique' (Miyake-Apple View). The technique since then has been used to evaluate cataract surgical techniques, to analyze complications, to review IOL designs and fixation techniques, to pre-clinically evaluate surgical devices, and to study variations of local anatomy related to cataract/IOL surgery. The method is also useful as an educational as well as a presentational tool, and it has now been accepted world-wide. The pathogenesis of aphakic/pseudophakic CME, physiological evaluation centering on blood-aqueous barrier function, and preclinical evaluation using the Posterior video technique have all played a significant role in establishing today's safe cataract/IOL implantation surgery. LA: Japanese
Dr. K. Miyake, Shohzankai Medical Foundation, Miyake Eye Hospital, Nagoya, Japan. miyake@spice.or.jp
Classification:
9.4.11.2 Glaucomas in aphakia and pseudophakia (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders > 9.4.11 Glaucomas following intraocular surgery)
3.8 Pharmacology (Part of: 3 Laboratory methods)