Surgical management for postkeratoplasty glaucoma: a meta-analysis.

PURPOSE: To perform a meta-analysis on postkeratoplasty glaucoma and directly compare the affect of trabeculectomy, cyclophotocoagulation (CPC), and glaucoma drainage device (GDD) on intraocular pressure (IOP) control and corneal graft survival. METHODS: We searched Medline (Ovid, PubMed), EMBASE, and The Cochrane Library databases for clinical articles that maintained our inclusion criteria. The primary outcome measures were IOP control and overall corneal graft survival. The secondary outcomes were failure rate of the primary glaucoma procedure and change in visual acuity. We used 1-way analysis of variance weighed by the number of participants in each study to compare the outcomes. RESULTS: Information from a total of 266 eyes was collected from 13 articles. Trabeculectomy reduced IOP by 13.6 mm Hg compared with 20.4 mm Hg with CPC and 20.2 mm Hg with GDD (P<0.001). The failure rate of glaucoma surgery was highest after trabeculectomy 37% (95% CI, 31.4%-41.9%) compared with 20.7% (95% CI, 17.6%-23.7%) after CPC and 16% (95% CI, 13.8%-18.9%) after GDD and this was statistically significant (P<0.001). GDD was associated with higher rate of corneal graft failure (35%) than either CPC or trabeculectomy (21% and 24%, P=0.001 and P<0.001, respectively). The percentage of patients who experienced worsening of vision was the highest after CPC (26%) and the least with GDD (20%). CONCLUSIONS: Our meta-analysis shows that in patients with postkeratoplasty glaucoma, GDD is associated with greater IOP control, the lowest glaucoma surgery failure rate, and less vision loss compared with other forms of glaucoma surgery. However, GDD surgery is also associated with higher rate of graft failure.

Different mechanisms of free fatty acid flip-flop and dissociation revealed by temperature and molecular species dependence of transport across lipid vesicles.

The mechanism of free fatty acid (FFA) transport across membranes is a subject of intense investigation. We have demonstrated recently that flip-flop is the rate-limiting step for transport of oleic acid across phospholipid vesicles (Cupp, D., Kampf, J. P., and Kleinfeld, A. M. (2004) Biochemistry 43, 4473-4481). To better understand the nature of the flip-flop barrier, we measured the temperature dependence of a series of saturated and monounsaturated FFA. We determined the rate constants for flip-flop and dissociation for small (SUV), large (LUV), and giant (GUV) unilamellar vesicles composed of egg phosphatidylcholine. For all FFA and vesicle types, dissociation was faster than flip-flop, and for all FFA, flip-flop and dissociation were faster in SUV than in LUV or GUV. Rate constants for both flip-flop and dissociation decreased exponentially with increasing FFA size. However, only the flip-flop rate constants increased significantly with temperature; the barrier to flip-flop was virtually entirely due to an enthalpic activation free energy. The barrier to dissociation was primarily entropic. Analysis in terms of a simple free volume (V(f)) model revealed V(f) values for flip-flop that ranged between approximately 12 and 15 Angstroms(3), with larger values for SUV than for LUV or GUV. V(f) values increased with temperature, and this temperature dependence generated the enthalpic barrier to flip-flop. The barrier for dissociation and its size dependence primarily reflect the aqueous solubility of FFA. These are the first results to distinguish the energetics of flipflop and dissociation. This should lead to a better understanding of the mechanisms governing FFA transport across biological membranes.

Fatty acid-albumin complexes and the determination of the transport of long chain free fatty acids across membranes.

Understanding the mechanism that governs the transport of long chain free fatty acids (FFA) across lipid bilayers is critical for understanding transport across cell membranes. Conflicting results have been reported for lipid vesicles; most investigators report that flip-flop occurs within the resolution time of the method (<5 ms) and that dissociation from the membrane is rate limiting, while other studies find that flip-flop is rate limiting and on the order of seconds. We have reinvestigated this problem and find that the methods used in studies reporting rapid flip-flop have not been interpreted correctly. We find that accurate information about transport of FFA across lipid vesicles requires that FFA be delivered to the vesicles as complexes with albumin (BSA). For example, we find that stopped-flow mixing of uncomplexed FFA with small unilamellar vesicles (SUV) containing pyranine yields the very fast influx rates reported previously (>100 s(-1)). However, these influx rates increase linearly with lipid vesicle concentration and can therefore not, as previously interpreted, represent flip-flop. In contrast, measurements of influx rates in SUV and giant unilamellar vesicles performed with oleate-BSA complexes reveal no dependence on vesicle concentration and yield influx rate constants of approximately 4 and approximately 0.5 s(-1), respectively. Rate constants for efflux and dissociation were determined from the transfer of oleate from vesicles to BSA and reveal similar influx and efflux but dissociation rate constants that are approximately 5-10-fold greater. We conclude that flip-flop is rate limiting for transport of FFA across lipid vesicles and slows with an increasing radius of curvature. These results, in contrast to those reporting that flip-flop is extremely fast, indicate that the lipid bilayer portion of biological membranes may present a significant barrier to transport of FFA across cell membranes.