The decreasing incidence and severity of retinopathy of prematurity.

PURPOSE: We sought to determine whether the incidence of retinopathy of prematurity (ROP) at our institution has changed since the Cryo-ROP recruitment period 10 years ago. METHODS: We determined the incidences of threshold ROP, prethreshold ROP, less-than-prethreshold ROP, and no disease for each of 3 birth weight classes (<750 g, 750 to 999 g, and 1000 to 1250 g) of infants born between July 1, 1995, and June 30, 1996, and cared for in the Vanderbilt Neonatal Intensive Care Unit. We then compared these with the rates from our institution during the Cryo-ROP study recruitment period (January 1, 1986, to November 30, 1987). RESULTS: The current incidence and severity of ROP have decreased substantially overall and for each weight group compared with the 1986-87 incidence (P < .001, Cochran-Mantel-Haenszel test). The incidence of "any ROP" decreased by 27% for infants with birth weights less than 750 g, by 51% for infants 750 to 999 g, and by 71% for infants 1000 to 1250 g. The incidence of "prethreshold or greater ROP" decreased by 70% for the 750 to 999 g and 77% for the 1000 to 1250 g weight groups. Although the decrease in "prethreshold or greater ROP" was not as dramatic (25%) for the infants less than 750 g, only 1 infant (10%) progressed to threshold disease in this group, whereas 7 (47%) did in 1986-87. The incidence of threshold ROP decreased by 84% for infants less than 750 g and by 66% for infants 750 to 999 g. No infant with birthweight greater than 999 g progressed to threshold ROP. CONCLUSIONS: The incidence of all levels of ROP has decreased substantially for all infants with birth weights less than 1251 g at Vanderbilt University Medical Center during the past decade. Putative factors responsible for this decrease may include surfactant use, continuous pulse oximetry, aggressive use of antenatal steroids, and improved neonatal nutritional support.

Characteristics of amphotericin B-induced endothelial cell injury.

The polyene antibiotic amphotericin B has been implicated in vascular injury in human subjects and lung injury in an animal model. Our objective was to determine whether amphotericin B directly injures endothelial cells and to investigate several possible mechanisms of injury. Confluent cultures of bovine endothelial cells were incubated with different concentrations of amphotericin B for varying time periods. Injury was assessed by using a chromium 51 release assay, adherent cell counts, and morphologic changes in the endothelial cell monolayers by phase microscopy. Amphotericin B increased 51Cr release in a dose- and time-dependent fashion. Corresponding to changes in 51Cr release, amphotericin B decreased adherent cell counts and disrupted the monolayers. Incubation with vehicle alone (sodium desoxycholate, 8.2 micrograms/ml) did not alter any of these parameters. Incubation of cells with a dose of antibiotic (1 micrograms/ml), which did not produce overt cell injury, significantly increased membrane permeability to K+ ions and activated the sodium/potassium adenosine triphosphatase (Na/K ATPase). Inhibition of the ATPase at this same antibiotic concentration (1 micrograms/ml) produced endothelial cell injury equivalent to the magnitude of injury observed with high doses of the antibiotic (10 micrograms/ml). In the presence of 10% fetal calf serum, the injury at 24 hours was significantly attenuated. This protective effect could not be attributed to binding of the drug by albumin because varying concentrations of bovine serum albumin in minimal essential medium without other serum constitutents had no effect on the magnitude of injury. Incubation of cells with several exogenous oxygen radical scavengers (dimethylthiourea, catalase, and mannitol) or a decrease in ambient oxygen tension during antibiotic exposure did not alter the magnitude of injury. The results demonstrate that amphotericin B directly injures endothelial cells in a dose- and time-dependent manner and demonstrate the importance of the Na/K ATPase for the maintenance of normal endothelial cell function and viability in response to this form of injury.

Increased adhesion of neutrophils to retinal vascular endothelial cells exposed to hyperosmolarity.

Recent studies suggest that leukocytes may contribute to capillary occlusion and endothelial cell injury in diabetic retinopathy. The present study is an attempt to determine whether high glucose concentration/hyperosmolar conditions would increase neutrophil adhesion to retinal endothelial cell monolayers. Confluent monolayers of bovine retinal endothelial cells were incubated for 24 hr in 96-well microtiter plates in 5.5, 20, 50 or 100 mM glucose using 20, 50 or 100 mM mannitol as osmotic controls. After 24 hr the cells were observed by phase microscopy, washed, and then incubated with isolated human neutrophils for 20 min. Non-adherent neutrophils were washed from the monolayers, and the number of adherent neutrophils was determined using an Elisa assay for neutrophil elastase. Adhesion of neutrophils to confluent monolayers of human umbilical vein and bovine aortic endothelial cells at all levels of glucose were assayed in a similar fashion for comparison. Neutrophil adherence to bovine retinal endothelial cells was significantly increased (P < 0.05, n = 8; paired t-test) at all elevated glucose concentrations compared with adherence at control (5.5 mM) glucose concentration. The effect was also concentration dependent with 20, 50 and 100 mM glucose resulting in 35, 57 and 70% increases respectively over controls. However, mannitol at equal concentrations produced similar increases in neutrophil adherence, indicating that the increases in adhesion caused by elevated glucose concentration were due to hyperosmolarity and not some special effect of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)