Retinopathy of prematurity.
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Blood Gas Monitoring, Transcutaneous↗
Biomedical subjects
D L Phelps
Publications and source records attributed to D L Phelps.
Ocular cosmesis in retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.
We report the externally apparent outcome in the natural history cohort (n = 4099) that was followed up prospectively in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. The overall incidence of an adverse cosmetic outcome in the survivors who were examined 12 months post term (n = 2759) was 15.1%. Adverse cosmetic outcomes included strabismus (12.8%), nystagmus (3.3%), total retrolental membrane (1%), epiphora (0.6%), corneal opacity (0.6%), cataract (0.3%), and episcleral hyperemia (0.3%). A comparable subgroup examined 24 months post term showed strabismus (14.4%), nystagmus (2.2%), epiphora (0.5%), corneal opacity (0.7%), cataract (0.5%), episcleral hyperemia (0.5%), lid fissure asymmetry (2.4%), and corneal diameter asymmetry (2.0%). The rate of adverse aesthetic outcome was greatest in eyes that had developed more severe acute retinopathy of prematurity and an unfavorable structural outcome. In patients with bilateral threshold retinopathy of prematurity who underwent no therapeutic ocular procedures, other than randomized assignment to undergo cryotherapy in one eye, more frequent adverse cosmetic outcomes were found in the untreated eyes.
Acute Disease↗
Retinopathy of prematurity.
ROP is a common disorder among extremely low-birth-weight premature infant survivors and may cause total vision loss in as many as 2% to 4% of those weighing less than 2 lb (1 kg) at birth. Regular examinations begun in the intensive care unit permit early detection and treatment of progressive ROP, reducing visual impairment. Ongoing research into antioxidants, angiogenesis, light exposure, and newer surgical techniques may offer new approaches for preventing and treating established ROP. Infants who have had ROP that regressed should continue regular ophthalmologic follow-up to detect and treat myopia, strabismus, and if they have cicatricial sequelae, late retinal detachments as teens or adults. Infants who develop retinal detachments should be referred for early intervention and special education programs and remain in regular ophthalmologic follow-up for the detection and treatment of further ophthalmic complications.
Humans↗
Identification of prostaglandins and hydroxyeicosatetraenoic acids in kitten retina: comparison with other species.
Conversion of arachidonic acid to eicosanoids by kitten retinae was investigated to evaluate whether the pattern of kitten retinal eicosanoids simulates that found in the human and other animal species. Freshly isolated kitten retinae were incubated with 20 microM radiolabeled arachidonic acid, and the metabolites were analysed by reverse phase-high pressure liquid chromatography, thin-layer chromatography and gas chromatography-mass spectroscopy. Kitten retinal tissues converted arachidonic acid into prostaglandins (PGs), thromboxane (Tx) and hydroxyeicosatetraenoic acids (HETEs). The major eicosanoid identified was 6kPGF1 alpha--the stable non-enzymatic hydrolysis product of prostacyclin. Other eicosanoids identified included TxB2, PGE2, PGF2 alpha, 12-hydroxy-heptadecatrienoic acid, 12-HETE, and 15-HETE. The spectrum of kitten retinal cyclooxygenase metabolites is similar to those obtained from bovine retina and human retinal vascular endothelium with prostacyclin being the major cyclooxygenase metabolite produced.
6-Ketoprostaglandin F1 alpha↗
Operational aspects of terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.
The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) is a randomized clinical trial sponsored by the National Eye Institute (NEI) designed to test whether cryotherapy applied to eyes of premature infants with a specified extent of stage 3+ ROP significantly decreases the incidence of an unfavorable outcome. An unfavorable outcome is defined as either retinal detachment or a retinal fold and was determined at 3 months posttreatment by the use of a masked photographic system. Enrollment into the trial was terminated on recommendation of the Data and Safety Monitoring Committee 9 months before the scheduled closing date for enrollment because of demonstrated treatment benefit. The purpose of this article is to discuss the operations involved in the orderly termination of enrollment and dissemination of results from this trial. These activities included preparation of trial participants and staff, release of trial information, continuing patient care, data collection and coding, and publication of trial results.
Blindness↗
Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.
In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (ROP), 4099 infants weighing less than 1251 g at birth underwent sequential ophthalmic examinations, beginning at age 4 to 6 weeks, to monitor the incidence and course of ROP. Overall, 65.8% of the infants developed ROP to some degree; 81.6% for infants of less than 1000 g birth weight. As expected, ROP incidence and severity were higher in lower birth weight and gestational age categories. Black infants appeared less susceptible to ROP, of all severity categories, than nonblack infants. The timing of retinal vascular events correlated more closely with postconceptional age than with postnatal age, implicating the level of maturity more than postnatal environmental influences in governing the timing of these vascular events. These results include the current incidence of various severity stages of ROP found in the United States and provide new insight into the development of ROP.
Cryosurgery↗
28-day survival rates of 6676 neonates with birth weights of 1250 grams or less.
Survival rates specific for birth weight, gestational age, sex, and race are described for 6676 inborn neonates who weighed less than 1251 g at birth and were born during 1986 through 1987. Overall 28-day survival increased with gestational age and birth weight, from 36.5% at 24 weeks' gestation to 89.9% at 29 weeks' gestation, or from 30.0% for neonates of 500 through 599 g birth weight to 91.3% for neonates of 1200 through 1250 g. The expected birth weight-specific survival advantage for female neonates and black neonates diminished when the data were controlled for gestational age, showing that certain previously reported survival advantages are based on lower birth weight for a given gestational age. Multivariate analysis showed that all tested variables were significant predictors for survival, in order of descending significance: gestational age and birth weight, sex, race, single birth, and small-for-gestational-age status. The powerful effect of gestational age on survival highlights the need for an accurate neonatal tool to assess the gestational age of very low birth weight neonates after birth.
Black or African American↗
Home oxygen administration and retinopathy of prematurity: survey of 1988 practices.
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Home Nursing↗
Effects of changes in oxygen tension on lipoxygenase metabolites. Serum 15-HETE is increased in kittens exposed to hyperoxia.
The chronic phase of O2-induced retinopathy is characterized by retinal neovascularization. We have previously demonstrated that 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE), a product of white cells, is proangiogenic. In this study, kittens exposed to in vivo hyperoxia produced increased amounts of 15-HETE. Nine litters of 30 kittens (aged 6-8 days) were used. Control kittens were left in room air; hyperoxic kittens were placed in 80% oxygen for 48 h; recovery kittens were returned to room air for 24 h following hyperoxic exposure. Following treatments, the animals were sacrified, and blood was evaluated for 15-HETE. Stimulated serum 15-HETE levels were assayed by high-performance liquid chromatography and GC-selected ion monitoring. While controls produced 0.48 +/- 0.16 (SE) nmol/ml of 15-HETE, values in the hyperoxic and recovery animals were increased at 0.7 +/0 0.2 and 0.68 +/- 0.15 nmol/ml (p less than 0.05 and p = 0.05, respectively). Increased production of this proangiogenic metabolite by WBCs (which can migrate out of blood vessels to set up extravascular angiogenic foci) may play a role in the genesis of the neovascularization process that occurs in response to oxygen-induced injury.
Animals↗
Oxygen-induced retinopathy: lack of adverse heparin effect.
Retinopathy of prematurity is a disorder of abnormal retinal vascular proliferation, and one hypothesis for its pathogenesis involves abnormal activity of angiogenic growth factors in the retina. One of these, acidic fibroblast growth factor, is found primarily in retina and brain tissues. Its mitogenic effect is greatly potentiated in vitro by heparin. Because retinopathy of prematurity occurs most often in premature infants who receive the greatest amount of heparin, we tested the hypothesis that heparin may adversely affect the retinopathy observed in kittens after hyperoxic (80% oxygen) exposure. Seventeen litters of kittens were randomly assigned to receive either saline or heparin s.c. injections from d 2 through recovery to 28 d of age; 65 h of high oxygen exposure was started on d 3 to induce a standard retinal injury in our model. There were no differences in the degree of retinopathy between the heparin-treated group [severity score 5.9 +/- 2.2 (mean +/- SD)], and the saline-treated group (severity score 7.1 +/- 1.7, p greater than 0.20, 80% power to detect a 2-point difference in score at alpha = 0.05). These findings do not support a concern that clinical doses of heparin potentiate retinopathy of prematurity.
Animals↗
Oxygen and developmental retinal capillary remodeling in the kitten.
During the recovery period after a high oxygen injury in the kitten, chronic hypoxia adversely affects the resulting retinopathy, but increasing oxygen breathing to 28% improves it. To test the effects of chronic hypoxia without an antecedent hyperoxic injury in the kitten, the animals were raised in 13% or 21% (room air) oxygen and their retinas examined at 3, 7, 14, or 21 days. They were also studied after 14 days of exposure to 30% or 40% oxygen to compare the graded effects of elevated oxygen to that of hypoxia on the development of the retinal capillary bed. Chronic hypoxia alone did not affect somatic growth or cause retinopathy. An inverse relationship was found between the rate of retinal vascularization and ambient oxygen. As inspired oxygen rose from 13%-40%, the proportion of the retina vascularized at 14 days fell from 76 +/- 12%-18 +/- 8% (mean +/- standard deviation, P less than 0.01). All 14-day animals had similar capillary density at the advancing edge of their retinal vasculature (mean diameter of the capillary meshwork = 71 +/- 12 microns) despite the impairment of forward progress observed in elevated oxygen. However, the width of the periarteriolar capillary-free zone increased from 65 +/- 10 microns in 13% oxygen-breathing animals to 104 +/- 5 microns in 40% oxygen-breathing animals (P less than 0.001). The animals raised in hypoxic conditions had more mature-appearing retinal vasculature at 21 days than did controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Predicting risk for bronchopulmonary dysplasia: selection criteria for clinical trials.
Early identification of neonates in whom bronchopulmonary dysplasia is most likely to develop permits appropriate enrollment into clinical trials testing early intervention therapies for the prevention or treatment of bronchopulmonary dysplasia. Analysis of 160 neonatal intensive care unit survivors to 28 days revealed that supplemental oxygen requirement at 28 days could be predicted by a logistic regression including (1) birth weight, gestational age, 5-minute Apgar score, and peak inspiratory pressure at 12 hours for 12-hour-old neonates and (2) birth weight, gestational age, peak inspiratory pressure at 12 hours, and mean airway pressure at 10 days for 10-day-old neonates. These two regression analyses were applied prospectively to three new data sets totaling 238 neonates to test their predictive ability. Neonates were classified into low-, moderate-, or high-risk groups on the basis of their predicted probability of requiring oxygen supplementation at 28 days; low = probability of less than 25%, moderate = probability of 25% to 75%, and high = probability greater than 75%. Although these populations were demographically distinct from the original group, the regression analyses performed well. The regression analysis for 12 hours of age classified 125 neonates at low risk of whom 9% required supplemental oxygen at 28 days, and the regression analysis for 10 days classified 141 neonates at low risk of whom 7% required supplemental oxygen. The 12-hour regression analysis classified 80 neonates at moderate risk of whom 33% required supplemental oxygen at 28 days and the 10-day regression analysis classified 49 neonates at moderate risk of whom 24% required supplemental oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)
Apgar Score↗
Retinopathy of prematurity.
Increasing numbers of immature infants are surviving with incompletely developed retinal vessels at risk for ROP. Since adverse perinatal events seem closely associated with the more severe forms of the disorder, neonatologists may be able to contribute most to the reduction of vision loss if they can optimize the neonatal course of these infants. However, to date, no particular intervention has been proven to be efficacious in preventing ROP. On the other hand, cryotherapy has been found effective in stopping the progress of severe ROP to retinal detachments about half the time. This places a responsibility on the neonatologist and ophthalmologist to assure that each at-risk infant is examined by 4-6 weeks of age to enable the prompt application of cryotherapy if severe ROP develops. This is presently the infant's best chance of retaining useful vision, and appropriate nursery policies should be developed to ensure its availability. Additional research is needed to understand the control of regression vs progression in ROP and to explore potential means of preventing the disease altogether.
Birth Weight↗
Vitamin E and retinopathy of prematurity: the clinical investigator's perspective on antioxidant therapy: side effects and balancing risks and benefits.
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Acute Kidney Injury↗
Surfactant replacement therapy at birth: final analysis of a clinical trial and comparisons with similar trials.
A randomized trial of surfactant replacement therapy at birth was conducted at the University of Rochester between June 1983 and November 1985. Thirty-four premature infants, 25 to 29 weeks' gestational age, received a preventilatory dose of a calf lung surfactant extract in saline prepared at the University of Rochester. A control group of 31 infants received a preventilatory dose of saline alone. The major finding of this trial is that a single preventilatory dose of calf lung surfactant extract reduces the severity of the respiratory distress syndrome during the first 24 hours of life. The beneficial effects, however, are not sustained in many infants and diminish after 24 hours of life. The survival rate was 71% in both the control and surfactant-treated groups. There was a lower incidence of pneumothorax in the surfactant-treated group. There were no differences in the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, and intraventricular hemorrhage. No adverse effects of surfactant replacement therapy were identified. Results of this study suggest that multiple postventilatory doses of surfactant will be required for optimal therapy.
Clinical Trials as Topic↗
The role of vitamin E therapy in high-risk neonates.
Infants are born with low tissue stores of tocopherol and accumulate this vitamin from feedings after birth. If prolonged malabsorption of tocopherol occurs, a recognized hemolytic anemia and spinocerebellar degeneration develops after a period of months to years. This is preventable with tocopherol supplementation. However, a benefit of tocopherol supplementation in premature infants who are transiently unable to feed after birth has been harder to prove. Pharmacologic doses have not definitively been shown to be beneficial in any of the putative oxygen toxicity syndromes, with the possible exception of PV/IVH. It is exciting that tocopherol appears to reduce significantly the incidence and severity of IVH, and this potential application underscores the urgent need for pharmacologic studies of this lipid nutrient. In order to administer the drug safely, we must establish the best means of assessing sufficiency and toxicity in premature infants. Measures of tissue capacity to resist oxidative stress appear to be the most promising of these tests at this time. In the interim, a working proposition is to provide sufficient tocopherol to these infants to raise the plasma levels into the range considered normal for term, breastfed infants.
Bronchopulmonary Dysplasia↗
Changes in oxygen tension and effects on cyclooxygenase metabolites: III. Decrease of retinal prostacyclin in kittens exposed to hyperoxia.
The acute phase of oxygen-induced retinopathy is associated with vasoconstriction and occlusion of the retinal vessels. Because this acute vasoobliterative phase could be due to the inhibition in retinal vessels of the production of the potent vasodilator and antithrombotic metabolite prostacyclin, animal experiments were performed to assess this possibility. Eight litters of 27 kittens (four to six days of age) were used. Control kittens were left in room air; hyperoxic kittens were placed in 80% oxygen for 48 hours; recovery kittens were returned to room air for 24 hours following hyperoxic exposure. Following treatments, the animals were killed, retinas isolated, and prostaglandin formation assessed. Retinal tissues produced 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, and thromboxane B2 from exogenous arachidonate. A significant (approximately 33%) reduction in retinal 6-keto-prostaglandin F1 alpha (the end product of prostacyclin) was observed both in the hyperoxic and recovery litter mates when compared with controls. Both of the experimental groups also demonstrated a reduction in total retinal prostanoids that paralleled the changes observed in prostacyclin, suggesting that the biochemical effect of hyperoxia on retinal vascular arachidonic acid metabolism occurred at the level of cyclooxygenase. A decrease in the local production of prostacyclin during hyperoxia is consistent with the histologic retinal changes observed during the acute phase of oxygen-induced retinopathy.
6-Ketoprostaglandin F1 alpha↗
Vitamin E in kitten oxygen-induced retinopathy. II. Blockage of vitreal neovascularization.
The effect of vitamin E (tocopherol) on oxygen-induced retinopathy was studied in the kitten after a quantitative scoring system was developed for their India ink injected retinal flat preparations. In 75 previously described kittens exposed to two or three days of oxygen from day 3, treatment from day 1 with vitamin E or placebo disclosed that kittens treated with vitamin E had less retinopathy. Theories of the mechanism of action of vitamin E would predict that, if given only after the oxygen exposure, vitamin E should be ineffective. This was tested in 37 kittens with placebo or drug begun only after withdrawal from oxygen. Unexpectedly, significantly less intravitreal neovascularization was found in kittens treated with vitamin E after oxygen exposure.
Animals↗