The use of biomarkers to stratify surgical care in women with ovarian cancer: Scientific Impact Paper No. 69 May 2022.

Biomarkers may offer unforeseen insights into clinical diagnosis, as well as the likely course and outcome of a condition. In this paper, the focus is on the use of biological molecules found in body fluids or tissues for diagnosis and prediction of outcome in ovarian cancer patients. In cancer care, biomarkers are being used to develop personalised treatment plans for patients based on the unique characteristics of their tumour. This tailoring of care can be used to pursue specific targets identified by biomarkers, or treat the patient according to specific tumour characteristics. Surgery is one of the core treatments for ovarian cancer, whether it is offered in primary surgery or following chemotherapy in delayed surgery. Biomarkers already exist to guide the treatment of tumours with chemotherapy, but very little research has determined the value of biomarkers in tailoring surgical care for ovarian cancer. Such research is required to identify new biomarkers and assess their effectiveness in a clinical setting as well as to help identify specific tumour types to guide surgery. Biomarkers could help to determine the success of removing the disease surgically, or help to identify tumour deposits that persist after chemotherapy. All of these aspects would improve current practice. This Scientific Impact Paper highlights research that may pave the way towards bespoke surgery according to the biological characteristics of a tumour and aid gynaecological oncologists to provide surgical treatment according to individual need, rather than a blanket approach for all.

Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants.

OBJECTIVES: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18-22 months corrected age in extremely low birth weight infants. METHOD: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 +/- 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18-22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. RESULTS: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. CONCLUSIONS: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18-22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.

Double wall versus single wall incubator for reducing heat loss in very low birth weight infants in incubators.

BACKGROUND: Studies have shown improved survival of newborn infants maintained in the thermoneutral range. The concept of an incubator with additional insulation, a double plexiglass wall, is appealing for very low birth weight infants as it may help to provide a thermoneutral environment. OBJECTIVES: To assess the effects of double walled incubator versus a single wall incubator on insensible water loss, rate of oxygen consumption, episodes of hypothermia, time to regain birth weight, duration of hospitalization and infant mortality in premature infants. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - 2006), EMBASE, previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants in all published languages, and CINAHL (1982 - 2006). SELECTION CRITERIA: Only studies using random or quasi-random methods of allocation were considered for this review. Eligible studies assessed at least one of the outcome variables identified as important to this topic. DATA COLLECTION AND ANALYSIS: Independent data extraction and quality assessment of included trials was conducted by the review authors. Data were analyzed using generic inverse variance methodology and weighted mean difference (WMD). Results are presented with 95% confidence intervals. Meta-analysis was undertaken using a fixed effect model. MAIN RESULTS: Three studies met the criteria. Four other studies were excluded, as they did not compare double versus single wall incubators (details of the studies are given in the included and excluded studies section). Double wall incubators have the advantage of decreasing heat loss, decreasing heat production and decreasing radiant heat loss when compared to single wall incubators. There is also the advantage of reduced oxygen consumption. A minimal increase in conductive heat loss was noted when compared to single wall incubators. All of these effects are small and do not support the proposition that double wall incubators have a beneficial effect on long term outcomes including mortality or the duration of hospitalization. AUTHORS' CONCLUSIONS: Although it appears that caring for extremely small infants in double wall incubators may theoretically result in shorter hospitalization and may have metabolic advantages, this review was unable to find any data in the literature to support or refute this hypothesis. The studies do not provide any evidence that the small decrease in heat loss improves clinical outcome. Therefore, the available data is insufficient to directly guide clinical practice.

Current perspectives on vitamin E in infant nutrition.

The human infant is born with low body stores of vitamin E. Thus, the infant requires an adequate intake of vitamin E soon after birth. If adequate sources of tocopherol are not provided, a clearly defined deficiency state characterized by hemolytic anemia and, after a period of years, spinocerebellar degeneration results. However, the benefit of pharmacologic doses of vitamin E given as prophylaxis against diseases believed to be related to oxygen toxicity (bronchopulmonary dysplasia, retinopathy of prematurity, and periventricular-intraventricular hemorrhage) is not clear. Possible benefits must be balanced against the potential for serious toxicity. Few data are available on the pharmacokinetics of tocopherols in infants, particularly with respect to esterified forms of tocopherol, and little is known about the toxicity associated with parenteral administration of the vitamin.

The role of tocopherol in oxygen-induced retinopathy: kitten model.

The effect of tocopherol (vitamin E) on oxygen-induced retinopathy was studied in 75 kittens following the development of a 12-point scoring system to quantitate the degree of retinopathy seen at three weeks. The tocopherol was found to be beneficial when given daily from the day of birth (P less than .0001) with oxygen exposures of two to three days (79% FiO2) beginning on day 3. Caution is urged in applying these data to humans because (1) hepatosplenomegaly was noted in the treated animals, and (2) the kitten model for oxygen-induced retinopathy is not entirely satisfactory, Pediatrics, 59:998-1005 1977, RETROLENTAL FIBROPLASIA, OXYGEN TOXICITY, VITAMIN E, RETINOPATHY, KITTEN.

Effects of marginal hypoxemia on recovery from oxygen-induced retinopathy in the kitten model.

Prolonged oxygen administration in premature infants is the most predictive variable for severe retinopathy of prematurity, after degree of prematurity itself. It was noted that infants receiving prolonged oxygen supplementation are probably hypoxemic relative to their healthy counterparts. Therefore, hypoxemia during recovery from a hyperoxic-induced retinal vascular injury was tested in the kitten model of oxygen-induced retinopathy. Twelve litters were exposed to 80% inspired O2 for 65 hours on day 3, and recovered in room air, 13% or 17% oxygen. The retinas were scored at 4 weeks, and 13% oxygen recovery (PO2 = 39 +/- 18 torr) was found to worsen significantly the retinopathy compared with that in room air-recovered littermates (P less than .01). Hemorrhages occurred more frequently in the retinas from the hypoxemic-recovered kittens. Clinical trials of this hypothesis are indicated in humans.

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)

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.

Atypical chronic lung disease patterns in neonates.

OBJECTIVE: To determine, in the postsurfactant era, the incidence and clinical characteristics of infants with atypical versus traditionally defined bronchopulmonary dysplasia (BPD) among premature infants with birth weights <1251 g. DESIGN: Retrospective cohort study. SETTING: A single regional neonatal intensive care unit (level III/IV). PATIENTS: Two hundred thirty-two premature infants <1251 g at birth consecutively admitted during a 2-year period. MAIN OUTCOME MEASURE: Incidence of classic BPD and atypical chronic lung disease (CLD) (occurring without preceding respiratory distress or after recovery from respiratory distress). RESULTS: Among 177 infants <1251 g who survived to 28 days, 27 (15%) had atypical CLD and 61 (34.5%) had classic BPD. Atypical CLD infants were significantly heavier and more mature than classic BPD infants (mean birth weights, 922 +/- 152 g vs 854 +/- 173 g; and mean gestational age, 26.8 +/- 1.3 weeks vs 26.1 +/- 1.6 weeks). Median duration of ventilator support (31 days; range, 2 to 127 vs 42 days; range, 4-145 days) and oxygen therapy (30 days; range, 11 to 163 vs 48 days; range, 19-180 days) were shorter in atypical CLD infants than in classic BPD infants. CONCLUSION: Atypical CLD comprised 31% of total cases of CLD. Atypical CLD appears to be less severe than classic BPD. These data suggest that initial, acute lung injuries are not the sole antecedents of neonatal CLD.

Breast-feeding by a mother with cystic fibrosis.

A 20-year-old white women with cystic fibrosis who breast-fed her normal infant is described. Extensive breast milk analysis revealed normal sodium and chloride concentrations but elevated total protein and low total fat content; IgG and IgM levels were low to absent. The infant tolerated breast-feeding well, with normal growth and without infections, but the nutritional status of the mother appeared to be adversely affected. This case illustrates that breast-feeding by a mother with cystic fibrosis appears to be feasible but is fraught with difficulties.

Tocopherol efficacy and safety for preventing retinopathy of prematurity: a randomized, controlled, double-masked trial.

To test the efficacy and safety of vitamin E in preventing retinopathy of prematurity, 287 infants with birth weights of less than 1.5 kg or gestational ages of less than 33 weeks were enrolled within 24 hours of birth in a randomized, double-masked trial of IV, followed by oral, placebo v tocopherol (adjusted to plasma levels of 3 to 3.5 mg/dL). In the 196 infants completing ophthalmic follow-up, tocopherol did not prevent retinopathy of prematurity of any stage (28% placebo treated v 26% tocopherol treated) or moderately severe retinopathy of prematurity (8% placebo treated v 11% tocopherol treated). Cicatricial sequelae were not significantly different (1/97 placebo treated v 3/99 tocopherol treated), with one placebo-treated infant and one tocopherol-treated infant having retinal detachments. Among all 232 infants examined, those treated with tocopherol had more retinal hemorrhage than placebo-treated infants (8/121 placebo treated v 16/111 tocopherol treated), and retinal hemorrhage correlated positively (P less than .01) with plasma levels of tocopherol after the first 2 weeks of age. Prospective monitoring of morbidity including late-onset sepsis, necrotizing enterocolitis, etc revealed no differences between groups except that grades 3 and 4 intraventricular hemorrhage occurred more frequently in infants weighing less than 1 kg at birth who had received tocopherol (14/42, 33%) v those who had received placebo (4/43, 9%) (P less than .02). Our data do not support the use of tocopherol for prophylaxis against retinopathy of prematurity in premature infants and suggest that IV tocopherol treatment starting on day 1 may increase the incidence of hemorrhagic complications of prematurity, particularly in infants with birth weights of less than 1 kg.

The "88% saturation test": a simple lung function test for young children.

OBJECTIVE: The 88% saturation test (88%-SAT) was developed as an alternative to standard spirometry for those young children unable to perform standard forced expiratory maneuvers. In adults, this test revealed rapid desaturation in those persons with a history of asthma when compared with healthy control subjects. Similar findings in children were tested. SETTING: Tertiary care hospital. PATIENTS: Thirty-three former premature infants (28.3 +/- 2.3 weeks gestation), aged 5 to 7 years, who were participating in a follow-up study, were enrolled in this study. DESIGN: The study compared the 88%-SAT with standard spirometry and respiratory health characteristics ascertained through a parental questionnaire. The 88%-SAT consists of continuous measurement of hemoglobin saturation by pulse oximetry (SaO2) while the subject breathes a nonhumidified 12% oxygen and nitrogen mixture for 10 minutes or until SaO2 decreases to 88%, whichever occurs first. Abnormal 88%-SAT was defined as a decrease of SaO2 to 88% within the 10-minute period, and abnormal spirometry was defined using standardized values. RESULTS: Of the 20 children who successfully completed both spirometry and the 88%-SAT, 10 had normal spirometry results and did not desaturate to 88%, and 5 had abnormal spirometry and 88%-SAT results. Four children did not desaturate during the 88%-SAT, but had abnormal spirometry results, and one child had abnormal 88%-SAT results, but normal spirometry. Ten additional children completed the 88%-SAT, but not standard spirometry. Three children were unable to complete either test. Of those 30 children tested, 7 (23%) had a history of reactive airways disease, and all 7 had abnormal 88%-SAT results. The 88%-SAT had greater sensitivity (100% vs 75%) and specificity (87% vs 63%) than spirometry in identifying children with known reactive airways disease. The mean McCarthy general cognitive index (GCI) of the group performing both spirometry and the 88%-SAT (n = 20) achieved a mean (+/- SD) GCI of 96.2 +/- 16.7, and the group (n = 30) that completed the 88%-SAT had a mean (+/- SD) GCI of 75.2 +/- 26.3 (chi 2 P < .012). The 10 children able to perform only the 88%-SAT had a mean GCI (+/- SD) of 72.8 +/- 26.9, and the 3 children unable to perform either test had a mean GCI (+/- SD) of 63 +/- 11. CONCLUSIONS: Our data suggest that the 88%-SAT may be more effective than spirometry for identifying reactive airways disease in young, uncooperative, or developmentally delayed children. The dry air of the hypoxic inspired gas may function as an airway challenge, leading to decreased oxygenation in patients with reactive airways.

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.

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.

Early dexamethasone-attempting to prevent chronic lung disease.

BACKGROUND: We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results. METHODS: Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo. RESULTS: No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively. CONCLUSIONS: This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia.

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)

Effect of acute-phase retinopathy of prematurity on grating acuity development in the very low birth weight infant. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

PURPOSE: To examine the development of grating acuity in four groups of eyes in the Multicenter Study of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP): eyes with no ROP; eyes with less-than-prethreshold ROP; eyes with prethreshold ROP; and eyes with threshold ROP that were randomized to serve as controls (not treated with cryotherapy). METHODS: Subjects were 1398 children with birth weights < 1251 g whose acute-phase ROP was documented as part of the CRYO-ROP study. Monocular grating acuity was measured using the Teller acuity card procedure when children reached 1, 2, 3 1/2, and 4 1/2 years of age. RESULTS: Eyes in the no-ROP and less-than-prethreshold groups showed nearly identical acuity development. Eyes with prethreshold ROP showed mean acuity similar to the no-ROP group at 1 and 2 years, but slightly below the no-ROP group at 3 1/2 and 4 1/2 years. Only 50% of eyes in the threshold untreated ROP group had measurable acuity. These eyes showed mean acuity scores that were approximately 1 octave below those of the no-ROP group at all four test ages. When data from eyes with ROP residua or other ocular abnormalities, and data from eyes of children who were unable to pass the study developmental screening items, were excluded, acuity development was similar among groups. CONCLUSIONS: Mild (less-than-prethreshold) ROP has no effect on the development of grating acuity in children between 1 and 4 1/2 years of age. Moderate (prethreshold) ROP is associated with reduced acuity at 3 1/2 and 4 1/2 years. In general, severe (threshold untreated) ROP results in moderate to severe reductions in acuity at all ages between 1 and 4 1/2 years. However, a small number of children with severe ROP show normal acuity development.

Color vision measured with pseudoisochromatic plates at five-and-a-half years in eyes of children from the CRYO-ROP study.

PURPOSE: To investigate the prevalence of color deficits at age 5 1/2 years in preterm children with birth weights of less than 1251 g who participated in the multicenter Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study. METHODS: Two cohorts of CRYO-ROP participants served as subjects: 1055 children who participated in a long-term study of the natural history of ROP at 5 of the 23 CRYO-ROP centers, and 187 children (from all 23 study centers) who had threshold ROP in both eyes and who were randomized to receive cryotherapy in 1 eye. Monocular color vision was tested at age 5 1/2 years, using the Standard Pseudoisochromatic Plates, part 2 (SPP2) for acquired color vision defects. RESULTS: In the Natural History cohort, prevalence of red-green (R-G) color deficits was 6.6% for males and 1.0% for females, similar to that of the general adult population. Prevalence of blue-yellow (B-Y) color deficits was 2.8% for males and 2.2% for females, more than 200 times that in the general adult population. Prevalence of B-Y deficits was not related to birth weight, gestational age, acute-phase ROP, optic atrophy, or retinal residua of ROP, but was related to visual acuity. In the Threshold ROP cohort, color vision deficits were no more likely in eyes that had received cryotherapy than in control eyes. CONCLUSIONS: The results confirm an increased prevalence of B-Y deficits in children born before term, and provide evidence that the increased prevalence is not related to birth weight, gestational age, or severity of ROP within this group of preterm children. No evidence was found to indicate that cryotherapy increased the rate of color vision deficits in eyes with threshold ROP.

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.

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.