Expression of thrombospondin-1 in ischemia-induced retinal neovascularization.
Thrombospondin-1 is an extracellular matrix protein that inhibits endothelial cell proliferation, migration, and angiogenesis. This study was performed to investigate the role of thrombospondin-1 in ischemic retinal neovascularization. In a murine model of retinal neovascularization, thrombospondin-1 mRNA was increased from postnatal day 13 (P13), with a threefold peak response observed on P15, corresponding to the time of development of retinal neovascularization. Prominent expression of thrombospondin-1 was observed in neovascular cells, specifically, cells adjacent to the area of nonperfusion. It has been suggested that vascular endothelial growth factor (VEGF) plays a major role in ischemia-induced retinal neovascularization of this model, so we studied the effects of VEGF on thrombospondin-1 expression. In bovine retinal microcapillary endothelial cells, VEGF induced a biphasic response of thrombospondin-1 expression; VEGF decreased thrombospondin-1 mRNA 0.41-fold after 4 hours, whereas it increased, with a threefold peak response, after 24 hours. VEGF-induced endothelial cell proliferation was completely inhibited by exogenous thrombospondin-1 and increased by 37.5% with anti-thrombospondin-1 antibody. The present findings suggest that, in the ischemic retina, retinal neovascular cells increase thrombospondin-1 expression, and VEGF may stimulate endogenous thrombospondin-1 induction, which inhibits endothelial cell growth. VEGF-mediated thrombospondin-1 induction in ischemia-induced angiogenesis may be a negative feedback mechanism. (+info)
Metabolic acidosis-induced retinopathy in the neonatal rat.
PURPOSE: Carbon dioxide (CO2)-induced retinopathy (CDIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP), was previously described by our group. In this model, it is possible that CO2-associated acidosis provides a biochemical mechanism for CDIR. Therefore, the effect of pure metabolic acidosis on the developing retinal vasculature of the neonatal rat was investigated. METHODS: A preliminary study of arterial blood pH was performed to confirm acidosis in our model. In neonatal rats with preplaced left carotid artery catheters, acute blood gas samples were taken 1 to 24 hours after gavage with either NH4Cl 1 millimole/100 g body weight or saline. In the subsequent formal retinopathy study, 150 newborn Sprague-Dawley rats were raised in litters of 25 and randomly assigned to be gavaged twice daily with either NH4Cl 1 millimole/100 g body weight (n = 75) or saline (n = 75) from day 2 to day 7. After 5 days of recovery, rats were killed, and retinal vasculature was assessed using fluorescein perfusion and ADPase staining techniques. RESULTS: In the preliminary pH study, the minimum pH after NH4Cl gavage was 7.10+/-0.10 at 3 hours (versus 7.37+/-0.03 in controls, mean +/- SD, P < 0.01). In the formal retinopathy study, preretinal neovascularization occurred in 36% of acidotic rats versus 5% of controls (P < 0.001). Acidotic rats showed growth retardation (final weight 16.5+/-3.0 g versus 20.2+/-2.6 g, P < 0.001). The ratio of vascularized to total retinal area was smaller in acidotic rats (94%+/-4% versus 96%+/-2%, P < 0.001). CONCLUSIONS: Metabolic acidosis alone induces neovascularization similar to ROP in the neonatal rat. This suggests a possible biochemical mechanism by which high levels of CO2 induce neovascularization and supports the suggestion that acidosis may be an independent risk factor for ROP. (+info)
Retinopathy of prematurity-mimicking retinopathy in full-term babies.
The purpose of this study was to analyze the fundus findings and associated abnormalities in full-term babies with retinopathy of prematurity (ROP)-mimicking retinopathy. In twenty-seven such babies suffering from this condition, retinal findings were retrospectively analyzed. These babies were not premature and had not required supplementary oxygen; there was no family history of the disease, and no known causes. Bilaterality and severity of retinopathy were compared between groups with associated systemic abnormalities and those without. Forty eyes in twenty-seven full-term babies had abnormal retinal findings; dragged retina accounted for 42.5%, and falciform retinal fold for 47.5%, and retrolental membrane for 10%. Nine babies had associated brain abnormalities, and in these, severe bilateral retinopathy was more likely to occur than in those without abnormalities. These results suggest that if full-term babies have associated abnormalities of the brain, the presence of retinopathy should be ascertained postnatally by cautious examination of the retina. (+info)
Risk factors for strabismus in children born before 32 weeks' gestation.
AIM: To investigate risk factors associated with strabismus in children born prematurely. METHODS: Prospective study of all children born before 32 weeks' gestation between 1 January 1990 and 31 December 1991 in a geographically defined population of approximately 3 million in the Northern Region of the United Kingdom. All children were examined aged 2 years by the same ophthalmologist and paediatrician. RESULTS: 558 children (98.6% of study group) were examined. Logistic regression showed an increased risk of strabismus in children with cicatricial retinopathy of prematurity (p=0.02), refractive error (p=0.003), family history of strabismus (p<0.0001), and poor neurodevelopmental outcome (p<0.0001), in particular impaired locomotor skills (p=0.008) and hand-eye coordination (p=0. 001). Gestational age and regressed acute ROP were not independent risk factors for strabismus (p=0.92 and 0.85 respectively). CONCLUSIONS: This study has identified factors which are independently related to strabismus (although not necessarily causative) and others which are related only indirectly. This may contribute both to the management of children born prematurely and to future studies of the aetiology of strabismus. (+info)
Bias due to incomplete follow up in a cohort study.
AIM: To investigate the bias introduced by incomplete follow up in a cohort study of ocular outcome after premature birth. METHODS: A geographically defined cohort of children born before 32 weeks' gestation was prospectively recruited at birth to study the ocular outcome at 2 years. On the basis of attendance at 2 years, the children's families were allocated to one of three groups: group 1 attended for follow up, group 2 were difficult to trace, and group 3 were very reluctant for assessment. All children were examined by a single ophthalmologist, masked to these groupings. RESULTS: 558 children (98.8% of study group) were examined, of whom 505 were in group 1, 20 in group 2, and 33 in group 3. The groups which were more difficult to study (groups 2 and 3) showed a significantly higher prevalence of ocular abnormalities, including strabismus (p=0. 02) and cicatricial retinopathy of prematurity (p=0.002) compared with those attending for follow up. Further, not all of these cases could have been identified by review of the children's previous records. Ocular abnormalities would be underestimated by 16% (11.3% in group 1 compared with 13.4% in the total cohort, p=0.77). CONCLUSIONS: This study suggests that the prevalence of abnormalities would be underestimated by incomplete follow up, as those subjects who were most difficult to obtain for study had a significantly higher prevalence of abnormalities. (+info)
Interobserver agreement for grating acuity and letter acuity assessment in 1- to 5.5-year-olds with severe retinopathy of prematurity.
PURPOSE: To evaluate interobserver test-retest reliability of the Teller Acuity Card procedure for assessment of grating acuity at ages 1, 2, 3.5, 4.5, and 5.5 years, for HOTV letter acuity at 3.5 and 4.5 years, and for Early-Treatment Diabetic Retinopathy Study (ETDRS) letter acuity at 5.5 years in the multicenter study of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP). METHODS: Subjects were the 73 participants in the CRYO-ROP study who had acuity assessed at one or more ages by two of the seven study visual acuity testers as part of a quality control procedure. All subjects had birth weights of less than 1251 g, and all had severe (threshold) ROP in one or both eyes. RESULTS: For sighted eyes, interobserver agreement for grating acuity (across all five test ages) was 0.5 octave or better in 57% of eyes and 1.0 octave or better in 85% of eyes. Interobserver agreement for letter acuity (3.5-, 4.5-, and 5.5-year test ages) was 0.5 octave or better in 71% of eyes and 1.0 octave or better in 93% of eyes. For all eyes (sighted and blind), Kendall rank correlation coefficients (Tau) were 0.86, 0.83, and 0.94 for grating, HOTV, and ETDRS acuity, respectively. Kappa statistics on data from all eyes indicated excellent interobserver agreement for grating, HOTV, and ETDRS acuity (0.73, 0.80, and 0.84, respectively). Interobserver agreement was not related to age or to severity of retinal residua of ROP. CONCLUSIONS: Excellent interobserver agreement for grating acuity measurements and for letter acuity measurements was obtained. Results suggest that with careful training and implementation of quality control procedures, high reliability of visual acuity results is possible in clinical populations of young children. (+info)
Vitreoretinal reactions and persistent hyaloid vessels.
In cases with persistent primary vitreous in full-term infants there were vitreoretinal reactions including vitreoretinal anastomoses of blood vessels, vitreoretinal strands, traction folds of the retina, avascular retinal areas, hypoplasia of retinal blood vessels, rarefaction of retinal ganglion cells, and ischaemic structural changes of the retina. New vessel formation on the surface of avascular retinal areas was supplied from persistent hyaloid blood vessels. This finding may be of some importance in explaining those cases histologically resembling classical retrolental fibroplasia with no history of prematurity or oxygen treatment. (+info)
Ophthalmological follow up of preterm infants: a population based, prospective study of visual acuity and strabismus.
BACKGROUND/AIMS: Prematurely born infants are known to have an increased rate of ophthalmological morbidity. The aim of the present study was to investigate visual acuity and ocular alignment in a population of preterm infants in a geographical area, in infants with and without retinopathy of prematurity (ROP). METHODS: A prospective population based study of ophthalmological status of preterm infants with a birth weight of 1500 g or less was performed during 3.5 years, with examinations at 6, 18, 30, and 42 months of corrected age. Visual acuity was tested using linear optotypes. Multiple regression analyses were used to analyse independent risk factors for poor vision and strabismus. RESULTS: Poor vision (< 0.3) was detected in 2.5% (6/237) of the children. Of these, only two (0.8%) had a severe visual impairment (< 0.1). Strabismus occurred in 13.5% (31/229). Children with cryotreated ROP and neurological complications ran the highest risk of poor vision and strabismus, according to multiple regression analysis. Among children without a history of ROP or neurological complications, 34% had a visual acuity < 0.7 and 5.9% had strabismus, compared with 61% and 22%, respectively, among the children with ROP or neurological complications. CONCLUSIONS: The overall incidence of subnormal vision and strabismus in children born prematurely was higher than in a full term population of the same age. On the basis of this study, follow up of all preterm infants screened for ROP is recommended and general guidelines are suggested. (+info)