Risk Of Retinopathy Of Prematurity Research Articles

Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth.

Insulin-like growth factor I (IGF-I) is necessary for normal development of retinal blood vessels in mice and humans. Because retinopathy of prematurity (ROP) is initiated by abnormal postnatal retinal development, we hypothesized that prolonged low IGF-I in premature infants might be a risk factor for ROP. We conducted a prospective, longitudinal study measuring serum IGF-I concentrations weekly in 84 premature infants from birth (postmenstrual ages: 24-32 weeks) until discharge from the hospital. Infants were evaluated for ROP and other morbidity of prematurity: bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). Low serum IGF-I values correlated with later development of ROP. The mean IGF-I +/- SEM level during postmenstrual ages 30-33 weeks was lowest with severe ROP (25 +/- 2.41 micro g/L), 29 +/- 1.76 micro g/L with moderate ROP, and 33 +/- 1.72 micro g/L with no ROP. The duration of low IGF-I also correlated strongly with the severity of ROP. The interval from birth until serum IGF-I levels reached >33 micro g/L was 23 +/- 2.6 days for no ROP, 44 +/- 4.8 days for moderate ROP, and 52 +/- 7.5 days for severe ROP. Each adjusted stepwise increase of 5 micro g/L in mean IGF-I during postmenstrual ages 30 to 33 weeks decreased the risk of proliferative ROP by 45%. Other complications (NEC, BPD, IVH) were correlated with ROP and with low IGF-I levels. The relative risk for any morbidity (ROP, BPD, IVH, or NEC) was increased 2.2-fold (95% confidence interval: 1.41-3.43) if IGF-I was <or=33 micro g/L at 33 weeks' postmenstrual age. These results indicate that persistent low serum concentrations of IGF-I after premature birth are associated with later development of ROP and other complications of prematurity. IGF-I is at least as strong a determinant of risk for ROP as postmenstrual age at birth and birth weight.

Telemedicine approach to screening for severe retinopathy of prematurity: a pilot study

Purpose To evaluate the use of remote reading of digital retinal photographs in the diagnosis of severe (referral-warranted) retinopathy of prematurity (ROP) during longitudinal screening for ROP. Study design Prospective, longitudinal cohort study. Subjects Forty-four consecutive premature infants at risk for ROP. Methods All infants were examined longitudinally, over a series of examinations, by indirect ophthalmoscopy (gold standard) and digital photography using the RetCam-120 Digital Retinal Camera (Massie Research Laboratories Inc., Dublin, CA) equipped with an ROP lens. Images were stored and read remotely by a masked reader. Referral-warranted ROP was defined as ROP in zone 1, the presence of plus disease or the presence of any stage 3 ROP. We determined whether and when referral-warranted ROP was diagnosed for each eye, of each infant, on each examination, during the course of each of the infant's screening. Results Severe (referral-warranted) ROP was diagnosed in 23 eyes by indirect ophthalmoscopy during their series of examinations. Digital photography had a sensitivity of 100% and a specificity of 96% in detecting referral-warranted ROP. The positive predictive value of digital photography was 92%, and the negative predictive value was 100%. In 87% of eyes, referral-warranted ROP was diagnosed by digital photography before or at the same time as indirect ophthalmoscopy. Conclusions Longitudinal remote reading of digital photographs using the RetCam-120 system has excellent specificity and sensitivity in detecting referral-warranted ROP. This pilot study has shown that remote reading of digital photographs has promise for telemedicine strategies in ROP screening.

Incidence and severity of retinopathy of prematurity in Vietnam, a developing middle-income country.

Although retinopathy of prematurity (ROP) is a leading cause of childhood blindness, its impact in lower income countries is not well documented. The World Health Organization has proclaimed that infants at risk for ROP should have screening eye examinations and access to treatment. A prospective study was conducted from January 1 through December 31, 2001, at Tu Du Hospital in Ho Chi Minh City for premature infants who weighed 1,500 g or less at birth or were 33 gestational weeks or younger. Serial examinations were used to classify ROP, and treatment outcomes were noted. Two hundred twenty-five consecutive infants were included in the data analysis. Birth weights ranged from 900 to 2,000 g (mean, 1,512 g). Gestational ages ranged from 26 to 36 weeks (mean, 31 weeks). ROP was present in 103 (45.8%) of the 225 infants. In infants who weighed 1,250 g or less at birth, the ROP rate was 81.2% (26 of 32 infants). Threshold ROP was present in 9.3% of the 225 infants but in 25% of the 32 infants. Twenty-four eyes received treatment, whereas 16 lacked the family resources. Of the 24 treated eyes, 18 (75%) had a favorable outcome. Of the 16 untreated eyes, only 3 had a favorable outcome. ROP incidence is high in Vietnam, similar to that in the United States. However, larger, older infants are at risk in Vietnam and the rate of severe ROP seems to be higher. This necessitates an ROP screening paradigm different from that currently used in the United States.

Does elevated peak bilirubin protect from retinopathy of prematurity in very low birthweight infants.

Bilirubin is a potent in vitro antioxidant. Despite repeated study, its in vivo significance has yet to be defined. Bilirubin is universally elevated in very low birthweight (VLBW) infants. Retinopathy of prematurity (ROP) is a disease thought to be associated with exposure to oxygen free radicals in VLBW infants. The objective of this study was to determine whether there was an association between peak bilirubin levels and ROP. The risk for ROP, stages III and IV was measured as a function of increasing peak bilirubin levels in VLBW infants admitted to the neonatal ICU. A similar analysis was performed on a subgroup of VLBW infants with prolonged (> or =28 days) oxygen requirement. The relation between peak bilirubin level and the duration of oxygen requirement was tested by logistic regression analysis. All analyses were conducted after controlling for birthweight and presence of intraventricular hemorrhage (IVH). There was an increased risk for ROP, stages III and IV (OR 1.187; 95% CI 1.013 to 1.390; p=0.034) with elevated peak serum bilirubin levels in the entire population. Duration of oxygen requirement was not related to peak bilirubin (p>0.1). In the subgroup of infants with prolonged oxygen requirement (> or =28 days), there was no association between peak serum bilirubin levels and ROP III and IV (p>0.1); however, there was an association with further increased duration of oxygen requirement (p=0.034). Elevated peak bilirubin does not protect from and may be a risk for ROP in VLBW infants.

Hyperglycemia and retinopathy of prematurity in very low birth weight infants.

Retinopathy of prematurity (ROP) remains a leading cause of morbidity in the very low-birth-weight (VLBW) infant. This study investigates a possible association between serum/blood glucose and the development of ROP. A retrospective case-control study of all infants born between 1992 and 1997 at the Johns Hopkins Hospital with birth weights less than 1000 g who developed Stage 3 or 4 ROP was conducted. Controls either had Stage 1 ROP or no eye disease and were matched 2:1 with ROP patients for gestational age, birth weight and year of birth. Odds ratios (ORs) of ROP were calculated for multiple exposures over the first month after birth, including oxygen concentration (FiO(2)), blood glucose levels, vitamin E, mean airway pressure and mean blood pressure. In a simple logistic regression analysis, we found an increased ROP risk for: (1) each 10 mg/dl increase of mean glucose (OR 1.96; 95% CI 1.13 to 3.42), (2) each 1% increase of mean FiO(2) (OR 1.06; 95% CI 1.004 to 1.13), (3) history of dopamine infusion (OR 5.4; 95% CI 1.16 to 25.2) and (4) intraventricular hemorrhage Grade 3 or 4 (OR 7.3; 95% CI 1.53 to 34.7). Using a multiple regression model, we found an increased ROP risk for each 10 mg/dl increase of mean glucose (OR 2.7; 95% CI 1.003 to 7.27). Each IU/kg/day of vitamin E supplementation reduced ROP risk (OR 0.37; 95% CI 0.16-0.86). In this study, we could demonstrate that glucose levels in the first month of life are associated with the development of ROP. Further studies have to determine if this association is causal or if hyperglycemia is just an expression of severity of illness.

A proposal of screening guideline for retinopathy of prematurity in Taiwan.

Retinopathy of prematurity (ROP) is one of the most important morbidity in premature infants. The latest American Academy of Pediatrics (AAP) screening guidelines for ROP are mandatory for infants with birth weights < or = 1500 g or gestational ages (GA) < or = 28 weeks. To determine the appropriate upper limits for ROP screening in Taiwan in terms of birth weight and gestational age, we performed a retrospective review of all 617 infants who were born at the National Taiwan University Hospital from January 1, 1994 to December 31, 1999, and survived beyond 28 days of life and received eye-ground evaluation under our current ROP screening guidelines. From the start of our study, the criteria for screening was birth weight <2000 g or gestational age < 35 weeks. The maximal stage of retinopathy observed was recorded. We found no ROP greater than stage I in infants with birth weights > 1500g and GA > 31 weeks. In comparing with our current guidelines, lowering the screening criteria to birth weight < or = 1500g or gestational age < or = 31 weeks reduced the number of infants requiring screening by 37.2%, while no case of ROP greater than stage 1 was missed. However, five cases of stage 2 ROP would have been missed in our study if the gestational age cut-off was < or = 28 weeks as recommended by AAP. Therefore, we recommend that in the tertiary nursery in Taiwan, the gestational age < or = 31 weeks or birth body weight < or = 1500 g should be screened for ROP regardless of clinical condition. The screening for larger infants with high risk of ROP requires further discretion of the attending physicians.

Retinopathy of prematurity: are we screening too many babies?

With advancement in neonatal care units, early detection of retinopathy of prematurity (ROP) in premature and very-low-birth-weight infants is important. Numerous studies have reported an increased risk of ROP in prematurely born infants, but only few have been long-term and strictly population-based. The aim of the present study was to find out whether birthweight <1251 grams and gestational age <30 weeks could provide a safe and efficient means of detecting treatable ROP. We have retrospectively tried to ascertain the incidence and associated risk factors that may contribute to the management of babies with ROP. Infants either with a birth weight below 1500 g or a gestational age of less than 32 weeks were screened for ROP during an 8-year period by a single examiner. Results An incidence of 64/205 (31.2%) ROP was noted. The mean age at detection was 5.5 +/- 2 weeks of life. The maximum stage reached was stage 1 in 27 (13.2%), stage 2 in 24 (11.7%) and stage 3 in 10 (4.8%) babies. Threshold ROP was present in three (1.5%) babies. Significantly fewer (150/205 = 73%) babies would have been examined had a birth weight of <1251 grams and a gestational age <30 weeks been applied. there were five (8%) babies with birth weight >1250 grams and eight (12%) babies with gestational age >30 weeks amongst babies with ROP but all were stage 1 or stage 2. All the stage 3 ROP and the threshold ROP cases were babies with birth weight <1000 grams and gestational age below 28 weeks. Ophthalmic examination may be safely and efficiently concentrated in babies with birth weight <1251 grams and gestational age below 30 weeks. Birth weight (P < 0.005) and gestational age (P < 0.01) were the only significant risk factors. During this 8-year period there was no significant decrease in the number of babies screened for ROP and the overall incidence of all stages of the disease has remained constant. In the present series a lower incidence of severe ROP was noted compared to most previous studies. Our experience from this study suggests the need for further refinement of screening guidelines in order to focus screening on the vision-threatening stages of ROP.

Changing profile of retinopathy of prematurity.

The aim of this study was to determine the evolving trends of retinopathy of prematurity (ROP) at a tertiary neonatal intensive care unit. In an ongoing screening programme for ROP, we estimated the incidence of ROP among at-risk neonates in a tertiary care unit. We compared our data over the last 12 months (1999-2000; period II) to the previously published data (1993-94; period I) to study changes in the spectrum of the disease. The overall incidence of ROP in period II was not significantly different from the incidence in period I (32 vs. 20 per cent, p > 0.05). However, a decreasing trend in the proportion of severe ROP (stage III) from 46 to 21 per cent in the later period was noted. The need for cryotherapy also dropped significantly compared with the earlier period (8 vs. 46 per cent respectively, p < 0.05). On multivariate analysis, apnea (p < 0.001; RR = 12.5; 95 per cent CI, 3.03-50.9; clinical sepsis (p < 0.001; RR = 5.7; 95 per cent CI, 1.6-20.7); and male sex (p < 0.001; RR = 6.3; 95 per cent CI 1.6-25.5) emerged as significant risk factors. Although the incidence of ROP is static, the more severe form of the disease (stage III) is showing a decline. Our data suggests that efficient management of apnea and sepsis may be crucial in further minimizing the risk of ROP.

Duration of acidosis and recovery determine preretinal neovascularization in the rat model of acidosis-induced retinopathy

Purpose. Systemic acidosis is a risk factor for retinopathy of prematurity (ROP). The present study tested the hypotheses that: a) a short period of acidosis is sufficient to produce neovascularization and b) recovery from acidosis is not needed for the development of preretinal neovascularization. Methods. Newborn Sprague-Dawley rats raised in 38 litters of 25 were randomly assigned within litters to 1, 3, or 6 days of acidosis, induced by twice daily gavage with NH 4 Cl (10mM/kg) beginning on the second day of life. Recovery time ranged from 0 to 15 days. All animals were raised in room air. Animals were sacrificed and retinal vasculature was assessed for preretinal neovascularization and retinal vascular areas. Results. Neovascularization occurred in up to 34% of rats exposed to 1 day of acidosis, 38% of rats exposed to 3 days of acidosis, and 55% of rats exposed to 6 days of acidosis. The incidence of neovascularization was maximal after 2 to 5 days of recovery regardless of the duration of NH 4 Cl exposure. However, recovery was not a requirement for the development of neovascularization. Conclusions. Periods of systemic acidosis as brief as 24 hours are associated with preretinal neovascularization in our newborn rat model of ROP using expanded litters. Systemic acidosis may damage the developing retinal vasculature and induce neovascularization, even without a period of recovery. A brief episode of systemic acidosis may be a risk factor for ROP in human neonates. Further attention should be directed to systemic acid-base balance in infants at risk for ROP.

Association of candidemia and retinopathy of prematurity in very low birthweight infants

Objective To determine if the presence of candidemia in infants is associated with an increased incidence of threshold retinopathy of prematurity (ROP). Design Retrospective, case-controlled study. Participants and controls Forty-six infants admitted to the Texas Children’s Hospital Neonatal Intensive Care Unit between 1989 and 1999 with a birth weight 1500 g or less, estimated gestational age (EGA) 28 weeks or less, and in whom candidemia developed were matched to a control group of 46 infants based on corresponding birth weight, EGA, and year of birth. Methods Records of each infant were reviewed to determine the presence and severity of ROP. Main outcome measures Development of threshold ROP, including retinal detachment. Results Forty-three infants (93.5%) with candidemia and 39 (84.8%) without candidemia had ROP. Twenty-four infants (52.2%) with candidemia reached threshold and required surgical intervention, compared with 11 infants (23.9%) without candidemia (adjusted odds ratio [OR], 7.4; 95% confidence interval [CI], 1.7–32.1; P = 0.008). Retinal detachment developed in 10 of 24 candidemic infants (41.7%) who reached threshold ROP, compared with 2 of 11 infants (18.2%) without candidemia (OR, 4.4; 95% CI, 0.73–26.9; P = 0.1). Conclusions Candidemia is associated with increased risk of threshold ROP. Infants with Candida sepsis should be monitored closely for the development of ROP and progression after treatment.

Retinopathy of Prematurity: Practical Clinical Approach

After completing this article, readers should be able to: 1. Describe the forms that should be used to record all retinopathy of prematurity (ROP) screening examinations. 2. Characterize the roles of ophthalmologists and neonatologists in developing local screening policies. 3. Delineate which preterm infants require screening for ROP and when the first screening examination should occur. 4. Describe the procedure for laser therapy to treat ROP and postsurgical follow-up. The neonatologist and neonatal intensive care unit (NICU) staff have a serious responsibility to minimize vision loss from retinopathy of prematurity (ROP). It requires a team effort throughout the hospitalization to reduce the incidence and severity of ROP and particularly conscientious tracking of patients during the phase of active disease to detect and treat the few cases that become severe enough to threaten retinal detachment. It is particularly frustrating in this most visual of diseases that the pathology occurs inside the eye where the threat is not visible and at the particular time when the infants are recovering from so many other insults and are nearly ready for home! Among infants of similar gestations, those who have the more unstable hospital course have the higher risk of serious ROP. It is important to remember that interventions that prolong pregnancy and reduce intraventricular hemorrhage, pneumothorax, serious sepsis, and chronic lung disease all reduce the risk of vision-threatening ROP. To date it is impossible to prevent all morbidities, but each year brings increased knowledge about how to reduce their incidence and hopefully the incidence of severe ROP. An effective ROP screening program requires the cooperative efforts of the neonatal team, screening ophthalmologists, and discharge coordinators. Unlike many screening programs in which the “screening test” is inexpensive, the time and effort of ophthalmologists is considerable in this program, and rarely are their consulting fees paid. Participating in ROP …

Association of postnatal dexamethasone use and fungal sepsis in the development of severe retinopathy of prematurity and progression to laser therapy in extremely low-birth-weight infants.

The objective of this study was to evaluate the role of postnatal dexamethasone use and fungal sepsis in the development of severe retinopathy and progression to laser therapy. Postnatal steroids have been frequently used in the management of infants with chronic lung disease, airway edema, and hypotension, but their use is not free from adverse effects. Postnatal dexamethasone use has been associated with increased risk for the development of fungal sepsis, but the influence of glucocorticoid therapy on retinopathy of prematurity (ROP) is controversial. Candida sepsis has been shown to be associated with severe ROP and the need for laser therapy in some studies but not in others. Medical records of all <1000 g birth weight infants (n=158) admitted to Louisiana State University Health Sciences Center between July 1, 1996 and June 30, 1999 were reviewed. After exclusion of those infants who either died (n=25) or transferred (n=3) before eye examination, demographic and clinical data of 130 infants were analyzed by chi-squared analysis, Mann-Whitney U test, t-test, analysis of variance, and logistic regression. All data are mean+/-SD. Gestational age was 26.4+/-1.7 weeks; birth weight was 797+/-130 g. Twenty-six infants were Caucasian, the rest African-American. Seventy-five (58%) received antenatal steroids. Eighty-eight (68%) of the infants received postnatal steroids. All infants were exclusively fed premature infant formulae. Sepsis developed in 44 (34%) infants and fungal sepsis in 14 (11%). Incidence of ROP was 77% (100/130), severe ROP (stage > or =3) 52% (68). Severe ROP was more frequent in Caucasian infants (p=0.005) and in infants who received postnatal dexamethasone (p< or =0.0001). The development of threshold ROP (zone 1 or 2 with stage 3+, five contiguous or eight total clock hours of the retina) and requirement for laser therapy were higher in Caucasians (p=0.0002) and in infants with fungal sepsis (p=0.001). Antenatal steroids had no effect on the severity of ROP or the need for laser treatment. Postnatal dexamethasone use was significantly associated with fungal sepsis 13/14 (93%). After controlling for gestational age, race, days on supplemental oxygen, and fungal sepsis, cumulative postnatal dexamethasone use was independently associated with severe ROP [OR 1.2 (1.04-1.33)], and fungal sepsis [OR 8.2 (2.0-33.0)] was independently associated with the need for laser therapy. Postnatal steroid use is an independent risk factor for development of severe ROP. The risk of threshold ROP requiring laser treatment was higher in infants who developed fungal sepsis.

Discussion

The risk management program for retinopathy of prematurity (ROP) outcome (RM-ROP) is a useful multiple logistic risk model available to clinicians to assist in defining the risk of threshold ROP developing in an eye at three different points in time: at the first eye examination, at the onset of any ROP, and at the time when prethreshold disease is documented.1 The second portion of the program, designed to give the risk of an unfavorable outcome when threshold is reached, depending on treatment or no treatment, was not used by Dr. Onofrey and colleagues, because all patients who had threshold disease develop were treated. This statistical model was derived from the examinations of 4099 premature infants in the CRYO-ROP study. Dr. Onofrey and colleagues used this model in studying the risk for 292 infants of similar birth weight at their institution. They confirmed the importance of certain risk factors for development of threshold ROP included in the RM-ROP models: lower birth weight, younger gestational age, vessels ending in zone 1 at the first examination, and plus disease being present at the first examination showing prethreshold ROP. Although race and multiplicity of birth were not significant factors for threshold disease developing in their group of patients, data from the much larger group of patients in the CRYO-ROP study showed an increased risk for threshold ROP developing for white race and multiple births.2,3

Compliance with outpatient follow-up recommendations for infants at risk for retinopathy of prematurity

Objectives: We undertook this study to determine how frequently at-risk infants were scheduled for and brought to follow-up appointments for retinopathy of prematurity (ROP) examination after hospital discharge and to identify barriers to follow-up. Methods: The records of 126 infants with or at risk for ROP at the time of hospital discharge were retrospectively reviewed. Data recorded included the presence or absence of a timely outpatient follow-up appointment, the identity of the person who scheduled the appointment (hospital staff or parents), attendance rate for appointments made, race or ethnicity, and insurance status. Results: Sixty-two of 126 (49%) infants were scheduled for a timely outpatient examination. Sixty-four of 126 (51%) required telephone contact from our office to be scheduled for an appointment. Eight of 21 (38%) African American infants had an appointment scheduled without additional intervention by our office personnel, and 6 of 21 (29%) were brought to an appointment in a timely manner. Twenty-two of 33 (68%) white infants had an appointment scheduled without additional intervention by our office personnel, and 20 of 33 (61%) were brought to an appointment in a timely manner. African American patients were less likely than white patients to be brought to a follow-up appointment (P = .022). Eleven of 15 (73%) patients, whose appointments were scheduled by hospital personnel before discharge, were brought to their follow-up appointment, compared with 39 of 105 (37%) patients, whose parents were requested to schedule their own appointment (P = .008). Conclusion: Almost 50% of infants with or at risk for ROP were not scheduled for a timely outpatient follow-up appointment, putting these neonates at risk for ROP-related blindness. Patients whose appointments were scheduled by hospital personnel before discharge were more likely to be brought to a follow-up examination. Extensive utilization of office support staff was required to ascertain the status of infants who did not have appointments scheduled or who were not brought to follow-up appointments. (J AAPOS 2000;4:282-6)

Commentary on guidelines for screening for retinopathy of prematurity

I n the early 1990s one of us (W.H.) recommended to the Canadian Association of Pediatric Ophthalmologists (CAPO) that standards should be established for screening for retinopathy of prematurity (ROP) in premature infants in Canadian nurseries. From 1994 to 2000 a CAPO ad hoc committee met on numerous occasions and produced several drafts, leading to the guidelines in the preceding document. The guidelines have been approved by CAPO, the Canadian Ophthalmological Society, and the Fetus and Newborn Committee of the Canadian Paediatric Society. Screening programs should target infants at risk for severe ROP. There is no consensus regarding the minimum gestational age and birth weight of premature infants to be screened. 1 There are only a few evidencebased studies that have provided supportive data for the guidelines. The infants believed to be at highest risk for significant ROP are those born at 30 weeks' gestation or less, and those with a birth weight of 1500 g or less.2-4 Ordinarily, ROP does not appear until 4 to 6 weeks after birth, and severe ROP that would require treatment does not usually manifest before 6 weeks. However, earlier reports describe Rush disease, included as zone I plus disease in the international classification of ROP,5 occurring as early as 3 weeks but not reaching a severity requiring treatment until 6 weeks or later. 6-S This more severe variant of ROP is less amenable to treatment unless treated early. The consensus was to recommend that screening begin 4 to 6 weeks after birth. The fundamental objective of screening is to identify eyes with progressive severe stage 3 ROP that is likely to compromise vision and the eye if left untreated. Although it is not clearly defined, there is a

Threshold retinopathy of prematurity in neonates less than 25 weeks' estimated gestational age

Introduction: The survival rate of extremely premature infants has increased. No recent study has investigated the characteristics of retinopathy of prematurity (ROP) or the incidence of threshold ROP in the most severely premature infants. We undertook this study to determine the risk of developing ROP and threshold ROP in the growing sub-population of infants <25 weeks' estimated gestational age (EGA). Methods: A retrospective review of infants born before the 25th week of gestation between the years 1994 and 1997 was performed. Of 49 infants examined (97 eyes), 42 were born in the 24th week of gestation and 7 were born in the 23rd week. Mean follow-up was 6.3 months (range, 2.5–37 months). Ophthalmology screening examinations were initiated at 5 weeks of age and continued until the infants were no longer at risk for serious ROP. Results: ROP developed in all (97) eyes. Thirty-nine of 97 (40%) eyes in 20 of 49 (41%) infants developed threshold ROP, diagnosed at a mean post-conceptional age of 34 weeks. Thirteen (13%) eyes of 7 (14%) patients developed prethreshold disease and regressed without treatment. Conclusion: There is an increased incidence of threshold disease in infants ≤25 weeks' EGA compared with children of greater EGA. Threshold disease may occur at an earlier post-conceptional age in this subgroup of neonates. (J AAPOS 2000;4:183–5)

New developments in neonatology: less severe retinopathy of prematurity?

To determine the effects of surfactant replacement therapy (SRT), high-frequency oscillatory ventilation (HFOV), and general improvements in quality of care on the incidence of severe retinopathy of prematurity (ROP). Retrospective comparison of the incidence and severity of ROP in two groups of preterm infants admitted to our neonatal intensive care unit (NICU) in two consecutive 5-year periods (1986-1995) and screened for ROP. During the second study period, natural surfactant was introduced in the treatment of respiratory distress syndrome (RDS) and HFOV was used for treatment of respiratory insufficiency of any origin. The effects of these developments and general improvements on the incidence of severe ROP were analyzed with stepwise logistic regression. The overall incidence of ROP from 1986-1990 was not significantly different from the incidence of ROP from 1991-1995. The incidence of severe ROP (ROP stage 3 or greater) was significantly lower in the second period (15.7% versus 6.4%, P=.015). For infants <1000 g, the incidence of overall ROP was increased significantly during the second study period (47.6% versus 60.1 %, P=.045), although the incidence of severe ROP remained unchanged. Only SRT was associated with a decreased risk for severe ROP; HFOV and general improvements in quality of care had no influence on the outcome. In patients with RDS, the incidence of severe ROP decreased significantly during the second period. Of the recent new developments in neonatology, only SRT was associated with a decreased risk for severe ROP.

In vitro fertilisation and stage 3 retinopathy of prematurity.

To re-examine the risk of children born by assisted conception developing stage 3 retinopathy of prematurity (ROP) and to define whether the risk of ROP varies with the method of assisted conception. This was a retrospective study carried out between December 1995 and December 1998 of infants in a single neonatal unit serving the Brent and Harrow area of North West Thames requiring screening and treatment of ROP. The infants screened were identified from the ROP screening database. Those conceived by in vitro fertilisation (IVF) and other forms of assisted conception were identified by reviewing the neonatal notes and the maternal obstetric records. Birth weight, gestational age and the type of assisted conception were recorded. The presence or absence of any stage of ROP, its location and severity and the cases requiring treatment were recorded. One hundred and seventy-nine infants fulfilled the screening criteria during this period. Acute ROP was detected in 32.4% (58 infants) and stage 3 ROP developed in 15.6% (28 infants). Twenty-one infants (11.7%) were born after assisted conception, with 12 (6.7%) being conceived by IVF. The others were conceived on clomiphene (8) or after intrauterine insemination (1). Assisted conception accounted for 21.4% of all those reaching stage 3 disease and 28.6% of those infants requiring treatment. Of the 12 infants conceived by IVF, 41.6% (5 infants) developed acute ROP which progressed to threshold ROP in all infants (100%). Of the assisted conception babies requiring treatment for ROP, 83.3% were conceived by IVF. The other child had been conceived on clomiphene. The gestational age and birth weight of the IVF infants reaching stage 3 ROP were 26.6 +/- 0.89 weeks and 937 +/- 170.2 g. The gestational age and birth weight in the rest of the infants reaching stage 3 ROP were lower than in those conceived by assisted conception (25.739 +/- 1.13 weeks and 735.29 +/- 117.70 g); however, this did not approach statistical significance (p = 0.35 and p = 0.13, respectively). In this study 11.7% of the group requiring screening were conceived by assisted conception. Of all babies requiring treatment for ROP, 28.6% were born after assisted conception. Of the assisted conception group, 83.3% were conceived by IVF. Assisted conception using IVF rather than other techniques appears to be the major risk factor for the development of threshold ROP. We would advise increased vigilance when screening babies conceived by the IVF methods of assisted conception.

Non-ophthalmologist screening for retinopathy of prematurity

AIMTo determine if a non-ophthalmologist can accurately screen for retinopathy of prematurity (ROP) by evaluating the posterior pole blood vessels of the retina. ROP is a common ocular disorder of...

Missense Mutations in Norrie Disease Gene Are Not Associated with Advanced Stages of Retinopathy of Prematurity in Kuwaiti Arabs

Retinopathy of prematurity (ROP) is a disease characterized by retinal neovascularization, possibly leading to retinal detachment and finally blindness. In a proportion of ROP cases, the disease progresses to advanced stages despite rigorous intervention. Missense mutations of the Norrie disease (ND) gene have been associated with progression of the disease in ROP cases from the USA. We have investigated the presence of ND gene mutations in 102 premature newborns of Kuwaiti Arab origin to replicate this finding in a different population/racial group. 56 (55%) of these newborns had normal eyes and served as controls. In 35 (34%) cases, the ROP regressed spontaneously during stage 1–3. In 11 (11%) cases, ROP progressed to advanced stages. A PCR-RFLP method was used to detect the mutations in exon 3 of the ND gene and confirmed the DNA sequence by direct sequencing of the PCR product. The [R121W] mutation of the ND gene was not detected in the premature newborns screened from our Kuwaiti population/group. For the second mutation [L108P], a genotype (PP) was present in 98% of the premature newborns screened and only in 1 of 56 normal infants was the (LL) genotype detected. Our population is genetically homogenous in that genotype (PP) was detected at codon 108 in almost all controls and ROP cases. We did not find an association between the presence or absence of missense mutations of the ND gene and the risk of severe ROP.