Changes in Course of Retinopathy of Prematurity from 1986 to 2013: Comparison of Three Studies in the United States.

PURPOSE: To compare infant and retinopathy of prematurity (ROP) characteristics from 3 clinical studies conducted over a 27-year period in the United States. DESIGN: Secondary analysis of results of 3 clinical studies. PARTICIPANTS: Infants with birth weight (BW) <1251 g. METHODS: Analysis of data from the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) and Early Treatment for Retinopathy of Prematurity (ETROP) trials and the primary data from the Telemedicine Approaches for the Evaluation of Acute-Phase Retinopathy of Prematurity (e-ROP) study. MAIN OUTCOME MEASURES: Infant characteristics and onset, severity, and time course of ROP. RESULTS: Across the 3 studies, mean (standard deviation) BW and mean gestational age (GA) decreased over time from CRYO-ROP (954 g [185 g], 27.9 weeks [2.2 weeks]) to ETROP (907 g [205 g], 27.4 weeks [2.2 weeks]) to e-ROP (864 g [212 g], 27.0 weeks [2.2 weeks]), with an increase in the percentage of infants enrolled weighing <750 g (15.8% CRYO, 24.9% ETROP, 33.4% e-ROP; P<0.0001). The percentage of infants who developed ROP varied only minimally (65.8% CRYO, 68.0% ETROP, 63.7% e-ROP; P = 0.003). Moderately severe ROP (defined as prethreshold or referral warranted) varied (17.8% CRYO, 12.3% ETROP, 19.4% e-ROP; P<0.0001), whereas the time of onset of any ROP did not vary (34.3 weeks CRYO, 34.1 weeks ETROP, 34.8 weeks e-ROP). CONCLUSIONS: The BW and GA of infants enrolled in ROP studies in the United States have decreased over the past 27 years, whereas ROP prevalence and onset of disease are stable.

Retinopathy of prematurity in infants weighing less than 500 grams at birth enrolled in the early treatment for retinopathy of prematurity study.

PURPOSE: To describe patient characteristics, classification, and onset of prethreshold retinopathy of prematurity (ROP), and ocular findings at 6 months corrected age in infants with birth weights <500 g who were enrolled in the Early Treatment for Retinopathy of Prematurity (ETROP) Study. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Sixty-three infants with birth weights <500 g who developed ROP and were enrolled in the ETROP Study. METHODS: Infants <1251 g at birth were logged at 26 study centers from October 1, 2000, to September 30, 2002, and underwent examinations for ROP. Infants who developed ROP and whose parents/legal guardians consented were enrolled in the ETROP Study. Infants who developed high-risk prethreshold ROP were randomized; 1 eye was treated early with peripheral retinal ablation and the other eye was managed conventionally, or, in asymmetric cases, the high-risk eye was randomized to early peripheral retinal ablation or conventional management. All eyes reaching prethreshold ROP were examined when infants reached 6 months corrected age. MAIN OUTCOME MEASURES: Retinopathy of prematurity incidence, characteristics, and ocular findings among participants. RESULTS: Thirty-four infants reached prethreshold or worse severity in 1 or both eyes. Retinopathy of prematurity was located in zone I in 43.3% of all prethreshold eyes, and plus disease was present in 46.7%. Median postmenstrual age for diagnosis of all prethreshold ROP was 36.1 weeks, but earlier (35.1 weeks) for eyes that developed high-risk prethreshold ROP. In the 27 surviving infants with prethreshold ROP, ophthalmic examination at 6 months corrected age showed a normal posterior pole in 22 (81.5%), a favorable structural outcome with posterior pole abnormalities in 4 (14.8%), and an unfavorable structural outcome (stage 4B) in 1 (3.7%). One infant developed amblyopia, 4 infants developed nystagmus, 4 infants developed strabismus, and 8 infants developed myopia >-5.00 diopters. CONCLUSIONS: This is the first report on characteristics of prethreshold ROP in infants with birth weights <500 g. These infants are at high risk for developing prethreshold ROP, although many initially achieve a favorable structural outcome. They are at risk of developing strabismus, nystagmus, high myopia, and abnormal retinal structure and should therefore receive continued long-term follow-up. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison of strategies for grading retinal images of premature infants for referral warranted retinopathy of prematurity.

PURPOSE: To determine the accuracy of identifying referral-warranted retinopathy of prematurity (RW-ROP, defined as any zone I ROP, stage 3 or worse, or plus disease) from retinal image sets using three grading protocols: a single optic disk-centered image, a set of 3 horizontal images, and a 5-image set. METHODS: In this secondary analysis of images from the e-ROP study, a weighted sample of 250 image sets from 250 infants (125 with RW-ROP and 125 without RW-ROP) was randomly selected. The sensitivities and specificities for detecting RW-ROP and its components from a single disk center image, along with nasal and temporal retinal images, were calculated and compared with the e-ROP grading of RW-ROP of all 5 retinal images (disk center and nasal, temporal, superior, and inferior retinal images). RESULTS: RW-ROP was identified with a sensitivity of 11.2% (95% CI, 6.79%-17.9%) using a single disk center image, with a sensitivity of 70.4% (95% CI, 61.9%-77.9%) using 3 horizontal images, and a statistically higher sensitivity of 82.4% (95% CI, 75.0%-89.0%) using all 5 images (P = 0.002). The specificities were 100%, 86.4%, and 90.4%, respectively. For grading using 3 horizontal images, sensitivity was 14.3% for plus disease, 25% for zone I ROP, and 71.2% for stage 3 or worse compared to 40.8%, 50%, and 79.8% for grading using 5-image sets, respectively. CONCLUSIONS: Both a single, disk-centered, posterior pole image and 3 horizontal images were less effective than a 5-image set in determining the presence of RW-ROP on qualitative grading by trained readers.

Glaucoma in the Early Treatment for Retinopathy of Prematurity (ETROP) study.

PURPOSE: To report the clinical characteristics of infants with severe retinopathy of prematurity (ROP) and glaucoma-based on review of the Early Treatment for Retinopathy of Prematurity (ETROP) study. METHODS: All infants randomized in the ETROP trial were included. Each infant developed high-risk prethreshold ROP in at least one eye. Infants were examined until 6 years postnatal age. The following data were collected: corneal clarity, depth of the anterior chamber, status of the optic nerve and cup/disk ratio, retinal structure, and visual acuity. The diagnosis of glaucoma was based on the investigators best clinical judgment. All infants diagnosed with glaucoma were included in the study. RESULTS: A total of 12 of 718 eyes (1.67%) were diagnosed with glaucoma. Of these, 5 were first reported as having glaucoma at 9 months, 2 at 2 years, 1 each at 3 and 4 years, and 3 at 5 years. The anterior segment was shallow in 7 eyes. Three eyes had normal retinal structure, 1 had macular dragging, and 8 had retinal detachments involving the fovea (stage 4B or worse). At the 6-year follow-up examination only one eye with glaucoma had measurable vision. CONCLUSIONS: Although earlier treatment of significant ROP has resulted in better retinal structure and visual acuity outcomes, nearly 2% of the eyes with high-risk prethreshold ROP developed glaucoma at some point during the first 6 years of life.

Correlation of recognition visual acuity with posterior retinal structure in advanced retinopathy of prematurity.

OBJECTIVE: To compare Early Treatment Diabetic Retinopathy Study visual acuity outcome with retinal structural outcome at the 6-year follow-up examination of infants randomized in the Early Treatment for Retinopathy of Prematurity study. METHODS: We compared the results in 606 eyes of subjects in whom both functional (visual acuity) and retinal structural assessments were obtained at age 6 years. Visual acuity assessments were performed by masked testers,and retinal examinations were performed by certified ophthalmologists. MAIN OUTCOME MEASURES: Visual acuity and retinal structure at age 6 years. RESULTS: Concordant outcomes occurred in 462 eyes(76.2%): 402 eyes had favorable functional and structural outcomes and 60 eyes had unfavorable functional and structural outcomes. Discordant outcomes occurred in 92 eyes (15.2%): 86 eyes had unfavorable functional and favorable structural outcomes and 6 eyes had favorable functional and unfavorable structural outcomes.Of the 86 eyes with unfavorable functional and favorable structural outcomes, 43 had optic atrophy (23 eyes) and/or retinal abnormalities that were less severe than those considered to be unfavorable (32 eyes). In 52 eyes (8.6%), retinal structure could not be assessed or the visual acuity was untestable. CONCLUSION: Posterior pole appearance correlates well with visual acuity in 6-year-old infants with a history of advanced retinopathy of prematurity.

Correlation of recognition visual acuity with posterior retinal structure in advanced retinopathy of prematurity.

OBJECTIVE To compare Early Treatment Diabetic Retinopathy Study visual acuity outcome with retinal structural outcome at the 6-year follow-up examination of infants randomized in the Early Treatment for Retinopathy of Prematurity study. METHODS We compared the results in 606 eyes of subjects in whom both functional (visual acuity) and retinal structural assessments were obtained at age 6 years. Visual acuity assessments were performed by masked testers, and retinal examinations were performed by certified ophthalmologists. MAIN OUTCOME MEASURES Visual acuity and retinal structure at age 6 years. RESULTS Concordant outcomes occurred in 462 eyes (76.2%): 402 eyes had favorable functional and structural outcomes and 60 eyes had unfavorable functional and structural outcomes. Discordant outcomes occurred in 92 eyes (15.2%): 86 eyes had unfavorable functional and favorable structural outcomes and 6 eyes had favorable functional and unfavorable structural outcomes. Of the 86 eyes with unfavorable functional and favorable structural outcomes, 43 had optic atrophy (23 eyes) and/or retinal abnormalities that were less severe than those considered to be unfavorable (32 eyes). In 52 eyes (8.6%), retinal structure could not be assessed or the visual acuity was untestable. CONCLUSION Posterior pole appearance correlates well with visual acuity in 6-year-old infants with a history of advanced retinopathy of prematurity. APPLICATION TO CLINICAL PRACTICE When the retinal structure is normal but visual acuity is poor in infants with a history of severe retinopathy of prematurity, other diagnoses such as optic atrophy and cortical visual impairment could at least partially account for the discrepancy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00027222.

The effect of surgical preparation technique on the bacterial load of surgical needles and suture material used during strabismus surgery.

PURPOSE: To investigate the effectiveness of 3 surgical preparation techniques in decreasing bacterial contamination of needles and suture material during strabismus surgery. METHODS: Consecutive patients requiring 2-muscle strabismus surgery were randomized into 1 of 3 groups. In Group A, patients' periocular skin and bulbar conjunctivae underwent preparation with 5% povidone-iodine; the drape was placed without regard to eyebrows; and an open wire-loop lid speculum was used. Group B patients underwent the same preparation as Group A patients; however, the eyelashes and eyebrows were scrubbed with 5% povidone-iodine on cotton tip applicators, and the drape was placed to exclude the eyebrows from the surgical field. Group C patients underwent the same preparation as Group B patients; however, a bladed lid speculum was used during surgery to exclude some of the eyelashes from the surgical field. After the procedure, all needles and suture materials were sent separately for aerobic culture. The data were analyzed for differences in contamination rates between the groups. RESULTS: Of 77 patients, 24 (31.4%) had either a needle and/or suture contaminant. Groups A, B, and C had mean contamination rates of 29.6%, 34.6%, and 29.2%, respectively. There was no significant statistical variation in contamination among the 3 groups. The most common organism identified was a coagulase-negative staphylococcus strain. CONCLUSIONS: More meticulous sterile preparation of the surgical field did not result in a meaningful reduction in suture or needle contamination rates during strabismus surgery.

Prevalence and course of strabismus through age 6 years in participants of the Early Treatment for Retinopathy of Prematurity randomized trial.

PURPOSE: To present strabismus data for children who participated in the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial. METHODS: The prevalence of strabismus, categorized as present or absent, was tabulated for all children with history of high-risk prethreshold retinopathy of prematurity (ROP) who participated in the ETROP randomized trial and were examined at 9 months to 6 years of age. Relationships among strabismus and demographic measures, eye characteristics, and neurodevelopmental factors were analyzed. RESULTS: Among the 342 children evaluated at 6 years, the prevalence of strabismus was 42.2%. Even with favorable acuity scores in both eyes, the prevalence of strabismus was 25.4%, and with favorable structural outcomes in both eyes the prevalence of strabismus was 34.2%. Of children categorized as visually impaired as the result of either ocular or cerebral causes, 80% were strabismic at the 6-year examination. Of 103 study participants who were strabismic at 9 months, 77 (74.8%) remained so at 6 years. Most strabismus was constant at both the 9-month (62.7%) and the 6-year examination (72.3%). After multiple logistic regression analysis, risk factors for strabismus were abnormal fixation behavior in one or both eyes (P < 0.001), history of amblyopia (P < 0.003), unfavorable structural outcome in one or both eyes (P = 0.025), and history of anisometropia (P = 0.04). Strabismus surgery was performed for 53 children. By 6 years, the cumulative prevalence of strabismus was 59.4%. CONCLUSIONS: Most children with a history of high-risk prethreshold ROP develop strabismus at some time during the first 6 years of life.

Corneal power measurements in fixating versus anesthetized nonfixating children using a handheld keratometer.

PURPOSE: To compare keratometry measurements on a fixating patient with readings from the same nonfixating patient intraoperatively using the Nidek KM-500 handheld keratometer. METHODS: Consecutive patients who were scheduled for strabismus or nasolacrimal surgery between 5 and 11 years of age were included in the study. Handheld keratometry was performed preoperatively on both eyes with the child fixating and intraoperatively with the child anesthetized. Three readings were taken on each eye. The steepest and flattest corneal meridians were recorded. Intraclass correlation coefficients were calculated to assess reliability, and interchangeability was assessed by the use of the Bland-Altman method. RESULTS: Included in the study were 55 eyes of 28 patients. The average fixating keratometry reading was 44.10 +/- 1.45 D for right eyes and 44.12 +/- 1.42 D for left eyes. The average nonfixating keratometry reading was 44.06 +/- 1.62 D for right eyes and 44.02 +/- 1.54 D for left eyes. The intraclass correlation coefficient for the average keratometry obtained fixating versus nonfixating was 0.96 for right eyes and 0.95 for left eyes. The Bland-Altman analysis showed fairly large limits of agreement between readings, but most readings fall within the limits of variability. The mean time to obtain the intraoperative measurements was 4.26 minutes. CONCLUSIONS: In our study the Nidek KM-500 handheld keratometer provided reliable readings when used intraoperatively on anesthetized nonfixating children and required minimal time to perform.

Retinopathy of prematurity outcome in infants with prethreshold retinopathy of prematurity and oxygen saturation >94% in room air: the high oxygen percentage in retinopathy of prematurity study.

OBJECTIVES: To determine the rate of progression from prethreshold to threshold retinopathy of prematurity (ROP) in infants excluded from Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) because their median arterial oxygen saturation by pulse oximetry (SpO2) values were >94% in room air at the time of prethreshold diagnosis and to compare them with infants who were enrolled in STOP-ROP and had median SpO2 < or =94% in room air. METHODS: Fifteen of the 30 centers that participated in STOP-ROP elected to participate in the High Oxygen Percentage in Retinopathy of Prematurity study (HOPE-ROP) from January 1996 to March 1999. Infants were followed prospectively from the time prethreshold ROP was diagnosed until ROP either progressed to threshold in at least 1 study eye (adverse outcome) or resolved (favorable outcome). RESULTS: A total of 136 HOPE-ROP infants were compared with 229 STOP-ROP infants enrolled during the same time period from the same 15 hospitals. HOPE-ROP infants were of greater gestational age at birth (26.2 +/- 1.8 vs 25.2 +/- 1.4 weeks) and greater postmenstrual age at the time of prethreshold ROP diagnosis (36.7 +/- 2.5 vs 35.4 +/- 2.5 weeks). HOPE-ROP infants progressed to threshold ROP 25% of the time compared with 46% of STOP-ROP infants. After gestational age, race, postmenstrual age at prethreshold diagnosis, zone 1 disease, and plus disease at prethreshold diagnosis were controlled for, logistic regression analysis showed that HOPE-ROP infants progressed from prethreshold to threshold ROP less often than STOP-ROP infants (odds ratio: 0.607; 95% confidence interval: 0.359-1.026). CONCLUSIONS: The mechanisms that result in better ROP outcome for HOPE-ROP versus STOP-ROP are not fully understood. It seems that an infant's SpO2 value at the time of prethreshold diagnosis is a prognostic indicator for which infants may progress to severe ROP. When other known prognostic indicators are factored in, the SpO2 is of borderline significance.