Incidence and Early Course of Retinopathy of Prematurity.

In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (ROP), 4099 infants weighing less than 1251 g at birth underwent sequential ophthalmic examinations, beginning at age 4 to 6 weeks, to monitor the incidence and course of ROP. Overall, 65.8% of the infants developed ROP to some degree; 81.6% for infants of less than 1000 g birth weight. As expected, ROP incidence and severity were higher in lower birth weight and gestational age categories. Black infants appeared less susceptible to ROP, of all severity categories, than nonblack infants. The timing of retinal vascular events correlated more closely with postconceptional age than with postnatal age, implicating the level of maturity more than postnatal environmental influences in governing the timing of these vascular events. These results include the current incidence of various severity stages of ROP found in the United States and provide new. insight into the development of ROP.

Atomistic formulas for local properties in systems with many-body interactions.

Atomistic formulas are derived for the local densities and fluxes used in the continuum description of energy and momentum transport. Two general methods for the distribution of potential energy among a system's constituent particles are presented and analyzed. The resulting formulas for the heat flux and stress tensor and the equations for energy and momentum transport are exact consequences of the definitions of the densities and the equations of classical mechanics. The formulas and equations obtained are valid for systems with very general types of many-body interactions.

A hybrid method in combining treatment effects from matched and unmatched studies.

The most common data structures in the biomedical studies have been matched or unmatched designs. Data structures resulting from a hybrid of the two may create challenges for statistical inferences. The question may arise whether to use parametric or nonparametric methods on the hybrid data structure. The Early Treatment for Retinopathy of Prematurity study was a multicenter clinical trial sponsored by the National Eye Institute. The design produced data requiring a statistical method of a hybrid nature. An infant in this multicenter randomized clinical trial had high-risk prethreshold retinopathy of prematurity that was eligible for treatment in one or both eyes at entry into the trial. During follow-up, recognition visual acuity was accessed for both eyes. Data from both eyes (matched) and from only one eye (unmatched) were eligible to be used in the trial. The new hybrid nonparametric method is a meta-analysis based on combining the Hodges-Lehmann estimates of treatment effects from the Wilcoxon signed rank and rank sum tests. To compare the new method, we used the classic meta-analysis with the t-test method to combine estimates of treatment effects from the paired and two sample t-tests. We used simulations to calculate the empirical size and power of the test statistics, as well as the bias, mean square and confidence interval width of the corresponding estimators. The proposed method provides an effective tool to evaluate data from clinical trials and similar comparative studies.

Progression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity study: findings at 4 to 6 years of age.

PURPOSE: To report the prevalence of myopia and high myopia in children <6 years of age born preterm with birth weights <1251 g who developed high-risk prethreshold retinopathy of prematurity and who participated in the Early Treatment for Retinopathy of Prematurity trial. METHODS: Surviving children from the cohort of 401 participants who had developed high-risk prethreshold ROP in one or both eyes underwent cycloplegic retinoscopy at 6 and 9 months corrected age and yearly between 2 and 6 years postnatal age. Eyes were randomized to receive treatment at high-risk prethreshold ROP or conventional management with treatment only if threshold ROP developed. Myopia (spherical equivalent ≥0.25 D) or high myopia (≥5.00 D) in eyes at 4-, 5-, and 6-year examinations was reported. RESULTS: At ages 4, 5, and 6 years, there was no difference in the percentage of eyes with myopia (range, 64.8%-69.9%) and eyes with high myopia (range, 35.3%-39.4%) between earlier treated and conventionally managed eyes. CONCLUSIONS: Approximately two-thirds of eyes with high-risk prethreshold ROP during the neonatal period are likely to be myopic into the preschool and early school years. In addition, the increase in the proportion of eyes with high myopia that had been observed in both earlier-treated and conventionally managed eyes between ages 6 months and 3 years does not continue between ages 3 and 6 years.

Incidence of cataract development by 6 months' corrected age in the Early Treatment for Retinopathy of Prematurity study.

PURPOSE: To report the incidence of cataract development by 6 months' corrected age in preterm children who participated in the Early Treatment for Retinopathy of Prematurity study. METHODS: Infants who developed prethreshold retinopathy of prematurity (ROP) in one or both eyes and were determined by the RM-ROP2 model to have a high risk of poor structural outcome without treatment were randomized to receive early treatment (ET), defined as laser photocoagulation at high-risk prethreshold ROP, or to be conventionally managed (CM), receiving treatment only if threshold ROP developed. Data on eyes developing a cataract by 6 months' corrected age were analyzed. RESULTS: Of 401 randomized infants, 366 survived patients were followed, and 8 eyes of 7 patients (1.9%) developed cataracts by 6 months' corrected age. Among these patients, mean birth weight was 754 g, and mean gestational age was 25.7 weeks. Mean gestational age at treatment was 36.3 weeks for ET patients and 39.5 weeks for CM patients. Three ET eyes and 5 CM eyes developed a cataract. Of the CM eyes, 3 with and 2 without laser treatment developed a cataract. All 6 treated eyes had plus disease when treated. Three eyes had ROP in zone 1, whereas the other 3 had ROP in zone 2. All eyes were treated using a diode laser. CONCLUSIONS: By 6 months' corrected age, a small number of both ET and CM eyes developed cataracts following diode laser treatment for retinopathy of prematurity. Absence of obvious intraoperative complications does not preclude subsequent cataract development, which can occur without laser treatment.

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.

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. 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.

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.

Astigmatism progression in the early treatment for retinopathy of prematurity study to 6 years of age.

PURPOSE: To examine the prevalence of astigmatism (≥ 1.00 diopter [D]) and high astigmatism (≥ 2.00 D) from 6 months after term due date to 6 years of age in preterm children with birth weight of less than 1251 g in whom high-risk prethreshold retinopathy of prematurity (ROP) developed and who participated in the Early Treatment for ROP study. DESIGN: Observational cohort study. PARTICIPANTS: Four hundred one infants in whom high-risk prethreshold ROP developed in 1 or both eyes and were randomized to early treatment (ET) versus conventional management (CM). Refractive error was measured by cycloplegic retinoscopy. Eyes were excluded if they underwent additional retinal, glaucoma, or cataract surgery. INTERVENTION: Eyes were randomized to receive laser photocoagulation at high-risk prethreshold ROP or to receive treatment only if threshold ROP developed. MAIN OUTCOME MEASURES: Astigmatism and high astigmatism at each study visit. RESULTS: For both ET and CM eyes, there was a consistent increase in prevalence of astigmatism over time, increasing from 42% at 4 years to 52% by 6 years for the group of ET eyes and from 47% to 54%, respectively, in the CM eyes. There was no statistically significant difference between the slopes (rate of change per month) of the ET and CM eyes for both astigmatism and high astigmatism (P = 0.75). CONCLUSIONS: By 6 years of age, astigmatism of 1.00 D or more developed in more than 50% of eyes with high-risk prethreshold ROP, and nearly 25% of such eyes had high astigmatism (≥ 2.00 D). Presence of astigmatism was not influenced by timing of treatment, zone of acute-phase ROP, or presence of plus disease. However, there was a trend toward higher prevalence of astigmatism and high astigmatism in eyes with ROP residua. Most astigmatism was with-the-rule (75°-105°). More eyes with type 2 than type 1 ROP had astigmatism by 6 years. These findings reinforce the need for follow-up eye examinations through early grade school years in infants with high-risk prethreshold ROP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Grating visual acuity results in the early treatment for retinopathy of prematurity study.

OBJECTIVE: To compare grating (resolution) visual acuity at 6 years of age in eyes that received early treatment (ET) for high-risk prethreshold retinopathy of prematurity (ROP) with that in eyes that underwent conventional management (CM). METHODS: In a randomized clinical trial, infants with bilateral, high-risk prethreshold ROP (n = 317) had one eye undergo ET and the other eye undergo CM, with treatment only if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to ET or CM. MAIN OUTCOME MEASURE: Grating visual acuity measured at 6 years of age by masked testers using Teller acuity cards. RESULTS: Monocular grating acuity results were obtained from 317 of 370 surviving children (85.6%). Analysis of grating acuity results for all study participants with high-risk prethreshold ROP showed no statistically significant overall benefit of ET (18.1% vs 22.8% unfavorable outcomes; P = .08). When the 6-year grating acuity results were analyzed according to a clinical algorithm (high-risk types 1 and 2 prethreshold ROP), a benefit was seen in type 1 eyes (16.4% vs 25.2%; P = .004) undergoing ET, but not in type 2 eyes (21.3% vs 15.9%; P = .29). CONCLUSION: Early treatment of eyes with type 1 ROP improves grating acuity outcomes, but ET for eyes with type 2 ROP does not. APPLICATION TO CLINICAL MEDICINE: Type 1 eyes should be treated early; however, based on acuity results at 6 years of age, type 2 eyes should be cautiously monitored for progression to type 1 ROP. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Visual field extent at 6 years of age in children who had high-risk prethreshold retinopathy of prematurity.

OBJECTIVE: To compare monocular visual field extent at 6 years of age in eyes with high-risk prethreshold retinopathy of prematurity (ROP) randomized to early treatment (ET) with eyes that underwent conventional management (CM) and were treated at threshold or regressed without treatment. METHODS: Subjects were 370 surviving study participants who developed high-risk prethreshold ROP and were enrolled in the Early Treatment for Retinopathy of Prematurity Study between October 1, 2000, and September 30, 2002. When the participants were 6 years of age, vision testers unaware of ROP status used white-sphere kinetic perimetry to measure visual field extent along the superotemporal, inferotemporal, inferonasal, and superonasal meridians. RESULTS: The extent of the visual field was 0.1° to 3.7° larger in ET eyes when blind eyes were assigned a score of 0°. When data were examined from eyes of participants with 1 sighted ET eye and 1 sighted CM eye, ET eyes showed a small (1.3°-3.1°) reduction, which was statistically significant only along the superonasal meridian (P = .005). In bilaterally sighted children, visual field extent was not significantly reduced for high-risk type 1 ET eyes (-0.9° to 1.8°). However, in ET eyes with high-risk type 2 disease, visual field extent was significantly smaller compared with that of CM eyes (3.6°-8.7° superonasal field [P = .003]; inferonasal field [P < .001]). CONCLUSION: Early treatment preserves peripheral vision, with only a small reduction of visual field extent. APPLICATION TO CLINICAL PRACTICE: Early treatment for high-risk prethreshold ROP does not adversely affect visual field extent clinically.

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.

Final visual acuity results in the early treatment for retinopathy of prematurity study.

OBJECTIVE: To compare visual acuity at 6 years of age in eyes that received early treatment for high-risk prethreshold retinopathy of prematurity (ROP) with conventionally managed eyes. METHODS: Infants with symmetrical, high-risk prethreshold ROP (n = 317) had one eye randomized to earlier treatment at high-risk prethreshold disease and the other eye managed conventionally, treated if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to either early treatment or conventional management. The main outcome measure was ETDRS visual acuity measured at 6 years of age by masked testers. Retinal structure was assessed as a secondary outcome. RESULTS: Analysis of all subjects with high-risk prethreshold ROP showed no statistically significant benefit for early treatment (24.3% vs 28.6% [corrected] unfavorable outcome; P = .15). Analysis of 6-year visual acuity results according to the Type 1 and 2 clinical algorithm showed a benefit for Type 1 eyes (25.1% vs 32.8%; P = .02) treated early but not Type 2 eyes (23.6% vs 19.4%; P = .37). Early-treated eyes showed a significantly better structural outcome compared with conventionally managed eyes (8.9% vs 15.2% unfavorable outcome; P < .001), with no greater risk of ocular complications. CONCLUSIONS: Early treatment for Type 1 high-risk prethreshold eyes improved visual acuity outcomes at 6 years of age. Early treatment for Type 2 high-risk prethreshold eyes did not. Application to Clinical Practice Type 1 eyes, not Type 2 eyes, should be treated early. These results are particularly important considering that 52% of Type 2 high-risk prethreshold eyes underwent regression of ROP without requiring treatment. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Progression of type 2 to type 1 retinopathy of prematurity in the Early Treatment for Retinopathy of Prematurity Study.

OBJECTIVE: To examine the frequency and timing of progression from type 2 to type 1 retinopathy of prematurity (ROP) in the Early Treatment for Retinopathy of Prematurity Study. METHODS: Infants with prethreshold ROP that was no worse than low risk in 1 or both eyes, based on the RM-ROP2 model, were examined every 2 to 4 days for at least 2 weeks. Using the Early Treatment for Retinopathy of Prematurity Study-defined classification of eyes as having type 1 or type 2 prethreshold ROP, we analyzed the time to conversion from type 2 to type 1. Data were analyzed for 1 randomly selected eye for each child. RESULTS: Of 294 eyes at first diagnosis of type 2 ROP, 65 (22.1%) progressed to type 1 (mean [SD] interval, 9.0 [6.6] days; median, 7.0 days). Of 217 eyes with type 2 ROP that had an examination in less than 7 days, 25 (11.5%) were diagnosed with type 1 ROP in less than 7 days. Of 200 eyes that continued to have type 2 disease at the first follow-up examination and underwent a subsequent examination, 24 (15.7% of the 153 eyes that had an examination in <7 days) developed type 1 ROP in less than 7 days. The risk of progression from type 2 to type 1 in less than 7 days was greatest between 33 and 36 weeks' postmenstrual age, regardless of zone of retinopathy. CONCLUSIONS: Type 1 ROP can be identified with weekly examinations in most eyes with initial diagnosis of type 2 ROP; a small subset progresses to type 1 in less than 7 days. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00027222.

Astigmatism in the Early Treatment for Retinopathy Of Prematurity Study: findings to 3 years of age.

PURPOSE: To examine the prevalence of astigmatism (> or =1.00 diopter [D]) and high astigmatism (> or =2.00 D) at 6 and 9 months corrected age and 2 and 3 years postnatal age, in preterm children with birth weight of less than 1251 g in whom high-risk prethreshold retinopathy of prematurity (ROP) developed and who participated in the Early Treatment for Retinopathy of Prematurity (ETROP) Study. DESIGN: Randomized, controlled clinical trial. PARTICIPANTS: Four hundred one infants in whom prethreshold ROP developed in one or both eyes and who were randomized after they were determined to have a high risk (> or =15%) of poor structural outcome without treatment using the Risk Management of Retinopathy of Prematurity (RM-ROP2) program. Refractive error was measured by cycloplegic retinoscopy. Eyes with additional retinal, glaucoma, or cataract surgery were excluded. INTERVENTION: Eyes were randomized to receive laser photocoagulation at high-risk prethreshold ROP (early treated [ET]) or to be conventionally managed (CM), receiving treatment only if threshold ROP developed. MAIN OUTCOME MEASURES: Astigmatism and high astigmatism at each visit. Astigmatism was classified as with-the-rule (WTR; 75 degrees -105 degrees ), against-the-rule (ATR; 0 degrees -15 degrees and 165 degrees -180 degrees ), or oblique (OBL; 16 degrees -74 degrees and 106 degrees -164 degrees ). RESULTS: The prevalence of astigmatism in ET and CM eyes was similar at each test age. For both groups, there was an increase in prevalence of astigmatism from approximately 32% at 6 months to approximately 42% by 3 years, mostly occurring between 6 and 9 months. Among eyes that could be refracted, astigmatism was not influenced by zone of acute-phase ROP, presence of plus disease, or retinal residua of ROP. Eyes with astigmatism and high astigmatism most often had WTR astigmatism. CONCLUSIONS: By age 3 years, nearly 43% of eyes treated at high-risk prethreshold ROP developed astigmatism of > or =1.00 D and nearly 20% had astigmatism of > or =2.00 D. Presence of astigmatism was not influenced by timing of treatment of acute-phase ROP or by characteristics of acute-phase or cicatricial ROP. These findings reinforce the need for follow-up eye examinations in infants with high-risk prethreshold ROP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Effect of drug solubility on polymer hydration and drug dissolution from polyethylene oxide (PEO) matrix tablets.

The purpose of the study was to investigate the effect of drug solubility on polymer hydration and drug dissolution from modified release matrix tablets of polyethylene oxide (PEO). Different PEO matrix tablets were prepared using acetaminophen (ACE) and ibuprofen (IBU) as study compounds and Polyox WSR301 (PEO) as primary hydrophilic matrix polymer. Tablet dissolution was tested using the USP Apparatus II, and the hydration of PEO polymer during dissolution was recorded using a texture analyzer. Drug dissolution from the preparations was dependent upon drug solubility, hydrogel formation and polymer proportion in the preparation. Delayed drug release was attributed to the formation of hydrogel layer on the surface of the tablet and the penetration of water into matrix core through drug dissolution and diffusion. A multiple linear regression model could be used to describe the relationship among drug dissolution, polymer ratio, hydrogel formation and drug solubility; the mathematical correlation was also proven to be valid and adaptable to a series of study compounds. The developed methodology would be beneficial to formulation scientists in dosage form design and optimization.

Progression of myopia and high myopia in the early treatment for retinopathy of prematurity study: findings to 3 years of age.

PURPOSE: Examine the prevalence of myopia and high myopia, at 6 and 9 months postterm and 2 and 3 years postnatal in preterm children with birth weights < 1251 g who developed high-risk prethreshold retinopathy of prematurity (ROP) in the neonatal period and participated in the Early Treatment for ROP Study. DESIGN: Randomized controlled clinical trial. PARTICIPANTS: Four hundred one infants who developed prethreshold ROP and were determined to have a significant risk (>/=15%) of poor structural outcomes without treatment. Children underwent cycloplegic retinoscopy at examinations between 6 months postterm and 3 years' postnatal age. INTERVENTION: Eyes were randomized to receive treatment at high-risk prethreshold ROP (early treated [ET]) or conventional management (CM), with treatment only if threshold ROP developed. MAIN OUTCOME MEASURES: Myopia (spherical equivalent >/= 0.25 diopters [D]) or high myopia (>/=5.00 D) at each visit. RESULTS: Prevalences of myopia were similar in treated eyes in the ET and CM groups, increasing from approximately 58% to 68% between 6 and 9 months, with little change thereafter. Both ET and CM eyes showed an increasing prevalence of high myopia, approximately 19% at 6 months and increasing 4% to 8% at successive examinations. Zone of ROP and presence or absence of plus disease had little effect on prevalence of myopia or high myopia between ages 6 months and 3 years. However, eyes with ROP residua (straightened temporal vessels or macular heterotopia) showed a higher prevalence of myopia and high myopia than eyes without residua. CONCLUSIONS: Approximately 70% of high-risk prethreshold ROP eyes were myopic in early childhood, and the proportion with high myopia increased steadily between ages 6 months and 3 years. Timing of treatment of high-risk prethreshold ROP did not influence refractive error development. There was little difference in prevalence of myopia or high myopia between eyes with zone I and eyes with zone II ROP, nor between eyes with plus disease and eyes with no plus disease. However, prevalence of myopia and high myopia was higher in eyes with retinal residua of ROP than in eyes with normal-appearing posterior poles, highlighting the importance of follow-up eye examinations of infants who had prethreshold ROP.