Reproducibility of Optovue RTVue Optical Coherence Tomography Retinal Thickness Measurements and Conversion to Equivalent Zeiss Stratus Metrics in Diabetic Macular Edema.

PURPOSE: To evaluate the reproducibility of central subfield thickness (CST) and volume measurements from optical coherence tomography (OCT) images obtained with Zeiss Stratus and Optovue RTVue, and formulate equations to convert these measurements from RTVue to 'equivalent' Stratus values. METHODS: Cross-sectional observational study from 309 eyes of 167 participants with diabetes and at least one eye with central-involved diabetic macular edema (DME; Stratus CST ≥ 250 µm) that underwent two replicate Stratus scans followed by two replicate RTVue scans centered on the fovea. RESULTS: The Bland-Altman coefficient of repeatability for relative change in CST (the degree of change that could be expected from measurement variability) was not significantly different on Stratus and RTVue scans (10% and 16%, respectively). The replicate Stratus CST was within 10% of the initial Stratus measurement 93% of the time; the CST conversion equation predicted a Stratus value calculated from the observed RTVue value within 10% of the observed Stratus thickness 91% of the time. Bland-Altman limit of agreement for relative change in CST between measurements observed on different machines was 23%, comparing predicted versus actual Stratus measurement. CONCLUSIONS: RTVue thickness reproducibility appears similar to Stratus. Conversion equations to transform RTVue measurements to Stratus-equivalent values within 10% of the observed Stratus RT are feasible. CST changes greater than 10% when using the same machine or 20% when switching from Stratus to RTVue, after conversion to Stratus equivalents, are likely due to a true change beyond measurement error. TRANSLATIONAL RELEVANCE: Conversion equations to translate central retinal thickness measurements between OCT instruments is critical to clinical trials.

Reproducibility of spectral-domain optical coherence tomography retinal thickness measurements and conversion to equivalent time-domain metrics in diabetic macular edema.

IMPORTANCE: Understanding measurement variability and relationships between measurements obtained on different optical coherence tomography (OCT) machines is critical for clinical trials and clinical settings. OBJECTIVE: To evaluate the reproducibility of retinal thickness measurements from OCT images obtained by time-domain (TD) (Stratus; Carl Zeiss Meditec) and spectral-domain (SD) (Cirrus; Carl Zeiss Meditec, and Spectralis; Heidelberg Engineering) instruments and formulate equations to convert retinal thickness measurements from SD-OCT to equivalent values on TD-OCT. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional observational study was conducted in private and institutional practices. Persons with diabetes mellitus who had at least 1 eye with central-involved diabetic macular edema, defined as Stratus central subfield thickness (CST) of 250 µm or greater, participated. An additional normative cohort (individuals with diabetes but without diabetic macular edema) was enrolled. Each study eye underwent 2 replicate Stratus scans followed by 2 replicate Cirrus or Spectralis scans (real-time image registration used) centered on the fovea. MAIN OUTCOMES AND MEASURES: Optical coherence tomography CST and macular volume. RESULTS: The Bland-Altman coefficient of repeatability for relative change in CST (the degree of change that could be expected from measurement variability) was lower with Spectralis (7%) compared with Cirrus (14%) and Stratus (12% and 15% within Cirrus/Stratus and Spectralis/Stratus groups, respectively). For each cohort, the initial Stratus CST was within 10% of the replicate Stratus measurement nearly all of the time; the conversion equations predicted a Stratus CST within 10% of the observed thickness 86% and 89% of the time for Cirrus/Stratus and Spectralis/Stratus groups, respectively, which is similar to the agreement on Stratus test-retest. The Bland-Altman limits of agreement for relative change in CST between machines (the degree of change that could be expected from measurement variability [combining within and between instrument variability]) were 21% for Cirrus and 19% for Spectralis when comparing predicted vs actual Stratus measurement. CONCLUSIONS AND RELEVANCE: Reproducibility appears to be better with Spectralis than with Cirrus and Stratus. Conversion equations to transform Cirrus or Spectralis measurements to Stratus-equivalent values, within 10% of the observed Stratus thickness values, appear feasible. Central subfield thickness changes beyond 10% when using the same machine or 20% when switching machines, after conversion to Stratus equivalents, are likely due to a change in retinal thickness rather than measurement error.

Retinal thickness in people with diabetes and minimal or no diabetic retinopathy: Heidelberg Spectralis optical coherence tomography.

PURPOSE: To evaluate macular thickness in people with diabetes but minimal or no retinopathy using Heidelberg Spectralis optical coherence tomography (OCT). METHODS: In a multicenter, cross-sectional study of mean retinal thickness, on Spectralis OCT in the nine standard OCT subfields, spanning a zone with 6-mm diameter, center point, and total retinal volume were evaluated. Central subfield (CSF) thickness was evaluated for association with demographic and clinical factors. Stratus OCT scans also were performed on each participant. RESULTS: The analysis included 122 eyes (122 participants) with diabetes and no (n = 103) or minimal diabetic retinopathy (n = 19) and no macular retinal thickening on clinical exam. Average CSF thickness was 270 ± 24 µm. Central subfield thickness was significantly greater in males relative to females (mean 278 ± 23 µm vs. 262 ± 22 µm, P < 0.001). After adjusting for gender, no additional factors were found to be significantly associated with CSF thickness (P > 0.10). Mean Stratus OCT CSF thickness was 199 ± 24 µm. CONCLUSIONS: Mean CSF thickness is approximately 70 µm thicker when measured with Heidelberg Spectralis OCT as compared with Stratus OCT among individuals with diabetes in the absence of retinopathy or with minimal nonproliferative retinopathy and a normal macular architecture. CSF thickness values ≥ 320 µm for males and 305 µm for females (~2 SDs above the average for this normative cohort) are proposed as gender-specific thickness levels to have reasonable certainty that diabetic macular edema involving the CSF is present using Spectralis measurements.

Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: diabetic retinopathy clinical research network.

PURPOSE: To evaluate factors ¶associated with favorable outcomes after vitrectomy for diabetic macular edema. METHODS: Data were collected prospectively on 241 eyes undergoing vitrectomy for diabetic macular edema. Multivariate models were used to evaluate associations of 20 preoperative and intraoperative factors with 6-month outcomes of visual acuity and retinal thickness. RESULTS: Median central subfield thickness decreased from 412 µm to 278 µm at 6 months, but median visual acuity remained unchanged (20/80, Snellen equivalent). Greater visual acuity improvement occurred in eyes with worse baseline acuity (P < 0.001) and in eyes in which an epiretinal membrane was removed (P = 0.006). Greater reduction in central subfield thickness occurred with worse baseline visual acuity (P < 0.001), greater preoperative retinal thickness (P = 0.001), removal of internal limiting membrane (P = 0.003), and optical coherence tomography evidence of vitreoretinal abnormalities (P = 0.006). No associations with clinician's preoperative assessments of the posterior vitreous were identified. CONCLUSION: These results suggest that the removal of epiretinal membranes may favorably affect visual outcome after vitrectomy. Preoperative presence of vitreoretinal abnormalities appeared to be associated with somewhat greater reductions in retinal thickness but not with visual acuity outcome. These results may be useful for future studies evaluating vitrectomy for diabetic macular edema.

Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema.

OBJECTIVE: Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). DESIGN: Multicenter, randomized clinical trial. PARTICIPANTS: A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea. METHODS: Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (> or =24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system. MAIN OUTCOME MEASURES: Best-corrected visual acuity and safety at 1 year. RESULTS: The 1-year mean change (+/-standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9+/-11, P<0.001) and ranibizumab + deferred laser group (+9+/-12, P<0.001) but not in the triamcinolone + prompt laser group (+4+/-13, P=0.31) compared with the sham + prompt laser group (+3+/-13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes. CONCLUSIONS: Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation.

Factors associated with improvement and worsening of visual acuity 2 years after focal/grid photocoagulation for diabetic macular edema.

PURPOSE: To identify factors associated with the visual acuity outcome after focal/grid photocoagulation for diabetic macular edema (DME) among eyes randomized to the focal/grid photocoagulation treatment group within the Diabetic Retinopathy Clinical Research Network (DRCR.net) trial comparing triamcinolone with focal/grid laser. DESIGN: Multicenter, randomized, clinical trial. PARTICIPANTS: Three hundred thirty eyes with DME assigned to the focal/grid photocoagulation group, visual acuity 20/40 to 20/320, and optical coherence tomography (OCT) central subfield thickness > or =250 microns. METHODS: Eyes were treated with a protocol-defined photocoagulation technique, which was repeated at 4-month intervals for persistent or recurrent edema. Separate logistic regression models were used to evaluate the associations of demographic, clinical, OCT, and fundus photographic variables with visual acuity improvement or worsening of > or =10 letters from baseline to 2 years. The association of the initial visual acuity outcome after treatment with the subsequent visual acuity course also was evaluated. MAIN OUTCOME MEASURES: Visual acuity measured with the electronic Early Treatment Diabetic Retinopathy Study method. RESULTS: Worse baseline visual acuity was the only factor found to be associated with more frequent visual acuity improvement (P<0.001), and both greater baseline OCT-measured retinal volume (P = 0.001) and better baseline visual acuity (P = 0.009) were found to be associated with more frequent visual acuity worsening. Visual acuity outcomes were similar in eyes with and without prior macular or panretinal photocoagulation. The initial visual acuity outcome at 4 months was not generally predictive of the subsequent course. Many eyes that worsened > or =10 letters from baseline to 4 months subsequently improved, and many eyes that initially improved, subsequently worsened. CONCLUSIONS: At this time, focal/grid photocoagulation remains the standard management for DME and these results do not alter this paradigm.

Exploratory analysis of diabetic retinopathy progression through 3 years in a randomized clinical trial that compares intravitreal triamcinolone acetonide with focal/grid photocoagulation.

OBJECTIVE: To compare the effect of intravitreal triamcinolone acetonide with focal/grid photocoagulation on the progression of diabetic retinopathy. METHODS: We performed an exploratory analysis of participants with diabetic macular edema randomly assigned to receive laser therapy or intravitreal triamcinolone acetonide (1 or 4 mg). Fundus photographs were obtained at baseline and 1, 2, and 3 years. The main outcome measure was progression to proliferative diabetic retinopathy or worsening of 2 or more severity levels on reading-center masked assessment of 7-field fundus photographs, plus additional eyes that received panretinal photocoagulation or had a vitreous hemorrhage. RESULTS: From July 15, 2004, through May 5, 2006, 840 eyes from 693 participants were enrolled in the study and randomly assigned to receive laser therapy (n = 330), 1 mg of triamcinolone acetonide (n = 256), or 4 mg of triamcinolone acetonide (n = 254). The cumulative probability of progression of retinopathy at 2 years was 31% (laser group), 29% (1-mg group), and 21% (4-mg group) (P = .64 in the 1-mg group and .005 in the 4-mg group compared with the laser group). These differences appeared to be sustained at 3 years. CONCLUSIONS: Intravitreal triamcinolone acetonide (4 mg) appeared to reduce the risk of progression of diabetic retinopathy. Given the exploratory nature of this analysis and because intravitreal triamcinolone adverse effects include cataract formation and glaucoma, use of this treatment merely to reduce the rates of progression of proliferative diabetic retinopathy or worsening of the level of diabetic retinopathy does not seem warranted at this time.

Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema.

OBJECTIVE: To report 3-year outcomes of patients who participated in a randomized trial evaluating 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone compared with focal/grid photocoagulation for treatment of diabetic macular edema. METHODS: Eyes with diabetic macular edema and visual acuities of 20/40 to 20/320 were randomly assigned to focal/grid photocoagulation or 1 mg or 4 mg of triamcinolone. At the conclusion of the trial, 3-year follow-up data were available in 306 eyes. RESULTS: Between 2 years (time of the primary outcome) and 3 years, more eyes improved than worsened in all 3 treatment groups. Change in visual acuity letter score from baseline to 3 years was +5 in the laser group and 0 in each triamcinolone group. The cumulative probability of cataract surgery by 3 years was 31%, 46%, and 83% in the laser and 1-mg and 4-mg triamcinolone groups, respectively. Intraocular pressure increased by more than 10 mm Hg at any visit in 4%, 18%, and 33% of eyes, respectively. CONCLUSIONS: Results in a subset of randomized subjects who completed the 3-year follow-up are consistent with previously published 2-year results and do not indicate a long-term benefit of intravitreal triamcinolone relative to focal/grid photocoagulation in patients with diabetic macular edema similar to those studied in this clinical trial. Most eyes receiving 4 mg of triamcinolone as given in this study are likely to require cataract surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00367133.

Retinal thickness on Stratus optical coherence tomography in people with diabetes and minimal or no diabetic retinopathy.

PURPOSE: To evaluate optical coherence tomography (OCT) thickness of the macula in people with diabetes but minimal or no retinopathy and to compare these findings with published normative data in the literature from subjects reported to have no retinal disease. DESIGN: Cross-sectional study. METHODS: In a multicenter community- and university-based practices setting, 97 subjects with diabetes with no or minimal diabetic retinopathy and no central retinal thickening on clinical examination and a center point thickness of 225 microm or less on OCT (Stratus OCT; Carl Zeiss Meditec, Dublin, California, USA) were recruited. Electronic Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, seven-field stereoscopic color fundus photographs, and Stratus OCT fast macular scan were noted. Main outcome measures were central subfield (CSF) thickness measured on Stratus OCT. RESULTS: On average, CSF thickness was 201 +/- 22 microm. CSF thickness was significantly greater in retinas from men than retinas from women (mean +/- standard deviation, 209 +/- 18 microm vs 194 +/- 23 microm; P < .001). After adjusting for gender, no additional factors were found to be associated significantly with CSF thickness (P > .10). CONCLUSIONS: CSF thicknesses on Stratus OCT in people with diabetes and minimal or no retinopathy are similar to thicknesses reported from a normative database of people without diabetes. CSF thickness is greater in men than in women, consistent with many, but not all, previous reports. Studies involving comparisons of retinal thickness with expected norms should consider different mean values for women and men.

A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema.

OBJECTIVE: To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME). DESIGN: Randomized phase II clinical trial. PARTICIPANTS: One hundred twenty-one eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32 to 20/320. INTERVENTIONS: Random assignment to 1 of 5 groups: (A) focal photocoagulation at baseline (n = 19), (B) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks (n = 22), (C) intravitreal injection of 2.5 mg of bevacizumab at baseline and 6 weeks (n = 24), (D) intravitreal injection of 1.25 mg of bevacizumab at baseline and sham injection at 6 weeks (n = 22), or (E) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (n = 22). MAIN OUTCOME MEASURES: Central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks. RESULTS: At baseline, median CST was 411 mum and median Snellen VA equivalent was 20/50. Compared with group A, groups B and C had a greater reduction in CST at 3 weeks and about 1 line better median VA over 12 weeks. There were no meaningful differences between groups B and C in CST reduction or VA improvement. A CST reduction > 11% (reliability limit) was present at 3 weeks in 36 of 84 (43%) bevacizumab-treated eyes and 5 of 18 (28%) eyes treated with laser alone, and at 6 weeks in 31 of 84 (37%) and 9 of 18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in 1 eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (n = 2), congestive heart failure (n = 1), elevated blood pressure (n = 3), and worsened renal function (n = 3). CONCLUSION: These results demonstrate that intravitreal bevacizumab can reduce DME in some eyes, but the study was not designed to determine whether treatment is beneficial. A phase III trial would be needed for that purpose.

Treatment of strabismic amblyopia with refractive correction.

PURPOSE: To report data on the response of previously untreated strabismic amblyopia to spectacle correction. DESIGN: Prospective, interventional case series. METHODS: Twelve patients with previously untreated strabismic amblyopia were prescribed spectacles and examined at five-week intervals until visual acuity was not improved from the prior visit. RESULTS: Amblyopic eye acuity improved by 2 lines or more from spectacle-corrected baseline acuity in nine of the 12 patients (75%), resolving in three (interocular difference

Retinal nerve fiber layer thickness in amblyopic eyes.

PURPOSE: To compare the peripapillary retinal nerve fiber layer (RNFL) thickness of sound and amblyopic eyes. DESIGN: Prospective observational case series. SETTING: Institutional. STUDY POPULATION: Patients with unilateral strabismic, anisometropic, or combined amblyopia. OBSERVATION: Fast RNFL analysis with ocular coherence tomography (OCT) of sound and amblyopic eyes. MEASURE: Mean RNFL thickness. RESULTS: For the 17 patients (mean age 10.7 years) in whom both eyes were imaged, the mean thickness of the sound eye was 109.2 microm (median 112.7) and of the amblyopic eye was 104.2 microm (median 105.0), and the average difference (sound eye less amblyopic eye) was 5.0 microm (median 3.0) (95% confidence interval -2.3, 12.2, P = .17). The sound eye was 10 microm or more thicker than the amblyopic eye in four patients; the amblyopic eye was 10 microm or more thicker than the sound eye in one patient; and the difference was within 10 microm in 12 patients. Test-retest data were obtained for 23 pairs of sound eyes and 21 pairs of amblyopic eyes, with 75% of the test-retest pairs within 7%. CONCLUSIONS: We found a small, but not clinically significant, difference in nerve fiber layer (NFL) thickness between amblyopic and sound eyes. Reliability was excellent, with most eyes testing within 7% of the first test.

Treatment of anisometropic amblyopia in children with refractive correction.

OBJECTIVE: To evaluate the effectiveness of refractive correction alone for the treatment of untreated anisometropic amblyopia in children 3 to <7 years old. DESIGN: Prospective, multicenter, noncomparative intervention. PARTICIPANTS: Eighty-four children 3 to <7 years old with untreated anisometropic amblyopia ranging from 20/40 to 20/250. METHODS: Optimal refractive correction was provided, and visual acuity (VA) was measured with the new spectacle correction at baseline and at 5-week intervals until VA stabilized or amblyopia resolved. MAIN OUTCOME MEASURES: Maximum improvement in best-corrected VA in the amblyopic eye and proportion of children whose amblyopia resolved (interocular difference of < or =1 line) with refractive correction alone. RESULTS: Amblyopia improved with optical correction by > or =2 lines in 77% of the patients and resolved in 27%. Improvement took up to 30 weeks for stabilization criteria to be met. After stabilization, additional improvement occurred with spectacles alone in 21 of 34 patients observed in a control group of a subsequent randomized trial, with amblyopia resolving in 6. Treatment outcome was not related to age, but was related to better baseline VA and lesser amounts of anisometropia. CONCLUSION: Refractive correction alone improves VA in many cases and results in resolution of amblyopia in at least one third of 3- to <7-year-old children with untreated anisometropic amblyopia. Although most cases of resolution occur with moderate (20/40-20/100) amblyopia, the average 3-line improvement in VA resulting from treatment with spectacles may lessen the burden of subsequent amblyopia therapy for those with denser levels of amblyopia.

A randomized trial to evaluate 2 hours of daily patching for strabismic and anisometropic amblyopia in children.

OBJECTIVE: To compare 2 hours of daily patching (combined with 1 hour of concurrent near visual activities) with a control group of spectacle wear alone (if needed) for treatment of moderate to severe amblyopia in children 3 to 7 years old. DESIGN: Prospective randomized multicenter clinical trial (46 sites). PARTICIPANTS: One hundred eighty children 3 to 7 years old with best-corrected amblyopic-eye visual acuity (VA) of 20/40 to 20/400 associated with strabismus, anisometropia, or both who had worn optimal refractive correction (if needed) for at least 16 weeks or for 2 consecutive visits without improvement. INTERVENTION: Randomization either to 2 hours of daily patching with 1 hour of near visual activities or to spectacles alone (if needed). Patients were continued on the randomized treatment (or no treatment) until no further improvement was noted. MAIN OUTCOME MEASURE: Best-corrected VA in the amblyopic eye after 5 weeks. RESULTS: Improvement in VA of the amblyopic eye from baseline to 5 weeks averaged 1.1 lines in the patching group and 0.5 lines in the control group (P = 0.006), and improvement from baseline to best measured VA at any visit averaged 2.2 lines in the patching group and 1.3 lines in the control group (P<0.001). CONCLUSION: After a period of treatment with spectacles, 2 hours of daily patching combined with 1 hour of near visual activities modestly improves moderate to severe amblyopia in children 3 to 7 years old.

Randomized trial of treatment of amblyopia in children aged 7 to 17 years.

OBJECTIVE: To evaluate the effectiveness of treatment of amblyopia in children aged 7 to 17 years. METHODS: At 49 clinical sites, 507 patients with amblyopic eye visual acuity ranging from 20/40 to 20/400 were provided with optimal optical correction and then randomized to a treatment group (2-6 hours per day of prescribed patching combined with near visual activities for all patients plus atropine sulfate for children aged 7 to 12 years) or an optical correction group (optical correction alone). Patients whose amblyopic eye acuity improved 10 or more letters (> or =2 lines) by 24 weeks were considered responders. RESULTS: In the 7- to 12-year-olds (n = 404), 53% of the treatment group were responders compared with 25% of the optical correction group (P<.001). In the 13- to 17-year-olds (n = 103), the responder rates were 25% and 23%, respectively, overall (adjusted P = .22) but 47% and 20%, respectively, among patients not previously treated with patching and/or atropine for amblyopia (adjusted P = .03). Most patients, including responders, were left with a residual visual acuity deficit. CONCLUSIONS: Amblyopia improves with optical correction alone in about one fourth of patients aged 7 to 17 years, although most patients who are initially treated with optical correction alone will require additional treatment for amblyopia. For patients aged 7 to 12 years, prescribing 2 to 6 hours per day of patching with near visual activities and atropine can improve visual acuity even if the amblyopia has been previously treated. For patients 13 to 17 years, prescribing patching 2 to 6 hours per day with near visual activities may improve visual acuity when amblyopia has not been previously treated but appears to be of little benefit if amblyopia was previously treated with patching. We do not yet know whether visual acuity improvement will be sustained once treatment is discontinued; therefore, conclusions regarding the long-term benefit of treatment and the development of treatment recommendations for amblyopia in children 7 years and older await the results of a follow-up study we are conducting on the patients who responded to treatment.

A randomized pilot study of near activities versus non-near activities during patching therapy for amblyopia.

BACKGROUND: To plan a future randomized clinical trial, we conducted a pilot study to determine whether children randomized to near or non-near activities would perform prescribed activities. A secondary aim was to obtain a preliminary estimate of the effect of near versus non-near activities on amblyopic eye visual acuity, when combined with 2 hours of daily patching. METHODS: Sixty-four children, 3 to less than 7 years of age, with anisometropic, strabismic, or combined amblyopia (20/40 to 20/400) were randomly assigned to receive either 2 hours of daily patching with near activities or 2 hours of daily patching without near activities. Parents completed daily calendars for 4 weeks recording the activities performed while patched and received a weekly telephone call in which they were asked to describe the activities performed during the previous 2 hours of patching. Visual acuity was assessed at 4 weeks. RESULTS: The children assigned to near visual activities performed more near activities than those assigned to non-near activities (by calendars, mean 1.6 +/- 0.5 hours versus 0.2 +/- 0.2 hours daily, P < 0.001; by telephone interviews, 1.6 +/- 0.4 hours versus 0.4 +/- 0.5 hours daily, P < 0.001). After 4 weeks of treatment, there was a suggestion of greater improvement in amblyopic eye visual acuity in those assigned to near visual activities (mean 2.6 lines versus 1.6 lines, P = 0.07). The treatment group difference in visual acuity was present for patients with severe amblyopia but not moderate amblyopia. CONCLUSIONS: Children patched and instructed to perform near activities for amblyopia spent more time performing those near activities than children who were instructed to perform non-near activities. Our results suggest that performing near activities while patched may be beneficial in treating amblyopia. Based on our data, a formal randomized amblyopia treatment trial of patching with and without near activities is both feasible and desirable.

A population-based study of the effects of birth weight on early developmental delay or disability in children.

Improving medical treatment of extremely low-birth-weight infants over the last 20 to 30 years resulted in increased survival rates. The developmental sequela of salvaged infants is of great interest to perinatologists. The primary purposes of the current study were to assess the effect of birth weight (BW) on developmental delay or disability (DDD) in the first three years of life and determine whether there is a BW threshold below which all infants should be evaluated to determine if intervention services for children with DDD should be received. Three statewide databases were merged: 1998 Birth Vital Statistics; 1997-1998 Medicaid eligibility files; and 1998-2001 Children's Medical Services' Early Intervention Program (CMS-EIP) data. Infants who died within the first year of life and plural births were excluded. The final dataset consisted of 170,874 records. A child was determined to have a DDD if a developmental delay, or an established condition, such as sensory impairment, genetic, metabolic, neurological, or severe attachment disorders, was diagnosed through a multidisciplinary evaluation. Logistic regression models were used to relate BW to DDD, controlling for sociodemographic, behavioral, and perinatal variables. Adjusted odds ratios (OR) were calculated to describe the effects of BW on DDD. There was a significant effect of BW on DDD (Adjusted OR &equals 97.50, 40.01, 15.84, 3.29, 1.39, 1.00, 1.52 for BW categories 450-749, 750-999, 1000-1499, 1500- 2499, 2500-2999, 3000-4749, 4750-6050 g, respectively). In these categories, 70%, 56%, 36%, 11%, 4%, 3%, and 6% of surviving singleton infants, respectively, suffered a DDD in their first 3 years of life. Four medical, five sociodemographic, and two behavioral factors were significant in addition to BW. An equation for predicting the probability of DDD given these factors was obtained, and its use exemplified. BW is strongly associated with DDD. Over 60% of infants weighing < 1000 g and nearly half (46%) of those weighing < 1500 g at birth are diagnosed with a DDD before 3 years of age. The probability of DDD for a specific infant also varies by sociodemographic, other perinatal, and behavioral factors. The results of this paper suggest that all surviving infants of BW < 1000 g, and perhaps < 1500 g, should be automatically referred for evaluation.