Graham E. Quinn

Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: implications for screening programs.

Objective. Retinopathy of prematurity (ROP) is a potentially avoidable cause of blindness in children. The proportion of blindness as a result of ROP varies greatly among countries depending on their level of development, being influenced by the availability of neonatal care, neonatal outcomes, and whether effective screening and treatment programs are in place. The objective of this study was to compare characteristics of premature infants who developed severe ROP between 1996 and 2002 in highly developed countries with less developed countries. Methods. This was an observational study. A questionnaire was completed by ophthalmologists in countries with low, moderate, and high development rankings (3 highly developed countries and from 10 less well-developed countries) who screen for ROP in which they supplied birth weights and gestational ages (GAs) of infants who were treated for threshold ROP or identified with more advanced stages of the disease. Birth weights and GAs of infants with severe ROP were measured. Results. The mean birth weights of infants from highly developed countries ranged from 737 to 763 g compared with values ranging from 903 to 1527 g in less developed countries. Mean GAs of infants from highly developed countries ranged from 25.3 to 25.6 weeks compared with 26.3 to 33.5 weeks in less developed countries. A total of 13.0% of 1091 infants from poorly developed countries exceeded United Kingdom screening criteria; 3.6% exceeded a criteria of <34 weeks’ GA and/or <1750 g birth weight. Conclusions. These findings suggest that larger, more mature infants are developing severe ROP in countries with low/moderate levels of development compared with highly developed countries. ROP screening programs need to use criteria that are appropriate for their local population.

In Vivo Human Choroidal Thickness Measurements: Evidence for Diurnal Fluctuations

PURPOSE The authors applied partial coherence interferometry (PCI) to estimate the thickness of the human choroid in vivo and to learn whether it fluctuates during the day. METHODS By applying signal processing techniques to existing PCI tracings of human ocular axial length measurements, a signal modeling algorithm was developed and validated to determine the position and variability of a postretinal peak that, by analogy to animal studies, likely corresponds to the choroidal/scleral interface. The algorithm then was applied to diurnal axial eye length datasets. RESULTS The postretinal peak was identified in 28% of subjects in the development and validation datasets, with mean subfoveal choroidal thicknesses of 307 and 293 microm, respectively. Twenty-eight of 40 diurnal PCI datasets had at least two time points with identifiable postretinal peaks, yielding a mean choroidal thickness of 426 microm and a mean high-low difference in choroidal thickness of 59.5 +/- 24.2 microm (range, 25.9-103 microm). The diurnal choroidal thickness fluctuation was larger than twice the SE of measurement (24.5 microm) in 16 of these 28 datasets. Axial length and choroidal thickness tended to fluctuate in antiphase. CONCLUSIONS Signal processing techniques provide choroidal thickness estimates in many, but not all, PCI datasets of axial eye measurements. Based on eyes with identifiable postretinal peaks at more than one time in a day, choroidal thickness varied over the day. Because of the established role of the choroid in retinal function and its possible role in regulating eye growth, further development and refinement of clinical methods to measure its thickness are warranted.

EARLY COMMITMENT OF NEURAL SUBSTRATES FOR FACE RECOGNITION

We present evidence of a striking failure of plasticity in the neural substrates of face recognition, which suggests that the distinction between faces and other objects, and the localisation of faces relative to other objects, is fully determined prior to any postnatal experience. A boy who sustained brain damage at 1 day of age has the classic lesions and behavioural profile of adult-acquired prosopagnosia. He has profoundly impaired face recognition, whereas his recognition of objects is much less impaired. This implies that the human genome contains sufficiently explicit information about faces and nonface objects, or visual features by which they can be distinguished, that experience with these categories is not necessary for their functional delineation and differential brain localisation.

Prevalence of Myopia between 3 Months and 5 '/-- Years in Preterm Infants with and without Retinopathy of Prematurity

Purpose: The purpose of the study was to examine spherical equivalent refractive errors, especially myopia, at six ages between 3 months and 5’/, years post-term in preterm children with birth weights of less than 1251 g. Design: A cohort study. Participants: There were a total of 827 participants in the multicenter study of cryotherapy for retinopathy of prematurity (ROP). Approximately one third of the eyes did not develop ROP, whereas two thirds developed mildto-severe ROP. None of the eyes underwent ctyotherapy. Intervention: Refractive error was measured at 3 months, 1 year, and 5’/2 years after term due date at the five long-term follow-up centers. In most eyes, refractive error also was measured at 2, 3’/*, and 4’/* years. Main Outcome Measure: Myopia was defined as 0.25 diopter (D) or greater with high myopia as 5 D or greater. Results: The proportion of eyes with myopia in this preterm population was increased compared to published data on full-term children and was related to severity of both acute-phase and cicatricial-phase ROP. The percentage of eyes with myopia varied little across ages, ranging from 21.2% at 1 year to 15.7% at 4’1’~ years. The percentage of eyes with high myopia doubled from 1.8% to 3.9% between 3 months and 1 year and remained stable thereafter. The distribution of refractive errors in eyes with mild acute-phase ROP was similar to that of eyes with no ROP. In contrast, eyes with moderate or severe acute-phase ROP showed an increased prevalence of high myopia. The distribution of refractive errors changed between 3 months and 1 year with little change after 1 year. This pattern of refractive development differs from that of full-term infants. Birth weight, severity of ROP, and degree of myopia at 3 months predicted the presence of myopia and high myopia at 5’1, years of age. Conclusions: The distribution of refractive errors in preterm infants from age 3 months to 51/2 years varies with severity of acute-phase ROP and cicatricial disease. Changes in refractive error distribution occur primarily between 3 months and 1 year and involve a decrease in the proportion of eyes with hyperopia and an increase in the proportion with high degrees of myopia. Ophfhalmology 7998; 705:7292- 7300

Development of Myopia in Infants with Birth Weights Less than 1251 Grams

The authors report on the incidence of myopia in a large group of premature infants with birth weights of less than 1251 g followed as part of the multicenter study of Cryotherapy for Retinopathy of Prematurity. None of the eyes reported here underwent cryotherapy. Eyes were refracted using cycloplegic retinoscopy at 3 months (n = 2916), 12 months (n = 2626), and 24 months (n = 961 at 5 of the 23 centers) after term. Myopia was observed in approximately 20% of the children at each test age. The percentage of high myopia (greater than or equal to 5 diopters) doubled from 2% to 4.6% between 3 and 12 months and remained stable thereafter. Lower birth weight and increasing severity of retinopathy of prematurity (ROP) were strong predictors of myopia and high myopia. In addition, anisometropia, astigmatism, and the presence of posterior pole residua from ROP also were associated with a higher incidence of myopia and high myopia.

Vitamin E prophylaxis to reduce retinopathy of prematurity: A reappraisal of published trials

OBJECTIVE We conducted a meta-analysis of the published randomized clinical trials of vitamin E prophylaxis designed to reduce retinopathy of prematurity (ROP) to determine whether increased serum concentrations of vitamin E reduced the incidence of severe, threshold (Stage 3+) ROP in the very low birth weight (VLBW) infant subset. STUDY DESIGN Among the six trials considered eligible for analyses, the incidence for all stages of ROP and for Stage 3+ ROP was computed for all randomly assigned infants (intention-to-treat analysis) and for those infants completing the trials. Odds ratios (ORs) and pooled estimates for event rate reductions (and the respective 95% confidence intervals [CIs]) were calculated for these outcome end points. RESULTS There were 704 VLBW infants in the vitamin E prophylaxis groups and 714 in control groups; 536 (76.1%) infants in the vitamin E and 551 (77.2%) in the control groups completed the trials. In all trials the mean serum vitamin E concentrations were within or above the physiologic range in the vitamin-treated groups and at or below the physiologic ranges in the control groups. The overall incidence of any stage ROP was similar between the groups: 39.8% in the vitamin E group and 43.5% in the control group. The overall incidence for Stage 3+ ROP was lower in the vitamin E-treated groups than in the control group (2.4% in vitamin E vs 5.3% in control). The pooled OR for developing Stage 3+ ROP with vitamin E prophylaxis was 0.44 (95% CI, 0.21, 0.81, p < 0.02). The reciprocal of the pooled estimate of mean risk reduction (2.8%, 95% CI: 0.55%, 5.1%) for Stage 3+ ROP revealed that on average, vitamin E prophylaxis given to 35 VLBW infants would prevent one case of threshold, Stage 3+ ROP. CONCLUSIONS Considering that there was a 52% reduction in the incidence of Stage 3+ ROP, we suggest that the role of vitamin E in reducing severe ROP be re-evaluated. We could not assess the adverse effect rates from vitamin E therapy in the trials analyzed; therefore, we recommend a well-controlled and focused trial in which the issues of benefit, adverse effects, and cost can be assessed with vitamin E prophylaxis in extremely low birth weight (< 1000 gm) infants.

Myopia and ambient lighting at night

Myopia, or short-sightedness, occurs when the image of distant objects, focused by the cornea and lens, falls in front of the retina. It commonly arises from excessive postnatal eye growth, particularly in the vitreous cavity. Its prevalence is increasing and now reaches 70-90% in some Asian populations,. As well as requiring optical correction, myopia is a leading risk factor for acquired blindness in adults because it predisposes individuals to retinal detachment, retinal degeneration and glaucoma. It typically develops in the early school years but can manifest into early adulthood. Its aetiology is poorly understood but may involve genetic and environmental factors,, such as viewing close objects, although how this stimulates eye growth is not known. We have looked at the effects of light exposure on vision, and find a strong association between myopia and night-time ambient light exposure during sleep in children before they reach two years of age.

Severity of Neonatal Retinopathy of Prematurity Is Predictive of Neurodevelopmental Functional Outcome at Age 5.5 Years

Objective. The purpose of this study was to assess the relation between neonatal retinopathy of prematurity (ROP) in very low birth weight infants and neurodevelopmental function at age 5.5 years. Methods. Longitudinal follow-up of children occurred in 2 cohorts of the Multicenter Cryotherapy for Retinopathy of Prematurity Study. The extended natural history cohort followed 1199 survivors of <1251 g birth weight from 5 centers. The threshold randomized cohort (ThRz) followed 255 infants <1251 g from 23 centers who developed threshold ROP and who consented to cryotherapy to not more than 1 eye. At 5.5 years both cohorts had ophthalmic and acuity testing and neurodevelopmental functional status determined with the Functional Independence Measure for Children (WeeFIM). Results. Evaluations were completed on 88.7% of the extended natural history cohort; 87% had globally normal functional skills (WeeFIM: >95). As ROP severity increased, rates of severe disability increased from 3.7% among those with no ROP, to 19.7% of those with threshold ROP. Multiple logistic regression analysis demonstrated that better functional status was associated with favorable visual acuity, favorable 2-year neurological score, absence of threshold ROP, having private health insurance, and black race. Evaluations were completed on 87.4% of the ThRz children. In each functional domain, the 134 children with favorable acuity in their better eye had fewer disabilities than did the 82 children with unfavorable acuity: self-care disability 25.4% versus 76.8%, continency disability 4.5% versus 50.0%, motor disability 5.2% versus 42.7%, and communicative-social cognitive disability 22.4% versus 65.9%, respectively. Conclusion. Severity of neonatal ROP seems to be a marker for functional disability at age 5.5 years among very low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had threshold ROP, particularly if they have unfavorable visual acuity.

Agreement among pediatric ophthalmologists in diagnosing plus and pre-plus disease in retinopathy of prematurity

PURPOSE Plus disease has become the major criterion for laser treatment in infants with retinopathy of prematurity (ROP), but its assessment is subjective. Our purpose was to compare quadrant-level and eye-level assessment of plus disease and pre-plus disease among 3 experienced ROP examiners and to report their rate of agreement. METHODS One hundred eighty-one high-quality RetCam images from premature infants were graded by 3 of the authors. Dilation and tortuosity were judged separately using a scale of normal or sufficiently abnormal to meet criteria for pre-plus or plus disease. RESULTS There was disagreement on the presence of plus disease for 18 images (10%), on tortuosity sufficient for plus disease (plus tortuosity) for 26 images (14%), and on dilation sufficient for plus disease (plus dilation) for 26 images (14%). Of 67 images judged to have pre-plus disease or worse, there was disagreement on the presence of plus disease for 18 images (27%), on plus tortuosity for 25 images (37%), and on plus dilation for 21 images (31%). For distinguishing plus or pre-plus disease from normal, there was disagreement on pre-plus tortuosity for 38 of 181 images (21%) and on pre-plus dilation for 58 of 181 images (32%). CONCLUSIONS Three experienced ROP examiners disagreed frequently on the diagnosis of plus or pre-plus disease when evaluating cropped clinical photographs of infants, many of which had borderline plus disease. Further study is required to determine the implications of these observations on clinical decision making.

Effect of Age on Response to Amblyopia Treatment in Children

OBJECTIVE To determine whether age at initiation of treatment for amblyopia influences the response among children 3 to less than 13 years of age with unilateral amblyopia who have 20/40 to 20/400 amblyopic eye visual acuity. METHODS A meta-analysis of individual subject data from 4 recently completed randomized amblyopia treatment trials was performed to evaluate the relationship between age and improvement in logMAR amblyopic eye visual acuity. Analyses were adjusted for baseline amblyopic eye visual acuity, spherical equivalent refractive error in the amblyopic eye, type of amblyopia, prior amblyopia treatment, study treatment, and protocol. Age was categorized (3 to <5 years, 5 to <7 years, and 7 to <13 years) because there was a nonlinear relationship between age and improvement in amblyopic eye visual acuity. RESULTS Children from 7 to less than 13 years of age were significantly less responsive to treatment than were younger age groups (children from 3 to <5 years of age or children from 5 to <7 years of age) for moderate and severe amblyopia (P < .04 for all 4 comparisons). There was no difference in treatment response between children 3 to less than 5 years of age and children 5 to less than 7 years of age for moderate amblyopia (P = .67), but there was a suggestion of greater responsiveness in children 3 to less than 5 years of age compared with children 5 to less than 7 years of age for severe amblyopia (P = .09). CONCLUSIONS Amblyopia is more responsive to treatment among children younger than 7 years of age. Although the average treatment response is smaller in children 7 to less than 13 years of age, some children show a marked response to treatment.