An international comparison of retinopathy of prematurity grading performance within the Benefits of Oxygen Saturation Targeting II trials.

PurposeTo investigate whether the observed international differences in retinopathy of prematurity (ROP) treatment rates within the Benefits of Oxygen Saturation Targeting (BOOST) II trials might have been caused by international variation in ROP disease grading.MethodsGroups of BOOST II trial ophthalmologists in UK, Australia, and New Zealand (ANZ), and an international reference group (INT) used a web based system to grade a selection of RetCam images of ROP acquired during the BOOST II UK trial. Rates of decisions to treat, plus disease grading, ROP stage grading, ROP zone grading, inter-observer variation within groups and intra-observer variation within groups were measured.ResultsForty-two eye examinations were graded. UK ophthalmologists diagnosed treat-requiring ROP more frequently than ANZ ophthalmologists, 13.9 (3.49) compared to 9.4 (4.46) eye examinations, P=0.038. UK ophthalmologists diagnosed plus disease more frequently than ANZ ophthalmologists, 14.1 (6.23) compared to 8.5 (3.24) eye examinations, P=0.021. ANZ ophthalmologists diagnosed stage 2 ROP more frequently than UK ophthalmologists, 20.2 (5.8) compared to 12.7 (7.1) eye examinations, P=0.026. There were no other significant differences in the grading of ROP stage or zone. Inter-observer variation was higher within the UK group than within the ANZ group. Intra-observer variation was low in both groups.ConclusionsWe have found evidence of international variation in the diagnosis of treatment-requiring ROP. Improved standardisation of the diagnosis of treatment-requiring ROP is required. Measures might include improved training in the grading of ROP, using an international approach, and further development of ROP image analysis software.

The temporal retinal vessel angle and infants born preterm.

AIM: To determine the temporal retinal vessel angle in babies and its relation to preterm birth. METHODS: Digital images were obtained during routine screening for retinopathy of prematurity (ROP). The temporal retinal vessel angle was measured in 164 eyes of 82 babies born "very preterm" (24-27 weeks gestational age (GA)), "preterm" (28-31 weeks GA), and "near term" (>/=32 weeks GA). RESULTS: Mean temporal vessel angle (TVA) for all three GA groups together is 80.0 degrees (SD 17.0 degrees ) for the right eye and 80.5 degrees (16.7 degrees ) for the left eye. The range is right eye 59-106 degrees , left eye 69-97 degrees , with 95% data above 67 degrees for the right and 63 degrees for the left eye. For babies born near term, TVA is 82 degrees in each eye. There is a high degree of interocular symmetry between right and left eyes and a statistically insignificant trend for increasing TVA with increasing GA. The presence and stage of ROP affected one parameter of the left eye alone. CONCLUSIONS: These data provide normative data on the TVA in babies and will facilitate, especially if there is interocular asymmetry, determining whether there is macular displacement.

Do infants of birth weight less than 1500 g require additional long term ophthalmic follow up?

AIM: To survey existing ophthalmic follow up protocols in the United Kingdom for very low birthweight (VLBW) children. In addition, relative risk analysis was performed using data from a cohort study to assess which factors (birth weight, gestational age, retinopathy of prematurity (ROP) status) led to a high risk of developing amblyogenic factors. METHODS: Questionnaires were sent to every orthoptic department in the United Kingdom (n = 288) for information on their policy on the follow up of VLBW children. RESULTS: Responses were received from 125 departments (43%). There was a large variation in criteria used for follow up; 21% of respondents using birth weight (BW) and gestational age (GA), 22% using stage 3 or treated ROP, the remainder using a combination of these factors. There was no consensus regarding when follow up should commence (from 3 months to 3 years) or cease (1-8 years). Relative risk analysis revealed that birth weight under 1500 g, GA under 33 weeks, and the presence of severe ROP were significant risk factors for developing one or more amblyogenic factors. CONCLUSION: There is no consensus on whether VLBW children need to be reviewed. There is a greatly increased risk of ophthalmic deficits in those with severe ROP or severe neurological disorders, and also in those with mild or no ROP. Children in the latter group who are not routinely followed up, have a high risk of developing treatable refractive errors and strabismus. This raises the question of whether an additional screening examination is merited.

Change of refractive state and eye size in children of birth weight less than 1701 g.

AIMS: To determine the refractive status and ocular dimensions of a cohort of children at age 10-12 years with birth weight below 1701 g, and also the relation between the neonatal ophthalmic findings and subsequent refractive state. METHODS: 293 low birthweight children who had been examined in the neonatal period were assessed at 10-12 years of age. The examination consisted of autorefraction, keratometry, and A-scan. Results of right eyes were compared with published normative data. RESULTS: 293 of the birth cohort of 572 children consented to participate. The average mean spherical equivalent (MSE) in the low birthweight cohort was +0.691 dioptre, significantly higher than the control data (+0.30D, p = 0.02). The average change in MSE over the 10-12 year period was -1.00 dioptre (n = 256), but only 62.1% of cases showed a shift in refractive error of the appropriate magnitude and direction. The presence of any retinopathy of prematurity (ROP) increases the risk of developing anisometropia sixfold. CONCLUSIONS: Low birth weight and ROP both significantly impact the refractive state in the long term. At age 10-12 years children born preterm have an increased prevalence of all refractive errors. In low birthweight children refractive state is relatively stable over the first decade of life with a shift towards myopia of 1 dioptre.

Global prevalence of childhood cataract: a systematic review.

Childhood cataract is an avoidable cause of visual disability worldwide and is a priority for VISION 2020: The Right to Sight. There is a paucity of information about the burden of cataract in children and the aim of this review is to assess the global prevalence of childhood cataract. The methodology for the review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a literature search for studies reporting estimates of prevalence or incidence of cataract among children (aged<18 years) at any global location using the Cochrane Library, Medline and Embase up to January 2015. No restrictions were imposed based on language or year of publication. Study quality was assessed using a critical appraisal tool designed for systematic reviews of prevalence. Twenty prevalence and four incidence studies of childhood cataract from five different geographical regions were included. The overall prevalence of childhood cataract and congenital cataract was in the range from 0.32 to 22.9/10000 children (median=1.03) and 0.63 to 9.74/10000 (median=1.71), respectively. The incidence ranged from 1.8 to 3.6/10000 per year. The prevalence of childhood cataract in low-income economies was found to be 0.42 to 2.05 compared with 0.63 to 13.6/10000 in high-income economies. There was no difference in the prevalence based on laterality or gender. This review highlights substantial gaps in the epidemiological knowledge of childhood cataract worldwide, particularly from low and lower middle-income economies. More studies are needed using standard definitions and case ascertainment methods with large enough sample sizes.

The effect of oxygen saturation targeting on retinal blood vessel growth using retinal image data from the BOOST-II UK Trial.

PURPOSE: Retinopathy of prematurity (ROP) is a disorder of developing retinal blood vessels in preterm infants. The purpose of this nested study was to investigate the effects of higher (91-95%) and lower (85-89%) oxygen saturation (SpO2) targeting on retinal blood vessel growth in preterm infants. METHODS: Retinal blood vessel growth in the higher (91-95%) and lower (85-89%) oxygen saturation (SpO2) targeting groups was compared. Suitable RetCam (Clarity, Pleasanton, CA, USA) images collected in the BOOST-II UK trial were used. The distances between the centre of the optic disc and the ROP ridge in the temporal and nasal retina were measured in pixel units. RESULTS: Images from 38 infants were studied, 20 from the higher SpO2 target group and 18 from the lower SpO2 target group. On average, temporal blood vessels extended further from the optic disc than nasal blood vessels, mean (standard deviation (SD)) 463.39 (55.05) pixels compared with 360.13 (44.47) pixels, respectively, P<0.0001. Temporal blood vessels extended less far from the optic disc in the higher SpO2 target group than in the lower SpO2 target group: mean (SD) 449.83 (56.16) pixels compared with 480.02 (49.94), respectively, P=0.055. Nasal retinal blood vessel measurements were broadly similar in the higher and lower SpO2 target groups; mean (SD) 353.96 (41.95) compared with 370.00 (48.82) pixels, respectively, P=0.38. CONCLUSIONS: Relatively high oxygen saturation targeting (91-95%) was associated with a trend (P=0.055) towards reduced retinal blood vessel growth in this study of preterm infants.

UK population based study of severe retinopathy of prematurity: screening, treatment, and outcome.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the few causes of childhood blindness in which severe vision impairment is largely preventable. Ophthalmic screening for ROP is required to identify disease that requires treatment whereby the development of potentially blinding disease can be minimised. OBJECTIVES: To make the first UK population based estimate of the incidence of babies with severe ROP (stage 3 or more); to document their clinical characteristics and management and to evaluate the appropriateness of current ROP screening guidelines in the UK. PATIENTS: Cases were recruited through a national surveillance programme with 1 year ophthalmic follow up and data from clinician completed questionnaires. RESULTS: Between 1 December 1997 and 31 March 1999, 233 preterm babies with stage 3 ROP were identified. Severity (location, extent, and presence of plus disease) was associated with degree of prematurity, most severe in the most premature babies. Fifty nine percent were treated. The UK screening protocol was followed in two thirds of cases, but in the remainder it was begun too late or was too infrequent. Three quarters of the cases were followed up at 1 year, and 13% had a severe vision deficit as a result of ROP. CONCLUSIONS: Visual deficit as a result of ROP in premature babies continues to be a severe disability in some of the survivors of neonatal intensive care. Further efforts are needed to organise treatment regionally to improve outcome and standards of practice.

Lipid-protein constituents of human corneal arcus.

Extracts of fresh senile human peripheral cornea with varying degrees of arcus were prepared by soaking minced tissue in buffered saline/EDTA. Apolipoprotein B was, at most, an occasional feature of these extracts; interactions involving glycosaminoglycans were not evident; and the lipid composition, particularly of the cholesterol ester fraction, was also not consistent with a recent origin from plasma components and particularly form low density lipoprotein. Assuming this origin, substantial secondary changes must follow insudation, involving protein loss and lipid reesterification, as is described for lipid deposits forming intracellularly at other sites. The manner of these changes in deposit forming extracellularly in the avascular peripheral cornea is not clear.

Light and retinopathy of prematurity: does retinal location offer a clue?

Nursery illumination has been implicated in the pathogenesis of retinopathy of prematurity (ROP), although the results of recent studies are conflicting. The data base for this article is a prospective ROP study on 607 infants of birth weight less than or equal to 1700 g including 35 larger siblings from multiple births when 1 infant fulfilled the birth weight criteria. Retinopathy commences preferentially in the nasal retina of the most immature neonate and is less likely to develop, or its onset is delayed, in the superior and inferior regions. These findings cannot be fully accounted for by regional vascular and neuroanatomical variations. Radiometric and physiological evidence suggests that the very immature neonate, most at risk of developing severe ROP, receives the greatest retinal irradiance. Furthermore, ROP commences in the areas of the retina receiving the highest light dose, and its onset is either retarded or inhibited in the darker retinal regions. Further studies are required to determine whether early exposure to light is a factor in the development of ROP. If a causal relationship is proven, here at least is one modality that can easily and immediately be controlled.

Visual acuity and pupillary responses to spatial structure in infants.

PURPOSE: To determine the age of onset of the pupil grating response (PGR). To compare estimates of resolution acuity obtained by pupillometric and behavioral methods in early infancy. METHODS: Dynamic infrared pupillometry was undertaken on 19 newborn infants while they fixated a uniform background upon which a 0.1 c/deg sine wave grating was briefly presented. Pupillary responses were also recorded to an increment in luminance of a spatially homogeneous target. Longitudinal measurements of PGRs were obtained from a subset of eight infants between 3.5 and 38 weeks of age. In this group, behavioral estimates of visual resolution obtained using the acuity card procedure were compared with the highest spatial frequency grating to elicit a PGR. RESULTS: When presented with the pattern stimulus, newborn infants did not show any pupil reaction indicative of a PGR. This finding could not be attributed to immaturity of pupillomotor function: All infants showed marked pupillary construction to diffuse light stimulation. By 1 month of age, pupillary responses to pattern stimuli were reliably present. For these and older infants, the spatial frequency of the finest grating to elicit a PGR was comparable to the behaviorally determined resolution threshold: mean difference (+/- 95% confidence interval) = 0.28 +/- 0.23 octaves. CONCLUSIONS: A PGR could not be detected in newborn infants. From 1 month of age, responses to spatial structure can provide objective estimates of visual acuity comparable to those determined by established methods.

Light and the neonatal eye.

The lighting environment where the baby born prematurely is placed is different from that experienced in utero. As early exposure to light may affect the immature visual system we have attempted to quantify the neonatal ocular light dose. Lighting surveys performed in 7 neonatal units (NNUs) suggested that mean unit illuminance was 470 lux (range 192-890 lux) and intensive care areas within the NNU were significantly brighter than their corresponding low dependency nurseries. The spectral power distribution of fluorescent lights in NNUs was weighted towards the blue end of the spectrum. Datalogging studies demonstrated that between about 30% and 98% of environmental light was incident on the eyelid, which acts as a predominantly red-pass filter, permitting 21% transmission at 700 nm with less than or equal to 5% transmission at 580 nm. Eye-lid opening frequency was quantified: 45% less than or equal to 26 weeks gestational age and decreasing to 7% at 28 weeks gestational age. The onset of the pupillary reflex to light was between 30 and 34 weeks postmenstrual age, the mean diameter was 3.46 mm before this event and 3.02 mm afterwards. Retinal irradiance values calculated from these data show that it is a function of postmenstrual age. Further studies are required to determine its effect on the immature visual system.

Thermal transition studies of a mature xanthelasma by differential scanning calorimetry.

A large xanthelasma which had been present for at least 5 years was removed surgically from a normolipaemic female age 54 years, and examined in the fresh state by differential scanning calorimetry. Thermal transitions recorded over the range 30-40 degrees C suggest that the lipid present, predominantly esterified cholesterol, is not bound to protein or other tissue components, and that the chronicity of mature xanthelasmata as with ectopic lipid deposits at other sites is enhanced by chemical modification of lipid and effects on component phase behaviour, which are significant at local skin temperature.

Environmental light and the preterm infant.

The lighting environment of the preterm baby is quite unlike that experienced at any other time of life. Physical and physiological factors control how much light reaches the retina of the preterm baby. With respect to the former, although many neonatal intensive care units are brightly and continuously lit, there is a trend to employ lower levels of illumination and to introduce cycling regimens. Physiological determinants of the retinal light dose include: eyelid opening and transmission, pupil diameter and the transmission characteristics of the ocular media. Early exposure to light does not significantly hasten or retard normal visual development, and it is not a factor in the development of retinopathy of prematurity. However, ambient neonatal intensive care unit illumination may be implicated in some of the more subtle visual pathway sequelae that cannot be attributed to other major complications of preterm birth including altered visual functions and arrested eye growth.

Microcornea associated with retinopathy of prematurity.

Eight children with retinopathy of prematurity (ROP) in whom the corneal diameters were abnormally small in one or both eyes are reported. The mechanisms for microcornea in ROP are discussed. The differential diagnosis of microphthalmos is briefly considered.

Ophthalmic manifestations of primary oxalosis.

The clinical and pathological findings of a 6-month-old infant with primary oxalosis, who died in renal failure, are presented. The oxalate crystalline deposition in the retinal pigment epithelium corresponded to the flecked retinopathy observed ophthalmoscopically. The difficulties in establishing a precise biochemical diagnosis are discussed and the relevant ophthalmic literature is reviewed.

Transmission of light across the adult and neonatal eyelid in vivo.

Light transmission characteristics of the human adult and neonatal eyelid were measured in vivo. Light was delivered via a grating monochromator through a fibre-optic mounted onto a contact lens placed under the eyelid, and detected using a photodiode on its external skin surface. Data from 5 adult and 9 preterm neonatal subjects indicate that the eyelid acts as a predominantly red-pass filter, with mean transmissions at 700 nm of 14.5% in the adult and 21.4% in the neonate, declining to less than or equal to 3% in both groups below 580 nm. The relevance of this data to clinical electrophysiology and to estimates of retinal irradiance is discussed.

Validation of a photographic method of measuring corneal diameter.

A photographic method for measuring corneal diameter using the Medical-Nikkor f200 mm lens is described. Measurements were compared with those obtained by calipers (46 eyes of 25 patients) and by placing a ruler either near the eye (123 eyes of 64 patients) or on the nose (98 eyes of 55 patients). Over all we found good correlation between photographic and caliper measurements (r = 0.94). No significant correlation was found between photographic measurements and estimates made with the ruler either near the eye or on the nose (r = 0.65 and 0.31 respectively). Modifications to our system are suggested which may provide an accurate, simple, non-invasive method of measuring corneal diameter in ophthalmic clinics.

Tapetoretinal degeneration in the cerebro-hepato-renal (Zellweger's) syndrome.

Electrophysiological and histopathological study of a baby suffering from Zellweger's syndrome and presenting progressive retinal dysfunction showed this to be related to degenerative changes in the photoreceptor cells and pigment epithelium and to defective myelination of the optic nerve. Disturbances of bile acid and lysine metabolism were also demonstrated, lending support to the concept that Zellweger's syndrome is attributable to a widespread inadequacy of intracellular oxidative function.

Defining and measuring treatment outcome in unilateral amblyopia.

AIM: To offer a critique of current methods of defining amblyopia treatment outcome and to examine alternative approaches. METHOD: Literature appraisal and descriptive case presentations. RESULTS: Currently, the outcome of amblyopia treatment is expressed as the number of acuity chart lines gained or, alternatively, achievement of an arbitrarily adopted level of visual acuity. As binocular vision is optimised with equal visual input from each eye the authors propose that the optimum outcome of amblyopia therapy is to achieve a visual acuity in the amblyopic eye equal to that of its fellow. In addition, improvement should be graded as the proportion of change in visual acuity with respect to the absolute potential for improvement (that is, that pertaining in the fellow eye at end of treatment). CONCLUSIONS: There are two methods of appropriately describing the outcome of amblyopia treatment: firstly, by the difference in final visual acuity of amblyopic and fellow eye (residual amblyopia); secondly, the proportion of the deficit corrected.

Usher syndrome in the city of Birmingham--prevalence and clinical classification.

AIMS: To estimate the prevalence of Usher syndrome in the city of Birmingham, and to establish a database of patients who have been classified into different clinical subtypes essential for future gene mutation analysis. METHODS: Symptomatic cases of Usher syndrome (US) resident in the city of Birmingham in June 1994 were ascertained through multiple sources. Ophthalmic and audiological reassessment together with examination of medical records and patient questionnaires allowed classification of three subtypes, US 1, US 2, and US 3. In addition, family pedigrees were examined and blood was taken from index patients for DNA extraction. RESULTS: In the population aged over 15 years the prevalence was 6.2 per 100 000 population for all US subtypes. The prevalence for US 1 and US 2 was 5.3 per 100 000 population. This is greater than previously reported. In the age group 30-49 years the prevalence approached 1 in 10 000. Clinical classification found 33% US 1, 47% US 2, and 20% US 3. CONCLUSION: This higher prevalence rate and greater frequency of US 2 and US 3 may reflect a more complete ascertainment.