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 epidemiology, clinical characteristics, histopathology and management of juvenile- and adult-onset corneoscleral limbus xanthogranuloma.

PURPOSE: Adult-onset xanthogranuloma (AOX) of the corneoscleral limbus is a rare inflammatory condition of unknown aetiology. Similar to limbal juvenile xanthogranuloma (JXG), it presents as a growing mass at the corneoscleral junction. Limbal AOX and JXG can lead to sight-threatening complications if not managed in a timely manner. This systematic review summarises the main clinical and histopathological features of limbal AOX/JXG and discusses the management of this uncommon disease. METHODS: We performed a literature search in the MEDLINE database for all historical entries, using the search terms "limbus", "limbal" and "xanthogranuloma", and retrieved all articles reporting on limbal xanthogranuloma. After refining the search to articles relevant to limbal AOX, we were able to identify ten adult cases of limbal AOX and compare those with all reported cases of limbal JXG. RESULTS: Clinically, AOX usually presents as an isolated smooth, yellowish, dome-shaped nodule at the corneoscleral junction, similar to an ocular presentation of JXG, with which it also shares similar histopathological features. CONCLUSION: Limbal JXG and AOX may represent the same disease entity. Diagnosis relies on the clinical presentation, pathology and immunohistochemical profile. Spontaneous regression is unlikely, and thus prompt surgical intervention should be considered to prevent sight-threatening complications. Xanthogranuloma should be included in the differential diagnosis of corneoscleral limbal masses in patients of all age groups.

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.

Surgical outcome and risk stratification for primary retinal detachment repair: results from the Scottish Retinal Detachment study.

OBJECTIVES: To report the early surgical outcome, risk of failure and predictive value of rhegmatogenous retinal detachment (RRD) classification based on all participants in the Scottish Retinal Detachment study. METHODS: Over 2 years, all incident cases of RRD in Scotland were approached for recruitment. Early postoperative success was defined as an attached retina following one procedure with a minimum follow-up of 6-8 weeks. Using a regression model, the influence of clinical factors on the failure risk was estimated and the sensitivity and specificity of the Royal College of Ophthalmologists (RCOphth) grading for RRD and the vitrectomy in retinal detachment stratification risk formula (VR-SRF) in predicting operative failure were assessed. RESULTS: Primary outcome data were available for 86.2% (975/1130) of patients. The overall primary success rate was 80.8% (95% CI 78.1 to 83.3%). The presence of preoperative proliferative vitreoretinopathy of any degree and each additional clock hour of detachment increased the risk of failure by an OR of 2.4 and 1.13 respectively (p<0.05). A specificity of >95% in predicting early surgical failure was noted for highly complex RRDs according to the VR-SRF formula and the RCOphth classification. CONCLUSIONS: Consistent with previous series, the overall early success rate of RRD repair was 80% after one operation. The type of surgical repair did not influence overall success rates. Significant predictors of failure are the presence of preoperative proliferative vitreoretinopathy of any grade and the extent of detachment. The analytical value of current classification systems in predicting failure is most useful in complex RRDs.

The fellow eye in retinal detachment: findings from the Scottish Retinal Detachment Study.

AIM: To characterise the predisposing pathology and clinical features in the fellow eyes of patients recruited as part of the Scottish Retinal Detachment Study. METHODS: The Scottish Retinal Detachment Study was a 2-year prospectively recruited population-based epidemiology study that sought to recruit all incident cases of primary rhegmatogenous retinal detachment (RRD) in Scotland. RESULTS: A total of 1202 incident cases of primary RRD were recruited in Scotland, over a 2-year period and in 94% (1130 cases) detailed data on the clinical features of fellow eyes with RRD were available. Full-thickness retinal breaks were found in 8.4% (95/1130) of fellow eyes on presentation. Lattice degeneration was present in 14.5% (164/1130) of fellow eyes. Thirteen per cent (148/1130) of affected fellow eyes had a best corrected visual acuity of 6/18 or worse with previous RRD, the second most common cause of poor vision. Overall, 7.3% (88/1202) of cases had RRD in both eyes; 60% of cases with consecutive bilateral RRD presented before the macula were affected. CONCLUSIONS: Rhegmatogenous pathology in the fellow eye represents an important threat to vision. Fellow-eye detachments are more common in pseudophakic individuals and those with a more myopic refractive error. Fellow-eye RRD has a greater likelihood of prompt presentation.

Early retinal blood vessel growth in normal and growth restricted rat pups raised in oxygen and room air.

BACKGROUND/AIMS: Premature infants are born with incompletely vascularised retinas and are at a risk of developing retinopathy of prematurity (ROP). Rate of prenatal and postnatal body growth is important in the pathogenesis of ROP. The aim of this study was to develop a physiology-based rat model in order to study the effect of growth restriction and oxygen on early retinal vascular development. METHODS: Rat mothers were fed either a normal (18% casein) or low (9% casein) protein diet (to cause pup growth restriction) from the last week of gestation. After birth, mother and pups were placed in either room air or a specialised oxygen chamber that delivered a rapidly fluctuating hyperoxic oxygen profile. The oxygen profile was based on that from a premature infant who developed severe ROP. On day 14, retinas were dissected, flat-mounted and stained using biotinylated lectin. Images were captured by confocal microscopy. The avascular areas of the retinas were measured and compared. RESULTS: Growth restricted rat pups had significantly larger retinal avascular areas than 'normally grown' rat pups (Mann-Whitney U test, p<0.001). Growth restricted rat pups raised in fluctuating oxygen had significantly larger retinal avascular areas than growth restricted rat pups raised in room air (Mann-Whitney U test, p=0.001). CONCLUSIONS: The authors have developed a novel model for ROP that involves inducing both intrauterine and postnatal growth restriction and also exposes neonatal rat pups to fluctuating oxygen. This physiology-based model can be used to study the effects of growth, nutrition and oxygen on early retinal vascular development.

SNP mistyping in genotyping arrays--an important cause of spurious association in case-control studies.

Using genome-wide association studies to identify genetic variants contributing to disease has been highly successful with many novel genetic predispositions identified and biological pathways revealed. Several pitfalls for spurious association or non-replication have been highlighted: from population structure, automated genotype scoring for cases and controls, to age-varying association. We describe an important yet unreported source of bias in case-control studies due to variations in chip technology between different commercial array releases. As cases are commonly genotyped with newer arrays and freely available control resources are frequently used for comparison, there exists an important potential for false associations which are robust to standard quality control and replication design.

Pain in neonates during screening for retinopathy of prematurity using binocular indirect ophthalmoscopy and wide-field digital retinal imaging: a randomised comparison.

OBJECTIVE: To compare the pain experienced by premature infants undergoing wide-field digital retinal imaging (WFDRI) and binocular indirect ophthalmoscopy (BIO) for retinopathy of prematurity (ROP) screening. METHODS: Infants were recruited at Edinburgh Royal Infirmary Neonatal Unit, Edinburgh, UK. Eyes were examined by WFDRI and BIO with eyelid speculum by two experienced paediatric ophthalmologists in random order. A pain score (Premature Infant Pain Profile (PIPP)) for WFDRI and BIO was generated. RESULTS: A total of 76 infants were recruited. The (mean, SD) PIPP score for WFDRI was 15.0, 2.1 and for BIO was 15.2, 2.4 (paired t test p=0.47). The authors observed that infants started crying with corresponding physiological changes as soon as the eyelid speculum was inserted and crying stopped on speculum removal. CONCLUSION: WFDRI and BIO with eyelid speculum are similarly painful for infants. The authors speculate that the eyelid speculum rather than the examination method may contribute most to the pain experienced.

The epidemiology of rhegmatogenous retinal detachment: geographical variation and clinical associations.

AIMS/BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition. Obtaining an accurate estimate of RRD incidence in the population is essential in understanding the healthcare burden related to this disorder. METHODS: A systematic review of all population-based epidemiology studies of RRD published between January 1970 and January 2009 from Medline database searches was performed. RESULTS: RRD incidence demonstrates significant geographical variation and its incidence has been reported to be between 6.3 and 17.9 per 100,000 population. For studies with a sample size >300 the median annual incidence per 100,000 population was 10.5 (IQR 8.1-13.2) and the mean proportion of bilateral RRD was 7.26%. Overall, the mean prevalence of lattice degeneration was 45.7+/-20.3% and myopia was 47.28+/-12.59%. CONCLUSIONS: Estimates of RRD incidence have varied threefold, but inclusion criteria and other design features have differed across studies making direct comparisons difficult. The overall incidence of RRD is not yet well established: more incidence studies of adequate methodology are needed to explore temporal changes in incidence. RRD incidence varies with ethnicity and is strongly associated with increasing age, myopia and certain vitreo-retinal degenerations. Due to changes in cataract surgery trends, the proportion of pseudophakic RRD presenting to specialised centres appears to be increasing.

Wide-field digital retinal imaging versus binocular indirect ophthalmoscopy for retinopathy of prematurity screening: a two-observer prospective, randomised comparison.

AIM: To compare the diagnostic accuracy of wide-field digital retinal imaging (WFDRI) with the current "gold standard" of binocular indirect ophthalmoscopy (BIO) for retinopathy of prematurity (ROP) screening examinations. METHODS: A consecutive series of premature infants undergoing ROP screening at Edinburgh Royal Infirmary were eligible for recruitment into this prospective, randomised, comparative study. Infants were screened using both WFDRI (Retcam II with neonatal lens) and BIO by two paediatric ophthalmologists who were randomised to the examination technique. Both examiners documented their clinical findings and management plans in a masked fashion. WFDRI eye findings were compared with those of BIO. RESULTS: A total of 81 infants were recruited, and information from 245 eye examinations was analysed. The sensitivity of WFDRI in detecting any stage of ROP, stage 3 ROP and "plus" disease was 60%, 57% and 80%, respectively, and specificity 91%, 98% and 98%, respectively. The proportional agreement between WFDRI and BIO was 0.96 for detecting stage 3 disease and 0.97 for detecting "plus" disease. There was very good agreement on management decisions (kappa 0.85). CONCLUSION: When used in a routine ROP screening setting, a randomised comparison of WFDRI and BIO, WFDRI showed relatively poor sensitivity in detecting mild forms of ROP in the retinal periphery. This resulted in difficulty in making decisions to discharge infants from the screening programme. Sensitivity was better for more severe forms of ROP, but at present WFDRI should be regarded as an adjunct to, rather than a replacement for, BIO in routine ROP screening.

Retinopathy of prematurity in small-for-gestational age infants compared with those of appropriate size for gestational age.

AIM: To compare the incidence of retinopathy of prematurity (ROP) in small-for-gestational age (SGA) infants compared with appropriate-for-gestational age (AGA) infants undergoing eye screening in the Lothian region of south east Scotland 1990-2004. METHODS: All infants in Lothian born with birth weight <1500 g and/or gestational age <32 weeks underwent eye screening by two experienced paediatric ophthalmologists. The presence of any stage of ROP (1-5), severe (stage 3 or greater) ROP and treated ROP was compared between the SGA and AGA infants using chi(2) or Fisher exact tests. SGA was defined as birth weight below the 10th centile for gestational age. RESULTS: A total of 1413 babies with birth weights <1500 g and/or gestational age <32 weeks underwent eye screening; 329 (23%) were SGA. SGA infants born at gestational ages 26-31 weeks were more likely to develop any stage of ROP (p<0.01) than their AGA peers. SGA infants were also more likely to develop severe ROP (gestational age 26-27 weeks, p<0.01; 28-29 weeks, p = 0.01; 30-31 weeks, p = 0.01). CONCLUSIONS: SGA infants who underwent eye screening in the Lothian region of south east Scotland from 1990 to 2004 were significantly more likely to develop ROP and more severe disease than AGA infants.

A cluster of deep bacterial infections following eye surgery associated with construction dust.

SUMMARY: Three cases of serious eye infection (two endophthalmitis, one orbital cellulitis; two caused by Staphylococcus aureus, one caused by viridans streptococci) occurred shortly after surgery (two cataracts, one retinal detachment repair) within two weeks. There had been construction work adjacent to the theatres during this time, and fine dust was found on horizontal surfaces. Further surgery was cancelled, the construction work was completed and theatres were cleaned before recommencing with no further infections. Following a review of factors that may be involved in the pathogenesis of endophthalmitis, it is proposed that the mechanism of infection in these cases may have been due to the presence of foreign material enhancing the pathogenicity of the small numbers of organisms often found in intra-ocular fluids during surgery. This hypothesis could be tested in experimental models of endophthalmitis.

Trans-orbital intra-cranial air gun injury.

PURPOSE: To describe a case of trans-orbital intra-cranial air gun injury with a discussion on air gun related morbidity and mortality. METHODS: Case report and literature review. RESULTS: The air gun pellet travelled through the orbit without penetrating the globe. It passed into the middle cranial fossa through the superior orbital fissure and lodged in the temporal lobe. The patient was managed conservatively with antibiotics and antiepilectis. CONCLUSIONS: Air gun design has changed in recent years resulting in an increased morbidity and mortality. Stricter legislation on the sale and use of these weapons needs to be implemented.

A survey of visual impairment in children attending the Royal Blind School, Edinburgh using the WHO childhood visual impairment database.

PURPOSE: To assess the aetiology and changing patterns of childhood blindness in one school for the blind in the UK and to assess the use of the World Health Organisation Prevention of Blindness (WHO/PBL) methodology and reporting form in a developed country. METHODS: One hundred and seven children in one school for the blind and visually impaired in Edinburgh were examined using the WHO/PBL childhood blindness assessment form. RESULTS: Of the 107 children examined, 87 (81%) were blind or severely visually impaired (corrected visual acuity of <6/60 (20/200) in the better eye). Perinatal related blindness (40%), hereditary disease (26%) and developmental factors (26%) formed the three largest aetiological categories. CONCLUSION: The pattern of childhood blindness seen in this study was similar to reports from other developed countries. The WHO/PBL reporting form allows detailed comparisons between countries and over time. Additional fields for more detailed reporting of cerebral visual impairment and associated handicaps would increase the usefulness of the WHO/PBL form for population-based studies and for use in developed countries.