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.

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.

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.

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.

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.

Identification of a new 'TIGR' mutation in a family with juvenile-onset primary open angle glaucoma.

Positional mapping of families segregating for juvenile-onset primary open angle glaucoma (JOAG) has previously identified a locus (GLCIA) for this condition on the long arm of chromosome I. Recently, three mutations in the TIGR gene (Trabecular meshwork Inducible Gluco-corticoid Response protein) have been described in a total of ten familial, three sporadic, and one normal subject. One of the familial cases has also been indicated to be of an adult-onset type. Herein, we report the identification of a new mutation in the TIGR gene in a six generation well-documented Edinburgh family with JOAG. We have sampled and screened the living affected members of this family and identified an 'A'-to-'G' transition at amino acid 337 that has changed the glutamine (Gln) to arginine (Arg). This newly identified mutation resides 27 amino acids 5-prime from the previously reported mutation of Gly-to-Val. This mutation created a new MspI restriction site that has co-segregated perfectly with inherited affected haplotype of the pedigree and, furthermore, it has not been observed in 142 chromosomes of randomly selected subjects of the same population. This report, therefore, confirms the role of the TIGR gene in the etiology of JOAG and adds a new mutation to the three reported previously.

How large must an iridotomy be?

Four cases of acute angle closure glaucoma in eyes with a small but patent Nd-YAG laser iridotomy are presented, and similar cases in the literature are reviewed. Theoretically a 15 microns diameter iridotomy should be large enough to prevent angle closure glaucoma due to pupil block. Mechanisms by which larger iridotomies fail to prevent angle closure glaucoma, and the role of provocation tests following iridotomy, are discussed. An iridotomy should be at least 150-200 microns in diameter if acute angle closure glaucoma is to be reliably prevented.

A photometric study of the effect of pupil dilatation on Nd:YAG laser iridotomy area.

A photometric study of the effect of pupil dilatation on Nd:YAG laser iridotomy area was performed in 21 eyes of 21 patients. The iridotomy area was 0.075 (0.055) mm-2 (mean (SD)) before pupil dilatation and 0.073 (0.070) mm-2 after pupil dilatation (t test NS). Iridotomy area after pupil dilatation correlated with iridotomy area before pupil dilatation (r = 0.815, p < 0.01) but did not significantly correlate with measures of iridotomy shape or position, or with changed iris area following pupil dilatation. Two iridotomies became reduced to less than 20% of their initial area following pupil dilatation. Our findings suggest that the only effective method of avoiding development of unacceptably small iridotomy area after pupil dilatation is to create a sufficiently large iridotomy at the time of initial laser surgery.

A randomised prospective comparison of operative peripheral iridectomy and Nd:YAG laser iridotomy treatment of acute angle closure glaucoma: 3 year visual acuity and intraocular pressure control outcome.

AIM: To compare visual acuity and intraocular pressure outcomes 3 years after treatment of acute angle closure glaucoma (AACG) by operative peripheral iridectomy (PI) or Nd:YAG laser iridotomy (YAG PI). METHODS: A prospective study of consecutive patients presenting to one ophthalmology department with uniocular AACG during a 2 year period. Following informed consent patients were randomised to bilateral PI or bilateral YAG PI. Three years after treatment the mean Snellen visual acuity converted to logMAR scores of the two groups was compared using the unpaired Student's t test. The number of patients with normal intraocular pressure with no further treatment in each group was compared using the chi 2 test with Yates's correction. RESULTS: 21 patients underwent bilateral PI and 27 bilateral YAG PI. Three years after treatment visual acuity was 0.30 (SD 0.28) log MAR units for PI eyes and 0.57 (0.67) logMAR units for YAG PI eyes (p = 0.08, NS). 15 (70.4%) PI eyes and 19 (71.8%) YAG PI eyes had an intraocular pressure less than 21 mm Hg with no further treatment (NS). CONCLUSIONS: There was no significant difference in visual acuity or intraocular pressure control 3 years after treatment of AACG with PI or YAG PI.

Case of penetrating orbitocranial injury caused by wood.

A case of retained intraorbital and intracerebral wooden foreign body following an orbitocranial penetrating injury through the lower lid of an adult is described. Initial failure to recognise the true nature of the injury led to intracerebral abscess formation and monocular blindness. Diagnosis and management of such cases are discussed.

Is the partial pressure of carbon dioxide in the blood related to the development of retinopathy of prematurity?

AIMS: To determine the role of carbon dioxide in the development of retinopathy of prematurity (ROP). METHODS: This was a retrospective cohort study of 25 consecutive infants admitted to the neonatal unit with continuously recorded physiological data. The daily mean and standard deviation (SD) of transcutaneous carbon dioxide partial pressure (tcPCO(2)) was compared between infants who had stage 1 or 2 ROP and stage 3 ROP. The time spent hypocarbic (<3 kPa) and/or hypercarbic (>10 kPa and >12 kPa) was also compared between these groups. Intermittent arterial carbon dioxide tension was also measured and compared with the simultaneous tcPCO(2) data. RESULTS: There were no significant differences in carbon dioxide variability or time spent hypocarbic and/or hypercarbic between the ROP groups on any day. 86% of transcutaneous values were within 1.5 kPa of the simultaneous arterial value. CONCLUSION: TcPCO(2) measurement can be a very useful management technique. However, in this cohort neither variable blood carbon dioxide tension nor duration of hypercarbia or hypocarbia in the first 2 weeks of life was associated with the development or severity of ROP.

Diode laser treatment for retinopathy of prematurity: structural and functional outcome.

AIMS: The anatomical and functional outcome of 13 babies with retinopathy of prematurity (ROP) treated with binocular indirect ophthalmoscope diode laser photocoagulation was assessed. METHODS: Thirteen babies (25 eyes) at median postmenstrual age (PMA) 25.5 weeks and median birth weight 725 g were treated with binocular indirect ophthalmoscope (BIO) diode laser photocoagulation when threshold retinopathy of prematurity (ROP) was detected at median PMA 35 weeks. Retinopathy was more severe in the nasal retina in 15 eyes. The median severity of retinopathy was 6 clock hours grade 3 disease. All babies were treated under general anaesthetic with no significant ocular or systemic complications during treatment. The median number of burns was 1200. RESULTS: Resolution of active retinopathy occurred 1-2 weeks following treatment in all but one baby. All eyes had favourable anatomical and functional outcome as defined by the Cryo-ROP study group at a median age of 19.5 months of follow up. CONCLUSION: BIO diode laser treatment is as effective as cryotherapy with less morbidity.

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.

Screening for retinopathy of prematurity: are a lid speculum and scleral indentation necessary?

We wanted to investigate the value of using a lid speculum and scleral indentation in performing binocular indirect ophthalmoscopy (BIO) in neonates at risk of retinopathy of prematurity (ROP). We performed a prospective masked comparison of BIO examinations using either a lid speculum and scleral indentation (SI) or no scleral indentation (NSI), in our neonatal intensive care unit. We did 57 consecutive BIO examinations of infants weighing less than 1500 g and/or having a gestational age of less than 32 weeks. With NSI, zone I ROP was reliably seen in 53 of 57 examinations; the superior, nasal, and temporal aspects of zone II were seen in 45 of 57 examinations; inferior zone II, in 22 of 57 examinations; and zone III in 1 of 57 examinations. SI facilitated complete peripheral fundus examination in all cases but had to be abandoned in two infants due to acute changes in oxygen saturation levels. Five infants developed threshold disease, and in two of them details of the active ROP ridge were missed with NSI. The gentle use of an eyelid speculum and globe rotation allows rapid and relatively atraumatic assessment of the peripheral fundus, even in babies who are being ventilated. Although threshold ROP may be diagnosed by observation of posterior retinal vessel dilation and tortuosity ("plus" disease), accurate grading of ROP is likely to require SI. In the absence of clearly developed "plus" disease, borderline or prethreshold disease may occasionally be missed using BIO with NSI. SI is necessary to examine the inferior midperipheral retinal vasculature (zone II) and the far peripheral temporal retina (zone III) and is associated with few complications.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.