Ranibizumab pretreatment in diabetic vitrectomy: a pilot randomised controlled trial (the RaDiVit study).

PurposeOur aim was to evaluate the impact of intravitreal ranibizumab pretreatment on the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy. The objective was to determine the feasibility of a subsequent definitive trial and estimate the effect size and variability of the outcome measure.Patients and methodsWe performed a pilot randomised double-masked single-centre clinical trial in 30 participants with tractional retinal detachment associated with proliferative diabetic retinopathy. Seven days prior to vitrectomy surgery, participants were randomly allocated to receive either intravitreal ranibizumab (Lucentis, Novartis Pharmaceuticals UK Ltd, Frimley, UK) or subconjunctival saline (control). The primary outcome was best-corrected visual acuity 12 weeks following surgery.ResultsAt 12 weeks, the mean (SD) visual acuity was 46.7 (25) ETDRS letters in the control group and 52.6 (21) letters in the ranibizumab group. Mean visual acuity improved by 14 (31) letters in the control group and by 24 (27) letters in the ranibizumab group. We found no difference in the progression of tractional retinal detachment prior to surgery, the duration of surgery, or its technical difficulty. Vitreous cavity haemorrhage persisted at 12 weeks in two of the control group but none of the ranibizumab group.ConclusionRanibizumab pretreatment may improve the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy by reducing the extent of post-operative vitreous cavity haemorrhage. However, the effect size appears to be modest; we calculate that a definitive study to establish a minimally important difference of 5.9 letters at a significance level of P<0.05 would require 348 subjects in each arm.

The effect of intralesional steroid injections on the volume and blood flow in periocular capillary haemangiomas.

AIM: To examine the effect of steroid therapy on the volume estimates and blood flow characteristics of childhood periorbital capillary haemangiomas. PATIENTS AND METHODS: Children at risk of amblyopia due to periorbital haemangiomas were treated with intralesional steroid injections (between 1 and 4 courses) and serial assessment of the volume and blood-flow characteristics of the lesions measured using colour Doppler ultrasonography. The characteristics of the haemangiomas in these children were compared with a cohort of untreated cases. RESULTS: Eight of nine treated children were female, this proportion being significantly different from the equal sex distribution of an untreated cohort (p < 0.05). All children in the steroid-treated group presented within 1 month of birth, compared to the untreated children, who presented at an average of 2.1 months of age (range 0-14, median 2.9 months) (p = 0.04) and they required significantly longer follow-up in the Orbital service (mean 65 months, range 26-105), compared with an average of 35 months (range 4-92, median 23) in the untreated group (p = 0.002). The maximum estimated volume of the lesions were significantly larger in the treated group (treated group mean 8.9 ml, untreated group mean 4.1 ml; p = 0.016), with a trend towards higher maximum measured blood velocities in the treated group (treated mean 64 cm compared with untreated mean 52 cm; p = 0.1). Steroid injections appear to reduce the volume and blood flow of haemangiomas, this suppression persisting for several months (between 5 and 20) before the lesion later displays the cyclic fluctuations in volume and flow seen with untreated lesions. All treated haemangiomas had some residual vascular anomaly, detectable on ultrasonography, at last follow-up--this being despite absence of clinical signs in most cases. CONCLUSION: Periorbital capillary haemangiomas requiring steroid therapy for risk of amblyopia were significantly commoner in females, were larger lesions and presented at an earlier age. Intralesional steroids appear to cause a reduction of blood flow, with a transient reduction in volume and a suppression of the natural cyclic variation seen without treatment. The changes after a course of steroid therapy appear to last for between 5 and 20 months, this period of suppression of the lesion probably being particularly useful during infancy and early childhood when the child is at greatest risk of amblyopia.

Imaging the vitreous: optical coherence tomography and ultrasound imaging.

Imaging the vitreous in optically transparent and translucent ocular media using OCT and in optically opaque ocular media using ultrasound is discussed.Optical coherence tomography and colour flow mapping are briefly described. Images of tomograms, B-mode sections, and colour flow maps illustrate the use of these techniques in imaging the vitreous.

Natural history of periocular capillary haemangiomas: changes in internal blood velocity and lesion volume.

AIM: Although the clinical characteristics of childhood periocular capillary haemangiomas are well known, serial measurements of blood velocity and lesion size are unknown. This investigation was designed to measure the changes in maximum blood velocity and estimated size of lesion in children with capillary haemangioma not requiring active intervention. STUDY DESIGN: Retrospective case-note review for a cohort of children with capillary haemangioma involving the eyelid and orbit. PATIENTS AND METHODS: Children with periocular capillary haemangioma, under the care of the Orbital unit at Moorfields Eye Hospital between 1996 and 2005, were monitored clinically and with repeated ultrasonographic examination. Volume estimates were calculated as an ovoid based on the three maximum orthogonal measurements for the haemangioma, and blood velocity was assessed by Colour Flow Mapping, Colour Doppler Energy Imaging, and Spectral Doppler techniques using a Sequoia 512 Acuson scanner. RESULTS: Twenty-four children (12 boys) had initial assessment by 18 months of age, and the haemangioma increased in size in 14/24 (58%), the increase being between 4 and 931% of initial volume estimate. The largest measured size for an individual haemangioma appears inversely related to the child's age at measurement, this mirroring a similar trend in measurements for the maximum blood velocity. Blood velocity measurements also tend to decrease with time, the peak velocity being before 1 year of age in the majority (15/24; 62%). In many children, both volume estimates and blood velocities show a cyclic variation-this occurring with increasing intervals between the maxima, before a final decay in both parameters. Although, for the whole group, there was no correlation (correlation coefficient=0.29) between estimated size and measured blood velocity, some individual children showed a significant correlation between the two parameters. The age at maximum blood velocity appeared to precede the age at maximum volume in most children, and in many there was an orbital anomaly detectable on ultrasonographic examination, even with complete clinical resolution of the haemangioma. CONCLUSIONS: Ultrasonographic examination of periocular capillary haemangiomas show that these lesions have a very high blood velocity in feeding vessels-about 2-3 orders of magnitude greater than normal capillary beds-and that the velocity and volume of such lesions undergo a cyclic variation during their natural history. Evidence suggests that both velocity and volume decrease with time, although often not returning to zero on ultrasonography (unlike the clinical resolution of the lesions). In most children, blood velocity peaks before volume estimates and this might suggest that decreasing perfusion leads to later tissue atrophy and involution of the haemangioma.

Errors leading to unexpected pseudophakic ametropia.

PURPOSE: Determination of the reasons for clinically significant unplanned ametropia following cataract surgery and the results of management of the ametropia. METHODS: Retrospective review of 11 consecutive cases of tertiary referral for management of pseudophakic ametropia to the authors. Corrective surgery involved either lens implant exchange or LASIK refractive surgery. Final outcome was assessed by uncorrected and best spectacle corrected visual acuity and manifest refractive outcome. RESULTS: Five cases (45%) were due to significant error in axial length determination at pre-surgery biometry. Six cases (55%) were due to surgeon or surgical team error, where the surgeon implanted a lens of power at variance with that specified pre-operatively. Nine patients elected to undergo refractive surgery to correct the ametropia and 2 elected to wear a spectacle lens. Seven underwent lens implant exchange and 2 patients underwent LASIK keratorefractive surgery. Eight of nine patients were within 1 dioptre of intended spherical equivalent after refractive surgery and 1 patients was -1.5 dioptre myopic. CONCLUSIONS: Most cases of serious unintended ametropia after cataract surgery are avoidable. Care should be taken with the biometry and procedural checks to minimise error. When lens implant exchange or LASIK was performed the final refractive results were satisfactory.

Silicone intraocular lens compression and double lens implants in diseased eyes.

PURPOSE: To assess the outcomes of double lens implants in hyperoptic eyes with associated pathology. METHOD: Double lens implants were used in 4 eyes of 4 patients each with a different ophthalmic or neuro-ophthalmic disease. Biometry was performed in the standard contact fashion and lens power formulae used included SRK/T, Holladay and Hoffer Q. RESULTS: Average spherical equivalent refraction improved from +6.875 D to +0.38 D. Absolute average prediction error was greatest for SRK/T (2.65 D) and least for Holladay (1.73 D). Refractive suprises were influenced by the underlying disease process. One patient showed central lens compression. CONCLUSION: Underlying disease can produce biometry errors. Structural ophthalmic or neurological disease is not a contraindication to the use of double lens implants. Double lens implants are useful to correct refractive error in the presence of underlying disease.

A histological procedure to determine dental age.

Sclerosis of dentine has become one of the well established indicators of ageing and age determination. In this study a new technique was reported where a photomicrographic image of a cross section of sclerotic dentine was converted to a grey scale of 256 tones and then reduced to black and white and read by computer using specially developed software. A regression analysis was applied to a sample of 62 teeth (age range 17-84 years) and an age determination within an error limit of 11 years was obtained. Using a Neural Network software however the error was reduced to 8 years.

Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients.

OBJECTIVE: To document the clinical features, systemic associations, and visual outcome in a large number of patients with posterior scleritis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: There were 137 patient records showing patients with a diagnosis of posterior scleritis who were attending or had attended the scleritis clinic at Moorfields Eye Hospital between 1974 and 1996. Ninety-nine records were suitable for detailed analysis. METHODS: The medical records and B-mode ultrasound examinations were reviewed. MAIN OUTCOME MEASURES: The clinical features, systemic associations, treatment, and outcome of each patient were determined. RESULTS: Posterior scleritis occurred at all ages. The mean age at onset was 49.3 years. Posterior scleritis began before age 40 in 30% of patients and was twice as common in women as in men. The B-mode ultrasound examination showed diffuse and nodular changes in the posterior sclera. Necrotizing posterior scleritis was not identified. Twenty-nine percent of patients had an associated systemic disease that included systemic vasculidites, autoimmune diseases, and lymphoma. Such patients more commonly had nodular changes on B-mode ultrasound examination. Early treatment controlled posterior scleral inflammation and limited visual loss. Thirty-one percent of patients lost two or more lines of vision. Statistical analysis revealed that patients older than age 50 had an increased risk of having an associated systemic disease and were more likely to experience visual loss. Patients with associated systemic disease required more aggressive immunosuppressive therapy and more frequently had accompanying anterior scleritis. There was no association between unilateral, bilateral, or recurrent disease and the presence of systemic disease or visual loss from posterior scleritis. CONCLUSIONS: The B-mode ultrasound examination reveals that posterior scleritis occurs far more often than previously thought and can lead to rapid and permanent visual loss. All patients with posterior scleritis must be assumed to be at risk of visual loss. Forty percent of patients had no anterior scleral inflammation, and 9% had no detectable physical signs. All patients need to be investigated for an associated systemic disease and all require early treatment to minimize loss of vision.

Age determination by teeth examination: a comparison between different morphologic and quantitative analyses.

Age determination by teeth examination is one of the main means of determining personal identification. Current studies have suggested different techniques for determining the age of a subject by means of the analysis of microscopic and macroscopic structural modifications of the tooth with ageing. The histological approach is useful among the various methodologies utilized for this purpose. It is still unclear as to what is the best technique, as almost all the authors suggest the use of the approach they themselves have tested. In the present study, age determination by means of microscopic techniques has been based on the quantitative analysis of three parameters, all well recognized in specialized literature: 1. dentinal tubules density/sclerosis 2. tooth translucency 3. analysis of the cementum thickness. After a description of the three methodologies (with automatic image processing of the dentinal sclerosis utilizing an appropriate computer program developed by the authors) the results obtained on cases using the three different approaches are presented, and the merits and failings of each technique are identified with the intention of identifying the one offering the least degree of error in age determination.

Ultrasonic assessment of rhinostomy size following external dacryocystorhinostomy.

AIM: To assess the dimensions and patency of the surgical epithelial fistula after external dacryocystorhinostomy, using B mode ultrasonography to define the postoperative soft tissue anastomosis. METHODS: 12 patients undergoing 16 external dacryocystorhinostomies, with the creation of large osteotomies, were included in a prospective study. The horizontal and vertical dimensions of the bone ostium was recorded during surgery and compared with the ultrasonographic dimensions of the soft tissue anastomosis at 1 day, 2 weeks, and 6 months after surgery. Functional patency was confirmed with dye testing and irrigation. RESULTS: Compared with an osteotomy of between 100 and 380 mm2 (mean 235 mm2), the soft tissue anastomosis on the day after surgery was, in all cases, markedly smaller (72-252 mm2; mean 144 mm2, or 61% of the bone window). The soft tissue anastomosis decreased to between 8 and 208 mm2 (mean 98 mm2; 68% of immediate postoperative value) at 2 weeks and 3-208 mm2 (mean 71 mm2; 49% of immediate postoperative value) at 6 months. 14 of the 16 (88%) dacryocystorhinostomies were functional at the end of the study, the two failures being associated with marked contracture of the soft tissue anastomosis; the outcome of surgery correlated significantly with the area of the anastomosis at 2 weeks (chi 2 = 16.3; p < 0.01) and at 6 months (chi 2 = 16.0, p = 0.01). CONCLUSIONS: B mode ultrasonography provides a simple and effective method for assessing the size of the soft tissue anastomosis after external dacryocystorhinostomy and there is a significant reduction in size after surgery, to which the functional outcome of surgery appears related. As the initial soft tissue anastomosis cannot be larger than (and is, on average, about 60% of) the area of the osteotomy, this emphasises the paramount importance of a large rhinostomy to the success of lacrimal surgery.

[Circadian variation of sudden cardiac death in young people with and without coronary disease]. / Variazione circadiana della morte cardiaca improvvisa in una popolazione giovanile con e senza malattia coronarica.

Sudden cardiac death is not well known and provoking factors are yet mainly unknown. To clarify whether sudden cardiac death has a circadian rhythm in young people we have studied 40 patients < 45 years who died in Brescia between 1984 and 1993 of sudden cardiac death showing at autopsy features of coronary artery disease (CAD) and 12 patients aged < 30 years who died of sudden cardiac death without autoptic features of CAD. We observed a circadian rhythm in the hours of the morning in the two groups, more evident in patients without CAD. In patients with autoptic features of CAD, we also observed a higher rate of events during the winter months. We would like to stress the importance of the adrenergic system as a trigger able to produce the event. We believe that the role of the sympathetic nervous system is more important than other risk factors (for example platelet aggregability and blood viscosity) to precipitate sudden cardiac death, mainly because the circadian rhythm was more evident in patients without CAD. An increase of the data-base and a more detailed analysis of subgroups is necessary if we concretely want to prevent sudden cardiac death fitting antiarrhythmic therapy with circadian distribution of major events. We underline the practical impact of "chronorisk" together with the other cardiovascular risk factors.

Predictive factors for the development of rubeosis following proton beam radiotherapy for uveal melanoma.

AIMS/BACKGROUND: Proton beam radiotherapy can effectively treat primary uveal melanomas of any size. Some patients, however, develop adverse late effects following treatment and the purpose of this study was to determine which factors give rise to a poor local outcome. METHODS: The hospital records from a first cohort of 127 patients treated by protons from 1989 to 1992 were reviewed retrospectively. The presence of rubeosis was selected as a measure of significant ocular damage. Split file analysis was performed with 73 cases forming a test group with the remaining 54 cases acting as a validation group. RESULTS: Large tumour size and the presence of retinal detachment were significant, independent risk factors for developing rubeosis for both the test and validation groups. These factors also predicted subsequent enucleation for uncontrolled ocular pain. Patients with tumours too large to plaque and with an associated retinal detachment had a 90% chance of developing rubeosis within 4 years of proton beam radiotherapy. CONCLUSIONS: Patients with a uveal melanoma too large for plaque therapy and an associated retinal detachment run a very high risk of developing rubeosis after proton beam radiotherapy and one third of individuals developing rubeosis required enucleation for pain even if local tumour control was satisfactory.

[Ischemic cardiopathy in the young: coronarographic and autopsy picture in 100 subjects]. / La cardiopatia ischemica nel giovane: quadro coronarografico ed autoptico in 100 soggetti.

Many aspects of coronary artery disease in young people are not completely understood. Our study concerns a series of 100 patients < 45 years with acute coronary artery disease. Sixty patients survived and 40 died suddenly. All subjects have been divided into four groups: Group I includes 20 deceased patients with anatomic features of acute myocardial infarction. Group II includes 20 subjects dead without features of acute myocardial infarction. Group III includes 30 patients surviving the first acute myocardial infarction. Group IV includes 30 patients surviving unstable angina. The coronary arteries have been studied by anatomic dissection in Group I and II and with coronarography in Groups III and IV. The left main was only involved in Group I and II patients. Multivessel disease was more frequent in Group I and II, but the difference was not significant. These results underline that coronary artery disease with multivessel involvement is not rare in young patients. The rare occurrence of left main disease at coronary angiography could be the consequence of the natural preselection determined by sudden death.

Severe microcornea with anterior segment malformation in a mother and her son.

A male infant with microcornea, anterior segment dysgenesis and congenital cataracts, but with a normal ocular posterior segment is reported. His mother also had extreme microcornea, no useful vision from birth, but had globes of grossly normal size.

Orbital ultrasound in the ocular ischaemic syndrome.

The ocular ischaemic syndrome illustrates well the effects of hypoperfusion of the globe and is a useful model for studying disorders of the orbital circulation. Recent advances in orbital ultrasound techniques have provided a non-invasive method of examining flow velocities in the orbital vessels, particularly the ophthalmic artery. Orbital ultrasound studies were performed on 3 cases of the ocular ischaemic syndrome. Continuous or intermittent reversal of blood flow in the ophthalmic artery was seen in all cases. How this phenomenon relates to the symptoms and signs in affected patients, and the role of orbital ultrasound in the investigation of the ocular ischaemic syndrome, are discussed.

Ocular enlargement following infantile corneal opacification.

Congenital hereditary endothelial dystrophy (CHED) is not generally thought to be associated with other ocular abnormalities. Ultrasonography in a series of twenty eyes (ten patients) with CHED shows ocular enlargement similar to that occurring in uncomplicated axial myopia. There was an inverse relationship between the degree of enlargement and the visual acuity or visual result following penetrating keratoplasty suggesting that infantile corneal oedema sufficient to cause stimulus deprivation may result in abnormal enlargement of the globe.