Clinical features associated with survival of patients with lymphoma of the ocular adnexa.

PURPOSE: Although systemic or eyelid involvement by ocular adnexal lymphoma carries a worse prognosis, there have been few reports of the outcome in relation to clinical presentation. The outcome of malignant ocular adnexal lymphoma was, therefore, related to presenting clinical symptoms and signs. DESIGN AND METHODS: A retrospective, noncomparative case-note review of 326 patients treated in the Orbital Clinic at Moorfields Eye Hospital. The associations between presenting symptoms or signs and three outcome measures (v.i.) were assessed by univariate and multiple variable regression together with Kaplan-Meier analysis. MAIN OUTCOME MEASURES: (i) Presence of extra-orbital disease at the time of presentation; (ii) development of systemic lymphoma after new presentation with solely ocular adnexal disease; and (iii) death attributable to widespread lymphoma. RESULTS: Presentation with disseminated disease was rarer with over 1 year's ophthalmic symptoms (odds ratio (OR) 0.7; 95% CI 0.5-0.9) and much more frequent with bilateral adnexal disease (OR 5.8; 95% CI 3.0-11.2). With solely adnexal disease at presentation, subsequent extra-orbital lymphoma was more frequent and earlier with lacrimal gland disease (as compared to those without; hazard ratio (HR) 1.9; 95% CI 1.2-4.5) or with eyelid disease (compared to those without; HR 2.4; 95% CI 1.2-4.5), or with bilateral disease (compared to unilateral disease; HR 2.6; 95% CI 1.4-5.2). Prior or concurrent systemic disease was the most significant predictive factor for lymphoma-related death (HR 6.8; 95% CI 4.3-10.9), but tumour-related death was also commoner and earlier with bilateral disease (HR 2.4; 95% CI 1.4-4.0) or where a relative afferent papillary defect was present (HR 2.8; 95% CI 1.6-4.9). Similarly, the rate of tumour-related death was slightly less where symptoms had been present for more than a year (HR 0.8; 95% CI 0.7-1.0) and slightly greater in the elderly (HR 1.03; 95% CI 1.01-1.05). Conjunctival lymphoma had the lowest rate of extra-orbital spread and lymphoma-related death, the rate of these two events being sequentially greater for patients with predominantly deep orbital lymphoma, lacrimal gland lymphoma, or eyelid lymphoma. CONCLUSION: These data suggest that presenting symptoms and signs of patients with ocular adnexal lymphoma are significantly associated with the risk of systemic disease at orbital presentation, the rate of subsequent spread, and the rate of lymphoma-related death.

Clinical, radiological and pathological examination of periocular dermoid cysts: evidence of inflammation from an early age.

INTRODUCTION: Periocular dermoid cysts are common and leakage of the lipid or keratin contents leads to an inflammation-often asymptomatic-around the cyst, which may cause adherence of the dermoid cyst to neighbouring structures. PURPOSE: To investigate the frequency of clinical and radiological signs of inflammation with periocular dermoid cysts, to relate this to the histopathological examination of the excised specimens, and to assess whether the degree of inflammation is related to age at presentation. PATIENTS AND METHODS: A retrospective non-comparative series of 124 patients with periocular dermoid cysts that had undergone imaging. Case-notes were reviewed for clinical and histopathological details and there was independent review of the radiological imaging. RESULTS: Surgery was undertaken at between 1 and 66 years of age, most patients being under 10 years, and the duration of symptoms varied from 4 weeks to 30 years. Symptoms of inflammation-mainly intermittent lid swelling with localised redness and pain-occurred in all age groups, the proportion being greatest in the fourth decade. Clinical signs of inflammation at the time of clinic visit were relatively few, although 8% had some localised erythema and 7% had tenderness at the site of lesion. In more than two-thirds of the excised cysts, pathological examination demonstrated various degrees of chronic inflammation, even in those cysts removed before the age of 5 years. CONCLUSION: Even if the patient does not have symptoms or signs of inflammation, most periocular dermoid cysts show histological evidence of inflammation due to leakage of the lipid and keratin contents from the cyst, the incidence being similar at all ages.

Primary orbital melanoma masquerading as vascular anomalies.

PURPOSE: To review two cases of primary orbital melanoma presenting like orbital vascular anomalies. METHODS: Retrospective review of clinical presentation, treatment, radiology and pathology for two patients under the care of the Orbital Clinic at Moorfields Eye Hospital. RESULTS: Both lesions presented with the appearance and behaviour of vascular anomalies. In one case, a spindle cell melanoma appeared to be a low flow vascular anomaly with a loculated secondary haemorrhage and, in the other case, a melanoma of soft parts was considered to be an arteriovenous malformation and responded partially to embolisation. CONCLUSION: Primary malignant melanoma may present as a secondary vascular lesion of the orbit and this very rare tumour should be considered in the differential diagnosis of any vascular anomaly.

Infratentorial hypointense lesion volume on T1-weighted magnetic resonance imaging correlates with disability in patients with chronic cerebellar ataxia due to multiple sclerosis.

In multiple sclerosis (MS), hypointense lesions on T1-weighted magnetic resonance imaging are thought to represent areas of tissue disruption and axonal loss. In previous studies of MS patients, infratentorial T1 hypointense lesions were found to be rare. In MS patients selected to have chronic cerebellar ataxia, we have determined the extent of infratentorial T1 hypointense lesions and their relationship with disability. We recruited nine patients with chronic cerebellar ataxia due to MS. An expanded disability status scale (EDSS) assessment was performed on each. The patients' brains were then imaged with axial-oblique dual-echo fast spin-echo and contrast-enhanced T1-weighted conventional spin-echo sequences. The number and total volume of infratentorial high-signal lesions on T2-weighted images and infratentorial hypointense lesions on T1-weighted images were calculated by a blinded observer using a computer-assisted contouring technique. A total of 96 infratentorial high-signal lesions were present, of which 62 (64.6%) appeared isointense and 34 (35.4%) hypointense with respect to the surrounding brain substance on the T1-weighted images. There was a median of 3 (range 0-10) and median volume of 0.43 ml (range 0-0.85 ml) infratentorial T1 hypointense lesions per patient. The EDSS score correlated with both the number (r=0.68, p=0.043) and the volume per patient (r=0.89, p=0.001) of infratentorial T1 hypointense but not T2 high-signal lesions. Infratentorial T1 hypointense lesions are often seen in patients with MS and chronic cerebellar ataxia. They may play a significant role in the disability suffered by these patients.

Detection of optic nerve atrophy following a single episode of unilateral optic neuritis by MRI using a fat-saturated short-echo fast FLAIR sequence.

We describe an MRI technique for quantifying optic nerve atrophy resulting from a single episode of unilateral optic neuritis. We imaged 17 patients, with a median time since onset of optic neuritis of 21 months (range 3-81 months), using a coronal-oblique fat-saturated short-echo fast fluid-attenuated inversion-recovery (sTE fFLAIR) sequence. The mean cross-sectional area of the intraorbital portion of the optic nerves was calculated by a blinded observer from five consecutive 3 mm slices from the orbital apex forwards using a semiautomated contouring technique and compared with data from 16 controls. The mean optic nerve area was 11.2 mm2 in the affected eye of the patients, 12.9 mm2 in the contralateral eye (P = 0.006 compared to the affected eye) and 12.8 mm2 in controls (P = 0.03 compared to the affected eyes). There was a significant negative correlation between disease duration and the size of the affected optic nerve (r = -0.59, P = 0.012). The measurement coefficient of variation was 4.8%. The sTE fFLAIR sequence enables measurement of optic nerve area with sufficient reproducibility to show optic nerve atrophy following a single episode of unilateral optic neuritis. The correlation of increasing optic nerve atrophy with disease duration would be consistent with ongoing axonal loss in a persistently demyelinated lesion, or Wallerian degeneration following axonal damage during the acute inflammatory phase.

Major orbital complications of endoscopic sinus surgery.

BACKGROUND: The paranasal sinuses are intimately related to the orbit and consequently sinus disease or surgery may cause severe orbital complications. Complications are rare but can result in serious morbidity, the most devastating of which is severe visual loss. METHODS: A retrospective review was undertaken of four cases of severe orbital trauma during endoscopic sinus surgery. RESULTS: All the cases suffered medial rectus damage, one had additional injury to the inferior rectus and oblique, and two patients were blinded as a result of direct damage to the optic nerve or its blood supply. CONCLUSION: Some ophthalmic complications of endoscopic sinus surgery are highlighted, the mechanisms responsible are discussed, and recommendations for prevention, early recognition, and management are proposed.

Assessing the risk of early multiple sclerosis in patients with clinically isolated syndromes: the role of a follow up MRI.

OBJECTIVES: With increasing evidence that permanent tissue damage occurs early in the course of multiple sclerosis, it is important that treatment trials include patients in the earliest stages of the disease. For many patients with multiple sclerosis the first presentation is a clinically isolated syndrome. Not all patients with a clinically isolated syndrome develop multiple sclerosis, however, and treatment of all such patients would be unwarranted. A single abnormal brain MRI identifies patients at a higher risk for the early development of multiple sclerosis, but current criteria are limited by either poor specificity (T2 lesions) or sensitivity (contrast enhancing lesions). The aim of the study was to assess the positive predictive value, sensitivity, and specificity of MRI indices for the development of multiple sclerosis after 1 year from two MRI examinations obtained 3 months apart. METHODS: MRI examinations were performed in 68 patients with a clinically isolated syndrome, with a clinical assessment after 1 year. RESULTS: Contrast enhancing lesions at both time points were the most predictive indices for developing multiple sclerosis (positive predictive value 70%) but had low sensitivity (39%). The combination of T2 lesions at baseline with new T2 lesions at follow up had the best overall positive predictive value (53%), sensitivity (83%), and specificity (76%). In patients with T2 lesions at baseline, the presence or absence of new T2 lesions at follow up significantly altered the risk of multiple sclerosis within 1 year (55% and 5% respectively, p<0.001). Multiple sclerosis also developed in 10% of patients with a normal baseline MRI. CONCLUSIONS: Serial imaging in patients with clinically isolated syndromes improved the positive predictive value, sensitivity, and specificity of MRI for the development of early multiple sclerosis and also identified patients at a lower risk of early multiple sclerosis than would have been expected from their abnormal baseline MRI. Selection of patients with clinically isolated syndromes for therapeutic intervention or clinical trials may benefit from serial MRI, to target those at greatest risk of early development of multiple sclerosis.

In vivo 1H-magnetic resonance spectroscopy of the spinal cord in humans.

Magnetic resonance spectroscopy (MRS) has been used in a variety of conditions affecting the central nervous system. Until now, only the brain has been studied, and spectroscopy of the spinal cord has not been previously reported. During the past 12 months, we have been experimenting with MRS of the cervical spinal cord of healthy volunteers. We present this technique, its current limitations, and possible future technological improvements and potential applications.

Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival.

BACKGROUND: The histological characteristics of ocular adnexal lymphomas have previously provided only a limited guide to clinical outcome for affected patients. This clinicopathological relation was re-examined using the Revised European American Lymphoma (REAL) system to classify the tumours in a large cohort of patients. METHODS: The biopsies and clinical follow up data for 192 patients with ocular adnexal lymphoma were reviewed, the biopsies being regraded in accordance with the REAL classification. For each of five histological groups, logistic regression analysis was used to determine the odds ratios (OR) for the presence of systemic disease at the time of orbital diagnosis and Cox regression analysis was used to assess the hazard ratios (HR) for disseminated disease and lymphoma related death. For 108 patients in whom extraorbital spread occurred, the histological category of lymphoma was compared with the sites of dissemination. RESULTS: At presentation, the frequency of previous or concurrent extraorbital disease increased from marginal zone lymphoma (OR 1.0), diffuse lymphoplasmacytic/lymphoplasmacytoid lymphoma (OR 2.3), follicle centre lymphoma (OR 3.8), diffuse large B cell lymphoma (OR 4.0) to other histological lymphoma variants (OR 26.8). For all histological types, the estimated risk of extraorbital disease and lymphoma related death continued for many years and the proportion of patients with at least one extraorbital recurrence after 5 years was 47% for MZL, 48% for LPL, 64% for FCL, 81% for DLCL, and 95% for other lymphoma variants. The corresponding estimated rates for 5 year lymphoma related mortality were 12%, 19%, 22%, 48%, and 53% respectively. CONCLUSIONS: Patients with ocular adnexal lymphoma can be classified by REAL into five distinct groups, which show a progressive increase in the risks of extraorbital disease at diagnosis, of disease dissemination with time, and of tumour related death.

The value of intubation dacryocystography after dacryocystorhinostomy.

We retrospectively reviewed 104 dacryocystograms carried out on 72 patients who had previously undergone dacryocystorhinostomy, to assess the diagnostic contribution of the radiological investigation in patients with persistent or recurrent symptoms. In patients whose symptoms were referable to the operated side, dacryocystography was performed as part of further pre-operative assessment. In 42% of these patients it demonstrated an anatomical or physiological abnormality that explained the symptoms. However, no clear reason for the recurrence of symptoms was demonstrated in 58% of cases.

MRA versus digital subtraction angiography in acute subarachnoid haemorrhage: a blinded multireader study of prospectively recruited patients.

We performed a blinded multireader study comparing MR angiography (MRA) with digital subtraction angiography (DSA) in 34 prospectively recruited patients who presented with acute subarachnoid haemorrhage (SAH). Two observers independently reviewed the MRA and DSA studies some months after clinical presentation. Presence of an aneurysm was rated on a 4-point confidence scale. Cases in which the initial interpretation of the observers varied were jointly reviewed to reach a consensus opinion. DSA was deliberately chosen not to represent the reference standard and the clinical course and surgical findings were used to explain significant differences between the consensus readings of MRA and DSA. Diagnostic confidence and interobserver agreement were, overall, higher on DSA than on MRA studies (kappa DSA = 0.64 versus kappa MRA = 0.52 with 95% CI for delta = kappa DSA-kappa MRA [-0.06, 0.31]). With both methods, discrepancies between observers were due to aneurysms overlooked rather than false-positive readings by one observer. Diagnostic accuracy therefore improved when the readings of the two observers were combined, particularly for MRA. Intermethod agreement was only fair and similar for both readers (kappa reader 1 = 0.37 versus kappa reader 2 = 0.32 with 95% CI for delta = kappa reader 1-kappa reader 2 [-0.02, 0.11]). Both interobserver and intermethod agreements improved when the data were analysed on a per-study (positive or negative study) rather than on a per-aneurysm basis. Differences in the consensus reading were due to five aneurysms (four single and one multiple) detected only with MRA and five (two single and three multiple) detected only with DSA. MRA and DSA should be regarded as complementary in the investigation of patients with acute SAH. DSA can no longer be regarded as the reference standard.

MRI of the intraorbital optic nerve in patients with autosomal dominant optic atrophy.

Measurements of the intraorbital optic nerve were made using high-resolution coronal MRI in 10 adults with autosomal dominant optic atrophy. Comparisons were made with previous studies of 10 normal adult subjects. The cross-sectional diameters of the optic nerve and the perineural subarachnoid space were measured and a ratio of there diameters at anterior, mid and posterior positions along the optic nerve was determined. We found a statistically significant difference in the mean optic nerve: sheath ratio between the control group and patients with autosomal dominant optic atrophy. At anterior, mid and posterior locations along the optic nerve it is significantly smaller in patients with optic atrophy. We have demonstrated that the loss of ganglion cells, previously documented in dominant optic atrophy, is associated with a significant loss of optic nerve tissue and thinning of the nerve along its length.

Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a functional magnetic resonance imaging study.

OBJECTIVES: Recovery to normal or near normal visual acuity is usual after acute demyelinating optic neuritis, despite the frequent persistence of conduction abnormalities as evidenced by the visual evoked potential (VEP). This raises the possibility that cortical adaptation to a persistently abnormal input contributes to the recovery process. The objective of this study was to investigate the pattern of cerebral response to a simple visual stimulus in recovered patients in comparison to normal subjects. METHODS: Functional magnetic resonance imaging (fMRI) was used to study the brain activation pattern induced by a periodic monocular 8Hz photic stimulus in seven patients who had recovered from a single episode of acute unilateral optic neuritis, and in seven normal controls. VEPs and structural optic nerve MRI were performed on patients. RESULTS: Stimulation of either eye in controls activated only the occipital visual cortex. However, in patients, stimulation of the recovered eye also induced extensive activation in other areas including the insula-claustrum, lateral temporal and posterior parietal cortices, and thalamus; stimulation of the clinically unaffected eye activated visual cortex and right insula-claustrum only. The volume of extraoccipital activation in patients was strongly correlated with VEP latency (r = 0.71, p = 0.005). CONCLUSIONS: The extraoccipital areas that were activated in patients all have extensive visual connections, and some have been proposed as sites of multimodal sensory integration. The results indicate a functional reorganisation of the cerebral response to simple visual stimuli after optic neuritis that may represent an adaptive response to a persistently abnormal input. Whether this is a necessary part of the recovery process remains to be determined.

Spots before the eyes: a prevalence and clinicoradiological study of senile scleral plaques.

AIMS: To investigate the prevalence and clinical associations of senile scleral plaques. METHODS: Unselected, consecutive computed tomographic (CT) images of elderly people were reviewed for the presence of calcification indicating senile scleral plaques. RESULTS: No definite calcification was seen in 100 men or 100 women aged 60-69 years; equivocal changes were seen in one woman. There were three definite examples and one equivocal case of calcification in 100 women and four definite cases in 100 men aged 70-79 years. However, in a group of 71 men and women patients aged 80 years or more, 16 definite cases were seen, indicating a prevalence of 22%. CONCLUSIONS: Apart from advanced age, and a mild association with the extent of calcification of the carotid siphon, no clinical or radiological features were identified which consistently characterized a total of 28 patients with this form of ocular calcification; an association with cataract probably reflected simply the recruitment base. Scleral plaques would appear to be a degenerative phenomenon without clinical significance, most likely to be detected in patients presenting with unrelated ophthalmological complaints.

Radiological and clinicopathological features of orbital xanthogranuloma.

BACKGROUND: Orbital xanthogranuloma, a diagnosis confirmed histologically, occurs rarely in adults and children. With its characteristic macroscopic appearance the adult form may be associated with a spectrum of biochemical and haematological abnormalities including lymphoproliferative malignancies. METHOD: The clinicopathological features and imaging appearances on computed tomography and magnetic resonance imaging of this condition are described in eight adults and a child. RESULTS: Radiological evidence of proptosis was present in seven patients. In all nine patients an abnormal infiltrative soft tissue mass was seen, with increased fat in six cases. All patients had associated enlargement of extraocular muscles suggestive of infiltration and five had lacrimal gland involvement. Encasement of the optic nerve, bone destruction, and intracranial extension was present only in the child with juvenile xanthogranuloma. Haematological and/or biochemical abnormalities were detected in seven patients and seven patients had other systemic diseases which were considered to have an immune basis. One patient subsequently developed non-Hodgkin's lymphoma. CONCLUSION: The investigation and management of orbital xanthogranulomas requires a multidisciplinary approach even though the diagnosis may be suspected clinically. Imaging delineates the extent of disease and involvement of local structures and may influence the differential diagnosis. The juvenile form may be more locally aggressive, causing bone destruction with consequent intracranial extension.

The neuroimaging evidence for chronic brain damage due to boxing.

A number of imaging techniques have been used to investigate changes produced in the brain by boxing. Most morphological studies have failed to show significant correlations between putative abnormalities on imaging and clinical evidence of brain damage. Fenestration of the septum pellucidum, with formation of a cavum, one of the most frequent observations, does not appear to correlate with neurological or physiological evidence of brain damage. Serial studies on large groups may be more informative. Magnetic resonance spectroscopy and cerebral blood flow studies have been reported in only small numbers of boxers; serial studies are not available to date.