Computer modelling study of the mechanism of optic nerve injury in blunt trauma.

AIM: The potential causes of the optic nerve injury as a result of blunt object trauma, were investigated using a computer model. METHODS: A finite element model of the eye, the optic nerve, and the orbit with its content was constructed to simulate blunt object trauma. We used a model of the first phalanx of the index finger to represent the blunt body. The trauma was simulated by impacting the blunt body at the surface between the globe and the orbital wall at velocities between 2-5 m/s, and allowing it to penetrate 4-10 mm below the orbital rim. RESULTS: The impact caused rotations of the globe of up to 5000 degrees /s, lateral velocities of up to 1 m/s, and intraocular pressures (IOP) of over 300 mm Hg. The main stress concentration was observed at the insertion of the nerve into the sclera, at the side opposite to the impact. CONCLUSIONS: The results suggest that the most likely mechanisms of injury are rapid rotation and lateral translation of the globe, as well as a dramatic rise in the IOP. The strains calculated in the study should be sufficiently high to cause axonal damage and even the avulsion of the nerve. Finite element computer modelling has therefore provided important insights into a clinical scenario that cannot be replicated in human or animal experiments.

Regression of invasive conjunctival squamous carcinoma in an HIV-positive patient on antiretroviral therapy.

Case history of an African woman presenting with advanced HIV and a painful conjunctival lesion is presented. A conjunctival biopsy revealed invasive squamous cell carcinoma, with orbital invasion on computed tomography scan. She was commenced on antiretroviral therapy. She refused surgery to remove the eye and orbital contents (exenteration), and was referred to palliative care. Gradually, her immune status and ocular symptoms improved. At ophthalmic review, the tumour had apparently completely regressed. This unprecedented phenomenon may be due to antiretroviral therapy. Discussion covers conjunctival carcinoma and behaviour of HIV-related tumours with antiretroviral therapy. Antiretroviral drugs may offer a better alternative to disfiguring surgery in the future.

A computational study of the passive mechanisms of eye restraint during head impact trauma.

A finite element model of the eye and the orbit was used to examine the hypothesis that the orbital fat provides an important mechanism of eye stability during head trauma. The model includes the globe, the orbital fat, the extra-ocular muscles, and the optic nerve. MRI images of an adult human orbit were used to generate an idealized geometry of the orbital space. The globe was approximated as a sphere 12 mm in radius. The optic nerve and the sclera were represented as thin shells, whereas the vitreous and the orbital fat were represented as nearly incompressible solids of low stiffness. The orbital bone was modelled as a rigid shell. Frontal head impact resulting from a fall onto a hard floor was simulated by prescribing to the orbital bone a triangular acceleration pulse of 200 g (1962 m/s(2)) peak for a duration of 4.5 ms. The results show that the fat provides the crucial passive mechanism of eye restraint. The mechanism is a consequence of the fact that the fat is incompressible and that its motion is restricted by the rigidity of the orbital walls. Thus, the acceleration loads of short duration cannot generate significant distortion of the fat. In contrast, the passive muscles provide little support to the globe. When the connection between the orbital fat and the eye is absent the eye is held mainly by the optic nerve. We discuss the possible role that this loss of contact may have in some cases of the evulsion of the eye and the optic nerve.

The pathology of whiplash maculopathy and retinopathy : Illustrated observations derived from a fatal roller-coaster accident.

We present a single case report of a 20-year-old female who died following a severe whiplash head and neck injury sustained during a roller-coaster incident. We present the pathology of her eyes, which we believe to be the first pathological illustration of whiplash maculopathy and retinopathy to be reported within the medical literature. This article presents the macroscopic and microscopic pathology identified in this case and discusses the possible causation of the findings.

Mechanistic hypothesis for eye injury in infant shaking : An experimental and computational study.

The terms abusive head injury and shaken baby syndrome are used to describe a unique pattern of nonaccidental traumatic injuries occurring in children that many clinicians and researchers have good reason to believe is caused by violent shaking. Typical injuries include severe brain injury, with intracranial and retinal hemorrhages, but the pathogenesis of injuries is poorly understood. A major paradox in head trauma in infants is that the injuries induced by a shaking event are much more severe than those caused by even very violent single-impact head trauma, despite the relatively low accelerations in shaking.We have developed a finite element computer model of the eye, orbit, and orbital bone and used it to simulate the effects of single-impact and oscillatory motion inputs. The model was informed by data from semiquantitative in vitro anatomical traction experiments on in situ rabbit eyes. The new results reported here strongly suggest that suction between the eye and its surrounding fat dominates the dynamical stability of the system composed of the eye, its socket, and the components and material supporting the eye. Computer simulations incorporating this functional anatomical relationship show that deceleration of the head generates pressure gradients inside and outside the eye; these could cause damaging shear stresses in structures such as the retina and blood vessels. Simulations also show that oscillating the bone of the orbit causes the eye to move anteriorly and posteriorly with an increasing amplitude, building up the stresses within the eye over time. This is the first time that any biomechanical mechanism has been identified that might explain the disproportionally severe injuries caused by an oscillatory mechanism such as violent shaking of an abused infant. However, further study is required and this conclusion is therefore preliminary and provisional.

Eccrine hidrocystoma of the eyelid.

AIM: To report on the clinical features of eccrine hidrocystoma involving the eyelid. METHODS: Data on a series of consecutive patients with histopathologically confirmed diagnosis were reviewed. RESULTS: Among 34 patients, 69 tumours were identified. The mean age at diagnosis was 59 years (range 39-91 years). The majority (71%) of patients had only a single tumour. The tumours appeared as a small (median size=1 mm) clear cystic lesion with 87% located near the eyelid margin. CONCLUSIONS: The eccrine hidrocystoma is a benign small cystic tumour that characteristically occurs close to but does not involve the eyelid margin.

Unintentional inversion of corneal buttons during penetrating keratoplasty: clinico-pathological report of two cases.

AIM: This report describes the clinico-pathological features of unintentionally inverted corneal buttons in two patients. METHODS: A clinico-pathological report. RESULTS: Two patients who underwent repeat keratoplasty for failed grafts were found to have inverted corneal buttons on histopathological examination. A detailed description of the pathological features of the inverse keratoplasty and the clinical outcome after repeat keratoplasty is presented. CONCLUSION: Inadvertent inverse keratoplasty should be considered as a rare cause of corneal graft failure. The serious complication of anterior chamber epithelialization seems to be unlikely and the prognosis following repeat penetrating keratoplasty appears to be very good.

Prediction of prognosis in patients with uveal melanoma using fluorescence in situ hybridisation.

BACKGROUND/AIMS: Uveal melanoma is the commonest malignancy of the eye, with a high proportion of patients dying of metastatic disease. Tumours showing a loss of chromosome 3 and gains of chromosome 8 are associated with a worse prognosis. The efficiency of fluorescence in situ hybridisation (FISH) in determining copy numbers of these chromosomes was assessed in individual tumours and related to patient survival. METHODS: 33 fresh frozen samples were analysed with centromeric probes for chromosomes 3 and 8. Patient outcomes were divided into two groups: (1) absence of genetic abnormalities (no genetic imbalance) and (2) presence of genetic abnormalities (genetic imbalance). The log rank test was used to compare survival, which was represented by Kaplan-Meier survival curves. RESULTS: Of the 33 tumours analysed, 16 showed evidence of genetic imbalances. Of these 16 tumours, 14 patients had died by the end of the study, with 10 having died of liver metastases. Of the tumours without evidence of genetic imbalances, five patients had died by the end of the study, although none had died as a result of either liver metastases or from the primary uveal melanoma. The difference in survival between the two groups was highly significant (p<0.0001). CONCLUSION: The authors have shown that FISH analysis for chromosome 3 and 8 is a reliable and efficient technique in the analysis of fresh frozen tumour specimens and is valuable in the prediction of prognosis in individuals with uveal melanomas.

Expression of integrins, degradative enzymes and their inhibitors in uveal melanoma: differences between in vitro and in vivo expression.

Posterior uveal melanoma is the most common intraocular malignancy in adults. Metastasis occurs in approximately 40% of all cases and spread is primarily to the liver. Once secondary hepatic disease has developed the prognosis is poor. Metastasis involves a series of adhesion and de-adhesion events, coupled with regulated tissue degradation to facilitate tumour cell invasion and spread to both local and distant sites. These processes are assisted by the expression of integrins and degradative enzymes by both tumour and host cells. Using a series of 10 uveal melanomas, we investigated the expression of a panel of integrins, degradative enzymes and their inhibitors that have been shown to be associated with metastasis. In addition, we undertook to establish if there might be differential expression in response to growth under artificial conditions. All the tumours expressed matrix metalloproteinases (MMP)-2 and-9, tissue inhibitor of metalloproteases (TIMP)-2, urokinase plasminogen activator (u-PA), plasminogen activator inhibitor (PAI)-1 and PAI-2. Differences in the expression of the integrins alpha1beta1, alpha2beta1 and alpha6beta1 were observed; in particular, these differences appeared to relate to expression as a consequence of growth in culture. In summary, uveal melanoma cells express both degradative enzymes and their respective inhibitors, which are important in metastasis. It would appear that differential expression of integrins is present, probably as a response to in vitro stimulation.

Reduced expression of TAP-1 and TAP-2 in posterior uveal melanoma is associated with progression to metastatic disease.

In order to determine the effects of the loss or reduced expression of molecules associated with antigen presentation (transporter associated with antigen presentation [TAP]-1, TAP-2, low molecular weight protein [LMP]-2 and LMP-7), we examined the expression of these molecules in primary uveal melanoma lesions. Paraffin-embedded sections from 29 primary uveal melanoma lesions were analysed for expression of TAP-1, TAP-2, LMP-2 and LMP-7 using specific primary antibodies followed by a three-stage immunoperoxidase technique. Microscopic examination was undertaken to determine differences in expression of these molecules on the tumour and the surrounding stroma. Overall, 72% (21 out of 29) of the tumours showed some loss or reduced expression of TAP-1, TAP-2, LMP-2 and/or LMP-7. Statistical analysis of these results showed that progression to metastatic disease was strongly associated with reduced expression of TAP-1 (P < 0.05) and TAP-2 (P < 0.01), taking patient age, tumour site and histology into account. We conclude that the reduced expression of molecules important in eliciting an immune response, such as TAP-1 and TAP-2, may facilitate the metastatic spread of uveal melanoma lesions and may have important implications for prospective immunotherapy.

ACP Best Practice No 164: Necropsy techniques in ophthalmic pathology.

Much important information can be obtained at necropsy by the pathological examination of the eye and its adnexal structures in adults and children. This information may be related to the cause of death (for example, violent shaking trauma in physical child abuse), or may pertain to disease processes affecting the eye, the orbit, and surrounding structures outside the orbit. This article reviews the technical methods used to remove the following: the vitreous (for example, for biochemistry); the eye itself (anterior approach); the eye and orbital contents (posterior approach); the eye, orbit and orbital walls; and the eye, orbital walls, and surrounding structures. The removal of the eye and adnexal ocular structures must be recognised as a "culturally sensitive" issue, which must be approached cautiously. It should only be undertaken for sound scientific reasons, with the fully informed consent of the relatives and/or the coroner (or equivalent authority), and with properly agreed procedures for the eventual retention or disposal of the ocular tissues. For this reason, this article reviews not only the scientific indications and methods for the removal of such tissues, but also the legal and ethical issues that must underpin this pathology "best practice".