Immune mechanisms in uveitis. What can be learned from in vivo imaging?

In many aspects, in vivo imaging is superior to other techniques, such as conventional histology, because it allows the stepwise process of leukocyte migration to be dissected. The potential uses of the in vivo imaging techniques have yet to be achieved. The transfer of lymphocytes with fluorescent dyes can be marked. APCs that ingest fluorescent antigen and use fluorescent antibodies specifically to label different types of APCs in the anterior segment can be identified. Combining these techniques could result in more exciting insights into uveitis and the mechanisms of the immune system. For example, one can confidently expect to be able to observe the extravasation of CFSE-marked DO11.10 T cells and their subsequent interaction with APCs containing red fluorescent OVA. The use of green fluorescent protein to measure the expression of various proteins has occurred in a variety of in vitro and in vivo models. To identify activated T cells specifically, heterozygous knock-in mice have been generated that have a cDNA for enhanced green fluorescent protein substituted for the IL-2 coding region on one allele [91]. Activated T cells from these IL-2-green fluorescent protein mice up-regulate the expression of the IL-2 gene and consequently synthesize the green fluorescent protein marker. The authors recently demonstrated the presence of these activated cells in vivo in the mouse iris [16]. With both the green fluorescent protein and the brighter yellow fluorescent protein the authors anticipate being able to detect in vivo the expression of various cytokines, such as IL-2, the Th1 cytokine IFN-gamma, or the Th2 cytokine IL-4, in T cells infiltrating the eye. First steps have been undertaken to establish in vivo imaging in human eyes. Toxicity of fluorescent dyes currently used for animal research and movement artifacts of the tissue under investigation amplified by the high magnification necessary for cell research, however, remain the major challenges to study leukocyte migration in human uveitis.     

What changes can we expect in the brain of glaucoma patients?

Elevated intraocular pressure in glaucoma can injure retinal ganglion cells and trigger the spread of disease to connected target vision structures of the brain. Glaucomatous degeneration has been observed in retrobulbar and intracranial optic nerve, lateral geniculate nucleus, and visual cortex of the brain. Oxidative damage and glutamate toxicity are implicated in transsynaptic central nervous system injury in glaucoma, similar to other neurodegenerative diseases. The perception of glaucoma as a disorder of "visual neurons" within the eye and brain may contribute to understanding progressive disease, and encourage comprehensive treatment strategies to prevent vision loss in glaucoma.     

What can we learn from the disc appearance about the risk factors in glaucoma?

The author has been involved in 3 studies, the multicentre collaborative normal-tension glaucoma study, a study of 4 phenotypes of glaucomatous disc appearances and their associations, and a study reporting on biostatistical evidence for 2 distinct chronic open-angle glaucoma populations. These studies have some common threads whose clinical implications are discussed.     

What hope for the future? GNAQ and uveal melanoma

Uveal melanomas (UM) are aggressive ocular tumours that spread to the liver. They are characterised by alterations of chromosome 3 and 8, which are highly predictive of a poor prognosis. Unfortunately, being able to identify those patients with aggressive disease has not, as yet, translated into improved survival. Recently, mutations of guanine nucleotide-binding protein G(q) subunit alpha (GNAQ, or G-alpha-q), which effectively turn it into a dominantly acting oncogene, have been identified in approximately half of UM. These mutations are specific to UM and other non-cutaneous melanomas, and are not found in normal tissues, thus making them potential therapeutic targets. Here, the authors review the background to GNAQ in UM and explore what makes it such an interesting target for the future treatment of patients.     

What is the signal in noise?

Visual perception is limited by both the strength of the neural signals, and by the noise in the visual nervous system; however, little is known about what aspects of the input noise the human visual system is sensitive to, i.e., what is the signal in noise? In order to investigate this question we asked observers to discriminate differences in the strength of one-dimensional white noise. We measured their response consistency and classification images and compared the results with an ideal energy detector. Our results and modelling show that discrimination of noise is limited by the observer's template (i.e., the weighted combination of energy in each stimulus component) plus higher order nonlinearities (systematic noise), and by sources of random internal noise. We found that systematic noise is present only near detection threshold. Surprisingly, we found that the human template is "adaptive"-- its shape depends on the spatial frequency band of the noise-suggesting that sensitivity to spatial noise is not simply determined via passive filtering.     

The Portsmouth-based glaucoma refinement scheme: a role for virtual clinics in the future?

Background

Glaucoma referrals continue to impart a significant burden on Hospital Eye Services (HES), with a large proportion of these false positives.

Aims

To evaluate the Portsmouth glaucoma scheme, utilising virtual clinics, digital technology, and community optometrists to streamline glaucoma referrals.

Method

The stages of the patient trail were mapped and, at each step of the process, 100 consecutive patient decisions were identified. The diagnostic outcomes of 50 consecutive patients referred from the refinement scheme to the HES were identified.

Results

A total of 76% of ‘glaucoma'' referrals were suitable for the refinement scheme. Overall, 94% of disc images were gradeable in the virtual clinic. In all, 11% of patients ‘attending'' the virtual clinic were accepted into HES, with 89% being discharged for community follow-up. Of referrals accepted into HES, the positive predictive value (glaucoma/ocular hypertension/suspect) was 0.78 vs 0.37 in the predating ‘unrefined'' scheme (95% CI 0.65–0.87). The scheme has released 1400 clinic slots/year for HES, and has produced a £244 200/year cost saving for Portsmouth Hospitals'' Trust.

Conclusion

The refinement scheme is streamlining referrals and increasing the positive predictive rate in the diagnosis of glaucoma, glaucoma suspect or ocular hypertension. This consultant-led practice-based commissioning scheme, if adopted widely, is likely to incur a significant cost saving while maintaining high quality of care within the NHS.     

What can physicians learn from the blogs of patients with uveitis?

AIM: To identify the sources of anxiety from patient blogs. MATERIALS AND METHODS: Blogs were identified using www.blogsearch.google.com. and the following noted: age, sex, location, type of uveitis, symptoms, and the sources of anxiety. RESULTS: 103 blogs were identified. Anterior uveitis was the most common type followed by multifocal choroiditis and sympathetic ophthalmia. Sources of anxiety include acute pain, redness, photophobia and visual loss, initial misdiagnosis and monetary expenses. CONCLUSIONS: Physicians should focus on pain relief and counsel on visual loss including its impact on career or livelihood needs. Patients seen in emergency situations need early referral.