Research Lecture Advance Programme 2003/04

Vision Science and its Clinical Applications

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Abstracts

Spare the Rod and Spoil the Eye

The retina is an outgrowth of the brain, but it suffers from disease in a quite different manner to other neural tissues. The reason must be that there are "local factors" in the eye that make it susceptible to disease. The most obvious local factor is the presence of photoreceptors- 6 M cones, and 140 M rods. These have unique properties, which make them susceptible to damage. This talk gives the evidence that the two main causes of blindness- diabetes, and age- related macular degeneration- are due to the unestrained activity of photoreceptors. This hypothesis also explains the natural history the histopathology, and suggests ways of preventing these conditions.

An overview of information colour coding in the cockpit and associated analysis of visual fitness for the task

In the cockpit, colour coding is used to select, gather or quantify information. So, any loss or ambiguity in colour perception may dramatically impair the pilot's performance.

First, a review of colour displays over time exhibits the main changes that occurred in the human machine interface. Initially, sparse and localized coloured signals were supported by isolated lights or by secondary light sources, partially reflecting a range of wavelength. Nowadays, in the glass cockpit concept, increasing the number of hues involved in colour coding has led to a much higher amount of information displayed meanwhile keeping the user's workload acceptable. Coloured areas are in spatial contiguity and may overlap in emissive panels. This is a great change regarding the visual properties of colour perception.

Second, colour testing in the course of medical fitness assessment, is considered in relation with the operational use of colour in the cockpit. Most of the tests are derived from the clinical domain to ensure that the observer is free of any colour perception impairment. Tests based on an actual aeronautical use of colour are rather rare. Even in this latter case, they were developed to cover the traditional involvement of colour in the instrument panel (such as the chromoptometric Beyne's lantern).

Third, the main characteristics of an appropriate colour test are discussed. The visual display should reproduce the main luminous and chromatic parameters of the electronic in-flight panels. The size and the spatial arrangement of coloured patterns should replicate the range of the potential applications and discrimination of hues should be achieved for isoluminant stimuli. The entire set of original hues should be tested.

The visual properties involved in the task must be taken into account when selecting a fitness assessment. Colour use in the cockpit changes overtime, colour perception testing must be updated.

Towards a definition of "normal" colour vision

Although colour processing is probably the best understood aspect of vision, many observed differences in colour matching and chromatic sensitivity, both in normal trichromats and colour deficient observers, remain poorly understood. In this talk I propose to explore the main factors that cause intersubject differences in chromatic signals, and to show how such differences affect the outcome of colour matching and colour discrimination thresholds.

Novel experimental techniques yield more accurate measurements of changes in chromatic sensitivity and this has resulted in better understanding of "normal" colour vision and a useful, functional definition for the standard "normal trichomat". Examples of clinical applications of the use of such techniques will be presented. This new approach makes it easier to detect abnormal responses, to quantify the severity of chromatic sensitivity loss and to identify the parameter changes that are likely to have caused this loss.

Intrinsically photosensitive retinal ganglion cells in mammals: functions and mechanisms

In mice, a number of non-image forming light responses, including the pupillary light reflex survive the complete loss of rod and cone photoreceptors. The non-rod non-cone photoreceptors that drive these responses employ an opsin photopigment with a *max around 480nm and reside in the inner retina. Their cellular identity has recently been addressed. It seems that a subset of retinal ganglion cells that project to the suprachiasmatic nuclei (SCN) of the hypothalamus, the site of the primary circadian clock in mammals, are intrinsically photosensitive. These cells contain the putative photopigment melanopsin. Melanopsin expressing retinal ganglion cells also project to the oliviary pretectal nuclei.

Disrupting the melanopsin gene provides an opportunity to study the role of this protein in pupillary responses. Although the survival and targeting of the melanopsin class of retinal ganglion cells are not affected by melanopsin loss, their photosensitivity is abolished. Despite this effect, melanopsin knockouts retain a pupillary light reflex. However, combining the melanopsin knockout with lesions of both rod and cone phototransduction cascades renders mice unresponsive to light. Thus, either the melanopsin or rod/cone systems alone can drive pupil responses, but in the absence of both no other photosystem can perform this function.

The finding that both classical and novel photoreceptors can drive pupil responses establishes a challenge to elucidate the interaction between these pathways. Studying both melanopsin knockouts and mice lacking rods and cones has allowed us to explore the role of outer and inner retinal photoreception in the regulation of pupil size. Our findings to date confirm that the information provided by the rod/cone and melanopsin systems is complementary. Rods and/or cones are responsible for pupil responses under relatively dim light, while the melanopsin system drives constriction under bright light conditions (>1012 photons/cm2/s). The activity of both inner and outer photoreceptors is required to produce a normal pupil response to all intensities.

A combination of rod/cone and melanopsin photoreceptors is also involved in other light responses including circadian photoentrainment and the regulation of the neuroendocrine axis.

Towards harmonisation of ophthalmology requirements in aviation: are there differences in interpretation amongst European countries?

There are more than 30 countries within JAA with many different cultural and medical backgrounds. Clear description of requirements in relation to medical / ophthalmic standards is therefore needed to avoid misunderstandings and to ensure that eye examinations are carried out and results interpreted in an equivalent way in each country. This can lead to important safety requirements and will lead to licensing harmonization within JAA.

The aim is clear, but are the requirements as currently stated clear enough? How does JAR-FCL 3 work in practice? It is generally recognised that applicants with certain deficiencies that may fail in one country can reapply and often pass in another JAA country?

Improvements to current practices will be discussed by examining new visual task requirements, differences in medical assessment procedures and the corresponding ophthalmological implications.

Nutritional supplements and dry eye

Dietary Omega-3 Fatty Acid Intake and Risk of Clinically Diagnosed Dry Eye Syndrome in Women.

Trivedi K, Dana MR, Gilbard JP, Buring JE, Schaumberg DA. Departments of Medicine and Ophthalmology, Brigham and Women's Hospital, and Schepens Eye Research Institute, Harvard Medical School, Boston MA.

Purpose: To determine the association between dietary intake of omega-3 fatty acids and risk of dry eye syndrome (DES). Methods: A total of 32,470 female health professionals aged between 45 and 84 years who provided information on diet and DES were chosen from the 39,876 women participating in the Women's Health Study. Intake of omega-3 fatty acids was assessed by a validated food frequency questionnaire. DES was assessed using self-reports of clinically diagnosed DES. We used logistic regression models to estimate the odds ratios (OR) and 95% confidence intervals (CI) to describe the relationships of omega-3 fatty acid intake and DES. We also analyzed the relationship between consumption of fish and DES in a similar way. Results: After adjusting for age, other demographic factors, postmenopausal hormone therapy, and total fat intake, the OR (CI) for the highest versus the lowest dietary intake of omega-3 fatty acids was 0.83 (0.70-0.98), P for trend=0.04. In addition, we observed a significant association between tuna fish consumption and DES (OR=0.82, CI=0.67-1.00 for 2 to 4 servings/week, and OR=0.34, CI=0.13-0.81 for 5 to 6 four-ounce servings/week versus <2 servings/week; P for trend=0.004). Results were similar in other models additionally controlling for diabetes, hypertension, and connective tissue diseases.

Conclusion: These results suggest that women with a higher dietary intake of omega-3 fatty acids are at decreased risk of developing DES. Although this is the first study that has evaluated this relationship, and confirmation from other studies is needed, the findings are consistent with clinical observations and postulated biological mechanisms. Thus, further research on the role of omega-3 fatty acids in the prevention and/or treatment of DES would be of interest.

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