Determinación de la concentración de proteína

The research reported in this thesis has advanced understanding of testing visual fields in children, reporting the feasibility of testing and investigating methods for assessing test reliability. The findings highlight the differences in testing between adults and children, demonstrating that it is not sufficient to simply apply evidence gained from adult literature to children. For example, it is evident that the sole use of automated reliability measures in judging test reliability is inappropriate in children, yet the static test algorithms developed for adults appear capable of detecting visual field defects in children with glaucoma. Thus, to provide information on the role of perimetry in the management of children with ophthalmic disease, future research should focus on recruiting children with the specific ophthalmic disease in question.

SOPs were developed from this study and, as reported earlier, further work is necessary (and planned) to develop these to be used in clinical practice and to inform future clinical guidelines.

Formal perimetry (as opposed to novel, game-based approaches such as SVOP) is available to clinicians in a hospital setting, and can be used to monitor visual fields throughout a person’s life. As such, findings in childhood provide a ‘baseline’ that is potentially still relevant decades later. The section below will identify remaining gaps within the literature and set out a ‘pathway’ to develop greater understanding of the role of formal perimetry in the management of childhood ophthalmic disease, with an understanding of the lifelong care many children

Our investigations were performed with an understanding of the change in available perimeters in clinics. Whilst Goldmann perimetry remains the widely used clinical gold-standard, other techniques investigated here are feasible, but as of yet, not as reliable in young children. The emerging availability of ‘third-party’ perimeters (from Takagi and Inami), replicating Goldmann standards, have not yet been sufficiently explored within the literature to advise their use in children. This paucity of evidence, combined with the potential for failure of existing Goldmann apparatus leaves a potential compromise in patient care and thus there is a need for future research to prioritise available (rather than novel) techniques – namely an investigation of the apparent ‘like-for-like’ replacements offered by Takagi and Inami.

Further research should then explore the role of perimetry as a tool for monitoring disease progression. Currently, there is no consensus on the best method for tracking progressive visual field loss in adult glaucoma, extending to a lack of agreement on which algorithm to use, the best statistical method (pointwise, global etc.) and frequency of testing required to detect change. Given the lack of consensus over tracking progression in adults, there is limited evidence upon which inferences can be made and applied to children, and it is uncertain as to whether it would appropriate to do so. Tracking disease progression in children is further complicated by a lack of understanding of the effect of an insult to a developing visual system, which could give rise to trajectories of progressive visual loss not seen in adults.

For children with glaucoma, there is also a need to affirm known features of adult glaucoma, namely; to assess whether test results (visual field sensitivities) are more variable in severely damaged fields, define the number of serial tests needed to confirm progression, and investigate structure/function relationships – in particular, explore the relationship between perimetric findings, RNFL reflectance intensity and OCT findings/sites of damage.

Once there is a clearer understanding of the way in which glaucomatous field loss progresses in childhood glaucoma, it will be possible to create new tests to be applied to children currently too young to be reliably assessed. These new tests can be targeted to detect loss in known susceptible areas of the field, thus reducing the number of required test points, with awareness that not all loss can be detected without a standard ‘grid’ pattern. These tests will have limited value in defining a ‘baseline’ visual field sensitivity that can be tracked across the life course, but even with a small applicable age range, and limited long-term value, a novel algorithm could provide information on VF sensitivity in a group of children in whom it is currently not possible to obtain meaningful results. Any adaptations of conventional static algorithms would need to assess the optimal balance between the number/location of central static test points and test duration – reducing the number of test points, but maintaining the accuracy of testing at each point. As such, techniques to shorten test duration such as TOP (which relies on scores from nearby anatomical locations to infer sensitivity at adjacent points) may not be suitable, but a standard staircase method could be successful.

Using simplified static strategies from a younger age also has the potential to familiarise children with perimetric procedures, improving reliability later in childhood. This contrasts with current attempts to measure visual fields in children, which focus on supra-threshold stimuli and use eye-tracking technology to detect shifts in fixation – a behaviour that is actively suppressed during conventional perimetry.

Our data on children with neuro-ophthalmic disease highlight the difficulty in testing a challenging group of unwell children. Given the limited ability of these children, future work should examine the ability of each element of kinetic testing to detect neuro-ophthalmic defects. For example, in a child who struggles to perform kinetic perimetry using 2 isopters (far and mid-peripheral stimuli) with plotting of the blind spot, an investigation of which elements hold the greatest potential to detect defects, and monitor for progressive loss could allow clinicians to use limited test points to assess the visual field. Adapting protocols for a select group of children in this way should be performed with an understanding of the types of defect that could be potentially missed.

For children with neuro-ophthalmic disease, there is a lack of understanding of normal levels of ‘noise’ between test results, the number of tests required before having definitive perimetric evidence of progression and what constitutes a clinically significant change in visual field sensitivity. Addressing these questions will help to determine the intrinsic value of perimetric results in the clinical management of childhood neuro-ophthalmic disease i.e. at what level does a perimetric test result influence clinical decisions? A retrospective review of

perimetric findings, matching changes in visual field sensitivity with changes in findings from imaging and other clinical features, is key to addressing this question.

Finally, it is necessary to develop clinical tools to aid tracking progression with kinetic perimetry (similar to those that exist for static perimetry). Our newly developed R package is the first step in this process – providing a template for organising test responses into matrices suitable for analysis. Further work is necessary to develop progression-tracking measures. For example, automated tracking of changes in isopter extent per quadrant and reporting change in total isopter area are useful clinical tools that need to be automated, providing summary scores without extensive user input.

Combining the findings here with the future work outlined above would allow for greater understanding of how to measure visual fields in children, the role of perimetry in tracking visual field loss, and the way in which these can contribute to clinical care. Once this evidence is present, it will be necessary to update current guidelines, describing accurately the role of perimetry in the management of children with glaucoma and neuro-ophthalmic disease.