Advances in ophthalmic structural and functional measures in multiple sclerosis: do the potential ocular biomarkers meet the unmet needs?

PURPOSE OF REVIEW: Multiple sclerosis is a heterogeneous disorder. Biomarkers to monitor disease activities are highly desirable especially because of the recent shift toward personalized medicine that coincides with the expansion of disease-modifying therapy. The visual system is highly involved in multiple sclerosis, and the rapid advancement of ophthalmic techniques has boosted the development of potential ocular biomarkers for multiple sclerosis management. RECENT FINDINGS: Recent studies have found that the rapid thinning of the peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) occurs in the progressive stage. Furthermore, the inter-eye thickness difference of the GCIPL could be used in identifying unilateral optic neuritis to facilitate the early diagnosis of multiple sclerosis. Moreover, the retinal microvascular alterations measured as vessel density were found to be related to the disability and visual function, although a standardized protocol to measure retinal microvascular alterations has not been well established. Additionally, aberrant ocular motility, such as fixation microsaccades, can be used to measure disability objectively. SUMMARY: The fast expansion of potential ocular biomarkers measured as retinal microstructural, microvascular, and ocular motility changes may facilitate the diagnosis and management of multiple sclerosis.

Methods of visual assessment in children with cortical visual impairment.

PURPOSE OF REVIEW: Cortical visual impairment (CVI) is the leading cause of pediatric visual impairment in developed countries. Currently, there is no standardized method of visual assessment in these children, who usually cannot participate in tests designed for typically developing children. A reproducible method of visual assessment that accurately reflects the multitude of visual deficits in CVI is critical to evaluate proposed therapies for this disorder. This review analyzes current research on methods of visual assessment in children with CVI. RECENT FINDINGS: Earlier studies focused on measuring visual acuity in children with CVI. More recent studies have emphasized other aspects of visual function, such as contrast sensitivity, motion detection, and visual search. Current research topics include questionnaires, functional vision assessment (CVI Range), neuropsychological tests of visual perception, and eye tracking. Eye tracking shows promise for visual assessment in both clinical and research settings because it is objective and quantitative, with the ability to assess diverse visual parameters. SUMMARY: Current research on visual assessment in children with CVI focuses on measuring deficits of visual function beyond visual acuity. This research represents an important step toward designing clinical trials to identify effective therapeutics for this increasingly prevalent disorder with heterogeneous manifestations.

Calculated Decisions: Visual acuity testing (Snellen chart).

The Snellen chart assesses binocular and monocular visual acuity.

The measurement of visual acuity in children: an evidence-based update.

Over the past decade, a number of large clinical trials have provided important information relating to the reliability and repeatability of commonly used paediatric tests of vision and their role in the diagnosis and management of paediatric ocular diseases. The aim of this review is to summarise recent findings on the use of paediatric visual acuity tests in clinical practice and to discuss the validity and accuracy of visual acuity measurements in infants and young children. We provide a broad overview of the benefits and challenges of measuring visual acuity in children and then discuss age-appropriate tests for measuring visual acuity in infants through to school-age children. We also discuss normative values for visual acuity in each age group and, where possible, provide comparisons of results between tests with a particular focus on the importance of optotype design.

[Current state of pupil-based diagnostics for glaucomatous optic neuropathy]. / Aktueller Stand der pupillenbasierten Diagnostik der glaukomatösen Optikusneuropathie.

There are considerable differences between pupillary reactions to light in glaucoma patients and healthy subjects which can be identified by various techniques. These methods are based on the early asymmetry of the afferent conduction in the visual pathway, on the examination of the visual field by focal light stimuli or on visual stimuli in analogy with multifocal electrophysiological tests. Latest findings in pupillary research also suggest a possible use of the intrinsically photosensitive (melanopsin expressing) retinal ganglion cells in glaucoma diagnostics. The current results of pupillary experiments in glaucoma patients are encouraging for further research in this field because suitable objective screening methods for glaucoma are continually being sought.

[Functional glaucoma diagnosis]. / Funktionelle Glaukomdiagnostik.

Achromatic perimetry is the gold standard in glaucoma diagnosis for detecting functional defects from glaucomatous optic neuropathy. Because achromatic perimetry is only able to detect scotomas after loss of up to 30-40% of retinal ganglion cells, early diagnosis using this method is rarely possible. Therefore, a lot of new perimetric procedures have been developed in recent years to detect new scotomas at a very early stage. This review summarizes the theoretical background of retinal ganglion cells in order to better understand the theoretical approaches of new perimetric methods. In addition, the most important commercial perimetric devices currently available are presented.

Habitual vs optimal distance visual acuity.

PURPOSE: The maintenance of a good level of vision is desirable for developmental and social reasons; it is also a requirement that should not be overlooked in the clinical research environment. This study set out to quantify and analyse any difference between 'habitual' (pre-sight test) and 'optimal' (post-refraction) distance visual acuity in an optometric population. It is intended that the outcome of this work will inform not only clinicians but also those undertaking vision research. METHODS: Binocular logMAR visual acuity was determined at 6 m before and after optometric intervention in patients attending optometric practice for a routine sight test. Cases were recorded seriatim but restricted to the 'core' refraction range representative of typical optometric practice; three further exemption criteria included subject illiteracy, the necessity for a non-standard test distance and contact lens wear. Over a 12-month period, two-thirds of patients examined satisfied the study inclusion criteria; it is the clinical data of these 1288 individuals that are described and analysed here. RESULTS: These data provide a quantitative demonstration that an optometric intervention will most likely improve the habitual distance visual acuity of subjects, irrespective of gender, age group, time interval since last test, refractive status and whether or not the subject is a habitual spectacle wearer. The improvement found was typically within one logMAR chart line (<5 letters), being greatest in spectacle-wearing teenagers and in individuals beyond retirement age (increasing to eight letters in elderly habitual non-spectacle wearers); also in non-wearers who left an interval of 2 years or more between sight tests. CONCLUSIONS: Clinical and laboratory-based investigators are advised that a current and optimal refractive correction should be worn by subjects of all ages enrolled in vision-related studies. Refractive defocus may introduce or exaggerate test outcome variability.

Visual function at 11 years of age in preterm-born children with and without fetal brain sparing.

OBJECTIVE: We have demonstrated earlier an accelerated maturation of the visual evoked potential in the first year of life in preterm infants with antenatal brain sparing. We have now assessed visual functioning at 11 years of age in the same cohort and compared the groups with and without brain sparing. DESIGN/METHODS: One hundred sixteen survivors included in a study on the outcome of preterm infants born at <33 weeks' gestation with and without fetal brain sparing and admitted to the NICU were followed extensively. Ninety-eight infants (85%) were again assessed at 11 years of age. Data were available for fetal Doppler measurements indicating brain sparing, neonatal cerebral ultrasound scanning, and developmental outcome in the first 5 years. Mean birth weight was 1303 g; mean gestational age was 29.8 weeks. The infants were divided into 2 groups with and without brain sparing. Visual functioning was estimated by measuring visual acuity, visual fields, eye position, and binocular function and by visual motor tests. RESULTS: Six percent of the children were found to have a visual acuity of <0.8, 12% had strabismus, and 14% to 46% showed abnormal results on the visual motor tests. No statistical differences were found between the 2 groups. However, children with severe cerebral ultrasound diagnoses in the neonatal period were found to have significantly more abnormalities on visual functioning and lower scores on visual motor tests than children without these morbidities. CONCLUSIONS: Children with fetal brain sparing do not demonstrate a different development of their visual functioning at late school age. However, an abnormal cerebral ultrasound in the neonatal period is associated with impaired visual function in later life.

Desenvolvimento de um instrumento automatizado para medida do campo visual do olho humano / Development of an automated instrumento for human visual field measurements

Neste artigo é descrito o desenvolvimento de um instrumento computadorizado para medidas do campo visual do olho humano. Apresentam-se detalhes da implementação do primeiro protótipo (hardware e software) e resultados preliminares em testes in vivo. Sabe-se que algumas patologias de grande risco para qualidade da visão, como o glaucoma (aumento da pressão intra-ocular), provocam lentamente a morte de células sensoriais (cones e bastonetes)na retina. Normalmente, o paciente só percebe o problema quando aproximadamente 50 por cento destas células já estiverem mortas. Um dos instrumentos que pode auxiliar no diagnóstico precoce destas patologias é campímetro automatizado. Apesar de existirem instrumentos importados que realizam este exame, eles contêm softwares que utilizam bases de dados geradas a partir de exames em população com características demográficas bastante diferentes daquelas encontradas no Brasil. Normalmente, essas bases de dados são provenientes dos EUA e Europa, mas sabe-se que a predisposição a diversas patologias está associada às condições demográficas (por exemplo, descobriu-se que na população de pele negra a incidência de glaucoma é maior quando comparada com a população de cor branca, em termos gerais e para residentes em uma mesma região geográfica). Além da raça, fatores como temperatura, clima e radiação solar podem também influenciar a sensibilidade visual. Assim, o desenvolvimento de um instrumento que incorpore uma base de dados colhida em olhos da população brasileira, possibilitará exames mais precisos no país. Apresenta-se aqui as diferentes etapas do desenvolvimento deste instrumento e os resultados preliminares.

Improving visual function diagnostic metrics with the use of higher-order aberration information from the eye.

PURPOSE: This paper reviews the currently used visual function diagnostic metrics, acuity, refractive error, and contrast sensitivity, and suggests ways to create new metrics using the information that has recently become available due to advances in measuring the higher-order aberrations of the eye. Particularly, emphasis is placed on finding metrics that address certain aspects of vision rather than on general metrics. METHODS: Two metrics based on the modulation transfer function are introduced, the Visual Quality Factor (VQF), which is a value based on the modulation transfer function between the spatial frequencies of 3 and 12 cycles per degree (c/deg) giving a measure of the overall degradation of visual quality due to aberrations, and the Subjective Sharpness Factor (SSF), which is a value based on the modulation transfer function between the spatial frequencies of 15 and 40 c/deg, giving a measure of the decrease in perceived image "sharpness" due to aberrations. Two metrics based on the point spread function are suggested, Point Spread Quality (PSQ), which is a measure of the "compactness" of the point spread, and Multiplicity Factor, which is a measure of the multiplicity of perceived images by measuring the number of discrete peaks in the point spread function. RESULTS: The VQF and SSF values for both monochromatic and polychromatic cases are analyzed with regard to the number of acuity letters lost using data from a published study. CONCLUSIONS: The SSF is found to be the best overall correlate with acuity performance if the degradation of the letter stimuli is not excessive.