Geoff P. Sampson

Repeatability of Measuring Corneal Subbasal Nerve Fiber Length in Individuals With Type 2 Diabetes

Purpose: To analyze the repeatability of measuring nerve fiber length (NFL) from images of the human corneal subbasal nerve plexus using semiautomated software. Methods: Images were captured from the corneas of 50 subjects with type 2 diabetes mellitus who showed varying severity of neuropathy, using the Heidelberg Retina Tomograph 3 with Rostock Corneal Module. Semiautomated nerve analysis software was independently used by two observers to determine NFL from images of the subbasal nerve plexus. This procedure was undertaken on two occasions, 3 days apart. Results: The intraclass correlation coefficient values were 0.95 (95% confidence intervals: 0.92–0.97) for individual subjects and 0.95 (95% confidence intervals: 0.74–1.00) for observer. Bland-Altman plots of the NFL values indicated a reduced spread of data with lower NFL values. The overall spread of data was less for (a) the observer who was more experienced at analyzing nerve fiber images and (b) the second measurement occasion. Conclusions: Semiautomated measurement of NFL in the subbasal nerve fiber layer is highly repeatable. Repeatability can be enhanced by using more experienced observers. It may be possible to markedly improve repeatability when measuring this anatomic structure using fully automated image analysis software.

Corneal Markers of Diabetic Neuropathy

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Wide-field assessment of the human corneal subbasal nerve plexus in diabetic neuropathy using a novel mapping technique.

Abstract To develop a rapid optimized technique of wide-field imaging of the human corneal subbasal nerve plexus. A dynamic fixation target was developed and, coupled with semiautomated tiling software, a rapid method of capturing and montaging multiple corneal confocal microscopy images was created. To illustrate the utility of this technique, wide-field maps of the subbasal nerve plexus were produced in 2 participants with diabetes, 1 with and 1 without neuropathy. The technique produced montages of the central 3 mm of the subbasal corneal nerve plexus. The maps seem to show a general reduction in the number of nerve fibers and branches in the diabetic participant with neuropathy compared with the individual without neuropathy. This novel technique will allow more routine and widespread use of subbasal nerve plexus mapping in clinical and research situations. The significant reduction in the time to image the corneal subbasal nerve plexus should expedite studies of larger groups of diabetic patients and those with other conditions affecting nerve fibers. The inferior whorl and the surrounding areas may show the greatest loss of nerve fibers in individuals with diabetic neuropathy, but this should be further investigated in a larger cohort.

Combining Ganglion Cell Topology and Data of Patients with Glaucoma to Determine a Structure―Function Map

PURPOSE To introduce techniques for deriving a map that relates visual field locations to optic nerve head (ONH) sectors and to use the techniques to derive a map relating Medmont perimetric data to data from the Heidelberg Retinal Tomograph. METHODS Spearman correlation coefficients were calculated relating each visual field location (Medmont M700) to rim area and volume measures for 10 degrees ONH sectors (HRT III software) for 57 participants: 34 with glaucoma, 18 with suspected glaucoma, and 5 with ocular hypertension. Correlations were constrained to be anatomically plausible with a computational model of the axon growth of retinal ganglion cells (Algorithm GROW). GROW generated a map relating field locations to sectors of the ONH. The sector with the maximum statistically significant (P < 0.05) correlation coefficient within 40 degrees of the angle predicted by GROW for each location was computed. Before correlation, both functional and structural data were normalized by either normative data or the fellow eye in each participant. RESULTS The model of axon growth produced a 24-2 map that is qualitatively similar to existing maps derived from empiric data. When GROW was used in conjunction with normative data, 31% of field locations exhibited a statistically significant relationship. This significance increased to 67% (z-test, z = 4.84; P < 0.001) when both field and rim area data were normalized with the fellow eye. CONCLUSIONS A computational model of axon growth and normalizing data by the fellow eye can assist in constructing an anatomically plausible map connecting visual field data and sectoral ONH data.

Corneal sensitivity as an ophthalmic marker of diabetic neuropathy.

Purpose. The objective of this study was to explore the discriminative capacity of non-contact corneal esthesiometry (NCCE) when compared with the neuropathy disability score (NDS) score—a validated, standard method of diagnosing clinically significant diabetic neuropathy. Methods. Eighty-one participants with type 2 diabetes, no history of ocular disease, trauma, or surgery and no history of systemic disease that may affect the cornea were enrolled. Participants were ineligible if there was history of neuropathy due to non-diabetic cause or current diabetic foot ulcer or infection. Corneal sensitivity threshold was measured on the eye of dominant hand side at a distance of 10 mm from the center of the cornea using a stimulus duration of 0.9 s. The NDS was measured producing a score ranging from 0 to 10. To determine the optimal cutoff point of corneal sensitivity that identified the presence of neuropathy (diagnosed by NDS), the Youden index and “closest-to-(0,1)” criteria were used. Results. The receiver-operator characteristic curve for NCCE for the presence of neuropathy (NDS ≥3) had an area under the curve of 0.73 (p = 0.001) and, for the presence of moderate neuropathy (NDS ≥6), area of 0.71 (p = 0.003). By using the Youden index, for an NDS ≥3, the sensitivity of NCCE was 70% and specificity was 75%, and a corneal sensitivity threshold of 0.66 mbar or higher indicated the presence of neuropathy. When NDS ≥6 (indicating risk of foot ulceration) was applied, the sensitivity was 52% with a specificity of 85%. Conclusions. NCCE is a sensitive test for the diagnosis of minimal and more advanced diabetic neuropathy and may serve as a useful surrogate marker for diabetic and perhaps other neuropathies.

Low spatial frequency contrast sensitivity deficits in migraine are not visual pathway selective

Some people who experience migraine demonstrate reduced visual contrast sensitivity that is measurable between migraines. Contrast sensitivity loss to low spatial frequency gratings has been previously attributed to possible impairment of magnocellular pathway function. This study measured contrast sensitivity using low spatial frequency targets (0.25–4 c/deg) where the adaptation aspects of the stimuli were designed to preferentially assess either magnocellular or parvocellular pathway function (steady and pulsed pedestal technique). Twelve people with migraine with measured visual field abnormalities and 17 controls participated. Subjects were tested foveally and at 10° eccentricity. Foveally, there was no significant difference in group mean contrast sensitivity. At 10°, the migraine group demonstrated reduced contrast sensitivity for both the stimuli designed to assess magnocellular and parvocellular function (P < 0.05). The functional deficits measured in this study infer that abnormalities of the low spatial frequency sensitive channels of both pathways contribute to contrast sensitivity deficits in people with migraine.

Interactions between luminance and colour channels in visual search and their relationship to parallel neural channels in vision

We have compared visual search under conditions that tend to isolate the magnocellular, parvocellular and koniocellular channels of the human visual system. We used isoluminant red–green stimuli that do not modulate short-wavelength sensitive (SWS) cones to isolate the parvocellular pathway, isoluminant SWS-cone isolating stimuli to stimulate only the koniocellular system and addition of small luminance contrasts to selectively activate the magnocellular pathway. We found that in the case of conjunction search, where attentional resources were required, the red–green (parvocellular) system can use accompanying small luminance (magnocellular) signals to improve visual search. On the other hand, when using SWS-cone isolating stimuli to selectively stimulate the blue–yellow (koniocellular) system, addition of similar luminance signals did not increase the efficiency of the serial visual search. The results indicate that S-cone signals may be processed in a separate pathway that does not get converging inputs from the magnocellular pathway. This is unlike the case with the red–green opponent system, which functions more synergistically with the magnocellular system.

Retinal Tissue Thickness is Reduced in Diabetic Peripheral Neuropathy

ABSTRACT Aim: To investigate the relationship between diabetic peripheral neuropathy (DPN) and retinal tissue thickness. Methods: Full retinal thickness in the central retinal, parafoveal, and perifoveal zones and thickness of the ganglion cell complex and retinal nerve fiber layer (RNFL) were assessed in 193 individuals (84 with type 1 diabetes, 67 with type 2 diabetes, and 42 healthy controls) using spectral domain optical coherence tomography. Among those with diabetes, 44 had neuropathy defined using a modified neuropathy disability score recorded on a 0–10 scale. Multiple regression analysis was performed to investigate the relationship between diabetic neuropathy and retinal tissue thickness, adjusted for the presence of diabetic retinopathy (DR), age, sex, duration of diabetes, and HbA1c levels. Results: In individuals with diabetes, perifoveal thickness was inversely related to the severity of neuropathy (p < 0.05), when adjusted for age, sex, duration of diabetes, and HbA1c levels. DR was associated with reduced thickness in parafovea (p < 0.01). The RNFL was thinner in individuals with greater degrees of neuropathy (p < 0.04). Conclusions: DPN is associated with structural compromise involving several retinal layers. This compromise may represent a threat to visual integrity and therefore warrants examination of functional correlates.

Focal loss volume of ganglion cell complex in diabetic neuropathy

The aim was to investigate the relationship between diabetic peripheral neuropathy (DPN) and abnormalities in ganglion cell complex (GCC); specifically, focal loss volume (FLV) and global loss volume (GLV).

Review of guidelines for children's vision screenings

The aim of childrens vision screenings is to detect visual problems that are common in this age category through valid and reliable tests. Nevertheless, the cost effectiveness of paediatric vision screenings, the nature of the tests included in the screening batteries and the ideal screening age has been the cause of much debate in Australia and worldwide. Therefore, the purpose of this review is to report on the current practice of childrens vision screenings in Australia and other countries, as well as to evaluate the evidence for and against the provision of such screenings. This was undertaken through a detailed investigation of peer‐reviewed publications on this topic. The current review demonstrates that there is no agreed vision screening protocol for children in Australia. This appears to be a result of the lack of strong evidence supporting the benefit of such screenings. While amblyopia, strabismus and, to a lesser extent refractive error, are targeted by many screening programs during pre‐school and at school entry, there is less agreement regarding the value of screening for other visual conditions, such as binocular vision disorders, ocular health problems and refractive errors that are less likely to reduce distance visual acuity. In addition, in Australia, little agreement exists in the frequency and coverage of screening programs between states and territories and the screening programs that are offered are ad hoc and poorly documented. Australian children stand to benefit from improved cohesion and communication between jurisdictions and health professionals to enable an equitable provision of validated vision screening services that have the best chance of early detection and intervention for a range of paediatric visual problems.