Corneal nerve tortuosity in diabetic patients with neuropathy. (17/109)

PURPOSE: Corneal confocal microscopy is a reiterative, rapid, noninvasive in vivo clinical examination technique capable of imaging corneal nerve fibers. Nerve fiber tortuosity may indicate a degenerative and attempted regenerative response of nerve fibers to diabetes. The purpose of this study was to define alterations in the tortuosity of corneal nerve fibers in relation to age, duration of diabetes, glycemic control, and neuropathic severity. METHODS: The cornea and collected images of the subbasal nerve plexus of 18 diabetic patients (stratified into mild, moderate, and severe neuropathic groups using conventional clinical measures of neuropathy) and 18 age-matched nondiabetic control subjects were scanned, and a novel mathematical paradigm was applied to quantify the extent of nerve tortuosity, which was termed the tortuosity coefficient (TC). RESULTS: TC was significantly different between the four clinical groups (F(3) = 12.2, P < 0.001). It was significantly greater in the severe neuropathic group than in control subjects (P < 0.003) and in the mild (P < 0.004) and moderate (P < 0.01) neuropathic groups. TC did not correlate significantly with the age (r = -0.003, P > 0.05), duration of diabetes (r = -0.219, P > 0.05), or hemoglobin A1c (HbA1c; r = 0.155, P > 0.05) of diabetic patients. CONCLUSIONS: Corneal confocal microscopy allows rapid, noninvasive in vivo evaluation of corneal nerve tortuosity. This morphologic abnormality relates to the severity of somatic neuropathy and may reflect an alteration in the degree of degeneration and regeneration in diabetes.  (+info)

Optical mapping of the functional organization of the rat trigeminal nucleus: initial expression and spatiotemporal dynamics of sensory information transfer during embryogenesis. (18/109)

We examined the functional organization of the rat trigeminal nuclear complex and its developmental dynamics using a multiple-site optical recording technique. Brainstem preparations were dissected from embryonic day 12 (E12)-E16 rat embryos, and stimulation was applied individually to the three branches of the trigeminal nerve (V1-V3). The action potential activity of presynaptic fibers was detected from E13, and the glutamate-mediated postsynaptic response was significantly observed from E15 on. At E14, the evoked signals usually consisted of only the action potential-related fast component. However, when extracellular Mg2+ was removed, a significant dl-2-amino-5-phosphonovaleric acid-sensitive slow component appeared. These results suggest that postsynaptic function mediated by NMDA receptors is latently generated as early as E14. The response area of the three branches of the trigeminal nerve showed some functional somatotopic organization, with the ophthalmic (V1) nerve area medially located and the mandibular (V3) nerve area laterally located. The center of the trigeminal nuclear complex in which the activity of neurons and synaptic function was greatest shifted caudally with development, suggesting that the functional architecture of the trigeminal nuclear complex is not fixed but changes dynamically during embryogenesis. By electron microscopy, we could not observe clear correlations between functional data and morphological information; when we surveyed E16 preparations, we could not identify typical synaptic structures between the 1,1'-dioctyldecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled trigeminal nerve terminals and the neurons in the trigeminal nuclear complex. This implies that postsynaptic function in the trigeminal nuclear complex is generated before the appearance of the morphological structure of conventional synapses.  (+info)

Noninvasive assessment of corneal sensitivity in young and elderly diabetic and nondiabetic subjects. (19/109)

PURPOSE: To investigate the effect of age and diabetes on corneal sensitivity using the noncontact corneal aesthesiometer (NCCA). METHODS: One hundred sixteen nondiabetic subjects and 111 diabetic subjects (33 type I and 78 type II) were recruited and divided into three age groups: Young (or=60 years). The exclusion criteria included patients with severe retinopathy requiring treatment, a history of invasive ocular surgery, or a history of conditions known to affect corneal sensitivity. The corneal cooling sensation threshold, for the right eye of each subject, was assessed with a double-staircase method-of-limits technique with the NCCA. This instrument uses a controlled pulse of air to produce a small, localized reduction in the surface temperature of the eye, which is detected by the nerves in the corneal epithelium. RESULTS: Analysis of the scatterplot of each subject's central cooling sensation threshold revealed a gradual loss of sensitivity with increasing age (nondiabetic, r(2) = 0.349; diabetic, r(2) = 0.131). Within the nondiabetic group, inter-age-group comparisons found significant differences between the central corneal cooling sensation thresholds for the three age groups (t-test, P < 0.01). Within the diabetic group, a significant difference was found between the Middle and Older categories only (t-test, P < 0.05). In summary, the Young group was more sensitive than the Middle group, which was more sensitive than the Older group. Within both type I and type II diabetic subjects, there was neither a significant relationship between duration of the disease and corneal sensitivity (t-test, P > 0.05) nor a gender-based difference (t-test, P > 0.05). CONCLUSIONS: There is a gradual reduction in corneal sensitivity with increasing age in both nondiabetic subjects and diabetic subjects, along with an increasing variation in the measured threshold. There is no relationship between corneal sensitivity and the time since diagnosis of diabetes for a thermally cooling stimulus, suggesting that the A partial differential and C fibers of the corneal innervation are affected differently by abnormal glucose metabolism in the diabetic cornea.  (+info)

Corneal reinnervation after LASIK: prospective 3-year longitudinal study. (20/109)

PURPOSE: To measure the return of innervation to the cornea during 3 years after LASIK. METHODS: Seventeen corneas of 11 patients who had undergone LASIK to correct myopia from -2.0 D to -11.0 D were examined by confocal microscopy before surgery, and at 1, 3, 6, 12, 24, and 36 months after surgery. In all available scans, the number of nerve fiber bundles and their density (visible length of nerve per frame area), orientation (mean angle), and depth in the cornea were measured. RESULTS: The number and density of subbasal nerves decreased >90% in the first month after LASIK. By 6 months these nerves began to recover, and by 2 years they reached densities not significantly different from those before LASIK. Between 2 and 3 years they decreased again, so that at 3 years the numbers remained <60% of the pre-LASIK numbers (P <0.001). In the stromal flap most nerve fiber bundles were also lost after LASIK, and these began recovering by the third month, but by the third year they did not reach their original numbers (P <0.001). In the stromal bed (posterior to the LASIK flap interface), there were no significant changes in nerve number or density. As the subbasal nerves returned, their mean orientation did not change from the predominantly vertical orientation before LASIK. Nerve orientation in the stromal flap and the stromal bed also did not change. CONCLUSIONS: Both subbasal and stromal corneal nerves in LASIK flaps recover slowly and do not return to preoperative densities by 3 years after LASIK. The numbers of subbasal nerves appear to decrease between 2 and 3 years after LASIK. The orientation of the regenerated subbasal nerves remains predominantly vertical.  (+info)

Changes in mechanical, chemical, and thermal sensitivity of the cornea after topical application of nonsteroidal anti-inflammatory drugs. (21/109)

PURPOSE: In addition to their well-known anti-inflammatory actions, some of the nonsteroidal anti-inflammatory drugs (NSAIDs) appear to have an analgesic effect. In human subjects, the changes in threshold and intensity of sensations evoked by mechanical, chemical, and thermal stimulation of the cornea induced by topical administration of two commercial NSAIDs, diclofenac sodium (Voltaren; Novartis, Basel, Switzerland) and flurbiprofen (Ocuflur; Allergan, Irvine, CA), were studied. METHODS: Corneal sensitivity was measured in 10 young, healthy subjects with a gas esthesiometer. Chemical (10%-70% CO2 in air), mechanical (0-264 mL/min), and thermal (corneal temperature changes between -4.5 degrees C and +3 degrees C around the normal value) stimuli were applied to the center of the cornea. The intensity and perceived magnitude of the psychophysical attributes of the evoked sensation were scored at the end of the pulse in a 10-cm, continuous visual analog scale (VAS). The threshold was expressed as the stimulus intensity that evoked a VAS score >0.5. Sensitivity was measured in both eyes of each subject on two separate days, one without treatment and the other 30 minutes after topical application of 0.03% flurbiprofen (seven subjects) or 0.1% diclofenac sodium (six subjects). RESULTS: Diclofenac attenuated significantly all the sensation parameters evoked by high-intensity mechanical, chemical, and thermal stimuli. Flurbiprofen produced a slight reduction of the sensations evoked by mechanical and chemical stimulation that became significant only for the irritation caused by chemical stimuli of maximum intensity (70% CO2). None of the drugs modified significantly the detection threshold of the different stimuli. CONCLUSIONS: Flurbiprofen had a very limited effect on sensations evoked by corneal stimulation, whereas diclofenac reduced the intensity of sensations evoked by stimuli of different modality, suggesting a mild local anesthetic effect of this drug on all types of corneal sensory fibers. Such anesthetic action could explain the analgesic effect that has been reported after topical application of diclofenac in inflamed human eyes.  (+info)

The inhibitory interaction between human corneal and conjunctival sensory channels. (22/109)

PURPOSE: To explore human corneal and conjunctival sensory channels at suprathreshold level. METHODS: Ten healthy human subjects participated in the study. The Belmonte pneumatic esthesiometer was used to apply mechanical and chemical stimuli to the central cornea and temporal conjunctiva of the left eye. Stimuli were applied in a paired and unpaired way for conjunctival stimulation. A 100-point visual analog scale (VAS) was used to rate the intensity of the stimulus. RESULTS: The magnitudes of the sensation evoked from the conjunctiva were different when using different methods for presenting stimuli to the ocular surface. When stimuli were applied to the conjunctiva alone, the magnitude of the sensation was stronger than when the stimuli were applied in pairs to the cornea and conjunctiva for both mechanical (P = 0.04) and chemical (P = 0.02) stimulation. CONCLUSIONS: The relatively strong discomfort evoked from the cornea appears to suppress partially the relatively weaker conjunctival stimulation. This manifested as the conjunctival sensory transducer function being shallower (less intense sensation) when immediately preceded by corneal stimulation than when the conjunctival sensory transducer functions were measured alone (unpaired). The underlying mechanism could be adaptation or some other inhibitory effect, such as diffuse noxious inhibitory control. At some level therefore, corneal and conjunctival sensory channels are not independent.  (+info)

Topical combination of NGF and DHA increases rabbit corneal nerve regeneration after photorefractive keratectomy. (23/109)

PURPOSE: To investigate the effect of nerve growth factor (NGF) in combination with docosahexaenoic acid (DHA) on corneal nerve regeneration in a rabbit model after PRK and correlate the findings with functional tear test. METHODS: Unilateral PRK was performed on 21 New Zealand albino rabbits. Three groups, each consisting of six rabbits, were randomized to receive twice-weekly treatments with DHA, NGF, or NGF plus DHA delivered by collagen shield. A fourth group, the control, received treatment with albumin. Rabbits were observed for 8 weeks, and tear secretion tests were conducted every 15 days. The eyes were prepared for immunostaining. Monoclonal antibodies for class II beta-tubulin, calcitonin gene-related peptide (CGRP), substance P (SP), and Ki-67 were used. Cell nuclei were stained with 4',6'-diamino-2-phenylindole (DAPI). Positive staining areas in relation to total area were calculated with image-analysis software. RESULTS: There were no significant differences in the tear-secretion test results among the four groups. However, none of the eyes treated with NGF plus DHA showed rose bengal staining 30 days after PRK, compared with 50% in the control group and 33% in the DHA-treated group. A higher percentage of Ki-67-positive cells, a marker of cell proliferation, was observed in the DHA plus NGF-and NGF-treated groups compared with DHA alone or the control. Eight weeks after PRK, tubulin-positive and CGRP-positive epithelial and subbasal nerve bundle areas were significantly higher in the DHA plus NGF group than in the control and NGF or DHA alone. No differences were noted in the SP-positive nerve bundles between the different treatments and the control treatment. CONCLUSIONS: NGF plus DHA treatment after PRK in rabbits is associated with increased corneal nerve surface area, increased epithelial proliferation, and decreased rose bengal staining compared with NGF, DHA, or vehicle control alone. The combination of NGF plus DHA yields faster nerve recovery after PRK and may have therapeutic usefulness in the treatment of post-PRK dry eye and other neurotrophic keratopathies.  (+info)

Mapping of the normal human corneal sub-Basal nerve plexus by in vivo laser scanning confocal microscopy. (24/109)

PURPOSE: To produce a two-dimensional reconstruction map of the living human sub-basal corneal nerve plexus using in vivo confocal microscopy. METHODS: Laser scanning in vivo confocal microscopy was performed on three normal eyes of three healthy human subjects. Subjects were asked to fixate on targets arranged in a grid to enable examination of the cornea in a wide range of positions. Using the section mode, a mean of 573 +/- 176 images of the sub-basal plexus were obtained for each subject. The data were arranged and images were mapped for each subject into confluent montages. RESULTS: Mean dimensions of the corneal areas mapped were 4.95 +/- 0.53 mm horizontally and 5.14 +/- 0.53 mm vertically. In all subjects, the sub-basal nerve plexus appeared to radiate toward a whorl-like complex centered 1 to 2 mm inferior to the corneal apex. Outside this area, the nerve fiber bundles in the remainder of the cornea were arranged in a radiating pattern. Mean nerve density was significantly higher in the inferocentral whorl region (25,249 +/- 616 microm/mm2) compared with the central cornea (21,668 +/- 1411 microm/mm2) (Mann-Whitney U test; P = 0.05). CONCLUSIONS: This is the first study to elucidate the overall distribution of sub-basal nerves in the healthy, live central to mid-peripheral human cornea by laser scanning in vivo confocal microscopy. The whorl pattern of the sub-basal nerves is similar to that seen in the epithelium in corneal verticillata and may lend support to the theory that epithelial cells and nerves migrate centripetally in tandem.  (+info)