Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye.

BACKGROUND: We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy. METHODS: For this case-control study, we recruited chronic migraine patients and compared them with a sex- and age-similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a Heidelberg Retinal Tomography III confocal microscope with a Rostock Cornea Module. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton-tip applicator, measurement of tear break-up time, and completion of a validated dry eye questionnaire. RESULTS: A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs. 71.0 ± 15.0 fibers/mm2 , P < .001). Nerve fiber length was decreased in the chronic migraine group compared with the control group, but this difference was not statistically significant (21.5 ± 11.8 vs. 26.8 ± 5.9 mm/mm2, P < .084). Nerve branch density was similar in the two groups (114.0 ± 92.4 vs. 118.1 ± 55.9 branches/mm2 , P < .864). Tortuosity coefficient and log tortuosity coefficient also were similar in the chronic migraine and control groups. All migraine subjects had symptoms consistent with a diagnosis of dry eye syndrome. CONCLUSIONS: We found that in the sample used in this study, the presence of structural changes in nociceptive corneal axons lends further support to the hypothesis that the trigeminal system plays a critical role in the pathogenesis of migraine. In vivo corneal confocal microscopy holds promise as a biomarker for future migraine research as well as for studies examining alterations of corneal innervation. Dry eye symptoms appear to be extremely prevalent in this population. The interrelationships between migraine, corneal nerve architecture, and dry eye will be the subject of future investigations.

A fluidics comparison of Alcon Infiniti, Bausch & Lomb Stellaris, and Advanced Medical Optics Signature phacoemulsification machines.

PURPOSE: To compare three phacoemulsification machines for measurement accuracy and postocclusion surge (POS) in human cadaver eyes. DESIGN: In vitro comparisons of machine accuracy and POS. METHODS: Tip vacuum and flow were compared with machine indicated vacuum and flow. All machines were placed in two human cadaver eyes and POS was determined. RESULTS: Vacuum (% of actual) was 101.9% +/- 1.7% for Infiniti (Alcon, Fort Worth, Texas, USA), 93.2% +/- 3.9% for Stellaris (Bausch & Lomb, Rochester, New York, USA), and 107.8% +/- 4.6% for Signature (Advanced Medical Optics, Santa, Ana, California, USA; P < .0001). At 60 ml/minute flow, actual flow and unoccluded flow vacuum (UFV) was 55.8 +/- 0.4 ml/minute and 197.7 +/- 0.7 mm Hg for Infiniti, 53.5 +/- 0.0 ml/minute and 179.8 +/- 0.9 mm Hg for Stellaris, and 58.5 +/- 0.0 ml/minute and 115.1 +/- 2.3 mm Hg for Signature (P < .0001). POS in an 32-year-old eye was 0.33 +/- 0.05 mm for Infiniti, 0.16 +/- 0.06 mm for Stellaris, and 0.13 +/- 0.04 mm for Signature at 550 mm Hg, 60 cm bottle height, 45 ml/minute flow with 19-gauge tips (P < .0001 for Infiniti vs Stellaris and Signature). POS in an 81-year-old eye was 1.51 +/- 0.22 mm for Infiniti, 0.83 +/- 0.06 mm for Stellaris, 0.67 +/- 0.01 mm for Signature at 400 mm Hg vacuum, 70 cm bottle height, 40 ml/minute flow with 19-gauge tips (P < .0001). CONCLUSIONS: Machine-indicated accuracy, POS, and UFV were statistically significantly different. Signature had the lowest POS and vacuum to maintain flow. Regarding POS, Stellaris was close to Signature; regarding vacuum to maintain flow, Infiniti and Stellaris were similar. Minimizing POS and vacuum to maintain flow potentially are important in avoiding ocular damage and surgical complications.

Comparison of Hanna and Hessburg-Barron trephine and punch systems using histological, anterior segment optical coherence tomography, and elliptical curve fitting models.

BACKGROUND: This study analyzes the characteristics of donor and recipient tissue preparation between the Hessburg-Barron and Hanna punch and trephine systems by using elliptical curve fitting models, light microscopy, and anterior segment optical coherence tomography (AS-OCT). METHODS: Eight millimeter Hessburg-Barron and Hanna vacuum trephines and punches were used on six cadaver globes and six corneal-scleral rims, respectively. Eccentricity data were generated using measurements from photographs of the corneal buttons and were used to generate an elliptical curve fit to calculate properties of the corneal button. The trephination angle and punch angle were measured by digital protractor software from light microscopy and AS-OCT images to evaluate the consistency with which each device cuts the cornea. RESULTS: The Hanna trephine showed a trend towards producing a more circular recipient button than the Barron trephine (ratio of major axis to minor axis), ie, 1.059 ± 0.041 versus 1.110 ± 0.027 (P = 0.147) and the Hanna punch showed a trend towards producing a more circular donor cut than the Barron punch, ie, 1.021 ± 0.022 versus 1.046 ± 0.039 (P = 0.445). The Hanna trephine was demonstrated to have a more consistent trephination angle than the Barron trephine when assessing light microscopy images, ie, ±14.39° (95% confidence interval [CI] 111.9-157.7) versus ±19.38° (95% CI 101.9-150.2, P = 0.492) and OCT images, ie, ±8.08° (95% CI 106.2-123.3) versus ±11.16° (95% CI 109.3-132.6, P = 0.306). The angle created by the Hanna punch had less variability than the Barron punch from both the light microscopy, ie, ±4.81° (95% CI 101.6-113.9) versus ±11.28° (95% CI 84.5-120.6, P = 0.295) and AS-OCT imaging, ie, ±9.96° (95% CI 95.7-116.4) versus ±14.02° (95% CI 91.8-123.7, P = 0.825). Statistical significance was not achieved. CONCLUSION: The Hanna trephine and punch may be more accurate and consistent in cutting corneal buttons than the Hessburg-Barron trephine and punch when evaluated using elliptical curve fitting models, light microscopy, and AS-OCT.

Molecular mapping of a site for Cd2+-induced modification of human ether-à-go-go-related gene (hERG) channel activation.

Cd(2+) slows the rate of activation, accelerates the rate of deactivation and shifts the half-points of voltage-dependent activation (V(0.5,act)) and inactivation (V(0.5,inact)) of human ether-à-go-go-related gene (hERG) K(+) channels. To identify specific Cd(2+)-binding sites on the hERG channel, we mutated potential Cd(2+)-coordination residues located in the transmembrane domains or extracellular loops linking these domains, including five Cys, three His, nine Asp and eight Glu residues. Each residue was individually substituted with Ala and the resulting mutant channels heterologously expressed in Xenopus oocytes and their biophysical properties determined with standard two-microelectrode voltage-clamp technique. Cd(2+) at 0.5 mM caused a +36 mV shift of V(0.5,act) and a +18 mV shift of V(0.5,inact) in wild-type channels. Most mutant channels had a similar sensitivity to 0.5 mM Cd(2+). Mutation of single Asp residues located in the S2 (D456, D460) or S3 (D509) domains reduced the Cd(2+)-induced shift in V(0.5,act), but not V(0.5,inact). Combined mutations of two or three of these key Asp residues nearly eliminated the shift induced by 0.5 mM Cd(2+). Mutation of D456, D460 and D509 also reduced the comparatively low-affinity effects of Ca(2+) and Mg(2+) on V(0.5,act). Extracellular Cd(2+) modulates hERG channel activation by binding to a coordination site formed, at least in part, by three Asp residues.