In vivo corneal confocal microscopy and optical coherence tomography on eyes of participants with type 2 diabetes mellitus and obese participants without diabetes.

PURPOSES: To examine corneal nerve and retinal nerve characteristics of participants with type 2 diabetes mellitus (T2DM) compared with obese participants without diabetes to discover potential nerve vulnerabilities. METHODS: All participants underwent a complete medical examination including a physical examination and blood sample tests. The ophthalmologic examination included best-corrected visual acuity, intraocular pressure, Schirmer test, tear film breakup time, slit-lamp examination, dilated fundus photography, in vivo corneal confocal microscopy (IVCCM), and optical coherence tomography (OCT). RESULTS: The study cohort consisted of 83 eyes of 83 individuals: a group of 44 participants with T2DM, and a control group of 39 obese participants with no history of diabetes. Comparing measurements on the two groups, participants with T2DM had lower values with statistical significance for retinal nerve fiber layer (RNFL) nasal superior thickness (p = 0.010) and three corneal nerve (CN) parameters: fiber length (p = 0.025), total branch density (p = 0.013), and fiber area (p = 0.009). There was a borderline significant difference in CN fiber width (p = 0.051) and RNFL nasal inferior thickness (p = 0.056). No other significant differences were observed in the IVCCM and OCT parameters. No statistically significant correlation was found between CN and RNFL parameters. CONCLUSIONS: Progression from a pre-diabetic obese state to a T2DM condition might entail a loss or diminishment of certain corneal nerve fibers or retinal nerve fibers, but not necessarily a loss of both corneal and retinal nerve fibers simultaneously. Using IVCCM and OCT together enables monitoring of both corneal and retinal health of the eye.

Plasminogen activator activity in tears of pregnant women.

PURPOSE: Plasminogen activator activity (PAA) in tears of pregnant women was investigated at various gestation times to assess the availability of plasminogen activator for aiding potential corneal wound healing processes during pregnancy. METHODS: PAA was measured by a spectrophotometric method. The analysis used 91 tear samples from pregnant and non-pregnant women, supplemented with 10 additional tear PAA measurements from non-pregnant women obtained in a previous study. RESULTS: Tear levels of PAA in pregnant women formed a bimodal distribution. Either the tear PAA level was zero or non-zero during pregnancy. When non-zero, the tear PAA level was dissociated from gestation time and not different than non-pregnant and post-pregnant levels. The frequency of occurrence of zero level tear PAA increased with gestation: 16%, 17% and 46% had zero tear PAA in samples taken from women in the first, second and third trimester, respectively. CONCLUSIONS: Overall, of the tear samples taken from women during pregnancy, a total of 26% were at zero tear PAA. The remaining tear samples had non-zero tear PAA values throughout gestation equivalent to non-pregnant tear PAA values, suggesting local control of the source of PAA in tears. Given the importance of the plasminogen activator system in tears to wound healing in the cornea, and the high occurrence of zero tear PAA in our sample of pregnant women, elective corneal surgery would be contraindicated. If corneal surgery is nevertheless necessary, the tear PAA level would be worth checking and patients with low level should be closely observed during the postoperative period.

Urokinase down-regulation by aprotinin in rabbit corneal cells after photorefractive keratectomy.

PURPOSE: To examine the effect of aprotinin eye drops on urokinase-type plasminogen activator (uPA) gene expression in rabbit corneal cells during wound healing after photorefractive keratectomy (PRK). METHODS: Both eyes of 22 rabbits were subjected to PRK. One eye of each rabbit was treated with antibiotic eye drops five times while the contralateral eye was treated at the same time with antibiotic eye drops and a serine protease inhibitor. The animals were sacrificed at different time frames, and 2-4 rabbits were used for each time point. Half of each cornea was used for the determination of the amount of uPA mRNA after reverse transcription and real-time quantitative polymerase chain reaction, while frozen sections were prepared from the other halves for in situ zymography to detect uPA activity. RESULTS: The level of uPA mRNA in corneal cells was markedly increased in corneal samples obtained hours after PRK. The time-dependent up-regulation of uPA mRNA was strongly dependent on the diameter of the area from which the epithelial cells were removed before the surgery. Independently of the time scale of uPA up-regulation, application of eye drops containing aprotinin significantly diminished the uPA expression. In situ zymography confirmed that aprotinin has also decreased overall uPA activity. CONCLUSIONS: Aprotinin down-regulates uPA gene expression in corneal cells during the wound-healing phase after PRK.

Iris cross-sectional area decreases with pupil dilation and its dynamic behavior is a risk factor in angle closure.

PURPOSE: To estimate the change in iris cross-sectional (CS) area with pupil dilation using anterior segment optical coherence tomography comparing eyes with angle closure (AC) to open angle glaucoma (OAG). METHODS: Sixty-five patients from the Wilmer Glaucoma service, 36 with definite or suspected OAG and 29 with definite or suspected AC, underwent anterior segment optical coherence tomography imaging under 3 conditions (pupil constriction to light, physiologic dilation in the dark, and after pharmacologic dilation). The nasal and temporal iris CS areas were measured with custom software, 3 times in each of 4 meridians. The principal outcome variables were iris CS area and change in iris CS area/mm pupil diameter change. The relation of these parameters to potential variables that would influence iris area was estimated by multivariate regression. RESULTS: CS area was smaller in eyes with larger pupil diameter, those that had undergone trabeculectomy, and those of European-derived persons (P<0.05 for all in a univariate analysis). In a multivariate model with CS area as the dependent variable, larger pupil diameter (with a 0.19 mm decrease in CS area for each 1 mm of pupil enlargement, P=0.0002), and trabeculectomy remained significant factors. In a second multivariate model, AC irides had less change in CS area/mm pupil enlargement than OAG or OAG suspects (P=0.01). Change in iris CS area was essentially complete in 5 seconds (n=10 eyes). CONCLUSIONS: The iris loses nearly half its volume from a pupil diameter of 3 to 7 mm, probably by eliminating extracellular fluid. Smaller iris CS area change with physiologic pupil dilation is a potential risk factor for AC. Dynamic iris CS area change deserves testing as a prospective indicator of AC.

Plasminogen activator inhibitor in human tears after laser refractive surgery.

PURPOSE: To observe levels of plasminogen activator inhibitor (PAI) in human tears after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). SETTING: University medical center eye clinic. METHODS: Tear samples were collected from 46 eyes having PRK and 13 eyes having LASIK immediately before and after surgery and on the first (LASIK), third (PRK), and fifth (PRK) postoperative days. Analyses used enzyme-linked immunoassay, yielding 61 PRK PAI-1 determinations and 146 PRK and 35 LASIK PAI-2 determinations. RESULTS: All determinations of PRK PAI-1 were below the detection limit of 1 ng/mL of the original tear sample. In the PRK eyes, the mean PAI-2 concentration was 19.8 ng/mL +/- 23.4 (SD) in preoperative tears, 112.7 +/- 60.5 ng/mL immediately postoperatively, 12.1 +/- 19.5 ng/mL after 3 days, and 15.5 +/- 20.4 ng/mL after 5 days. In the LASIK eyes, the mean PAI-2 concentration was 19.0 +/- 33.1 ng/mL preoperatively, 111.5 +/- 69.2 ng/mL immediately postoperatively, and 15.7 +/- 18.8 ng/mL after 1 day. CONCLUSIONS: The similarity in the general time pattern of PAI-2 after PRK and LASIK suggests commonality in the enzymatic control response to corneal surgical wounding. Taken in the context of previous work, the observed levels of PAI-2 concentration in eyes with and without opacification suggest that in the postsurgical period, PAI-2 is not the controlling mechanism for the later development of corneal opacification and haze.

Urokinase-type plasminogen activator to prevent haze after photorefractive keratectomy, and pregnancy as a risk factor for haze in rabbits.

PURPOSE: To observe the effect of urokinase-type plasminogen activator (uPA) on the development of subepithelial haze after photorefractive keratectomy (PRK) and to assess pregnancy as a risk factor for haze. METHODS: In 30 rabbits, both eyes of 27 were subjected to PRK and both eyes of 3 served as the nonsurgical control. In the first part of the experiment, for 7 days after PRK, three rabbits (one was pregnant) received aprotinin in one eye and no aprotinin in the contralateral eye. uPA activity was measured by a spectrophotometric method from tear samples in these eyes. In the second part, for 5 days after PRK, 24 rabbits (8 were pregnant) were treated with uPA in one eye and no uPA in the contralateral eye. Haze grading was performed according to the system of Hanna. RESULTS: In the first experiment, the aprotinin-treated eyes and the aprotinin-untreated eye of the pregnant rabbit showed development of haze. In the second, there were clear corneas in 24 of 24 uPA-treated eyes and in 15 of 24 uPA-untreated eyes. Post-PRK haze formed in 9 of 24 uPA-untreated eyes (7 of the 9 haze observations in pregnant rabbits). Within the uPA-untreated group, haze formed in corneas of 7 of 8 pregnant versus 2 of 16 nonpregnant rabbits. There was a strong association between the uPA treatment and clear corneas (P = 0.003) and between pregnancy and haze (P = 0.002). CONCLUSIONS: The present results suggest that pregnancy is a risk factor for post-PRK haze in untreated rabbit eyes and that uPA is effective in preventing the occurrence of haze.

Aqueous flow through the iris-lens channel: estimates of differential pressure between the anterior and posterior chambers.

PURPOSE: To explore the hypothesis that differential pressure between the anterior and posterior chambers arises from the dynamics of aqueous flow across the iris-lens channel. METHODS: Navier-Stokes equations of fluid dynamics were derived and evaluated numerically for a viscous homogeneous isotropic fluid (aqueous) passing through the iris-lens channel, which is a spherical disc-shaped region conforming to the lens curvature while maintaining a separation distance (channel height) over a certain disc width (channel length). The effect of iridotomy was assessed using Poiseuille flow dynamics. RESULTS: In the absence of measured values, ranges of anatomic and physiological variables were used for calculations. The magnitude of the posterior to anterior pressure difference was greater with increases in channel length or aqueous flow and with decreases in channel height or pupil diameter. With a nominal channel length of 0.5 mm, aqueous outflow of 2.2 microl/min, and pupil diameter of 1 mm, the pressure difference increased from 0.9 to 10 mm Hg when the channel height decreased from 7 to 3 microm. A channel height of 10 microm or greater reduced the pressure difference below 1 mm Hg for the full range of other channel parameters considered. A 50-microm iridotomy reduced the pressure difference below 1 mm Hg. CONCLUSIONS: The flow of aqueous through the iris-lens channel is driven by the pressure differential between the posterior and anterior chambers. Viscous forces within the aqueous govern the magnitudes of the flow resistance and the pressure differential. The geometry and dimensions of a specific iris-lens channel will determine whether the pressure differential is of clinical significance.

Plasminogen activator activity and inhibition in rabbit tears after photorefractive keratectomy.

Plasminogen activator is a normal component of tear fluid that plays a role in corneal wound healing processes. This work examines whether inhibitor-induced low levels of plasminogen activator activity (PAA) during corneal re-epithelialization after excimer laser photorefractive keratectomy (PRK) correlates with the eventual occurrence of haze in rabbit eyes. Tear samples were collected with glass capillaries from 16 eyes of eight New Zealand rabbits, using i.m. injection of pilocarpine hydrochloride for stimulation. Tears were collected before and after PRK surgery, and then daily for 5 days, and every fourth day thereafter for 3 months. Both eyes underwent PRK treatment. One eye of each rabbit was treated as a control while the contralateral eye was treated with aprotinin, a serine protease inhibitor, over the first 7 days. PAA in the tear samples was measured by a spectrophotometric method using human plasminogen and chromogenic peptide substrate S-2251. For the eight control eyes after PRK, the PAA values were significantly lower (day 1) and higher (days 2 and 3) than the equilibrium PAA (p<0.001). The corneas remained clear in each of these control eyes. For the eight contralateral aprotinin-treated eyes after PRK, the PAA values on days 1-7 were significantly lower than the equilibrium PAA (p<0.001). All eight of these aprotinin-treated eyes developed corneal haze after 2 months. There was no significant difference (p=0.06) between control and aprotinin-treated eyes for the equilibrium PAA after 19 days. We conclude that a corneal wound healing abnormality (haze) develops in rabbit eyes after PRK when PAA levels are reduced using aprotinin for a week following PRK.

Timing of changes in interstitial and venous blood glucose measured with a continuous subcutaneous glucose sensor.

The objective of this study was to use a subcutaneous continuous glucose sensor to determine time differences in the dynamics of blood glucose and interstitial glucose. A total of 14 patients with type 1 diabetes each had two sensors (Medtronic/MiniMed CGMS) placed subcutaneously in the abdomen, acquiring data every 5 min. Blood glucose was sampled every 5 min for 8 h, and two liquid meals were given. A smoothing algorithm was applied to the blood glucose and interstitial glucose curves. The first derivatives of the glucose traces defined and quantified the timing of rises, peaks, falls, and nadirs. Altogether, 24 datasets were used for the analysis of time differences between interstitial and blood glucose and between sensors in each patient. Time differences between blood and interstitial glucose ranged from 4 to 10 min, with the interstitial glucose lagging behind blood glucose in 81% of cases (95% CIs 72.5 and 89.5%). The mean (+/-SD) difference between the two sensors in each patient was 6.7 +/- 5.1 min, representing random variation in sensor response. In conclusion, there is a time lag of interstitial glucose behind blood glucose, regardless of whether glycemia is rising or falling, but intersensor variability is considerable in this sensor system. Comparisons of interstitial and blood glucose kinetics must take statistical account of variability between sensors.

Gender and age effects on pulsatile ocular blood flow.

PURPOSE: To examine gender and age effects on pulsatile ocular blood flow (POBF). METHODS: Normal subjects, 152 females and 107 males, were separated into younger (40-50) and older (50-60) age groups. RESULTS: For younger women, mean POBF (15.3 +/- 3.7 microl/s) was significantly different (p < 0.01) than for older women (13.8 +/- 3.5 microl/s), younger men (13.2 +/- 3.3 microl/s), and older men (13.3 +/- 3.1 microl/s). The mean POBFs for each of the latter three groups were not significantly different (p > 0.41) from one another. The four groups showed no significant differences in intraocular pressure (p > 0.07) or refraction (p > 0.46). Pulse rate for younger women was significantly higher (p < 0.05) than for the older two groups, but there were no significant pulse rate differences (p > 0.08) between other groups. POBF was not correlated with IOP (r2 < 0.04), refraction (r2 < 0.009) or pulse rate (r2 < 0.04). CONCLUSION: Gender and age play an important role in POBF.