Cold-induced Corneal Edema in Patients With Trigeminal Nerve Dysfunction

Cold-induced Corneal Edema in Patients With Trigeminal Nerve Dysfunction Keith H. Baratz, M.D., Stefan D. Trocme, M.D., and William M. Bourne, M.D.

Two previous cases of cold-induced corneal edema have been reported in patients with corneal anesthesia secondary to a trigeminal nerve disorder. We studied six patients with complete unilateral corneal anesthesia after trigeminal ablation. Subjects' eyes were exposed to 4 C air from a fan for one hour. We measured corneal thickness, corneal surface temperature, and endothelial permeability to fluorescein. During cold exposure, two of the six study eyes exhibited reversible corneal swelling (11% and 26% over baseline value). All anesthetic corneas were consistently colder (13.8 ± 0.7 C) than the contralateral corneas (21.0 ± 1.7 C, P .001). Baseline endothelial permeability and aqueous humor flow rates were similar in both the study and control groups. After cold exposure, the study eyes had a significant transient increase in permeability compared to the controls (7.5 ± 2.4 x 10- 4 em/min vs 2.9 ± 1.4 x 10- 4 em/min, P = .007). Baseline endothelial photomicrographs also showed increased pleomorphism (fewer hexagonal cells) in the anesthetic corneas. These data suggest that sensory de nervation of the eye influences ocular temperature regulation and corneal endothelial cell morphologic characteristics. Some anesthetic corneas are prone to cold-induced edema, which may result from excessive cooling.

=

Two RECENT REPORTS describe patients with unilateral cold-induced corneal edema associ-

ated with ipsilateral trigeminal neuropathyY In both cases, substantial corneal swelling ensued rapidly after exposure to a cold ambient temperature. Edema subsided within several hours after returning to room temperature (20 C). In each patient, only the anesthetic cornea was measurably affected, even though the contralateral eye was subjected to the same environmental conditions. Thorgaard, Holland, and Krachmer' measured the corneal surface temperature in their subject with a contact thermocouple. They found both eyes to be the same temperature during cold exposure. The conclusion drawn from these studies was that the denervated cornea was prone to cold-induced edema. A mechanism for such a neural influence is not known. We examined a group of patients with unilateral trigeminal nerve dysfunction in order to determine whether cold-induced edema is a universal finding in the anesthetic cornea. In an effort to measure endothelial morphologic characteristics and function we have included specular microscopy and fluorophotometry in the examination of these patients. Corneal surface temperature was also monitored, because this variable may influence corneal edema. Studies performed by Mapstone" on the temperature and the infrared emission characteristics of the anterior segment indicate the usefulness of noncontact infrared bolometry for corneal temperature measurements. Subjects and Methods

Accepted for publication Aug. 19, 1991. From the Department of Ophthalmology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. This study was supported in part by National Institutes of Health grant EY02037; Research to Prevent Blindness, New York, New York; and the Mayo Foundation, Rochester, Minnesota. Reprint requests to William M. Bourne, M.D., Department of Ophthalmology, Mayo Clinic, 200 First St. S.W., Rochester, MN 55905.

548

We selected six patients with complete unilateral trigeminal nerve dysfunction resulting from surgical treatment at least three years previously for cluster headaches. Subjects 1, 2, 3, 5, and 6 underwent selective percutaneous radiofrequency thermocoagulation of the gasserian ganglion affecting the first and second divisions of the trigeminal nerve. Subjects 2

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and 4 underwent complete retrogasserian rhizotomy of the sensory root of the trigeminal nerve via suboccipital craniectomy (Subject 2 underwent both thermocoagulation and rhizotomy on the same side, one month apart). Subject 1 underwent bilateral procedures, and the remaining five subjects underwent unilateral procedures. After informed consent, each patient underwent a thorough ophthalmic examination of visual acuity, pupils, visual fields, extraocular movements, applanation tonometry, slit-lamp biomicroscopy, and ophthalmoscopy. Symmetry of pupil size and interpalpebraI fissures was noted in order to exclude the possibility of a concomitant Horner's syndrome. Corneal sensation was tested by Cochet-Bonnet esthesiometry. This measures the cornea's sensory threshold to the tip of a fine 6-cm-Iong nylon filament extended from a pencil-shaped barrel.' As the nylon filament is drawn up into the barrel, the filament becomes stiffer and less easily bent, thereby exerting more pressure at the tip. Tear secretion was measured using conventional filter-paper strips both before (Schirmer I test) and after (basal tear secretion test) instillation of 0.5% proparacaine solution. Baseline corneal thickness was calculated as the mean of three consecutive measurements with a modified optical pachymeter." Each eye had baseline wide-field endothelial photography and slit-lamp photography performed. These were used to determine anterior chamber volume," which is necessary for anterior segment fluorophotometry. The autofluorescence of each cornea and anterior chamber was measured with a two-dimensional scanning ocular fluorophotometer." Anterior segment fluorophotometry was performed the next day. At 2 A.M. one drop of 2% sodium fluorescein was instilled in each eye. This dose was repeated at five-minute intervals for a total of five drops in the contralateral control eye and two drops in the study eye. Preliminary studies indicated that equivalent doses of fluorescein eye drops produce higher stromal concentrations in denervated corneas compared to normal corneas. At hourly intervals from 8 A.M. to 11 A.M., a two-dimensional scanning ocular fluorophotometer measured corneal stromal and aqueous humor fluorescence at 488 nm in a manner described by McLaren and Brubaker." After the 11 A.M. measurement, the subjects entered a cold room maintained at 4 C. They were placed 35 to 40 cm in front of a rotary desk-top fan directed at the face. Corneal surface temperature was mea-

549

sured with an infrared bolometer (Linear Laboratories, Model C600-M, Mountain View, California), the probe being held 2 cm from the cornea. Corneal temperature was recorded for each eye at IS-minute intervals during cold exposure. While in the cold room, we also monitored blink frequency and symmetry of eyelid closure. After 60 minutes, the subjects left the cold room. Fluorophotometry, optical pachymetry, bolometry, and slit-lamp examination were then performed every 15 minutes for two hours and then hourly for an additional two to three hours. All values of corneal thickness represent the mean of three consecutive readings with the optical pachymeter. Corneal endothelial permeability was calculated from the fluorophotometry data using the methods of Jones and Maurice': Permeability = k c.ca q rca where q is the mean stromal thickness, which is estimated to be the total central thickness." and rca is the fluorescein distribution ratio between the cornea and the anterior chamber, on the basis of the observation that protein binding of fluorescein produces a stroma:aqueous humor ratio of fluorescein greater than unity at steady state." Th e trans f er coe ffici cient k c.ca =

ACc (rcaC a - Cc) At

where C, = average corneal concentration of fluorescein over the time interval ~t, and C, = average anterior chamber concentration of fluorescein over the interval M, and ~Cc = the change in corneal fluorescein concentration over the interval ~t. The average fluorescein concentrations were determined from concentrations measured at the beginning and end of each time interval:

We made two additional adjustments in our calculations of endothelial permeability in order to attempt to correct for the uncertainties introduced when corneal thickness changes over the measurement interval. First, the effect of active corneal swelling or thinning upon the fluorescein distribution ratio (rca) was estimated. As the cornea swells, the stromal protein concentration will decrease, assuming soluble proteins do not transfer into or out of the

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cornea. From the law of mass action," the adjusted distribution ratio is:

where r'ea is the steady-state distribution ratio for fluorescein in human corneas of normal thickness, and qo and qt represent the corneal thickness at the beginning and end, respectively, of the time interval measured. We used 1.6 as the value for r'ea. ll The second correction that we made to allow for the effects of changing corneal thickness was the estimate of stromal fluorescein concentration. In our fluorophotometry system, the size of the focal diamond on the cornea, which is formed by the intersection of the exciting laser beam and the optical pathway into the photomultiplier tube, is thicker than the cornea itself. Therefore, the fluorescence obtained from the focal diamond reflects corneal fluorescein as well as the adjacent air, tear film, and aqueous humor. As the cornea swells, the efficiency of the focal diamond increases, because a greater proportion of the diamond is included within the cornea. Given a mild to moderate degree of corneal swelling, we may assume in our system that the relationship between the efficiency of the focal diamond, ef.d, and the changing corneal thickness is linear: e f .d = mq + b For our equipment, m 0.29.

0.86 mrn " and b

=

The true corneal fluorescein concentration, C; was determined on the basis of the focal diamond efficiency at the corneal thickness at which the fluorescence measurement was made: C' or C C e_.=..J: e-

er.d

C'

e mq +b

where C", is the uncorrected measurement of corneal fluorescein concentration. Specular photomicrographs of the central corneal endothelium of each eye were projected at a magnification of x 500. The vertices of 100 adjacent cells for each cornea were marked and then digitized to find cell area and the number of sides per cell. Polygonality and the coefficient of variation of cell area (standard devia-

tion divided by mean) were determined from these data. All data were analyzed using the two-tailed Student t-test for paired samples. A probability of .05 or less was considered statistically significant.

Results

Corneal esthesiometry-Complete unilateral corneal anesthesia was confirmed by CochetBonnet esthesiometry inall six patients (a reading of 0 on a scale of 0 to 6.0, with 0 being complete anesthesia). Subject 1, who had been treated for bilateral cluster headaches, had complete anesthesia on one side but near-normal skin and corneal sensation on the other side. The central corneal sensation on the latter side was measured as 4.0. The control eyes in the other five subjects had a mean central corneal sensation of 5.9 (range, 5.5 to 6.0). Because the one cornea in Subject 1 had only mildly decreased sensation, it was included with the control group of fellow eyes. Corneal thickness-As a result of cold exposure, two of the six anesthetic corneas swelled (Table 1). Before cold exposure, baseline corneal thicknesses in these eyes were similar to their fellow controls. None of the control eyes nor any of the other four study eyes exhibited corneal edema. Remarkable swelling was defined as a 5% increase in thickness over baseline value. The corneal thickness of the study eye increased 11 % (0.540 to 0.608 mm) in Subject 1 and 26% (0.515 to 0.647 mm) in Subject 2. In both cases, swelling was evident at the first postcold pachymetric measurement, 15 minutes after leaving the cold room. At this time, thicknesses were 0.573 mm and 0.627 mm, but the maximal thickness was not attained until 90 minutes and 45 minutes after leaving the cold room in Subjects 1 and 2, respectively. In both subjects, the visual acuity in the affected eye had decreased from 20/20 to 20/40, whereas the control eye had remained at 20/20. Slitlamp examination of these corneas exhibited stromal haze and Descemet's folds. The findings were more pronounced in Subject 2, whose cornea also had epithelial bedewing. Both corneas gradually returned to their baseline thicknesses within two hours. Temperature-At room temperature, the denervated eyes had a corneal surface temperature similar to the contralateral control eyes

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TABLE 1 RESULTS OF PACHYMETRY AND FLUOROPHOTOMETRY AFTER COLD EXPOSURE IN STUDY EYES AND CONTROL EYES CORNEAL THICKNESS

ENDOTHELIAL PERMEABILITY [x 10- 4 eM/MIN)

(MM)

VALUE

VALUE

BASELINE

15 TO 45

50 TO 267

AQUEOUS

BASELINE

VALUE AT

MINUTES

MINUTES

HUMOR

INTRAOCULAR

MAXIMUM MEAN EYES

VALUE

TEMPERATURE

BASELINE

AFTER COLD

BASELINE

COLD

AFTER COLD

AFTER COLD

FLOW RATE

PRESSURE

IN COLD (C)'

VALUE

EXPOSURE

VALUE

EXPOSURE!

EXPOSURE

EXPOSURE

(pL/MIN)

(MMHG)

3.60 1.80 2.20 4.42 1.87

12 12

Subject 3

13.5

0.510

Subject 4 Subject 5

14.4 13.6

0.560 0.598

Corneal Thickness and Permeability of Study Eyes 0.608 5.19 1.08 6.93 3.87 0.647 2.97 4.04 11.58 4.25 0.528 4.22 1.37 5.51 3.75 0.575 5.69 2.16 6.97 4.41 0.602 4.12 2.85 6.54 4.35

Subject 6

12.9

0.603

0.633

Mean (± SO)

13.8

0.554

0.600

4.44

(0.7)

(0.040)

(0.043)

(1.05)

Subject 1

20.2

Subject 2 Subject 3 Subject 4

24.0 20.8

0.548 0.517

Subject 1 SUbject 2

14.9 13.8

21.1 18.7

0.540 0.515

0.522 0.565

15 2.30 (1.19)

7.51

4.13

(2.35) (0.30) Corneal Thickness and Permeability of Control Eyes 0.573 4.40 4.38 1.62 3.56 0.515 5.00 5.50 4.08 4.65 0.530 4.12 2.40 1.84 3.65 0.568 4.10 5.91 4.63 4.92 0.600 3.19 2.72 2.34 5.08 0.627

Subject 5 Subject 6

21.5

0.595 0.617

Mean (± SO)

21.0 (1.7)

0.561 (0.040)

0.569 (0.042)

P value*

.001

.057

.213

15 18 12

2.78

14.0

(1.17)

(2.45)

3.35 3.16 2.34 4.00 1.58

13 13 13

17 12 15

4.52 (1.01)

3.82 (1.27)

2.90 (1.37)

4.37 (0.72)

2.89 (0.94)

13.8 (1.83)

.879

.054

.007

.275

.753

.738

'Mean temperature in each eye was determined as the mean of the bolometer measurements after 30, 45. and 60 minutes of cold exposure. rrhe 90-minute interval was from 15 minutes before entering the cold room to 15 minutes after leaving the cold room. *Two-sided Student t-test for paired samples.

(34.3 C vs 34.9 C). Upon cold exposure, all eyes became colder. The study group of eyes became markedly colder than their fellow eyes, however (Table 1). The mean temperature of the study corneas, as found by calculating the mean of the temperature readings after 30, 45, and 60 minutes of cold exposure, was 13.8 ± 0.7 C compared to 21.0 ± 1. 7 C for the controls (P = .001). The mean temperature for the two study corneas that swelled was 14.9 and 13.8 C compared to 13.6 C for those study corneas that displayed no marked change in thickness. The eyelid fissure width and blinking were similar between both eyes of all subjects. The temperature difference between the normal and anesthetic sides was not confined to the globes. The entire skin surface region supplied by the involved portions of the trigeminal nerve was colder on the denervated side. After removal

from the cold, both eyes in all subjects returned to normal precold temperatures. This occurred by the time of the first postcold measurement, approximately 15 minutes after leaving the cold room. Endothelial permeability-Fluorophotometry data were examined for five of the six subjects who underwent cold exposure (Table 1, Fig. 1). Data from Subject 6 were excluded from this portion of the study because the fluorescein concentration in the anesthetic cornea was extremely high (> 3,000 ng Zml). We considered our equipment to be inaccurate at such high concentrations. Baseline permeability values before cold exposure were similar in the study and control groups (4.44 ± 1.05 vs 4.52 ± 1.01 x 10:-4 em/min). During cold exposure, both groups exhibited a decrease in permeability that was

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AMERICAN JOURNAL OF OPHTHALMOLOGY

10

.

."""""" Cold

~

H

~

,... o

Eyelid closure was also similar in both eyes, and lagophthalmos was not observed.

?

~

8 a.rn.

• Control eyes CStudyeyes TMean", SO

I

I

1f 11

c!

Discussion

'P=O,OO7 I

Noon

I

I

I

5 p.m.

Time

Fig. 1 (Baratz, Trocme, and Bourne). Corneal endothelial permeability to fluorescein before, during, and after cold exposure in five subjects. more profound in the anesthetic eyes. The difference between the two groups, however, was only of borderline significance (2.30 ± 1.19 vs 3.82 ± 1.27 x 10- 4 cm Zmin: P = .054). After cold exposure, there was a dramatic, transient increase in permeability in the study group. A similar effect was not evident in the control group. During the 30 minutes after the first postcold-exposure measurement (15 to 45 minutes postcold exposure), the endothelial permeability of the anesthetic eyes differed significantly from the controls (7.51 ± 2.35 vs 2.90 ± 1.37 x 10- 4 cm Zmin: P = .007). From 50 to 267 minutes after cold exposure, the permeabilities were again similar.

Intraocular pressure and aqueous humor flow-

The baseline intraocular pressure was normal in all subjects (Table 1). Aqueous humor production was measured fluorophotometrically during the 8 A.M. to 11 A.M. baseline recordings. There was no statistically significant difference between the study group and control group of eyes (2.78 ± 1.17 vs 2.89 ± 0.94 ~l/min).

Endothelial morphologic characteristics-En-

dothelial characteristics between the study eyes and their contralateral controls were significantly different (Fig. 2). Pleomorphism, measured as an inverse function of the mean percentage of hexagonal cells, was significantly greater in the anesthetic eyes (Table 2). The study eyes averaged 56% ± 5% hexagonal endothelial cells compared to 66% ± 6% in the controls (P = .009); the mean and coefficient of variation of cell area were similar in the anesthetic and control groups (Table 2). Tear production-Tear production measured by filter-paper strips before and after anesthesia was achieved with anesthetic eye drops was normal and similar in both eyes of all subjects.

We included the second eye of Subject 1 in the control group even though it had mildly decreased sensation. We thought that this was justified because its functional measurements were similar to those of the control group and clearly different from its mate (Table 1). Conversely,the morphologic measurements in the second eye of Subject 1 resembled those of the denervated eyes (polymegethism and pleomorphism) more than those of the control group (Table 2). In any case, if both eyes of Subject 1 are omitted from the study, the statistically significant differences are still present (mean temperature in cold, P = .002, N = 5; endothelial permeability 15 to 45 minutes after cold exposure, P = .025, N = 4; and percent of hexagonal cells, P = .009, N = 5). Edema of the cornea subjected to cold in vitro has been extensively studied.":" Reversibility of swelling when the cornea returns to physiologic temperature has also been clearly demonstrated. In vivo studies have been performed in rabbits in which flow-through contact lenses perfused with cold saline solution-induced corneal edema." In humans, cold-induced corneal changes unrelated to trigeminal neuropathy have only been described in severe environmental conditions.F:" Cooling of the in vitro cornea results in a decreased electric potential across the endothelial surface.":" Additionally, the reversibility of swelling is oxygen-dependent and inhibited by antimetabolites, implicating the energy-dependent endothelial pump as the temperature-sensitive mechanism. Bito, Roberts, and Saraf" examined the cornea's response to cold in hibernating woodchucks." Comparable to experiments in other mammals, the cornea in vitro became edematous at temperatures of 5 C and 11 C. Interestingly, the in vivo corneas of hibernating woodchucks thickened only 7% at temperatures less than 10 C. The reason for the in vivo cornea's resistance to cold-induced edema is not known. Nor is it known whether intact neural pathways to the cornea are instrumental in preventing edema in such circumstances. In our study, one third of the denervated corneas swelled markedly (defined as a 5%

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553

Fig. 2 (Baratz, Trocme, and Bourne). Wide-field specular photomicrographs of corneal endothelium from anesthetic eye (top) and normal eye (bottom) from Subject 2 at normal ambient temperature, demonstrating polymegethism and pleomorphism in the anesthetic eye. increase over baseline thickness) during cold exposure, whereas none of the normal eyes did. A confounding variable was evident that made data interpretation more difficult; all anesthetic eyes became considerably colder than the contralateral control eyes. Therefore, a tendency for corneas to swell upon cold exposure cannot be solely attributed to the denervated state but may also be a function of how cold the tissue becomes. The corneas that swelled, however, were not colder than the denervated corneas that did not swell. We cannot determine from this study whether the decreased temperature

in the denervated corneas is sufficient to account for the observed swelling, or whether other factors are involved. This temperature difference is in contrast to the findings described by Thorgaard, Holland, and Krachmer.' Wilson, Garrity, and Bourne! did not report corneal temperatures during cold exposure. Previous reports of cold-related corneal disease in normal eyes described individuals exposed to extreme conditions.F:" In these early cases, the corneal findings included epithelial defects and stromal haze, but corneal thicknesses were not reported. lt is unclear whether

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TABLE 2 CORNEAL ENDOTHELIAL MORPHOLOGIC CHARACTERISTICS IN STUDY EYES AND CONTROL EYES COEFFICIENT OF EYES

MEAN CELL

VARIATION OF

HEXAGONAL

AREA (I'M')

CELL AREA

CELLS (%j

StUdy Eyes

Subject 1

373

0.31

54

Subject 2

410

0.31

Subject 3

393

OAO

52

Subject 4

398

0.41

50

Subject 5

371

0.30

Subject 6

285

0.23

58 61

Mean

372

0.33

56

(:t SD)

(45)

(0.07)

(5)

Subject 1

347

0.34

57

Subject 2

373

0.24

71

60

Control Eyes

Subject 3

455

0.28

72

Subject 4

0.29

64

Subject 5

369 311

0.32

63

Subject 6

359

0.31

70

Mean

369

0.30

66

(:t SD)

(47)

(0.04)

(6)

P value'

.905

.570

.009

'Two-sided Student r-test for paired samples.

these changes resulted from cold-induced alterations in corneal hydration or from actual freezing of the tissues. It has not been described whether normal in vivo human corneas swell when subjected to less harsh conditions comparable to the 10 to 15 C temperatures attained by our study eyes. One study showed that during a small decrease in temperature (from 35 C to 25 C) no swelling in rabbit corneas in vitro was observed despite a decrease in electric potential across the endotheliurn." The hypothesis offered was that a passive decrease in endothelial permeability, as evidenced by a decreased electric conductivity, or a temperature-dependent increase in water viscosity was sufficient to offset the diminished ion pump rate.19.21.22 It is possible that these homeostatic mechanisms allowed the control eyes to maintain a steady corneal thickness over the temperature range at which we studied them. Perhaps the control eyes might not have been able to maintain normal hydration if colder temperatures were attained. These proposed ideas, however, do not negate the possibility of a direct neural influence on corneal thickness.

November, 1991

Interactions between nerves and corneal endothelial cells have not been elucidated. One researcher has been able to identify nerve terminals on the corneal endothelium in rabbits." Some interactions between the epithelium and nerve supply have been established. Alper." after producing trigeminal nerve lesions succeeded by tarsorrhaphy in monkeys, found that the denervated eye produced a thinner corneal epithelial layer with less mitotic activity. Other in vitro and in vivo studies have disclosed that corneal epithelial factors can induce growth and differentiation of neuronal tissue.P:" In these studies, similar interactions between neural tissue and endothelium were not

found."

In our patients, the endothelium of the study eyes expressed greater pleomorphism compared to the controls. Perhaps this results from a lack of trophic neural factors. Such factors could reach the endothelium via corneal nerves or by dissolution in the aqueous humor of compounds produced in the anterior chamber or by the ciliary body. This idea is merely speculative, as no supporting laboratory evidence exists. An alternative explanation for endothelial pleomorphism may be chronic cold stress, because the denervated eye would be frequently colder than normal in persons living in cold environments. Fluorophotometry of the anterior segment was used as an adjunct to evaluate endothelial function. The baseline values in the study and control groups were similar. The decrease in fluorescein permeability in the anesthetic group during cold exposure was of borderline significance (P = .054). The small sample size may be contributory. If fluid viscosities and the passive diffusion of solutes are considerably altered by cooling in this tissue, then the colder study eyes might be expected to have less fluorescein movement across the endothelium during this time. Another possibility is the solvent drag effect resulting from net fluid flux across a membrane. If the cornea swells during cold exposure, the movement of water into the cornea from the anterior chamber may interfere with the simple diffusion of fluorescein out of the cornea. This would cause a misleadingly low permeability value during the time of active swelling. If solvent drag were operative, one would expect the lowest measured permeability to be in the cornea that swells the greatest and essentially no change in those corneas that do not become edematous. This was not the case in our study. The cornea that swelled the

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Cold-induced Corneal Edema and Trigeminal Dysfunction

most had the highest permeability during cold exposure (4.04 x 10- 4 cm Zhr), whereas the only other cornea that swelled had the lowest permeability (1.08 x 10- 4 cm Zhr). The study corneas that did not swell still exhibited a decreased permeability compared to their controls. The immediate postcold period was characterized by a marked increase in fluorescein permeability in the anesthetic eyes. Again, all study eyes showed such a response, including those that did not swell. Study-cornea 2, which swelled the most, did have the highest permeability for the first 30 minutes after returning from the cold room. The corneal thickness remained relatively stable during this time interval, so a solvent drag effect cannot be easily implicated. Fluid viscosity also should not have been a factor, because the tissues returned to normal temperature by the first postcold measurement at the start of the 30-minute interval. Our study found no difference in baseline aqueous humor flow rates between the denervated and control eyes. In Subject 2, whose cornea also exhibited the greatest cold-induced edema, however, the aqueous flow rate was markedly lower in the anesthetic eye compared to that of the fellow eye (1.80 vs 3.16 ~l/min). The patient studied by Wilson, Garrity, and Bourne! also had a lower aqueous flow rate in the eye with sensory denervation (2.82 vs 4.33 ~l/min). In reviewing fluorophotometry data from 80 healthy subjects previously reported from our institution," we found an asymmetry of aqueous flow rate greater than 0.70 ~l/min in only two individuals. Belmonte and associates28-30 have extensively studied neuronal activity to the eye in relation to intraocular pressure. They found that changes in intraocular pressure caused alterations in the neuronal discharges from afferent ciliary nerves" as well as from efferent ciliary nerves." Prolonged stimulation of the cervical sympathetic ganglion also caused a 12% to 19% decrease in aqueous flow rate." Hypothetically, a neural feedback loop involving the affere?t activity of the trigeminal nerve could exist as a mechanism for controlling intraocular pressure. The temperature regulation of the anesthetic cornea proved to be an unexpected variable. The cornea, lacking a direct blood supply, is reliant upon its local environment, including the eyelids, tear film, surface evaporation, aqueous humor, environmental temperature, and regional blood flow for the determination of its temperature. In this study, cold exposure caused a decrease in temperature of the dener-

555

vated cornea in comparison to the contralateral controls. Mapstone" and Rysa" theorized that marked asymmetry of corneal temperature was caused by vascular influences. The increased corneal temperatures of eyes with uveitis and decreased temperatures of eyes ipsilateral to carotid stenoses were given as examples. Other determinants of corneal temperature caused less dramatic changes and asymmetries. In our subjects, this temperature asymmetry was not limited to the globe but was observed in the region supplied by the first division of the trigeminalnerve. This regional effect is further evidence that tear surface and aqueous humor dynamics are an unlikely cause for excessive cooling. More likely, the sensory denervation of the eye and skin interrupts any feedback mechanisms by which the efferent system may regulate vasodilation to that portion of the face. 33,34

References 1. Thorgaard, G. L., Holland, E. J., and Krachmer, J. H.: Corneal edema induced by cold in trigeminal nerve palsy. Am. J. Ophthalmol. 103:641, 1987. 2. Wilson, S. E., Garrity, J. R., and Bourne, W. M.: Edema of the corneal stroma induced by cold in trigeminal neuropathy. Am. J. Ophthalmol. 107:52, 1989. 3. Mapstone, R.: Measurement of corneal temperature. Exp. Eye Res. 7:237, 1968. 4. Cochet, P., and Bonnet, R.: L'esthesie corneene. Clin. Ophthalmol. 4:3, 1960. 5. Mishima, S., and Hedbys, B. 0.: Measurement of corneal thickness with the Haag-Streit pachometer. Arch. Ophthalmol. 80:710, 1968. 6. Johnson, S. B., Coakes, R. L., and Brubaker, R. F.: A simple photogrammetric method of measuring anterior chamber volume. Am. J. Ophthalmol. 85:469,1978. 7. McLaren, J. W., and Brubaker, R. F.: A twodimensional scanning ocular fluorophotometer. Invest. Ophthalmol. Vis. Sci. 26:144, 1985. 8. Jones, R. F., and Maurice, D. M.: New methods of measuring the rate of aqueous flow in man with fluorescein. Exp. Eye Res. 5:208, 1966. 9. Carlson, K. H., Bourne, W. M., McLaren, J. W., and Brubaker, R. F.: Variations in human corneal endothelial cell morphology and permeability to fluorescein with age. Exp. Eye Res. 47:27, 1988. 10. Taarnhoj, J., Schlecht, L., McLaren, J. W., and Brubaker, R. F.: Calibration of measurements in vivo of fluorescein in the cornea. Exp. Eye Res. 51:113, 1990. 11. Ota, Y., Mishima, S., and Maurice, D. M.: Endothelial permeability of the living cornea to fluorescein. Invest. Ophthalmol. Vis. Sci. 13:945, 1974.

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