An improved technique for patched eye corneal swelling studies

Clinical Article

An Improved Technique for Patched Eye Cornea1 Swelling Studies Paul Erickson,

OD,

PhD, FAAO,

and Timothy

The purpose of this study was to develop a patching technique that avoids the artifacts of physical damage to the cornea1 epithelium and reduction in intraocular pressure and to validate the application of the patching technique to the study of closed eye corneal swelling. Fifteen men between the ages of 20 and 40 years who were adapted to daily soft contuct lens wear participated. Uniform-thickness lenses (Dk/L = 17.5) were worn under the patched eye for 2, 4, and 6 hours during separate sessions and under the closed eye overnight. Epithelial integrity, effectiveness of lid closure, and comeal swelling were monitored during the patched eye sessions. Comeal swelling was measured during the owemight session. In a separate 4-hour session with a 200~pm uniform-thicknesslens (DWL = 8.75), intraocular pressureand cornea1swellingwere measured.The fellow eye servedas a control. Techniquesinvolving gauzepatchescaused signij?cantepithelialdistortionand were abandoned.The useof surgicaltapealonefailed to maintain eyeclosurefor the required time period. The bestresults were obtainedwith the Natural Eyepatch(Keekr Instruments). Swellingfolloweda cubicpolynomial time courseand stabilizedby 4 hoursfor all five sites evaluatedover a 7-mm chord of the vertical cornea1meridian. Patchedeye cornealswellingwas not a goodpredictor of individual overnight comeal swelling.No si&icant differences in epithekalintegrity or intraocularpressure betweenrestand control eyes were found. The Natural Eyepatch is a reliableand valid devicefor maintainingeyeclosurein cornea1swellingstudies.The resultsindicatethat the4-hour comealswellingresponse Address reprint requests to Paul Erickson, Bausch 6. Lomb Optics Center, 1400 North Goodman Street, Rochester, NY 14692. Accepted for publication

July 10, 1995.

1995 ICLC, Vol. 22, September/October, 0 Elsevier Science Inc. 1995 655 Avenue of the Americas, New York, NY 10010

L. Comstock,

OD,

MS, FAA0

generatedwith this techniqueprovidesa reliablemeansfor assessing the closedeye effectsof contact lenseson ropographical cornealthickness. Keywords: Contact lenses; topographical patch; intraocular

comeal swelling;

eye

pressure

Introduction Eye patching is commonly usedfor amblyopia therapy, to reduce discomfort after intraocular surgery, and for the treatment of cornea1and conjunctival surface abnormalities. Patching has also been adopted as a tool for cornea1 and contact lens research to ensure eyelid closure during sleeple5and to simulate those conditions during waking hours.5-11 Light patching, typically a strip of tape holding the upper lid closed, doesnot appear to affect the magnitude of corneal swelling during sleep.334Cornea1 swelling, however, tends to be greater as patching pressureis increased.“” Levy et al. l1 attributed this effect to patch-induced intraocular hypotony, although Fatt12 has suggestedthat the increasedswelling responsemay be simply a manifestation of restricted blood flow into the palpebral conjunctiva. Frucht-Pery et a1.13reported that patching can produce a variety of cornea1 signsand symptoms such as distortion and epithelial defects and that such effects increase with patch tightness. The purposeof this study was to develop and validate a patching technique for usein the assessment of closed eye cornea1 swelling that maintained effective closurewithout inducing potentially confounding effects on epithelial integrity, optical surface regularity, and intraocular pressure.

0892-8967/95/$10.00 SSDI 0892-8987(95)00061-X

Methods

and Materials

Table 1. Study Lens Thickness and 0, Transmissibility

Subjects Fifteen male subjects were recruited from among employees at the Bausch & Lomb Optics Center. All subjects were between the ages of 20 and 40 years and were adapted daily wearers of soft contact lenses. Subjects read and signed a statement of informed consent before enrollment and participation in the study.

Study A

B C l

Procedures Several patching techniques were screenedfor potential use in the patch validation experiments. The patch was worn over the nondominant sighting eye and was covered with a black occluder patch to prevent tampering. The techniques screenedwere the use of surgical tape only, the combination of gauzepadsand surgical tape, and the DonaldsonNatural Eyepatch (Keeler Instruments). The criteria on which the techniques were evaluated were effectiveness of lid closure, epithelial integrity, and surfacedistortion. For each technique evaluated, the eyelid and the cheek were wiped to remove excessoils and debris. A single strip of surgical tape was apphed to the eyelid and cheek for the tape-only technique. A gauze pad was fastened beneath a minimum of three strips of surgical tape for the combination patch. For the final technique, the adhesivesurfaceof the Natural was applied to the upper eyelid as close as possibleto the eyelasheswithout touching them. Two adhesive-backed velcro dots were applied to the cheek below the lower eyelid in alignment with the Natural tab. The tab was then fastened to the velcro to hold the eyelid tightly shut (Figure I). For each technique, the patching assembly was covered loosely by a headband-securedblack occluder eyepatch. The selected technique was validated with the use of hydrogel lensesworn under the patched eyelid. The lenses usedfor each of the validation experiments were processed in the Bausch & Lomb Research and Development pilot laboratory. All lenseswere fabricated from hefilcon C, a

Power (D)

Center Thickness (id

DWL Central and Average *

-0.50 -0.50 -0.75

100 100

17.5 17.5

200

a.75

Lenses had uniform thickness over a-mm optical zone.

Food and Drug Administration-approved Group II contact lensmaterial having a 57% water content and a Dk of 17.5 barrers at 35°C. Table 1 describesthe geometry and the Dk/L of the specific lensesused in each of the validation experiments. Study A was conducted to determine the timedependent stabilization of cornea1thickness increase associated with patched eye lens wear. Uniform thickness lenses(100 pm) were worn for periodsof 2, 4, and 6 hours under the patched lid during three separatesessions.Corneal thicknesswasmeasuredwith a Holden-Payor pachometer” adapted to a Rodenstock 2000 biomicroscope. Corneal thickness was measuredat five points in the vertical meridian of the test eye. The proper position of the pachometer beam and split image wasachieved for each corneal position by having subjects fixate one of five light emitting diode (LED) targets vertically arranged on a display panel, as illustrated in Figure 2. Peripheral cornea1positionshave been describedboth by the angle of ocular rotation (a) required to fixate the target and by the linear distance (Y,) of the point from the corneal apex. These variables are related by the equation15 Y, = R,sin a( 1 + Qsin2 a) -l/z where R, is the central cornea1radiusof curvature and Q is the cornea1asphericity. LED1

l

LED*?w_-----

LED50

Figure 1. Natural eyepatch in place on test eye.

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ICLC, Vol. 22, September/October 1995

Figure 2. Schematic of pachometry fixation apparatus. ai, version angle;Yi, distancefrom LED 3 to LED i (LED separation= 15 mm); d,, distance from COR to cornea1apex = 12.3 mm; dz, distance from cornea1 apex to LED 3 = 48 mm.

Patched Eye Cornea1 Swelling: Erickson and Comstock Table 2. Cornea1Positionsof PachometryMeasurements Fixation Light

Light Position Cornea1Position (mmfrom Angle a (mmfrom center) Chord for site “i”’ center) (“) (mm)

1 s

30 15 0

26.5 14.0 0

“1” “3” “2”

4 5

- 15 -30

- 14.0

“4”

- 26.5

“5”

-3.53 - 01.86

7.05 0 3.72

1.86 3.53

3.72 7.05

cornea1 swelling response, necessary for testing the IOP hypothesis. Cornea1 thickness was measured as in Experiment A. IOP was determined before and after patching by the average of three readings with an American Optical Non-Contact II Tonometer, Model 12415. Contact applanation tonometry was avoided because increased cornea1 thickness produces an artifactual apparent increase in IOP with contact applanation tonometry’9-2* and topical corneal anesthetics have been implicated as a cause of shortterm cornea1swelling.22

’ “1” is the most inferior site; “5” is the mostsuperiorsite.

Results

As shown in Figure 2, the calculation of angle a requires knowledge of the distance from the cornea1 apex to the center of rotation (COR) of the eye. Becauseno one point defines the COR,16 a rough approximation must be used. Fry and Hill17 found that for vertical rotations within 30 elevation and 40” depression,the average COR is approximately 12.3 mm posterior to the cornea1 apex. From Figure 2,

Qualitative Screeningof PatchingTechniques

tan ai = YJ(d, + d,) = Yj60.3 mm. Then, ai = arctan (YJ60.3). Using the samplemean vertical cornea1meridian R, of 7.7 mm and a population mean estimate for Q of - 0.26,” cornea1positions for these studieswere estimated to be as shown in Tabk 2. The sequenceof cornea1loci measuredon test eyes was determined by random preslection to avoid bias. The central cornea1thickness of the control, nonlens-wearing, and nonpatched eye was measuredafter the completion of all thickness measurementson the test eye. Central cornea1swelling accompanying overnight wear of the lens used in Experiment A was measuredin Experiment B. Contact lens wear was suspendedfor 24 hours before the overnight study. Baselinecentral cornea1thicknesswas measuredimmediately after lens insertion. Subjects were then instructed to go to bed for 8 hours of sleep. At awakening, subjects’ eyes remained closed until positioned before the pachometer for final central cornea1 thickness measurements.The purpose of this experiment was to provide data against which patched eye swelling resultscould be compared. Using the patching duration establishedduring Experiment A, Experiment C was conducted to ascertain the effects of the patch on intraocular pressure(IOP) and the relation of IOP changes on cornea1 swelling. Lenseswith double the uniform thickness of those usedin experiments A and B (200 pm) were worn under the patched eyelid. The lens thickness was increased to ensure a substantial

The useof surgicaltape only, similar to the “light” patch of Levy et al. , ’ ’ maintained incomplete lid closure in some subjectsover the required time. The addition of a gauze pad, resemblingthe “tight” patch of Levy et al., I1 produced discomfort accompanied by significant cornea1 distortion (seeFigure 3) in most subjects. On the basisof our initial experienceswith these techniques, we concluded that further assessment of them in cornea1swelling studieswasnot justified. The selectedtechnique, which avoided the problemsof the methodsdescribedabove, involved the application of a DonaldsonNatural Eyepatch. It wasthe general consensus of the subjectsthat the addition of the headband occluder provided a more acceptablecosmetic appearancecompared with the Natural alone. An added benefit of the occluder eyepatch was that it prevented the subjectsfrom inadvertently tampering with the Natural during the study. Validation Experiments Topographical patched eye swelling profiles are illustrated in Figure 4. Swelling was clearly most rapid for all sitesduring the first 2 hours of wear. Central swelling increasedslightly between 4 and 6 hours, whereasswelling at the 7-mm chord appears to have stabilized by 4 hours. Swelling peaked at 4 hours for the 3.75mm chord. The

Figure 3. Fluoresceinphotographillustratingsevereepithelialdistortion secondaryto wearingthe “tight” eyepatch.

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Clinical

Article

Swelling

(%)

10

I

20 2 .--------------------------~-------~--

t

---

-1

0 6

4

3

2

1

LOCATION

Figure 4. Mean topographicalcornea1swellingprofiles(%) for 2

(squares),4 (crosses) and 6 (asterisks)hoursunderuniform lens thicknessconditions.

Figure 6. Mean cornea1swellingOS.time for superior(asterisks) and inferior (squares) sites at the 3.74-mm chord diameter under uniform-thickness conditions. Error bars indicate standard error.

k, = (D - d)/(D - k,d) shapeof the swelling time functions is illustrated in Figures 5, 6, and 7. To test the hypothesis that swelling had essentially stabilized by 4 hours, Tukey’s least significant difference test was run on the swelling data with time as the main effect. The results are shown in T&k 3. Swelling at 2 hours differed significantly from swelling at both 4 and 6 hours. Swelling at 4 and 6 hours did not differ significantly, supporting the hypothesis that swelling stabilized by 4 hours. Time-dependent swelling data for these studieswere fitted to a polynomial model of the general form S = (k,t + k,t* + k,t3)k, where S is swelling for a given cornea1site, t is time, and ki are constants determined by curve fitting. The constant k4 was added here to reflect the chord diameter of the site of interest and was determined by the function

Figure 5. Mean central cornea1swellingvs. time underuniformthickness conditions. Error bars indicate standard error.

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where D is the total cornea1diameter, d is the chord diameter of interest, and k5 is a constant determined iteratively. This expressionrangesin value from 1 (cornea1center, d = 0) to 0 at the limbus (d = D). For this study, the values of the constants were found by nonlinear parameter estimation23to be k, = 23.2, k2 = -3.98, k3 = 0.225, and k, = 0.75 for time in hours. Time-dependent swelling for this lens predicted by this function for various chord diameters is shown in Figure 8. The averageovernight central cornea1swelling measured in experiment B was 67.8 + 15.3 p,rn (13.2 ? 3.2%). Central cornea1swelling data for all subjectswere tested for correlation

between

overnight

swelling

and swelling

for

each of the patching durations. These results are shown in Table 4. These results show that none of the patching durations were good predictors of individualovernight cornea1 swelling.

Figure 7. Mean cornea1swellingvs. time for superior(squares) and inferior (crosses) sitesat the 7.0-mmchord diameterunder uniform-thickness

conditions.

Error bars indicate standard error.

Patched Eye Corneal Swelling: Erickson and Cornstock Table 4. Correlationof Overnight Cennal Cornea1Swellingto

Table 3. Significanceof SwellingChangesvs. Time

PatchedEyeCentral Cornea1Swelling

Duration (h)

Duration 6)

2

2 4 6

0.008 0.015

4

6

0.008

0.015 0.962

0.962

Experiment C included the measurementof IOP in conjunction with cornea1 swelling. The results are shown in Table 5. The difference in IOP change between test and control eyeswas not statistically significant. Central cornea1swelling was also examined for correlation to IOP change for the patching period. The correlation wasextremely small (T = - 0.02) and not statistically significant. The hypothesis that patched eye IOP was reduced relative to control eye IOP can be rejected. Consequently, the hypothesis that the patching technique usedin this experiment producescornea1swelling by inducing hypotony can alsobe rejected. Discussion For the purposeof conducting closedeye cornea1swelling studies,the Natural eyepatch representsan excellent compromise between simple taping, which is insufficient to maintain complete eye closure, and bulky pads, which on the basisof our qualitative screening and previous literature,11,13lead to excessive cornea1 distortion and potentially confounding effects of IOP changes. These advantagesare alsorelevant to other indications for eye patching. Our statistical analysis (Table 3) showed that cornea1 thickness changesoccurring acrossthe central 7 mm between 4 and 6 hours were insignificant. However, the polynomial model (Figure 8) implies that, on average, thickness Swelling

(micrometers)

5o3 40

central 4mm chord

30

8mm

20

1 Omm

chord

Correlation (4

Study Duration (h) 2 4 6

Significance (D)

-0.049

0.868 0.708 0.337

0.110 -0.277

r2 0.002 0.012 0.077

stabilizesat 5 hours. Becausethe thickness differences between 4 and 6 hours were small (averaging lessthan 2 pm per site) and inconsistent in direction, we prefer the 4-hour patching duration. The time course and shapeof the central responseare similar to those reported for natural eye closure for similar periods of time.24 Coefficients for the third order polynomial are similar in magnitude but opposite in sign to those reported by O’Neal and Polse25for central cornea1deswelling over the same time course. The incorporation of a fourth coefficient, the value of which changesnonlinearly with distance from cornea1center adequately describesthe swelling response for noncentral sites. Furthermore, it readily accommodatesa condition of zero swelling at the limbus. Although differences between the superior and inferior cornea1swelling responsesin our samplewere not statistically significant, there is somesuggestionin the data that the superior cornea reachesa stable thickness more rapidly than the inferior comeal. This observation is consistent with previous findings that the superior cornea shows greater oxygen flux than doesthe inferior cornea immediately after eyelid retraction,26 but that these differences disappear26or even reverse27 after a per’0 1 d of uniform exposureto atmospheric oxygen. Larger samplesizeswill be required to assess this question. The relatively poor correlation between patched eye and overnight cornea1swelling might be the result of individual differences in the degree of eyelid closure during sleep.2 Although such differences might have been eliminated by patching the eye during sleep, the departure from normal conditions of overnight wear would have limited its value in predicting individual overnight cornea1 swelling responses.The time course and effect on swelling of the low-grade inflammatory responsehabitually occurring under the closedeye2a32might alsocontribute to intrasubject

chord

Table 5. Changein Central Cornea1Swellingvs. Change

10

in IOP

0

Parameter 0

12

3 Time

4

5

6

(h)

Figure 8. Time-dependentswellingfor selectedchord diameters

on the basisof the derivedthird order polynomialfunction.

Central swelling(%) SE IOP (mm Hg) SE

ICE,

Vol.

Test

Control

+11.1

-0.3 (0.3) -1.6 (0.4)

(0.5)

- 1.3 (0.3)

22,

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Clinical Article differences between patched eye and overnight cornea1 swelling. In any case, our results suggest that patched eye cornea1 swelling during waking periods is not a good quantitative predictor of natural overnight cornea1 swelling for individual subjects. Nevertheless, our results indicate that the 4-hour cornea1 swelling response generated by this technique provides a reliable means for assessing the closed eye effects of contact lenses on topographical cornea1 thickness.

References 1. Marshall D: The effect of polymegethism on the human closed-eye cornea1 swelling and recovery response. MS Thesis, Ohio State University, 1988. 2. Refojo MF, Koch JM, Leong FL: The effect of lid closure on overnight cornea1 swelling with 2 types of silicone rubber lenses in rabbit eyes. Invest Ophthalmol Vis Sci 1989; 3O(Suppl):480. 3. Cox I, Ames K: Effect of patching on the overnight cornea1 swelling response with rigid contact lenses. Optom Vis Sci 1989;66:207-208. 4. Staarmann MT, Schoessler JP: Contact lenses and eye closure: Comparative analysis using three different methods to induce comeal swelling. @torn Vis Sci 1991;68:374379. 5. Sweeney DF: Factors contributing to the human cornea1 oedema response. PhD Thesis, University of New South Wales, New South Wales, Australia, 1991. 6. Mandell RB, Lieberman G: Cornea1 response to high Dk, extended-wear rigid contact lenses. Am J Optom Physiol Optics 1985;62:95P. 7. Andrasko GJ: Cornea1 deswelling response to hard and hydrogel extended wear lenses. Invest Ophthalmol Vis Sci 1986; 27:2&23. 8. O’Neal MR, Polse KA: Decreased endothelial pump function with aging. Invest Ophthalmol Vis Sci 1986;27:457-463. 9. Polse KA, Sarver MD, Kenyon E, Bonnano J: Gas permeable hard contact lens extended wear: ocular and visual responses to a 6-month period of wear. CLAO J 1987;13:31-38. 10. Polse KA, Brand R, Mandell R, Vastine D, Demartini D, Flom R: Age differences in cornea1 hydration control. Invest Ophtimol Vis Sci 1989;30:392-399. 11. Levy B, Nguyen N, Abott RL, Gee M, Sviedrys A: Hypotony and cornea1 edema secondary to patching in normal eyes. Optom Vis Sci 1992;69:72-75. 12. Fatt I: Conventional thinking. Optician 1992;203:33-36. 13. Frucht-Pery J, Stiebel H, Hemo I, Ever-Hadani P. Effect of eye-patching on ocular surface. Am ] Ophthulmol 1993;115: 629-633.

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14. Holden BA, Poise KA, Fonn D, Mertz GW: Effects of cataract surgery on comeal function. Invest Ophthalmol Vis Sci 1982;22:343-350. 15. Brennan NA, Smith G, Macdonald JA, Bruce AS: Theoretical principles of optical pachometry. Ophthalmic Physiol Opt 1989;9:247-254. 16. Fry GA, Hill WW: The center of rotation of the eye. Am J Optom Arch Am Acad @tom 1962;39:581-595. 17. Fry GA, Hill WW: The mechanics of elevating the eye. Am J Optom Arch Am Acad Optom 1963;40:707-716. 18. Kiely PM, Smith G, Carney LG: The mean shape of the human cornea. Optica Actu 1982;29:1027-1040. 19. Goldmann H, Schmidt T: Ober Applanationstonometrie. Ophthalmologica 1957;134:221-242. 20. Hansen FK, Ehlers N: Elevated tonometer readings caused by a thick cornea. Acta Ophthalmol 1971;49:775-778. 21. Whitacre MM, Stein RA, Hassanein K: The effect of cornea1 thickness on applanation tonometry. Am J Ophthalmol 1993; 115:592-596. 22. Herse PR, Siu A: Short-term effects of proparacaine on human cornea1 thickness. Acta Ophthulmol 1992;70:74C-744. 23. Ackerman E, Gatewood LC, Rosevear JW, Molnar GD: Blood glucose regulation and diabetes. In: Heinmets F (Ed. ) . Biomathematics. Vol. I. New York, Marcel Dekker, 1969, pp. 131-156. 24. Harris MG, Sarver MD, Brown LR: Cornea1 edema with hydrogel lenses and eye closure: Time course. Am .I Optom Physiol Opt 1981;58:18-20. 25. O’Neal MR, Polse KA: In vivo assessment of mechanisms controlling cornea1 hydration. Invest Ophthalmol Vis Sci 1985; 26:849-856. 26. Fitzgerald JP, Efron N: Oxygen uptake profile of the human cornea. Clin EQ @tom 1986;69:149-152. 27. Benjamin WJ, Ruben CM: Human cornea1 oxygen demands at superior, central, and inferior sites. J Am @tom Assoc 1995;66:423-428. 28. Sack RA, Tan KO, Tan A: Diurnal tear cycle: Evidence for a nocturnal inflammatory constitutive tear fluid. Invest Ophthalmol Vis Sci 1992;33:626640. 29. Vannas A, Sweeney DF, Holden BA, Sapyska E, Salonen EM, Vaheri A: Tear plasmin activity with contact lens wear. Curr Eye Res 1992;11:243-251. 30. Tan KO, Sack RA, Holden BA, Swarbrick HA: Temporal sequence of changes in tear film composition during sleep. Curr Eye Res 1993;12:1001-1007. 31. Connors MS, Stoltz RA, Webb SC, et al.: A closed eye contact lens model of cornea1 inflammation. Part 1: Increased synthesis of cytochrome P450 arachidonic acid metabolites. Invest Ophthalmol Vis Sci 1995;36:828-840. 32. Connors MS, Stoltz RA, Davis KL, et al.: A closed eye contact lens model of cornea1 inflammation. Part 2: Inhibition of cytochrome P450 arachidonic acid metabolism alleviates inflammatory sequelae. Invest Ophthalmol Vis Sci 1995; 36:841-850.

Patched Eye Comeal Swelling: Erickson and Crmstock Paul Erickson received an OD from Pacific University and a PhD (vision science) from the University of Waterloo. His professional experience before joining Bausch &. Lomb in 1984 includes 6 years in optometric practice and 2 years on the Northeastern Oklahoma State University School of Optometry faculty. He is currently Vice President for Research and Development of the Bausch &I Lomb Contact Lens division. Dr. Erickson is a Fellow of the American Academy of Optometry and a member of numerous professional and scientific organizations.

Dr. Tim Comstock is the Manager of the Research Clinic for the Bausch & Lomb Contact Lens Division Research Clinic, Rochester, NY. Dr. Comstock received his Doctor of Optometry degree from The Ohio State University in 1987. He completed the Cornea and Contact Lens Fellowship at Ohio State in 1989, earning a Master of Science degree in Physiological Optics. His current research activities include evaluations of developmental soft contact lens designs, materials, and methods of manufacture, with an emphasis on toric lenses. Dr. Comstock is a Fellow of the American Academy of Optometry, a member of the Contact Lens Section of the AOA, and a member of ARVO.

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