© 2003 American College of Veterinary Ophthalmologists

Veterinary Ophthalmology

(2003)

6

, 1, 19–22

Blackwell Science, Ltd

Early postnatal development of central corneal thickness in dogs

Fabiano Montiani-Ferreira,* Simon Petersen-Jones,* Nicholas Cassotis,† David T. Ramsey,* Patricia Gearhart* and Fernando Cardoso‡

*

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, D-208 Veterinary Medical Center, East Lansing, MI 48824–1314, USA,

†

Dover Veterinary Hospital, 96 Durham Road, Dover, NH,

‡

College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI, USA

Abstract

Objective

To investigate the changes in corneal thickness that occur during maturation of the canine eye over the first months of life.

Animals studied

Dogs of two different breeds with ages ranging from 14 days to 42 weeks of age.

Procedures

The central corneal thickness was measured by ultrasonic pachymetry every week for the first month after eyelid opening (around 14 days) and then every month until 42 weeks of age. Segmented regression was applied to capture the two phases observed in the central corneal thickness plotted against age. Breed, eye and gender were also included in the model.

Results

Mean central corneal thickness (CCT) values initially decreased following eyelid opening, with the lowest point being reached at around 6 weeks of age. Then CCT gradually increased as the dogs matured. Differences between left and right eye were not significant. Breed and gender effects were significant factors in the statistical model.

Conclusions

Following eyelid opening there is an initial decrease in corneal thickness until approximately 6 weeks of age, which presumably mirrors maturation of corneal endothelial cell function. After 6 weeks of age the CCT increases with age until approximately 30 weeks of age after which there was only a gradual increase over the remainder of the study period. A similar pattern of changes in corneal thickness in humans has been previously recorded.

Key Words:

cornea, corneal development, corneal thickness, dogs, ultrasonic

pachymetry

Address communication to:

Dr Simon Petersen-Jones

Tel.: + 1 517 353 3278Fax: + 1 517 355 5164e-mail: peter315@cvm.msu.edu

INTRODUCTION

The canine eye is not fully mature at birth. When the eyelidsopen at around 14 days of age the cornea is not clear, becauseit is more hydrated than in the mature animal. In the 2–4weeks following eyelid opening, the cornea clears sufficientlyto permit ophthalmoscopy.

1

To the authors’ knowledgethe changes in canine corneal thickness that occur duringmaturation of the cornea immediately following eyelidopening have not been reported.

Ultrasonic corneal pachymetry is the most accurate andreliable

in vivo

method currently available to measurecorneal thickness in animals and humans.

2,3

The techniquepermits measurement of the cornea in a normal physiologicstate, i.e. the conscious, unsedated animal. The instrumentmeasures the time required for ultrasonic energy to traversethe cornea and, using a pre-set constant for velocity ofsound, converts this to a measure of thickness.

Canine corneal thickness has been the subject of a numberof reports.

2,4–6

Mean canine central corneal thicknessdescribed in these papers varies from 0.495

±

0.1167–0.620

±

0.050 mm. It has previously been shown in the literaturethat corneal thickness differs with age and body weight.

2,4–6

However, none of these previous studies have directlyaddressed the progressive changes in thickness, which occurin the weeks following eyelid opening in the developingcanine cornea.

The objective of this study was to record the changes incentral corneal thickness of the canine cornea from the timeof eyelid opening to 10 months of age.

MATERIALS AND METHODS

All procedures using dogs were conducted in accordancewith the ARVO Statement for the Use of Animals inOphthalmic and Vision Research.

20

M O N T I A N I

-

F E R R E I R A

E T

A L

.

© 2003 American College of Veterinary Ophthalmologists,

Veterinary Ophthalmology

,

6

, 19–22

Central corneal thickness was measured in 50 dogs usingan ultrasonic pachymeter (Pachette™, Ultrasonic PachymeterModel DGH 500, Exton, PA, USA) with the speed of soundin the cornea pre-set at 1640 m/s. Of the total number ofdogs 31 were Labrador Retrievers (17 males and 14 females),and 19 were Beagle cross Briards (5 males and 14 females).

Following application of a topical anesthetic (pro-paracaine hydrochloride 0.5% ophthalmic solution USP,Alcon Laboratories, Forth Worth, TX, USA), the pachyme-ter probe was placed on the center of the cornea andseveral readings taken and averaged. Measurements wererepeated for several different time-points during the first10 months of life. They were taken weekly for the firstmonth, beginning at eyelid opening, and then monthlythereafter in the same animals, when possible. Some animalswere only measured at one time-point, while others weremeasured at several different ages. There were a total of 251averaged measurements from the 50 dogs. The number oftime points recorded for each dog is shown in Table 1.

Statistical analyzes of the measurements were performedby repeated measures analysis of variance (

) andby segmented nonlinear least square regression (PROCMIXED and PROC NLIN, SAS 2001, version 8.2, SASInstitute Inc., Cary, NC, USA). The repeated measures

technique was used as a preliminary analysis todetermine the significance of breed, eye, gender and ageeffects included in the model and to obtain adjusted means.Segmented regression was applied to capture the two phasesobserved in the corneal development. The first phase,corresponding to a decrease in thickness in the newborn,was modeled by a quadratic polynomial function of age, andthe second phase corresponding to the corneal growth wasmodeled with a logistic growth curve. A knot linking the twosegments was specified at 6 weeks of age when the lowestaverage corneal thickness was recorded. Parameter estimatesreported were statistically significant with a

P

-value of< 0.05.

RESULTS

The central corneal thickness of the left and right eyes werenot significantly different and these measurements wereaveraged to obtain a mean central corneal thickness for eachanimal at each time point. Labrador Retrievers had an aver-age overall corneal thickness of 0.5192

±

0.0056 mm, whichwas significantly greater (

P

> 0.05) than the average

recorded for the Beagle/Briards (0.4996

±

0.0080 mm). Maledogs had thicker corneas (0.5197

±

0.0079 mm) that weresignificantly different (

P

< 0.05) when compared to females(0.4990

±

0.0057 mm) during the observed period.The mean central corneal thickness (CCT) adjusted for

breed (Labrador Retriever basis) and gender effects (femalebasis) and averaged over left and right eyes was modeled asfunction of age (in weeks) by a quadratic polynomial equa-tion of form: CCT

=

a

+

b

×

age

+

c

×

age

2

, for age

=

6 weeks,and as a logistic growth curve of form: CCT

=

k

/(1

+

((

k

−

n

o

))

e

–

r

×

(

age

−

6

)

, for age

>

6 weeks. Here

k

is the value of CCTat mature age,

r

is growth rate and

n

o

is the value of CCT at6 weeks. The value of

n

o

was set equal to

a

+

b

×

6

+

c

×

6

2

, inorder to make the prediction equation continuous at theknot (age = 6 weeks) linking the two segments. The estimatedparameters and respective standard error were:

a

=

0.5325

±

0.0232,

b

=

–

0.0241

±

0.0124,

c

=

0.000832

±

0.00152,

k

=

0.5391

±

0.00650 and

r

=

0.1785

±

0.0266.The calculated value for

n

o

=

0.4178, which correspondedto the minimal corneal thickness on the prediction curve. Theprediction equations suggested for mean corneal thicknessfor dogs between 2 and 42 weeks of age were:

CCT

=

0.5325

−

0.0241

×

age

+

0.000832

×

age

2

, for age (in weeks)

≤

6,

and

CCT

=

0.5391/(1

+

((0.5391

−

0.4178)/0.4178))

e

−

0.1785

×

(

age

−

6)

,for age (in weeks) > 6.

Observed mean corneal thickness adjusted for breed andgender effects considering all dogs in this study, predictioncurve and 95% confidence interval on individual predictionsare presented in Fig. 1. The prediction curve and the meanmeasurements adjusted per gender (female basis) are pre-sented for Labrador Retrievers in Fig. 2 and Beagle/Briardsin Fig. 3. In Fig. 4 the corneal development of 10 Beagle/Briards that had repeated measurements are presented.

DISCUSSION

The results of this study document central corneal thicknessdevelopment in dogs over the first 10 months of life. Centralcorneal thickness significantly decreases following eyelidopening, with the lowest point being reached at around

Table 1. Number of dogs and number of time-points evaluated per breed. N1 = number of measurements used in the analysis after being averaged per dog, per time-point

Number of dogs per number of time points evaluated

Total dogs N1Time-points 1 5 6 7 8 9 10 12 13 15

Labrador 15 8 1 2 4 1 31 116Beagle/Briard 9 2 4 1 3 19 135Overall 24 8 1 2 4 1 2 4 1 3 50 251

© 2003 American College of Veterinary Ophthalmologists,

Veterinary Ophthalmology

,

6

, 19–22

21

6 weeks of age. Corneal thickness then gradually increases asthe dogs mature. The overall changes in canine cornealthickness during development observed in dogs in this studywere comparable to the changes found in humans in whichthe cornea undergoes a gradual and significant decreasein corneal thickness after birth.

7,8

In human subjects thecorneal thickness significantly decreases from the valuesfound in premature and full-term babies to those found insmall children aged between 2 and 4 years.

9

The maturation of the corneal endothelium may accountfor the initial decrease in corneal thickness seen in pup-pies following eyelid opening. As endothelial cells startto function and induce a state of relative dehydration of

the corneal stroma the postnatal corneal clearing occurs andin parallel the corneal thickness decreases. After 6 weeks ofage the increase in central corneal thickness is probablydue to general growth of the eye as the dog matures. Accord-ing to our findings, corneal thickness continues to increasewith age but the rate of growth significantly slows down after30 weeks of age. Previous studies have shown that the caninecorneal thickness continues to increase into adulthood.

2

Gwin

et al.

1982

5

and Gilger

et al.

1991

2

previouslyshowed that corneal thickness differed with increasing ageand body weight. Additionally, as previously reported byGilger et al. 1991, we found that male dogs have significantlythicker corneas than females. Although there was not anequal number of males and females in our study, the analysis

Figure 1. Mean corneal thickness for all dogs in the study adjusted for female Labrador Retriever basis. Open circles represent individual animal measurements (average of left and right eyes); the dark solid curve represents the predicted value from the segmented equation presented in this study, and dashed lines represent a 95% confidence interval on individual predictions.

Figure 2. Mean corneal thickness of Labrador Retriever dogs adjusted for gender (female basis). Open circles represent individual animal measurements (average of left and right eyes) and the dark solid curve represents the predicted value from the segmented equation presented in this study.

Figure 3. Mean corneal thickness of Beagle/Briard dogs adjusted for gender (female basis). Open circles represent individual animal measurements (average of left and right eyes) and the dark solid curve represents the predicted value from the segmented equation presented in this study.

Figure 4. Corneal development of 10 Beagle/Briards from 2 to 42 weeks of age. Open diamonds represent individual animal measurements (average of left and right eyes). These measurements are connected by solid lines within each individual.

22 M O N T I A N I - F E R R E I R A E T A L .

© 2003 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 6, 19–22

of least square means subtracted the breed effect to calculategender effect.

Comparing our data with the results found by Moodieet al. 200110 for corneal thickness in the cat, we concludedthat the feline cornea is thinner than the canine, but fitsa regression curve similar in shape to the one we foundin puppies after 6 weeks of age. Moodie et al. 2001 onlyrecorded central corneal thickness in kittens after 9 weeks ofage so it is not known if the corneal thickness of kittens alsodecreases in the weeks following eyelid opening.

Our findings show a significant difference in centralcorneal thickness between Labrador Retrievers and Beaglecross Briards. Labrador Retrievers are heavier than Beaglecross Briards dogs. To test the hypothesis that cornealthickness always increase in parallel to the dog’s weight,additional studies need to be made in breeds with differentweights. Interestingly, a difference in corneal thicknessbetween human races has also been recorded in the litera-ture: African Americans were found to have thinner corneasthan Caucasians.11

ACKNOWLEDGMENTS

Dr Al Stinson for gently allowing us to use his LabradorRetriever kennel and Donna Letavish for technical assist-ance. Sponsored by CAPES Foundation, Brazilia, Braziland by the Veterinary Medicine Department, UniversidadeFederal do Parana (UFPR), Curitiba, Brazil.

REFERENCES

1. Glaze MB. The cornea. In: Veterinary Pediatrics, 1st edn. (ed.Hoskins JD) W.B. Saunders Company, Philadelphia, 1990; 432–458.

2. Gilger BC, Whitley RD, McLaughlin SA et al. Canine cornealthickness measured by ultrasonic pachymetry. American Journal ofVeterinary Research 1991; 10: 1570–1572.

3. Korah S, Thomas R, Muliyil J. Comparison of optical and ultrasoundpachymetry. Indian Journal of Ophthalmology 2000; 48: 279–283.

4. Stapleton S, Peiffer R. Specular microscopic observations of theclinically normal canine corneal endothelium. American Journal ofVeterinary Research 1979; 40: 1803–1804.

5. Gwin RM, Lerner I, Warren JK, Gum G. Decrease in caninecorneal endothelial cell density and increase in corneal thickness asfunctions of age. Investigative Ophthalmology and Visual Science 1982;22: 267–271.

6. Ekesten B, Torrang I. Age-related changes in ocular distances innormal eyes of Samoyeds. American Journal of Veterinary Research1995; 1: 127–133.

7. Autzen T, Bjornstrom L. Central corneal thickness in full-termnewborns. Acta Ophthalmologica (Copenh) 1989; 67: 719–720.

8. Portellinha W, Belfort R, Jr. Central and peripheral corneal thick-ness in newborns. Acta Ophthalmologica (Copenh) 1991; 69: 247–250.

9. Ehlers N, Sorensen T, Bramsen T, Poulsen EH. Central cornealthickness in newborns and children. Acta Ophthalmologica (Copenh);1976; 54: 285–290.

10. Moodie KL, Hashizume N, Houston DL et al. Postnatal developmentof corneal curvature and thickness in the cat. Veterinary Ophthalmology2001; 4: 267–272.

11. La Rosa FA, Gross RL, Orengo-Nania S. Central corneal thicknessof Caucasians and African Americans in glaucomatous and nonglau-comatous populations. Archives of Ophthalmology 2001; 119: 23–27.