postnatal development of corneal curvature and thickness in the cat

© 2001 American College of Veterinary Ophthalmologists

Veterinary Ophthalmology

(2001)

4

, 4, 267–272

Blackwell Science Ltd

Postnatal development of corneal curvature and thickness in the cat

K. L. Moodie,* N. Hashizume,* D. L. Houston,* P. J. Hoopes,* E. Demidenko,† B. S. Trembly‡ and M. G. Davidson§

*

Department of Surgery, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA,

†

Section of Biostatistics and Epidemiology, Dartmouth Medical School, Hanover, New Hampshire, USA,

‡

Department of Engineering, Dartmouth College, Hanover, New Hampshire, USA,

§

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA

Abstract

Objective

To evaluate the postnatal development of central corneal curvature and thickness in the domestic cat.

Animals studied

Six Domestic Short-haired (DSH) kittens starting at 9 weeks of age and 6 adult cats.

Procedures

Kittens were evaluated biweekly to monthly for a 12-month period, starting at age 9 weeks. Corneal development was monitored by hand-held keratometry and ultrasound biomicroscopy. Standard regression analysis using a nonlinear least squares method was used to generate a formula that would predict corneal curvature as a function of age.

Results

Mean keratometry (K) values for the 9-week-old cats were 54.51 (

±

1.02) diopters (D) and these values steeply declined over the next 3 months to 44.95 (

±

0.90) D. Thereafter, K-values gradually decreased to reach a plateau by 12–15 months of age of 39.90 (

±

0.42) D. Because K-values still appeared to be slightly diminishing at this point, six other > 2-year-old cats were evaluated by keratometry and were found to have K-values of 38.99 (

±

0.81). Two to four diopters of astigmatism was common in young kittens whereas adult cats had a low mean degree of astigmatism (< 1 D). A formula that predicted keratometry values in diopters (K) as a function of age in weeks (w) was established as follows: K = 39.83 + 26.87 exp(–0.074 w). The central cornea increased in thickness primarily during the first 4 months of life with 9 week-old kittens having values of 0.379 (

±

0.012) mm; 16-week-old kittens, 0.548 (

±

0.021) mm and 67 week-old cats, 0.567 (

±

0.012) mm.

Conclusions

The maturation process of the feline cornea proceeds over the first 1–2 years of life to attain an adult status that is characterized by a roughly spherical state of approximately 39 D corneal curvature, substantially flatter than the human cornea, and a central thickness similar to the human cornea. Research studies of the refractive or optical properties of the cornea in which cats are used as experimental animals should be conducted on animals greater than 18 months of age.

Key Words:

astigmatism, cornea, corneal development, corneal thickness, feline,

keratometry

Address communications to:

Michael G. Davidson

Tel.: (919) 513–6420Fax: (919) 513–6336e-mail: [email protected]

INTRODUCTION

The cornea is the predominate optical surface in the eye ofmost nonaquatic animal species, accounting for 70–80% ofthe total refractive power of the eye in many mammals.Domestic cats have a number of congenital and acquiredocular diseases affecting the cornea that might affect refrac-

tive state of the eye. Additionally, owing to shared anatomicand physiologic features of the cornea between humans andcats, the latter are commonly used in comparative ophthalmicresearch. For example, cats are common animal models instudies of human corneal wound healing following sur-gery,

1–8

and studies related to optical defocus on refractivedevelopment and ocular growth.

9–13

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In cats, a sophisticated and refined remodeling of thecornea occurs during the early postnatal period to maintainan optically focused image on the retina that is necessaryfor visual pathway development.

11,14

While the topogra-phy,

11,15,16

central corneal curvature,

17–21

and thickness ofthe feline cornea

22–25

are the subject of a number of reports,relatively few studies have addressed the anatomic featuresof the developing feline cornea, especially with the use ofmodern diagnostic tools such as electronic, hand-heldkeratometers. The purpose of this study was to investigatethe corneal curvature and central corneal thickness of thedeveloping feline cornea over the first 1–2 years of life, andto determine at what age an adult status of the cornea isachieved. From these data, a formula that predicts cornealcurvature as a function of age was generated.

MATERIALS AND METHODS

All procedures using cats were conducted in accordance withthe ARVO Statement for the Use of Animals in Ophthalmicand Vision Research and the protocol was approved by theauthors’ Institutional Animal Use and Care Committee. Six,8-week-old Domestic Short-haired (DSH) female kittens(Liberty Research Laboratory, Ithaca, NY, USA) were accli-mated to their environment for 1 week prior to performingocular measurements. All animals were given Telazole

®

(Fort Dodge, Ames, Iowa, USA), 10–14 mg/kg IM, andatropine, 0.02–0.04 mg/kg, IM, for sedation prior to per-forming these procedures. Keratometry values wereobtained first, then the cornea was topically anesthetized(Ophthaine, Squibb, Princeton, NJ, USA), and ultrasoundbiomicroscopy values obtained as described below. Data col-lection was obtained by the same two individuals throughoutthe study.

Central corneal curvature was measured using a hand-held keratometer (Alcon, Renaissance Series Hand HeldKeratometer, Fort Worth, Texas, USA), used according tothe manufacturer’s recommendations. Measurements weretaken from each animal every week from 9 weeks until9 months of age, then weekly to biweekly until 67 weeks ofage. Because the K-values in these cats at the termination ofthe experiment (67 weeks) appeared to be slightly decliningstill, six additional female cats, 2–3 years of age and obtainedfrom the same source (Liberty Laboratories), were evaluatedat a single time point to generate adult cat values. Fourreadings of each eye were obtained on each cat at each timeperiod and averaged. This keratometry unit used providescorneal curvature values in diopters (D) and radii of curva-ture in millimeters. Keratometry (K) values were obtainedfrom each major meridian and are designated as K1 for thehorizontal meridian, and K2 for the vertical meridian. Aver-age K-values were determined by averaging these twomeridians [ (K1 + K2)/2].

Central corneal thickness measurements were obtainedusing an ultrasound biomicroscopy (UBM, HumpheryInstruments Model 850, San Leandro, CA, USA) at 9, 10

and 12 weeks of age, then monthly thereafter until 50 weeksof age. Measurements were obtained near the center of thecornea using the on-screen calipers. An eyecup was placedcentrally on the cornea, and the probe was held perpen-dicular to the corneal surface. Three measurements wereobtained at each reading.

Statistical analyzes of keratometry and corneal thicknessvalues were performed by a standard regression analysisusing a nonlinear least squares method (S-Plus 2000, Math-soft Inc, Seattle, WA, USA). Unless otherwise indicated,data are expressed as group mean values with the standarderror in parentheses. All estimated parameters cited arestatistically significant with a

P

-value of < 0.05.

RESULTS

K1, K2, and average K-values for the right and left eyes didnot vary significantly in the same animal so these data werecombined to obtain a mean K-value for each animal.

Nine-week-old kittens had highly curved corneas with amean K-value of 54.51 (

±

1.02) D. Average K-values thensteeply declined over the next 3 months to a mean value of44.95 (

±

0.90) D in 5-month-old cats. Thereafter, K-valuesgradually decreased to reach a plateau by approximately1 year of age and were 39.90 (

±

0.42) D at 67 weeks of age(Fig. 1). Because K-values still appeared to be slightlydiminishing at this point, six other 2–3-year-old cats wereevaluated by keratometry and were found to have K-valuesof 38.99 (

±

0.81) D (Fig. 1).The mean keratometry values as a function of age had an

exponential form with the general expression of: K = A + Bexp(–Cw), where K is the radius of curvature in diopters,A, B and C are constants, and w is the cat’s age in weeks(Fig. 2). By using the keratometry values and age in a nonlinearleast squares method, the constants were determined as:A = 39.83 (0.07), B = 26.87 (0.41) and C = 0.074 (0.0014),with standard errors in parentheses.

Figure 1. Mean corneal curvature in diopters of six DSH cats. Bars represent standard error.

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The following formula is therefore suggested to predictK-values of young cats at different ages:

K = 39.83 + 26.87 exp(–0.074 w)

The inverse formula, indicating at what age in weeks theaverage radii of curvature reaches value K can be expressed as:

w = –log [ (K – 39.83)/26.87]/0.074

Analysis of the K-values in the two major meridians (K1 andK2) also indicated that the young kitten cornea showed alarger difference between these two values, or a high degreeof astigmatism. The corneas gradually reached a morespherical state with a relatively low degree of astigmatism(0.925 D) at 12–15 months (Fig. 3). The predicted magni-tude of astigmatism vs. age followed the formula:

Absolute value of K2-K1 = 0.925 + 1.672 exp(–0.13 w)

Figure 2. Corneal curvature of six DSH cats. Open circles represent individual animal measurements; the dark solid curve is the best fit by exponential function using nonlinear least squares. The estimated curve represents the mean K as a function of cat age and is displayed at the top of the graph. The thin solid lines represent the 95% confidence interval. The thin dashed lines represent a 95% confidence interval for the 2–3-year-old cats evaluated.

Figure 3. Degree of astigmatism (absolute value of K2–K1) of six DSH cats. Open circles represent individual animal measurements, and the dark solid curve is the best fit by exponential function using nonlinear least squares. The estimated curve represents the mean K as a function of cat age and is displayed at the top of the graph. Horizontal thin line is the estimated mean corneal astigmatism of the adult cat (0.925 D).


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The relationship between the K-values in the two majormeridians as a function of age was analyzed by evaluating thevalue of K2-K1 vs. age, and found to also have an exponentialfunction with the following equation and constants:

K2-K1 = –0.75 + 1.25 exp(–0.049 w)

Thus, at 10 weeks of age (where this equation yields a valueof zero), the astigmatism showed no trend towards whichmeridian was higher in value (i.e. K1 and K2 values wereequally likely to be the highest or most powerful meridian).Thereafter, a gradual negative trend with age occurred suchthat in the 67-week-old cat, K2 tended to be less than K1 bya mean of 0.75 D (Fig. 4). Thus, in these cats, there was atendency towards slight astigmatism with the most powerfulmeridian being horizontal.

Central corneal thickness did not vary significantly atany given age between the right and left eyes. Centralcorneal thickness exhibited an initial increase primarilyduring the first 4 months of life with 9 week-old kittenshaving values of 0.379 (

±

0.012) mm; 16 week-old kittens0.548 (

±

0.021) mm and 67 week-old adult cats 0.567(

±

0.012) mm (Fig. 5).

DISCUSSION

The results of this study document central corneal curvaturedevelopment in DSH cats over the first 12–15 months oflife. The 9-week-old kitten possessed a cornea that wassteeply curved (54.5 D) whereas the adult cat showed a cur-vature of approximately 39 D. The most dramatic changein the optical surface of the cornea occurs during the first9 months of life, with a decrease in corneal dioptric strengthof 12–15 D. A more gradual decrease in corneal curvature

continues from 9 until 15 months of age. The design of thisstudy did not allow monitoring of the same six cats after15 months of age. However, measurements of six cats ofthe same strain, who were 2–3 years of age, showed a meandioptric power approximately 1 D less than that of the 15-month-old-cats, suggesting that some continued developmentof the cornea occurs between 15 and 24 months of age.Extrapolation of the data from these two sets of cats suggestthat while most of the development of the feline corneaoccurs before 9 months of age, the final dioptric power ofthe cornea is not reached until approximately 18 months ofage. Keratometric data reported here were very similar tothose reported in two previous studies in kittens (6–35 weeks

Figure 4. The difference between K2 and K1 values in six DSH cats as a function of age. Open circles represent individual animal measurements, and the dark solid line the best fit by exponential function displayed at the top of the graph. Horizontal thin line is the estimated difference for the adult cat (–0.75 D).

Figure 5. Central corneal thickness in six DSH cats. Open circles represent individual animal measurements, and the dark solid curve is the best fit by exponential function displayed at the bottom of the graph.




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of age and 10 weeks of age), whose corneal curvature wassequentially measured using nonelectronic, table-mountedkeratometers.

17,19

Additionally, the mean corneal curvaturevalues found in the 2–3 years-old cats measured in this study(38.99 D) are nearly identical to those previously reportedfor 25 adult DSH cats (mean = 38.93 D) measured usingelectronic hand-held keratometry.

21

Evaluation of the corneal curvature values from the twodifferent meridians also demonstrates that the kitten corneatended to be more highly irregular with 2–4 D of astig-matism compared with the adult cat with a low degree ofastigmatism < 1 D. The high degree of astigmatism in theneonatal and juvenile cat found here is consistent with previ-ous photokeratoscopic

26

and keratometric

19

observations inkittens, and is similar to the situation in human infants,where a high incidence and degree of astigmatism is noted.

27

In the current study, there was no apparent trend for themajor, or most powerful meridian (i.e. one with the highestdioptric power) in the very young kittens. In the cats > 1 yearof age, when astigmatism was present, the K1 values, or valuesin the horizontal corneal meridian, tended to be the majormeridian. This situation is in contrast to humans where the mostcommon type of astigmatism, at least in young adults, has itsmajor meridian in the vertical axis and is referred to as ‘withthe rule’ astigmatism.

14

The degree of astigmatism found inthese kittens probably has a substantial effect on visual acuity.

Central corneal thickness was measured in this studyusing ultrasound biomicroscopy and analysis with on-screen calipers. While this mode of measuring the cornealthickness has not been previously validated, values foradult cats reported here (0.567

±

0.012 mm) comparedclosely with those previously reported using electronicpachymetry (0.578

±

0.06424 and 0.546

±

0.048 mm),

25

suggesting that this method is accurate for pachymetry.Corneal thickness values have not been previously reportedfor neonatal and juvenile cats, and results of the currentstudy suggest the majority increase in corneal thickness occursearly, reaching > 95% of adult thickness at 4 months of age.

It should be noted that the keratometric values and pre-dictive formulas for corneal curvature vs. age in the currentstudy were generated on females of a specific laboratorystrain of mixed breed cats. Differences in corneal curvaturethat are gender related, could potentially exist. However, ina previous study of adult cats, male and female cat cornealcurvatures did not vary significantly.

21

Breed differencesmay exist which could influence these results, although theDSH (mixed breed) cat studied here would represent themost common globe phenotype evaluated by the clinicianor researcher. Whether other breeds of cats, e.g. brachyc-ephalic breeds, would have substantially different cornealdevelopment and adult corneal curvature would requireadditional study. While the predictive formulas were gener-ated for age (in weeks) and not body weight, a previous studyhas shown that, within a specific strain of laboratory cat,these two parameters are highly correlative (

r

= 0.98).

19

Additionally, as body weight vs. age might be expected to

vary in males vs. females, and between breeds or strains ofcats, use of age in the predictive formula may in fact be moreaccurate than body weight.

In summary, the growth and development of the felinecornea proceeds from a high central curvature and highastigmatic state in the young kitten to a roughly sphericalshape with approximately 39 D of refractive power in theadult. The adult feline cornea has central corneal curvaturethat is considerably flatter than that found in adult humans,and a tendency for slight ‘against the rule’ astigmatism. Datafrom the predictive formula on corneal curvature vs. agesuggest that comparative research studies of the refractiveor optical properties of the cornea in which cats are used asexperimental animals should be conducted on animalsgreater than 18 months of age.

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postnatal development of corneal curvature and thickness in the cat

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