- Email: [email protected]
ASSESSMENT OF INTRAOCULAR PRESSURE BY APPLANATION AND REBOUND TONOMETRY IN GUINEA PIGS OF DIFFERENT AGES
Author’s Accepted Manuscript ASSESSMENT OF INTRAOCULAR PRESSURE BY APPLANATION AND REBOUND TONOMETRY IN GUINEA PIGS OF DIFFERENT AGES Martí Cairó, María Teresa Peña, José Rios, Adrià Melero, Jaume Martorell, Marta Leiva www.sasjournal.com
PII: DOI: Reference:
S1557-5063(17)30268-9 http://dx.doi.org/10.1053/j.jepm.2017.10.004 JEPM754
To appear in: Journal of Exotic Pet Medicine Cite this article as: Martí Cairó, María Teresa Peña, José Rios, Adrià Melero, Jaume Martorell and Marta Leiva, ASSESSMENT OF INTRAOCULAR PRESSURE BY APPLANATION AND REBOUND TONOMETRY IN GUINEA PIGS OF DIFFERENT AGES, Journal of Exotic Pet Medicine, http://dx.doi.org/10.1053/j.jepm.2017.10.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
AEMV Forum
Assessment of Intraocular Pressure by Applanation and Rebound Tonometry in Guinea Pigs of Different Ages Martí Cairó, DVM María Teresa Peña, DVM, PhD, Dip. ECVO José Rios, MSc Adrià Melero, DVM Jaume Martorell, DVM, PhD, Dip. ECZM (Small Mammals) Marta Leiva, DVM, PhD, Dip. ECVO* From the Fundació Hospital Clínic Veterinari, Universitat Autònoma de Barcelona, Spain (Cairó, Peña, Melero, Martorell, Leiva). b. Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Spain (Cairó, Peña, Martorell, Leiva). c. Laboratory of Biostatistics & Epidemiology, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain and Biostatistics and Data Management Platform, IDIBAPS, Hospital Clínic, Barcelona, Spain (Rios). Address correspondence to M. Leiva,DVM, PhD, Dip. ECVO, Departament de medicina i cirurgia animals. Edicifi V, Facultat de Veterinària, Campus UAB, 08913 Bellaterra, Barcelona, Spain, Email address: [email protected]. Phone: +34 93 5811387. Fax: +34 93 5813428 Abstract Fifty-two guinea pigs (Cavia porcellus) with normal ophthalmic examination were included in this study to determine whether there are differences in the intraocular pressure (IOP) according to age, while assessing the clinical usefulness of two different tonometry methods for this species. The animals were divided into 2 groups according to age: young (4 weeks-old, 29 animals) and adult (3–36 months, 23 animals). Tonometry was performed oculus utro (OU) in the central cornea according to the manufacturer's recommendations. Only measurements with low standard deviation (SD<5%) were included. Rebound tonometry was performed first OU; following topical anesthesia, applanation tonometry was then performed OU. The time required to obtain an IOP value was recorded for each eye. Descriptive statistics were calculated and Lin Concordance Coefficient (LCC) was performed to describe concordance between methods. Mean TonoVet® IOP readings were 8.53±1.28 mmHg and 13.20±1.28 mmHg for young and adults, respectively
(p<0.05). Tono-Pen VET® readings could not be obtained in young animals, but yielded a mean of 10.93±3.61 mmHg in adults. No differences were found between left and right eyes (p>0.05) nor between genders (p>0.05). TonoVet® readings were obtained faster than Tono-Pen VET® readings (less than 1 min vs 3.38±1.27 min, respectively (p<0.05)). Lin Concordance Coefficient between methods was 0.37 (95% CI 0.19; 0.53), documenting a poor concordance between the two methods. The study states that normal IOP values are lower in young than in adult guinea pigs. Moreover, the results obtained from this investigation demonstrated that TonoVet® tonometry is a rapid and well-tolerated procedure when performed on guinea pigs of any age, whereas Tono-Pen VET® tonometry is a more timeconsuming technique that can only be used on guinea pigs older than 3 months. Key words: Intraocular pressure; eye; laboratory animal; guinea pig; Cavia porcellus
Guinea pigs (Cavia porcellus) are domesticated diurnal rodents that originate from the Andean region of South America and are commonly used as experimental animals and are popular pets in many western societies.1,2 Ophthalmic research with guinea pigs has been performed for many years and includes, among others, infectious ocular surface disease, effects of immunosuppression on corneal ulceration, and development of myopia and cataracts.3-6 Given the growing popularity of guinea pigs and their high prevalence of ocular disease,7 reference values for the most common ophthalmic tests are needed. Currently, published data for diagnostic ophthalmic testing in healthy guinea pigs include phenol red thread tear test, Schirmer tear test 1 and 2, central corneal touch threshold and IOP. 7-12
Tonometry is an essential procedure when performing a complete ophthalmic examination and may be classified as direct or indirect. Direct tonometry is an invasive procedure, usually reserved for research applications, achieve through cannulation of the anterior chamber and measurement of the IOP with a manometer.13 Indirect methods can be further classified as indentation, applanation or rebound tonometry, with the latter two being the most common methods for measuring IOP in laboratory animals.14 Applanation tonometry is considered the standard tonometry method, even though it does not provide accurate measurements for animal species with a corneal diameter smaller than 5mm. 14 As a result, rebound tonometers have been designed, and were initially developed for use in small rodents. Although established reference values for rebound tonometry have been published for the guinea pig, rabbit, mouse and chinchilla (Table 1),7,12,1522
all published data have been reported in adults, even though differences in IOP
between young and adult animals have been described in species such as rhesus monkeys, American alligators and dogs.23-26 The objective of this research investigation was to determine whether there are differences in the intraocular pressure (IOP) to the age in guinea pigs, while assessing the clinical usefulness of two different tonometry methods for this species.
MATERIALS AND METHODS Animals A total of 57 guinea pigs of different age and gender were initially included for the study. Eighteen were client-owned animals, and 39 were obtained from a commercial facility. All guinea pigs had a physical and ophthalmic examination, including slit-lamp biomicroscopy (Kowa SL-15, Kowa Company Ltd., Tokyo, Japan.) and indirect ophthalmoscopy (Heine Omega 500, Heine, Herrsching, Germany.).
Only animals with no systemic or ocular disease were included in the study. Animals were classified into two groups depending on age: Group Y (young animals of 4 weeks of age), and Group A (adult animals with ages between 3-36 months). Rebound and applanation tonometries All the intraocular pressure measurements were performed by the same ophthalmologist (MC) between 4:00 and 6:00PM. If no restraint from a second examiner was necessary, measurements were performed as in Fig.1; when needed, an experienced veterinarian manually restrained the animals taking care not to put pressure on the globe or neck, while the ophthalmologist performed tonometry. Rebound tonometry (TonoVet®, Icare Finland Oy, Helsinki, Finland.) was performed OU, with the first eye tested being randomly selected. According to manufacturer’s recommendations, tonometry was performed by directing the filament perpendicular to the central cornea at a distance of approximately 4-8mm from the cornea. The “D” (dog validation) setting was used for this purpose. The TonoVet® expresses a mean IOP of 6 successful readings and only measures with low standard deviation (<5%) were recorded. Following rebound tonometry, a drop of topical anesthetic (Tetracaine hydrochloride 0.5%, Colircusí Anestésico 0.5%, Alcon Cusí S.A., Masnou, Spain.) was applied OU. One minute after administering the topical anesthetic, applanation tonometry (Tono-Pen VET®, Reichert Inc., NY, USA.) was performed, and again the first eye tested was randomly selected. Tono-Pen VET® calibration was performed once at each examination setting. Intraocular pressure measurements were an average of four successful readings on the central cornea. Only values with low standard deviation (<5%) were recorded. For both forms of tonometry methods, any generated average which included
an erroneous reading was discarded and the measurement repeated. Time taken to perform each tonometry method was recorded in minutes. Statistical analysis Statistical analysis between the two groups of age and both tonometry methods was performed using a commercial software (SPSS 20.0, IBM, NY, USA.). Readings from the right and left eyes were described separately to avoid any bias27 and descriptive statistics were performed for both groups. Lin concordance coefficient (LCC) and its corresponding 95% confidence intervals (CIs)28 were used to assess the agreement between values from both tonometers. Lin concordance coefficient evaluates how the IOP measurements between both tonometers adjust to a perfect agreement, as a lineal regression which crosses point (0,0) and has a slope of 45% (y=0+1*x). The results of LCC are a value from 0 to 1, being 1 perfect agreement. Agreement between
methods
may
be
classified
as very
poor (<0.21), poor (0.21-
0.40), moderate (0.41-0.60), substantial (0.61-0.89) or almost perfect (0.81-1.00). Additionally, a Bland & Altman graphic approximation was performed to assess the non-concordance profile.29 The Bland & Altman figure represents the mean value of both averages, which should correspond to the real mean value in perfect concordance, related to the difference between both methods, which in perfect concordance should be near to 0. Independent
t-test
was
used
to
analyze
the
differences
between
TonoVet® and Tono-Pen VET® for gender, eye and age, and paired Wilcoxon test for differences in time to perform each reading. Statistical analysis was performed converting each value to seconds and “<1 minute” was included as 60s. Level of significance in all comparisons was set at P ≤ 0.05.
RESULTS Fifty-two animals were included in the study: Group Y included 29 animals (14 males, 15 females) and group A included 23 animals (8 males, 15 females). In the majority of cases, only light restraint (placing three or four fingers gently on the animal’s head) was necessary to perform measurements with either tonometer. Mean TonoVet® measurements were 8.53±1.28 mmHg and 13.20±1.28 mmHg in group Y and A, respectively (P<0.05). Tono-Pen VET® readings could not be obtained in group Y due to the relatively large size of the tonometer tip compared to the corneal diameter, whereas in group A, the mean IOP obtained was 10.93±3.61 mmHg. Significant differences were not found between left and right eyes or between genders in either group (P>0.05). Regarding the comparison between TonoVet® and Tono-Pen VET® measurements in group A, the LCC indicated that agreement between both methods was poor, 0.37 (95% CI 0.19; 0.53) (Fig.2). Tono-Pen VET® measurements were lower than TonoVet® measurements by a mean of 2.12mmHg (Fig.3). Additionally, a biased LCC was calculated correcting each TonoVet® value in -2.12mmHg. Lin concordance coefficient recalculation yielded 0.46 (95%CI: 0.26; 0.63). Although agreement improved from poor to moderate, this change was considered insufficient for both methods to be concordant. Mean time taken to obtain Tono-Pen VET® measurements OU in the A group was 3.38±1.27 minutes and <1 minute for TonoVet® measurements, both in young and adult guinea pigs (P<0.05).
DISCUSSION Intraocular pressure in different species may be affected by several factors such as
age, restraint method, temperament of the patient, presence of corneal disease and time of the day in which tonometry is performed.11,12,23-26,30-43 Previous IOP studies in guinea pigs stated type of tonometry and time of the day as determinant factors to establish a reference IOP value for this species.7,8,11,12 The present study found a difference in IOP between young and adult guinea pigs, and base on these results provides reference values for young animals. Moreover TonoVet® tonometry appears to be a rapid and well-tolerated procedure that can be performed on guinea pigs of any age, whereas Tono-Pen VET® tonometry is a more time-consuming technique only available for use animals older than 3 months of age. Differences in IOP between young and adult animals observed in the present study are in concordance with previously published articles. Ofri et al, reported that IOP in lions was lower in young animals compared to adults.41 These results correlated with those reported by Jaafar et al. as mean IOP in children younger than 12 years old was 45% lower than in adults.43 Conversely, several studies in dogs, infant rhesus monkeys and American alligators have described a significant gradual decrease in IOP between young and adults.24-26,39,44 Other studies did not find significance in IOP differences between young and adult animals.23,42 Refractive error, corneal curvature, corneal thickness or axial length of the eye are suggested to play a role in the effect of age on IOP.41 This measures were not performed in the present study and should be considered in future studies to elucidate the clinical relevance of IOP differences between young and adult animals. Mean
Tono-Pen
VET®
values
obtained
in
adult
guinea
pigs
(10.93±3.61mmHg) differ from the reference values previously reported in this species (16.5±3.2mmHg and 18.27±4.55mmHg).7,8 Those differences may be related to restraint method, age and temperament of the animal, and time of the day in which tonometry was performed.11 Unfortunately none of the previous studies that
establish the reference applanation tonometry values in this species have reported age
or restraint method;7,8,11,12 parameters
that, although not specifically
demonstrated in guinea pigs, have been associated with significant IOP variations in other species.43 Tonometry values may be significantly affected in dogs, horses and humans by compression of both jugular veins, traction on the eyelids, tied collars, and body or head position.30-34 The majority of IOP measurements in the present study were obtained with no restraint which may have eliminated an increase in IOP due to neck compression. Circadian rhythm has also been described as an important factor when evaluating IOP in many animal species.11,26,36,37,45-47 Higher IOP values during the light phase have been described in dogs, rhesus monkeys, chicks and horses26,36,46,47
whereas
cats,
rabbits
and
guinea
pigs
have
shown
the
opposite.11,37,45 Ansari-Mood et al established rebound and applanation tonometry values for the guinea pig in 2 hour intervals over a 24 hour period. In the present study, all measurements were obtained between 4 and 6 pm, corresponding to the lowest IOP values in the study. This fact may have influenced the differences between the values obtain in this study and the previously published by other authors. 7,8,11 Tonometer calibration, specially in the rebound tonometer, is crucial to compare different values obtained in each study. Ansari-Mood et al. and Rajaei et al. used the undefined species setting ("p") which is reserved in the TonoVet ® for further calibrations. In the present study, the dog setting ("d") was used. The setting may have played a role in the different TonoVet® mean values obtained in each study for adult animals (13.20±1.28 mmHg vs 6.81±1.41 mmHg).
Mean TonoVet® values in adult guinea pigs in the current study (13.20±1.28mmHg) closely approximated those found by micromanometry methods (14.4±3.5mmHg).
40
However, that study was performed under sedation with a
combination of ketamine and xylazine, which has been demonstrated to affect IOP in different species.15,48-50 Direct comparison with the present study is therefore not appropriate. One of the purposes of the present study was to compare rebound and applanation tonometry on adult guinea pigs. This was not possible due to the poor concordance between methods. Despite the poor concordance between tonometry methods, interestingly the mean Tono-Pen VET® were significantly lower than the TonoVet® IOP measurements by approximately 2mmHg. The concordance between the two tonometry methods may have been influenced by the size of the sample groups, interindividual variation, or by the use of “d” setting on the TonoVet®. Due to this low concordance between methods, use of the same tonometer for repeated IOP measurements on the same guinea pig or in a research setting is strongly recommended to obtain consistent and accurate results. Further studies with larger groups and with specifically calibrated tonometer may be warranted to establish a comparison between methods. Rebound tonometry has been described previously as subjectively easier to perform than applanation tonometry.15,51 This statements agrees with the results of the present study, in which the time to obtain a valid measurement was significantly less for rebound than for the applanation tonometry. Shortening the time required to obtain a measurement is important to induce less handling stress in the fragile species3 and to reduce the chance of corneal damage. In addition, Tono-Pen VET® was only feasible in guinea pigs older than 3 months, which is consistent with
previous observations suggesting a minimal corneal diameter of 5mm to perform tonometry with the Tono-Pen VET®.14 Although axial eye length in developing guinea pigs has been previously described,4 no information regarding corneal diameter is available. While corneal diameter was not specifically measured in this study, TonoPen VET® tip (3.0mm diameter) was estimated to cover approximately 50-70% of the cornea in the young animal group. In conclusion, reference IOP values are lower in young (8.53±1.28 mmHg) than in adult (13.20±1.28 mmHg) guinea pigs when assessed by rebound tonometry. Furthermore, TonoVet® is a rapid and well-tolerated procedure feasible at any age, whereas Tono-Pen VET® is a more time-consuming technique only feasible in guinea pigs older than 3 months.
ACKNOWLEDGMENTS The authors would like to acknowledge Dr. Michael Davidson for his careful review of the manuscript.
REFERENCES 1. Donnelly TM, Brown CJ: Guinea pig and chinchilla care and husbandry. Vet Clin North Am Exot Anim Pract 7:351–373, 2004 2. Quesenberry KE, Donnelly TM, Mans C: Biology, husbandry, and clinical techniques of guinea pigs and chinchillas, in: Quesenberry KE, Carpenter J (eds): Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery (ed 3). St. Louis, Missouri, Elsevier/Saunders pp 279–294, 2012 3. Foster CS, Zelt RP, Mai-Phan T: Immunosuppression and selective inflammatory
cell depletion: studies on a guinea pig model of corneal ulceration after ocular alkali burning. Arch Ophthalmol 100:1820–1824, 1982 4. Howlett MHC, McFadden SA: Form-deprivation myopia in the guinea pig (Cavia porcellus). Vision Res 46:267–283, 2006 5. Simpanya MF, Ansari RR, Suh KI, et al: Aggregation of lens crystallins in an in vivo hyperbaric oxygen guinea pig model of nuclear cataract: dynamic lightscattering and HPLC analysis. Invest Ophthalmol Vis Sci 46:4641–4651, 2005 6. Watkins NG, Hadlow WJ, Moos AB, et al: Ocular delayed hypersensitivity: a pathogenetic mechanism of chlamydial-conjunctivitis in guinea pigs. Proc Natl Acad Sci USA 83:7480–7484, 1986 7. Williams D, Sullivan A: Ocular disease in the guinea pig (Cavia porcellus): a survey of 1000 animals. Vet Ophthalmol 13 Suppl:54–62, 2010 8. Coster ME, Stiles J, Krohne SG, et al: Results of diagnostic ophthalmic testing in healthy guinea pigs. J Am Vet Med Assoc 232:1825–1833, 2008 9. Trost K, Skalicky M, Nell B: Schirmer tear test, phenol red thread tear test, eye blink frequency and corneal sensitivity in the guinea pig. Vet Ophthalmol 10:143– 146, 2007 10. Wieser B, Tichy A, Nell B: Correlation between corneal sensitivity and quantity of reflex tearing in cows, horses, goats, sheep, dogs, cats, rabbits, and guinea pigs. Vet Ophthalmol 16:251–262, 2013 11. Ansari mood M, Mehdi-Rajaei S, Sadjadi R, et al: Twenty-four-hour measurement of intraocular pressure in guinea pigs (Cavia porcellus). J Am Assoc
Lab Anim Sci 55:95–97, 2016 12. Rajaei SM, Mood MA, Sadjadi R, et al: Intraocular pressure, tear production, and ocular echobiometry in guinea pigs (Cavia porcellus). J Am Assoc Lab Anim Sci 55:475–479, 2016 13. Andrade SF, Cremonezi T, Zachi CAM, et al: Evaluation of the Perkins handheld applanation tonometer in the measurement of intraocular pressure in dogs and cats. Vet Ophthalmol 12:277–284, 2009 14. Williams DL: Common features of exotic animal ophthalmology, in Williams D: Ophthalmology of Exotic Pets. West Sussex, Wiley-Blackwell pp 9–14, 2012 15. Hofmeister EH, Williams CO, Braun C, et al: Influence of lidocaine and diazepam on peri-induction intraocular pressures in dogs anesthetized with propofolatracurium. Can J Vet Res 70:251–256, 2006 16. Müller K, Mauler DA, Eule JC: Reference values for selected ophthalmic diagnostic tests and clinical characteristics of chinchilla eyes (Chinchilla lanigera). Vet Ophthalmol 13 Suppl:29–34, 2010 17. Pereira FQ, Bercht BS, Soares MG, et al: Comparison of a rebound and an applanation tonometer for measuring intraocular pressure in normal rabbits. Vet Ophthalmol 14:321–326, 2011 18. Saeki T, Aihara M, Ohashi M, et al: The efficacy of tonolab in detecting physiological and pharmacological changes of mouse intraocular pressure— Comparison with TonoPen and microneedle manometery. Curr Eye Res 33:247– 252, 2008
19. Lima L, Montiani-Ferreira F, Tramontin M, et al: The chinchilla eye: morphologic observations, echobiometric findings and reference values for selected ophthalmic diagnostic tests. Vet Ophthalmol 13 Suppl:14–25, 2010 20. Montiani-Ferreira F, Mattos BC, Russ HHA: Reference values for selected ophthalmic diagnostic tests of the ferret (Mustela putorius furo). Vet Ophthalmol 9:209–213, 2006 21. Sapienza JS, Porcher D, Collins BR, et al: Tonometry in clinically normal ferrets (Mustela putorius furo). Prog Vet Comp Ophthalmol 1:291–294, 1991 22. Mermoud A, Baerveldt G, Minckler DS, et al: Intraocular pressure in Lewis rats. Invest Ophthalmol Vis Sci 35:2455–2460, 1994 23. Mughannam AJ, Cook CS, Fritz CL: Change in intraocular pressure during maturation in Labrador Retriever dogs. Vet Ophthalmol 7:87–89, 2004 24. Whittaker CJ, Heaton-Jones TG, Kubilis PS, et al: Intraocular pressure variation associated with body length in young American alligators (Alligator mississippiensis). Am J Vet Res 56:1380–1383, 1995 25. De Rousseau CJ, Bito LZ: Intraocular pressure of rhesus monkeys (Macaca mulatta) II. Juvenile ocular hypertension and its apparent relationship to ocular growth. Exp Eye Res 32:407–417, 1981 26. Gelatt KN, MacKay EO: Distribution of intraocular pressure in dogs. Vet Ophthalmol 1:109–114, 1998 27. Ray WA, ODay DM: Statistical Analysis of Multi-Eye Datain Ophthalmic Research. Invest Ophthalmol Vis Sci 26:1186–1188, 1985
28. Lin LI-K: A Concordance Correlation Coefficient to Evaluate Reproducibility. Biometrics 45:255, 1989 29. Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Int J Nurs Stud 47:931–936, 2010
30. Klein HE, Krohne SG, Moore GE, et al: Effect of eyelid manipulation and manual jugular compression on intraocular pressure measurement in dogs. J Am Vet Med Assoc 238:1292–1295, 2011 31. Teng C, Gurses-Ozden R, Liebmann JM, et al: Effect of a tight necktie on intraocular pressure. Br J Ophthalmol 87:946–948, 2003 32. Pauli AM, Bentley E, Diehl KA, et al. Effects of the application of neck pressure by a collar or harness on intraocular pressure in dogs. J Am Anim Hosp Assoc 42:207–211, 2006 33. Broadwater JJ, Schorling JJ, Herring IP, et al: Effect of body position on intraocular pressure in dogs without glaucoma. Am J Vet Res 69:527–530, 2008 34. Komáromy AM, Garg CD, Ying G-S, et al: Effect of head position on intraocular pressure in horses. Am J Vet Res 67:1232–1235, 2006 35. Katz RS, Henkind P, Weitzman ED: The circadian rhythm of the intraocular pressure in the New Zealand White rabbit. Invest Ophthalmol 14:775–780, 1975 36. Giannetto C, Piccione G, Giudice E: Daytime profile of the intraocular pressure and tear production in normal dog. Vet Ophthalmol 12:302–305, 2009 37. Del Sole MJ, Sande PH, Bernades JM, et al: Circadian rhythm of intraocular
pressure in cats. Vet Ophthalmol 10:155–161, 2007 38. Leske MC, Connell A, Wu SY: Distribution of intraocular pressure: The Barbados Eye Study. Arch Ophthalmol 115:1051-1057, 1997
39. Ekesten B, Narfstrom K: Age-related changes in intraocular pressure and iridocorneal angle in Samoyeds. Prog Vet Comp Ophthalmol 2:37–40, 1992 40. Taskintuna I, Taskintuna I, Banker AS, et al: An animal model for cidofovir (HPMPC) toxicity: intraocular pressure and histopathologic effects. Exp Eye Res 64:795–806, 1997 41. Ofri R, Steinmetz A, Thielebein J, et al: Factors affecting intraocular pressure in lions. Vet J 177:124–129, 2008 42. Plummer CE, Ramsey DT, Hauptman JG: Assessment of corneal thickness, intraocular pressure, optical corneal diameter, and axial globe dimensions in miniature horses. Am J Vet Res 64:661–665, 2003 43. Jaafar MS, Kazi GA: Normal intraocular pressure in children: a comparative study of the Perkins applanation tonometer and the pneumatonometer. J Pediatr Ophthalmol Strabismus 30:284–287, 1993 44. Ekesten B, Narfstrom K: Correlation of morphologic features of the iridocorneal angle to intraocular pressure in Samoyeds. Am J Vet Res 52:1875–1878, 1991 45. Wang X, Dong J, Wu Q: Twenty-four-hour measurement of IOP in rabbits using rebound tonometer. Vet Ophthalmol 16:423–428, 2013 46. Nickla DL, Wildsoet C, Wallman J: The circadian rhythm in intraocular pressure and its relation to diurnal ocular growth changes in chicks. Exp Eye Res 66:183–193,
1998 47. Bertolucci C, Giudice E, Fazio F, et al: Circadian Intraocular Pressure Rhythms in Athletic Horses under Different Lighting Regime. Chronobiol Int 26:348–358, 2009 48. Hofmeister EH, Mosunic CB, Torres BT: Effects of ketamine, diazepam, and their combination on intraocular pressures in clinically normal dogs. Am J Vet Res 67:1136–1139, 2006 49. van der Woerdt A, Gilger B, Wilkie DA: Effect of auriculopalpebral nerve block and intravenous administration of xylazine on intraocular pressure and corneal thickness in horses. Am J Vet Res 56:155–158, 1995 50. Smith PJ, Gum GG, Whitley RD, et al: Tonometric and tonographic studies in the normal pony eye. Equine Vet J Suppl 10:36–38, 1990 51. Leiva M, Naranjo C, Peña MT: Comparison of the rebound tonometer (ICare) to the applanation tonometer (Tonopen XL) in normotensive dogs. Vet Ophthalmol 9:17–21, 2006
Table 1. Reference IOP values for laboratory animals. 7,8,12,16-22
Species
IOP (mmHg)
Tonometer
Author
17.71 ± 4.17
TonoPen XL
Lima et al. (2010)
2.9 ± 1.8
TonoVet
Muller et al. (2010)
14.50 ± 3.27
TonoPen
Montiani-Ferreira et al. (2006)
22.8 ± 5.5
TonoPen
Sapienza et al. (1991)
16.5 ± 3.2
TonoPen XL
Williams et al. (2010)
18.27 ± 4.55
TonoPen
Coster et al. (2008)
6.81 ± 1.41
TonoVet
Rajaei et al. (2016)
17.3 ± 5.25
TonoPen
Mermoud et al. (1994)
8.1 ± 0.6
TonoLab
Saeki et al. (2008)
9.8 ± 0.4
Microneedle
Saeki et al. (2008)
15.44 ± 2.16
Tono-Pen Avia
Pereira et al. (2011)
9.51 ± 2.62
TonoVet
Pereira et al. (2011)
Chinchilla
Ferret
Guinea pig
Lewis rat
Mouse
Rabbit
Table 2. Descriptive statistics comparison for TonoVet and Tono-Pen Vet measurements in young and adult Guinea pigs. Group
Tonometer TonoVet®
Eye
Mean (SD) (mmHg)
OD
13.17 (1.95)
OS
13.22 (2.24)
OD
10.96 (3.38)
Time <1min
Group A Tono-Pen VET®
TonoVet®
3.38±1.27 min OS
10.91 (3.98)
OD (28)
8.59 (1.27) <1min
OS (30)
8.48 (1.33)
OD
-
OS
-
Group Y Tono-Pen VET®
-
FIGURE LEGENDS Figure 1. (a) Rebound tonometry is being performed on a guinea pig. (b) Applanation tonometry is being performed on the same animal. Note that in both measurements, only light restraint by the operator is necessary. Figure 2. Agreement between IOP measurements between TonoVet® (TV) and Tono-Pen VET®(TP) evaluated by LCC. Each symbol represents either right or left IOP measurement and the straight line represents perfect agreement. Figure 3. The Bland and Altman scatterplot showed lack of agreement between both methods, mainly due to a consistently lower IOP value for the Tono-Pen VET® compared with the TonoVet® represented by the mean of each measurement against the differences of both measurements.
PII: DOI: Reference:
S1557-5063(17)30268-9 http://dx.doi.org/10.1053/j.jepm.2017.10.004 JEPM754
To appear in: Journal of Exotic Pet Medicine Cite this article as: Martí Cairó, María Teresa Peña, José Rios, Adrià Melero, Jaume Martorell and Marta Leiva, ASSESSMENT OF INTRAOCULAR PRESSURE BY APPLANATION AND REBOUND TONOMETRY IN GUINEA PIGS OF DIFFERENT AGES, Journal of Exotic Pet Medicine, http://dx.doi.org/10.1053/j.jepm.2017.10.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
AEMV Forum
Assessment of Intraocular Pressure by Applanation and Rebound Tonometry in Guinea Pigs of Different Ages Martí Cairó, DVM María Teresa Peña, DVM, PhD, Dip. ECVO José Rios, MSc Adrià Melero, DVM Jaume Martorell, DVM, PhD, Dip. ECZM (Small Mammals) Marta Leiva, DVM, PhD, Dip. ECVO* From the Fundació Hospital Clínic Veterinari, Universitat Autònoma de Barcelona, Spain (Cairó, Peña, Melero, Martorell, Leiva). b. Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Spain (Cairó, Peña, Martorell, Leiva). c. Laboratory of Biostatistics & Epidemiology, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain and Biostatistics and Data Management Platform, IDIBAPS, Hospital Clínic, Barcelona, Spain (Rios). Address correspondence to M. Leiva,DVM, PhD, Dip. ECVO, Departament de medicina i cirurgia animals. Edicifi V, Facultat de Veterinària, Campus UAB, 08913 Bellaterra, Barcelona, Spain, Email address: [email protected]. Phone: +34 93 5811387. Fax: +34 93 5813428 Abstract Fifty-two guinea pigs (Cavia porcellus) with normal ophthalmic examination were included in this study to determine whether there are differences in the intraocular pressure (IOP) according to age, while assessing the clinical usefulness of two different tonometry methods for this species. The animals were divided into 2 groups according to age: young (4 weeks-old, 29 animals) and adult (3–36 months, 23 animals). Tonometry was performed oculus utro (OU) in the central cornea according to the manufacturer's recommendations. Only measurements with low standard deviation (SD<5%) were included. Rebound tonometry was performed first OU; following topical anesthesia, applanation tonometry was then performed OU. The time required to obtain an IOP value was recorded for each eye. Descriptive statistics were calculated and Lin Concordance Coefficient (LCC) was performed to describe concordance between methods. Mean TonoVet® IOP readings were 8.53±1.28 mmHg and 13.20±1.28 mmHg for young and adults, respectively
(p<0.05). Tono-Pen VET® readings could not be obtained in young animals, but yielded a mean of 10.93±3.61 mmHg in adults. No differences were found between left and right eyes (p>0.05) nor between genders (p>0.05). TonoVet® readings were obtained faster than Tono-Pen VET® readings (less than 1 min vs 3.38±1.27 min, respectively (p<0.05)). Lin Concordance Coefficient between methods was 0.37 (95% CI 0.19; 0.53), documenting a poor concordance between the two methods. The study states that normal IOP values are lower in young than in adult guinea pigs. Moreover, the results obtained from this investigation demonstrated that TonoVet® tonometry is a rapid and well-tolerated procedure when performed on guinea pigs of any age, whereas Tono-Pen VET® tonometry is a more timeconsuming technique that can only be used on guinea pigs older than 3 months. Key words: Intraocular pressure; eye; laboratory animal; guinea pig; Cavia porcellus
Guinea pigs (Cavia porcellus) are domesticated diurnal rodents that originate from the Andean region of South America and are commonly used as experimental animals and are popular pets in many western societies.1,2 Ophthalmic research with guinea pigs has been performed for many years and includes, among others, infectious ocular surface disease, effects of immunosuppression on corneal ulceration, and development of myopia and cataracts.3-6 Given the growing popularity of guinea pigs and their high prevalence of ocular disease,7 reference values for the most common ophthalmic tests are needed. Currently, published data for diagnostic ophthalmic testing in healthy guinea pigs include phenol red thread tear test, Schirmer tear test 1 and 2, central corneal touch threshold and IOP. 7-12
Tonometry is an essential procedure when performing a complete ophthalmic examination and may be classified as direct or indirect. Direct tonometry is an invasive procedure, usually reserved for research applications, achieve through cannulation of the anterior chamber and measurement of the IOP with a manometer.13 Indirect methods can be further classified as indentation, applanation or rebound tonometry, with the latter two being the most common methods for measuring IOP in laboratory animals.14 Applanation tonometry is considered the standard tonometry method, even though it does not provide accurate measurements for animal species with a corneal diameter smaller than 5mm. 14 As a result, rebound tonometers have been designed, and were initially developed for use in small rodents. Although established reference values for rebound tonometry have been published for the guinea pig, rabbit, mouse and chinchilla (Table 1),7,12,1522
all published data have been reported in adults, even though differences in IOP
between young and adult animals have been described in species such as rhesus monkeys, American alligators and dogs.23-26 The objective of this research investigation was to determine whether there are differences in the intraocular pressure (IOP) to the age in guinea pigs, while assessing the clinical usefulness of two different tonometry methods for this species.
MATERIALS AND METHODS Animals A total of 57 guinea pigs of different age and gender were initially included for the study. Eighteen were client-owned animals, and 39 were obtained from a commercial facility. All guinea pigs had a physical and ophthalmic examination, including slit-lamp biomicroscopy (Kowa SL-15, Kowa Company Ltd., Tokyo, Japan.) and indirect ophthalmoscopy (Heine Omega 500, Heine, Herrsching, Germany.).
Only animals with no systemic or ocular disease were included in the study. Animals were classified into two groups depending on age: Group Y (young animals of 4 weeks of age), and Group A (adult animals with ages between 3-36 months). Rebound and applanation tonometries All the intraocular pressure measurements were performed by the same ophthalmologist (MC) between 4:00 and 6:00PM. If no restraint from a second examiner was necessary, measurements were performed as in Fig.1; when needed, an experienced veterinarian manually restrained the animals taking care not to put pressure on the globe or neck, while the ophthalmologist performed tonometry. Rebound tonometry (TonoVet®, Icare Finland Oy, Helsinki, Finland.) was performed OU, with the first eye tested being randomly selected. According to manufacturer’s recommendations, tonometry was performed by directing the filament perpendicular to the central cornea at a distance of approximately 4-8mm from the cornea. The “D” (dog validation) setting was used for this purpose. The TonoVet® expresses a mean IOP of 6 successful readings and only measures with low standard deviation (<5%) were recorded. Following rebound tonometry, a drop of topical anesthetic (Tetracaine hydrochloride 0.5%, Colircusí Anestésico 0.5%, Alcon Cusí S.A., Masnou, Spain.) was applied OU. One minute after administering the topical anesthetic, applanation tonometry (Tono-Pen VET®, Reichert Inc., NY, USA.) was performed, and again the first eye tested was randomly selected. Tono-Pen VET® calibration was performed once at each examination setting. Intraocular pressure measurements were an average of four successful readings on the central cornea. Only values with low standard deviation (<5%) were recorded. For both forms of tonometry methods, any generated average which included
an erroneous reading was discarded and the measurement repeated. Time taken to perform each tonometry method was recorded in minutes. Statistical analysis Statistical analysis between the two groups of age and both tonometry methods was performed using a commercial software (SPSS 20.0, IBM, NY, USA.). Readings from the right and left eyes were described separately to avoid any bias27 and descriptive statistics were performed for both groups. Lin concordance coefficient (LCC) and its corresponding 95% confidence intervals (CIs)28 were used to assess the agreement between values from both tonometers. Lin concordance coefficient evaluates how the IOP measurements between both tonometers adjust to a perfect agreement, as a lineal regression which crosses point (0,0) and has a slope of 45% (y=0+1*x). The results of LCC are a value from 0 to 1, being 1 perfect agreement. Agreement between
methods
may
be
classified
as very
poor (<0.21), poor (0.21-
0.40), moderate (0.41-0.60), substantial (0.61-0.89) or almost perfect (0.81-1.00). Additionally, a Bland & Altman graphic approximation was performed to assess the non-concordance profile.29 The Bland & Altman figure represents the mean value of both averages, which should correspond to the real mean value in perfect concordance, related to the difference between both methods, which in perfect concordance should be near to 0. Independent
t-test
was
used
to
analyze
the
differences
between
TonoVet® and Tono-Pen VET® for gender, eye and age, and paired Wilcoxon test for differences in time to perform each reading. Statistical analysis was performed converting each value to seconds and “<1 minute” was included as 60s. Level of significance in all comparisons was set at P ≤ 0.05.
RESULTS Fifty-two animals were included in the study: Group Y included 29 animals (14 males, 15 females) and group A included 23 animals (8 males, 15 females). In the majority of cases, only light restraint (placing three or four fingers gently on the animal’s head) was necessary to perform measurements with either tonometer. Mean TonoVet® measurements were 8.53±1.28 mmHg and 13.20±1.28 mmHg in group Y and A, respectively (P<0.05). Tono-Pen VET® readings could not be obtained in group Y due to the relatively large size of the tonometer tip compared to the corneal diameter, whereas in group A, the mean IOP obtained was 10.93±3.61 mmHg. Significant differences were not found between left and right eyes or between genders in either group (P>0.05). Regarding the comparison between TonoVet® and Tono-Pen VET® measurements in group A, the LCC indicated that agreement between both methods was poor, 0.37 (95% CI 0.19; 0.53) (Fig.2). Tono-Pen VET® measurements were lower than TonoVet® measurements by a mean of 2.12mmHg (Fig.3). Additionally, a biased LCC was calculated correcting each TonoVet® value in -2.12mmHg. Lin concordance coefficient recalculation yielded 0.46 (95%CI: 0.26; 0.63). Although agreement improved from poor to moderate, this change was considered insufficient for both methods to be concordant. Mean time taken to obtain Tono-Pen VET® measurements OU in the A group was 3.38±1.27 minutes and <1 minute for TonoVet® measurements, both in young and adult guinea pigs (P<0.05).
DISCUSSION Intraocular pressure in different species may be affected by several factors such as
age, restraint method, temperament of the patient, presence of corneal disease and time of the day in which tonometry is performed.11,12,23-26,30-43 Previous IOP studies in guinea pigs stated type of tonometry and time of the day as determinant factors to establish a reference IOP value for this species.7,8,11,12 The present study found a difference in IOP between young and adult guinea pigs, and base on these results provides reference values for young animals. Moreover TonoVet® tonometry appears to be a rapid and well-tolerated procedure that can be performed on guinea pigs of any age, whereas Tono-Pen VET® tonometry is a more time-consuming technique only available for use animals older than 3 months of age. Differences in IOP between young and adult animals observed in the present study are in concordance with previously published articles. Ofri et al, reported that IOP in lions was lower in young animals compared to adults.41 These results correlated with those reported by Jaafar et al. as mean IOP in children younger than 12 years old was 45% lower than in adults.43 Conversely, several studies in dogs, infant rhesus monkeys and American alligators have described a significant gradual decrease in IOP between young and adults.24-26,39,44 Other studies did not find significance in IOP differences between young and adult animals.23,42 Refractive error, corneal curvature, corneal thickness or axial length of the eye are suggested to play a role in the effect of age on IOP.41 This measures were not performed in the present study and should be considered in future studies to elucidate the clinical relevance of IOP differences between young and adult animals. Mean
Tono-Pen
VET®
values
obtained
in
adult
guinea
pigs
(10.93±3.61mmHg) differ from the reference values previously reported in this species (16.5±3.2mmHg and 18.27±4.55mmHg).7,8 Those differences may be related to restraint method, age and temperament of the animal, and time of the day in which tonometry was performed.11 Unfortunately none of the previous studies that
establish the reference applanation tonometry values in this species have reported age
or restraint method;7,8,11,12 parameters
that, although not specifically
demonstrated in guinea pigs, have been associated with significant IOP variations in other species.43 Tonometry values may be significantly affected in dogs, horses and humans by compression of both jugular veins, traction on the eyelids, tied collars, and body or head position.30-34 The majority of IOP measurements in the present study were obtained with no restraint which may have eliminated an increase in IOP due to neck compression. Circadian rhythm has also been described as an important factor when evaluating IOP in many animal species.11,26,36,37,45-47 Higher IOP values during the light phase have been described in dogs, rhesus monkeys, chicks and horses26,36,46,47
whereas
cats,
rabbits
and
guinea
pigs
have
shown
the
opposite.11,37,45 Ansari-Mood et al established rebound and applanation tonometry values for the guinea pig in 2 hour intervals over a 24 hour period. In the present study, all measurements were obtained between 4 and 6 pm, corresponding to the lowest IOP values in the study. This fact may have influenced the differences between the values obtain in this study and the previously published by other authors. 7,8,11 Tonometer calibration, specially in the rebound tonometer, is crucial to compare different values obtained in each study. Ansari-Mood et al. and Rajaei et al. used the undefined species setting ("p") which is reserved in the TonoVet ® for further calibrations. In the present study, the dog setting ("d") was used. The setting may have played a role in the different TonoVet® mean values obtained in each study for adult animals (13.20±1.28 mmHg vs 6.81±1.41 mmHg).
Mean TonoVet® values in adult guinea pigs in the current study (13.20±1.28mmHg) closely approximated those found by micromanometry methods (14.4±3.5mmHg).
40
However, that study was performed under sedation with a
combination of ketamine and xylazine, which has been demonstrated to affect IOP in different species.15,48-50 Direct comparison with the present study is therefore not appropriate. One of the purposes of the present study was to compare rebound and applanation tonometry on adult guinea pigs. This was not possible due to the poor concordance between methods. Despite the poor concordance between tonometry methods, interestingly the mean Tono-Pen VET® were significantly lower than the TonoVet® IOP measurements by approximately 2mmHg. The concordance between the two tonometry methods may have been influenced by the size of the sample groups, interindividual variation, or by the use of “d” setting on the TonoVet®. Due to this low concordance between methods, use of the same tonometer for repeated IOP measurements on the same guinea pig or in a research setting is strongly recommended to obtain consistent and accurate results. Further studies with larger groups and with specifically calibrated tonometer may be warranted to establish a comparison between methods. Rebound tonometry has been described previously as subjectively easier to perform than applanation tonometry.15,51 This statements agrees with the results of the present study, in which the time to obtain a valid measurement was significantly less for rebound than for the applanation tonometry. Shortening the time required to obtain a measurement is important to induce less handling stress in the fragile species3 and to reduce the chance of corneal damage. In addition, Tono-Pen VET® was only feasible in guinea pigs older than 3 months, which is consistent with
previous observations suggesting a minimal corneal diameter of 5mm to perform tonometry with the Tono-Pen VET®.14 Although axial eye length in developing guinea pigs has been previously described,4 no information regarding corneal diameter is available. While corneal diameter was not specifically measured in this study, TonoPen VET® tip (3.0mm diameter) was estimated to cover approximately 50-70% of the cornea in the young animal group. In conclusion, reference IOP values are lower in young (8.53±1.28 mmHg) than in adult (13.20±1.28 mmHg) guinea pigs when assessed by rebound tonometry. Furthermore, TonoVet® is a rapid and well-tolerated procedure feasible at any age, whereas Tono-Pen VET® is a more time-consuming technique only feasible in guinea pigs older than 3 months.
ACKNOWLEDGMENTS The authors would like to acknowledge Dr. Michael Davidson for his careful review of the manuscript.
REFERENCES 1. Donnelly TM, Brown CJ: Guinea pig and chinchilla care and husbandry. Vet Clin North Am Exot Anim Pract 7:351–373, 2004 2. Quesenberry KE, Donnelly TM, Mans C: Biology, husbandry, and clinical techniques of guinea pigs and chinchillas, in: Quesenberry KE, Carpenter J (eds): Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery (ed 3). St. Louis, Missouri, Elsevier/Saunders pp 279–294, 2012 3. Foster CS, Zelt RP, Mai-Phan T: Immunosuppression and selective inflammatory
cell depletion: studies on a guinea pig model of corneal ulceration after ocular alkali burning. Arch Ophthalmol 100:1820–1824, 1982 4. Howlett MHC, McFadden SA: Form-deprivation myopia in the guinea pig (Cavia porcellus). Vision Res 46:267–283, 2006 5. Simpanya MF, Ansari RR, Suh KI, et al: Aggregation of lens crystallins in an in vivo hyperbaric oxygen guinea pig model of nuclear cataract: dynamic lightscattering and HPLC analysis. Invest Ophthalmol Vis Sci 46:4641–4651, 2005 6. Watkins NG, Hadlow WJ, Moos AB, et al: Ocular delayed hypersensitivity: a pathogenetic mechanism of chlamydial-conjunctivitis in guinea pigs. Proc Natl Acad Sci USA 83:7480–7484, 1986 7. Williams D, Sullivan A: Ocular disease in the guinea pig (Cavia porcellus): a survey of 1000 animals. Vet Ophthalmol 13 Suppl:54–62, 2010 8. Coster ME, Stiles J, Krohne SG, et al: Results of diagnostic ophthalmic testing in healthy guinea pigs. J Am Vet Med Assoc 232:1825–1833, 2008 9. Trost K, Skalicky M, Nell B: Schirmer tear test, phenol red thread tear test, eye blink frequency and corneal sensitivity in the guinea pig. Vet Ophthalmol 10:143– 146, 2007 10. Wieser B, Tichy A, Nell B: Correlation between corneal sensitivity and quantity of reflex tearing in cows, horses, goats, sheep, dogs, cats, rabbits, and guinea pigs. Vet Ophthalmol 16:251–262, 2013 11. Ansari mood M, Mehdi-Rajaei S, Sadjadi R, et al: Twenty-four-hour measurement of intraocular pressure in guinea pigs (Cavia porcellus). J Am Assoc
Lab Anim Sci 55:95–97, 2016 12. Rajaei SM, Mood MA, Sadjadi R, et al: Intraocular pressure, tear production, and ocular echobiometry in guinea pigs (Cavia porcellus). J Am Assoc Lab Anim Sci 55:475–479, 2016 13. Andrade SF, Cremonezi T, Zachi CAM, et al: Evaluation of the Perkins handheld applanation tonometer in the measurement of intraocular pressure in dogs and cats. Vet Ophthalmol 12:277–284, 2009 14. Williams DL: Common features of exotic animal ophthalmology, in Williams D: Ophthalmology of Exotic Pets. West Sussex, Wiley-Blackwell pp 9–14, 2012 15. Hofmeister EH, Williams CO, Braun C, et al: Influence of lidocaine and diazepam on peri-induction intraocular pressures in dogs anesthetized with propofolatracurium. Can J Vet Res 70:251–256, 2006 16. Müller K, Mauler DA, Eule JC: Reference values for selected ophthalmic diagnostic tests and clinical characteristics of chinchilla eyes (Chinchilla lanigera). Vet Ophthalmol 13 Suppl:29–34, 2010 17. Pereira FQ, Bercht BS, Soares MG, et al: Comparison of a rebound and an applanation tonometer for measuring intraocular pressure in normal rabbits. Vet Ophthalmol 14:321–326, 2011 18. Saeki T, Aihara M, Ohashi M, et al: The efficacy of tonolab in detecting physiological and pharmacological changes of mouse intraocular pressure— Comparison with TonoPen and microneedle manometery. Curr Eye Res 33:247– 252, 2008
19. Lima L, Montiani-Ferreira F, Tramontin M, et al: The chinchilla eye: morphologic observations, echobiometric findings and reference values for selected ophthalmic diagnostic tests. Vet Ophthalmol 13 Suppl:14–25, 2010 20. Montiani-Ferreira F, Mattos BC, Russ HHA: Reference values for selected ophthalmic diagnostic tests of the ferret (Mustela putorius furo). Vet Ophthalmol 9:209–213, 2006 21. Sapienza JS, Porcher D, Collins BR, et al: Tonometry in clinically normal ferrets (Mustela putorius furo). Prog Vet Comp Ophthalmol 1:291–294, 1991 22. Mermoud A, Baerveldt G, Minckler DS, et al: Intraocular pressure in Lewis rats. Invest Ophthalmol Vis Sci 35:2455–2460, 1994 23. Mughannam AJ, Cook CS, Fritz CL: Change in intraocular pressure during maturation in Labrador Retriever dogs. Vet Ophthalmol 7:87–89, 2004 24. Whittaker CJ, Heaton-Jones TG, Kubilis PS, et al: Intraocular pressure variation associated with body length in young American alligators (Alligator mississippiensis). Am J Vet Res 56:1380–1383, 1995 25. De Rousseau CJ, Bito LZ: Intraocular pressure of rhesus monkeys (Macaca mulatta) II. Juvenile ocular hypertension and its apparent relationship to ocular growth. Exp Eye Res 32:407–417, 1981 26. Gelatt KN, MacKay EO: Distribution of intraocular pressure in dogs. Vet Ophthalmol 1:109–114, 1998 27. Ray WA, ODay DM: Statistical Analysis of Multi-Eye Datain Ophthalmic Research. Invest Ophthalmol Vis Sci 26:1186–1188, 1985
28. Lin LI-K: A Concordance Correlation Coefficient to Evaluate Reproducibility. Biometrics 45:255, 1989 29. Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Int J Nurs Stud 47:931–936, 2010
30. Klein HE, Krohne SG, Moore GE, et al: Effect of eyelid manipulation and manual jugular compression on intraocular pressure measurement in dogs. J Am Vet Med Assoc 238:1292–1295, 2011 31. Teng C, Gurses-Ozden R, Liebmann JM, et al: Effect of a tight necktie on intraocular pressure. Br J Ophthalmol 87:946–948, 2003 32. Pauli AM, Bentley E, Diehl KA, et al. Effects of the application of neck pressure by a collar or harness on intraocular pressure in dogs. J Am Anim Hosp Assoc 42:207–211, 2006 33. Broadwater JJ, Schorling JJ, Herring IP, et al: Effect of body position on intraocular pressure in dogs without glaucoma. Am J Vet Res 69:527–530, 2008 34. Komáromy AM, Garg CD, Ying G-S, et al: Effect of head position on intraocular pressure in horses. Am J Vet Res 67:1232–1235, 2006 35. Katz RS, Henkind P, Weitzman ED: The circadian rhythm of the intraocular pressure in the New Zealand White rabbit. Invest Ophthalmol 14:775–780, 1975 36. Giannetto C, Piccione G, Giudice E: Daytime profile of the intraocular pressure and tear production in normal dog. Vet Ophthalmol 12:302–305, 2009 37. Del Sole MJ, Sande PH, Bernades JM, et al: Circadian rhythm of intraocular
pressure in cats. Vet Ophthalmol 10:155–161, 2007 38. Leske MC, Connell A, Wu SY: Distribution of intraocular pressure: The Barbados Eye Study. Arch Ophthalmol 115:1051-1057, 1997
39. Ekesten B, Narfstrom K: Age-related changes in intraocular pressure and iridocorneal angle in Samoyeds. Prog Vet Comp Ophthalmol 2:37–40, 1992 40. Taskintuna I, Taskintuna I, Banker AS, et al: An animal model for cidofovir (HPMPC) toxicity: intraocular pressure and histopathologic effects. Exp Eye Res 64:795–806, 1997 41. Ofri R, Steinmetz A, Thielebein J, et al: Factors affecting intraocular pressure in lions. Vet J 177:124–129, 2008 42. Plummer CE, Ramsey DT, Hauptman JG: Assessment of corneal thickness, intraocular pressure, optical corneal diameter, and axial globe dimensions in miniature horses. Am J Vet Res 64:661–665, 2003 43. Jaafar MS, Kazi GA: Normal intraocular pressure in children: a comparative study of the Perkins applanation tonometer and the pneumatonometer. J Pediatr Ophthalmol Strabismus 30:284–287, 1993 44. Ekesten B, Narfstrom K: Correlation of morphologic features of the iridocorneal angle to intraocular pressure in Samoyeds. Am J Vet Res 52:1875–1878, 1991 45. Wang X, Dong J, Wu Q: Twenty-four-hour measurement of IOP in rabbits using rebound tonometer. Vet Ophthalmol 16:423–428, 2013 46. Nickla DL, Wildsoet C, Wallman J: The circadian rhythm in intraocular pressure and its relation to diurnal ocular growth changes in chicks. Exp Eye Res 66:183–193,
1998 47. Bertolucci C, Giudice E, Fazio F, et al: Circadian Intraocular Pressure Rhythms in Athletic Horses under Different Lighting Regime. Chronobiol Int 26:348–358, 2009 48. Hofmeister EH, Mosunic CB, Torres BT: Effects of ketamine, diazepam, and their combination on intraocular pressures in clinically normal dogs. Am J Vet Res 67:1136–1139, 2006 49. van der Woerdt A, Gilger B, Wilkie DA: Effect of auriculopalpebral nerve block and intravenous administration of xylazine on intraocular pressure and corneal thickness in horses. Am J Vet Res 56:155–158, 1995 50. Smith PJ, Gum GG, Whitley RD, et al: Tonometric and tonographic studies in the normal pony eye. Equine Vet J Suppl 10:36–38, 1990 51. Leiva M, Naranjo C, Peña MT: Comparison of the rebound tonometer (ICare) to the applanation tonometer (Tonopen XL) in normotensive dogs. Vet Ophthalmol 9:17–21, 2006
Table 1. Reference IOP values for laboratory animals. 7,8,12,16-22
Species
IOP (mmHg)
Tonometer
Author
17.71 ± 4.17
TonoPen XL
Lima et al. (2010)
2.9 ± 1.8
TonoVet
Muller et al. (2010)
14.50 ± 3.27
TonoPen
Montiani-Ferreira et al. (2006)
22.8 ± 5.5
TonoPen
Sapienza et al. (1991)
16.5 ± 3.2
TonoPen XL
Williams et al. (2010)
18.27 ± 4.55
TonoPen
Coster et al. (2008)
6.81 ± 1.41
TonoVet
Rajaei et al. (2016)
17.3 ± 5.25
TonoPen
Mermoud et al. (1994)
8.1 ± 0.6
TonoLab
Saeki et al. (2008)
9.8 ± 0.4
Microneedle
Saeki et al. (2008)
15.44 ± 2.16
Tono-Pen Avia
Pereira et al. (2011)
9.51 ± 2.62
TonoVet
Pereira et al. (2011)
Chinchilla
Ferret
Guinea pig
Lewis rat
Mouse
Rabbit
Table 2. Descriptive statistics comparison for TonoVet and Tono-Pen Vet measurements in young and adult Guinea pigs. Group
Tonometer TonoVet®
Eye
Mean (SD) (mmHg)
OD
13.17 (1.95)
OS
13.22 (2.24)
OD
10.96 (3.38)
Time <1min
Group A Tono-Pen VET®
TonoVet®
3.38±1.27 min OS
10.91 (3.98)
OD (28)
8.59 (1.27) <1min
OS (30)
8.48 (1.33)
OD
-
OS
-
Group Y Tono-Pen VET®
-
FIGURE LEGENDS Figure 1. (a) Rebound tonometry is being performed on a guinea pig. (b) Applanation tonometry is being performed on the same animal. Note that in both measurements, only light restraint by the operator is necessary. Figure 2. Agreement between IOP measurements between TonoVet® (TV) and Tono-Pen VET®(TP) evaluated by LCC. Each symbol represents either right or left IOP measurement and the straight line represents perfect agreement. Figure 3. The Bland and Altman scatterplot showed lack of agreement between both methods, mainly due to a consistently lower IOP value for the Tono-Pen VET® compared with the TonoVet® represented by the mean of each measurement against the differences of both measurements.