Manometric Intraocular Pressure Research Articles

Agreement of tonometer for measuring intraocular pressure in Wistar rats: a systematic review

Glaucoma is the most common cause of irreversible blindness in the world. It is associated with elevated intraocular pressure (IOP). Fluctuations in tonometer readings have implications for glaucoma research, where accurate IOP measurements are vital for evaluating disease progression and treatment efficacy. Researchers should carefully select the appropriate tonometer and consider biases associated with different tonometers. Validation against standard measurements can improve IOP measurement accuracy in rat models. In conclusion, this systematic review will emphasize on the importance of selecting the appropriate tonometer for IOP measurement in rat models, considering potential biases and their implications for glaucoma research. Accurate and consistent IOP measurement in rat models is crucial for understanding glaucoma pathophysiology and developing effective treatments. This systematic review aims to assess agreement among tonometers used for measuring IOP in Wistar rat models primarily focusing on TonoLab, TonoVet, and Tono-pen. The review was conducted using PRISMA guidelines. Two articles were included for qualitative synthesis. The studies compared manometric IOP with TonoLab, rebound tonometer, and Tono-pen XL readings. It was observed that TonoLab consistently underestimated IOP, while Tono-pen XL tended to overestimate IOP compared to manometric measurements. The study’s findings will help researchers in making decisions about tonometer selection, leading to more reliable outcomes in glaucoma research using rat models. Further research, specifically RCT’s (randomized controlled trial) is needed to confirm the results and enhance IOP measurement precision in rat models.

Validation of the Reichert® Tono-Vera® Vet rebound tonometer in normal exvivo canine eyes.

To determine the accuracy of the Reichert® Tono-Vera® Vet rebound tonometer for canine intraocular pressure (IOP) measurement. Five normal canine exvivo globes. The anterior chambers of five freshly enucleated normal canine eyes were cannulated and connected to a reservoir of Plasma-Lyte A and a manometer. Starting at a manometric IOP of 5 mmHg, the pressure was progressively increased to 80 mmHg by raising the reservoir. Triplicate IOP measurements were taken with the Tono-Vera® Vet from the central cornea using the dog setting and compared to the manometric pressure by linear regression analysis and Bland-Altman plots. There was a strong positive linear regression trend when comparing central corneal Tono-Vera® Vet IOPs to manometric pressures (r2 = .99) with solid agreement between the two methods. Compared to manometric IOPs, the Tono-Vera® Vet underestimated IOPs at higher pressures ≥70 mmHg. Measurement of IOPs from the central cornea with the Tono-Vera® Vet provided accurate results over a large range in normal canine globes compared to direct manometry. The mild to moderate underestimation of IOPs at high pressures was not considered clinically relevant.

Validation of the eyeTelemed IOPvet indentation tonometer for use in dogs.

To assess the accuracy of canine intraocular pressure (IOP) estimates from the eyeTelemed IOPvet indentation tonometer. Part 1 included 54 eyes from 28 Beagle dogs-23 ADAMTS10-mutants with open-angle glaucoma and 5 normals. Part 2 involved five normal canine exvivo globes. Part 1 (in vivo) compared IOPvet estimates in normal and glaucomatous dogs to Reichert Tono-Vera® Vet rebound tonometry. The three IOPvet estimates were green (normal; <20 mmHg, according to the manufacturer), yellow (elevated; 20-30 mmHg), and red (high; >30 mmHg). In Part 2 (ex vivo), the pressure inside freshly enucleated normal canine eyes was progressively increased from 5 to 80 mmHg and compared to IOPvet estimates. Descriptive statistics compared IOPvet estimates to rebound tonometry and direct manometry, with the threshold from normal to glaucoma set at 30 mmHg. In Part 1 (in vivo), normal pressures (≤30 mmHg) were mainly identified correctly as green or yellow-110 of 111 estimates, corresponding to a specificity of 99%. Only 16 of 125 affected estimates were correctly displayed in the >30-mmHg range; the remaining 109 showed ≤30 mmHg, corresponding to a sensitivity of 13%. In Part 2 (ex vivo), all normal pressures were correctly estimated with green, but 64 of 88 manometric IOPs >30 mmHg were falsely estimated as 20-30 mmHg. The IOPvet is inaccurate in estimating canine IOP with a low sensitivity at identifying dogs with IOP > 30 mmHg. Canine-specific instrument revision is required to correctly identify elevated (yellow = 20-30 mmHg) and high (red >30 mmHg) IOPs.

Validation of the Icare® TONOVET plus rebound tonometer in normal rabbit eyes

To determine the accuracy and precision of the Icare® TONOVET Plus rebound tonometer for measuring intraocular pressure (IOP) in normal rabbit eyes, as well as compare it to three other commercially available tonometers: the Icare® TONOVET (TV01), Tono-Pen Vet™, and Tono-Pen AVIA Vet™. The anterior chambers of both eyes of three New Zealand White rabbits were cannulated, post-mortem. IOP was measured using each of the above four tonometers at manometric pressures ranging between 5 mmHg and 70 mmHg. Data were analyzed by linear regression, ANOVA, and Bland-Altman plots. A p-value of ≤0.05 was considered significant for all statistical tests. IOP values obtained with the TONOVET Plus (in ‘lapine’ mode) were significantly closer to manometric IOP than those obtained with the other tonometers tested. The TV01 (in ‘d’ dog setting) and Tono-Pen AVIA Vet™ were significantly more accurate compared to the Tono-Pen Vet™. All tonometers had high levels of precision, though the TONOVET Plus and TV01 were significantly more precise compared to the Tono-Pen AVIA Vet™. All tonometers tended to underestimate IOP, particularly at high pressures, however the TONOVET Plus was highly correlated with manometric IOP in the clinically relevant range of 5–50 mmHg. The TONOVET Plus is an appropriate choice of instrument for measuring IOP in rabbit eyes in both research and clinical settings.

Intraocular Pressure Measurement by Rebound Tonometry (TonoVet) in Normal Pigeons (Columba livia).

We evaluated the applicability of a rebound tonometer (TonoVet) in pigeon eyes and established normal reference intraocular pressure (IOP) values in healthy pigeons; 20 eyes of euthanized pigeons were used for calibration of the TonoVet and 48 eyes of 24 adult pigeons were used for measurement of reference IOP. First, IOP of pigeon eyes ex vivo were measured using the 'd' and the 'p' modes of the TonoVet and compared to manometric IOP values from 5 to 80 mm Hg. Then, to establish normal reference values, IOP was measured from clinically normal pigeons in vivo. The 'd' and the 'p' modes of the TonoVet showed a strong linear correlation with the manometric IOP (R2 = .996 and .991, respectively). The obtained regression formulas were: y1 = 0.439x + 2.059 and y2 = 0.330x - 0.673, respectively (y1, 'd' mode of TonoVet; y2, 'p' mode of TonoVet; x, manometric IOP). The 'd' and the 'p' modes consistently measured one-half and one-third of the actual IOP, respectively. Therefore, the formula obtained through the 'd' mode was applied to obtain reference values. The calibrated IOP of normal pigeon eyes was 19.5 ± 4.4 mm Hg. The actual IOP could be calculated using the presented formula. Considering the limitations of the 'p' mode, use of the 'd' mode is more appropriate. Therefore, the TonoVet rebound tonometry under the 'd' mode is a reliable method for measuring IOP in pigeons.

Tonometer validation and intraocular pressure reference values in the normal chinchilla (Chinchilla lanigera).

To determine accuracy and precision of three commonly used tonometers (TonoVet® and TonoLab® (ICare Oy, Finland)-rebound tonometers, and Tono-Pen VET™ (Reichert, NY)-applanation tonometer) in normal chinchillas, and to establish a normal intraocular pressure (IOP) reference range in this species. The anterior chambers of three chinchilla eyes were cannulated ex vivo and readings obtained at manometric IOPs from 5 to 80 mmHg, using each of the three tonometers in random order. Data were analyzed by linear regression, ANOVA, and Bland-Altman plots. Tonometry was performed in both eyes of 60 chinchillas (age 8 weeks-16.2 years) using the TonoVet® and relationship between age and IOP analyzed using linear regression. For all statistical tests, P < 0.05 was significant. Intraocular pressure values obtained using the Tono-Pen VET™ and TonoVet® (in dog calibration mode;'d') showed strong linear correlation with manometry within the physiologic and clinically relevant range of IOP (0-50 mmHg). The TonoVet® 'd' setting displayed significantly greater precision over the full range of IOP evaluated than the Tono-Pen VET™, and both TonoVet and Tono-Pen VET™ were significantly more accurate than the TonoLab® tonometer. Mean ± SD IOP (TonoVet® 'd') in chinchillas was 9.7 ± 2.5 mmHg, and the 95% reference interval was 4.7-14.7 mmHg. Both the Tono-Pen VET™ and TonoVet® provided clinically acceptable estimates of IOP in chinchillas. The TonoVet® provides accurate and precise IOP values, while Tono-Pen VET™ derived measurements showed greater variability. Values obtained either with the TonoLab® or TonoVet® used in the 'unspecified' calibration setting were inaccurate in this species.

Goldmann Tonometer Prism with an Optimized Error Correcting Applanation Surface.

PurposeWe evaluate solutions for an applanating surface modification to the Goldmann tonometer prism, which substantially negates the errors due to patient variability in biomechanics.MethodsA modified Goldmann or correcting applanation tonometry surface (CATS) prism is presented which was optimized to minimize the intraocular pressure (IOP) error due to corneal thickness, stiffness, curvature, and tear film. Mathematical modeling with finite element analysis (FEA) and manometric IOP referenced cadaver eyes were used to optimize and validate the design.ResultsMathematical modeling of the optimized CATS prism indicates an approximate 50% reduction in each of the corneal biomechanical and tear film errors. Manometric IOP referenced pressure in cadaveric eyes demonstrates substantial equivalence to GAT in nominal eyes with the CATS prism as predicted by modeling theory.ConclusionA CATS modified Goldmann prism is theoretically able to significantly improve the accuracy of IOP measurement without changing Goldmann measurement technique or interpretation. Clinical validation is needed but the analysis indicates a reduction in CCT error alone to less than ±2 mm Hg using the CATS prism in 100% of a standard population compared to only 54% less than ±2 mm Hg error with the present Goldmann prism.Translational RelevanceThis article presents an easily adopted novel approach and critical design parameters to improve the accuracy of a Goldmann applanating tonometer.

Validation of rebound tonometry for intraocular pressure measurement in the rabbit

Rabbits play a growing role in research into glaucoma surgical models and ocular drug delivery models. However, the lack of an accurate method for measuring intraocular pressure (IOP) in this animal has been a significant deficit. In this study we validated the use of the TonoVet rebound tonometer and provide conversion tables for its use in rabbits. Experiments were performed on 18 adult New Zealand White rabbits. The TonoVet measurements were obtained and compared to manometric readings by anterior chamber (AC) cannulation. The TonoVet position and ‘d’ (dog or cat) and ‘p’ (other species) modes were compared. The sensitivity of the TonoVet tonometer in assessing IOP changes was also tested. There was a strong linear correlation for both the ‘d’ mode (mean slope = 0.84 ± 0.03, r(2) = 0.99 ± 0.03) and the ‘p’ mode (mean slope = 0.64 ± 0.02, r(2) = 0.97 ± 0.01) of the TonoVet with manometric IOP. However, the TonoVet had a tendency to underestimate IOP compared to manometry and conversion formulae were possible to calculate for both modes. The orientation of the TonoVet handle had no effect on IOP reading, as long as the groove was horizontal. No significant differences were observed when comparing right and left eyes (P > 0.05). IOP recovered four days after cannulation. Younger rabbits had lower IOP compared with older rabbits (P < 0.01). Timolol produced a 2.5 mmHg reduction in IOP 2 h later as detected by the TonoVet. Using the conversion table presented, the TonoVet is a reliable and precise tool for the measurement of IOP in rabbits.

Does Optic Nerve Head Surface Topography Change Prior to Loss of Retinal Nerve Fiber Layer Thickness: A Test of the Site of Injury Hypothesis in Experimental Glaucoma

PurposeTo test the hypothesis that optic nerve head (ONH) deformation manifesting as changes in its mean surface height precedes thinning of the peripapillary retinal nerve fiber layer (RNFL) in experimental glaucoma (EG).Methods68 rhesus macaque monkeys each had three or more baseline imaging sessions under manometric intraocular pressure (IOP) control to obtain average RNFL thickness (RNFLT) and the ONH surface topography parameter mean position of the disc (MPD). Laser photocoagulation was then applied to the trabecular meshwork of one eye to induce chronic, mild-to-moderate IOP elevation and bi-weekly imaging continued. Event analysis was applied to determine for each parameter when an ‘endpoint’ occurred (signficant change from baseline) for eight different endpoint criteria. Specificity was assessed in the group of 68 fellow control eyes. Classical signal detection theory and survival analysis were used to compare MPD with RNFLT.ResultsRegardless of the endpoint criterion, endpoints were always more frequent for MPD than for RNFLT. The discriminability index (d’) was 2.7 ± 0.2 for MPD and 1.9 ± 0.2 for RNFLT (p<0.0001). Endpoints were reached by MPD an average of 1-2 months earlier than by RNFLT (p<0.01). At the onset of the first specific, detectable MPD change in EG eyes, there was still no significant change in RNFLT on average (p=0.29) and only 25% of individual eyes exhibited signficant reduction. In contrast, at onset of signficant RNFLT change, MPD had already changed an average of 101 µm from baseline (p<0.0001) and 71% of the individual eyes had exhibited significant change. The magnitude of MPD change was more than could be explained on the basis of axon loss alone.ConclusionsThis study demonstrates that the average surface height of the ONH changes prior to any detectable loss of average peripapillary RNFL thickness in non-human primate eyes with experimental glaucoma.

Validation of the TonoVet®rebound tonometer in normal and glaucomatous cats

Objective To validate intraocular pressure (IOP) readings obtained in cats with the TonoVet(®) tonometer. Animals studied IOP readings obtained with the TonoVet(®) were compared to IOP readings determined by manometry and by the Tono-Pen XL(™) in 1 normal cat and two glaucomatous cats. TonoVet(®) and Tono-Pen XL(™) readings were also compared in a further six normal and nine glaucomatous cats. Procedures The anterior chambers of both eyes of three anesthetized cats were cannulated and IOP was varied manometrically, first increasing from 5 to 70 mmHg in 5 mmHg increments, then decreasing from 70 to 10 mmHg in 10 mmHg decrements. At each point, two observers obtained three readings each from both eyes, with both the TonoVet(®) and Tono-Pen XL(™) . IOP was measured weekly for 8 weeks with both tonometers in six normal and nine glaucomatous unsedated cats. Data were analyzed by linear regression. Comparisons between tonometers and observers were made by paired student t-test. Results The TonoVet(®) was significantly more accurate than the Tono-Pen XL(™) (P = 0.001), correlating much more strongly with manometric IOP. In the clinical setting, the Tono-Pen XL(™) underestimated IOP when compared with the TonoVet(®) . Conclusions Both the TonoVet(®) and Tono-Pen XL(™) provide reproducible IOP measurements in cats; however, the TonoVet(®) provides readings much closer to the true IOP than the Tono-Pen XL(™) . The TonoVet(®) is superior in accuracy to the Tono-Pen XL(™) for the detection of ocular hypertension and/or glaucoma in cats in a clinical setting.

Calibration of the TonoLab Tonometer in Mice with Spontaneous or Experimental Glaucoma

To measure the accuracy of TonoLab (TioLat, Helsinki, Finland) tonometry in mice with spontaneous or induced experimental glaucoma. Chronic intraocular pressure (IOP) elevation was induced in one eye of 32 mice by injection of polystyrene beads and viscoelastic material. Three to 6 weeks later, the eyes were cannulated and manometrically set to 10, 20, 30, 40, or 50 mm Hg. The mice were 8-week and 8-month-old C57BL/6, 8-week-old DBA/2J, and 8-week-old CD1. The TonoLab calibration was also tested on five aged DBA/2J mice with spontaneous glaucoma. The relation of the TonoLab reading to manometric IOP was evaluated in multivariate linear regression models with axial length, IOP history, and mouse strain as independent variables. The slope of the relationship between TonoLab and manometric IOP in all the mice was 0.998, with an intercept of 2.3 mm Hg (adjusted R in univariate regression = 0.86). Neither the mice with bead-induced glaucoma nor those with spontaneous glaucoma (older DBA/2J mice) differed significantly from the control animals in having an excellent correlation between TonoLab and manometer IOP. Longer and wider mouse eyes had slightly higher tonometrically measured IOP, whether glaucomatous or control (multivariate regression, adjusted R(2) = 0.90, P < 0.0001). There was no difference in tonometric accuracy among the three mouse strains: CD1, C57BL/6, and DBA/2J, nor between 8-week and 8-month-old C57BL/6 mice (multivariate regression, P = 0.32). The TonoLab accurately reflects IOP in both normal mice and in eyes of mice with experimental or spontaneous glaucoma, with no detectable effect of age.

Evaluation of rebound tonometry in non-human primates

To determine the accuracy and reproducibility of intraocular pressure (IOP) measurements obtained with the TonoVet ® rebound tonometer in cynomolgus macaques and to determine the effects of corneal thickness on measurements obtained by the TonoVet ®. The anterior chambers of both eyes of anesthetized monkeys were cannulated with branched 23-G needles; one branch was connected to a vertically adjustable reservoir and the other to a pressure transducer. IOP was increased by 5 mmHg increments and then decreased by 10 mmHg decrements. IOP was measured using the TonoVet ® at each increment and decrement by 2 independent observers and at every other increment and every decrement by a single observer using ’minified’ Goldmann applanation tonometry. Central corneal thickness was measured with a PachPen TM ultrasonic pachymeter. TonoVet ® readings correlated well with manometric IOP (slope = 0.972, r 2 coefficient = 0.955). No significant differences were observed when comparing eyes or operators; however there was a non-significant trend for TonoVet ® readings taken in right eyes to be closer to manometric IOP than those taken in left eyes. The TonoVet ® had a non-significant tendency to underestimate manometric IOP. TonoVet ® readings obtained during the decremental phase of the experiment were significantly closer ( p < 0.004) to manometric IOP than those obtained during the incremental phase. Central corneal thickness significantly increased ( p < 0.0001) over the course of the experiment. The TonoVet ® rebound tonometer is a reliable and accurate tool for the measurement of IOP in cynomolgus macaques. This tonometer has several advantages, including portability, ease of use, and brief contact with the corneal surface making topical anesthetics unnecessary.

Manometric Calibration and Comparison of TonoLab and TonoPen Tonometers in Rats With Experimental Glaucoma and in Normal Mice

To compare the TonoPen and TonoLab tonometers to each other and to manometrically set intraocular pressure (IOP) in the eyes of normal mice, normal rats, and rats with chronic IOP elevation. The measurement of IOP by the TonoPen and TonoLab tonometers was made in 21 normal rat eyes, 10 normal mouse eyes, and 16 rats that had either 2 or 4-week experimental glaucoma. IOP was varied from 10 to 50 mm Hg in steps of 10 mm Hg under conditions in which the eye was either open or closed to the reservoir controlling IOP. In normal rat eyes, TonoPen overestimated manometric IOP at 10 mm Hg and underestimated it by up to 6 mm Hg at higher IOP, whereas the TonoLab matched set IOP within 1 mm Hg. In glaucoma rat eyes, the TonoLab accurately reflected manometric IOP under open stopcock conditions (linear regression: y = 0.99x -0.62, R = 0.98), whereas in the closed stopcock condition, IOP measured lower at the higher IOP levels (P = 0.0059, paired t test). In uncannulated rat glaucoma eyes, the tonometer used first gave higher IOP [paired t test, P = 0.015 (TonoLab first); P = 0.005 (TonoPen first)]. In normal mouse eyes under the open stopcock condition, the TonoLab nearly matched manometric IOP (linear regression: y = 0.98x + 1.57, R = 0.98). In mouse and rat eyes, including rats with chronic IOP elevation, the TonoLab accurately reflected manometrically set IOP in an efficient manner.

The Induction/Impact Tonometer: a New Instrument to Measure Intraocular Pressure in the Rat

Non-invasive intraocular pressure (IOP) measurement in rats can be performed with a variety of methods, none of which seems appropriate for scaling down for the mouse eye. In an attempt to develop such a method for non-invasive IOP measurement in mice, an alternative concept, that of rebound tonometry, was explored using an induction/impact (I/I) tonometer probe. IOP measurement using the rebound concept is based on bouncing a probe onto the eye and detecting its motion. Motion parameters of the probe, which vary according to eye pressure, are used to calculate the IOP.As a first step towards this goal a prototype I/I tonometer was evaluated for IOP measurement of the rat eye. Two similar instruments were constructed and tested for their ability to measure accurately and reliably rat IOP by comparing the measurements against the manometric (true) IOP as determined by cannulation ex vivo. Good correlation between the true IOP and the I/I measurements (R2=0.95) was detected for IOP between 7.4 and 56mmHg. Although individual eyes tested showed some variability in the relationship of the measured IOP with the true IOP, this variability was minimal.Starting probe–cornea distance between 3 and 5mm, and angle of impact up to 25° relative to the visual axis at the corneal apex, did not affect the reproducibility of the I/I tonometer.Comparison of I/I tonometer measurements to direct manometric determination of IOP by in vivo cannulation of eyes in anesthetized normal female Wistar rats correlated reasonably well (R2=0.67) with manometrically determined IOP within the narrow range of normal rat IOPs (10–16.5mmHg), underestimating the true (manometric) IOP by an average of 11.6%.The I/I tonometer is a reliable and accurate instrument for non-invasive IOP measurement in rat eyes that can potentially be adapted for IOP measurement in mice.

Indentation and Applanation Tonometry in Rabbits

Two types of tonometers, indentation and applanation, were compared for their ability to accurately measure intraocular pressure (IOP) in rabbit eyes. Manometric measurements were made by vitreous cannulation to minimize the physiological and technical disadvantages associated with simultaneous aqueous chamber manometric measurement and tonometric pressure recording. Each of ten pressure levels from 15 to 60 mm Hg were measured by two independent observers. At most pressure levels, neither instrument accurately measured IOP as determined by vitreous chamber cannulation. The two instruments, however, responded similarly to each other at all pressure levels tested. In every instance, mean measurements made by applanation tonometry were lower than those recorded by indentation tonometry. Graphs have been prepared for use in converting measurements taken from rabbit eyes using these instruments to manometric IOP.