Central & Peripheral Cornea and Ocular Response

Introduction

Cornea is a major area of interest for ophthalmologists as they seek to advance current refractive procedures. It is referred to as a viscoelastic system that can be described using its physical features (central corneal thickness (CCT)) and behaviour (biomechanics) (Dana et al. 2015). Studies, for example, Visual Hypertension Treatment, demonstrate that CCT represents a risk factor for the advancement of glaucoma independent on the IOP (Dana et al. 2015). Corneal hysteresis (CH) does not account for natural corneal property. Rather, it evaluates the capability of the cornea to ingest and disperse energy. Along these lines, CH can assist doctors to foresee how the eyes will respond to high intraocular pressure (IOP) and which eyes are more prone to optic nerve head harm and adverse visual field outcomes (Dana et al. 2015). Estimations of central and peripheral corneal curvature are valuable for detecting and examining corneal conditions, for example, keratoconus and for observing corneal shape after visual surgery or refractive processes, such as orthokeratology (Chen and Lam 2009).

Consequently, structural features of the central and peripheral cornea are extremely important for endothelial function for diagnostic purposes or before different surgical interventions to correct a defect. The measurement of CCT and peripheral corneal thickness (PCT) is used for health interventions. Corneal health can be assessed by gauging corneal thickness. Any changes in the corneal could indicate various pathologies. Hence, in clinical practices, it is recommended to get the most precise corneal pachymetry value for every patient (Ortiz et al. 2014). Additionally, corneal thickness also plays a vital role in intraocular pressure measurement, or when corneal refractive surgery is scheduled. That is, the value obtained determines whether the patient requires a surgery, the choice of a specific surgical method, follow-up planning, and/or the challenges related to postoperative outcomes. According to Ortiz et al. (2014), multiple factors could affect the thickness of the corneal pachymetry, and they include age of the patient, the presence of any corneal deterioration, time of the day, and the use of contact lenses (p. 44). It is also imperative to understand that corneal thickness may also experience refractive error. Intraocular pressure is a major risk factor linked to the start and the progression of glaucoma, which is a disorder that results in severe visual challenges that eventually causes blindness if not managed effectively (Yamashita et al. 2011). Hence, precise measurement of intraocular pressure is extremely useful for effective treatment of glaucoma patients.

The assessment of corneal parameters is imperative in ophthalmic reviews. Ophthalmologists use these parameters to acquire valued information on potential causes of glaucoma, to determine the right power of intraocular lens, monitor and to evaluate refractive conditions. Pentacam is a non-invasive equipment that ensures a thorough assessment of the morphological features of the corneal by applying a 3-D model depicting the thickness, volume, and spatial segment. Pentacam uses the Scheimpflug imaging technique to evaluate the corneal thickness and curvature (Gunes et al. 2015). In Ocular Response Analyser (ORA), four parameters are generated, including corneal hysteresis (CH), corneal resistance factor (CRF), Goldman-correlated IOP (IOPg) and corneal-compensated IOP (IOPcc) (Osman et al. 2016, p. 123).

Aim

The research aims to investigate the influence of central and peripheral corneal thickness and curvature on intraocular pressure and corneal biomechanics using two different machines – the Ocular Response Analyser (ORA) with parameters: IOPg, IOPcc, CRF and CH, and Pentacam (Scheimpflug imaging) CCT, PCT curvature of the cornea.

Hypothesis

Alternative hypothesis (H1) – there is a relationship between morphological features of the central and peripheral cornea on ocular response analyser measures of IOP and corneal biomechanics

Null hypothesis (H0) – there is no relationship.

A Review of Literature

The IOP observation is vital following penetrating keratoplasty (PKP) since extreme IOP can cause the graft to failure, and it is common in transplanted eyes with rates as high as 42% (Al Farhan 2016). The Goldmann applanation tonometry (GAT) has always been used as “the gold standard for gauging IOP, but high astigmatism and irregular surface after the PKP can affect the precision, and reduced rigidity of the ocular wall in some instances, including keratoconus, could lead to poor measurement of the IOP using GAT” (Feizi & Pakravan 2012, p. 20). Consequently, there have been efforts to circumvent the issue facing the gold standard in grafted eyes to get an ideal option (Al Farhan 2016).

Ocular Response Analyzer (ORA) Measurement

From a broader point of view, available evidence suggests that corneal morphological features influence outcomes of different ocular measurements and processes (Zhang et al. 2013). It has however been difficult to evaluate biomechanical properties of corneal features in vivo. New developments have eliminated such difficulties. For instance, the use of the Reichert Ocular Response Analyzer (ORA) has provided an immediate clinical assessment of the corneal biomechanical reaction. Consequently, ophthalmologists now have novel methods to apply in preoperative screening of refractive surgical procedures in patients. The ORA depends on speedy air gust to distort the cornea and captures data of the two corneal biomechanical parameters known as corneal hysteresis (CH) and corneal resistance factor (CRF) (Zhang et al. 2013). The CH is generally used to demonstrate the vicious features while the CRF is understood to show the overall viscoelastic resistance of the cornea.

Most researchers have widely applied the ORA to assess biomechanical features of the cornea, and they have demonstrated that various clinical diseases could affect corneal biomechanical properties, for instance, the decline in CH with keratoconus and corneal surgical procedures (Zhang et al. 2013; Ortiz et al. 2014). Further, some studies have attempted to explore the precise clinical factors and value of CH and CRF as corneal biomechanical parameters (Zhang et al. 2013). Recent findings demonstrate that CRF has a strong correlation with corneal spherical-like aberration, particularly in serious cases of keratoconus, which means that it is a vital factor for consideration in keratoconus qualification (Zhang et al. 2013). Further, keratoconus is a condition that affects the cornea through a progressive thinning and anterior extension, finally causing asymmetrical conical change of the shape of the cornea. Results demonstrated that the corneal biomechanical properties have corresponding association with spherical aberrations noted in individuals with keratoconus, and to a larger extent could be associated with the corneal difference according to inherent keratoconus disease factors.

The ORA, developed by Reichert Ophthalmic Instruments, Depew, New York, is a latest non-contact tonometer gadget that evaluates response of the cornea to indentation through rapid air pulse (Zhang et al. 2013; Feizi & Pakravan 2012). It is developed to generate two types of measurement for corneal biomechanical properties, namely corneal hysteresis (CH) and the corneal resistance factor (CRF) (Zhang et al. 2013) and measures IOP, independent of corneal thickness and rigidity. The corneal hysteresis occurrence emanates from the viscoelastic stifling in the cornea. That is, the capability of the tissue to absorb and dispel energy is reduced. On the other hand, the CRF optimizes the relations to CCT, showing the entire biomechanical strength of the cornea based on the enhanced corneal biomechanical parameter.

Apart from CH and CRF measurements, ORA analyses also include the Goldmann-correlated IOP (IOPg), corneal-compensated IOP (IOPcc) (Al Farhan 2016). The IOPcc measures IOP, which is less influenced by the corneal features relative to Goldmann applanation tonometer (GAT) (Al Farhan 2016).

Once the cornea has deformed inwards due to air pulse, it undergoes inward applanation (Feizi & Pakravan 2012). After few milliseconds following the inward applanation, the air puff closes off, creating low pressure in a balanced manner. In this period, the cornea regains its normal shape. Further, during the same process, the “corneal once more go through an outward applanation” (Feizi & Pakravan 2012, p. 20). An electro-optical collimation detector system is responsible for evaluating any corneal curvature changes in the three-millimetre diameter for both inward and outward applanation. It also depends on a random coefficient to change these distortions into two applanation pressures. From a theoretical standpoint, both pressures should have similar values, but this is not observed. Hysteresis, which is a factor of corneal viscosity, is the variation between outward and inward applanation pressures (Feizi & Pakravan 2012). Corneal thickness and rigidity generally affect hysteresis. The CRF, as measured by the ORA, is seen as influenced by the elastic features found in the cornea, and it seems to be a measure of the total perceived resistance of the cornea. That is, the CRF measures the aggregate outcomes of both the elastic and viscous resistance met by the air puff while deforming the surface the cornea (Al Farhan 2016). The Goldmann-related IOP (IOPg) is usually derived from the average of these two applanation pressures while cornea-compensated IOP (IOPcc) is used to gauge IOP values independent of corneal properties, such as central thickness (Feizi & Pakravan 2012, p. 20).

A study conducted by Ostadimoghaddam et al. (2012) revealed that positive association existed between CH value and CCT. Additionally, positive correlation was also observed between superior corneal thickness, inferior corneal thickness, and central corneal elevation (Ostadimoghaddam et al. 2012). There was also positive relationship between CH and corneal volume. Anterior chamber, however, yielded significant negative correlation on CH value, volume, depth, and angle. The shape feature also had negative correlation. Finally, there was no significant association noted between CH and other corneal parameters (Ostadimoghaddam et al. 2012).

Ostadimoghaddam et al. (2012) also observed positive correlation between CRF and corneal topographic parameters. According to the findings, significant positive association was observed between “CRF and central, superior and inferior corneal thickness while significant negative correlation was also noted between CRF, superior, and inferior corneal power” (Ostadimoghaddam et al. 2012, p. 13). Other parameters did not indicator any important relationships.

Further, Ostadimoghaddam et al. (2012) noted positive correlation between intraocular pressure and corneal topographic parameters. Significant correlation of IOPg was present in central and thinnest corneal thickness, superior corneal thickness, minimum posterior power, and maximum posterior power. However, significant negative correlation was noted between central corneal power, inferior and superior corneal power. Other parameters did not present any significant correlation with IOPg.

Finally, corneal compensated intraocular pressure had significant correlation with corneal topographic parameters (Ostadimoghaddam et al. 2012). Significant correlation was determined between IOPcc with anterior chamber volume and anterior chamber depth. There was however no significant correlation between IOPcc and other parameters.

By focusing on the variation between “the outward and inward applanation pressures, CH attempts to show the damping process in cornea” (Ostadimoghaddam et al. 2012, p. 14). In this case, findings demonstrate that CH is a positive measure of corneal biomechanical features. Normal values for CH range between 8 mmHg and 15 mmHg. Most studies also find values within this range (Ostadimoghaddam et al. 2012), and researchers have used such values to conclude. Consequently, they have concluded that CH has a positive correlation with CCT. Further, Ostadimoghaddam et al. (2012) claimed that an increase in CCT was associated with overall resistance to cornea deformation, which also increased. Hence, these changes led to higher levels of CH. It is observed that about 90% of the corneal thickness is made up of stromal layer. As such, corneal stroma is a major factor in determining biomechanical and refractive characteristics of the cornea. For the most part, the thickness of the cornea can be a vital factor for consideration when deciding corneal biomechanical features. The ordinary human corneal stroma when affected could be identified with the biomechanical unsteadiness of the tissue (Ostadimoghaddam et al. 2012). Different reviews have found that the particular engineering of the most foremost section of the corneal stroma (100-120 μm) controls the dependability of the corneal shape (Ostadimoghaddam et al. 2012).

Nevertheless, the outcomes in this study by Ostadimoghaddam et al. (2012) uncovered a more grounded positive relationship of CRF than CH with CCT. Ostadimoghaddam et al. (2012) also noted that previous findings additionally expressed that CRF had a solid positive relationship with CCT assessed with ultrasonography in the typical group, but CH had a lower association. Then again, other past studies also found that hysteresis and CRF evaluated using the ORA have “a positive yet modest relationship to CCT – higher value for CCT are associated with the higher value for the hysteresis (visco-flexibility) and CRF (versatility)” (Ostadimoghaddam et al. 2012, p. 14). In concurrence with conclusions from these studies, Ostadimoghaddam et al. (2012) additionally showed that corneal thickness has a vital part in the damping procedure, especially in the versatile properties of cornea. Despite the relationship seen between CCT with CH and CRF in this research, some findings revealed that eyes with the similar CCT yielded fluctuating levels of CH, suggesting that other unknown variables might affect corneal biomechanics. For instance, El-Malah (2013) found that CH value was low in research participants who had cases of glaucomatous eyes relative to others who had normal eyes. CH depicts a dynamic property of the cornea to resist changes. It is observed that more elastic or distensible ocular morphological features perhaps are linked to development of glaucoma lesions, and based on the findings of El-Malah (2013), lower biomechanical condition of the cornea be associated with weaker lamina cribrosa.

The modest levels of relationship found in this study between these factors propose that other obscure biomechanical variables should likewise contribute towards the qualities of CH. Such obscure variables could be linked to damages or changes in the optic nerve head, which confirm damages related to glaucoma (Nongpiur et al. 2015). As results by Ostadimoghaddam et al. (2012) showed, one of these elements may be corneal volume. Findings of this review indicated positive relationship between corneal hysteresis and corneal volume. However, there was no any noteworthy relationship between CRF and corneal volume. Evidence likewise showed that corneal volume was somewhat an enhanced indicator for CH but not CRF, alluding that CH may mirror more composite effect of corneal thickness and layer difference (Ostadimoghaddam et al. 2012). Corneal volume is a 3-D parameter and, therefore, it can assume a more compelling role than corneal thickness, the 2-D parameter, in evaluating biomechanical features of cornea (Ostadimoghaddam et al. 2012). Other findings illustrated the critical role of corneal volume in distinguishing keratoconus (Tafti et al. 2010). Tafti et al. (2010) recommended that Pentacam determined parameters like corneal volume dispersion and rate increment in volume can be useful in identifying gentle and modest types of keratoconus from ordinary corneas.

Results presented by Ostadimoghaddam et al. (2012) uncovered the negative relationship between CH and corneal shape figure. The higher negative curvature feature values were related with the higher estimations of corneal hysteresis and as it moved near zero, lower figures of CH result were observed (Ostadimoghaddam et al. 2012). Bearing in mind this relationship, nearsighted people may have diverse corneal hysteresis compared with hyperopic individuals. Ostadimoghaddam et al. (2012) observed a negative association between CH and volume, angle, and depth of the anterior section. Reduced levels of corneal hysteresis were linked to deeper anterior chamber depth (Ostadimoghaddam et al. 2012). Different reviews have revealed the relationship of CH with corneal diameter (Ostadimoghaddam et al. 2012). Subsequently, it may be expected that longer separation between corneal top and limbus is comparable with other lower segments of the cornea (Ostadimoghaddam et al. 2012). As per the results of the study by Ostadimoghaddam et al. (2012), IOPg had a negative relationship with dioptric force of all sections of frontal cornea, and a positive association with corneal thickness and power in posterior of the cornea that ought to be examined in future reviews. Finally, Ostadimoghaddam et al. (2012) found no significant relationship between IOPcc and CCT. Specifically, as findings demonstrated, IOPcc had an insignificant effect from other influencing corneal features, and in those vital relationships, no solid stronger coefficient existed. This shows IOPcc may be an autonomous measure of IOP from other corneal components. In addition, CCT did not have any significant relationship with anterior chamber depth or angle when measured with Pentacam Scheimpflug imaging, and it was an independent factor (Liu, Ferri & Lazzaro 2011).

Pentacam Scheimpflug Imaging

The Pentacam was initially presented as an anterior section analyser that uses the Scheimpflug photography technique (McAlinden, Khadka & Pesudovs 2011, p. 7731). In a more current model, specifically the Pentacam high-resolution (HR) tomographer, the resolution of images has improved, and more data from various sources are now processed (McAlinden, Khadka & Pesudovs 2011). Amid image acquisition with the Pentacam, which lasts about 2 seconds, a pivoting Scheimpflug camera takes images from cross-segments of the front part, which are lit up by opening lights at various meridians (McAlinden, Khadka & Pesudovs 2011). Since every one of these openings overlaps in the focal point of the cornea, the exactness of focal estimations is enhanced. The software analyses all information from all areas, remakes a 3-D representation of the foremost segment, and creates readings of various parameters. Pentacam Scheimpflug is currently considered superior and capable of delivering quality images of the cornea, anterior chamber, and lens, offering a wide range of assessments across the anterior part. Hence, it is vital in measuring corneal thickness and assessing their relationship.

Utilising the information from the two corneal surfaces, the Pentacam evaluates the thickness of the cornea at all areas of interests. This tool has been shown to produce exceptionally repeatable and reproducible pachymetry readings contrasted with ultrasound pachymeters (Hashemi & Mehravaran 2010). Pentacam estimations of the corneal thickness are practically identical with ultrasound values, and the concurrence between Pentacam and ultrasonic values is superior to that of the Orbscan, particularly in post-surgical eyes (Hashemi & Mehravaran 2010, p. 44). With regard to the display, the Pentacam produces colour-coded pachymetry maps that one may fuse in the 4-map displays. Like in other measurement gadgets, numeric aspects can be overlaid to encourage auditing of the maps (Hashemi & Mehravaran 2010). On the side box, the thickness qualities and areas of the student focus, zenith, and most slender purpose of the cornea are displayed. An innovative display choice, nevertheless, is the relative pachymetry map where corneal thickness information is created utilising a toric ellipsoid reference surface (Hashemi & Mehravaran 2010). Based on the map, the thickness of “any given indicator is compared with the ordinary thickness at that point” (Hashemi & Mehravaran 2010, p. 44). This implies that a typical map indicates 0% at all areas, despite the fact that the thickness increases at the edges. The corneal thickness spatial profile and the rate of increment in thickness from the narrow part of the cornea towards the end are distinctive between keratoconic and typical corneas. The Pentacam programming uses such examination in the “Refractive” and “Pachymetric” presentations to help recognize ectatic challenges and distinguish them from alterations observe following keratorefractive surgery.

Hashemi and Mehravaran (2010) compared Orbscan II and Pentacam to determine their accuracy on corneal curvature and power. Notably, the Orbscan II is furnished with a Placido plate, and it can quantify the corneal curvature straightforwardly. The Pentacam, on the contrary, is just height based and subsequently curvature and power information are obtained from elevation data. Corneal power display alternatives with the Pentacam incorporate the sagittal (pivotal) and unrelated curvature of the foremost and back corneal surfaces, and also the actual net power, the keratometric control deviation, the refractive power, and the corresponding k-reading power. In most pre-defined displays, for example, the topometric, refractive, and distinctive 4-map displays, the sagittal power map is shown. Notwithstanding, the tangential power is recognised for having less pivotal inclination and a superior apparatus for distinguishing unusually steep areas of the cornea, for example, a keratoconus cone. When observing the map, a close steepness exceeding 48.0 D can be a characteristic of keratoconus (Hashemi & Mehravaran 2010).

Various studies have attempted to identify the best Pentacam power values for intraocular lens power evaluation in post refractive surgery eyes (Hashemi & Mehravaran 2010). A few reports recommend utilising the Holladay corresponding keratometry reading (EKR) or the actual net corneal power. An essential part of the structured display is the EKR appropriation chart, which can be an indicator of postoperative result in which low ranges and sharp pinnacles support better results. In any case, alert is required in the utilisation of the Pentacam information because irrespective of higher precision, the data ought to just be utilised as a part of specific estimation equations, for example, the Holladay 2 and the BESSt algorithm (Hashemi & Mehravaran 2010).

Nguyen, Liu, and Liu (2016) demonstrated that Scheimpflug gadgets can give exceptionally repeatable CCT estimations that are analogous to, but not likely substitutable with, ultrasound pachymetry CCT. Earlier research has demonstrated that profoundly reproducible CCT estimations can be attained using the Pentacam, Sirius, Galilei, and Corvis ST (Nguyen, Liu & Liu 2016). Among these gadgets, the Galilei has reported the highest score for intraoperator repeatability. This might be to a limited extent owing to its double rotational camera feature, which can control the CCT gauge from two distinctive Scheimpflug cameras. Nevertheless, it is imperative to recognise that various findings generally detail different CCT measurement results for different devices. A review focusing on CCT estimations recorded from Scheimpflug devices with ultrasound pachymetry has been distributed already. A few examinations have revealed no variation in mean CCT attained through either ultrasound pachymetry or with the Pentacam. Conversely, a few different reviews have shown a huge contrast in the mean CCT measured by Pentacam and by ultrasound pachymetry (Nguyen, Liu & Liu 2016). Additionally, the Sirius-CCT estimation is comparable, however, fundamentally not the same as the ultrasound pachymetry CCT. Despite sharing a typical imaging technology, different Scheimpflug gadgets seem to acquire CCT estimations that are statistically not quite the same as each other. Although these variations might be small, care is required when comparing CCT values across various evaluation tools. It remains to be cleared up whether these variations might be adequately small for them to be considered unimportant or negligible in clinical settings (Nguyen, Liu & Liu 2016).

While different corneal parameters might be related with glaucomatous risk freely of their impact on IOP measurement, the investigation of corneal biomechanics may help in better comprehension of factors that contribute to estimation errors. IOP is an adjustable risk factor seen as closely related with glaucomatous advancement. A desired objective in glaucoma administration is estimating IOP, as close as could reasonably be expected, to the “actual” IOP (Nguyen, Liu & Liu 2016). An intracameral gauging of IOP might be the most precise technique for accomplishing this goal, but it is clinically unfeasible. Along these lines, different methodologies have been proposed and presented to help stabilise impacts that biomechanical elements of the cornea have on IOP estimation. Regression approaches have been developed with standard corrections for estimates derived through applanation tonometry, considering the impacts of CCT. However, studies now emerge with evidence that corneal biomechanical properties, for example, corneal hysteresis, may better clarify the source of estimation error in tonometry than CCT (Nguyen, Liu & Liu 2016).

Discussion and Conclusion

Evidence available demonstrates that there is a relationship between morphological features of the central and peripheral cornea on ocular response analyser measures of IOP and corneal biomechanics. Hence, the null hypothesis is rejected. The ORA, one major common tonometers, has become the most preferred clinical gadget for assessing biomechanical properties (Zheng et al. 2016). In spite of the fact that multiple factors can affect CH and CRF, for example, corneal health condition, corneal thickness, IOP and the properties of the entire eye, they are broadly acknowledged as vital factors for understanding the biomechanical condition of the cornea and clinical assessment of eye diseases.

Corneal thickness and peripheral corneal thickness had a compelling part in influencing biomechanical properties of this tissue. Furthermore, significant correlation between CH and corneal volume was also determined (Ostadimoghaddam et al. 2012). Since corneal volume is a 3-D parameter, it can assume a more compelling part relative to corneal thickness, a 2-D parameter, in presenting biomechanical properties of cornea. It is presently acknowledged that IOP can have imperative impacts on most corneal biomechanical measurements obtained from the ORA, as specified in past research. Hence, it is conceivable that this IOP variation may have added to the noted variations in the ORA measurements. CH had a low correlation with IOP while a strong positive relationship was found between CRF and IOP (Zheng et al. 2016). In any case, the findings presented in some studies were not quite the same. These variations might be brought on by differences in techniques of measuring pressure, experimental species and the kind of mount utilised as a part of the trial set up. For example, the present review specifically measured IOP using a pressure transducer while other studies used transcorneal pressure.

The values for CH and CRF were almost consistent in other studies. CCT had a positive correlation with CH. From a broader perspective, the thickness of the cornea can be a vital factor in evaluating corneal biomechanical properties. In the ordinary human corneal stroma, any adjustment of the standard orthogonal structure of the fibrils in keratoconus might be identified with the biomechanical unsteadiness of the tissue (Ostadimoghaddam et al. 2012).

It was also imperative to recognise the differences between normal eyes and eyes with existing conditions. For instance, (Zheng et al. 2016) showed that the measurements of CH and CRF in left eyes were less than values noted in right eyes, but Et was higher in the left eyes when contrasted with right eyes. Intraocular biomechanical variations extended with the increase in IOP, an observation that could be associated with corneal oedema.

With an IOP of 40 mmHg and a temperature around 15 °C, the corneal imbibition pressure may lessen and draw water into the corneal stroma (Zheng et al. 2016). The subsequent increment in water volume can change corneal biomechanical properties without clear morphological impacts. Given that the “border pressure” instigating this outcome is marginally unique for every cornea, the impact created by the expanding IOP can change for corneas and incite increased variation between eyes at high levels of pressure. Additionally, Medeiros et al. (2011) also observed a significant strong correlation between the CCT and PCT. Appropriately, it might be inferred that the thinning or thickening of the cornea (with or without keratoconus) is a normal occurrence and ought not to be restricted to a specific area (for instance the central segment of the cornea) (Sedigh & Shenasi 2011). Biomechanical effects may also be relevant in determining changes in the curvature (Medeiros et al. 2011). It was also established that Pentacam Scheimpflug Imaging was exceptionally repeatable and reproducible pachymetry and, thus, provided reliable measures relative to other tools.

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