Wednesday, August 30, 2017

TONOMETERS






INTRAOCULAR PRESSURE (IOP):

Normal IOP may be defined as that pressure which does not lead to glaucomatous optic nerve head damage. IOP is determined by a balance between production and drainage of aqueous humor in the eye. Normally, the IOP ranges from 10-21 mmHg.

FACTORS EXERTING LONG-TERM INFLUENCE ON IOP
FACTORS EXERTING SHORT-TERM INFLUENCE ON IOP
1.Genetics:
1. Diurnal variation
2.Age
2. Postural variation
3.Sex
3. Exertional influences
4.Refractive error
4.Lid and eye movement
5.Race
5. Intraocular conditions

6. Systemic conditions

7. Environmental conditions

8. General anesthesia

9. Food and drugs

TONOMETERS:

Tonometers are used to measure IOP. They are of different types depending on the shape of deformation they produce. 

INDENTATION TONOMETERS: 

In indentation tonometry the shape of deformation is in the form of a truncated cone. However, the precise shape is variable and unpredictable. The tonometer also displaces a relatively large intraocular volume. As a result of these peculiar characteristics, conversion tables have been developed to calculate IOP. These tonometers are also affected by scleral rigidity. Thin scleras giving abnormally low and thick/rigid scleras giving abnormally high IOP values. An example is the Schiotz tonometer.
Schiotz tonometer

APPLANATION TONOMETERS:

In applanation tonometers the shape of deformation is simple flattening. Since the shape is constant, its relationship to IOP can be derived from mathematical calculations. Applanation tonometers are of 2 types: (1) Variable force: It measures the force required to applanate (flatten) a standard area of the corneal surface e.g. Goldmann Tonometer (GT). (2) Variable area: It measures the area of the cornea, which is flattened by a known force (weight), e.g. Maklakov Tonometer.

Goldmann Applanation Tonometer

The GT is regarded as a gold standard in IOP evaluation. Goldmann based his tonometer on the Imbert-Fick law, a modification of the Maklakov-Fick law. According to this law, the external force (W) against a sphere equals the pressure in the sphere (Pt) times the area flattened (applanated) by the external force (A).
W=Pt x A
However, the Imbert-Fick Law has been modified to account for the surface tension, the force to bend the cornea and inner area of flattening. 
The cornea is anesthetized and fluorescein is instilled. The tonometer head is slowly made to touch the central cornea until the mires (semicircles) are visible. Subsequently, the counter attached to the tonometer is turned till the inner parts of the mires are in contact with each other.

Sources of error in Goldmann tonometry:


1. Semicircles: Wider menisci cause falsely higher pressure estimates. Improper vertical alignment will also lead to a falsely high IOP estimate.
2. Corneal variables:
a.   Thickness: GAT works best at a central corneal thickness (CCT) of 525 ┬Ám. Thinner corneas are associated with falsely low IOPs and thicker with falsely high IOP.
b.   Curvature: Increased curvature associated with falsely high IOPs. An increase of 1 mmHg is seen with every 3Ds increase in corneal power.
c.    Astigmatism: IOP is underestimated for with-the-rule and overestimated for against-the-rule astigmatism. There is 1 mmHg of error for every 4D of astigmatism. To minimize this error rotate the biprism until the dividing line between the prisms is 450 to the major axis of the ellipse or an average of horizontal and vertical readings taken. An irregular cornea also distorts the mires.
3. Prolonged contact: Leads to corneal injury as well as a false lowering of IOP.
4. Calibration: Monthly calibrations of the instrument are important to avoid errors.
Disinfection: It is done by soaking the applanation tip for 5-15 minutes in diluted sodium hypochlorite (1:10 household bleach), 3% hydrogen peroxide or 70% isopropyl alcohol. The tip can also be wiped with alcohol, hydrogen peroxide, povidone-iodine, 1:1000 merthiolate or dry tissues. Ten minutes of continuous rinsing in running tap water removes HBV surface antigen.

REBOUND TONOMETER:

iCare

An example of the rebound tonometer is the iCare device (Helsinki, Finland). The iCare Pro can assess IOP with the patient lying down. A 1.8 mm diameter plastic ball on a stainless steel wire is held in place by an electromagnetic field in a handheld battery-powered device. When a button is pushed, a spring drives the wire and ball forward rapidly. When the ball hits the cornea, the ball and wire decelerate; the deceleration is more rapid if the IOP is high and slower if the IOP is low. The speed of deceleration is measured and is converted by the device into IOP. 
No anesthetic is necessary for this device. It shows good agreement with Goldmann and Tono-pen readings. However, IOP measurements obtained with this tonometer are influenced by CCT, with higher IOP readings with thicker corneas. This tonometer is also affected by other biomechanical properties of the cornea, including corneal hysteresis (CH) and corneal resistance factor (CRF). The disposable tips also increase the cost of the instrument. An advantage is the small size, so it can be used in children and those patients who have corneal abnormalities, including after corneal -grafts or –implants (Corneal inlays or rings).

PASCAL DYNAMIC CONTOUR TONOMETER:

Pascal tonometer

Dynamic contour tonometer (DCT) or Pascal tonometer (SMT Swiss Microtechnology AG, Port, Switzerland) has a 7-mm diameter concave-surface probe which adapts to the cornea’s contour and without altering its shape or curvature. An electronic pressure sensor embedded in the tonometer’s concave probe surface enables direct measurement of transcorneal pressure. Nearly 100 IOP readings are taken per second. In contrast to the Goldmann tonometer, measurements with the DCT are reported to be influenced less by corneal thickness, and perhaps corneal curvature and rigidity. Some measurement differences have been noted with the Goldmann Tonometer (mean overestimation 2.3 mmHg).  Therefore, the two tonometers may not be interchangeably used. However, the DCT can provide valuable information in persons whose corneal thickness is far from the mean or in patients who have undergone refractive surgery. DCT can also be used to measure the ocular pulse amplitude. The ocular pulse amplitude is defined as the difference between diastolic and systolic intraocular pressure. The ocular pulse is generated by the pulsatile ocular blood flow in the choroid. This forms a part of the concept of vascular theory of glaucoma.
The instrument has to be used in conjunction with a slit-lamp, has disposable tips which increase cost, requires prolonged tip contact and specialized training to use it.

ORA AND CORVIS TONOMETERS:

ORA and CORVIS tonometers not only measure the IOP, but also provide information on the biomechanical properties of the cornea and thus have the potential to correct IOP readings for these factors. Corneal biomechanical variables and the dynamic corneal behaviour can also be assessed independently. Studies have shown that low corneal hysteresis is more likely a risk factor for glaucoma, rather than CCT. Goldmann Tonometry is influenced by CCT, which affects reliability of the instrument.


Ocular Response Analyzer

Ocular Response Analyzer [ORA] (Reichert Inc., Depew, New York, USA) is an airpulse tonometer. It utilizes a dynamic bi-directional applanation process to measure biomechanical properties of the cornea and IOP. A precisely collimated air-pulse causes the cornea to move inwards, past  applanation, and into a slight concavity. Milliseconds after applanation, as the air pulse force decreases, the cornea begins to return to its normal configuration. In the process, it once again passes through an applanated state. An electro-optical system monitors the curature of the cornea throughout the deformation process, taking 400 data samples during the 20-millisecond measurement. 2 independent pressure values are derived from the inward and outward applanation events. A difference between the 2 gives the corneal hysteresis. 
Thus, the ORA introduces two new concepts relating to the deformability of the cornea: corneal hysteresis (CH) and corneal response factor (CRF). These reflect the viscoelastic properties of the cornea. CH reflects the capacity of the cornea to absorb and dissipate energy and forms the basis for the instrument’s correction of IOP. The result of this correction is known as “corneal compensated IOP” (IOPcc). This new pressure is apparently less affected by corneal properties than that provided by a conventional applanation tonometer. The CRF indicates the overall resistance exerted by the cornea and is related to central corneal thickness and IOP. Whilst there is promising published evidence, the role of CH and CRF in the diagnosis and management of patients with glaucoma is yet to be fully established. The disadvantages are: The machine is fixed to a table and requires frequent maintenance. However, it does provide reliable IOP measurements.

Corvis ST

The Corneal Visualization Scheimpflug Technology Tonometer [Corvis ST] (Oculus, Wetzlar, Germany) allows quantitative and visual assessment of the biochemical properties of the cornea. The instrument incorporates an air pulse tonometer and in-built pachymeter. The instrument incorporates an ultra high-speed Scheimpflug camera and records the anterior chamber at the moment of corneal deformation in real time. It measures variables related to corneal deformability such as the time, velocity and length of the first and second applanations, maximal concavity, and the deformation amplitude.  These biomechanical variables have to be assessed further to understand their role in the development and progression of glaucoma. 

TONO-PEN:

Tonopen

The tonopen XL is based on the Mackay-Marg indentation tonometer. It is a handheld instrument with a strain gauge that creates an electrical signal as the footplate flattens the cornea(microstrain gauge technology). It is portable, simple to use, can be used in both sitting and lying positions and also offers easy calibration and use, by providing a digital readout. The final IOP is calculated on the basis of 4 readings, providing the coefficient of variation, which must be less than 5% for accurate measurements. It has disposable latex covers; it can be used through contact lenses and can be used over irregular corneas due to the smaller diameter of the contact area (2.36 mm2 for tonopen, versus 7.35 mm2 for the GAT). While some studies found it to correspond to GAT measurements, others found it to unreliable over IOPs above 20mmHg.

NON-CONTACT TONOMETER (NCT):

Non Contact Tonometer

In this instrument a puff of room air is used to create a constant force which deforms the central cornea. A collimated light beam emerges from the machine and is detected by an optoelectronic system. The moment the central cornea is flattened, the greatest numbers of light rays are received by the detector, giving rise to the peak intensity of light. The point from an internal reference point to the point of maximum light detection is then converted into IOP.
The time interval for an average NCT to measure is 1-3 milliseconds (1/500th of a cardiac cycle). It is random to the phase of cardiac cycle. Thus the ocular pulse becomes a significant factor in the detection of IOP. In order to obviate that, 3 readings can be taken and an average calculated.

SENSIMED TRIGGERFISH:


Sensimed Triggerfish

The SENSIMED Triggerfish® (CLS, Sensimed AG, Lausanne, Switzerland) consists of a silicone contact lens with an embedded pressure sensor that enables continuous IOP monitoring. The sensor takes pressure measurements over 30 seconds every 5 minutes to provide 288 measurements after 24 h of lens wear. The soft disposable contact lens embedded with a miniaturised telemetric sensor detects the circumferential changes in the area of the corneo-scleral junction. A flexible adhesive antenna worn around the eye wirelessly receives from the contact lens the continuous acquired information and transmits it to a portable recorder via a thin, flexible cable. The portable recorder, worn by the patient, stores the acquired data during the monitoring session. At the end of the recording period, the data is transferred via Bluetooth from the recorder to the software previously installed on the practitioner’s computer.
The software enables specialists to manage and visualise the patient’s continuous IOP profile. The data provided by the SENSIMED Triggerfish® complements punctual tonometer measurements and offers a qualitative profiling of the patient’s IOP for up to 24 hours.

Friday, August 18, 2017

GANGLION CELL COMPLEX ANALYSIS



Retinal ganglion cells (RGCs) are large, complex cells. The RGCs begin in the inner plexiform layer (IPL), the layer formed by the dendrites of the RGCs. Here they synapse with the bipolar and amacrine cells of the middle retina. Subsequently, they extend from the inner retina and travel all the way to the lateral geniculate nucleus (LGN) in the midbrain. 

Their cell bodies (soma) make up the ganglion cell layer (GCL), while the axons emerging from the RGCs form the retinal nerve fiber layer (RNFL). The axons traverse the retina; converge at the scleral foramen forming the neuro-retinal rim (NRR) of the optic nerve head (ONH). Subsequently, they continue onto the optic chiasm and LGN. 


Glaucoma evaluation by macular imaging was first suggested by Zeimer. Since the RNFL is only composed of axons, assessing the RGC itself might be a more direct way to measure ocular damage due to glaucoma rather than measurement of the circumpapillary RNFL (cpRNFL).

On a cross-sectional OCT image, all the 3 segments of the ganglion cells (IPL, GCL & RNFL) are known as ganglion cell complex (GCC). 

Ganglion Cell Complex
Approximately 50% of the total RGCs in the retina synapse in the central 5 mm of the macula. Thus, all OCT machines perform GCC scans that are centered on the fovea to a diameter of between 6-9 mm.  Depending on the machine, the average GCC thickness is approximately 95-100 microns. 

Studies have shown that the receiver area under the curve (AUC) for GCC scans is about 0.92. This is better than the AUC for RNFL which is around 0.92. It is assumed that this is because in glaucoma the inner retinal layers are affected more compared to the outer retinal layers.

Cirrus

The Cirrus OCT (Zeiss) uses a "macular cube (512x128) acquisition protocol” which generates a cube through a 6 mm square grid of 128 B-scans, each consisting of 512 A-scans. Another 200x200 protocol acquires 200 A and B scans each. A built-in GCC analysis algorithm software detects and measures the thickness of macular GCC in a 6x6x2 mm elliptical annulus centered on the fovea. The annulus consists of an inner vertical diameter of 1 mm chosen to exclude parts of the fovea where the layers are very thin and difficult to detect accurately and an outer vertical diameter of 4 mm, chosen to coincide with the area at which the GCC again becomes thin and difficult to detect. 

The thickness values recorded are mean thickness, mean minimum thickness (thickness of the thinnest sector) and the topography of the macular region divided into 6 sectors, expressed in micrometers: superior, inferior, superior & inferior temporal and superior & inferior nasal. Each spoke represents the average number of pixels along that spoke. The data is compared with a normative database in the form of maps, graphs and tables in which the colors are the same as in the ONH protocol. GCC thickness in the normal range is represented by green backgrounds. The thinnest 5- and 1% of measurements are represented by yellow and red backgrounds respectively. The hypernormal (95th-100th percentiles) thicknesses are presented in white color. The thickness acquisition leads to development of "Thickness Maps". The results are then compared with normative data to form the "Deviation Maps". It is found that early glaucoma manifests changes in the mean minimum thickness in the inferior temporal sector.

  

Thickness acquisition map:  It shows the thickness of the GCL+IPL in the 6mm x 6mm cube, represented as an elliptical annulus centered about the fovea.

Deviation map: This shows a comparison of the results compared to a normative database. GCC thickness in the normal range is represented by green backgrounds. The thinnest 5- and 1% of measurements are represented by yellow and red superpixels on the gray scale photograph respectively. The hypernormal (95th-100th percentiles) thicknesses are presented in white color.
Thickness table: It shows average and minimum thicknesses within the elliptical annulus.
Sectoral thickness map: It is displayed in an elliptical manner divided into 6 sectors- 3 superior and 3 inferior. They are color coded similar to the RNFL thickness maps.
Horizontal and vertical B-scans: These are extracted from the macular cube; with the locales marked on the macular map.

RTVue
The RTVue (Optovue) measures the GCC by scanning 1 horizontal line and 15 vertical lines at 0.5 mm intervals, covering a 7 mm2 region, centered on the fovea. The machine acquires 14928 A-scans within 0.6 seconds. The results are then processed to provide thickness maps of the GCC, pattern-based parameters of Focal Loss Volume (FLV) and Global Loss Volume (GLV).

The GLV is found to correspond to the total deviation map and the FLV to the pattern deviation map seen on visual fields. A deviation map is calculated by comparing the thickness map to the normative databases. The machine also provides a "significance map" which illustrates the areas which have a statistically significant change from normal.



Spectralis
The Spectralis (Heidelberg) measures the entire retinal thickness rather than the RGC layer. The machine scans the central 200 area, using 61 lines (300x250 OCT volume scan) to measure the retina thickness. A color-code thickness map is produced using a 8x8 grid centered on the fovea. The grid is symmetrical to the fovea-to-disc axis of each eye. It also displays the asymmetry between the superior and inferior hemisphere of each eye (hemisphere asymmetry). The machine also provides a mean thickness map.

3D-OCT 2000
3D OCT 2000 (Topcon) measures the RNFL thickness, the RGC with the IPL (GCIP) and GCC. It uses raster scanning of a 7 mm2 area centered on the fovea with a scan density of 128 (horizontal) X 512 (vertical) scans. The boundaries of the anatomical layers are determined by the program software using a validated, automated segmentation algorithm.
The “macula inner retinal layers” (MIRL) analysis software analyzes a 6 mm x 6 mm region centered at the fovea. The software divides the macular square into a 6 x 6 grid containing 100 cells of 0.6 mm x 0.6 mm, to assess regional abnormalities in MIRL thickness. Average regional thickness of GCC, GCIP and RNFL in each cell is calculated and compared to the normative database of the device. 
Studies have found that the average GCC thickness for diagnosing glaucoma stages did not differ significantly among the 3 OCT machines.

In a study using the RTVue, the mean GCC was found to have significantly higher diagnostic power than the macular retinal thickness in discriminating between normal eyes and those with perimetric glaucoma.
A study of 3D OCT 2000 found that all GCC parameters decreased from normal to pre-perimetric glaucoma (PPG) and from PPG to early glaucoma. The values of GCIP and GCC parameters differed significantly among the 3 groups (p <0.001). However, the RNFL thickness of the macula between healthy eyes and those with PPG did not differ significantly (p <0.05).

According to Meshi, structural evaluation (OCT) might be a more sensitive measure of ocualr health in early stage glaucoma, whereas functional evaluation (perimetry) may be a more sensitive measure of glaucoma progression in moderate-to-advanced stages.

However, repeatability of the changes is important in evaluation of progression. Thinning of the macula can also be produced by aging, which needs to be excluded by other tests and clinical evaluation of the patient for glaucoma.

Studies have also found that patients showing only hemifield changes on VF (the other hemifield being normal), showed changes in the GCC thickness even in the normal hemifield. MIRL parameters are comparable to those of cpRNFL thickness in diagnosing glaucoma early. This is especially useful when cpRNFL measurements are not reliable, such as in eyes with small or large optic discs, in tilted discs or peripapillary atrophy.
A study by Iverson showed high specificity (91%) for GCC thickness parameters in normal eyes but only moderate specificity (77%) in glaucoma suspects. However, half of the GCC measurements classified as outside normal limits were not replicable on subsequent scans.

There are some limitations of GCC analysis. The OCT machines only scan the macular region thus, information regarding areas nasal to the optic disc are not acquired. Abnormal thickening of the inner retina, such as macular edema and retinal fibrosis may lead to erroneous GCC measurements. The findings of individual machines are also not comparable to each other.

OCT technology is evolving to provide better evidence of structural damage in glaucoma. It has been suggested that VF changes can be combined with GCC changes to develop an algorithm in order to better investigate the structural-functional aspects of glaucoma progression.