Pressure Effect in the Eye

Pressure effect in the eye

Giving pressure to the eye might give phosphene. When one evokes pressure by indenting the eyeball, two mechanical effects are produced: the eyeball is deformed and simultaneously the intraocular pressure (IOP) is raised considerably, and reducing the retinal perfusion pressure to values near to zero [9]. By perfusion means the flow of a fluid or the pouring of a fluid [10]. The low pressure of the perfusion in the retina causes something which is called retinal ischemia which means that the retina suffers insufficient of blood supply [10]. Hence, it is either because of the mechanical stretch and compression of the retina or the retinal ischemia that causes pressure phosphene [9].

Elevating pressure in the eye might lead to retinal ganglion cell death [1]. For normal eye, the normal value of intraocular pressure is between 10mmHg to 20 mmHg [2], or 15 mmHg [8]. Therefore, the permissible pressure that can be introduced into the eye should be less than 20mmHg. However, according to the experiment conducted to the cat’s eye as described in the paper [9], the IOP might reach up to 150 mmHg and giving some response to the ganglion cells. By introducing deformation to the eye for relatively long duration may leads to retinal ischemia. The responses of the ganglion cells to the light compared with the response to the pressure from the experiment conducted in paper [9] is shown in Figure 1.

In the experiment, when the eyeball deformation was maintained for about 10 sec, the on-center neuron usually lasted as long as the deformation was present [9]. While when the indentation was about 20 sec, the activity decreased in most of the on-center neuron about 12-16 sec after the onset of deformation. Ischemic effect was probably responsible for this decrease [9]. When applying a sudden increase of IOP, the on-center ganglion cells response were activated with some delay while the off-center response reduced their activity.

Introducing indentation to the eye gives 3 mechanical effects [9]:

1. Increase in the inner and outer surface of the eyeball causing a tangential stretch of the retina.2. Increase in IOP up to about 150mmHg 3. Increase outflow of aqueous humour through the Schlemm canal

Figure 1. PST (Poststimulus Time Histogram) of retinal ganglion cell responses to diffuse light stimulation (left column) and eyeball deformation in the dark (middle and right columns) [9].

According to [5], the increment of intraocular pressure is the main causes of neuronal damage in human glaucoma. Long term pressure elevation leads to excavation of the disk that might be caused by direct mechanical alteration in the nerve fibers or the local blood supply at the optic disk. While short term pressure elevation causes functional impairment mainly by reduction in the oxygen supply to the retina. However, there is some certain duration at which the pressure might not causes bad effect as long as the pressure which interrupts the blood supply, does not last for more than 100 min or residual blood flow to the retina is maintained at a perfusion pressure of about 20 mmHg.

Perfusion pressure for the eye is defined as the difference between the arterial BP (blood pressure) and the intraocular pressure (IOP) which is considered a substitute for the venous pressure [6]. People with

low perfusion pressure have more chance to have glaucoma [6]. The lower the IOP, the slower the disease (glaucoma) progresses [7].

According to [7], the higher the IOP also contributes to the higher fluctuation of IOP. And also from the same paper, there is an indication that IOP variation is perhaps the most important IOP related risk factor for glaucoma progression.

Paper: Ultrashort laser pulse retinal damage mechanism and their impact on thresholds [4]

For laser pulses between several picoseconds and 10 ms,the threshold retinal damage is caused by micro bubble formation around melanosomes in the retinal pigment epithelium (RPE). Below 1ns, both stress confinement in melanosomes and self-focusing reduce the threshold for damage as measured in corneal radiant exposure, although the mechanism for damage is the same. Below several picoseconds, laser-induced breakdown produces intra-retinal damage, sparing the RPE at threshold levels.

In the range of nanosecond pulse, lesions in the retina caused by a mechanism other than thermal heating which is causing photocoagulation of the retinal layers. This mechanism is called microcavitation. It occurs when the pulse is reduced below 5-10 microsecond.

For ultra short pulsed laser, the pressure propagation can be neglected since it doesn’t have time to propagate away from the particle [4]. This non-propagating pressure creates a stress confinement which means an increase of the internal pressure produced in a particle by laser-induced thermal expansion. Stress confinement is produced when the laser pulsed duration is less than the stress relaxation time [4]. The stress relaxation time for 1–2 mm melanosomes is of the order of 300ps, and for the 30nm melanin granules it is approximately 10ps. This would indicate that the stress confinement would increase as the pulse duration is reduced from nano to pico.

Laser Energy Threshold

Paper:Threshold for retinal injury from multiple near infrared ultrashort laser pulses [11]

In this paper, the Minimum Visible Lesion (MVL) in the paramacula of the primate retina is determined by using an 800nm laser wavelength with 1000 pulses per sec at 130fs pulse duration. The exposure were at 1 hr and 24 hr for 1, 10, 100, 1000, and 10000 pulses. The MVL-ED50 at the threshold decreased from 0.55 microJoule for a single pulse to 0.15 microJoule/pulse for 10 pulses and then only to 0.11 microJoule/pulse for 10,000pulses.

Thermal Effect

Laser-tissue interaction is mediated by a thermal or thermo-mechanical process depending on operational parameters of the laser, in which the key parameter is the wavelength of the laser [3]. Furthermore, the wavelength determines the penetration depth and the light distribution in the tissue which is dependent upon optical properties such as refractive index, absorption coefficient, scattering coefficient, and anisotrophy factor of tissue.

Paper: Biophysical Mechanism of Transient Optical Stimulation of Peripheral Nerve [16]

This paper describes the mechanism of pulsed laser interaction with tissue.

Experimental setup:

Four kinds of laser used: Holmium:yttrium alumunium garnet (Ho:YAG) laser at 2.12 micrometer with pulsed width 350 microsecond, alexandrite laser at 750nm with 350 microsecond pulsed width, pulsed diode optical nerve stimulator at wavelength of 1.87 micrometer with tuneable pulsed width (1-10ms), and Free Electron Laser (FEL) at tuneable wavelength (2-10 micrometer) with 5 microsecond pulsed width.

Target: rat sciatic nerve

The interaction of laser with tissue will lead to photobiological effects which can be divided into 3 potentially mechanic categories:

1. Photochemical2. Photothermal3. Photomechanical

Photochemical

Photochemical effects depend on the absorption of light to act as a reagent in a stoichiometric reaction catalyzed by a specific photosintesizer. Photochemical phenomenon is not responsible for optical stimulation since the infrared photon energy is too low (<0.1 eV) for driving direct photochemistry and the applied irradiance is most certainly insufficient for any multiphoton effect.

Photothermal

Photothermal effects result from the transformation of absorbed light energy into heat. This energy transformation may lead to hypethermia (the rise of body temperature when the body produces or absorbs more heat than it can dissipate,-wikipedia), coagulation, or ablation of the tissue.

Photothermal effects are nonspecific and are mediated by absorption of optical energy and governed by principles of heat conduction.

Photomechanical

Photomechanical effects are secondary to rapid heating with short laser pulse (less than 1 microsecond) that produces mechanical forces such as explosive events and laser induced pressure waves. Photomechanical effects can be divided again into 3 distinct categories: thermoelastic expansion, ablative recoil, and expansion secondary to temperature increase or phase change.

The Effect of electric field

Laser beam is an electromagnetic wave, and therefore it would create an electric field on the tissue surface. Furthermore, it would create a current. For surface stimulation, a current of 0.95 +- 0.58 A/cm2 is needed. During the experiment, the alexandrite laser is used for investigating whether electric field is able to create a stimulation or not. And the result suggests that electric field from the laser does not stimulate the tissue.

Paper: Microphotocoagulation: Selective effects of repetitive short laser pulses [12]

Material:

Laser: cw argon-ion laser beam (514nm) with external acoustic-optical modulator for chopping.

Object: retina of chinchilla rabbit were exposed to trains of short laser pulses or to single long exposures light impinges on the RPE). For short pulses, the duration of the pulses was always 5 microsec. The pulse energy varied between 2,3,6, and 10 microjoule. Trains of 1, 25, 100, and 500 pulses were used. Repetition rate was 500 Hz. While for long exposures, the duration was 100 ms, 500ms and 1 sec with powers between 5 and 50mW.

The energy of laser light can be absorbed within the tissue by uniformly distributed chromophores and water or by discrete pigment granules. Thermal effects will contribute if the exposure times of the laser light are more than 1 ms (Theoritically, widespread thermal damage occurs if the exposure duration is more than the relaxation time of the target of the structure. Relaxation time is defined as the time needed for the tissue to reach the temperature at a distance r from the source has its maximum temperature). If the exposure times is much more than the relaxation time (long duration pulses), the heat transfer will occurs and the adjacent tissue will be heated relatively uniformly, causing nonspecific necrosis. During and after exposure, heat dissipates out of the absorbing volume and then causing undesired bad effects. For example, in clinical retinal photocoagulation, with the exposure times of several hundred milliseconds, the nonabsorbing neural retina is thermally damaged because it is directly adjacent to the absorbing retinal pigment epithelium (RPE).

In another paper [13], relaxation time is defined as the time required for the peak temperature rise in a heated region of tissue to decrease to 37% of the total rise. A common belief is that if the pulse duration

of the laser is less than the relaxation time, the thermal damage will be reduced. By applying a repetition of laser pulse, the temperature of the illuminated tissue might increase more since there would be temperature superposition effects. And several theoretical and experimental studies show that even the time between pulse is several magnitude of relaxation time, the temperature superposition effect might still occurs [13].

If the pulses duration of the laser source is less than the exposure time, spatial confinement will be achieved because the rise of the temperature outside the target structure is too small to cause any significant collateral damage.

In order to calculate the temperature response due to laser exposure, several thermal models have been proposed. The thermal models are treated as a uniformly absorbing layer or the spacing of the granules is assumed to be wide enough so that the temperature at the boundary of one granule is independent of heat flow from the neighboring granules.

The relaxation time for a single granule is about 100ns. While for melanin-loaded 4micrometer-thick homogeneous apical part of the RPE, the relaxation time is about 5 microsec. The spatial temperature profile of the RPE and the neural retina si shown in the following figure:

Figure 2. Spatial temperature profile of the RPE and the neural retina in the laser beam axis after irradiation with a 5,5 microjoule short pulse (5microsecond) . Dashed line: temperature profile after a long pulse (1 sec) at threshold power (11 mW). The arrowhead indicates the reference point.

While the temperature profile of the neural retina at a distance of 5 micrometer away from the RPE is shown in the following figure:

Figure 3. The temperature of neural retina at a distance of 5 micrometer away from RPE as a function of time. The laser source is 514nm wavelength, 5 microsec pulsed, 5.5microjoule, 500 Hz.

In this experiment conducted in the paper, there is no blanching or bleeding observed .

Each laser pulse leads to a short temperature increase in the RPE. Before the next laser pulsed is delivered, heat dissipates and the RPE has cooled to about 10% of the peak temperature. The increment of the temperature after the next pulsed has arrived is < 0.9 C/microjoule of pulse energy inside the adjacent structure. And for extreme case where the number pulses is 500 pulses, the peak temperature increase is less than 7C.

Paper: Determination of threshold average temperature for cell death in an in vitro retinal model using thermography [14]

This paper describes the threshold temperature for a cell death.

Method:

Laser source: argon laser 514nm for duration 0.1s and 0.25s

Object: in vitro retinal cells. The laser illuminates the RPE.

Results: The temperature rise threshold and the actual average temperature for a cell to death is shown in the following figure:

Figure 4. The rise temperature and the actual temperature of a cell to death [14].

The actual temperature is calculated by adding the ambient temperature (35C) to the rise temperature.

Paper: Non-linear absorption studies of melanin [15]

This paper describes the non-linear absorption of melanin in which the characteristics are described by estimating the transmittance of it related with irradiance, pulse, and linear absorption coefficient. The characteristic of the nonlinearity is also described as a function of z position since the technique which is used for evaluating it is by using z scan method.

Method: Using Nd:YAG laser with 100ps-5ns pulse at wavelength 1064nm and 532nm. Pulse repetition is 10 Hz. Input pulse energies varied from 10 microjoule to 100 microjoule. The laser source is transmitted to the melanin sample, 25 mg synthetic melanin was suspended in 10ml 0.17 M Tris-HCL, pH 7.2 buffer.

Figure . Experimental Setup

Non linear optical properties of the melanin will affect the absorption coefficient of the melanosomes in the retina, therefore it will then affects the energy deposition of the laser source in the tissue to thermal or photochemical damage mechanism for cell death.

In short pulses studies, the melanin absorption creates an explosive source of photochemical energy, from which the shock waves can emanate and cause structural damage to the surrounding cell.

The model for the nonlinearity of the absorption coefficient and the transmittance are described by the following equation:

Where α1 is the linear coefficient which is straightforward derived from measurement of transmittance of the sample at low irradiance. While β is determined from an examination of the z-scan at higher irradiance.

Figure . Schematic of retina [15]

Various value of linear absorption coefficient of melanin:

Table 1. Published values of the linear absorption coefficient of melanin [15]

Table 2. Measured values for linear absorption coefficient and non-linear coefficient.

The results are described by the following graphs:

Figure . The melanosome transmittance as a function of linear absorption coefficient.

Figure . The melanosome transmittance as a function of pulse duration

Figure . The melanosome transmittance a function of irradiance.

Table 3. Non-linear changes in transmittance at MVL threshold.

Conclusion : the shorter the pulse of the laser, the nonlinearity is getting significant.

The absorption of light by material results in an exponential decay of the radiant exposure (energy per unit area at any depth) as a function of depth, predicted by Beer’s Law. Laser energy absorbed by tissue is typically converted to thermal energy and the amount of energy absorbed per unit volume of tissue can be directly related to the temperature rise in the tissue. The temperature rise is dependent on the density (kg/m3), and the specific heat (J/(kg K)) of the irradiated material.

The amount of the absorbed energy density Q is defined as the number of photon absorbed by the material per unit volume (J/m3). This energy density is the product of radiant exposure at some point and the probability of the absorption at that point in the tissue [3]:

Once the absorbed energy is known, the laser induced temperature rise is given by

Where ρ = density (kg/m3)

C = specific heat (J/(kg K)) of the irradiated material

References

[1]. Rosana Gerometta, et.al, “An Hypothesis on Pressure Transmission from Anterior Chamber to Optic Nerve”, Elsevier journal, 2011

[2]. Wikipedia : Intraocular Pressure, accessed on 28 May 2012.

[3]. Jonathon Wells, et al, “Pulsed Laser Pulsed Versus Electrical Energy for Peripheral Nerve Stimulation”, Elsevier Journal, 2006.

[4]. Benjamin A. Rockwell, et al, “Ultrashort Laser Pulse Retinal Damage Mechanism and Their Impact on Thresholds”, Elsevier Journal, 2010.

[5]. Franz Grehn, et.al, “Effects of Short term intraocular pressure increase on cat retinal ganglion cell activity”, Elsevier journal, 1984.

[6]. M. Christine Leske, “Ocular perfusion pressure and Glaucoma : clinical trial and epidemiologic findings”, Current Opinion in Ophthalmology journal, 2009

[7]. Kuldev Singh, et.al, “Intraocular pressure fluctuations: how much do they matter ?”, Current Opinion in Opthalmology Journal, 2009.

[8]. Ashih Agar, et.al, “Retinal ganglion cell apoptosis induced by hydrostatic pressure”, Elsevier Journal 2006.

[9]. O. J. Grusser, et.al, “Responses of retinal ganglion cells to eyeball deformation: a neurophysiological basis for pressure phosphenes”, Pergamon Press, 1989.

[10]. https://sites.google.com/site/crvoquickstart/retinal-ischemia

Accessed on 7 June 2012.

[11]. Clarence P. Cain, et al, “Threshold for retinal injury from multiple near infrared ultrashort laser pulses”, Health Physics Society 2002

[12]. Johann Roider, et.al, “Microphotocoagulation: Selective effects of repetitive short laser pulses”, Proc. Natl. Acad. Sci. USA, Medical Sciences, 1993

[13]. Bernard Choi, “Analysis of Thermal Relaxation during laser irradiation of tissue”, Lasers in Surgery and Medicine, 2001

[14]. Michael L. Dentao, et.al, “Determination of threshold average temperature for cell death in an in vitro retinal model using thermography”, Proc. SPIE Journal, 2009

[15]. David J. Stolarski, et.al, “Non-linear absorption studies of melanin”, SPIE Journal, 2002

[16]. Jonathon Wells, et.al, “Biophysical Mechanism of Transient Optical Stimulation of Peripheral Nerve”, Biophysical Journal, October 2007