Diode laser technology for ophthalmology

Monocrom offers diode laser technology for ophthalmology, in standard and sophisticated retinal photocoagulation methods based on diode-pumped solid-state lasers. The company’s solutions provide a broad power range, pulse and fluence modulation along with a compact, versatile and rugged design.

LQ 527 Solid-State Laser

Image Credit: Monocrom

Monocrom’s ophthalmic lasers are used for:

  • Diabetic macular edema (DME)
  • Glaucoma treatment
  • RPE stimulation
  • Age-related macular degeneration (AMD)
Diode laser technology for ophthalmology

Image Credit: Monocrom

Monocrom provides laser technology for selective retinal therapy (SRT) for highly accurate laser treatments based on a 527-nm laser with a repetition rate of up to 200 Hz and a pulse rate of 1.7 µs.

The laser technology selectively impairs the retinal pigment epithelium (RPE) without causing a major impact on the neural retina, the choroid and the photoreceptors. The laser radiation activates the migration and proliferation of RPE cells to enhance the metabolism at the affected retinal sites.

MP532 Multipath Resonator

Image Credit: Monocrom

Another cost-effective laser technology employed in ophthalmology are multipath resonators that are used to perform photodynamic therapy. These resonators can be easily implemented and are perfect for treating AMD and DME.

An eye on ophthalmic lasers

The World Health Organization (WHO) has stated that the leading cause of visual impairment is associated with refractive errors, such as hyperopia, myopia, presbyopia and astigmatism, revealing a global incidence of around 285 million people, so far.

If more of a focus is given to causes that lead to blindness (approximately 40 million people worldwide), then cataracts are at the top of the list with over 50% of the cases, followed by glaucoma, AMD, corneal opacities, childhood blindness, uncorrected vision errors, trachoma and diabetic retinopathy.5

Wherever a therapy or treatment is relevant, laser-assisted or laser-based methods represent a part of it in a majority of cases. However, medical laser technology is generally associated with costly and complex equipment, making it cost-prohibitive for a majority of population sectors. The actual reality is that the incidence of blindness is far more widespread in developing nations than compared to high-income areas, either in absolute or percentage numbers.6

Therefore, affordability, long lifetime and energy efficiency become the key drivers for both present day and future research and development strategies with respect to ophthalmological lasers.

Laser-tissue interaction

The interaction of laser with eye tissue (and indeed all biological tissues) can be categorized into photoionizing, photochemical and photothermal (refer to Figure 1).

Laser-tissue interaction is characterized by pulse duration and power density, according to 7.

Figure 1. Laser-tissue interaction is characterized by pulse duration and power density, according to 7. Image Credit: Monocrom

When photothermal interaction occurs, the absorbed radiation causes a sudden rise of temperature, leading to either protein denaturalization or photocoagulation, or even causing the vaporization of the water surrounding or retained inside the affected cells (photovaporization). These processes allow for accurate and localized cauterization.

Pulse duration. however, is in the order of the time required for the heat to dissipate toward neighboring tissues. Photoablation, within the photochemical category, suggests breaking the polymeric tissue into tinier volatile molecules. On the other hand, photoradiation includes the earlier administration of a photosensitizer, which is preferentially bound to a tissue of interest.

Once the agent is irradiated with the excitation wavelength of the photosensitizer, it gets stimulated and subsequently activates specific biochemical reactions that destroy cells (this process is also called photodynamic therapy). In the end, photodisruption or photoionization involves applying a pulse that is sufficiently strong to ionize the irradiated zone.

An acoustic shock wave is produced in the process which literally breaks down the tissue. The pulse time is so brief that the volume affected by heat is nearly coincident with the volume of the beam around the focus point.

Lasers in ophthalmology: Still the ultimate surgery tool

Throughout the world, laser-assisted refractive surgery performed to correct vision, such as astigmatism, hyperopia and myopia, is perhaps the most well-known method today with respect to the use of lasers in ophthalmology, at least in developed nations. As a matter of fact, over one million interventions are performed throughout the world every year, 4 and these interventions only account for the variant called laser-assisted in-situ keratomileusis (LASIK).

ArF excimer laser, the most prevalent laser used in this method, produces nanosecond pulses at 193 nm. Femtosecond-pulsed lasers (emitting in the 10XX nm region) have witnessed significant growth in the last 20 years, and they can indeed be regarded as state-of-the-art lasers for refractive surgery.

While the main objective in contemporary cataracts treatment involves the replacement of the human lens by an artificial one, femtosecond lasers can contribute immensely to the crucial steps of the process. This is the case when fragmentation of the impaired human lens occurs, or when corneal incisions need to be carried out for the replacement of the lens.

However, if the origins of laser in ophthalmology is retraced, retinal photocoagulation was the first laser-assisted therapy to be clinically tested and validated (in the early 1970s), and this was fueled by the discovery of the argon-ion laser in 1964. This continuous wave (CW) laser has two powerful emission lines at 488 and 514 nm, both demonstrating an exceptional absorption by hemoglobin.

Laser photocoagulation: A gold standard in ophthalmology

In the field of ophthalmology, laser photocoagulation is essentially a photothermal-based method whose main goal is to finely cauterize the irregular leakage of blood vessels in the retina (refer to Figure 2), which are associated with many eye disorders, such as DME and diabetic retinopathy.7

Eye structure.
Eye structure.

Figure 2. Eye structure. Image Credit: Monocrom

To do so, yellow or green lasers can be selected based on the typology of the photocoagulation treatment. Ultimately, however, from a light-tissue interaction standpoint, it is a question of the chromophore confined in the tissue being treated (refer to Figure 3). The blue wavelengths could be noted here.8

Absorption of hemoglobin and eye melanin depending on photon wavelength. 527 nm, 532 nm, and 577 nm are laser emission wavelengths corresponding to typical commercial lasers employed in retinal photocoagulation.

Figure 3. Absorption of hemoglobin and eye melanin depending on photon wavelength. 527 nm, 532 nm, and 577 nm are laser emission wavelengths corresponding to typical commercial lasers employed in retinal photocoagulation. Image Credit: Monocrom

While the entire therapeutic process is yet to be fully interpreted, the photocoagulated tissue plays a key role in slowing down or even halting the production of excess new blood vessels, also known as neovascularization, which consequently inhibits the further detachment of the retina and the progressive loss of vision.9 To date, 532 nm is the most extensively used wavelength in panretinal photocoagulation (PRP) for several reasons.

First and foremost, this wavelength is better absorbed by melanin than yellow lasers, and the hemoglobin absorption is still acceptable. Light scattering is also not a major problem. However, it does correspond to the SHG of Nd:YAG emission (when 1064 nm is the chosen gain band), one of the most familiar solid-state lasers to date. This means, it is a widespread and well-established technology.

In this context, Monocrom’s multipath solid-state laser, MP-532, is an example of a reliable, compact, and low-cost solution for PRP, which is beyond conventional Nd:YAG lasers in many aspects. The unique resonator design of the MP-532 solid-state laser combined with the use of Nd:GdVO4 as the active medium enables more than 5 W of peak power in pulsed operation (QCW) at 532 nm, with a pulse modulation ranging from 1 ms to continuous wave (CW).1

Nd:GdVO4 integrates a relatively larger pump absorption than Nd:YAG with similar thermal conductivity and emission cross-section. The Nd:GdVO4 thus represents the most optimal choice (even over Nd:YVO4) for high-power and compact laser heads, working either in QCW or CW. Stable and high power, high efficiency and low noise (<1% rms) are integrated into a compact, cost-effective, air-cooled laser head, thus making it ideal for incorporating into PRP equipment. In this case, 3 W is the highest nominal power in CW operation.1

Selective retinal therapy: A new era of ultra-precise laser treatments

In spite of the well-established and broadly extended method of PRP, a new technique was recommended in the 1990s and this was developed in the last 10 years. The concept was to preferentially damage dysfunctional tissues in the RPE, without altering the neighboring photoreceptors, neural retina and the choroid.

This latest approach was dubbed SRT. It was based on the fact that the RPE cells recovered after routine laser photocoagulation treatments, which highlighted the critical role of the RPE in the proliferation of retinal vascular diseases. Based on this concept, the destruction of neighboring tissues can be considered as an unnecessary side-effect of standard laser PRP.10

According to earlier theoretical analyses, SRT required a well-defined laser pulse in the μs range with pulse energy of around 1 mJ,11 and also a wavelength that is suitably absorbed by the melanin confined in the RPE tissue. As a matter of fact, the mechanism of laser-tissue interactions under these conditions could no longer be regarded as photocoagulation, but photovaporization instead.

Laser pulses that require μs and mJ together means peak power in the kW range. During the time of developing SRT, green diode lasers were only a research topic, and hence the direct diode solution was ruled out. Perhaps, it will continue to remain like this for the next 5 to 10 years.

Conversely, high peak power pulses in solid-state lasers need Q-switching; however, the pulse duration generally falls into the ns-range, mainly because of the length of the resonator, but is also affected by the gain of the active medium. Hence, alternative solutions were also investigated.

The demand for green wavelengths provided an advantage in this case. In lasers with active media emitting in the 1-μm region of the spectrum, the integration of an intra-cavity SHG crystal together with an active Q-switching element in the resonator enables the Q-pulses to be expanded from the ns to the μs range.

This method is based on a physical phenomenon known as “mode overcoupling.” When an SHG crystal is placed inside the resonator, the dynamics of optical gain and losses that take place during the formation of Q-pulses are modified. Consequently, the outcoming pulse can be expanded from a few ns to over 1 μs.11

Yet, the pulse shape is far from a nice symmetric and sharp peak. Instead, it causes an abrupt rise and this is followed by a slow exponential-like decay (refer to Figure 4). This poses a disadvantage for SRT because the distribution of power is not at all constant along the pulse. Hence, something more needs to be done to overcome this problem.

Stretched pulse shape from mode overcoupling (left). Ideal pulse shape combining mode overcoupling and AOM smart driving (right).

Figure 4. Stretched pulse shape from mode overcoupling (left). Ideal pulse shape combining mode overcoupling and AOM smart driving (right). Image Credit: Monocrom

For this reason, the Q-switching element should be used in a smart, customized manner. LQ-527, the diode-pumped solid-state laser head from Monocrom, integrates a compact U-shaped resonator with intracavity SHG crystal, with an acoustic-optical modulator (AOM) serving as the Q-switching element.

A specifically intelligent signal was developed to fuel the AOM, which is used during laser adjustment. The conversion efficiency of the intracavity SHG crystal is particularly tuned by adjusting its operating temperature as well as the relative angle between the laser beam and the optical axis, iteratively.

This results in the formation of a stretched laser pulse of 1.7 μs at 527 nm (refer to Figure 5). The highest energy for each pulse is 1 mJ and the instant power reveals the highest variation of 25%. The frequency of operation can also be as high as 200 Hz.

Stretched pulse shape by mode overcoupling and AOM smart driving. Central oscillogram corresponds to the optimized pulse, while left and right oscillograms correspond to small variations of the SHG crystal temperature, above and below, respectively.

Figure 5. Stretched pulse shape by mode overcoupling and AOM smart driving. Central oscillogram corresponds to the optimized pulse, while left and right oscillograms correspond to small variations of the SHG crystal temperature, above and below, respectively. Image Credit: Monocrom

Several clinical studies have already demonstrated the effectiveness of these laser parameters for SRT.12, 13, 14

Another major fact is that considering its accurate actuation across the RPE layer, the LQ-527 solid-state laser is an appropriate laser head to perform macula treatments. In this medical disorder, the damage to photoreceptors is a major problem in conventional photocoagulation techniques.

From the perspective of laser technicians, the inhibition of high peak power at the start of the pulse denotes an inherent benefit. By expanding the Q-pulse in time and flattening its power profile, all optical components are maintained much below their threshold of catastrophic optical damage (COD). This decisively plays a role in its reliability and, at the same time, reduces criticality in their components, which leads to competitive production costs.

A final remark

Within the medical sector, the weight of ophthalmologic lasers is quite incredible. Typically, this fact represents a valuable stimulation for competition in terms of innovation, cost-effectiveness and quality.

Safer and more effective laser-based treatments are simultaneously being designed , enriching the entire path from research to actual application. Undoubtedly, as far as medical lasers are concerned, it is the patient who matters, not the customer.

References

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  9. Stefánsson E., “The mechanism of retinal photocoagulation. How does the laser work?”, European Ophthalmic Review 2 (1), 76-79 (2009)
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  11. Roider J.et al., “Selective retina therapy (SRT) for clinically significant diabetic macular edema”, Graefe’s Archive for Clinical and Experimental Ophthalmology 248 (9), 1263–1272 (2010)
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