WO2020058549A1

WO2020058549A1 - Ophthalmic lens for spectral conversion of light and a method for manufacturing same

Info

Publication number: WO2020058549A1
Application number: PCT/ES2019/070611
Authority: WO
Inventors: Jesus Merayo Lloves; Álvaro FERNÁNDEZ-VEGA; Claudia NÚÑEZ ÁLVAREZ; Neville NAHESH OSBORNE; Amador MENÉNDEZ VELÁZQUEZ; Susana DEL OLMO AGUADO
Original assignee: Fundación Idonial; Instituto Oftalmológico Fernández Vega S.L; Fundación De Investigación Oftalmológica
Priority date: 2018-09-19
Filing date: 2019-09-18
Publication date: 2020-03-26
Also published as: ES2749195B2; ES2749195A1

Abstract

The invention relates to an ophthalmic lens for spectral conversion of light and to a method for manufacturing same. The lens for spectral conversion of light includes a glass sheet (4) and a polymeric structure, with an optically transparent support polymer, deposited on at least one face of the glass sheet (4). In said polymeric structures, there is a first luminescent species and a second luminescent species. The first luminescent species absorbs ultraviolet-blue radiation, transferring the energy to the second luminescent species, which emits radiation in the near red-infrared spectrum. This enables the radiation with wavelengths that are most harmful to the eye to be blocked and transforms them into radiation with wavelengths that are beneficial for the eye, while at the same time respecting the wavelengths which regulate the circadian rhythms and preserving an acceptable quality of vision. The biological results confirm the validity of the lens.

Description

OPHTHALMIC LENS FOR SPECTRAL LIGHT CONVERSION AND METHOD FOR MANUFACTURING IT

DESCRIPTION

Technical field of the invention

The present invention refers to an ophthalmic lens that acts as a spectral converter, blocking radiation with the wavelengths most harmful to the eye and transforming them into radiation with wavelengths beneficial to the eye, while respecting the wavelengths that They regulate circadian rhythms and preserve an acceptable quality of vision.

State of the Art

Light is an important component in the visual system. Different wavelengths of light interact with various eye structures. Under pathological conditions, light is an added risk factor that can increase cellular susceptibility.

Light, in its different wavelengths, is capable of interacting with a large number of chromophores present in the eyeball. Some eye pigments absorb specific wavelengths of light that help maintain cellular homeostasis, while others are negatively affected and induce oxidative stress.

The cornea is the main barrier at the eye level of ultraviolet (UV) radiation (absorbs 92% of UV-B and 60% of UV-A). UV radiation can produce changes in the cornea at the cellular level, reducing epithelial proliferation and the concentration of antioxidants, as well as the functionality of the Na + / k + ATPase pump, producing changes in corneal transparency, inflammation, and can lead to keratitis or other conditions. corneal. Other ocular structures such as aqueous humor and the lens also absorb a certain amount of UV radiation allowing only a small part to hit the retina. However, the absorption of UV radiation by aqueous humor produces an increase in the production of free radicals, which causes a reduction in glutathione levels, one of the main ocular antioxidant systems. The lens is affected in the same way by UV radiation with reduced levels of antioxidants and i generation of oxidative damage. In the posterior segment, there are studies in vitro and in vivo models of retinal neurodegenerations that have shown the harmful effects that light exposure (visible and / or short wavelength such as ultraviolet or blue) can have on suboptimal retinas .

Contrary to the harmful effect of short wavelengths of light (UV-blue spectrum), exposure to long-wavelength light (red-near-infrared spectrum) appears to have positive effects. Various studies have shown how exposure to light from the near-infrared red spectrum has beneficial effects in different medical areas. This process is called photobiomodulation and it has been observed to accelerate wound healing, reduce pain and have anti-inflammatory properties. Furthermore, it has also been noted that it enhances recovery from ischemic heart damage, reduces neuronal damage from strokes in humans, and other brain damage in pathological animal models.

At the cellular level, irradiation at low doses with light in the near red-IR spectrum can generate various biological effects such as cell proliferation, synthesis of collagen and procollagen, release of growth factors from cells, stimulation of macrophages and lymphocytes , and an increase in the production ratio of extracellular matrix. It also has neutralizing effects on reactive oxygen species and induces reduced expression of apoptotic proteins and overexpression of anti-apoptotic proteins, attenuating cell death.

There are filters incorporated into ophthalmic lenses that protect the eye. There are essentially two types of filters. Some are filters based on diffraction networks such as photonic crystals, which transmit certain wavelengths and reflect others (in this case they reflect blue so that they do not penetrate the eye). Other filters are purely absorptive filters, which absorb light of certain wavelengths (such as blue) and lose it in the form of heat.

In the last decades, different luminescent species (based on organic and some inorganic compounds) with interesting properties have been developed that have been used in disciplines such as photovoltaics or the LED industry. The high quantum yield (ratio of emitted photons to absorbed photons) of some of these species -especially organic molecules- have allowed advances and improvements in optical amplifiers, lasers, photodetectors and solar concentrators. In photovoltaic solar energy, spectral conversion systems are used in order to capture the widest possible band of the electromagnetic spectrum and convert it to radiation whose wavelengths coincide with the bandgap of the solar cell. However, in the field of ophthalmology the challenge is much more complex, since as it has been mentioned, only certain areas of the spectrum should be captured, allowing the maximum possible light transmittance for the rest of the areas, in order not to distort previously mentioned parameters such as visual quality and Cardiac rhtyms.

Brief description of the invention

As noted, conventional filters used in ophthalmic lenses absorb a large fraction of the bandwidth corresponding to blue light.

The invention proposes a filter that absorbs only specific bands of the spectrum in the UV-blue zone, achieving a minimum absorption around 476 nm so as not to alter the circadian rhythms or biological clocks (sensitive to this type of light) and maintaining certain significant levels. absorption up to 450 nm (the zone from 380 nm to 450 nm is the one that produces the most damage to the retina). By not absorbing the entire strip of blue light, it is also possible not to alter the visual quality too much. All that absorbed light, instead of being lost in the form of heat, is converted spectrally to the near-infrared red, specifically to that area between 600 and 750 nm that provides many therapeutic benefits to the eye.

The development of luminescent filters to achieve the required spectral conversion is proposed in this invention. They block light of certain wavelengths, but instead of losing it in the form of heat, they convert it spectrally to another color. In this case they absorb blue light (with associated negative effects) and convert it to red - near infrared, providing the eye with an extra amount of this type of light that has therapeutic benefits.

Ultimately, in accordance with the present invention, a lens with optimized spectral redistribution is achieved that allows protection of the eye (by blocking UV-blue light) as well as therapy thereof (by providing extra amount of therapeutic red-IR light) close) and does so without altering circadian rhythms (by minimizing absorption around 476 nm) or significantly altering visual quality (by absorbing only a blue stripe and emitting only in a certain region of red; the rest of emission is near infrared, invisible to the human eye, and does not alter visual perception).

The inventors have found a suitable combination of luminescent species to achieve this goal without adversely affecting other aspects (such as significant image distortion or high blur). The present invention proposes a solution in view of the identified needs without negative effects. A selective spectral conversion ophthalmic lens is proposed which induces beneficial results by converting harmful wavelengths (UV-blue spectrum) into beneficial wavelengths (red-IR near spectrum) as defined in claim 1. The lens promotes a protective effect and therapeutic in eye pathologies related to the accumulation of light damage and in others where mitochondrial dysfunctions are involved.

Another object of this invention is a method to obtain said light spectral conversion lens for application in ophthalmology as defined in claim 8. The invention proposes a system with a multilayer configuration. This system includes several luminescent layers, preferably three. Each layer contains a luminescent species. Two layers are located on the upper face of the lens and contain UV-blue absorbing species. As a luminescent species, Lumogen Blau can be used. Two top layers have been found to be preferable to absorb and block a greater fraction of the harmful UV-blue light. Subsequently, this radiation is emitted and absorbed by another luminescent layer, located at the bottom of the lens, and re-emitted in the form of nearby red-IR light. This bottom layer may contain the luminescent species Lumogen Red.

Alternatively, the invention proposes a monolayer embodiment. In this case, several luminescent species, such as Lumogen Blau and Lumogen Red, are incorporated in the same layer. Lumogen Blau type molecules capture UV-blue light and transfer the energy non-radiatively in an energy cascade to the terminal Lumogen Red type molecules that will be responsible for re-emitting the radiation in a very specific area of the spectrum in the red -Go close. This is what is known as Forster resonance energy transfer (FRET).

Both developed configurations (monolayer and multilayer) make it possible to block light with harmful wavelengths and to intensify and provide an extra amount of light with beneficial wavelengths, this amount of light being greater in the multilayer configuration. It has been taken into account that, despite the harmful effect of blue light, it exerts a certain influence on circadian rhythms or biological rhythms. Therefore, a compromise situation has been identified in the blue zone of the spectrum allowing only a partial absorption of this type of light. Both preferred embodiments are detailed below. Brief description of the figures

FIG. 1: Illustrative graph of the optical properties of a luminescent filter (multilayer configuration).

FIG. 2: Cell viability graph under different conditions.

FIG. 3: Images of cells in culture in different situations.

FIG. 4: Schematic representation of two embodiments of ophthalmic lens.

Detailed description of the invention

With reference to the previous figures and for a better understanding of the invention, several particular embodiments are described in detail without limitation.

In essence, the invention works as a spectral converter that captures light in the ultraviolet-blue zone converting it to the red-near infrared zone of the electromagnetic spectrum. This allows the transmission of a significant fraction of light in the visible area of the spectrum so as not to alter visual quality, as well as a high transmission in a region of blue (centered around 476 nm) so as not to alter circadian rhythms.

To achieve this behavior, the following strategy is proposed:

Use organic molecules as luminescent species, which are incorporated into a polymer matrix of high optical transparency and refractivity index close to 1.5, such as PMMA, polyurethane, silicones.

This composite system (polymer matrix - luminescent species) is deposited on glass in the form of thin sheets, acting as a luminescent filter that spectrally converts light.

Luminescent species with light absorption / emission spectrum in the blue-UV zone of the spectrum are selected for adequate spectral conversion. Preferably Lumogen Blau is used. In addition, other species with absorption / emission in the red-near infrared zone are chosen. Preferably Lumogen Red is used. By the synergistic combination of both species, the UV-blue is converted to the near IR-red. For this, two alternative embodiments of the system are proposed: a multilayer and a single layer.

FIG. 1 shows a graph of the optical properties of a luminescent filter (the one corresponding to the multilayer configuration). The dotted line corresponds to the absorption spectrum and the solid line to the emission or photoluminescence spectrum. It looks like in the spectral range from 350nm to 400nm it absorbs almost 90% of incident radiation (dotted line), radiation that is converted to near-infrared red (solid line). It can also be seen that there is only partial absorption in the blue, with a minimum around 476 nm.

FIG. 2 is a graph of cell viability in which it is verified how the spectral conversion increases the viability in cells exposed to UV light or to the toxic agent CCCP.

FIG. 3 shows images of cells in culture exposed to different treatments. The beneficial effect of spectral conversion that increases cell survival can be observed in those cells exposed to different toxins (either light or chemical agents)

In sum, it can be seen from in vitro studies how this conversion can protect against damage caused by exposure to UV-blue light. It is even capable of reducing cell death caused by other toxic agents such as Carbonyl cyanide m-chlorophenyl hydrazone (CCCP), a chemical inhibitor of oxidative phosphorylation in the mitochondria causing cell death.

In FIG. 4 there is a schematic representation of two types of ophthalmic lens embodiments with incorporated luminescent species that are responsible for effecting spectral conversion from UV-blue to red-IR close.

In FIG. 4a shows a system that consists of the following elements: a glass (4), two luminescent layers (layer 1 and layer 3) on the upper face of the glass and another luminescent layer (layer 2) on the lower face of the same. Layers 1 and 3 contain the Lumogen Blau species and are responsible for capturing UV-blue radiation. Luminescent layer 2 contains the species Lumogen Red, absorbs the radiation emitted by layers 1 and 3, and in turn re-emits it into the near-infrared red zone of the electromagnetic spectrum.

In FIG. 4b a system is shown consisting of the following elements: a glass sheet 4 and a luminescent layer 10 on the upper face of the glass sheet 4. Luminescent layer 10 contains the luminescent species Lumogen Blau and Lumogen Red. The species luminescent Lumogen Blau is responsible for absorbing the UV-blue and transfer the energy non-radiatively to the Lumogen Red species, which then re-emits the radiation in the near red-IR zone of the spectrum.

Next, a manufacturing example is explained in more detail for both monolayer and multilayer lens embodiments, using in both cases methyl polymethacrylate (PMMA) as the support matrix.

- PMMA is added to a toluene vial to obtain a concentration of 150 mg / ml of PMMA in toluene.

- The vials containing the solution are heated (to 70 ° C) and shaken to dissolve the PMMA.

- The luminescent species (Lumogen Blau and / or Lumogen Red) are then added to the PMMA / toluene solution.

In the monolayer configuration:

- Both species (Lumogen Blau and Lumogen Red) are added to the same PMMA / toluene solution.

- The corresponding amount of Lumogen Blau is added to obtain a concentration of 9 mg of Lumogen Blau per mi (equal to a weight content of 6%, taking PMMA as a reference) and the appropriate amount of Lumogen Red is also added to obtain a concentration of 6 mg per ml (equal to a weight content of 4%).

- We will refer to this formulation as PMMA Lumogen Blau 6% Lumogen Red 4%.

- Once all the components are well dissolved, the solution is filtered and deposited on glass using spin-coating techniques.

Other different formulations have been tried, such as PMMA Lumogen Blau 6% Lumogen Red 6% and PMMA Lumogen Blau 6% Lumogen Red 8%. In all cases, the luminescence of the luminescent layer deposited on the glass is not too high, probably due to the formation of certain aggregates, although it may be sufficient for certain applications.

In the multilayer configuration:

- The appropriate amount of Lumogen Blau is added to the PMMA / toluene solution to obtain a concentration of 9 mg per ml (equal to a weight content of 6%, again taking PMMA as a reference). - The appropriate amount of Lumogen Red is added, in a different solution of PMMA / toluene, to obtain a concentration of 6 mg per ml (equal to a content by weight of 4%).

- Once all the components are well dissolved, the solutions are filtered and centrifuged on a clean glass substrate.

The formulations of the different layers are: PMMA Lumogen Blau 6% (layer 1), PMMA Lumogen Blau 6% (layer 3) and PMMA Lumogen Red 4% (layer 2). Strong luminescence is observed.

It has been complex to achieve an absorption around 390 nm of almost 90%. A priori, it would seem logical that greater absorption can be achieved simply by incorporating more Lumogen Blau molecules in the layer (higher Lumogen Blau concentration), but if the concentration is increased too much, there comes a time when aggregates are formed and it is inhibited or destroyed fluorescence. The proposed techniques overcome this problem with a multilayer structure.

Therefore, in this configuration, the concentration of Lumogen Blau with respect to PMMA has only been increased up to 6% so that it does not form aggregates and maintain significant fluorescence, but the absorption is not then as great as desired. For this, another layer with the same characteristics has been deposited on it. Thus, between these two layers deposited on the upper face of the glass, an absorption of 90% is achieved without destroying the fluorescence. The layer with the Lumogen Red species is then deposited on the underside, the concentration of this species being 4%.

Although Lumogen species have been used for the exemplary embodiments, the present proposal is applicable to other luminescent species with similar optical properties as regards absorption and emission in the UV-blue and red-IR areas of the spectrum.

Using the techniques described, for the first time a lens has been manufactured that simultaneously has protective and therapeutic effects for the eye. It manages not to alter other fundamental biological functions such as circadian rhythms (or biological clocks) or significantly alter visual quality.

Claims

1. Ophthalmic lens for spectral conversion of light comprising:

- a glass sheet (4);

- a polymeric structure;

characterized in that the polymeric structure is an optically transparent support polymer deposited on at least one face of the glass sheet (4), where said structure comprises at least a first luminescent species and a second luminescent species, where the first luminescent species absorbs the ultraviolet-blue radiation spectrum and the second luminescent species absorb the near-infrared red-radiation spectrum.

2. Ophthalmic lens according to claim 1, where the support polymer structure is polymethylmethacrylate, PPMA, which comprises a main layer (10), where the first luminescent species is Lumogen Blau and the second luminescent species is Lumogen Red, both integrated in the same main layer (10).

3. Ophthalmic lens according to claim 1, wherein the support polymer structure is PPMA and comprises a first layer (1) comprising the first species and a second layer (2) the second species.

4. Ophthalmic lens according to claim 3, where the first layer (1) is located on the face located above the glass sheet (4) and the second layer (2) is located on the face located under the glass sheet (4).

5. Ophthalmic lens according to claim 4, wherein the PPMA structure comprises a third layer (3) that comprises the first species and that is located between the first layer (1) and the glass sheet (4).

6. Ophthalmic lens according to any one of claims 2 to 5, wherein the Lumogen Blau concentration is between 5% -7% and the Lumogen Red concentration is between 3% -5%.

7. Ophthalmic lens according to claim 6, where the Lumogen Blau concentration is 6% and the Lumogen Red concentration is 4%.

8. Method for manufacturing an ophthalmic lens according to any one of the preceding claims 1 to 7, characterized in that it comprises the following steps:

- generate a polymeric structure;

- depositing the polymeric structure on at least one of the faces of a glass sheet (4);

characterized in that the polymeric structure is an optically transparent support polymer comprising at least a first luminescent species and / or a second luminescent species, where the first luminescent species absorbs the ultraviolet-blue radiation spectrum and the second luminescent species absorbs the spectrum of near-infrared red radiation.

9. The method according to claim 8, wherein the first luminescent species is Lumogen Blau and the second luminescent species is Lumogen Red.

10. Method according to claim 9, wherein generating the polymeric structure of the luminescent species comprises:

- dissolve PMMA and toluene to obtain a solution with a concentration of 150 mg PMMA / my solution;

- add luminescent species Lumogen Blau to obtain a concentration of 9 mg / ml, and / or Lumogen Red to obtain a concentration of 6 mg / ml;

- deposit on a glass by spin-coating techniques.