Device for retinal therapy

Abstract

A device for diagnostic and therapeutic procedures in ophthalmology, configured to deliver a photothermal treatment as well as a photobiomodulation treatment tuned to specific chromophores. The device may include a confocal scanning ophthalmoscope and a spectrometric dosimetry channel and is equipped with several safety features including a continuous automatic scanning of the eye and the eyelids.

Description

Device for retinal therapyTechnical domain

[0001] The present invention concerns a device suitable for the treatment of ophthalmic conditions by irradiating a portion of the retina with visible and / or infrared radiation, as well as for gathering diagnostic information or performing research measurements in ophthalmology.Related art

[0002] It is known in the art to treat ophthalmic conditions by application of radiant energy to the retina, especially to combat age- related macular degeneration and other degenerative diseases of the eye. These therapies use pulsed lasers to deliver a high dose of radiation that may be close to the lethal dose for cells of the retinal pigmented epithelium to stimulate the regeneration of retinal tissues. These therapies have shown efficacy, but they operate dangerously close to the threshold where the neuroretina tissue is permanently damaged.

[0003] Semiconductor lasers emitting in the near infrared, with a wavelength of A=808 nm or close are often used as radiation sources in this application. It is believed that the mechanism of action of the radiation on the retinal tissue is essential thermal at these wavelengths, and that the irradiation provokes a localized hyperthermia in the retinal pigmented epithelium that causes cell stress or death, followed by inflammation and regeneration.

[0004] Age-related macular degeneration (AMD) is the principal cause of irreversible vision loss worldwide. AMD is a chronic degenerative disease affecting the macula. The macula is the retina's central portion characterized by the highest photoreceptor density, allowing for focused, colorful, and detailed human vision. AMD's early pathological stages areOCULOX-2-PCTidentified today by an abnormal accumulation of lipofuscin; lipidic biowaste products attributable to cellular activity proper of vision processes. The early AMD pathological stages are clinically defined as dry-AMD; in such case, neovascularization and retinal leakages are excluded.

[0005] The avascular (non-exudative) progression of AMD is relatively slow and can take more than 6 years. It progresses to the more severe geographic atrophy stages, which can be associated with significant visual impairment.

[0006] Neovascular, exudative, or wet-AMD, is the more aggressive pathological form, believed to be the consequence, the evolution of the poor or unsuccessful management of the dry-AMD stage. Within the cohort of prevalent patients diagnosed with AMD, wet-AMD accounts for just 10%. Inversely, 90% of AMD patients with mild and severe visual impairments have already converted to the late, more severe wet-AMD stages. Today, standard medical practice strongly supports treatment only for severe wet-AMD, whereas for dry-AMD, dietary supplement recommendations result in the only solid established options.

[0007] Preventive clinical measures aimed at delaying or preventing the onset and progression of diseases are becoming increasingly popular in many clinical disciplines. This proactive approach to healthcare is becoming firmly anchored especially for all those chronic degenerative pathologies such as AMD . Many innovative clinical approaches focus on strategies to tackle AMD management by proposing preventive solutions at very early pathological signs to stop progression and exclude conversion to the later, more aggressive exudative pathological stages .

[0008] The pathogenesis of AMD is still controversial, but the entire community is consensual on the complex and multifactorial characteristics of this pathology. The age-related reduced-impaired cellular metabolism of the retinal pigmented epithelium (RPE) layer is generally blamed for being among the main risk factors responsible for AMD onset .OCULOX-2-PCT

[0009] The RPE is a mono-cellular layer located at the border of two critical eye tissues: the choriocapillaris and the neural retina . The RPE cells, at this pivotal location, are among the main actors in maintaining the homeostasis of the entire chorioretinal complex by actively transporting nutrients from the choriocapillaris to the avascular neuro-retinal layers and evacuating metabolism-related waste products, e.g., elimination of the photobleached and exhausted photoreceptors outer segments , .

[0010] The accumulation of metabolic waste products within RPE and the adjacent tissue is attributed to the impediment and reduction of physiological diffusion required to ensure the delicate metabolic balance of this tissue complex .

[0011] The reduced-impaired RPE metabolic activity is accused of imposing a state of chronic low-grade tissue inflammation, which is recognized to be a significant risk factor for the development of dry-AMD and, more generally, the driving force leading to profound tissular changes, e.g., mesenchymal transition - wet-AMD.

[0012] Protocols focused on obtaining such tissue reactions are generally clinically identified as sub-threshold micropulse laser (SMPL) treatments. Those are reported to be effective in several retinal disorders, including proliferative diabetic retinopathy, diabetic macula oedema, macular oedema resulting from branch retinal vein occlusion, and central serous chorioretinopathy.

[0013] The photo-biological therapeutic effects promoted by the absorption of tissue endogenous chromophores (i.e., in the absence of inoculated photosensitizer, as is the case for photodynamic therapy) have interested ever since a considerable portion of the clinical community. Despite numerous studies, a clear clinical consensus on this specific lighttissue interaction mode has not been reached. Nevertheless, in some specific applications, the approach, today identified as photo biomodulation (PBM), has obtained unprecedented clinical results -.OCULOX-2-PCTAlthough it is expected to play a role in precision medicine, the photo- biological and photoelectrical mechanisms underlying PBM, as well as its complex effects on tissue, are yet to be fully understood. This therapeutic approach operates through various mechanisms, such as enhancing mitochondrial function in photoreceptors, mitigating inflammation, and optimizing the performance of supportive cells.Short disclosure of the invention

[0014] An aim of the present invention is the provision of a device that can treat ophthalmic conditions in ways that are not possible with the equipment of the state of the art.

[0015] According to the invention, these aims are attained by the object of the attached claims, and especially by a device for retinal therapy that includes a first emitting a photothermic treatment beam that has a wavelength and an intensity suitable for generating a condition of localised hyperthermia in the retinal tissue. The inventive device also provides emits a photobiomodulation treatment beam, capable of being selectively absorbed by predetermined target molecules or chemical substances of the retina. The device is completed by a control unit that controls that the intensities of the photothermic treatment beam and of the photobiomodulation beam follow a predetermined treatment plan in which the photothermic treatment and the photobiomodulation one are applied one after the other in a same medical procedure, following a program that specifies the intensity profile of radiation over time and / or the radiation dose delivered to specified areas of the retina.

[0016] The photobiomodulation beam exploit a photo-biological interaction with the tissue, in contrast with the photothermic beam whose action is essentially that of a localised heating. To this end, the photobiomodulation beam source has, preferably, a wavelength that is chosen in function of the absorption spectrum of the target molecules or substances. In embodiments, the photothermic beam and theOCULOX-2-PCTphotobiomodulation beam may be emitted by a common source but, in other variants, they may differ in wavelength and come from two separate sources, the wavelength associated with the photobiomodulation treatment may be shorter than that of the photothermic one. The photothermic beam may have a wavelength of A=808 nm or close, while the second treatment beam may have the same wavelength, or a wavelength in the visible range of the electromagnetic spectrum.

[0017] In contrast with the photothermic beam that must be rather intense to achieve the desired thermal effect, the photobiomodulation beam does not need to reach the same intensity. While the photothermic beam is applied only in the form of short pulses and is collimated on a localised spot on the retina, the second treatment beam is applied for longer periods — in relative terms — and does not require the rigorous collimation of the photothermic beam. The second beam may illuminate the whole surface of the retina or a rather large portion thereof.

[0018] The target molecules or chemical substances may be active biomolecules, enzymes or proteins, for example chromophores of clinical significance that are expected to be present in the retinal tissue, Cytochrome C Oxidase is a key enzyme implied in cell respiration, and the second beam could be tuned to match the absorption spectrum of one of the constituents of this substance, such as the centres CUA, CUB, the Heme a3 and so on.

[0019] The source emitting the photobiomodulation beam could be tuneable, whereby the device can be configured to excite selectively a group of substance chosen at will, or else the second source may have a fixed wavelength chosen to excite a substance especially. The former variant may be usefully employed in clinical or biological research, while the latter could be more suitable for standardised medical procedures and tests.OCULOX-2-PCT

[0020] The tuneability, where required, could be given by a group of narrowband sources, for example LEDs with different emission spectra and settable intensities. The light emitted by the individual source is combined optically and constitutes the second treatment beam. The control unit in this case would be configured to set the individual intensities of the sources to obtain the desired spectrum.

[0021] Preferably, this variant of the invention with a tuneable source uses a spectrometer to analyse in real time the spectrum of the photobiomodulation beam. The control unit is configured to read this spectrum and extract retroaction signals that correct the intensity of the light emitted by the LED. In this manner, the control unit attempt to achieve the desired spectrum, compensating any change in the LED characteristics, for example changes induced by thermal shift and aging of the sources.

[0022] In cases where the tuneability of the source is not required, the photobiomodulation source may be constituted by a simple LED or by a group of LEDS providing the required spectrum of emission.

[0023] Preferably, the device of the invention includes a spectrophotometric channel to perform real-time measurement of a reflection spectrum of selectable regions of the retina. This may include a third light source, preferably a broadband source, that illuminates a selected region of the retina and a spectrometer that collects the reflected radiation. By analysing the reflection spectra and its variation, information about the dose delivered by the photothermic treatment or the effect of the treatment with the second therapeutic beam can be ascertained.

[0024] The third light source may emit visible and near-infrared light, for example between A = 700 nm and A = 1400 nm, preferably no more than A = 1400 nm.OCULOX-2-PCT

[0025] Embodiments of the invention may be used to deliver therapies taking advantage of the interaction between light and biological tissues are well diffused in different medical disciplines. In ophthalmology, photothermal and photo-biological light-tissue interaction successfully address many eye disorders. However, protocols and practices still have mild success with chronic-degenerative retinal disorders. The invention addresses the early pathological stages of age-related macular degeneration (AMD) by combining and optimizing photo-thermal and photo-biological laser-based treatment modalities to maximize their inherent principle of action. The device, besides the innovative "laser-combination therapy", features a highly modular construction allowing to increase patient's and operator's comfort. The optical arrangements allow to position and monitor patient eye in an expedited and semi-automatic fashion without the need of Goldmann contact lens. The device's architecture focuses on delivering fully controlled, safe, repeatable, and rapid treatment sessions. The device enables the physician to control and monitor treatments through a realtime and high-resolution confocal scanning laser ophthalmoscopy (cSLO) by continuously visualizing patient's retina. The user experience is further enhanced thanks to the fixed pre-programmed treatment protocols inspired by the experiences accumulated with the clinically known subthreshold micro pulse laser (SMPL) and photo biomodulation (PBM) practices. The developed device offers a completely new treatment modality that has the potential to harmonize clinical results with unprecedent outcomes and therefore obtain the consensus of the clinical community. The invention is introduced, described, and characterized by providing specifications and details on the visualization and treatment modules.

[0026] The invention aims to address the early pathological stages of an AMD by combining and optimizing photo-thermal and photo-biological light-based treatment modalities to take full advantage of their inherent principle of action.

[0027] The photo-thermal therapeutic effects result from the transitory, non-damaging, chorioretinal hyperthermic wave. In our case, tissueOCULOX-2-PCThyperthermy is induced through the absorption of a near-infrared (NIR) beam projected on the targeted retina structures. The NIR light is absorbed by the melanosomes, densely concentrated within the RPE, and by the underlying choroidal structures. Within defined heat gradients and temperature values, the targeted tissues react by initiating cell signalling processes involving heat-shock protein production, thus starting cascade biochemical reactions in response to the induced thermal stresses.Short description of the drawings

[0028] Exemplar embodiments of the invention are disclosed in the description and illustrated by the drawings in which:Figure 1 illustrates schematically a device according to the invention.Figure 2 represents an optical arrangement of an embodiment of the invention.Examples of embodiments of the present invention

[0029] Figure 1 illustrates schematically a possible structure of the inventive device that includes an optical system, here represented only, to simplify, by a front objective 180, configured to illuminate the retina of an eye with a photothermal treatment beam 131, a photobiomodulation beam 132, a diagnostic beam 135, and process the backscattered radiation 135 resulting from the diagnostic beam. This embodiment comprises independent sources 121, 122, 123 for the photothermal, respectively photobiomodulation and diagnostic beam, and a spectrometer 125 to analyse the backscattered radiation. The control and analysis unit 140 uses the output of the spectrometer to determine a dose received by the retinal tissue under treatment and adapts the output levels of the photothermal and photobiomodulation sources accordingly.OCULOX-2-PCT

[0030] Figure 2 represents, schematically, the optical arrangement of an embodiment of the invention integrates the technologies to deliver controlled and repeatable light-based retina therapies. The system includes two main modules: the monitoring modules and the light treatment modules.A. Monitoring Modules

[0031] The monitoring and real-time fundus visualization modules enable the operator to pinpoint the treatment location within the fundus. The fundus visualization is coupled with a high-speed eye pupil monitoring system to ensure accurate alignment with the subject eye's optical axis. In addition to those two essential monitoring modules, a tailored fixation target allows to orient / drive the patient's gaze arbitrarily within the device's visualization field.1) Confocal scanning laser ophthalmoscope (cSLO)

[0032] A confocal scanning laser ophthalmoscopy (cSLO, 250 in figure 2) permits direct fundus visualization / monitoring, semi-automatic refractive error correction, and real-time positioning of the treatment field. The output of the cSLO module is a live fundus image (512x512 pixels on 16 bits) over a field of view of 46° (considering emmetropic patient). The NIR probing beam (850 nm) scans the retina through dedicated optics; the backscattered confocal retinal emission is redirected to a dedicated MultiPixel Photo Counter (Det).2) Fixation target

[0033] A fixation target (515 nm, 15pW at the device's exit pupil) facilitates positioning and maintaining the patient's gaze orientation during device alignment and therapeutic procedures. This fixation target is integrated into the cSLO optical system. Its driving architecture allowsOCULOX-2-PCTtoggling activation / emission at the cSLO pixel frequency. This synchronizes the activation time and guarantees an arbitrary but constant and stable fixation target position at each frame.3) Pupil monitoring system

[0034] The system integrates three CMOS monochrome cameras, two of which (Cam1 and Cam2) are represented in figure 2. The cameras triangulate the exact patient's pupil position in the 3D space at 54 Hz and measure critical pupil characteristics at the rapid rate of 500 Hz. Two out of the three cameras (Basler DaA1280-54um) are found to be arranged on a transversal plane passing through the patient's eye canthus; the third camera (custom proprietary camera) is centrally positioned in front of the corresponding (right or left) maxillary sinus. A dedicated NIR (850 nm) illumination provides the required illumination to acquire the patient's anterior segment image stream. The central real-time proprietary camera measures and updates the patient's pupil's position and diameter to confirm alignment between the patient and the device. The critical realtime image-processing operations allow validating the safety sine-qua-non conditions enabling or cutting laser emission with a characteristic reaction time inferior to 4 ms. This safety feature is developed to avoid unwanted exposure of the eyelid, and the iris in case of involuntary eye blinking, saccade, and patient's head movement.B. Treatment Modules

[0035] In figure 2, components belonging specially to the treatment module are grouped in the block 260, being it understood that some element, such as the front lens, are shared by the treatment module and the monitoring system 250. The treatment module comprises a temperature-controlled laser diode Ito (M1F1S22-805.5-35C - Dilas GmbH, 808 nm), a 2D optical scanning system (Saturn 9B - Pangolin Laser System Inc., not explicitly represented and labelled in the figure), and a dedicated proprietary electronic control board managing the entire treatmentOCULOX-2-PCTmodule by coordinating functional requirements, safety-related conditions and being duly compliant to IEC 60601 and ISO 14971.1) Photo-thermal stimulation

[0036] The invention is developed to deliver one among of the most advanced clinically validated photo-thermal protocols known as subthreshold micropulse laser (SMPL). Many groups studied and tried to standardize protocols by maximizing phototherapy efficacy. Others focused on increasing efficiency by simultaneously projecting multiple laser spots, or by providing specific semiautomated protocols to reduce treatment time. Our technical implementation allows the treatment beam to have a temporal resolution of 4 ps, allowing arbitrary protocols to comply with updated clinical best practices.2) Photobiomodulation (PBM)

[0037] Photo biomodulation (PBM) protocol involves a continuous wave beam characterized by a low-power spatially uniform NIR light targeting a treatment field of 35°.C. Optical Systems

[0038] As illustrated in Fig. 2, two different optical systems, merging at the front lens (LFL), are combined into the device. All image planes (Li, L2, IC3, Iti, It2, It3, It4) are optical conjugate planes; thus the two systems are relaying the respective sources on the targeted retina tissues. All the pupil planes (Mi, Pti Pt2) are themselves optical conjugated planes. The treatment path (red rays) features, on the pupil plane PtO, an optical element used to switch from the two treatment modes. The treatment light source, after being projected to infinity by the lens L0, a relay (LA1+LA2) projects the entrance pupil of the beam to the first scanning mirror Pt1, which is projected by the relay B (LB1+LB2) to the second scanner Pt2. Such opticalOCULOX-2-PCTarrangements, allows Pt1 and Pt2 to be precise conjugate planes of Pe, the patient's eye entrance pupil.

[0039] The monitoring path 250 includes the cSLO and the fixation target. The fixation target, IfO shares the optical path with the cSLO. To allow a stable fixation target, IfO is activated precisely and simultaneously to cSLO image acquisition procedure. The cSLO module projects the light source IcO to the targeted retina tissues and collects the backscattered light, travelling through the same optical path up the beam-splitter BS-70:30, with the highly sensitive detector, Det, (Multi Pixel Photon Counter, S14420-3050 MG). To note that for the monitoring path the intermediate pupil plane is positioned between the galvo-scanner S1 and the polygonscanner S2.

[0040] The monitoring module 250 and treatment modules 260 share the optical path, starting from the dichroic mirror DM and continuing to the frontal lens LFL to correctly enter in patient's eye. The present embodiment discloses one treatment module in the block 260, delivering a NIR beam at, for example, A = 808 nm, for both photothermal and photobiomodulation. It is noted, however, that the invention is not limited to this configuration and includes embodiment with several treatment sources at different wavelengths, for example tuned to selected chromophores in the retinal tissue.

[0041] The dichroic mirror (DM) position is precisely selected to combine the light beams coming from the two previously described optical systems, allowing to generate, after passing the front lens LFL, the smallest possible beam footprint (at the device's exit pupil) to match with patient's pupil, Pe. The optical system is designed for a patient's entrance pupil diameter equal to or larger than 4 mm.OCULOX-2-PCTD. Safety

[0042] The device's safety is controlled at different levels by hardware logic and redundant pairs of microcontrollers monitoring in real-time the treatment beam's position, radian flux, pulse duration, and duty cycle. In case of blinks (eyelids transitionally cover the pupil) or when the pupil diameter is smaller than 4 mm, the pupil monitoring system immediately cuts laser emission. In addition to the multitude of measures put in place to manage risk, both treatment protocols will result in tissue temperature rise remaining well below the value that could potentially harm the highly delicate neuro-retinal layers. The risk / benefit ratio associated with the proposed therapeutic approach is expected to be very favourable. The invention offers a treatment designed to address the early pathological phases, risks are minimized, and benefits are maximized.E. Electronics

[0043] This embodiment includes an electronics treatment unit configured to collect several signals measured by the sensors distributed in the device to control function precisely. While non-critical signals are driven by microcontroller based on custom electronic boards, all elements involved in the system ensuring patient and operator safety are either driven by Field Programmable Gate Array (FPGA) like the pupil monitoring and retina feedback generated by cSLO or cabled in hardware logic such as the enabling signal of treatment laser. The host PC unit (HPU) embeds a human interface, allowing operators to generate requests for the controlling electronics and manage fundus the feedback displayed on the integrated monitor.F. Mechanics

[0044] The invention may include a standard chinrest system and ophthalmic joystick to accommodate and align the patient's eye to the device's optical axis.OCULOX-2-PCTII. DEVICE CHARACTERIZATIONA. Monitoring Modules Characteristics

[0045] Table I shows the characteristic values of the various monitoring modules: (i) cSLO excitation, (ii) fixation target, (iii) pupil monitoring excitation. As described above, the main output of the cSLO is a high- resolution, real-time image of the posterior segment of the eye, offering a 46° field of view to visualise the region to be treated. In addition, a fixation target (retinal spot diameter 50 pm) enables the patient's gaze to be fixed during treatment, while the pupil monitoring system allows to align and control patient's pupil stability using a set of 8 NIR LEDs to illuminate the anterior pole of the patient's eye correctly.B. Treatment Modules Characteristics

[0046] SMPL treatment enables micro-second pulses through a dedicated laser protocol, while PBM use a large field treatment beam. Both treatments operate at a wavelength of 808 nm, with variable power depending on the treatment. SMPL delivers a power of 1 W through a retinal spot of 0.4 mm diameter during 100 ps-pulse duration and repeated 100 times. Whereas PBM treatment, the power delivered to the retina is regulated to 600 pW by a 5 W laser source combined with a duty cycle fixed at 33% and pulsed at 2 kHz. Table II summarizes the main specifications of the two treatments at the retinal position.

[0047] Standard medical practices result in mild dry-AMD management success. A proactive preventive clinical approach aimed at delaying or even preventing disease progression is becoming a recognized clinical need. Photo-thermal and photo-biological light-based treatment modalities are clinical approaches offering preventive solutions that can be offered even at very early pathological stages. The innovative clinical device. The invention can deliver hyperthermic tissue conditioning and combine it with photo biomodulation therapy to regain physiological cellular activities andOCULOX-2-PCTfoster tissue repair. Finally, clinical pilot tests are planned to validate the multiplicative benefits of the proposed combined phototherapy. The pilot tests will focus on the safety and early efficacy endpoint to meet the first regulatory requirements and launch market introduction.Corneal.. .. . .. . i Wavelengt Peak Pulse Frequency Duty Cycle om ©ring o u e jnmj irradiance width [ms] Rate [Hz] [%][mW / cm2]Confocal Scanning, 850 351.7 0.1 2000 36.9Ophthalmoscope(cSLO)Fixation Target 515 1.2 x 10’111.5 x 10-3 4 4.3 x 103Pupil Monitoring880 NA500 75Illumination Table I: Specifications at the corneal position of the three monitoring modules: (i) cSLO, (ii) fixation target, (iii) pupil monitoring excitationRetinal Retinal Wavelengt Spot Peak Frequency Durationh [nm] Diameter Irradiance Rate [kHz] [ms][mm] [mW / cm2]Subthreshold micropulse laser 808 0.4 8 x 1052 10(SMPL) Photo biomodulation 808 1 1.6 2 60 x 103(PBM)Table II: Subthreshold micropulse laser (SMPL) and photo biomodulation (PBM) mode treatments specifications at the retinal position reference symbols in the figures

[0048] 100 device121 photothermal source122 photobiomodulation sourceOCULOX-2-PCT123 third, diagnostic source125 spectral analyser140 control unit180 front lens131 photothermal beam132 photobiomodulation beam133 third beam, dosimetry beam135 backscattered beam220 eye250 confocal scanning laser ophthalmoscope optical path260 treatment optical pathBS beam splitterCam1 pupil monitoring cameraCam2 pupil monitoring cameraDM dichroic mirrorDet single photon detectorIcO light source for the confocal scanning laser ophthalmoscopeItO light source for the photothermal / biomodulation beamsIc1-lc3 image planes, control systemIt1 -It4 image planes, treatment systemM1 pupil plane, control systemPt1-2 pupil planes, treatment systemL0 lens groupLA1 relay lensLA2 relay lensLB1 relay lensLB2 relay lensLFL front lensLc1 lens group51 galvo-scanner52 polygon scannerOCULOX-2-PCT

Claims

Claims1. A device for providing retinal therapy, comprising:- a light source emitting a photothermic treatment beam configured to create a condition of localised hyperthermia in the retinal tissue,- means to generate a photobiomodulation beam capable of being selectively absorbed by predetermined chemical substances of the retinal tissue, the photobiomodulation beam being configured to deliver a specific dose to the retinal tissue that is lower than a dose delivered by the photothermic treatment beam.- an intensity control unit configured to control an instantaneous intensity of the first light source and / or of the photobiomodulation light source,2. the device of the preceding claim, configured to follow a predetermined treatment program in which the photothermic treatment beam and the photobiomodulation beam are applied one after the other following a predetermined intensity profile in a same application.

3. The device of any one of the preceding claims, wherein the photobiomodulation beams is a continuous-wave beam4. The device of any one of the preceding claims, wherein the photobiomodulation beam produces a spatially uniform intensity distribution on the retinal tissue with a treatment field of at least 20°, preferably at least 35°.

5. The device of any one of the preceding claims, wherein the photobiomodulation beam is generated by a second light source having a wavelength different than a wavelength of the first light source.OCULOX-2-PCT6. The device of any one of claims 1-4, wherein the photobiomodulation beam and the photothermic treatment beam are generated by the same first light source.

7. The device of any one of the preceding claims, with a monitoring optical system configured to visualize in real time a fundus of an eye undergoing treatment.

8. The device of any one of the preceding claims, including a dosemeasuring optical system configured to illuminate a selected region of the retina with a third light source, collect radiation reflected from the selected region and determine a reflection spectrum, wherein the dose-measuring optical system is active during the photothermic treatment and / or during the treatment with the photobiomodulation beam.

9. The device of any one of the preceding claims, wherein the second treatment beam has shorter wavelength than the photothermic treatment beam.

10. The device of any one of the preceding claims, wherein the chemical substances are chromophores.

11. The device of any one of the preceding claims comprising a steering unit for deflecting the photothermic light beam, wherein the first light source emits a collimated beam impinging on an addressable illuminated spot on the retina, the control unit being programmed to cause the photothermic beam to cover a predetermined region of the retina by moving the illuminated spot in a sequence by controlling the steering unit.

12. The device of claims 8 and 11, wherein the dose-measuring optical system is optically collimated to measure an addressable measure spot on the retina, and the control unit is programmed to follow the illuminatedOCULOX-2-PCTspot with the measure spot during a treatment with the photothermic beam.OCULOX-2-PCT

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