Radioluminescent eye device for modulation of photoreceptor metabolism

Abstract

A phototherapeutic eye apparatus implanted in the eye or located proximate the eye. The apparatus comprises a solid state beta flux source for emitting beta particles and a luminophore material that is in contact with or proximate the solid state beta flux source. The luminophore material receives the beta particles and responsive thereto emits photons that escape the phototherapeutic eye apparatus and provide illumination to interior regions of the eye.

Description

RADIOLUMINESCENT EYE DEVICE FOR MODULATION OF PHOTORECEPTOR METABOLISMCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present invention claims priority under 35 USC 119(e) to the provisional patent application filed on October 14, 2023, and assigned application number 63 / 544,169 and to the provisional application filed on July 16, 2024 and assigned applicaton number 63 / 671 ,827. These provisional patent applications are incorporated in their entirety herein.FIELD OF THE INVENTIONThe present invention applies to long-life phototherapeutic medical devices, especially for use in ophthalmology.BACKGROUND OF THE INVENTIONDiabetes mellitus is one of the fastest-growing diseases afflicting the modern world. The increasing availability of low-quality food and a shift toward sedentary work environments drives this, as well as the subsequent onset of associated complications.One such complication is diabetic retinopathy (DR) — a disease characterized by macular edema resulting from neovascularization of the retina. Neovascularization is, in turn, driven by retinal hypoxia (that is, reduced oxygen uptake). DR can eventually cause vision loss and blindness.Reduced retinal oxygen uptake (retinal hypoxia) is the primary driver for the progression of diabetic retinopathy. The reduced oxygen uptake is due to the obliteration, shunting, and occlusion of capillaries in the diabetic retina.Another factor reducing oxygen perfusion is glycosylated hemoglobin's (HbA1 c) ten times higher affinity for oxygen retention when compared to non-glycosylated hemoglobin (HbAO). HbA1 c levels range 1 .5-2x higher in diabetic patients (9%) than inhealthy patients (5%). In other words, diabetics' high blood sugar prevents their blood from delivering adequate amounts of oxygen to body systems.Rod cell metabolism is inversely related to light level and is dominated by sodium (Na+) circulating in the outer rod segment. In the dark, Na+ circulates in and out of rod cells' open cGMP-gated Na+ channels, a phenomenon known as "dark current." When in this state, rod cells remain partially depolarized and burn copious amounts of energy to increase their sensitivity and enable perception of dimly lit scenes. As photons hit the rods, the phototransduction cascade leads to closure of cGMP-gated Na+ channels, hyperpolarizing the rods. When subjected to light, the rods provide enough data for the central nervous system (CNS) to process a functional image, precluding them from an increase in sensitivity that necessitates an increase in metabolism. Retinal hypoxia is driven by dark current's exacerbation of oxygen consumption. For example, exposure to scotopic (i.e., dim or low intensity) light in rods decreases their oxygen consumption by about 6000 02 molecules per photon.The resulting retinal hypoxia also drives the expression of VEGF (vascular endothelial growth factor) a protein that promotes the growth of leaky blood vessels. The resulting neovascularization (growth of additional blood vessels in the eye in abnormal locations or in excess of normal blood vessels) in the retina forms blood vessels that leak fluid and scar the surrounding tissue.Retinal hypoxia further triggers the VEGF signaling pathway, promoting neovascularization in the retina. Resultant malformed blood vessels grow into the eye, leaking vision-obstructing fluid, a condition called macular edema.Intravitreal anti-VEGF injections are a primary treatment modality for DR by blocking the VEGF pathways. These injections are designed to combat abnormal blood vessel growth, which is a hallmark of diabetic retinopathy, by blocking the action of VEGF. Thus, the anti-VEGF injections help prevent macular edema and subsequent blindness in DR patients.Although these injections significantly reduce neovascularization, they also present a host of negative side effects. High irritation and discomfort in the eye are the most common effects that tend to discourage many patients from adhering to their treatment regimen. Patients receiving anti-VEGF injections also have a 25-40% rate ofdeveloping glaucoma as the optic nerve is degraded over the treatment regimen, risking vision loss.Other risk factors, such as retinal detachment and blood clots, further detract from anti-VEGF injections' clinical appeal as a modality. From a financial perspective, anti-VEGF injections place a huge economic burden on those suffering from diabetic retinopathy. The injection is administered every 2-4 weeks at an outpatient or inpatient facility, bringing the average two-year cost for a US patient to about $30,328. When extrapolated to the approximate number of Americans suffering from DR (about 9.6 million people), this may cost the American healthcare system up to $135B annually.Over 150 million DR patients worldwide stand to benefit from an improved treatment modality. A phototherapeutic approach may be leveraged to reversibly modulate retinal metabolism and thereby reduce the occurrence of diabetic retinopathy and the resulting vision degradation. Additionally, light-adapting ocular phototherapy can improve outcomes of other hypoxia-driven ocular diseases such as glaucoma, sickle cell anemia, choroidal ischemia, and macular degeneration.Pan-retinal laser photocoagulation is another technique for treating advanced diabetic retinopathy. During pan-retinal photocoagulation, a specialized laser creates a pattern of small burns or laser spots across the retina. These laser burns induce controlled tissue damage, which, paradoxically, helps reduce abnormal blood vessel growth by sealing leaking vessels and reducing oxygen demand in the retina. The resulting damage to retinal vasculature also, ironically, improves oxygen's perfusion from blood vessels into the retina. These effects drive pan-retinal photocoagulation's efficacy in lowering retinal hypoxia, thereby lessening VEGF expression and thereby, subsequent macular edema.Pan-retinal photocoagulation, however, is not without side effects. The selective burning of retinal tissue permanently reduces the patient's vision acuity and contrast sensitivity. Because of this, pan-retinal photocoagulation is usually postponed until the patient is suffering from central vision problems. However, this treatment offers a suboptimal solution, settling for some permanent vision loss rather than complete vision loss.The longest period during which dark current exacerbates hypoxia is during sleep when the eyes are not receiving light. Therefore, it stands to reason that phototherapy should be administered during sleep to reduce hypoxia during this time.Most famously, PolyPhotonix Medical Ltd (of Sedgefield, United Kingdom) has developed a light-emitting sleep mask that is currently undergoing commercialization in the United Kingdom. This mask uses an organic light-emitting diode (OLED) array to deliver light through the eyelids and pupils during sleep.But Polyphotonix's sleep mask, as a light source external to the eye, fails to effectively deliver light to the retina. This is due to various factors. The primary factor is an order-of-magnitude variability in human eyelid transmissivity across the human population. Designing the mask for a specific transmissivity or range of transmissivities precludes a portion of the patient population from using this device successfully.Another confounding variable is that during deep sleep, pupil diameter is about three times smaller than during dark-adapted awake conditions. Lastly, the eye's upward slant during sleep, known as Bell's phenomenon, increasingly shifts the pupil away from the OLED light as sleep deepens. Rapid eye movement (REM) also compromises the coincidence of incoming light and the pupil. All these factors contribute to the inefficacy of a phototherapeutic sleep mask.Studies conducted by researchers at the California Institute of Technology have resulted in the development of various other approaches for light-adapting phototherapy to prevent neovascularization and the progressive worsening of DR.One such non-invasive phototherapeutic approach comprises a gaseous tritium light source (GTLS) in a contact lens. Within a housing or chamber of the GTLS, decaying beta particles strike a luminophore that, in turn, provides illumination.In pre-clinical trials, electroretinography (ERG) assessment of the efficacy of this device projects a 50% suppression of rod metabolism in the human eye. As described above, reducing rod metabolism lessens hypoxia and VEGF expression.Unfortunately, the use of the GTLS imposes a variety of design limitations when incorporated into a contact lens or when implanted intraocularly. The GTLS' gaseous chamber may be too large (300 pm OD, 2mm long) to be embedded in an intraocular lens (IOL) for implantation through rolled injection. The GTLS' oversized form factor andrigidity would likely cause them to rupture during this surgery. A rupture will, unfortunately, provide a measurable radiation dose to the patient, not to mention risking laceration of the sclera, cornea, and other eye anatomy by the glass vial's shards. As embedding the GTLS in the optic portion of an IOL would impede vision, the GTLS may be embedded in an lOL's haptics. Once again, the size and rigidity of the GTLS preclude them from being embedded in an IOL haptic, as IOL haptics are around 500 pm thick and must be flexible enough to be rolled with the thicker optic and injected through a circular orifice ~2.2 mm wide. This could also lead to GTLS rupture.The danger posed by a GTLS embedded in an IOL is still present when the GTLS is embedded in a contact lens. There is no guarantee that patients using such a light-emitting contact lens will safely install and remove the light-emitting contact lenses. Also, there is a huge Young's Modulus mismatch between the GTLS and the contact lens; the GTLS will not conform to the manipulated lens. This greatly increases the likelihood of GTLS rupture when the contact lens is handled by a patient, exposing them to a radiation dose, as well as laceration by shattered glass tubing of the GTLS.BRIEF DESCRIPTION OF THE DRAWINGSVarious embodiments of the inventive disclosure are described below. In the course of the description, reference will be made to the following drawings, which are not necessarily drawn to scale. The present embodiments are illustrated by way of example, and not by way of limitation, in the accompanying figures.Figures 1 - 3 illustrate three tritium light source configurations according ot the present invention.Figures 4 and 5 illustrate tritium light source arrays incorporating one of the TLS’s of Figures 1 - 4.Figures 6 and 7 illustrate ocular lenses housing a TLS of the present invention. Figures 8A, 8B, 9A, 9B, 10A, 10B, 1 1 A, 11 B, 12A, and 12B illustrate various techniques and the use of various materails to attenuate light emitted from the TLS of the present invention.Figures 13A and 13B illustrate a laser welding approach to the hermetic sealing of the TLS of the present invention.Figures 14A and 14B illustrate forming a eutectic bond for the TLS of the present invention.Figures 15A and 15B illustrate forming an anodic bond for the TLS of the present invention.Figures 16, 17, and 18A-18O each illustrate attachment of the TLS of the present invention to an ocular device.Figures 19 and 20 illustrate fabrication steps for forming the TLS devices of the present invention.Figure 21 A - 21 C illustrate a process for forming nad aligning a luminphore and a metal tritide layer such that light is emanated at the intersection of the two materials.Figures 22 - 24 illustrate sputtering chambers and constituent materails for use in forming the various TLS structures of the present invention.Figures 25A - 25C illustrate FIGS. 25A - 2D a TLS-based chandelier implant.Figures 26A - 26C illustrate various chandelier-based support structures for the TLS’s of the present invention.Figures 27A - 27C and 28A - 28C illustrate "on-off" mechanisms for controlling light emitted from the TLS.Figure 29A and 29B illustrate steps for forming a betaluminescent contact lens (BCL) comprising TLS’s of the present invention.Figure 30 illustrates components of an eye and the location of various TLS’s of the present invention.Figures 31 and 32 illustrate techniques and elements related to the TLS for distributing light to specific areas of the retina.DETAILED DESCRIPTION OF THE INVENTIONFor phototherapy to be clinically viable as a modulator of retinal hypoxia, there must be a size reduction for long-life illumination technology. Such a prophylactic will be enabled by the development of light sources that geometrically conform to their parent device when handled by their operator. Furthermore, such innovative size reduction enables the development of exotic, small-scale devices to address retinal hypoxia in a variety of patient populations and in a variety of applications.City Labs, assignee of the present application, has developed a robust manufacturing process for the production of novel solid-state betaluminescent films, referred to as tritide light sources (TLS). In some embodiments, the metal tritide 110, as an element of a metal tritide light source (TLS) 100 of Fig. 1 , is a thin metal film that has absorbed tritium atoms which are chemically bonded or trapped within the metal's lattice structure. Tritium is an isotope of hydrogen that emits beta electrons upon decay.The thin metal tritide film is disposed in contact with or proximate to a luminophore 120. When beta electrons are emitted into the luminophore, the luminophore generates photons, a mechanism referred to as beta luminescence. The TLS 100 is inexpensive to manufacture, low in tritium content, and functions independently of any external inputs.The TLS 100 is fabricated using microfabrication techniques known to those skilled in the art. A substrate 140 forms a portion of the TLS enclosure. The thin film metal tritide 110 is formed by sputter deposition and tritium loading of the deposited metal film. The luminophore 120 is positioned to absorb beta emissions originating from metal tritide 110. In various embodiments, the luminophore 120 is a powder or thin film. The absorption of beta emissions by the luminophore 120 generates photons that are emitted from it. A layer 130, in most embodiments, is comprised of a biocompatible, optically transparent material (e.g., glass). FIG. 1 depicts an embodiment of the TLS comprised of planar, "sandwiched" metal tritide 110 and powdered luminophore 120 layers between a package consisting of layers 130 and 140. This embodiment of the TLS lends itself to miniaturization and mechanical flexion (contingent on material choice). This embodiment of a TLS clearly demonstrates its miniaturization potential as a chamber-less, coplanar-manufactured component.In some embodiments of the TLS, a cavity, depression, protrusion, or another geometric feature 250 may be included to meet one or more optical, structural, or biocompatibility design inputs. FIG. 2 illustrates a TLS 200 including such a geometric feature 250, which may be fabricated through methods well-known in the art, such as a chemical etch. This feature 250 informs the shape of the metal tritide 210 and the luminophore 220, which conformally coats the substrate 240 as thin films. This embodiment of the TLS is also enclosed by a glass layer 230.FIG. 3 illustrates a TLS 300 that features a concavity 350, which may be fabricated through methods well-known in the art, such as ion milling. The metal tritide 310 conformally coats the substrate 340 along the profile informed by the concavity 350. Substrate 340 and layer 330 enclose a plurality of granular luminophores 320, which is constrained to the geometry defined by the concavity 350.The addition of surface features or textures to the substrate of the phototherapeutic device, such as the substrate illustrated in FIGS 1-3, has the further benefit of increasing effective surface area available both for the metal tritide and the luminophore, which can result in higher light output from a given area. An increase in effective surface area can be accomplished through many processes, including micromachining, embossing, etching, electrospinning, coating with micro- or nanoparticles, electrochemical roughening, abrasion, leaching, using a metal-organic framework, etc.The embodiments FIGS. 1, 2, and 3 are but three of the virtually limitless configurations in which a TLS may be fabricated through methods well-known in the art; each configuration presenting a unique apparatus for providing illumination to overcome the effects of retinal hypoxia. The solid-state, chamberless nature of the TLS enables its effiecint mass production through microfabrication techniques well-known in the art.Thus, generally, the present invention describes a light-emitting ocular device platform comprising a thin film TLS for the modulation of retinal hypoxia. In most use cases, the TLS arrangement is designed to deliver a constant, scotopic light dose to the patient's retina to lower retinal hypoxia.The thin film TLSs, as described herein, provide better miniaturization potential than the prior art GTLS approach described above. As 3-dimensional chamber-based components, the latter GTLSs are too large (300 pm) and cannot be easily thinned for incorporation into various eye devices and eye implant structures.City Labs' thin film TLS can be fabricated to "paper thin" dimensions (e.g., 50 pm or less), enabling a breakthrough for light source encapsulation in unprecedentedly small volumes. Some TLS-based embodiments may be miniaturized with maximum dimensions in the nanometer (nm) scale, thereby providing total volumes in the pico-liter(pL) range. GTLS, which are traditionally millimeter-scale glass chambers, cannot be miniaturized to these dimensions.The TLS' small form factor, orders of magnitude smaller than that of ocular device dimensions, enables their arrangement in various parent ocular devices (e.g., contact lenses, lOLs, glaucoma drainage devices).An array 400 (see FIG. 4) and an array 500 (see FIG. 5) of embedded microscopic TLSs 200 conform to the contortion of ocular devices, minimizing the TLS' proclivity to shatter (especially when compared to prior art GTLS' shattering proclivity) during medical operations including, but not limited to, the injection of an IOL into the eye or the insertion of a contact lens onto the eye. This feature greatly reduces the previously mentioned risk of ocular laceration and release of a radiation dose, as well as reducing regulatory burdens stemming from these potential occurrences. It is important to note that various versions of the TLS (see FIG. 1 , FIG. 2, and FIG. 3) may be arrayed in a parent ocular device (e.g., IOL, contact lens, phakic IOL).Another advantage of the arrangement of microscopic TLS of the present invention is that in such an embodiment the tritium activity contained in each TLS unit is inversely proportional to the number of TLS units embedded in the ocular device. That is, given the small size of each TLS, more TLS units can be embedded in the ocular device, and therefore, each TLS unit exhibits less tritium activity or decay. In these embodiments of the invention, the TLS functionally serves as light-emitting bulkheads containing small amounts of tritium. Such a configuration not only decreases the risk of a single TLS's failure, it also minimizes the severity of such a failure, as the parent device and recipient patient are exposed to far less tritium and far fewer shards of packaging material upon occurrence of a failure.The array 400 (see FIG. 4) comprises a plurality of TLS units 200 (of FIG. 2) disposed in an IOL haptic 620.The array 500 (see FIG. 5) comprises a TLS array in which a plurality of TLS units 200 (of FIG. 2) are embedded in an IOL haptic 622 (see FIG. 6)and are held together in the haptic by a tethering medium 510.Although arrays 400 and 500 are described as incorporating the TLS 200 described in FIG. 2, other embodiments of a TLS (e.g., 100, 300) can be utilized in place of the TLS 200 in the arrays 400 and 500.City Labs has developed a process for fabricating betaluminescent films based on City Labs' metal tritide technology. The fabrication process begins with the deposition (e.g., sputtering, e-beam evaporation, thermal evaporation) of a thin-film metal (e.g., titanium, scandium, magnesium, palladium, other hydride-capable metals, or an alloy, intermetallic, layered, composite, or multi-phase metallic structure), with a thickness ranging from about 50 nanometers and about 1 micron, on a substrate, for example, the substrate 140 of FIG. 1. The substrate material may comprise, for example, borosilicate glass. In some applications, the layer of deposited metal may be thinner or thicker than the range specified above.Subjecting the resultant film to tritium at appropriate temperatures and pressures forms a surface metal tritide 110 (see FIG. 1 for example) that emits beta flux. This process is called "tritium loading." The film may be diced to application-specific dimensions. The metal tritide material layer may be interchangeably referred to herein as a "beta source."When coated with a luminophore (e.g., phosphor) layer 120 (see FIG. 1 for example), the beta flux from the beta source irradiates the luminophore, thereby forming a thin film tritide light source (TLS), such as the TLS 100 of FIG. 1 . This structure has far greater miniaturization potential than the prior art GTLS-based phototherapeutic as described above, thereby enabling light delivery from a smaller (e.g., sub-pL) volume.Another capability demonstrated by the metal tritide betaluminescent device is the fabrication of the thin film TLS with photolithographic precision, thereby enabling precise control of the shape and ubication of illuminated regions (see, for example, the structure 2100 illustrated in FIG. 21). This patterning can be done on a substrate internal to the TLS package, such as a polymer, silicon, glass, or metal, or directly onto the thin film TLS' packaging 140 (e.g., borosilicate glass).FIG. 22 details an embodiment 2200 of the metal tritide fabrication process. In this embodiment of the metal tritide fabrication process, a sputter chamber 2230 is employed. This chamber is filled with a plasma 2220 that enables thin film sputtering ofa target material 2240 (mounted on a target holder 2270) onto a substrate 140 (seated on a stage 2290). Through sputtering methods well-known in the art, the target material is ejected from the target as particles 2250, striking the substrate 140 and forming a thin film metal tritide 110. During the previously described processes, gaseous tritium 2210 is introduced to the sputter chamber 2230. In this embodiment, gaseous tritium 2210 is loaded into the target material in both its thin film 110 phase and its ejected particulate 2250 phase.FIG. 23 details an embodiment 2300 of the TLS packaging process. In this embodiment, a sputter chamber 2220 is employed. A glass sputter target 2310 (mounted on target holder 2270) is subjected to sputtering methods well-known in the art. Glass particles 2320 are ejected from the glass target, striking the unpackaged TLS along the surface of the substrate 140 (seated on a stage 2290) and luminophore 120, forming a thin glass layer over them. This thin glass layer physically binds the TLS internals and creates a hermetic seal along its seam with TLS substrate 140. This hermetic seal is one of the primary variables that informs tritium leakage from the TLS.As seen in FIG 24, this metal tritide can also be directly deposited onto a luminophore powder or thin film layer 120 (e.g., ZnS), binding the luminophore layer 120 via encapsulation under the beta source 110. In this embodiment, 2400 of the tritide- luminophore coupling process, a sputter chamber 2230 is employed. The luminophore 120 is already laid on a glass layer 130, and the sputter chamber 2230 is filled with a plasma 2220. A metal sputter target 2240 (precursor to the thin metal film 110, mounted on substrate holder 2270) is subjected to sputter deposition methods well-known in the art. The sputter target 2240 ejects metal particles 2250, which strike the TLS substrate 130 (mounted on stage 2290) and luminophore layer 120, forming the thin metal film 110. This thin metal film physically entraps the luminophore 120, absolving the manufacturer from the use of a chemical binding agent for the fixation of the luminophore 120.The following paragraphs set forth a detailed discussion of one stepwise fabrication process for generating the TLS of the present invention (embodiment 100 for example) which is set forth below and is diagrammatically depicted in FIGS. 19 and 20 as a process 1900 and 2000, respectively.According to this fabrication technique, in a first step, the thin metal film 110 is deposited on a choice substrate 140. This may be accomplished through processes including thin film sputtering and thin film evaporation, using source materials such as titanium, scandium, magnesium, palladium, other hydride-capable metals, or various alloy, intermetallic, layered, composite, or multi-phase metallic structures. The substrate 140 onto which the film is deposited is, in some embodiments, a biocompatible, optically transparent material such as borosilicate glass. In other embodiments, the thin metal film 110 may be deposited on transparent, translucent, and semi-translucent substrates, including but not limited to fused silica, fused quartz, and polymers.In some embodiments of the deposition process, the substrate 140 is positioned in line with a source material, such as a scandium target. Particles from the source material are deposited onto the substrate 140, coating the entirety of the exposed face with the film 110 (scandium in one example) between 50 nm to 1 pm thick. Some embodiments may feature a metal film that is thicker or thinner than the aforementioned thicknesses.In some embodiments, a thin (~10 nm) cap layer of palladium (Pd) (not shown in FIG. 19) may be deposited on top of the metal film. In some embodiments, the thickness of this Pd layer may exceed or be less than 10 nm. This Pd layer has demonstrated an ability to act as a catalyst for hydride formation during tritium loading while also aiding in the prevention of oxide formation on the thin film. Embodiments of the manufacturing process, including this fabrication step, yield a more potent beta source.In some embodiments of the TLS fabrication approach, a lithographic fabrication step (see FIGS. 21 A, 21 B and 21C) may be added, in which the substrate 140 is masked before metal deposition, with "stencils" made from materials including, but not limited to, photoresist or shadow masks. These masking materials, when removed, inform the patterning of the resultant metal film, as illustrated in FIG 21 A, 21 B and 21 C.The next step of the TLS manufacturing process is the formation of a metal tritide 110 on the metal film. A metal tritide is chemically identical to a metal hydride, albeit that in the former, tritium (hydrogen-3) is bonded to the metal, and in the latter, protium (the non-radioactive form of hydrogen with one neutron and one proton) is bonded to themetal. This bonding is accomplished through tritium loading processes that require control of various environmental factors, such as temperature, pressure, and time. Higher loading temperatures and pressures favor the formation of the metal tritide when the metal is exposed to gaseous tritium.However, it is worth noting that embodiments of the invention may use varying metal types (e.g., titanium, scandium, magnesium, other hydride-capable metals, alloys, intermetallic, composite, layered, or multi-phase metallic structures), compositions, or geometries. Embodiments containing the previously described patterned metal film will absorb tritium along the patterned metal, emanating beta flux radially from the patterned metal tritide film 2110 of FIGS, 21 A, 21 B and 21C.In some embodiments, a thin (~10 nm) cap layer of palladium (Pd) (not shown in FIG. 19) may be deposited proximate to the metal film. In some embodiments, the thickness of this Pd layer may exceed or be less than 10 nm. This Pd layer has demonstrated an ability to act as a catalyst for hydride formation during tritium loading while also aiding in the prevention of oxide formation on the thin film.In an embodiment of the invention (such as illustrated in FIG. 22), the metal deposition and tritium loading steps may be performed concurrently. In this embodiment of the invention, a sputter chamber 2230 is filled with plasma 2220 and tritium gas 2210. Under these conditions, the sputter target 2240, sputtered particles 2250, and deposited thin film 110 trap tritium atoms in their lattice, forming a surface metal tritide on them.Hydrogen and deuterium loadings can also form metal hydrides, but these are not considered metal tritides. However, hydrogen and deuterium may be used for preliminary test loadings in the development of a metal tritide recipe, thereby characterizing the film quality associated with various loading recipes. Of course, the loading of hydrogen (protium) or deuterium cannot be used to create a betaluminescent device. It is also important to note that, semantically, "tritium metal hydride," "metal tritide," and "beta source" may be used interchangeably herein.The next step of the TLS manufacturing process is the fabrication of a luminophore layer (e.g., 120, 220, 320 of FIGS. 1 , 2 and 3) proximate to the metal tritide. Luminophores that are excitable by one or more phenomena, including absorption of beta particles, are employed in this fabrication step. Luminophores arewell-known in the art, including zinc sulfide (ZnS) and yttrium oxide (Y2O3), as well as corresponding dopants well-known in the art, such as copper (Cu), silver chloride (AgCI), gold (Au), or aluminum (Al), may be selected for the emission of visible light between about 400 and 600 nm wavelengths. This range contains the peak chromatic absorption of retinal rod cells.The luminophore layer may be formed in contact with the metal tritide using methods known in the art, such as electrophoretic luminophore deposition (EPD), e- beam evaporation, sputtering, and thermal evaporation. However, a preferred approach is the application of luminophore powders (-5-20 pm) such as ZnS:Cu to the metal tritide. In some embodiments, a polymer binder (e.g., lacquer) is used to bind the luminophore powders in contact with the metal tritide. However, this may reduce the brightness of the TLS, as the binder will inhibit the metal tritide's beta emissions from reaching the luminophore. This darkening effect is compounded by the darkening of the binder as it absorbs beta emissions. In some embodiments, the luminophore layer may also be bound via physical or chemical means, including, but not limited to, glass sealing and compression between optically transparent substrates. As depicted in FIG. 24, in other embodiments, the luminophore film / powder layer 120 may be encapsulated and bound through the deposition of the previously described metal layer 110.In some embodiments, the deposition of coatings such as indium oxide (ln20a) onto the luminophore can prevent the degradation of the luminophore material as bombarded by the beta decay. This deposition may be accomplished through methods such as a sol-gel method or sputtering.In other embodiments, crystalline luminophores (e.g., Csl:TI) may be used in place of a phosphor. These crystalline luminophores may be subjected to thermal, optical, or thermo-optical treatment (e.g., annealing) to preserve their transparency and luminescent properties. Such treatments may also be employed to restore thin film TLS functionality that has been degraded due to degradation of the luminophore material by beta decay.In certain embodiments of the present invention, the luminophore layer may be patterned using lithographic techniques using photoresist, shadow mask, or other masking materials.As shown in FIGS. 21 A, 21 B, and 21 C, a structure 2100 will emanate light at intersections 2130 of the luminophore 2120 and the metal tritide layers 2110, which is informed by each layer's patterning or lack thereof. This approach grants the inventors freedom to "paint" application-specific radioluminescent designs on the metal tritide layer.As described above, materials used as substrates in and / or for packaging the TLS include but are not limited to borosilicate glass, nanodiamond aggregates, and polyurethanes. These are selected for their biocompatibility and optical transparency.The TLS also requires hermetic, biocompatible packaging. The following embodiments / sealing approaches describe the transparent, biocompatible packaging component of the invention as made of borosilicate glass. However, in other embodiments of the invention, the previously described packaging materials may be employed.Some embodiments of the TLS do not require hermetic packaging and may be enclosed directly in a parent device, such as an IOL, transscleral chandelier, or contact lens. An example process defining this embodiment is the formation of an encapsulating layer (e.g., hydrogel, glass, polyimide) that affords the thin film TLS biocompatibility and safety but does not necessarily provide a hermetic seal.Packaging approaches to provide the TLS with a hermetic seal will be employed. In some embodiments, a glass layer and a substrate layer enclose the TLS by coating it with a sputtered or evaporated borosilicate glass film (as per the teaching of embodiment 2300 of FIG. 23) or blowtorching two borosilicate glass layers.Embodiment 1300 in FIGS. 13A and 13B depict a laser welding approach to the hermetic sealing of the TLS. The metal tritide 110 and luminophore 120 are built on substrate 140. Glass layer 130 is then placed onto the exposed surface of the incomplete TLS 100 (bond surface comprised of 120 and 140). A laser 1310 is aligned with a focusing medium 1320 and rasters across the edges of the TLS 100. The laser's energy heats the interface between glass 130 and substrate 140, forming a hermetic seal 1330.FIGS. 14A and 14B depict embodiment 1400 of TLS sealing that employs eutectic bonding. The metal tritide 110 and luminophore 120 are built on substrate 140.The non-light-emitting surface of the substrate 240 is coated with a metal bonding agent 1410. Glass layer 130 is then placed onto the exposed surface of the incomplete TLS 100 (contact surface comprised of 120 and 1410). The incomplete TLS is subjected to mechanical pressure indicated by arrowhead 1420 and elevated temperature indicated forming a hermetic seal 1440 at 130 and 1410's interface about the TLS' periphery.FIGS. 15A and 15B depict an embodiment 1500 of TLS sealing that employs anodic bonding. The metal tritide 110 and luminophore 120 are built on substrate 240. Glass layer 130 is then placed onto the exposed surface of the incomplete TLS 200 (surface comprised of 120 and 240). The incomplete TLS is subjected to mechanical pressure as indicated by an arrowhead 1530 and elevated temperature. An electrostatic field 1520 is applied to the incomplete TLS 100, with substrate 140 as the anode and glass 130 as the cathode. The application of mechanical pressure, heat, and an electrostatic field to elements 130 and 140 form a hermetic seal 1540 at their interface about the TLS' periphery.Other embodiments of the TLS fabrication process may conformally coat or pot the thin film TLS with materials including but not limited to borosilicate glass, parylene, and polyurethane. Chemical vapor deposition (CVD) may also be employed to conformally coat the TLS. Additional embodiments may employ encapsulation methods including but not limited to direct wafer bonding, adhesive bonding, glass frit bonding, transient liquid phase bonding, and metal thermo-compression bonding.It should be noted that the TLS may incorporate techniques known in the art for releasing a buildup of gaseous helium. These include the design of a physical leak, a diffusing surface, or other avenues through which helium may evolve from the TLS' physical bounds.The next two paragraphs summarize the above processes using two approaches for the manufacture of thin film TLS.In one embodiment 1900 of the thin film TLS 100 fabrication approach (see FIG. 19), a borosilicate glass wafer 140 may have a thin metal film 110 (e.g., Ti, Mg, Sc, Pd, other hydride-capable metals, or alloy, intermetallic, layered, composite, or multi-phase metallic structures) deposited onto it through sputtering, evaporation, or other methodsdisclosed in the art. This thin film may be lithographically patterned as previously known in the art as described in conjunction with FIGS. 21 A - 21 C.The resulting thin film is then subjected to a tritium loading, forming a metal tritide 110 on the borosilicate glass' surface. The metal tritide is then directly coated with a luminophore powder or film 120 (e.g., ZnS:Cu, ZnS:AI) through EPD, polymer binding, physical containment (see FIG. 24), or other methods known in the art. This luminophore layer may also be lithographically patterned, as disclosed in conjunction with FIG. 21 A - 21 C. The device may then be hermetically sealed with a substrate wafer using laser welding (see FIG. 13), anodic bonding (see FIG. 15), eutectic bonding (see FIG. 14), or other sealing methods disclosed in the present invention or known in the art.In another embodiment 2000 of the thin film TLS fabrication approach (see FIG. 20), a borosilicate glass wafer 140 has a thin metal film 110 (e.g., Ti, Mg, Sc, Pd, or an alloy, intermetallic, layered, composite, or multi-phase metallic structure) deposited onto it through sputtering, evaporation, or other methods disclosed in the art. This thin film may be lithographically patterned, as previously disclosed in conjunction with FIGS. 21 A - 21 C. The resulting thin film 110 is then subjected to a tritium loading, becoming a metal tritide on the borosilicate glass' surface. A second borosilicate glass wafer 130 is then directly coated with a luminophore powder or film 120 (e.g. ZnS:Cu, ZnS:AI) through EPD, polymer binding, physical containment (as shown and described in FIG. 24) or other methods disclosed in the art. This luminophore layer may also be lithographically patterned as disclosed in conjunction with FIGS. 21 A - 21 C. The luminophore-bearing and metal tritide-bearing wafers are aligned so the metal tritide layer 110 irradiates the luminophore layer 120 along their intersection 2130 of FIG. 21 B.The device may then be hermetically sealed with a substrate wafer using laser welding (see FIG. 13), anodic bonding (see FIG. 15), eutectic bonding (see FIG. 14), or other sealing methods disclosed in the present invention.According to the teaching of the present invention, the steps in the summarized embodiments 1900 and 2000 may be performed in varying orders, provided that the metal tritide makes contact with or is disposed proximate to the luminophore.In certain embodiments of the present invention, tritium radiation sources not based on metal tritide technology are employed to make the TLS. Organic molecules, including but not limited to 1 ,4-bis(phenylethynyl)benzene (DEB) and 1 ,4- diphenylbutadiyne (DPB) can be catalytically hydrogenated with gaseous tritium. This yields an organic molecule containing tritium atoms (e.g., TDEB, TDPB, respectively) acting as a beta source for the irradiation of luminescent materials. These molecules can be dissolved in a polymer (e.g., polystyrene) matrix containing low pm-scale organic luminophores (e.g., PBD, 3-hydroxyflavone, rubrene) that may be used individually or in combination to achieve the desired wavelength (400-600 nm). This process yields a plastic radioluminescent component that may be safeguarded from degradation (e.g., ln2O3 deposition) and packaged (e.g., glass laser welding, conformal coating) as delineated in previously described metal-based embodiments. Additionally, other tritiated polymers like polysiloxane have been shown to resist tritium-induced degradation.Various embodiments of the invention vary the tritium beta-flux source between a metal tritide and tritiated polymer. Embodiments of the invention present the available tritiated and luminescent components in various arrangements, such as in layers or a homogenous / non-homogeneous polymer matrix.As mentioned in the above background section, current treatment modalities for diabetic retinopathy, a pathophysiology of retinal hypoxia, suffer high patient noncompliance. Given this, a solution circumventing patient compliance as a prerequisite for treatment efficacy holds high clinical and market value. Such a solution may take shape in the form of a phototherapeutic implant that ubicates TLS in a position enabling long-term phototherapy for the eye's posterior segment. A plethora of ophthalmic devices may position the TLS to carry out this mission effectively.One category of ophthalmic devices is ocular lenses, which includes but is not limited to intraocular lenses 600 of FIG. 6 and phakic intraocular lenses (henceforth interchangeably referred to as implantable contact lenses and ICLs, an artificial collamer lens implanted between the iris and the front surface of a natural lens) 700 of FIG. 7. It's important to note that the term "ocular lens" applies to all types of lOLs and contact lenses. Other devices which may house TLS include transscleral implants (seeFIGS. 25A - 25D and 26A - 26C), lensless haptic structures 1800 of FIGS. 18A and 18B, "floating" intravitreal light sources, and attachments 1600 to existing ocular devices and implants as depicted in FIG. 16.The first embodiment of a light-emitting device platform for the reduction of retinal hypoxia is disclosed as follows. This embodiment is a foldable intraocular lens 600 of FIG. 6 (betaluminescent intraocular lens; BIOL) housing an arrangement of thin film TLS’s 500 of FIG. 5 each comprising a plurality of TLS’s 200.This arrangement is designed to deliver a constant, scotopic light dose to the patient's retina to lower retinal hypoxia. These thin film TLS have a higher miniaturization potential than the GTLS of the prior art. The prior art GTLS are too large (0.3 mm) to thin the contact lenses for intraocular implantation. The thin film TLS can be paper thin (typically 50 pm, but may be thinner or thicker), enabling a breakthrough for light source encapsulation in small geometries.In an embodiment for TLS fixation, various TLS may be embedded in a betaluminescent intraocular lens (BIOL) 600 in FIG. 6. As previously mentioned herein, certain prior art structures do not permit a BIOL as it relies on the use of bulky (0.3 mm) GTLS incompatible with rolled injection techniques often seen in cataract surgery.An intraocular lens, including a BIOL of the present invention, is based on the intraocular lenses used in cataract surgery. These intraocular lenses are made from biocompatible materials (e.g., DMA, siloxane, silicone hydrogels) and designed for insertion behind the cornea. BIOL materials may be rigid or flexible and are oxygen- permeable in most embodiments. So as not to impede the optic pathway, the TLS may be arrayed about the BIOL's periphery. In most embodiments of the invention, the TLS array (e.g., 400, 500 of respectiviely FIGS. 4 and 5) is embedded in the BIOL's haptics 622. In fringe embodiments of the invention, the TLS may be embedded in the BIOL's optic component 610 in a manner that does not block the optic pathway. This arrangement of TLS provides a scotopic light dose to the retina. To achieve the suppression of retinal metabolism while not affecting vision and / or sleep, the brightness of the BIOL may be tuned by varying the tritium content of each TLS unit. Additionally, the BIOL's output brightness may be tuned by varying the amount of TLS units encased in it. Furthermore, the thin film TLS may be arranged in a manner that promotes oxygendiffusion through the BIOL. The prior art contact lenses that use bulky GTLS do not afford these luxuries from an engineering design standpoint.In an embodiment for TLS fixation, various embodiments of the TLS, as described herein, may be embedded in a betaluminescent implantable contact lens 700 (BICL). See FIG. 7. ICLs are a device that serves as an alternative to glasses, laser eye surgery, and external contact lenses. ICLs are implanted between the eye's natural lens and the iris through rolled injection, much like lOLs. ICLs also have flexible haptic and optic components. Hence, in some embodiments of the present invention, TLS may be embedded in the BICL's haptic 710 of FIG. 7. In other embodiments, the TLS may be embedded in the BICL's optic component 720. The brightness of the BICL may be tuned by varying the tritium content of each TLS unit. Additionally, the BICL's output brightness may be tuned by varying the number of TLS units encased in it. Furthermore, the thin film TLS may be arranged in a manner that promotes oxygen diffusion through the BICL.In yet another embodiment of TLS fixation, a transscleral implant (see FIGS. 25A- 25D and 26A - 26C as further described below) is used as a platform for delivering phototherapy. This device is referred to as a "chandelier." Like a glaucoma drainage device, this device is inserted into the vitreous through an incision in the sclera. Transscleral fixation methods may include an internal retention seal, skirt, ring (see for example element 2512 in FIG. 25A), latch, an external plate or pad, the use of a suture 2541 of FIG. 25D through or around the device, biocompatible adhesive, or anchoring barbs or hooks that secure to the sclera. A combination of anchoring mechanisms can be used. For example, a combination of an internal seal and external plate can be used; the external plate being subsequently covered by the conjunctiva to mitigate against device infection. A "luminous body" protrudes through the incision and into the vitreous. The luminous body features an arrangement of TLSs, which deliver phototherapy to the posterior segment of the recipient’s eye. In one embodiment, the luminous body may be a solid protrusion (e.g., a rod or hemisphere) peppered with an array of TLSs. In other embodiments, the luminous body may be fully composed of TLS that are bonded together as "bulkheads" to form a "beehive" structure. This version of the luminous body may be a structure built from a solid body featuring an array ofencapsulated concavities containing the metal tritide and luminophore layers, such as in FIGS 2 - 4.In an embodiment 1700 of FIG. 17, the TLS may be embedded in an accessory to a separately indicated ophthalmic device. In some embodiments of the invention, the TLS 100 may be embedded in a clip 1600 as in FIG. 16 that is attached to an IOL or ICLs haptic of FIG. 17. FIG. 17 illustrates the attachment of a light-emitting clip 1600 to an IOL haptic 520. This attachment may be accomplished via arms 1610 (see FIG. 16) protruding from a TLS housing 1620. Arms 1610 form a feedthrough 1630, through which an IOL haptic may be fastened.In another embodiment 1800 (see FIGS. 18A and 18B), a lensless haptic may be fabricated for integration with an existing optic IOL or ICL lens. This device may be built as a hydrogel 1820 enclosing the TLS 100 mounted on a metallic wire 1810.Another embodiment of the invention ubicates the TLS inside of the eye without piggybacking on a separately indicated device or being mounted on the sclera. Alternatively, a device featuring a luminous body and haptic components for anchoring it may be implanted inside of the eye and fixed to or between various ocular structures, whose locations are indicated in FIG. 30.In one embodiment of the invention, a plurality of TLSs are joined to form a luminous body as previously described. The luminous body 3030 of FIG. 30 is suspended in the eye (e.g., the vitreous, the ciliary body) by a plurality of haptic fixtures (e.g., sutures, nitinol wire) that anchor on ocular anatomy (e.g., ciliary body).In yet another embodiment of the present invention, the TLSs are introduced to the eye as "floaters." These may be introduced as singular, microscopic TLS units or as "lumi-spores" of grouped TLSs. Floaters and lumi-spores 3010 (see FIG. 30) may be introduced to various areas in the eye, including but not limited to the vitreous body and the aqueous body. See element 3010 of FIG. 30 as an example of this embodiment's ubication.In another embodiment of the invention, a TLS may be fixed in the aqueous body. This is presented as element 3020 of FIG. 30.In FIG. 5:Reference numeral 500 represents an array of TLS’s as in FIG. 5;Reference numeral 2510 represents a TLS element as described in FIG. 25 A;Reference numeral 700 represents an implantable contact lenses, also referred to as an ICL;Reference numeral 2900 refers to betaluminescent contact lens.A non-invasive embodiment of the present invention takes the form of a betaluminescent contact lens 2900 (BCL) of FIG. 29A and 29B may be designed according to these teachings. These may be made from flexible or rigid, gas-permeable materials (e.g., silicone hydrogels, HEMA hydrogels); the BCL will contain an arrangement of TLSs, as illustrated in FIG. 4 and FIG. 5, for example. However, in this device, the TLS may be arranged in line with the optic pathway. This is because the BCL will be situated in front of the pupil, necessitating that its light-emitting element (the TLS array) be positioned to emit light through the pupil and into the optic pathway to irradiate the retinal rods. In this embodiment, the BCL may be worn overnight as the patient sleeps, meaning any visual obstruction the BCL may provide will not hinder patient function throughout the day. However, the thin film TLS' smaller size (as compared to the GTLS) enables the design of a spaced-out pattern that yields a functional degree of patient vision. Such a spaced-out pattern is also conducive to oxygen diffusion through artificial lenses and into the eye. Like in the BIOL, the BCL's light intensity may be tuned to deliver a biologically effective dose. Thin film TLS lends the BCL many of the same advantages as prior art, as seen in BIOL.Phototherapeutic lens platforms previously discussed in the art (e.g., BIOL, BICL, BCL) will be manufactured using a variety of materials (e.g., polydimethylsiloxane, silicone hydrogels, pHEMA hydrogels). Material choice affords the lenses biocompatibility, ease in implantation, and oxygen transmissivity. Adequate oxygen transmissivity is vital for retinal oxygenation. The lenses may be manufactured through processes including but not limited to injection molding, 3-D printing, lathe cutting, cast molding, and spin casting. This lens may also be polished through processes such as lathing.In some embodiments of the invention (such as the BCL embodiment 2900 in FIGS. 29A and 29B), the lens may be fabricated in two halves — an upper half 2910 anda lower half 2920. The upper half 2910 may first be fabricated in a two-part injection mold (mold 1 ), where a choice hydrogel is injected and polymerized via heat treatment. Mold 1 's bottom face is convex, and the top face is concave. Certain embodiments of mold 1 may feature protrusions on its top face, designed with the shape, arrangement, and form factor of the thin film TLS array 600 of FIG. 6 or the array 700 of FIG. 7. This will result in the upper half 2910 featuring an embossed array of "sockets" for the thin film TLS 100 (see FIG. 1) to be laid in during assembly.In other embodiments, the TLS array is laid on a non-embossed upper half 2910 and have the lower half 2920 formed around the array 400 / 700 and the lower half 2920, as described below. With array 400 / 700 laid onto the upper half 2910, it may be placed in a second mold (mold 2). Mold 2's bottom face is convex and identical in form factor to mold 1 's bottom face. However, mold 2's top face is concave and expanded away from the bottom face. With the upper half 2910 and the array 400 / 700 placed in mold 2, there exists a "headspace" between those components and mold 2's top face. This volume is then filled with the hydrogel of choice and polymerized, forming the lower half 2920 and enclosing the array 400 / 700 between the upper half 2910 and the lower half 2920. When removed from mold 2, the betaluminescent lens is complete. In some embodiments, the lens may then be subjected to polishing (e.g., lathing) processes.In various embodiments of the invention, it may be useful to incorporate mechanisms, separate from the metal tritide-luminophore coupling, that inform the brightness of the TLS. The following paragraphs discuss mechanisms that may accomplish this.With reference to FIG.S 9A and 9B , in one embodiment of the invention, the TLS headspace (bounds defined by glass 920 and substrate 970) may be filled with an attenuating medium 940 (e.g., Argon, Xenon) that absorbs some beta flux 950 from the metal tritide 960. The density of the attenuating medium informs how many beta emissions reach the phosphor 930, which in turn informs the amount of photons 910 emitted by the TLS. Over the device's lifetime, the gas of the attenuating medium 940 will diffuse out of the TLS (decreasing gaseous beta absorption and thereby increasing the TLS efficiency) as the tritium in the device decays (lessening brightness). The TLS' tritium content and gas diffusion may be designed to control the brightness of the deviceover the course of its lifetime, increasing its reliability or variability. FIG. 9B depicts the reduced amount of the attenuating medium 940 after about 12 years from the state at the time of FIG. 9A.In another embodiment of the invention (see FIGS. 11 A and 11 B), the TLS (bounds defined by glass 1130 and substrate 1170) may feature an optically inhibitive layer (e.g., polymer) that has a designed level of opacity that inhibits the effective brightness of the TLS. As beta flux 1150 emitted from the metal tritide 1160 strikes the luminophore 1140, photons of varying wavelengths are emitted. In some embodiments the optically inhibitive layer 1120 contains a pigment that attenuates photons of a designed wavelength 1112, while letting photons with a different wavelength 1111 pass through it. This layer will be designed to be resorbed over the device's lifetime, allowing more of the previously attenuated photons 1112 to pass through. In some embodiments, the layer is internal to the device and may be degraded through the absorption of tritium beta emission or by a designed chemical reaction. In other embodiments, the inhibitive layer is bioresorbable and conformally coated on the TLS packaging or the parent device (e.g., IOL / ICL haptics). This coating may be resorbed and uniformly thinned over time, as illustrated by FIG. 11 B. See the thinning of layer 1120 between the time of FIG. 11 A and 11 B.In another embodiment, (see FIGS. 12A and 12B) the TLS (bounds defined by glass 1230 and substrate 1270) features an optically inhibitive coating 1220, which is additively or subtractively peppered with non-coated gaps or indentations in FIG. 12A. As beta flux 1250 emitted from the metal tritide 1260 strikes the luminophore 1240, photons of varying wavelengths are emitted. The optically inhibitive coating 1220 absorbs photons 1212 of a designed wavelength and allows for photons 1211 of a designed wavelength to pass through it. The coating is resorbed by the environment 1280, and the indentations increase in size over time (see FIG. 12B). As the indentations increase in depth and width, previously inhibited photons 1212 find paths to exit the TLS, increasing its effective brightness.In another embodiment of the invention (see FIGS. 10A and 10B) , the TLS (bounds defined by glass 1030 and substrate 1070) may feature an optically inhibitive layer (e.g., polymer) that inhibits the effective brightness of the TLS. As beta flux 1050emitted from the metal tritide 1060 strikes the luminophore 1040, photons of varying wavelengths are emitted. In some embodiments (see FIG. 10A), the optically inhibitive layer 1020 contains a pigment 1090 that attenuates photons of a designed wavelength 1012, while letting photons with a different wavelength 1011 pass through it. The pigment contained 1090 may be designed to leech out of the inhibitive layer 1020 into the environment 1080, decreasing the attenuation of photons 1012 that exit the TLS. See FIG. 10B.Lastly, in embodiment 800 (see FIGS. 8A and 8B), the TLS (bounds defined by glass 820 and substrate 860) brightness is temporally defined by tritium's half-life (12.3 years). As time goes on, tritium decay of the metal tritide layer will reduce beta flux 840 that strikes the luminophore 830, as there are fewer tritium atoms 850 on board. Hence, the effective number of photons 810 produced by the TLS is halved every 12.3 years. See FIG. 8B.In other embodiments of the invention, the TLS may instantaneously be turned "on" and "off." In one such embodiment, the TLS is coated with or contains a film that contains liquid crystals (much like switchable Privacy Glass). This liquid crystal film is electrically connected to a piezoelectric power converter. This piezoelectric power converter is mechanically coupled to ocular anatomy that contracts in response to ambient light level (e.g., ciliary body, iris, pupil) such that when the eye light adapts, the film is opacified, and when the eye dark adapts, the film becomes translucent. In other embodiments, the piezoelectric power converter may be interrogated by an external stimulus, like an ultrasonic transducer mounted on glasses, a probe, or another interface.In another embodiment of the invention, an "on-off" mechanism may be introduced by way of external magnetic interrogation. In this embodiment, magnetic nanoparticles may be integrated with the TLS such that a designed magnetic field (applied by an external device) pulls them in line with the TLS, obstructing light emanating from them.FIGS. 28A, 28B, and 28C describe another embodiment of the invention 2800, in which an "on-off" mechanism is introduced by way of mechanically separating the beta source 2811 from the TLS' luminophores 2815. In embodiment 2800, the betasources 2811 are magnetic and housed in a glass package 2814. An external magnetic input 2816 may be applied to the TLS, separating beta sources 2811 from the luminophores 2815 (also housed in glass package 2814). This reduces the number of beta electrons 2812 that successfully strike the luminophores 2815, therefore reducing the number of photons 2813 emitted from the TLS.In another embodiment of the invention, the TLS may feature an "on-off" mechanism governed by the contraction of the eye's anatomy. This design would ensure that TLS light output is informed by the dark or light-adapted state of the eye.In another embodiment of the invention, a mechanical aperture can be incorporated. Although the following example pertains to an embodiment comprised of TLS contained within a device that is accessorial and mounted to a separately indicated IOL, a mechanical aperture may be engineered for other device platforms previously discussed in the art. In this embodiment, an aperture or "sliding door" is placed between the TLS contained in the accessorial device (e.g., mounted on an IOL haptic) and the phototherapeutic target anatomy (e.g., the retina). This aperture / sliding door is mechanically engineered to be pulled open by the dilation of the eye during dark adaptation, as well as to be pushed closed by the contraction of the pupil during light adaptation. This conceals light dose while the patient is not in a dark environment.In yet another embodiment, an "on-off" switch may be incorporated with the TLS by the coating of a photochromic polymer (akin to transition lens material). In light- adapted conditions, the photochromic polymer coated on the TLS will opacify, inhibiting light dose emitted from the TLS. In dark-adapted conditions, the TLS' light dose is uninhibited by the then-transparent photochromic polymer, propagating to the target anatomy (e.g., the retina).In another embodiment of an "on-off" switch, the TLS is implanted in the aqueous body. In an embodiment 2710, a TLS 100 is mounted on the end of a flexible (e.g., nitinol) wire 2712 of FIG. 27A, which protrudes from a rigid mounting mechanism 2713, which may be a hemispherical ring circumventing the iris or pupil. The previously mentioned flexible wire features one or more magnetic receivers 2711. In this embodiment, a magnetic field induced by a magnet 2721 (see also FIGS, 27B and 27C)may be applied to the device, applying a force to 2711 , thereby causing the wire2712 to bow, repositioning the TLS 100. When, as shown in embodimemnt 2720, the magnetic field or the wire's shape memory is used to pull the TLS out of line with the optic pathway, the device is in an "off." When, as shown in embodiment 2710, the TLS is in line with the optic pathway, the device is "on." Magnets 2721 are illustrated in FIG. 27C.In one prior art embodiment, a GTLS is disposed in the vitreous in a "chandelier" style implant. This implant is fashioned in a style similar to a glaucoma drainage device, which is implanted through an incision at the pars plana. TLS of the present invention, of a much smaller size than a GTLS, may be fashioned to be implanted in a similar, transscleral manner. In such an embodiment, the TLS may be formed on the surface of an object inserted through the pars plana, such as a cylinder, hemisphere, toroid, or varyingly shaped body.A TLS-based chandelier implant may feature a plethora of variations on this prior art design, which are described as follows:FIGS. 25A - 2D illustrate versions of an improved TLS-based chandelier implant. This chandelier-style TLS implant may feature one or multiple eyelets 2512 on a TLS carier 2511 (see FIG. 25A) and / or a holster to which the TLS is mounted. These eyelets enable fixation via a knotted suture 2544. Element 2510 (FIG. 25A) is a TLS with a single, symmetrical eyelet 2511 fabricated coaxial to the TLS. Element 2520 (FIG. 25B) is a TLS featuring two opposed eyelets 2522 on the TLS's curved face 2521 . Element 2530 (FIG. 25C) comprises a TLS 2531 inserted into a holster 2533 bearing two horizontally opposed, downward-facing eyelets 2532. Element 2540 (FIG. 25D) comprises a TLS 2541 inserted into a holster 2543 featuring two horizontally opposed, downward-facing eyelets 2542, and a dome-like cavity 2544. The dome-like cavity 2544 is utilized as a space in which a suture knot 2544 may be tucked during the insertion of the chandelier implant. This approach minimizes contact between foreign bodies and ocular / orbit tissue.Certain prior are GTLS chandelier implants did not feature patient customizability. An improved embodiment of a chandelier-styled TLS implant 2600 features the insertion of the TLS into a holster 2613 featuring a mechanical joint 2612, 2611 (e.g., hinges, ball joint) (see FIG. 26A) The TLS's angle 2621 may be adjustedand fixed at a desired angle. This feature allows the surgeon case-by-case tunability to vary the TLS' emitted light distribution, as well as any optical obstructions the TLS may cause.The embodiments depicted by FIGS. 26A - 26C include features that mitigate inefficiencies in phototherapy due to the dissipation of light onto non-target anatomy. Non-therapeutic light may be redirected to the target anatomy (e.g., retina, photoreceptors) by an additional optical feature, such as a reflective, metalized dome 2614 of FIG. 26A. Such reflective domes may be designed to concentrate all light emanated by the TLS 2511 into a cone 2615, 2617 (see FIG. 26B) that is directed at the target anatomy. The designed propagation of phototherapeutic light may be synergistically informed by both a reflector and the previously mentioned dynamic chandelier fixation device 2612.In some embodiments of the present invention, one or more TLS or miniature TLS bulkheads may be fixed in a plane secant to the sclera. This may be achieved through a plurality of transscleral incisions, through which mounting components are inserted. The light source is suspended by these mounting components, staying far from the optic pathway. This also reduces the length of the light source as a moment arm suspended in the vitreous, reducing its proclivity to cock in response to the eye's rotation.Some embodiments of the present invention use a bioadhesive to fix the TLS to ocular anatomy. Other embodiments may incorporate a textured surface, which promotes cell adhesion as a mode of device fixation.In another embodiment of the present invention, the TLS is coated with a photo- ablateable material that may be actively removed (e.g., laser ablation), modifying the device's light output. This enables physicians to compensate for tritium decay and phosphor degradation or to tune the light output of the device to achieve a desirable dose to the patient. In practice, this approach may be informed by electroretinography and / or other biometrics to determine the correct light dose for a patient.In some cases, recipients of implanted phototherapy devices may experience glare as a side effect of their phototherapy. This is especially true for patients who have also received other ophthalmic implants (e.g., multifocal lOLs). This phenomenon mayimpair the patient's ability to drive at night. To combat this effect, recipients of phototherapeutic implants may wear smart glasses (e.g., Apple Vision Pro, a trademark of Apple, Inc. Cupertino, CA. ) or night vision goggles to boost the brightness of the perceived scene to photopic light levels akin to those received in daylight. These light levels are orders of magnitude higher than night driving light levels, canceling all perception of the implanted light source as per Weber's law. In the future, self-driving cars may absolve the need for such corrective measures.Diabetic retinopathy manifests in a variety of ways across the retina, largely due to its anatomy. The peripheral retina is less oxygenated than the macula due to its relative lack of vasculature. In a patient with diabetic retinopathy, this makes the peripheral retina more hypoxic than the macula, making it the main expressor of intraocular VEGF. Therefore, there's a strong incentive to include a feature that directs phototherapy to the peripheral retina. Such a design is elegant as the peripheral retina is primarily responsible for peripheral, low-fidelity vision, while the macula is responsible for central, high-fidelity vision. Hence, by limiting phototherapy to the peripheral retina, any side effects associated with phototherapy will only be seen in the patient's peripheral vision.An embodiment of a transscleral implant that limits phototherapy to the peripheral retina is that of a TLS mounted on the sclera, with the TLS protruding into the vitreous. A portion of the TLS may be covered by an attachment, affecting the shape of the light cast onto the retina. One such configuration of this embodiment is that of an opaque sleeve that slips onto a cylindrical TLS. This device will cast light in a toroidal shape onto the retina, directly illuminating only the peripheral retina.Embodiments of the invention comprising ocular lenses containing TLS may also be designed to selectively illuminate the retina. This may be accomplished through the addition of a collimator on the TLS, which will cause light emitted to illuminate a small, defined region of the target anatomy. For example, light emitted by each TLS in an array confined to an lOL's haptics may be collimated to form an annular pattern of illuminated "dots" about the peripheral retina.Light from the phototherapeutic device can be distributed towards the periphery of the eye by etching an angled pattern into the substrate prior to metallization, tritidegeneration, and addition of phosphor. This mitigates against loss of contrast sensitivity for central vision during low light or mesopic activities like night driving.With reference to FIGS. 31 and 32. light from the phototherapeutic device can be distributed towards the periphery of the eye by forming an angled pattern into the substrate 3100, such as pyramids or trenches 3110 and metalizing 3120 tritium loading, and adding phosphor 3130 to these vertical faces. The device can be hermetically sealed or coated 3140.This design of the light source mitigates against loss of contrast sensitivity for central vision during low light or mesopic activities like night driving. More light is directed to the outer periphery of the retina as indicated by arrowhead 3150 and midperiphery as indicated by arrowhead 3160 than light is directed to the central area of the retina as indicated by arrowhead 3170 of the eyeball 3180.Light from the phototherapeutic device can be distributed towards the periphery of the eye by etching vertical or near vertical features into the substrate 3200 (see FIG. 32), such as fins, slats, columns, or prismatic shapes 3210) and metalizing (element 3220), tritium loading, and adding phosphor 3230 to these vertical faces. The device can be hermetically sealed or coated with elements 3240. This design of the light source mitigates against loss of contrast sensitivity for central vision during low light or mesopic activities like night driving. More light is directed to the outer periphery of the retina 3250 and mid-periphery 3260, with less light directed to the central area of the retina 3270 of the eyeball 3280.The present invention further includes various methods associated with the TLS devices of the present invention.A method for implanting a TLS for the purposes of phototherapy may involve creating the TLS, affixing it to an ocular device, loading it into an insertion device, using the insertion device to implant the TLS into the eye, and allowing fixturing components to deploy.Affixing of the TLS to the ocular device may be conducted prior to the surgery, and the device may be loaded into an insertion device prior to surgery, such as in a ready-to-use phototherapy kit.In the case of a corrective lens, the TLS may be affixed to a standard or a custom fabricated lens. Alternatively, the TLS may be affixed to the ocular device at the time of surgery either under a sterile field or followed by a seterilization step.As described herein, the invention presents a novel and non-obvious method for the management of diabetic retinopathy in patients with comorbid cataracts or at risk for cataracts. The method involves initially screening patients for risk factors for diabetic retinopathy and / or cataracts. Risk factors for cataracts include age, sunlight exposure, family history, having diabetes, duration of diabetes, A1 C levels, high blood pressure, eye injuries or surgeries, medications, smoking and alcohol, obesity, and nearsightedness.Risk factors for diabetic retinopathy include diabetes duration, blood sugar control, blood pressure, cholesterol, race, pregnancy, tobacco use, obesity, and other medical conditions. In patients needing or predicted to need cataract surgery in the near future, and those at risk of developing diabetic retinopathy, it is suggested to implant a phototherapeutic IOL. And thereafter monitor the patient for diabetic retinopathy development or progression. If the retinopathy progresses, supplement the phototherapy with appropriate therapeutic interventions. The phototherapeutic IOL may provide prophylactic effect, extend the duration between anti-VEGF injections, and / or remediate the diabetic retinopathy.The present invention also includes a method to ensure the stability and long term effectiveness of the phototherapy treatment by measuring the patients ERG (electroretinography) prior to phototherapy to establish a baseline. Illumination of the retina under dark adaptation can be performed to establish a patient-specific relationship between the ERG signals and light intensity. An appropriate TLS phototherapy device is then selected for the patient based on the necessary illumination to adequately suppress rod metabolism using the ERG signal data.Following implantation of the TLS phototherapy device, an ERG is performed to verify that the desired level of rod suppression has been achieved. If the level is insufficient, the brightness of the TLS may be increased (e.g. through laser ablation of an attenuating film or repositioning the TLS) or an additional TLS may be implanted.The ERG may be re-measured at subsequent visits to ensure adequate rod suppression and the TLS brightness can be tuned as necessary.The invention also relates to a method to reduce the impact of implantable photerapy on activities performed under low-light conditions by the user putting on smart glass, night vision goggles, or a vision enhancing headset. These devices boost the perceived brightness of the visual field thereby overcoming the background illumination of the phototherapy implant that can otherwise reduce visual perception, contrast sensitivity, and visual acuity. The wearer is then able to more easily carry out low-light activities, such as night driving.

Claims

WHAT IS CLAIMED IS:1 . A phototherapeutic eye apparatus, comprising: a solid state beta flux source for emitting beta particles; and a luminophore material in contact with or proximate the solid state beta flux source, the luminophore material for receiving the beta particles and responsive thereto for emitting photons that escape the phototherapeutic eye apparatus.

2. The phototherapeutic eye apparatus of claim 1 , further comprising a substrate on which the solid state beta flux source and the luminophore material are disposed and an encapsulating material hermetically sealing the phototherapeutic eye apparatus.

3. The phototherapeutic eye apparatus of claim 2 wherein the encapsulating material comprises glass.

4. The phototherapeutic eye apparatus of claim 2, wherein the substrate defines a depression, and wherein the luminophore material comprises a plurality of luminophore granules disposed within the depression.

5. The phototherapeutic eye apparatus of claim 1 , wherein the luminophore material comprises phosphor, zinc sulfide, a crystalline luminophore, or yttrium oxide, each one doped with silver chloride, gold, or aluminum, and wherein the luminophore material further comprises a luminophore powder or a luminophore film.

6. The phototherapeutic eye apparatus of claim 1 , wherein the luminophore material emits visible light with a wavelength of between 400 and 600 nm.

7. The phototherapeutic eye apparatus of claim 1 , wherein the solid state beta flux source comprises a metal film hydrogenated with tritium or comprises an organic molecular substance hydrogenated with tritium, the organic molecular substance further comprising 1 ,4-bis(phenylethynyl)benzene (DEB) or 1 ,4- diphenylbutadiyne (DPB).

8. The phototherapeutic eye apparatus of claim 1 , wherein the solid state beta flux source comprises a solid state beta flux source film or solid state beta flux source granules.

9. The phototherapeutic eye apparatus of claim 1 , wherein the solid state beta flux source comprises a metal film or a metal lattice with tritium disposed within the metal film or within the metal lattice.

10. The phototherapeutic eye apparatus of claim 9, wherein a material of the metal film or the metal lattice comprises titanium, scandium, magnesium, palladium, yttrium, ytterbium, or an alloy comprising one or more of titanium, scandium, magnesium, palladium yttrium, or ytterbium.1 1. A thin film phototherapeutic eye apparatus comprising the phototherapeutic eye apparatus of claim 1 , wherein a shape and ubication of the thin film phototherapeutic eye apparatus are achieved by photolithographic processing of the solid state beta flux source and the luminophore material.

12. The phototherapeutic eye apparatus of claim 1 , having a volume of less than 1 .0 mm3.

13. The phototherapeutic eye apparatus of claim 1 , having a volume of less than 0 .1 mm3.

14. The phototherapeutic eye apparatus of claim 1 , further comprising an attenuating medium for absorbing beta flux and thereby reducing illumination generated by the phototherapeutic eye apparatus.

15. The phototherapeutic eye apparatus of claim 14, wherein attenuation is controllable.

16. The phototherapeutic eye apparatus of claim 1 , further comprising a medium for attenuating photons emitted from the luminophore and thereby reducing illumination generated by the phototherapeutic eye apparatus.

17. The phototherapeutic eye apparatus of claim 16, wherein the medium for attenuating photons is wavelength selective.

18. The phototherapeutic eye apparatus of claim 16, wherein a magnitude of attenuation decreases with time.

19. The phototherapeutic eye apparatus of claim 1 , further comprising a material layer having a controllable or changeable opacity for controlling an amount of illumination provided by the photons.

20. The phototherapeutic eye apparatus of claim 1 , disposed in an intraocular device, or in a haptic of the intraocular device, or in a contact lens, or in a transscleral chandelier, or in an implantable contact lens, or in an implantable collamer lens.21 . An ocular device for implanting in an eye or for embedding in an implantable or extraocular device, the ocular device comprising a plurality of the phototherapeutic eye apparatuses of claim 1 .

22. The ocular device of claim 21 , wherein a number of the plurality of the phototherapeutic eye apparatuses is selected based on a desired brightness of light generated by photons that escape the phototherapeutic eye apparatus.

23. An intraocular or extraocular device comprising a plurality of the phototherapeutic eye apparatuses of claim 1 , the intraocular or extraocular device located to selectively illuminate an area of the retina or the entire retina.

24. A contact lens or an intraocular lens comprising a plurality of the phototherapeutic eye apparatuses of claim 1 located on or within the contact lens or the intraocular lens.

25. The contact lens or the intraocular lens of claim 24, wherein the plurality of phototherapeutic eye apparatuses are circumferentially, radially, or rectangularly disposed on the contact lens or the intraocular lens.

26. An intraocular lens, a phakic intraocular lens, an implantable collagen or collamer lens, a transscleral implant, a lens-less haptic structure, or a floating intravitreal comprising a plurality of the phototherapeutic eye apparatuses of claim 127. The phototherapeutic eye apparatus of claim 1 , wherein a tritium content of the solid state beta flux source is determined to control a number of photons emitted by the luminophore material.

28. The phototherapeutic eye apparatus of claim 1 , further comprising an attenuating medium disposed between the solid state beta flux source and the luminophore material, wherein a density of the attenuating medium determines a number of beta particles that reach the luminophore material.

29. The phototherapeutic eye apparatus of claim 1 , further comprising a layer or coating disposed between the solid state beta flux source and the luminophore material, the layer or coating attenuating beta flux.

30. The phototherapeutic eye apparatus of claim 1 , further comprising a material layer or mechanical device controlled by an ocular anatomy component that contracts in response to an ambient light level, such that when the eye light-adapts the material layer is opacified, and when the eye dark-adapts the material layer is translucent.31 . The phototherapeutic eye apparatus of claim 1 , further comprising a plurality of liquid crystals controlled by a piezoelectric converter, the piezoelectric converter controlled by an ocular anatomy component for generating a current to control the liquid crystals in response to an ambient light level, such that when the eye light- adapts the plurality of liquid crystals is opacified, and when the eye dark-adapts the plurality of liquid crystals is translucent.

32. The phototherapeutic eye apparatus of claim 1 , having a thickness of 250 pm or less.

33. The phototherapeutic eye apparatus of claim 1 , for implanting in an eye, wherein when implanted in the eye the luminophore material is deposited on surfaces of the apparatus directed away from a macula of the eye.

34. The phototherapeutic eye apparatus of claim 1 , for implanting in an eye, wherein when implanted in the eye the photons emitted from the luminophore material are directed toward a peripheral region of a retina.

35. The phototherapeutic eye apparatus of claim 1 , wherein the solid state beta flux source comprises a metal tritide, the phototherapeutic eye apparatus further comprising a substrate on which the metal tritide and the luminophore material are disposed, wherein an effective surface area of the substrate is determined to provide additional surface area for the metal tritide or the luminophore material.

36. The phototherapeutic eye apparatus of claim 35, wherein the additional surface area is provided by micromachining, embossing, etching, electrospinning, coating with microparticles or nanoparticles, electrochemical roughening, abrasion, leaching, or a metal-organic framework.

37. The phototherapeutic eye apparatus of claim 1 , further comprising an attenuating medium for absorbing beta flux and thereby reducing illumination generated by the phototherapeutic eye apparatus, wherein the attenuating medium comprisesargon or xenon, and wherein a density of the attenuating medium informs a number of beta particles that reach the luminophore material.

38. The phototherapeutic eye apparatus of claim 1 , further comprising a device for directly or indirectly switching illumination provided by the photons between an “on” state and an “off” state.

39. The phototherapeutic eye apparatus of claim 1 , further comprising a photo-ablateable material disposed proximate or in contact with the solid state beta flux source, wherein the photoablateable material is removable to modify a number of beta particle emissions from the solid state beta flux source and thereby a number of photons emitted from the luminophore material.

40. A method for forming the phototherapeutic eye apparatus of claim 1 , comprising: applying a solid state beta flux source for emitting beta particles to a substrate; and applying a luminophore material overlying the solid state beta flux source, the luminophore material for receiving the beta particles and responsive thereto for emitting photons that escape the phototherapeutic eye apparatus.41 . A method to reduce effect of an implanted phototherapeutic eye apparatus of claim 1 on a patient during performance of low-light activities, the method comprising, wearing smart glasses, night vision goggles, or a vision enhancing headset when performing low light level activities.

42. A phototherapeutic eye apparatus, comprising: a solid state beta flux source film for emitting beta particles, wherein a thickness of the film is 50 pm or less; and a luminophore material in contact with or proximate the film, the luminophore material for receiving the beta particles and responsive thereto for emitting photons that escape the phototherapeutic eye apparatus43. A method for implanting a phototherapeutic intraocular lens into an eye, comprising: forming a solid state beta particle source;placing a luminophore material proximate or in contact with the beta particle source; affixing the beta particle source and luminophore material to an intraocular lens; loading the intraocular lens into an insertion device; implanting the insertion device into the eye; and configuring the intraocular lens into a final position within the eye.

44. The method for implanting a phototherapeutic intraocular lens of claim 43, further comprising, affixing a corrective lens to the intraocular lens.

45. A method for managing diabetic retinopathy in comorbid patients with cataracts, the method comprising: determining that a patient has diabetes and cataracts; implanting a phototherapeutic eye apparatus into an eye of the patient, wherein the phototherapeutic eye apparatus comprises a solid state beta particle source and a luminophore material for receiving beta particles from the beta particle source and for emitting photons in response thereto; monitoring the patient for onset of diabetic retinopathy; and modifying the phototherapeutic eye apparatus responsive to the diabetic retinopathy.

46. A method for maintaining long term stability of a phototherapy treatment, comprising: measuring a patient’s electroretinography (ERG) prior to beginning phototherapy to establish an electroretinography baseline; illuminating a retina under dark adaptation conditions to establish a patientspecific relationship between the electroretinography and light intensity; implanting a phototherapeutic eye apparatus in an eye of the patient, the phototherapeutic eye apparatus comprising a solid state beta particle source and a luminophore material for receiving beta particles from the beta particle source and for emitting photons in response thereto; remeasuring the patient’s electroretinography to ensure sufficient rod suppression; andif light provided by the phototherapeutic eye apparatus is too dim to suppress rod metabolism, increase the number of emitted photons.

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