US20070182917A1 - Intra-ocular device with multiple focusing powers/optics - Google Patents

Intra-ocular device with multiple focusing powers/optics Download PDF

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Publication number
US20070182917A1
US20070182917A1 US11/350,437 US35043706A US2007182917A1 US 20070182917 A1 US20070182917 A1 US 20070182917A1 US 35043706 A US35043706 A US 35043706A US 2007182917 A1 US2007182917 A1 US 2007182917A1
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United States
Prior art keywords
lens
power
denotes
optic
vision
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Abandoned
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US11/350,437
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English (en)
Inventor
Xiaoxiao Zhang
Richard MacKool
Xin Hong
Michael Southard
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Alcon Inc
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Alcon Manufacturing Ltd
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Publication date
Application filed by Alcon Manufacturing Ltd filed Critical Alcon Manufacturing Ltd
Priority to US11/350,437 priority Critical patent/US20070182917A1/en
Assigned to ALCON MANUFACTURING, LTD. reassignment ALCON MANUFACTURING, LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HONG, XIN, MACKOOL, RICHARD J., ZHANG, XIAOXIAO, SOUTHARD, MICHAEL A.
Priority to CA2576029A priority patent/CA2576029C/en
Priority to DE602007000646T priority patent/DE602007000646D1/de
Priority to ES07101409T priority patent/ES2323092T3/es
Priority to AT07101409T priority patent/ATE424787T1/de
Priority to EP07101409A priority patent/EP1818023B1/en
Priority to AU2007200556A priority patent/AU2007200556B2/en
Priority to JP2007030089A priority patent/JP4598783B2/ja
Publication of US20070182917A1 publication Critical patent/US20070182917A1/en
Assigned to ALCON RESEARCH, LTD. reassignment ALCON RESEARCH, LTD. MERGER (SEE DOCUMENT FOR DETAILS). Assignors: ALCON MANUFACTURING, LTD.
Assigned to ALCON, INC. reassignment ALCON, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ALCON RESEARCH, LTD.
Priority to US12/776,807 priority patent/US8262728B2/en
Abandoned legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/14Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • A61F2/16Intraocular lenses
    • A61F2/1613Intraocular lenses having special lens configurations, e.g. multipart lenses; having particular optical properties, e.g. pseudo-accommodative lenses, lenses having aberration corrections, diffractive lenses, lenses for variably absorbing electromagnetic radiation, lenses having variable focus
    • A61F2/1654Diffractive lenses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/14Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • A61F2/16Intraocular lenses
    • A61F2/1613Intraocular lenses having special lens configurations, e.g. multipart lenses; having particular optical properties, e.g. pseudo-accommodative lenses, lenses having aberration corrections, diffractive lenses, lenses for variably absorbing electromagnetic radiation, lenses having variable focus
    • A61F2/1616Pseudo-accommodative, e.g. multifocal or enabling monovision
    • A61F2/1618Multifocal lenses

Definitions

  • the invention relates to a vision aid for the amblyopic population, inclusive of patients with age-related macular degeneration (AMD) or other low vision conditions.
  • the vision aid is an intra-ocular lens (IOL) device that has multiple focusing powers or optics.
  • AMD patients often have compromised fovea.
  • these functional retina receptors are often peripherally located and have larger spacing between each other. The increase spacing leads to decreased image resolution ability of the retina. For example, at 3 degrees nasal retina, the visual acuity is reduced to 0.4 compared to the 1.0 visual acuity at 0 degrees; at 5 degrees nasal retina, the visual acuity is reduced to 0.34 compared to the 1.0 visual acuity at 0 degrees (Millodot, 1966).
  • the first type is a single telescope as the visual aid.
  • the telescopes are often mounted on the spectacles, which are heavy and are not appealing cosmetically. Implanted telescopes often require very large incisions during surgery to implant.
  • the main disadvantage of using a telescope system alone is the resultant narrow visual field of view and overall poor image quality, which could cause a safety concern during motion.
  • the second type of vision aid is a prism.
  • the prism is to realign the line of sight to the peripheral retina. This application needs to overcome a binocular fusion problem in order to avoid double imagery. Also, the prism does not magnify the retinal images. Therefore, the problem of low visual resolution due to the larger peripheral retina receptor spacing is not resolved.
  • the third type of vision aid is a magnifying glass, sometimes combined with a prism.
  • This visual aid is often used as a desk mount device, which limits the application range for patients.
  • the handheld version of this visual aid has vision instability and focus problems for patients with hand tremors.
  • FIG. 1 shows Peripheral Visual Acuity from Bennett and Rabbetts “Clinical Visual Optics” page 37, Butterworth, Boston, 1984.
  • FIG. 1 It is known that the peripheral vision can still provide adequate resolution.
  • the resolution is progressively reduced ( FIG. 1 ).
  • visual acuity is reduced to 0.5 at 2 degrees nasally, to 0.4 at 3 degrees nasally, to 0.34 at 5 degree nasally, relative to the 1.0 visual acuity at 0 degrees.
  • Temporal, superior and inferior peripheral retinas are expected to have similar behavior at similar small degree off axis range. Accordingly, increasing or magnifying retina image size relative to the size associated with 14 inches reading distance could allow the peripheral retina to effectively resolve small text and objects comparable to what normal eyes can do with central 0 degrees retina.
  • the magnification could be 2 times for using 2 degrees peripheral retina, 2.5 times for using 3 degrees peripheral retina, or 3 times for using 5 degrees peripheral retina.
  • ReSTOR® lens optics Bifocal and multifocal optics are well known in the ophthalmic optics field. Alcon's ReSTOR® lens optics is an example. However, existing ophthalmic bifocal or multifocal optics have much lower add power by design because they are obligated to suit different patient needs.
  • the ReSTOR® lens has a 4 D IOL add power which is likely the highest add power known for commercially available products. Table 1 indicates that with a 4 D add power the magnification is only 1.2 times. That 1.2 times. value is not likely to be adequate for AMD application according to the needs shown in FIG. 1 . That is, 1.2 times magnification is only useful if the 0.5 degrees retina is not damaged by AMD.
  • One aspect of the invention pertains to a bifocal or multifocal IOL or system that provides at least two focusing powers or optics systems. While providing the distance power for normal wide visual field needs of AMD and other low vision patients, the IOL of the present invention enables such patients to focus reading materials at near distances by employing surface modulations in zone structure, preferably modulations is a diffractive zone structure resembling a series of ring configurations of increasing diameter.
  • Such near distances lead to clear retina images that are magnified larger than 1.2 times of those normal reading retinal images associated with reading distance of about 14 inches.
  • the near distance power leads to clear retina images that are magnified to 2-3 times of the normal reading retinal images.
  • Reading needs of AMD patients can be met with the invention preferably by bringing the magnified and focused retinal images to the peripheral retinal receptors when patients position the normal reading text to be focused via the near distance power.
  • the invention also provides the normal visual field of view needs that can not be provided by telescopic devices used for AMD and other low vision patients. This is achieved by making provisions to incorporate a distance focus power capability.
  • the stable IOL position provides stable vision for patients with hand tremors.
  • FIG. 1 is a conventional graphical representation of visual acuity as a function of eccentricity in the nasal retina.
  • FIG. 2 is a schematic representation of a bifocal/multifocal on a sulcus fixed IOL carrier in accordance with an embodiment of this invention.
  • FIG. 3 is a schematic representation of a bifocal/multifocal IOL in a capsular bag accordance with a further embodiment of the invention.
  • FIG. 4 is a schematic representation of a bifocal/multifocal IOL in an anterior chamber or sulcus, plus an IOL in a capsular bag, in accordance with another embodiment of the invention.
  • FIG. 5 is a conventional representation of different acuity scales depicting a relationship between them.
  • FIG. 6 is a schematic elevation view of a diffractive multifocal lens with a sawtooth surface modulation in accordance with an embodiment of the invention.
  • FIG. 7 is a top plan view of the embodiment of FIG. 6 , revealing a ring diffractive zone structure.
  • FIG. 8 is a schematic side view representation of the eye with an intraocular implant in accordance with an embodiment of the invention.
  • FIG. 9 is a schematic front view representation of the eye with the intraocular implant of FIG. 8 .
  • the inventors of the present invention are aware of sight problems faced by patients with AMD or low vision and are aware that such patients use add powers in reading glasses to help improve their seeing ability.
  • Placing a strong add power in a reading glass will provide a bigger magnified image, but such gives fewer photons per receptor than would be the case if the same strong add power were placed in an intraocular lens.
  • By placing the strong add power into the intraocular lens such provides better contrast sensitivity for patients with AMD or low vision disorders than would be the case if the strong add power is in the reading glass instead—reason for this difference is due to optics.
  • the strong add power By placing the strong add power into the intraocular lens, such provides a greater photon per receptor concentration as compared to strong add power in the reading glass.
  • the inventors have determined that the add power of the lens implant be greater than the current conventional level of 4 diopters on the lens itself—the effect on the patient's vision is about 2.75 diopters.
  • the add powers should be increased to any stronger add power that would effect the patient's vision by as much as 5, 7.5 and 10 diopters and potentially higher.
  • Device approach for Population 1 Use a bifocal/multifocal IOL 10 on a sulcus fixed IOL carrier as shown in FIG. 2 .
  • the distant power is plano or near plano for the patient's distance vision and normal visual field size.
  • the near add power will allow the patient to see close enough (e.g. 6-7 inches) so that the retinal image size of the normal reading text is resolvable by the good retinal receptor array.
  • this bifocal/multifocal can also be on an anterior chamber IOL carrier and put into the anterior chamber of the eye.
  • Device approach for Population 2 Use a bifocal/multifocal IOL 10 in a capsular bag as shown in FIG. 3 .
  • the distance vision power is selected for the patient's distance vision needs and normal visual field size.
  • the near vision power will allow the patient to see close enough (e.g. 6-7 inches) so that the retinal image size of the normal reading text is resolvable by the good retinal receptor array.
  • the multilens multifocal system has at least one telescopic view system (e.g. IOL 10 ) together with a non-telescopic view system (e.g., IOL 12 ).
  • the telescopic system provides magnified retina image for visual acuity improvement.
  • the non-telescopic view system provides the normal visual field of view.
  • a different embodiment can be used in which the natural crystalline lens will be kept to work with a bifocal/multifocal IOL in an anterior chamber or sulcus fixed IOL carrier.
  • the magnified retinal images are provided via the higher add power of the bifocal/multifocal IOL.
  • IOL lens carrier for the bifocal/multifocal IOL
  • iris fixated IOL carriers is envisioned.
  • This visual aid device could also be used together with commercially available AMD drugs and/or contact lenses and refractive ablations. The drug will steady and stabilize the vision to help the device improve the patient vision and the surgery or device can help to improve the patient's vision.
  • the present invention addresses the need to keep a larger visual field of view than that provided by the three basic types of vision aids available conventionally as previously discussed by using bifocal or multifocal optics.
  • the present invention also addresses the needs for an increase in portability for application and for an improvement in cosmetics over such conventionally basic types and by implementing the optics inside the eye in a conventional minimally invasive surgical procedure, unlike implanted telescopes.
  • the inventive bifocal or multifocal device or IOL provides at least two focusing powers. Patients' normal wide visual field needs are met by the distance power of the device. Patients' reading needs are met by allowing the patients to see focused images at a closer sight distance than the normal 14 inches for near distance. Image quality is also based on a focused image rather that a patient having to orient his/her head or eyes.
  • is the Image magnification of a optical system
  • f 1 is the object space focal length of the first optical lens of the system
  • f 2 is the object space focal length of the second optical lens of the system
  • f 1 ′ is the image space focal length of the first optical lens of the system
  • x 1 is the object distance from the object space focal point
  • is the separation distance between the principal plane of the first lens and the principal plane of the second lens.
  • Equation (1) Exemplary calculations using Equation (1) are tabulated in Table 1.
  • the invention modifies bifocal and multifocal optics to provide an “add” power >+6 diopters in the IOL plane.
  • the preferred “add” power is >+6 to +8 diopters depending on reading distance needs, although any greater power, such as 9 diopters or 10 diopters, is envisioned.
  • the “add” power is the difference between the near vision power and the distance vision power of the bifocal or multifocal IOL.
  • the construction of the bifocal/mutifocal optics of the present invention is a variation of constructions available conventionally. Such conventional constructions provide a lesser difference between the near vision power and the distance vision power than 6 diopters. Some examples of conventional constructions include that of U.S. Pat. No. 5,217,489 that mentions that the near vision power is greater than the distance vision power by 2.0-5.0 diopters and whose contents are incorporated herein by reference with respect to its bifocal intraocular lens structure.
  • U.S. Pat. No. 4,888,012 discloses an accommodative lens that differs from the present invention in at least the following two aspects.
  • the said accommodative lens is a lens that theoretically changes its power as the ciliary muscle compresses it, instead of a predetermined multifocal lens.
  • the accommodative lens only has a single focus instead of multiple foci simultaneously. Therefore, U.S. Pat. No. 4,888,012 does not disclose high add power values for multifocal lenses that have simultaneously multiple foci which the present invention refers to.
  • U.S. Pat. No. 6,432,246 B1 reveals a type of multifocal lens known as progressive multifocal lens. Such a lens achieves power variations across the lens optic by changing the surface radius of curvature. This is based on the principle of geometric optics instead of the diffractive optics principle.
  • the progressive multifocal lens has to deliver light over a wide range of foci and thus reduces the available light energy for individual focus. Therefore, it is not as effective as the diffractive optics multifocal IOL in this regard. Therefore, U.S. Pat. No. 6,432,246 B1 does not disclose high add power values for multifocal lenses that rely on diffractive optics principle to generated distinct and highly efficient multiple foci, which the present invention refers to.
  • Diffractive multifocal lenses are more effective in this regard.
  • Diffractive multifocal lenses are often made with surface modulation to achieve light interference for focus creation.
  • the add power of such lenses is related to the size of the concentric rings of the surface modulation structure.
  • a diffractive bifocal 20 can have a sawtooth shape surface modulation 22 as shown in FIG. 6 .
  • the ring structure 24 (also known as diffractive zone structure) is better illustrated by FIG. 7 .
  • the sawtooth shape has a feature of step height 26 as shown in FIG. 6 .
  • step heights 26 provided by the above equations are only examples, and other step heights can also be utilized.
  • the near vision focus power is provided by the diffraction zone structure 24
  • the distance vision focus power is provided by the region 28 outside the diffraction zone structure 24 and by the diffraction zone structure 24 .
  • a trifocal-style multifocal lens can also be applied for as a low vision aid use with high add power values.
  • Refractive multifocal lenses such as disclosed in U.S. Pat. No. 5,217,489 can be changed upon higher add power and improved light energy concentration at distance focus and near focus, as anticipated by the inventors.
  • the present invention has bifocal or multifocal lenses with distinct foci that is as diffractive and refractive as, although more diffractive and refractive than, that disclosed in U.S. Pat. No. 5,217,489, but not utilizing progressive multifocal lens in the manner of U.S. Pat. No. 6,432,246 B1.
  • FIGS. 9 and 10 a further embodiment is shown illustrating the concept of deflecting an image 30 to functional retina 32 and thereby avoid scotoma in the visual field.
  • the intraocular lens 34 is configured to effect the deflection as shown, which is helpful for low vision patients such as those with AMD and underwent Mascular Translocation surgeries.
  • Macular translocation is a surgical technique designed to move the area of the retina responsible for fine vision (macula) away from the diseased underlying layers (the retinal pigment epithelium and choroid). The macula is moved to an area where these underlying tissues are healthier. Consequently, safe treatment of the sick blood vessels [choroidal neovascularization (CNV)] with, for example, laser treatment can be performed without harming central vision.
  • CNV choroidal neovascularization
  • this embodiment of the invention could achieve binocular summation, which is at least about 40 percent more effective than monocular vision.
  • Different shift amounts of retinal image locations for the paired eyes are allowed by adjusting the IOL of this embodiment. It takes advantage of the availability of retinal portions with the best neural functions. Neural learning and adaptation restructures the visual pathway and forms image fusion for better vision.
  • the optics of this embodiment of the present invention to achieve the redirection of images is based on diffractive optics so that the IOL need not be thick and the implantation does not need large incisions.
  • the diffractive optics can be designed as an off centered diffractive single focus and could have an appearance as asymmetric diffractive rings on a centered IOL.
  • the diffractive optics of the embodiment of FIGS. 8 and 9 can provide good and suitable optical imagery.
  • the retinal imagery provided by this embodiment is no higher than what is suitably resolved by receptors and thus avoids aliasing. Aliasing constitutes false image signals that could provide wrong movement direction to patients.
  • FIGS. 8 and 9 may be combined with that of the embodiments of FIGS. 2-4 and 6 - 7 to provide features of each. That is, the lens optics has a diffractive zone structure such as that exemplified in FIGS. 6-7 with appropriate surface modulations to provide an add power of at least 6 diopters and is configured to deflect or redirect images based on diffractive optics in the manner of FIGS. 8 and 9 toward the functional retina to avoid scotoma in the visual field.
  • an AMD patient can look in the direction of objects to see them without the need to turn away to do so.
  • such an intraocular lens may be implanted in any of the positions shown in FIGS. 2-4 to attain improvement in the ability to see objects when looking in the direction of the object.
  • the diffractive zone structure 24 is made of the same lens material and is of uniform material composition.
  • any of the embodiments disclosed may be used in conjunction with administration of an AMD drug to stop and deter further development of AMD.
  • the AMD drug may be an ophthalmic pharmaceutical preparation for the treatment of advanced macular degeneration.

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US11/350,437 2006-02-09 2006-02-09 Intra-ocular device with multiple focusing powers/optics Abandoned US20070182917A1 (en)

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Application Number Priority Date Filing Date Title
US11/350,437 US20070182917A1 (en) 2006-02-09 2006-02-09 Intra-ocular device with multiple focusing powers/optics
CA2576029A CA2576029C (en) 2006-02-09 2007-01-26 Intra-ocular device with multiple focusing powers/optics
EP07101409A EP1818023B1 (en) 2006-02-09 2007-01-30 Intra-ocular device with multiple focusing powers/optics
AT07101409T ATE424787T1 (de) 2006-02-09 2007-01-30 Intraokularvorrichtung mit fokussierstärken/optiken
ES07101409T ES2323092T3 (es) 2006-02-09 2007-01-30 Dispositivo intraocular con multiples potencias de enfoque/opticas.
DE602007000646T DE602007000646D1 (de) 2006-02-09 2007-01-30 Intraokularvorrichtung mit Fokussierstärken/Optiken
AU2007200556A AU2007200556B2 (en) 2006-02-09 2007-02-08 Intra-ocular device with multiple focusing powers/optics
JP2007030089A JP4598783B2 (ja) 2006-02-09 2007-02-09 複数の合焦能力/オプティクスを有する眼内装置
US12/776,807 US8262728B2 (en) 2006-02-09 2010-05-10 Intra-ocular device with multiple focusing powers/optics

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WO2008089063A1 (en) * 2007-01-12 2008-07-24 Alcon Research, Ltd. Improving intermediate vision with phakic multifocal optics utilizing residual accommodation
US20100134754A1 (en) * 2007-01-11 2010-06-03 Xin Hong Alternating optical system: mixing and matching optics to maximize binocular visual benefits
WO2013105855A1 (en) 2012-01-11 2013-07-18 Procornea Holding B.V. Intraocular lens
US20150250583A1 (en) * 2014-03-10 2015-09-10 Amo Groningen B.V. Intraocular lens that improves overall vision where there is a local loss of retinal function
US10010407B2 (en) 2014-04-21 2018-07-03 Amo Groningen B.V. Ophthalmic devices that improve peripheral vision
US10588738B2 (en) 2016-03-11 2020-03-17 Amo Groningen B.V. Intraocular lenses that improve peripheral vision
US10758340B2 (en) 2013-03-11 2020-09-01 Johnson & Johnson Surgical Vision, Inc. Intraocular lens that matches an image surface to a retinal shape, and method of designing same
US11096778B2 (en) 2016-04-19 2021-08-24 Amo Groningen B.V. Ophthalmic devices, system and methods that improve peripheral vision
CN113331994A (zh) * 2021-07-29 2021-09-03 微创视神医疗科技(上海)有限公司 人工晶状体
US11963868B2 (en) 2020-06-01 2024-04-23 Ast Products, Inc. Double-sided aspheric diffractive multifocal lens, manufacture, and uses thereof

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US20070171362A1 (en) * 2004-12-01 2007-07-26 Simpson Michael J Truncated diffractive intraocular lenses
BRPI0920951A2 (pt) * 2008-11-20 2015-12-29 Alcon Inc lente intra-ocular, método para corrigir visão, método para fabricar uma lente oftálmica
US9931200B2 (en) 2010-12-17 2018-04-03 Amo Groningen B.V. Ophthalmic devices, systems, and methods for optimizing peripheral vision
EP2890287B1 (en) 2012-08-31 2020-10-14 Amo Groningen B.V. Multi-ring lens, systems and methods for extended depth of focus
CA2945584C (en) * 2014-04-18 2021-06-01 Investmed Kft. Secondary intraocular lens with magnifying coaxial optical portion
DE102014119010A1 (de) 2014-12-18 2016-06-23 Carl Zeiss Meditec Ag Intraokularlinse mit im optischen Teil integriertem Einlinsen-Teleskop
JP6873989B2 (ja) 2015-11-09 2021-05-19 Hoya株式会社 部分的または不完全型の光学素子を有する光学デバイス
EP3452852A4 (en) * 2016-05-05 2020-04-15 Theramedice LLC INTRAOCULAR LENS AND ASSOCIATED DESIGN AND MODELING METHODS
AU2018235011A1 (en) 2017-03-17 2019-10-24 Amo Groningen B.V. Diffractive intraocular lenses for extended range of vision
US11523897B2 (en) 2017-06-23 2022-12-13 Amo Groningen B.V. Intraocular lenses for presbyopia treatment
AU2018292030B2 (en) 2017-06-28 2024-02-08 Amo Groningen B.V. Extended range and related intraocular lenses for presbyopia treatment
AU2018292024A1 (en) 2017-06-28 2020-01-02 Amo Groningen B.V. Diffractive lenses and related intraocular lenses for presbyopia treatment
US11327210B2 (en) 2017-06-30 2022-05-10 Amo Groningen B.V. Non-repeating echelettes and related intraocular lenses for presbyopia treatment
CA3166308A1 (en) 2019-12-30 2021-07-08 Amo Groningen B.V. Lenses having diffractive profiles with irregular width for vision treatment
JP2021173984A (ja) * 2020-04-30 2021-11-01 省一 小野 視力支援装置

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JP4598783B2 (ja) 2010-12-15
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AU2007200556B2 (en) 2013-07-18
ES2323092T3 (es) 2009-07-06
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US8262728B2 (en) 2012-09-11
JP2007216017A (ja) 2007-08-30

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