nemoci-sympt/OCNI/presbyopia/zlepsujici-podpurne-vlivy

Company, Encore Vision - a compound

• Designed to shift the fluid dynamics in the crystalline lens
• Allowing some restoration of accommodation [1]

Accommodating implants

• Require some degree of monovision
• Most common and trusted forms of presbyopia correction
• Most invasive and least reversible
• Great choice for the younger emmetropic presbyope [1]

Aceclidine

• Miotic eye drops
• A mild parasympathomimetic agent used for narrow-angle glaucoma
• Mixed with a mild cycloplegic agent
• Seems to modulate the pupil diameter to about 1.7 mm
• Ideal for maximizing depth of field [1]

Vyšší obsah k. alfa-lipoové v přední komoře

Eyeglasses with progressive lenses

• Most popular solution for presbyopia for most people over age 40
• Line-free multifocal lenses
• Restore clear near vision [1]

Eyeglasses with bifocal lenses

• Much less popular
• Provide a more limited range of vision for many presbyopes [1]

Photochromic lenses

• Respect higher sensitivity to light and glare
• Due to aging changes in their eyes
• Darken automatically in sunlight
• Good choice for this reason
• Available in all lens designs, including progressive lenses and bifocals [1]
• Tohle se mi líbí
• Již mne x-krát napadlo, že s užíváním brýlí, které nám dokonale zkorigují dalekozrakost a znovu docílí toho, že fokus slunečních paprsků nám dopadá na sítnici do makuly jako zamlada, nemůže souviset snad s vyšší frekvencí a progresí makulárních degenerací jako daň za to, že to měníme bez ovlivnění příčin a rizik
• Jestli nakonec vznik presbyopie ve stáří není něco jako přirozená ochrana sítnice před nadměrným oxidačním stresem, když oko začne stárnout a pravděpodobně tedy ztrácet i antioxidanty ve sklivci

Reading glasses

• Another choice [1]

Carbachol and brimonidine drop

• For presbyopia correction
• Recent pilot study, 10 naturally emmetropic and presbyopic subjects
• Ages of 42 - 58
• Uncorrected distance visual acuity of at least 20/20 in both eyes
• Received 3% carbachol and 0.2% brimonidine in both combined and separate forms
• 3% carbachol alone and 0.2% brimonidine (control) alone in their non-dominant eye
• Researchers found statistically significant improvement in mean near visual acuity in all subjects
• Compared with those who received separate forms, carbachol alone or brimonidine alone [7]

• Monocular treatment of presbyopia with 1 drop a day of carbachol/brimonidine in the non-dominant eye
• Permits acceptable reading vision for many presbyopes, even older subjects [7]

• Drop constricts the pupil
• Increases depth of focus with the pinhole effect
• Similar to the Kamra corneal inlay (AcuFocus)
• Potential for reduced quality of vision or dimness sometimes is experienced with small-aperture optics
• Many patients are happy with their improved near and intermediate vision
• Following Kamra implantation
• Dominant eye usually masking perceived dimming monocularly in the non-dominant eye [7]

• Accommodation is achieved
• But distance vision blur is present [7]

• Accommodation induced by the parasympathomimetic
• Perhaps associated with the prolongation and potentiation of these effects by the alpha agonist [10]

Chirurgické zásahy

• nespočet různých metod ošetření a jejich kombinací - v přehledném článku zde

Contact lenses

• Reading glasses that you wear while your contacts are in

Lenses that include anti-reflective coating

• AR coating eliminates reflections that can be distracting and cause eye strain
• Helps reduce glare
• Increase visual clarity for night driving [1]

Multifocal contact lenses

• In gas permeable or soft lens materials [1]

Monovision

• One eye wears a distance prescription
• Other wears a prescription for near vision
• Brain learns to favor one eye or the other for different tasks
• Some people are delighted with this solution, others complain of
• Reduced visual acuity
• Loss of depth perception with monovision [1]

Corneal inlays

• 2 are already approved in the U.S. for treating presbyopia
• Kamra inlay, marketed by AcuFocus
• ReVision Optics Raindrop [1]

• In the cornea of the eye that's not dominant eye
• Increases depth of focus of the treated eye
• Reduces the need for reading glasses
• Without significantly affecting the quality of your distance vision [1]

• Inserting a small plastic ring with a central opening, into the cornea of one eye
• Opening acts like a pinhole camera
• Allows in focused light so that you can see close object [9]

• If you don't like the results
• Surgeon can remove the rings, leaving you free to consider other treatment options [9]

Enzymy

• Human-specific crosslink breakers
• Single greatest contributor to total unintentional collagen crosslinking in humans is a very complex molecule called glucosepane
• Drugs that cleave this molecule are likely to have the strongest rejuvenative effect on tissue elasticity
• Finding or engineering enzymes, instead of drugs, to break the crosslinks [31]
• Very slow rate at which glucosepane crosslinks form [31]
• Králíkům po Bromelainu se zlomily uši a oni je neudrželi vztyčené !!!!
• AGE-breaking will need to be explored [31]
• Takže by nebylo od věci udělat nějakou studii s užíváním třeba Wobenzymu ve vztahu k presbyopii !!!

EVO6 (Novartis)

• Lipoic acid choline ester 1.5% (EV06, Encore Vision)
• Designed to restore crystalline lens flexibility
• Hopefully, reverse the effects of aging in the eye

• Prodrug comprised of lipoic acid choline ester 1.5%
• Penetrates the cornea and then breaks down into two naturally occurring substances
• Lipoic acid
• choline [7]

• Lipoic acid then converts to the active agent
• Dihydolipoic acid
• Breaks down disulphide bonds in the lens
• Improving flexibility [7]

• EV06 may potentially
• Halt or reverse lens hardening
• Allow the lens to maintain or regain its ability to accommodate [7]

• Phase I-II masked, placebo-controlled proof-of-concept study
• 50 patients were treated daily for 90 days with topical EV06 and 25 patients with placebo
• EV06 showed a statistically significant difference from placebo
• In distant-corrected near vision at all time points measured (from day eight)
• At day 90, 82% of participants treated with EV06 had 20/40 near vision
• Vs. 48% in the placebo group [7]
• EV06 was well tolerated
• no loss in best-corrected distance vision

• EV06 may provide some exceptional visual benefits
• Nearly 20% of subjects could not see at the 20/40 level after three months [7]
• Pivotal phase III studies to begin in 2018 to evaluate long-term safety and duration of treatment
• Nuclear sclerosis cataract progression, for example, might be delayed
• Drops may actually help Contact Lens wearers stay in their contact lenses
• Often, multifocal contact lens patients drop out because of perceived discomfort and visual limitations
• Patients could wear a single-vision lens along with the drops instead of multifocals [7]

FOV Tears

• Binocular presbyopia-correcting drop
• Now available in Colombia, wia approval pipelines in Argentina, Peru and Spain.
• Combination of a parasympathetic, alpha agonists 1 and 2, an anti-cholinesterase and an NSAID
• Colombian researcher Felipe Vejarano, MD, a lead investigator for the drug
• Affects the ciliary muscle
• Causes a physiological accommodation - a mild miosis
• Dynamic pseudo-accommodation - dynamic miosis
• Changes with light intensity [7]
• A recent follow-up to a pilot study
• Tracked patients who used the drop for three months
• Only 14 emmetropic presbyopic subjects with an average age of 55—the
• Some promising results [7]
• Effect lasted 4-5 hours initially
• Duration increased to 8 hours if the patient used the drop over time
• Onset of the drop’s effects
• Accelerated with continual use [7]
• 25% of study participants said the drop took 5 - 10 minutes to take effect in week one
• Cca 70% said it took only 5- 10 minutes by the 3. month
• By the third month of use
• 100% of participants said they were totally independent of their near vision correction for normal activities [7]

• Drops improved near vision by two to three lines
• Distance vision increased by one line
• Decrease of 1mm Hg in patients’ intraocular pressure with continued use
• Patients felt the drops improved the uncomfortable sensation associated with dilation [7]

Kamra inlay

• Small, thin opaque device with a tiny opening in the centre
• Surgically implanted in the central cornea
• Directly in front of the pupil of the eye [26]
• Creates a 'pinhole camera' effect
• Also seen if you look through a pinhole in a piece of paper
• Sharpens near vision while maintaining clear distance vision [26]
• Implanted in the non-dominant eye
• Allows both eyes to be used for distance vision
• Inlay sharpens near vision in the non-dominant eye [26]
• Procedure takes around 15 minutes
• No stitches are needed
• Healing time may vary
• Most people are able to resume their normal activities within 24-48 h [26]

LASIK a kombinace s brýlemi

LASIK + single contact lens for near vision

• Good option for social events
• Acceptable vision both far away and up close
• Able to see
• In the distance with one LASIK-corrected eyes
• Eye with the contact lens for near vision
• Combination creates monovision [10]
• Some people with presbyopia don't adapt well to multifocal contact lenses
• Option is to wear reading glasses over their distance contacts [10]

Monovision LASIK + single vision eyeglasses

• Monovision LASIK (one eye corrected for distance and the other for near)
• Benefit from eyeglasses with single vision lenses
• To enhance their near vision for close-up activities
• Lenses to balance for the same specific distance, such as the distance to your computer

LASIK + wavefront eyeglasses

• After LASIK bothered by nighttime glare or halos around headlights and street lights
• New eyeglass lens technology called wavefront lenses
• Use computerized measurements of eyes to detect any optical imperfections
• Higher-order aberrations (HOAs), that remain after your LASIK surgery
• Able to sharpen night-driving vision [10]

Multiple vision correction surgeries

• Combination of surgical procedures
• LASIK in your 30s, but now you're in your mid-40s and your near vision is getting fuzzy
• PRK (photorefractive keratectomy)
• CK (conductive keratoplasty) on one eye
• Could help by creating a monovision condition.

LASIK + CK

• To create monovision

LASIK, PRK and CK

• After cataract surgery
• To sharpen both distance vision and near vision
• One or more types of refractive intraocular lenses (IOLs) at all distances after cataract surgery
• Accommodating IOL
• May be recommended for one or both eyes
• Multifocal IOL
• Provides superior distance vision
• May be used for one eye
• One that provides better near vision may be recommended for your other eye
• Mixing multifocal IOLs [2]

Lens refilling with an injectable polymer

• Has the potential of restoring accommodation following cataract surgery
• Leakage of the injectable material
• After-cataract formation resulting in loss of elasticity and opacification of the lens-bag complex
• Recently, simplified and highly reproducible lens refilling procedures have been introduced [18]

Lipoic acid (LA)-dependent disulfide reduction

• P-SH and PSSP levels were determined
• Choline ester of LA was synthesized
• Mice were treated with 2.5 µL of a formulation of 5% LACE three times per day at 8-hour intervals in the right eye (OD) for 5 weeks
• Concentration-dependent decrease in lens protein disulfides concurrent with an increase in lens elasticity [18]
• Aqueous humor concentrations of LA were higher in eyes of mice following topical ocular treatment with LACE than in mice following topical ocular treatment with LA
• The lenses of the treated eyes of the old mice were more elastic than the lenses of untreated eyes
• In most instances, the lenses of the treated eyes were even more elastic than the lenses of the 8-week-old control mice !!! [18]

Lipoic acid patented derivative drop

• Developed by Encore Vision
• To reduce crystalline protein disulfide bonds
• Aiming to soften the lens
• Preserving the natural shape-changing ability
• In 2016, the company begun a 90-day phase 1/2 clinical trial
• 66 presbyopic subjects between the ages of 45 and 55 years.

LiquidVision

• An eye drop regimen that might correct presbyopia
• Would be administered daily, or as needed, with a duration of five hours or more
• Working with a miotic/cyclopegic drug to create a “pinhole effect” and to deal with the accommodation
• Completed a one-day Phase IIb trial in 2016
• Promising results with no serious adverse side effects
• 2017 Phase IIb trial [5]
• Combine aceclidine (a miotic) with tropicamide (a cycloplegic) create
• A “super pinhole” effect
• Moderate accommodation

• Aceclidine
• Used for creating stronger pinhole effect with the pupil less than 2mm
• Between 1.9mm and 1.5mm in pupil diameter
• This creates strong accommodation
• Including ciliary spasm
• Distance vision blur [7]

• Tropicamide
• Moderates accommodation [7]

• Ratio and interaction between these two drugs
• Required to improve both near and distance vision at the same time

• 30-minute onset after application
• Designed to improve near and distance vision
• For daily use
• Not a permanent replacement of spectacles or contact lenses
• Patient uses the drops in the morning, drives to work, waits about 30 minutes for the drop to take effect
• Then it will last half a day or longer
• If you’re working on the computer, you don’t need correction
• If you need a second drop, you use a second drop

• Company hopes the drops will be on the market by 2021

Melatonin

• Pokud očím dobře dělají antioxidanty, co třeba takový univerzálně působící a pronikající melatonin ?
• Vymyslel už konečně někdo melatonin v očních kapkách ????

Miotic eye drops

• Increase accommodation
• Shift the fluid dynamics of the lens
• Promising results in mid-stage FDA trials [1]

Mióza - pin hole effect

• Stahnutí se zorničky pomůže k lepšímu zaostření do blízka

Monovision LASIK

• Modified LASIK procedure
• Same effect as monovision with contact lenses

Combining NSAIDs + parasympathetic agonists

Pilocarpine 1% and 0.1% diclofenac

• Intensity of the contraction was decreased
• Pupil
• Ciliary muscle [3]
• Allowing the lens to change shape and position for good vision at all distances
• NSAIDs eliminates local inflammation
• Appears as secondary to the chronic stimulation of pilocarpine
• Fixed pupil
• Posterior synechiae
• Pigment dispersion [3]

NÚ

• Z 58 pacientů
• 4 developed nausea immediately after instillation that quickly resolved
• 4 patients developed headache that gradually disappeared (duration 10–15 min)
• Local adverse events
• 2 cases each of dryness or burning
• 4 cases of stinging
• 4 cases of blurry distance vision, all of which dissipated over 5 min [10]

Muscarinic stimulation

• Carbachol,
• Pilocarpine
• The parasympathetic agonist
• Physostigmine
• An anticholinesterase inhibitor [3]

• In all cases, near vision was restored
• Success according to the quality and concentration of the stimulating agent
• Loss of far and half distance vision
• In all patients treated was observed
• Chronic stimulation with any of these drugs
• Caused an inflammatory reaction of the anterior uvea [3]

Non-steroidal anti-inflammatory (diclofenac) was added to pilocarpine

• Combination restored near vision
• Without causing blurred far and half distance vision or inflammatory reactions [3]

Dexamethasone +pilocarpine

• Inflammatory reaction was prevented
• Near vision was restored
• But blurred far and half distance vision was noticed [3]

• Uveal tract chronic stimulation using the parasympathomimetic caused
• Inflammatory reactions
• Pigment dispersion
• Posterior synechiae
• Spasmodic contractions of the ciliary muscle and iris
• Resulted in a fixed pupil and myopic shift [3]

• NSAIDs
• Able to inhibit cyclooxygenase(s) activity in the anterior uveal tract
• Decreasing
• Miosis
• Spasmodic ciliary contractions
• Pigment dispersion
• Posterior synechia [3]

• Combination of pilocarpine with diclofenac
• Most effective formula that could be used chronically for the treatment of presbyopia
• Without the occurrence of side-effects [3]
• Restoration of accommodation can be achieved by
• Stimulating ciliary muscle contractions with parasympathetic drug
• Modify the shape and position of the lens [3]

Studie

• 1% pilocarpina Poen, Poen, Buenos Aires, Argentina
• Voltaren 0.1%, Novartis, Buenos Aires, Argentina
• At 6 hour intervals during the daily hours
• 100 subjects treated age range of 45 years to 50 years - 5 year period
• 20 patients presented ocular burning and discomfort right after drop instillation [3]
• All of patients had a near vision of Jaeger 1 (J1) and a far vision of 20/20 with an eye drop instillation at 6 hour interval the daily hours
• None had ocular or systemic diseases
• 95% of the patients were under treatment
• 1% of the patients discontinued treatment for ocular burning and discomfort
• 4% preferred treatment with glasses
• In the first year of treatment, the enhanced accommodation improved near vision
• Was maintained for 5 years
• Distance vision remained at 20/20 and was unchanged during the same period [3]

NearVision conductive keratoplasty

• Marketed by Refractec
• Uses radio frequency waves to alter the shape of the cornea of one eye
• To improve near vision

Nižší osmolalita tekutiny přední komory

• čočka a jejjí aquaporiny by mohly lépe a více nasávat tekutinu a více zaostřit na blízko ?
• Pomohlo by např. i pít více vody ? Lze pozorovat vliv na zrak podobně jako na kůži a vymizení vrásek ?

Ocucure

• 111 patients suffering from presbyopia
• Males: 63, mean age: 34±14 and females: 48, mean age: 33±13 year, range: 20-60
• Divided in to two groups
• Leutivit (Placebo) 250mg tablets twice daily for 6-8 weeks [23]
• Ocucure (Test drug) 500mg two tablets twice daily for 6-8 weeks
• Presbyopia was improved in
• 17 patients (28.81%) out of 59 patients by the use of ocucure
• 6 patients (11.53%) out of 52 by the use of leutivit
• There was a significant improvement in presbyopic associated clinical features [23]

2 parasympathomimetics + 1 parasympatholytic

• Stimulates the ciliary muscle to accommodate
• Constricts the pupil
• Instilled bilaterally twice a day in a clinical trial
• 90% of subjects could see J4 to J1 within 1 year without adverse reactions [10]

Kapky: parasympathetic, NSAID, 2 alpha-agonist agents, an anticholinesterase agent

Složení

• Pilocarpine 0.247%
• Phenylephrine 0.78%
• Polyethyleneglycol 0.09%
• Nepafenac 0.023%
• Pheniramine 0.034%
• Naphazoline 0.003% [6]

Účinky

• Promises to ameliorate the symptoms of presbyopia
• Stimulation of iris and ciliary muscle
• Minimizing the drawbacks associated with a purely parasympathetic action [6]
• Pilocarpine
• Stimulates accommodation
• Miosis
• Ciliary body contraction
• May improve tear production by stimulating lacrimal gland secretion [10]
• Phenylephrine, Nepafenac, and Pheniramine counteract
• Ciliary muscle spasm
• Vascular congestion and hyperemia induced by pilocarpine
• Avoiding an excess of pupil constriction [10]
• Naphazoline
• Increases acetylcholine release
• Reduces norepinephrine release
• Empowering pilocarpine’s relaxing effect on dilator pupillae
• Relieving its side effects [10]
• Polyethyleneglycol
• Lubricant effect protects from the burning typically experienced from most of these compounds
• Improves the tolerance for using the eye drops [10]
• All patients enjoyed the near vision that they had after instilling the eye drops
• They would like to have a new drop of it to continue the benefits observed
• No adverse effects were reported [10]

Studie

• 14 presbyopic subjects (28 eyes)
• 9 natural emmetropes
• 5 stable emmetropes post LASIK surgery
• Average age of 48.21 years (range 41–55 years) [6]

Pirenoxine

• Pyridophenoxazine compound
• Resembling xanthommatin
• Introduced in 1958 as an eye drop to suppress progression of senile cataracts
• Now it is prescribed commonly
• Subconjunctival injection of pirenoxine
• Impeded development of cataracts induced by intraperitoneal injection of benzoquinone acetic acid in guinea pigs [28]
• Pirenoxine eye drops
• Prevented the visual acuity (VA) from decreasing in 72 patients with senile cataracts
• During 8 months to 2 years [28]
• Basic research has shown the anti-cataract activity of pirenoxine
• Oxidative stress, selenite, and calcium ions lead to development of cataract
• Pirenoxine
• Prevented lipid peroxidation in guinea-pig lenses
• Prohibited lens protein turbidity induced by UVC, selenite, and calcium
• Binds up to six selenite anions
• Possesses ditopic recognition properties [28]
• Pirenoxine eye drops
• Significantly suppressed hardening of the lens caused by exposure to tabacco smoke
• Might prevent presbyopia [28]
• Clinical study assessed separately by age
• Absence of a detectable change in the objective AA in the TG in subjects in their fifth decade of life
• Suggested that pirenoxine eye drops might prevent the decline in the objective AA, i.e., the progression of presbyopia
• Might prevent progression of presbyopia [28]

PresbyLASIK

• Multifocal LASIK procedure similar to wearing multifocal contact lenses
• Performed for several years in Europe

Presbyeyedrops©

• Eye drop based on a combination of two parasympathomimetics and a NSAID
• Pilot study involving 15 eyes
• Improvements of
• UDVA from 0.8 to 1.0
• UNVA from 0.54 to 0.8
• One patient reported nausea after the instillation
• One patient reported dryness
• One patient had a burning feeling. [10]

PRX-100 drops

• Being researched in Coronado, CA by Presbyopia Therapies
• Causes miosis (constriction) of the pupil without the typical accommodative effect
• Pinhole effect
• Effect
• In 30 minutes after application
• Last upwards of 5 h [27]
• Pilot study based in Tijuana, Mexico - 20 presbyopic patients
• All experienced marked improvement in near vision
• Side effect was a short-term “dimming” of vision
• Occurs because as the pupil constricts, less light is allowed in the eye
• Making things appear dimmer [27]
• Possible that both drops (PRX-100 & EV06) could be used in conjunction
• Getting the maximum benefit in combatting presbyopia near vision loss [27]

Pulsed ciliary muscle electrostimulation

• To improve near vision
• Likely through restoring accommodation in patients with emmetropic presbyopia.
• Non-randomized trial, 27 patients from 40 to 51 years old
• All patients had emmetropia and needed near sphere add between +0.75 and +1.50 diopters
• Four sessions (one every 2 weeks within a 2-month period)
• Bilateral pulsed (2 sec on; 6 sec off) micro-electrostimulation with 26 mA for 8 minutes
• Reading speed (number of words read per minute at 40 cm) were measured preoperatively and 2 weeks after each session
• no adverse events were noted
• Continuously improved in the treated group
• Post-hoc significant differences were found for monocular and binocular UNVA after the second treatment
• One patient (3.7%) was not satisfied
• 18 patients (66.7%) were very satisfied
• Ciliary muscle contraction to restore accommodation
• Was safe
• Improved the short-term accommodative ability of patients with early emmetropic presbyopia [16]

Refractive lens exchange - RLE

• Virtually the same as cataract surgery
• Surgeon can select a multifocal IOL or an accommodating IOL to restore near vision

Scleral expansion bands

• Old idea that is being updated by the company Refocus Group
• Redesigned the old implants placed in a scleral pocket
• Making their positioning more predictable and secure
• Result:
• More consistent and sustained accommodation
• With more tolerable surgical implants than the old designs [1]

Sorbitol v čočce

• Co by udělala presbyopie, kdyby čočka byla mírně silnější ? Zmizela by dalekozrakost ?

Stimulace aquaporinu 0

Vitamín K

• Pokud má zlepšovat a udržovat elasticitu cév a šlach, pak by to mohlo platit i u oční čočky ???

Vitamíny

• Věci o kterých se tak nějak ví a píše, že jsou obecně důležité pro oční zdraví

Omega-3 fatty acids

Vitamin C

Vitamin A

Lutein

Zinc