D. BALASUBRAMANIANL. V. PRASAD EYE INSTITUTEHYDERABAD 500034, INDIA

WHEN SCIENCE CATCHES WHEN SCIENCE CATCHES THE EYETHE EYE

IN THIS TALK, WE SHALL FOCUS LESS ON BIOLOGY AND CONCENTRATE MORE ON WHAT POLYMER CHEMISTRY,MATERIAL SCIENCE, OPTICS AND ENGINEERING SCIENCESHAVE BEEN CONTRIBUTING TO VISION SCIENCE.

FOCUS ON AREAS SUCH AS PRESBYOPIA, MYOPIA,DIABETIC RETINOPATHY, “SMART CONTACT LENSES”AND THE BIONIC EYE.

AND WONDER ABOUT WHAT TODAY APPEAR TO BE SOMESEEMINGLY IMPOSSIBLE THINGS TO DO.

LIGHT IS REFRACTED BY THE CORNEA AND THE LENS AND FOCUSSEDON THE RETINA; THE IRIS CONTRACTS AND EXPANDS TO LET IN THE APPROPRIATE LEVEL OF INCOMING LIGHT THROUGH THE PUPIL

80% of focusing is by cornea, 20% by the lens, but the refractive index of cornea does not vary as much as that of the lens does; accommodation is done by the lens

• Ciliary muscle contraction • Decrease in anterior chamber depth• Increase in lens thickness• changed anterior and posterior radius of

curvature

Concept OverviewConcept Overview

WITH AGE, THE LENS BECOMES STIFFER ANDACCOMMODATES LESS- CLILIARY MUSCLES ARE NOTABLE TO DEFORM THE LENS TO ADJUST TO THE CORRECTFOCAL LENGTH- DIOPTER VALUE (1/FL, in M);PRESBYOPIA

HENCE THE NEED FOR READING GLASSES

In 1784, Ben Franklin developed bifocal glasses. He was getting old and was having trouble seeing both up-close and at a distance. Getting tired of switching between two types of glasses, he devised a way to have both types of lenses fit into the frame. The distance lens was placed at the top and the up-close lens was placed at the bottom.

By this means, as I wear my spectacles constantly, I have only to move my eyes up or down, as I want to see distinctly far or near, the proper glass being always ready. This I find more particularly convenient since my being in France, the glasses that serve me best at table to see what I eat, not being the best to see the faces of those on the other side of the table who speak to me; and when one’s ears are not well accustomed to the sounds of a language, a sight of the movements in the features of him that speaks helps to explain, so that I understand French better by the help of my spectacles.”

BIFOCALS ARE NOT THE ONLY THE INVENTION OF BENJAMIN FRANKLIN!HE WON THE CONTRACT TO PRINT CURRENCY NOTES IN PENNSYLVANIA,INVENTED A MORE EFFICIENT STOVE, MADE AN ELECTRICAL BATTERY,THE LIGHTNING ROD, FOUNDED THE AMERICAN PHILOSOPHICAL SOCIETY,INITIATED THE FIRST CENSUS OF AMERICA……

WHAT CAN BE DONE TO RID OF BIFOCALS?WHAT CAN SCIENCE OF TODAY DO TO HELP?CAN WE GET RID OF NEAR VISION GLASSES?

Presbyopic CorrectionACCOMMODATIVE INTRAOCULAR LENSES

REPLACE THE LENS BY POLYMER GEL

POLYMER CHEMISTRY COMES TO HELP

PMMA, HYDROXYSILANES, HYDROGELS

Accommodation: Biomechanics

Structures involved in accommodation Crystalline lens; Ciliary muscle; Choroid; Suspensory

zonules

Innervation Parasympathetic Edinger-Westphal (EW) nucleus

Crystalens manufactured by Eyeonics (B & L)

Plate-haptic lens has a hinged design, permitting forward movement of the haptics as a result of pressure changes in the vitreous cavity

Accommodative IOL: Crystalens

Single-Optic A-IOL’s

Dick, 2005

Crystalens translating A-IOL

1-CU translating A-IOL

Crystalens AT 45 (Eyeonics Inc.)

12 month phase II clinical trial: the only FDA- approved accommodating IOL

Plate haptic silicone multi-piece IOL

263 patients with one-year follow-up*

90% achieved near VA of 20/40 or better

25% : 20/32 or better

Enhanced Single Optic Designs

However, inadequacy: single optic design of the lens; inadequate accommodation

A Dual Optic Accommodating IOL

High + Power Anterior

Low - Power Posterior

Haptics (3x)

• Use natural forces of ciliary processes

• Change optic-to-optic separation to vary vergence point

• Requires in-the-bag implantation

Concept Overview

• Distance • Accommodated

A-IOL Implantation being done by Dr. Virender Sangwan

Results

Logmar Mean Range

UDVA +0.19 ±

0.29

-0.14 to +0.78

BDVA -0.02 ±

0.11

-0.14 to +0.36*

Sphere (D)

Cylinder

(D)

-0.35 ± 1.8

D

-0.70 ±

0.85 D

-4.5 to + 4.5D* (0

in 9/24)

0 to -3 D (0 in

10/24)

Add (D) +1.8±

0.73D

0 to +3 Diopters

Smart Lens (H. Fine)

• The “SmartLens” concept: upon hydration, the polymer rod swells to a disc lens 9.5 mm in diameter and 2–4 mm thick, within approximately 30 s.

• a: Schematic; b: soft and compressible disc lens

Injectible A-IOLs

Haefliger & Parel, 1986

Phaco-Ersatz 2009Phaco-Ersatz 2009

1 19CuringCuring

CompletedCompleted

InjectionInjection

Apply MCVApply MCV

ExtractionExtraction

CapsulorhexisCapsulorhexis

IncisionIncision

LavageLavage

• Achieving emmetropia in relaxed state

• Ideal polymer with optimum accommodation & biocompatibility

• Surgical technique for hard cataract• PCO• Can chemistry/physics/material

science help here? Need help!

Unresolved ProblemsUnresolved Problems

WHY THIS OBESSION WITH MYOPIA AND PRESBYOPIA?

Because they are endemic in many parts of Asia, and India.

Myopia:China: 31.7 % of primary school children and 82.7 % ofUniversity students have impaired vision.

90% of youngsters in Singapore and Taiwan become myopicbefore they reach class X.

We do not have such estimates yet in India, but we estimate that 0.17% of children in India are blind (<6/60); of these 33% are due to refractive errors. Means >1.3 million are myopic.

Genetics, and ‘near work’ are two factors associated with myopia

Presbyopia:

Over 77 million Indians are over 60 years of age. This number is expected to rise to 117 million by 2025.

But presbyopia hits people already by the age of 40; Nirmalan et al. have estimated that 55% of people studied (age 47.5 ± 13 years) in Andhra Pradesh are presbyopic (at least +I D correction); females had a slightly higher odds (OR 1.4), rural residence OR 1.5, myopics OR 1.6and hyperopia OR 3.6.

Translated to the whole of India, this becomes an epidemic.

CORNEAL ONLAYS TO CORNEAL ONLAYS TO REDUCE MYOPIA PROGRESSIONREDUCE MYOPIA PROGRESSION

SLICE A SMALL LAYER OF THE CORNEAL OUTER SURFACE USING A SPECIAL BLADE, INSERT A VERY

THIN IMPLANTABLE LENS, AND LEAVE IT THERE. THIS SHOULD CORRECT THE REFRACTIVE ERROR.

IF NEED BE, THE LENS CAN BE REMOVED AND REPLACED BY ANOTHER

Epithelium

Stroma

Lens

EpitheliumStroma

Lens

Inlay

Onlay

Quite safe and

biocompatible

1 m↑, 12 m↓ after inlay

Onlay, hardly visibleFlatten the cornea, lift a chosen thickness of the

epitheliumor the stroma, insert a thin refractive plastic lens, and correct the refractive error; lens stays for even, or can

be replaced; Inlay used only to check biocompatibility.

Onlayis under trial to check long term stability of refractive

power.

↑

↑

↓

A CORNEAL ONLAY BEING DONE BY Drs. PRAVIN K. VADLAMUDI and

ASHIK Md

MYOPIA AFFECTS THE PERIPHERAL RETINA AS WELL.

WE MISS THIS DUE TO RETINAL RESOLUTION, AND THE CURVATURE OF THE EYE LENS, WHICH FOCUSES ON THE FOVEA, AND OF THE EYE ITSELF;

WE NEED TO LOOK AT THE PERIPHERAL REGIONS OF THE FOVEA AS WELL. BUT CURRENT SPECTACLE LENSES OR CONTACT LENSES DO NOT TAKETHIS INTO ACCOUNT; NEED RE-DESIGNED AND RE-GROUND LENSES.

See the myopia (a) and hyperopia (b) in retina,

even as the fovea is on focus

a b

→

Prototype spectacles that takes

care of peripheral retinal focusLundstrom L, Mira-Agedelo A. Artal P. Peripheral optical errors

and their change with accommodation differ between emmetropic and myopic

eyes. J. Vision, 2009

Invented by Dr. Josh Silver ofOxford Univ., this involves theuse of transparent silicone oil,whose amount can be adjusted

by the use as per needs. From the original (top left), it has improvedto the more convenient one (left).Being tried with over 40,000 usersin Ghana, this will be taken up by

WHO

ADAPTIVE EYEGLASSES

WHAT ABOUT THE CORNEA?

MILLIONS ACROSS THE WORLD NEED CORNEAL REPLACEMENT,AND THE NUMBER AVAILABLE FROM DONORS IS FAR LESS.

WHY NOT MAKE AN ARTIFICIAL CORNEA?MUST BE COMPATIBLE WITH THE UNDERLYING/SURROUNDING TISSUE;

TRANSPLANTABLE, ACCEPTABLY REFRACTIVE, FLEXIBLE, NON-ABRASIVE, LONG-LASTING, HYDRATED, OXYGEN- PERMEABLE

POLYMERS- BIO OR SYNTHETIC APPEAR POSSIBLE

RECOMBINANT HUMAN COLLAGEN, PLL-PLGA COPOLYMER, COPOLYMER OF PERFLUOROALKYLVINYL ETHER + TETRAFLUOROETHANE,

N-ISOPROPYL ACRYLAMIDE COPOLYMER,TYPE 1 COLLAGEN, WITH POLYVINYL ALCOHOL COPOLYMER COAT,

POLY-HYDROXYETHYL METHACRYLATE (PHEMA)

By far, the most promising seems to be from

Dr. May Griffith, OHRI, Canada; we are trying it at LVP

THE VITREOUS HUMOR

TRANSPARENT GEL BETWEEN THE LENS AND ATTACHED TO THE RETINA.

WITH AGE, THE VITREOUS GEL LIQUEFIES, AND SEPARATES FROM THE RETINAL SURFACE (POSTERIOR VITREOUS DETACHMENT, PVD).

THIS IS GOOD, SINCE PVD DECREASES THE CHANCES OF A DISORDER CALLED PROLIFERATIVE DIABETIC RETINOPATHY, WHERE NEW BLOOD VESSELS FORM AND CAUSE HEMORRHAGE,

AS THEY PEEL OFF

Normal proliferative

← →

IN DIABETICS, WE WOULD LIKE TO HASTEN PVD, SO THAT RETINOPATHY DOES NOT OCCUR- NO PEELING BASED HEMORRHAGE.

SO, NEED ENZYMES THAT RELEASE AND LIQUEFY THE VITREOUS.WE ARE CURRENTLY CLINICALLY TRYING THE PRODUCT “VITREOSOLVE”,

BUT NEED NEW IDEAS AND PRODUCTS- HELP FROM COLLEAGUES

TURN NOW TO THE RETINA

WHILE BIOLOGY IS TRYING HARD TO ADDRESS RETINAL DISORDERS, ELECTRONICS IS TAKING OVER- THE BIONIC EYE

→

Retinoblastoma, cancer in the eye-rampant in children in India:

treatment by surgery and usingcarboplatin. Extreme cases, enucleation

of the eye. Dosage difficult, as alsothe actual concentration reaching the site.

We have tried encapsulating the drug in PAMAM dendrimers, and deliveringit periocularly as also sub-conjunctivally. Are there better ways? Better nano-

materials to or other delivery vehicles?

carboplatin PAMAM dendrimerDr. S. G. Honavar

Camera on the glasses sees image; signals sent to hand-held device; processedinformation sent back to glasses and transmitted to a receiver under the surface

of the eye; receiver sends information to the electrodes in the retinal implant, andthe stimulated retina sends information to the brain. Partial visual recovery.

Professor Mark Humayun, earlier at Johns Hopkins, now at USC Los Angeles:“It’s amazing, even with 16 pixels, or electrodes, how much our first six subjectshave been able to do”; the newer implant has a higher resolution, with 60 pixels.

The pixel number will increase upon experience; currently about 75 subjects Have volunteered for the trial.

So, will there be a contact lens retinal implant? Not too far off!

EVEN MORE DARING QUESTIONS

Gene delivery using nanomaterials?

Eye drops that can reach the retina?

Tear fluid as a diagnostic material??

Re-engineer taste bud cells to repair the retina?

Transplant an entire donor eye

Contact lens as a navigator?

Babak Parviz, UW Seattle- incorporates electronic circuitry into a plastic lens, including LEDs for ‘on eye’ displays, radio for wireless communication, antenna for collecting power from a cell phone in the pocket. Useful for GPS, direction navigation, and to find quickest route to a target- military and security/spy use.

Contact lens turns James Bond!

L V Prasad Eye Institutewww.lvpei.org

Excellence Equity Efficiency

Thank you!