Biomechanics of Hyperopic Shift in Stage 4 Diffuse Lamellar Keratitis

and Central Toxic Keratopathy

Brian R Will, MDAdjunct Clinical Professor of OphthalmologyLoma Linda University School of Medicine

Loma Linda, California

Medical DirectorWill Vision and Laser Centers

Vancouver, Washington

No Financial Interest

Brian R Will, MDAdjunct Clinical Professor of OphthalmologyLoma Linda University School of Medicine

Loma Linda, California

Medical DirectorWill Vision and Laser Centers

Vancouver, Washington

No Financial Interest

Patient Series8 eyes with Stage 4 DLK All eyes studied using time matched

Pentacam imaging Tangential Power Map Elevation Map Scheimphlug photographic images

Optical Coherence Tomography Hi Resolution Corneal images

Imaging began at presentation of Stage 4 DLK

All eyes ultimately recovered 20/20 BSCVA

Central flatteningMid peripheral steepeningPeripheral flattening

Day 1 to 5

Central steepeningMid peripheral flatteningPeripheral steepening

Day 12 to 112

ReversalTangential

Power

Map

Analysis

Flap initially thin - Day 1 of Stage 4 DLK Residual Stromal Bed normal - Day 1

Flap markedly thickens by Day 12 Residual Stromal Bed marked thinning

Flap resumes normal thickness over time Residual Stromal Bed normal over time

Flap initially normal thickness

Thickens by 40 microns or more

Then becomes normal over time

Residual stromal bed normal

Thins by 50 microns or more

Then becomes normal over time

With injury / epithelial cell removal Anterior cornea swells Posterior cornea thins

Caused by changes in interstitial fluid pressure Change induced by inflammatory cytokines

Did not study the reversibility of the phenomenon Failed to recognize the biomechanical impact of these fluid shifts Incorrectly identified keratocyte apoptosis as the

mechanism for changes in Pif

Key Concepts - Biomechanics of the Hyperopic Shift Induced by effects of inflammatory

cytokines on interstitial fluid pressures (Pif)

Corneal shape is controlled by the complex relationship between Localized changes in Pif Localized changes in tissue tension Localized changes in tissue compliance

Flap edema created by compliance mismatch between flap and RSB

Local Control of Corneal Pif Complex interaction between keratocytes and ECM

modulated by Inflammatory cytokines Transmembrane proteins - Integrins Actin cell cytoskeleton Outside-In transmembrane signaling

Pif is Not uniform in the cornea Central cornea 5X more negative

than limbus Endothelial function cannot

create this gradient

Pif gradient drives fluid from periphery to center

Relationship between Pif and Tissue tension

Tissue compliance determines the volume of fluid (∆Vol) a tissue can hold at a given Pif (∆Pif)

Compliance is affected by tissue tension Higher tension - less compliant Lower tension - more compliant

∆ Pif

∆ Tissue Volume

Normal ComplianceNormal Thickness

LASIK FlapIncreased ComplianceTissue thickens

Residual Stromal BedDecreased ComplianceTissue thins

Biomechanical Dynamic

Inflammatory cytokines

Inflammatory cytokines

Inflammatory cytokines drive Pif negative

Flap has low tension and high compliance

Flap imbibes fluid, swells and thickens

Inflammatory cytokines drive Pif negative

Lowered Pif pulls fluid from the limbus

Mid peripheral cornea imbibes fluid, swells

and thickens

Inflammatory cytokines drive Pif negative

Lowered Pif pulls fluid from the limbus

Mid peripheral cornea imbibes fluid, swells

and thickens

As mid peripheral cornea swells the RSB exhibits increased tension + compression

Tension and compression decreases compliance of the RSB

RSB markedly thins centrally

Etiology of Hyperopic Shift Biologically modulated reversible

biomechanical event Controlling elements include:

Inflammatory cytokines Change in local interstitial fluid pressures Local tissue edema Local tissue tension Local tissue compliance

Mid-peripheral edema causes localized steepening and central flattening of RSB

Flap edema caused by compliance mismatch between flap and RSB

Clinical Applications Pentacam and Optical Coherence Tomography

demonstrate no evidence of tissue necrosis Tissue necrosis is a theory not supported by any

credible data and should be categorically rejected Roberts model of biomechanics is demonstrated

to be incorrect Similar biomechanical events occur to some

degree in nearly all cases of PRK, LASIK and LASEK

A better understanding of the impact of alteration in local Pif, tissue tension and tissue compliance will have significant effects on predictability of refractive endpoints and the avoidance and management of complications