Biomechanics of Hyperopic Shift in Stage 4 Diffuse Lamellar Keratitis and Central Toxic Keratopathy Brian R Will, MD Adjunct Clinical Professor of Ophthalmology Loma Linda University School of Medicine Loma Linda, California Medical Director Will Vision and Laser Centers Vancouver, Washington No Financial Interest

Patient Series 8 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

Tangential Power Map Analysis Day 1 to 5 Reversal Day 12 to 112 Peripheral flattening Mid peripheral steepening Central flattening Reversal Tangential Power Map Analysis Day 12 to 112 Peripheral steepening Mid peripheral flattening Central steepening

Flap initially normal thickness Thickens by 40 microns or more Flap initially thin - Day 1 of Stage 4 DLK Residual Stromal Bed normal - Day 1 Flap initially normal thickness Thickens by 40 microns or more Then becomes normal over time Flap markedly thickens by Day 12 Residual Stromal Bed marked thinning Residual stromal bed normal Thins by 50 microns or more Then becomes normal over time Flap resumes normal thickness over time Residual Stromal Bed 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 Residual Stromal Bed Decreased Compliance Tissue thins Normal Compliance Normal Thickness LASIK Flap Increased Compliance Tissue thickens

Biomechanical Dynamic Inflammatory cytokines drive Pif negative Flap has low tension and high compliance Flap imbibes fluid, swells and thickens Inflammatory cytokines 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