A dual-antigen self-amplifying RNA SARS-CoV-2 vaccine induces potent humoral and cellular immune responses and protects against SARS-CoV-2 variants through T cell-mediated immunity.

Self-amplifying RNA vaccines may induce equivalent or more potent immune responses at lower doses compared to non-replicating mRNA vaccines via amplified antigen expression. In this paper, we demonstrate that 1 µg of an LNP-formulated dual-antigen self-amplifying RNA vaccine (ZIP1642), encoding both the S-RBD and N antigen, elicits considerably higher neutralizing antibody titers against Wuhan-like Beta B.1.351 and Delta B.1.617.2 SARS-CoV-2 variants compared to those of convalescent patients. In addition, ZIP1642 vaccination in mice expanded both S- and N-specific CD3+CD4+ and CD3+CD8+ T cells and caused a Th1 shifted cytokine response. We demonstrate that the induction of such dual antigen-targeted cell-mediated immune response may provide better protection against variants displaying highly mutated Spike proteins, as infectious viral loads of both Wuhan-like and Beta variants were decreased after challenge of ZIP1642 vaccinated hamsters. Supported by these results, we encourage redirecting focus toward the induction of multiple antigen-targeted cell-mediated immunity in addition to neutralizing antibody responses to bypass waning antibody responses and attenuate infectious breakthrough and disease severity of future SARS-CoV-2 variants.

Covid-19 Social Distancing Interventions by Statutory Mandate and Their Observational Correlation to Mortality in the United States and Europe.

PURPOSE: Evaluate the correlation between statutory social distancing interventions and Covid-19 mortality independently in both the United States and Europe. The study is presented as a potential methodology to evaluate the effectiveness of statutory social distancing policy. PATIENTS AND METHODS: Twenty-seven states in the United States and, separately, 12 European countries were selected which had clearly defined and dated establishment of statewide or national mandates for social distancing measures from the Institute for Health Metrics and Evaluation (IHME) data. Mandated social distancing measures considered in this study include: School closures, Prohibition on mass gatherings, business closures, stay at home orders, severe travel restrictions, and closure of non-essential businesses. The state/country Covid-19 peak mortality rate (PMR) was defined as the initial averaged normalized maximum during which social distancing mandates were in effect. Mandate-days were defined as the total days legislative mandates were in place to the PMR. RESULTS: The normalized peak mortality rate in the US and in Europe did not demonstrate a statistically significant correlation to the total mandate days (R-squared=0.053, p=0.246, R-squared=2.4E-06, p=0.996). A significant correlation was found between normalized mortality rate and state/country population density (R-squared=0.524, p=0.00002,R-squared=0.397, p=0.0281). DISCUSSION: The analysis appears to suggest no mandate effective reduction in Covid-19 mortality rate to its defined initial peak when interpreting their mean-effect. A strong correlation to population density suggests human interaction frequency does affect the peak mortality rate.

Corneal Crosslinking Biomechanics Evaluated by a Novel and Easily Implemented Differential Tonometry Method.

Purpose: Evaluate potential corneal biomechanical changes following corneal crosslinking (CXL) by paired differential tonometry intraocular pressure (IOP) measurements with a Goldmann tonometer (GAT) prism and corneal compensating, correcting applanation tonometry surface (CATS) prism.Methods: IOP was measured prospectively on 23 unique eyes undergoing CXL for keratoconus with a GAT using a standard flat GAT prism and a curved corneal error correcting CATS prism before treatment and at 2 weeks, 2 months and 6 months after treatment. Concurrent measurements of central corneal thickness (CCT) and corneal hysteresis (CH) were completed.Results: Paired IOP measurements with standard GAT and corneal correcting CATS prisms indicated a significant sustained relative increase in the differential IOP between the two prisms after CXL (p = .002,0.051,0.062). CH initially decreased at two weeks post-CXL then returned to sustained pre-op levels (p = .033,0.20,0.20). CCT progressively decreased following CXL (p = .005).Discussion: Differential tonometry between standard GAT and corneal biomechanical compensating CATS prisms indicates findings consistent with increased corneal rigidity following CXL and may demonstrate a simple and sensitive method for measurement of relative corneal biomechanical changes due to pharmacologic agents and procedures.

Corticosteroids and cellulose purification improve, respectively, the in vivo translation and vaccination efficacy of sa-mRNAs.

Synthetic mRNAs are an appealing platform with multiple biomedical applications ranging from protein replacement therapy to vaccination. In comparison with conventional mRNA, synthetic self-amplifying mRNAs (sa-mRNAs) are gaining interest because of their higher and longer-lasting expression. However, sa-mRNAs also elicit an innate immune response, which may complicate their clinical application. Approaches to reduce the innate immunity of sa-mRNAs have not been studied in detail. Here we investigated, in vivo, the effect of several innate immune inhibitors and a novel cellulose-based mRNA purification approach on the type I interferon (IFN) response and the translation and vaccination efficacy of our formerly developed sa-mRNA vaccine against Zika virus. Among the investigated inhibitors, we found that corticosteroids and especially topical application of clobetasol at the sa-mRNA injection site was the most efficient in suppressing the type I IFN response and increasing the translation of sa-mRNA. However, clobetasol prevented formation of antibodies against sa-mRNA-encoded antigens and should therefore be avoided in a vaccination context. Residual dsRNA by-products of the in vitro transcription reaction are known inducers of immediate type I IFN responses. We additionally demonstrate a drastic reduction of these dsRNA by-products upon cellulose-based purification, reducing the innate immune response and improving sa-mRNA vaccination efficacy.

Improved Efficacy of Topical Latanoprost 0.005% Demonstrated by Corneal Biomechanical Correcting Modified Goldmann Prism.

PURPOSE: To evaluate intraocular pressure (IOP) reduction measured by a Goldmann applanation tonometer (GAT) prism and a modified surface Goldmann (CATS) prism with the institution of a topical prostaglandin analog (PGA) or alternatively a topical beta blocker. DESIGN: Prospective, open-label, randomized, controlled, and reference device comparison. METHODS: Thirty-six (36) treatment naïve glaucoma patients (72 eyes) were randomized equally to treatment with latanoprost 0.005% or timolol maleate 0.5%. Each patient underwent IOP measurement with standard GAT and CATS prisms before and at 1, 3, and 6 months of treatment. Central corneal thickness (CCT) and corneal hysteresis (CH) were also measured. Medication response was defined as a 20% reduction in IOP from baseline. RESULTS: The CATS prism demonstrated the IOP reduction with topical latanoprost at a mean of 1.9 mmHg lower than the IOP measured with GAT (p=0.01). The CATS and GAT prisms detected no difference in IOP reduction with timolol (p=0.23). The number of latanoprost treatment non-responders was reduced from 36.1% measured with GAT to 13.8% when measured with the CATS prism (p=0.005). Timolol indicated no difference in the treatment non-response rate at 22.2% (p=0.999). CH increased significantly with latanoprost treatment by an average of 0.55 mmHg (p=0.014) and remained unchanged with timolol at -0.014 mmHg (p=0.68). DISCUSSION: IOP reduction and responder rates were increased when measured with a CATS prism in patients using latanoprost and not with timolol use. Latanoprost-induced alterations in corneal biomechanics may dampen the actual IOP reduction measured with a standard GAT prism. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04178863.

Modified Goldmann prism intraocular pressure measurement accuracy and correlation to corneal biomechanical metrics: multicentre randomised clinical trial.

PURPOSE: Clinically evaluate intraocular pressure (IOP) measurements taken with a Goldmann applanation tonometer (GAT) prism and a modified surface Goldmann prism examining measurement differences correlated to central corneal thickness (CCT) and corneal hysteresis (CH) values. DESIGN: Prospective, open-label, randomised, controlled, multicentre reference device accuracy analysis. METHODS: A GAT and a modified surface GAT prism measured IOP on 243 unique eyes. The study design and methodology complied with International Standard Organization (ISO) tonometer evaluation guidelines, except the inclusion of thin (<500 µm) and thick (>600 µm) corneas. All eyes were randomised to IOP measurement by one of five standard Goldmann prisms and five modified prisms. Pressures were measured by six investigators, two times with each prism for a total of 1936 IOP measurements. Analysis included a multiple linear regression including CCT and CH correlation. RESULTS: The difference in IOP measurements of the standard and modified Goldmann prisms correlated well to CCT particularly in thin (<500 µm) and thick (>600 µm) corneas (R2=0.404, p=0.007). Corneal hysteresis (CH) also significantly correlated to the difference in prism measurements (R2=0.125, p=0.039). There was no significant overall mean IOP bias between the two prisms (+0.43 mm Hg in modified, p=0.19). DISCUSSION: The paired IOP measurement difference between GAT and a modified surface Goldmann replacement prism indicated a statistically significant correlation to CCT and CH. A simple modified replacement prism for any Goldmann-type tonometer may significantly improve IOP measurement accuracy by minimising corneal biomechanical errors associated with CCT and CH. TRIAL REGISTRATION NUMBER: NCT02990169 and NCT02989909.

Intraocular Pressure Measurement Accuracy and Repeatability of a Modified Goldmann Prism: Multicenter Randomized Clinical Trial.

PURPOSE: To clinically evaluate a modified surface Goldmann applanation tomometer (GAT) prism for intraocular pressure (IOP) accuracy, repeatability, and safety. DESIGN: Prospective, open-label, randomized, controlled, multicenter reference device reliability and validity analysis. METHODS: A GAT and a modified surface GAT prism measured IOP on 173 unique eyes. The study design and analysis complied with FDA 510(k) and ANSIZ80.10-2014 guidelines. All eyes were randomized to IOP measurement by 1 of 5 standard prisms or 5 modified prisms, each from a different manufacturing lot. Pressures were measured by 6 investigators, 2 times with each prism, for a total of 1384 IOP measurements. Analysis included Bland-Altman difference accuracy, intraoperator and interoperator IOP measurement, and manufactured lot repeatability. RESULTS: Bland-Altman indicated no IOP measurements pairs outside the ±5 mm Hg guidelines. Operator and manufactured lot repeatability F tests and 1-way ANOVAs indicated no statistical difference between the standard and modified prisms (all P > .10). The difference in IOP measurements of the standard and modified prisms correlated well to Dresdner central corneal thickness (CCT) correction (P = .01). CONCLUSION: A modified surface replacement prism is statistically equivalent to a flat-surfaced prism. The modified surface prism indicated statistically significant correction for CCT requiring further testing outside the ANSI standard limits (0.500 mm < CCT < 0.600 mm) to examine its full potential.

Goldmann tonometry tear film error and partial correction with a shaped applanation surface.

PURPOSE: The aim of the study was to quantify the isolated tear film adhesion error in a Goldmann applanation tonometer (GAT) prism and in a correcting applanation tonometry surface (CATS) prism. METHODS: The separation force of a tonometer prism adhered by a tear film to a simulated cornea was measured to quantify an isolated tear film adhesion force. Acrylic hemispheres (7.8 mm radius) used as corneas were lathed over the apical 3.06 mm diameter to simulate full applanation contact with the prism surface for both GAT and CATS prisms. Tear film separation measurements were completed with both an artificial tear and fluorescein solutions as a fluid bridge. The applanation mire thicknesses were measured and correlated with the tear film separation measurements. Human cadaver eyes were used to validate simulated cornea tear film separation measurement differences between the GAT and CATS prisms. RESULTS: The CATS prism tear film adhesion error (2.74±0.21 mmHg) was significantly less than the GAT prism (4.57±0.18 mmHg, p<0.001). Tear film adhesion error was independent of applanation mire thickness (R2=0.09, p=0.04). Fluorescein produces more tear film error than artificial tears (+0.51±0.04 mmHg; p<0.001). Cadaver eye validation indicated the CATS prism's tear film adhesion error (1.40±0.51 mmHg) was significantly less than that of the GAT prism (3.30±0.38 mmHg; p=0.002). CONCLUSION: Measured GAT tear film adhesion error is more than previously predicted. A CATS prism significantly reduced tear film adhesion error by41%. Fluorescein solution increases the tear film adhesion compared to artificial tears, while mire thickness has a negligible effect.

Goldmann and error correcting tonometry prisms compared to intracameral pressure.

BACKGROUND: Compare Goldmann applanation tonometer (GAT) prism and correcting applanation tonometry surface (CATS) prism to intracameral intraocular pressure (IOP), in vivo and in vitro. METHODS: Pressure transducer intracameral IOP was measured on fifty-eight (58) eyes undergoing cataract surgery and the IOP was modulated manometrically to 10, 20, and 40 mmHg. Simultaneously, IOP was measured using a Perkins tonometer with a standard GAT prism and a CATS prism at each of the intracameral pressures. Statistical comparison was made between true intracameral pressures and the two prism measurements. Differences between the two prism measurements were correlated to central corneal thickness (CCT) and corneal resistance factor (CRF). Human cadaver eyes were used to assess measurement repeatability. RESULTS: The CATS tonometer prism measured closer to true intracameral IOP than the GAT prism by 1.7+/-2.7 mmHg across all pressures and corneal properties. The difference in CATS and GAT measurements was greater in thin CCT corneas (2.7+/-1.9 mmHg) and low resistance (CRF) corneas (2.8+/-2.1 mmHg). The difference in prisms was negligible at high CCT and CRF values. No difference was seen in measurement repeatability between the two prisms. CONCLUSION: A CATS prism in Goldmann tonometer armatures significantly improve the accuracy of IOP measurement compared to true intracameral pressure across a physiologic range of IOP values. The CATS prism is significantly more accurate compared to the GAT prism in thin and less rigid corneas. The in vivo intracameral study validates mathematical models and clinical findings in IOP measurement between the GAT and CATS prisms.

Assessing the Effect of Piperacillin/Tazobactam on Hematological Parameters in Patients Admitted with Moderate or Severe Foot Infections.

INTRODUCTION: Piperacillin/tazobactam is a commonly used antibiotic for the empirical treatment of severe diabetic foot infections. One of the most feared complications of this drug is the development of pancytopenia. The aim of this study was to determine whether the use of piperacillin/tazobactam caused any hematological changes in patients admitted with severe diabetes-related foot infections from a specialist multidisciplinary foot clinic. Specifically, looking at whether it caused anemia, leukopenia, neutropenia, or thrombocytopenia. METHODS: A 1-year retrospective analysis of patients admitted to a tertiary care center for treatment of diabetes-related foot infection using piperacillin/tazobactam. Hematological indices, urea and electrolytes, and C-reactive protein (CRP) were recorded pretreatment, during treatment, and posttreatment. HbA1c, vitamin B12, folate, thyroid-stimulating hormone, and free thyroxin were also analyzed to exclude any potential confounders as a cause of pancytopenia. RESULTS: A total of 154 patients were admitted between 1 January 2016 and 31 December 2016 who received piperacillin/tazobactam for severe diabetes-related foot infection. On admission, white cell count and CRP were raised and fell significantly within the first 48 h. Other hematological factors did not change. Five patients developed a mild pancytopenia, of which three were unexplained. CONCLUSION: In this relatively small cohort, pancytopenia did not occur. As such, piperacillin/tazobactam appeared to have a low risk of adverse hematological outcomes and remains the treatment of choice for severe diabetes-related foot infections.

Goldmann applanation tonometry error relative to true intracameral intraocular pressure in vitro and in vivo.

BACKGROUND: Goldmann applanation tonometry (GAT) error relative to intracameral intraocular pressure (IOP) has not been examined comparatively in both human cadaver eyes and in live human eyes. Futhermore, correlations to biomechanical corneal properties and positional changes have not been examined directly to intracameral IOP and GAT IOP. METHODS: Intracameral IOP was measured via pressure transducer on fifty-eight (58) eyes undergoing cataract surgery and the IOP was modulated manometrically on each patient alternately to 10, 20, and 40 mmHg. IOP was measured using a Perkins tonometer in the supine position on 58 eyes and upright on a subset of 8 eyes. Twenty one (21) fresh human cadaver globes were Intracamerally IOP adjusted and measured via pressure transducer. Intracameral IOP ranged between 5 and 60 mmHg. IOP was measured in the upright position with a Goldmann Applanation Tonometer (GAT) and supine position with a Perkins tonometer. Central corneal thickness (CCT) was also measured. RESULTS: The Goldmann-type tonometer error measured on live human eyes was 5.2 +/-1.6 mmHg lower than intracameral IOP in the upright position and 7.9 +/- 2.3 mmHg lower in the supine position (p < .05). CCT also indicated a sloped correlation to error (correlation coeff. = 0.18). Cadaver eye IOP measurements were 3.1+/-2.5 mmHg lower than intracameral IOP in the upright position and 5.4+/- 3.1 mmHg in the supine position (p < .05). CONCLUSION: Goldmann IOP measures significantly lower than true intracameral IOP by approximately 3 mmHg in vitro and 5 mmHg in vivo. The Goldmann IOP error is increased an additional 2.8 mmHg lower in the supine position. CCT appears to significantly affect the error by up to 4 mmHg over the sample size.

Goldmann tonometer error correcting prism: clinical evaluation.

PURPOSE: Clinically evaluate a modified applanating surface Goldmann tonometer prism designed to substantially negate errors due to patient variability in biomechanics. METHODS: A modified Goldmann prism with a correcting applanation tonometry surface (CATS) was mathematically optimized to minimize the intraocular pressure (IOP) measurement error due to patient variability in corneal thickness, stiffness, curvature, and tear film adhesion force. A comparative clinical study of 109 eyes measured IOP with CATS and Goldmann prisms. The IOP measurement differences between the CATS and Goldmann prisms were correlated to corneal thickness, hysteresis, and curvature. RESULTS: The CATS tonometer prism in correcting for Goldmann central corneal thickness (CCT) error demonstrated a reduction to <±2 mmHg in 97% of a standard CCT population. This compares to only 54% with CCT error <±2 mmHg using the Goldmann prism. Equal reductions of ~50% in errors due to corneal rigidity and curvature were also demonstrated. CONCLUSION: The results validate the CATS prism's improved accuracy and expected reduced sensitivity to Goldmann errors without IOP bias as predicted by mathematical modeling. The CATS replacement for the Goldmann prism does not change Goldmann measurement technique or interpretation.

Pseudophakic cystoid macular edema prevention and risk factors; prospective study with adjunctive once daily topical nepafenac 0.3% versus placebo.

BACKGROUND: Define the effectiveness of a topical non-steroidal anti-inflammatory drug (NSAID) added to topical steroid use after uncomplicated phacoemulsification for the prevention of pseudophakic cystoid macular edema (PCME) using a prospective, randomized, double-masked, placebo-controlled clinical study. METHODS: Eyes (1000) were randomized to placebo (497) or nepafenac 0.3% (503) used once daily, post-operatively for 5 weeks at two ophthalmology clinics. Diagnosis of PCME was made by clinical, ocular coherence tomography (OCT), and with fluorescein angiography confirmation. Correlation of PCME to NSAID use and the presence of pre-operative risk factors for PCME were assessed including, contralateral PCME, diabetic retinopathy, retinal vein occlusion, macular hole, epiretinal membrane, macular degeneration, retinal detachment repair, and prostaglandin use. RESULTS: PCME was the most common complication associated with routine cataract surgery (4.2% with PCME risk factors, 2.0% with risk factors excluded). Topical nepafenac 0.3% significantly reduces the incidence of PCME compared to placebo when used after routine cataract surgery (p = .0001). When patients with pre-operative risk factors are excluded, the incidence of PCME between treatment and placebo groups is equivalent (p = 0.31). PCME relative risk (RR) was most significant in contralateral PCME (RR 19.5), diabetic retinopathy (RR 13.1), retinal vein occlusion (RR 12.9), macular hole (RR 7.7), and epiretinal membrane (RR 5.7). Prostaglandin use and previous retinal detachment were not shown to increase risk. CONCLUSION: Pseudophakic cystoid macular edema is common after phacoemulsification cataract surgery. Topical nepafenac 0.3% reduces PCME in patients with pre-operative risk factors for PCME compared to placebo but shows no benefit in patients without pre-operative risk factors. TRIAL REGISTRATION: NIH ClincalTrials.gov retrospectively registered January 15, 2017, NCT03025945 .

Goldmann Tonometer Prism with an Optimized Error Correcting Applanation Surface.

PURPOSE: We evaluate solutions for an applanating surface modification to the Goldmann tonometer prism, which substantially negates the errors due to patient variability in biomechanics. METHODS: A modified Goldmann or correcting applanation tonometry surface (CATS) prism is presented which was optimized to minimize the intraocular pressure (IOP) error due to corneal thickness, stiffness, curvature, and tear film. Mathematical modeling with finite element analysis (FEA) and manometric IOP referenced cadaver eyes were used to optimize and validate the design. RESULTS: Mathematical modeling of the optimized CATS prism indicates an approximate 50% reduction in each of the corneal biomechanical and tear film errors. Manometric IOP referenced pressure in cadaveric eyes demonstrates substantial equivalence to GAT in nominal eyes with the CATS prism as predicted by modeling theory. CONCLUSION: A CATS modified Goldmann prism is theoretically able to significantly improve the accuracy of IOP measurement without changing Goldmann measurement technique or interpretation. Clinical validation is needed but the analysis indicates a reduction in CCT error alone to less than ±2 mm Hg using the CATS prism in 100% of a standard population compared to only 54% less than ±2 mm Hg error with the present Goldmann prism. TRANSLATIONAL RELEVANCE: This article presents an easily adopted novel approach and critical design parameters to improve the accuracy of a Goldmann applanating tonometer.

Deformable Surface Accommodating Intraocular Lens: Second Generation Prototype Design Methodology and Testing.

PURPOSE: Present an analysis methodology for developing and evaluating accommodating intraocular lenses incorporating a deformable interface. METHODS: The next generation design of extruded gel interface intraocular lens is presented. A prototype based upon similar previously in vivo proven design was tested with measurements of actuation force, lens power, interface contour, optical transfer function, and visual Strehl ratio. Prototype verified mathematical models were used to optimize optical and mechanical design parameters to maximize the image quality and minimize the required force to accommodate. RESULTS: The prototype lens produced adequate image quality with the available physiologic accommodating force. The iterative mathematical modeling based upon the prototype yielded maximized optical and mechanical performance through maximum allowable gel thickness to extrusion diameter ratio, maximum feasible refractive index change at the interface, and minimum gel material properties in Poisson's ratio and Young's modulus. CONCLUSIONS: The design prototype performed well. It operated within the physiologic constraints of the human eye including the force available for full accommodative amplitude using the eye's natural focusing feedback, while maintaining image quality in the space available. The parameters that optimized optical and mechanical performance were delineated as those, which minimize both asphericity and actuation pressure. The design parameters outlined herein can be used as a template to maximize the performance of a deformable interface intraocular lens. TRANSLATIONAL RELEVANCE: The article combines a multidisciplinary basic science approach from biomechanics, optical science, and ophthalmology to optimize an intraocular lens design suitable for preliminary animal trials.

Thermal load from a CO2 laser radiant energy source induces changes in corneal surface asphericity, roughness, and transverse contraction.

PURPOSE: We examined corneal surface response to an isolated thermal load. METHODS: Cadaveric porcine eyes were pressurized and stabilized for processing and imaging. A carbon dioxide (CO2) laser (1.75 W) delivered a uniform disk of continuous wave thermal radiant energy to the exposed corneal stromal surface without ablation. Thermal load was determined by measuring corneal surface temperature during CO2 laser irradiation. Corneal profilometry was measured with broad-band optical interferometry before and after CO2 laser irradiation. Photomicrographs of the stromal surface were taken before and after irradiation, and the images were superimposed to examine changes in positional marks, examining mechanical alterations in the stromal surface. RESULTS: Thermal load from uniform laser irradiation without ablation produces central corneal steepening and paracentral flattening in the central 3-mm diameter. Q values, measuring asphericity in the central 2 mm of the cornea increased significantly and it was correlated with the temperature rise (R2=0.767). Surface roughness increased significantly and also was correlated with temperature rise (R2=0.851). The central stromal surface contracted and underwent characteristic morphologic changes with the applied thermal load, which correlated well with the temperature rise (R2=0.818). CONCLUSIONS: The thermal load created by CO2 laser irradiation creates a characteristic spectrum of morphologic changes on the porcine corneal stromal surface that correlates to the temperature rise and is not seen with inorganic, isotropic material. The surface changes demonstrated with the CO2 laser likely are indicative of temperature-induced transverse collagen fibril contraction and stress redistribution. Refractive procedures that produce significant thermal load should be cognizant of these morphologic changes.

Corneal surface asphericity, roughness, and transverse contraction after uniform scanning excimer laser ablation.

PURPOSE: To examine the interaction between the excimer laser and residual tissue. METHODS: Ten cadaveric porcine eyes with exposed corneal stroma and plastic test spheres underwent uniform 6-mm ablation with a scanning excimer laser. Corneal profilometry of the central 3 mm was measured with submicrometer resolution optical interferometry, before and after uniform excimer ablation. Eleven surface-marked eyes were photomicrographed before and after excimer ablation. Images were superimposed, and mark positional changes were measured. RESULTS: Uniform scanning excimer laser ablation of the corneal stroma produces a significant central steepening and peripheral flattening in the central 3-mm of the diameter. The central 1-mm corneal curvature radius (r) decreased from r = 10.07 ± 0.44 (95% CI) to 7.22 ± 0.30 mm, and the central 2-mm radius decreased from r = 10.16 ± 0.44 to 8.10 ± 0.43 mm. Q values, measuring asphericity in the 2-mm radius of the central cornea, were significantly lower before than after ablation (-5.03 ± 4.01 vs. -52.4 ± 18.7). Surface roughness increased significantly from 0.65 ± 0.06 to 1.75 ± 0.32 µm after ablation. The central 2 mm of the stromal surface contracted by 2.21% ± 0.80% at a sustained temperature of 5°C. Ablation of plastic spheres produced no significant change. CONCLUSIONS: The excimer laser interacts with the nonablated residual stromal surface in a characteristic fashion not seen with isotropic, inorganic material. Increases in asphericity, surface roughness, surface contraction, and stromal morphologic changes are supportive of this interaction. The surface changes demonstrated may be indicative of temperature-induced transverse collagen fibril contraction and stress redistribution, or the ablation threshold of the stromal surface may be altered. This phenomenon may be of increased importance using lasers with increased thermal load.