A New Biomechanical Deformation Response Parameter: Change in Central Corneal Thickness During Air Puff Induced Corneal Deformation.

PURPOSE: To investigate the percent change in central corneal thickness (%ΔCCT) during air-puff-induced deformation as an indicator of corneal biomechanical response. METHODS: Forty ex vivo human eyes from forty donors were imaged using the CorVis ST at experimentally controlled intraocular pressure (IOP) of 10, 20, 30, and 40 mmHg, followed by uniaxial strip testing to calculate tensile modulus. The CorVis ST research software tracked the anterior and posterior cornea edges and determined the dynamic corneal response (DCR) parameters. Eyes were excluded if image quality or posterior tracking issues were present. Custom algorithms were used to calculate CCT during deformation using a ray-tracing method to correct for Scheimpflug and optical distortion within each image. Correlation and stepwise regression analyses between the shape-related DCR parameters and %ΔCCT were conducted. A mixed model analysis was performed to test the effect of IOP and the strongest significant predictors of the stepwise regression on %ΔCCT. The significance threshold was set to p < 0.05. RESULTS: Thirty eyes were ultimately analyzed and CCT increased significantly from the pre-deformation state to the highest concavity state at each IOP level (p < 0.001). IOP and multiple shape DCRs were found to be significantly related to %ΔCCT (p < 0.0001). The strongest predictor of %ΔCCT was integrated inverse radius (IIR) (p < 0.0001; partial R2 = 0.4772) with no other parameter having a partial R2 value greater than 0.04. The mixed model analysis showed that IIR was the sole predictor (p = 0.0098) and IOP was no longer significant as a single predictor. However, the interaction of IIR with IOP (p = 0.0023) had a significant effect on %ΔCCT. CONCLUSION: Percent change in CCT is influenced by corneal stiffness as indicated by the significant relationship with IIR. The %ΔCCT may be a potential biomarker for determining differences in corneal deformation response with corneal diseases.

Effect of corneal cross-linking on biomechanical changes following transepithelial photorefractive keratectomy and femtosecond laser-assisted LASIK.

Purpose: To evaluate the change in corneal biomechanics in patients with postoperative ectasia risk when combining two common laser vision correction procedures (tPRK and FS-LASIK) with cross-linking (in tPRK Xtra and FS-LASIK Xtra). Methods: The study included 143 eyes of 143 myopic, astigmatic patients that were divided into non-cross-linked refractive surgery groups (non-Xtra groups, tPRK and FS-LASIK) and cross-linked groups (Xtra groups, tPRK Xtra and FS-LASIK Xtra) according to an ectasia risk scoring system. The eyes were subjected to measurements including the stress-strain index (SSI), the stiffness parameter at first applanation (SP-A1), the integrated inverse radius (IIR), the deformation amplitude at apex (DA), and the ratio of deformation amplitude between apex and 2 mm from apex (DARatio2mm). The measurements were taken preoperatively and at 1, 3, and 6 months postoperatively (pos1m, pos3m, and pos6m). Posterior demarcation line depth from the endothelium (PDLD) and from the ablation surface (DLA) were recorded at pos1m. Results: SP-A1 significantly decreased, while IIR, deformation amplitude, and DARatio2mm increased significantly postoperatively in all four groups (p < 0.01)-all denoting stiffness decreases. In the FS-LASIK group, the changes in IIR, DA, and DARatio2mm were 32.7 ± 15.1%, 12.9 ± 7.1%, and 27.2 ± 12.0% respectively, which were significantly higher (p < 0.05) compared to 20.1 ± 12.8%, 6.4 ± 8.2%, and 19.7 ± 10.4% in the FS-LASIK Xtra group. In the tPRK group, the change in IIR was 27.3 ± 15.5%, significantly larger than 16.9 ± 13.4% in the tPRK Xtra group. The changes of SSI were minimal in the tPRK (-1.5 ± 21.7%, p = 1.000), tPRK Xtra (8.4 ± 17.9%, p = 0.053), and FS-LASIK Xtra (5.6 ± 12.7%, p = 0.634) groups, but was significant in the FS-LASIK group (-12.1 ± 7.9%, p < 0.01). After correcting for baseline biomechanical metrics, preoperative bIOP and the change in central corneal thickness (△CCT) from pre to pos6m, the changes in the IIR in both FS-LASIK and tPRK groups, as well as DA, DARatio2mm and SSI in the FS-LASIK group remained statistically greater than their corresponding Xtra groups (all p < 0.05). Most importantly, after correcting for these covariates, the changes in DARatio2mm in the FS-LASIK Xtra became statistically smaller than in the tPRK Xtra (p = 0.017). Conclusion: The statistical analysis results indicate that tPRK Xtra and FS-LASIK Xtra effectively reduced the biomechanical losses caused by refractive surgery (tPRK and FS-LASIK). The decrease in corneal overall stiffness was greater in FS-LASIK than in tPRK, and the biomechanical enhancement of CXL was also higher following LASIK than after tPRK.

Comparison of corneal biomechanical parameters in healthy corneas with symmetric and asymmetric bow-tie topographic pattern with inferior and superior steepening.

PURPOSE: To compare the corneal biomechanical parameters in healthy corneas with symmetric and asymmetric bow-tie topographic patterns. METHODS: In this cross-sectional study, 144 eyes were divided based on inferior-superior asymmetry value (I-S) into symmetric (zero I-S: - 0.50 to + 0.50 D) and asymmetric bow-tie topographic patterns with inferior (positive I-S: + 0.51 to + 1.4 D) or superior (negative I-S: - 2.5 to - 0.51 D) steepening. The biomechanical assessment was performed using Corvis ST and ocular response analyzer (ORA). A general linear model univariate analysis was used to compare the parameters, while the central corneal thickness, intraocular pressure, and age were considered covariates. RESULTS: Only the peak distance (PD) at the highest concavity phase (P = 0.007) and tomographic biomechanical index (TBI, P = 0.001) showed statistically significant differences between the three groups. For TBI, this difference was statistically significant between the positive I-S group separately with the zero I-S group (P < 0.001), and with the negative I-S group (P = 0.022). For PD, the significant difference was between the negative I-S group separately with zero I-S (P = 0.019), and positive I-S groups (P = 0.018). There was a statistically significant correlation between the I-S value with PD (r = 0.281, P = 0.001) and TBI (r = 0.170, P = 0.044). CONCLUSIONS: Most corneal biomechanical parameters are not statistically significant compared to the zero I-S group. However, superior steepening is associated with a stiffer response based solely on the shorter PD values seen in this group, and the group with the inferior steepening shows the highest or more suspicious values based on TBI.

Biomechanical and Vascular Metrics Between Eyes of Patients With Asymmetric Glaucoma and Symmetric Glaucoma.

PRCIS: Corneal hysteresis (CH) and pulsatile ocular blood volume (POBV) were significantly lower in the eye with greater damage in asymmetric glaucoma, without a difference in intraocular pressure (IOP) or central corneal thickness (CCT), and no difference in elastic parameters. OBJECTIVE: To compare biomechanical and vascular metrics between the eyes of patients with asymmetric glaucoma (ASYMM) and those with symmetric glaucoma (SYMM). PATIENTS AND METHODS: Forty-five patients were prospectively recruited and divided into ASYMM, defined as cup-to-disc (C/D) ratio difference >0.1 between eyes and SYMM, with C/D difference ≤0.1. For ASYMM, the smaller C/D was defined as the best eye ("best") and the fellow eye was defined as the worst eye ("worse"). All metrics were subtracted as "worse" minus "best," including the viscoelastic parameter CH, and elastic parameters from the Corvis ST, including stiffness parameter at first applanation, stiffness parameter at highest concavity, integrated inverse radius, deformation amplitude ratio, IOP, CCT, mean deviation (MD), ganglion cell complex (GCC), and POBV were included. Paired t tests were performed between eyes in both groups. Statistical analyses were performed with SAS using a significance threshold of P <0.05. RESULTS: For ASYMM (16 patients), "worse" showed significantly lower CH (-0.76 ± 1.22), POBV (-0.38 ± 0.305), MD (-3.66 ± 6.55), and GCC (-7.9 ± 12.2) compared with "best." No other parameters were significantly different. For SYMM (29 patients), there were no significantly different metrics between eyes. CONCLUSIONS: Lower CH, POBV, GCC, and worse MD were associated with greater glaucomatous damage in asymmetric glaucoma without a difference in IOP or CCT. Lower CH and GCC are consistent with previous studies. POBV, a new clinical parameter that may indicate reduced blood flow, is also associated with greater damage.

Keratoconus cone location influences ocular biomechanical parameters measured by the Ocular Response Analyzer.

BACKGROUND: Keratoconus is characterized by asymmetry in the biomechanical properties of the cornea, with focal weakness in the area of cone formation. We tested the hypothesis that centrally-measured biomechanical parameters differ between corneas with peripheral cones and corneas with central cones. METHODS: Fifty participants with keratoconus were prospectively recruited. The mean ± standard deviation age was 38 ± 13 years. Axial and tangential corneal topography were analyzed in both eyes, if eligible. Cones in the central 3 mm of the cornea were considered central, and cones outside the central 3 mm were considered peripheral. Each eye was then measured with the Ocular Response Analyzer (ORA) tonometer. T-tests compared differences in ORA-generated waveform parameters between cohorts. RESULTS: Seventy-eight eyes were analyzed. According to the axial topography maps, 37 eyes had central cones and 41 eyes had peripheral cones. According to the tangential topography maps, 53 eyes had central cones, and 25 eyes had peripheral cones. For the axial-topography algorithm, wave score (WS) was significantly higher in peripheral cones than central cones (inter-cohort difference = 1.27 ± 1.87). Peripheral cones had a significantly higher area of first peak, p1area (1047 ± 1346), area of second peak, p2area (1130 ± 1478), height of first peak, h1 (102 ± 147), and height of second peak, h2 (102 ± 127), than central cones. Corneal hysteresis (CH), width of the first peak, w1, and width of the second peak, w2, did not significantly differ between cohorts. There were similar results for the tangential-topography algorithm, with a significant difference between the cohorts for p1area (855 ± 1389), p2area (860 ± 1531), h1 (81.7 ± 151), and h2 (92.1 ± 131). CONCLUSIONS: Cone location affects the biomechanical response parameters measured under central loading of the cornea. The ORA delivers its air puff to the central cornea, so the fact that h1 and h2 and that p1area and p2area were smaller in the central cone cohort than in the peripheral cone cohort suggests that corneas with central cones are softer or more compliant centrally than corneas with peripheral cones, which is consistent with the location of the pathology. This result is evidence that corneal weakening in keratoconus is focal in nature and is consistent with localized disruption of lamellar orientation.

Corneal Stress Distribution Evolves from Thickness-Driven in Normal Corneas to Curvature-Driven with Progression in Keratoconus.

Purpose: To introduce the novel parameter of Corneal Contribution to Stress (CCS) and compare stress distribution patterns between keratoconus (KCN) and normal corneas. Design: Prospective, observational, cross-sectional study. Participants: The study included 66 eyes of 40 subjects diagnosed with KCN and 155 left eyes from 155 normal control (NRL) subjects. Methods: Tomography was obtained to calculate the newly proposed CCS, defined according to the hoop stress formula without intraocular pressure, R/2t, where R is the radius of curvature and t is the thickness. CCS maps were calculated from pachymetry and tangential curvature maps. Custom software identified the 2-mm-diameter zones of greatest curvature (Cspot-max), thinnest pachymetry (Pach-min), greatest stress (CCSmax), and lowest stress (CCSmin). Stress difference (CCSdiff) was calculated as CCSmax - CCSmin. Distances between Cspot-max vs. Pach-min, vs. CCSmax, and vs. CCSmin, as well as between Pach-min vs. CCSmax and vs. CCSmin, were calculated. t tests were performed between cohorts, and paired t tests were performed within cohorts. Univariate linear regression analyses were performed between parameters and distances. The significance threshold was P < 0.05. Main Outcome Measures: Corneal stress parameters, corneal features of maximum curvature, minimum thickness, and distances between corneal stress parameters and corneal features. Results: CCSmax was significantly closer to Pach-min (0.79 ± 0.92) and Cspot-max (2.04 ± 0.85) than CCSmin (3.17 ± 0.38, 2.73 ± 1.53, respectively) in NRL, P < 0.0001, whereas CCSmin was significantly closer to Cspot-max (1.35 ± 1.43) than CCSmax (2.52 ± 0.72) in KCN, P < 0.0001. Cspot-max (severity) was significantly related to CCSdiff in KCN (P < 0.0001; R2 = 0.5882) with a weak relationship in NRL (P < 0.0080, R2 = 0.0451). Cspot-max was significantly related to the distance from Pach-min to CCSmax (P < 0.0001; R2 = 0.3737) without significance in NRL (P = 0.8011). Conclusions: Corneal stress is driven by thickness in NRL, with greatest stress at thinnest pachymetry and greatest curvature. However, maximum stress moves away from thinnest pachymetry with progression in KCN, and minimum stress is associated with maximum curvature. Severity in KCN is significantly related to greater difference between maximum and minimum stress, consistent with the biomechanical cycle of decompensation. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effect of intrastromal corneal ring segments on in vivo corneal biomechanics in keratoconus: 1-year results.

PURPOSE: To evaluate the 1-year effects of the implantation of intrastromal corneal ring segments (ICRS) in keratoconus (KC) on the dynamic corneal response (DCR) parameters obtained with the Corvis. SETTING: Fernández-Vega Ophthalmological Institute, Oviedo, Spain. DESIGN: Prospective, single-center, clinical study. METHODS: Included were patients who underwent ICRS implantation for KC over a period of 1 year. On the day of the surgery and at least 6 months after ICRS implantation, the following measurements were made: corrected distance and uncorrected distance visual acuity, corneal tomography indices with the Pentacam, biomechanically corrected intraocular pressure and the Corvis DCRs (integrated inverse concave radius, deformation amplitude ratio, stiffness parameter at first applanation, stress-strain index [SSI] and the highest concavity radius). RESULTS: 30 eyes were included with a mean follow-up time of 15 months. Statistical analysis showed that ICRS implantation induced significant improvements in corneal biomechanics measurements between preoperative and long-term follow-up as demonstrated by a significant increase in SSI (P = .003). To confirm that this difference was actually induced due to a stiffening between early postoperative (previously published) and long-term an additional t-test was done between month 1 and late follow-up which confirmed a significant stiffening in the value of SSI (P = .01). CONCLUSIONS: Patients implanted with ICRS alone for KC showed a significantly stiffer response due to increased structural support compared with preoperative values and 1 month postoperative.

3D Bioprinting of Acellular Corneal Stromal Scaffolds with a Low Cost Modified 3D Printer: A Feasibility Study.

PURPOSE: Loss of corneal transparency is one of the major causes of visual loss, generating a considerable health and economic burden globally. Corneal transplantation is the leading treatment procedure, where the diseased cornea is replaced by donated corneal tissue. Despite the rise of cornea donations in the past decade, there is still a huge gap between cornea supply and demand worldwide. 3D bioprinting is an emerging technology that can be used to fabricate tissue equivalents that resemble the native tissue, which holds great potential for corneal tissue engineering application. This study evaluates the manufacturability of 3D bioprinted acellular corneal grafts using low-cost equipment and software, not necessarily designed for bioprinting applications. This approach allows access to 3D printed structures where commercial 3D bioprinters are cost prohibitive and not readily accessible to researchers and clinicians. METHODS: Two extrusion-based methods were used to 3D print acellular corneal stromal scaffolds with collagen, alginate, and alginate-gelatin composite bioinks from a digital corneal model. Compression testing was used to determine moduli. RESULTS: The printed model was visually transparent with tunable mechanical properties. The model had central radius of curvature of 7.4 mm, diameter of 13.2 mm, and central thickness of 0.4 mm. The compressive secant modulus of the material was 23.7 ± 1.7 kPa at 20% strain. 3D printing into a concave mold had reliability advantages over printing into a convex mold. CONCLUSIONS: The printed corneal models exhibited visible transparency and a dome shape, demonstrating the potential of this process for the preparation of acellular partial thickness corneal replacements. The modified printing process presented a low-cost option for corneal bioprinting.

Intereye Differences in the Clinical Assessment of Intraocular Pressure and Ocular Biomechanics.

SIGNIFICANCE: Clinicians and researchers will have evidence whether intereye differences confound clinical measurements of intraocular pressure or of ocular biomechanical parameters. PURPOSE: The purpose of this study was to determine whether intraocular pressure and biomechanical parameters, as measured by the Ocular Response Analyzer (ORA) and by Cornea Visualization with Scheimpflug Technology (CorVis ST), are different between the first and second eye measured. METHODS: Intraocular pressure and biomechanical parameters were collected from both eyes of healthy participants (N = 139). The ORA measured corneal-compensated intraocular pressure, Goldmann-correlated intraocular pressure, and corneal hysteresis. The CorVis ST measured biomechanically corrected intraocular pressure, stiffness parameter at first applanation, and stiffness parameter at highest concavity. For each measurement, a paired t test compared the value of the first eye measured against that of the second eye measured. RESULTS: For the ORA, Goldmann-correlated intraocular pressure was significantly higher ( P = .001) in the first eye (14.8 [3.45] mmHg) than in the second eye (14.3 [3.63] mmHg). For the CorVis ST, biomechanically corrected intraocular pressure was significantly higher ( P < .001) in the second eye (14.7 [2.14] mmHg) than in the first eye (14.3 [2.11] mmHg). Stiffness parameter at first applanation (intereye difference, 6.85 [9.54] mmHg/mm) was significantly ( P < .001) higher in the first eye than in the second eye. Stiffness parameter at highest concavity was significantly higher ( P = .01) in the second eye (14.3 [3.18] mmHg/mm) than in the first eye (14.0 [3.13] mmHg/mm). CONCLUSIONS: Although there were statistically significant intereye differences in intraocular pressure and in biomechanical parameters for both devices, the variations were small and thus unlikely to affect clinical outcomes.

Corneal Biomechanics After SMILE, Femtosecond-Assisted LASIK, and Photorefractive Keratectomy: A Matched Comparison Study.

Purpose: To evaluate the change in corneal stiffness after small incision lenticule extraction (SMILE), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), and photorefractive keratectomy (PRK). Methods: Age, gender, spherical equivalent, and central corneal thickness (CCT)-matched cases undergoing SMILE with a 120-µ cap, FS-LASIK with a 110-µ flap, and PRK were enrolled. One-year change in the stress-strain index, stiffness parameter at first applanation, integrated inverse radius, deformation amplitude ratio at 2 mm, and deformation amplitude ratio at 1 mm were compared between the surgical groups by linear mixed-effect models. Results: Within each surgical group, 120 eyes completed 1 year of follow-up. The residual stromal bed (RSB) thickness and (RSB/CCTpostop) were 348.1 ± 35.0 (0.74), 375.4 ± 31.0 (0.77) and 426.7 ± 2 µm (0.88) after SMILE, FS-LASIK, and PRK, respectively. The 1-year change in all biomechanical indices was significant, except the stress-strain index with PRK (P = 0.884). The change in all indices with SMILE were significantly greater than with FS-LASIK and with PRK (all P < 0.01), except the deformation amplitude ratio at 1 mm change between SMILE and FS-LASIK (P = 0.075). The changes in all indices with FS-LASIK were significantly greater than with PRK (all P < 0.05). Conclusions: Although SMILE preserves the greatest amount of anterior cornea with a cap thickness of 120 µ, this also produces the smallest RSB and the greatest decrease in stiffness. Thus, the RSB is shown to be the predominant determinant of stiffness decreases, rather than the preserved anterior cornea. We recommend using a thinner cap to achieve a thicker RSB and a lesser decrease in the corneal stiffness in the SMILE procedure. Translational Relevance: After refractive surgery, RSB is predominant determinant of stiffness decreases, rather than the preserved anterior cornea.

Estimating pulsatile ocular blood volume from intraocular pressure, ocular pulse amplitude, and axial length.

The purpose of this study was to develop a method of estimating pulsatile ocular blood volume (POBV) from measurements taken during an ophthalmic exam, including axial length and using a tonometer capable of measuring intraocular pressure (IOP) and ocular pulse amplitude (OPA). Unpublished OPA data from a previous invasive study was used in the derivation, along with central corneal thickness (CCT) and axial length (AL), as well as IOP from the PASCAL dynamic contour tonometer (DCT) and intracameral (ICM) measurements of IOP for 60 cataract patients. Intracameral mean pressure was set to 15, 20, and 35 mmHg (randomized sequence) in the supine position, using a fluid-filled manometer. IOP and OPA measurements were acquired at each manometric setpoint (DCT and ICM simultaneously). In the current study, ocular rigidity (OR) was estimated using a published significant relationship of OR to the natural log of AL in which OR was invasively measured through fluid injection. Friedenwald's original pressure volume relationship was then used to derive the estimated POBV, delivered to the choroid with each heartbeat as a function of OR, systolic IOP (IOPsys), diastolic IOP (IOPdia), and OPA, according to the derived equation POBV = log (IOPsys/IOPdia) / OR. Linear regression analyses were performed comparing OPA to OR and calculated POBV at each of the three manometric setpoints. POBV was also compared to OPA/IOPdia with all data points combined. Significance threshold was p < 0.05. OR estimated from AL showed a significant positive relationship to OPA for both DCT (p < 0.011) and ICM (p < 0.006) at all three manometric pressure setpoints, with a greater slope for lower IOP. Calculated POBV also showed a significant positive relationship to OPA (p < 0.001) at all three setpoints with greater slope at lower IOP, and a significant negative relationship with IOPdia. In the combined analysis, POBV showed a significant positive relationship to OPA/ IOPdia (p < 0.001) in both ICM and DCT measurements with R2 = 0.9685, and R2 = 0.9589, respectively. POBV provides a straight-forward, clinically applicable method to estimate ocular blood supply noninvasively. Higher IOP in combination with lower OPA results in the lowest values of POBV. The simplified ratio, OPA/ IOPdia, may also provide a useful clinical tool for evaluating changes in ocular blood supply in diseases with a vascular component, such as diabetic retinopathy and normal tension glaucoma. Future studies are warranted.

Variability of CLMI-X parameters, zonal Kmax, and single-point Kmax in keratoconus progression.

OBJECTIVES: To compare the repeatability of Cone Location and Magnitude Index expanded (CLMI.X) parameters of 2 mm diameter zone of greatest corneal curvature (Cspot-Axi) and 1 mm diameter zone of thinnest pachmymetry (Spot-Pach) with the maximum single point keratometry (Kmax), 3 mm Zonal Kmax (Z-Kmax3), and thinnest single point pachymetry (TP) in keratoconus (KC). METHODS: In this Comparative repeatability study, data from 36 eyes of 36 normal individuals and 72 eyes of 72 KC patients (28 eyes with ≤50.0D and 44 eyes with >50.0D Z-Kmax3) were analyzed. For each enrolled eye, imaging was done 6 times (3 consecutive acquisitions with a half hour break). For each parameter, the within-subject standard deviation (Sw) was calculated from the data of the six exams. RESULTS: In the normal group, Cspot-Axi-Sw was different from Kmax-Sw (p = 0.0004). Also, Z-Kmax3-Sw was different from Kmax-Sw (p = 0.0297). The difference between Cspot-Axi-Sw and Z-Kmax3-Sw was statistically significant (p = 0.0482). In the KC group, Sw were significantly different between Cspot-Axi and Kmax (p < 0.0001), and between Z-Kmax3 and Kmax (p < 0.0001). In the Z-Kmax3 ≤ 50.0D subgroup, Sw were different between Cspot-Axi and Kmax (p = 0.0002). In the Z-Kmax3 > 50.0D subgroup, Sw were different between Cspot-Axi and Kmax (p < 0.0001), and between Z-Kmax3 and Kmax (p < 0.0001). Sw differences between Spot-Pach and TP were not significant in any of the study groups (all P > 0.05). CONCLUSIONS: In the diagnosis and follow up of KC, the zonal averages of Cspot-Axi and Z-Kmax3 are more reliable than the single point Kmax. The repeatability of Spot-Pach is similar to TP and both variables should suit the purpose equally.

Orbital fat swelling: A biomechanical theory and supporting model for spaceflight-associated neuro-ocular syndrome (SANS).

Spaceflight-Associated Neuro-ocular Syndrome (SANS) is a descriptor of several ocular and visual signs and symptoms which commonly afflicts those exposed to microgravity. We propose a new theory for the driving force leading to the development of Spaceflight-Associated Neuro-ocular Syndrome which is described via a finite element model of the eye and orbit. Our simulations suggest that the anteriorly directed force produced by orbital fat swelling is a unifying explanatory mechanism for Spaceflight-Associated Neuro-ocular Syndrome, as well as producing a larger effect than that generated by elevation in intracranial pressure. Hallmarks of this new theory include broad flattening of the posterior globe, loss of tension in the peripapillary choroid, decreased axial length, consistent with findings in astronauts. A geometric sensitivity study suggests several anatomical dimensions may be protective against Spaceflight-Associated Neuro-ocular Syndrome.

Optimized Artificial Intelligence for Enhanced Ectasia Detection Using Scheimpflug-Based Corneal Tomography and Biomechanical Data.

PURPOSE: To optimize artificial intelligence (AI) algorithms to integrate Scheimpflug-based corneal tomography and biomechanics to enhance ectasia detection. DESIGN: Multicenter cross-sectional case-control retrospective study. METHODS: A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Optikgeräte GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy. RESULTS: The area under the receiver operating characteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sensitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), developed with 18 features in 156 trees using 10-fold cross-validation, had a significantly higher AUC (0.945; DeLong, P < .0001) for detecting VAE-NT (84.4% sensitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001). CONCLUSIONS: AI optimization to integrate Scheimpflug-based corneal tomography and biomechanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning considering additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will continuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Clinical Ocular Biomechanics: Where Are We after 20 Years of Progress?

Purpose: Ocular biomechanics is an assessment of the response of the structures of the eye to forces that may lead to disease development and progression, or influence the response to surgical intervention. The goals of this review are (1) to introduce basic biomechanical principles and terminology, (2) to provide perspective on the progress made in the clinical study and assessment of ocular biomechanics, and (3) to highlight critical studies conducted in keratoconus, laser refractive surgery, and glaucoma in order to aid interpretation of biomechanical parameters in the laboratory and in the clinic.Methods: A literature review was first conducted of basic biomechanical studies related to ocular tissue. The subsequent review of ocular biomechanical studies was limited to those focusing on keratoconus, laser refractive surgery, or glaucoma using the only two commercially available devices that allow rapid assessment of biomechanical response in the clinic.Results: Foundational studies on ocular biomechanics used a combination of computer modeling and destructive forces on ex-vivo tissues. The knowledge gained from these studies could not be directly translated to clinical research and practice until the introduction of non-contact tonometers that quantified the deformation response of the cornea to an air puff, which represents a non-destructive, clinically appropriate load. The corneal response includes a contribution from the sclera which may limit corneal deformation. Two commercial devices are available, the Ocular Response Analyzer which produces viscoelastic parameters with a customized load for each eye, and the Corvis ST which produces elastic parameters with a consistent load for every eye. Neither device produces the classic biomechanical properties reported in basic studies, but rather biomechanical deformation response parameters which require careful interpretation.Conclusions: Research using clinical tools has enriched our understanding of how ocular disease alters ocular biomechanics, as well as how ocular biomechanics may influence the pathophysiology of ocular disease and response to surgical intervention.

A Review of Corneal Biomechanics and Scleral Stiffness in Topical Prostaglandin Analog Therapy for Glaucoma.

PURPOSE: The mechanism of action underlying prostaglandin analog (PGA) therapy involves changes in the expression of different metalloproteases to increase permeability of the sclera and allow increased aqueous humor outflow through this alternative drainage pathway. This alteration of structure impacts cornea/scleral biomechanics and may introduce artifact into the measurement of intraocular pressure (IOP) in the clinical setting. METHODS: A literature search reviewing the impact of PGA therapy on corneal and scleral biomechanics was conducted including basic studies, clinical studies with treatment naïve patients, and a clinical study examining the cessation of PGA therapy. Additional literature including engineering texts was added for greater clarity of the concepts underlying ocular biomechanics. RESULTS: One study with an animal model reported significant corneal stiffening with PGA treatment. Most longitudinal clinical studies examining the effects of initiation of PGA therapy in PGA naïve subjects failed to report biomechanical parameters associated with stiffness using the Corvis ST and only included those parameters strongly influenced by IOP. One study reported a significant reduction in scleral stiffness with IOP as a co-variate, highlighting the need to account for the effects of IOP lowering when assessing clinical biomechanics. The report of cessation of PGA therapy on corneal biomechanics showed no change in corneal compensated IOP after 6 weeks, raising the question of reversibility of the PGA-induced structural alteration. CONCLUSIONS: Given that the findings in several clinical studies may merely reflect a reduction in IOP, further studies are warranted using Corvis ST parameters associated with corneal and scleral stiffness. The gold standard for IOP measurement in the clinical setting is Goldmann applanation tonometry, a technique previously shown to be affected by corneal stiffness. Since PGA therapy has been reported to alter not only scleral biomechanics, but also corneal biomechanics, it is essential to consider alternative tonometry technologies in the clinic.

Hemodialysis Arteriovenous Access Cosmesis Scale (AVACS): A new measure for vascular access.

RATIONALE AND OBJECTIVE: This study aimed to develop a cosmesis scale to evaluate the cosmetic appearance of hemodialysis (HD) arteriovenous (AV) accesses from the perspective of the patient and clinician, which could be incorporated into clinical trials. STUDY DESIGN: Using a modified Delphi process, two AV access cosmesis scale (AVACS) components were developed in a four-round Delphi panel consisting of two surveys and two consensus meetings with two rounds of patient consultation. SETTING AND PARTICIPANTS: The Delphi panel consisted of 15 voting members including five interventional or general nephrologists, five vascular surgeons, three interventional radiologists, and two vascular access nurse coordinators. Four patients experienced with vascular access were involved in patient question development. ANALYTICAL APPROACH: For a component to be included in the AVACS, it had to meet the prespecified panel consensus agreement of ⩾70%. RESULTS: The clinician component of the AVACS includes nine questions on the following AV access features: scarring, skin discoloration, aneurysm/pseudoaneurysms and megafistula appearance. The patient component includes six questions about future vascular access decisions, interference with work or leisure activities, clothing choices, self-consciousness or attractiveness, emotional impact, and overall appearance. LIMITATIONS: Delphi panel methods are subjective by design, but with expert clinical opinion are used to develop classification systems and outcome measures. The developed scale requires further validation testing but is available for clinical trial use. CONCLUSIONS: While safety and efficacy are the primary concerns when evaluating AV access for HD, cosmesis is an important component of the ESKD patient experience. The AVACS has been designed to assess this important domain; it can be used to facilitate patient care and education about vascular access choice and maintenance. AVACS can also be used to inform future research on developing new techniques for AV access creation and maintenance, particularly as relates to AV access cosmesis.

Novel High-Resolution Imaging Using ANTERION Optical Coherence Tomography to Assess Fluid Reservoir Change in Scleral Lens Periphery.

OBJECTIVES: To assess scleral lens fluid reservoir (FR) change simultaneously in four quadrants with single acquisition using novel ANTERION anterior segment swept-source optical coherence tomography (SS-OCT). METHODS: A prospective, observational, clinical study of 18 subjects (30 eyes) was performed on adults fitted with a scleral lens for ocular surface disease (n=8), irregular cornea/scar (n=7), and corneal ectasia (n=15). ANTERION anterior segment SS-OCT imaging was obtained at the initial visit and at the follow-up to determine pre and post scleral lens settling, measured in microns, centrally and peripherally. Peripheral measurements were grouped into four quadrants. Repeated-measures ANOVA was performed comparing vault post minus pre differences by quadrant, and TTests comparing difference in FR by lens design were performed with a significant threshold at P <0.05. RESULTS: The mean central scleral lens settling was significant at -48.3±41.7 µm. The change in FR by quadrant was superior (S): -47.8±67.3 µm, inferior (I): -68.0±102.2 µm, nasal (N) -46.3±63.4 µm, and temporal (T): -56.7±49.3 µm. There were no significant differences in lens settling between the quadrants. Within the three categories, the irregular cornea group experienced significantly greater lens settling. There was no significant difference in central FR when comparing lens design or lens diameter. CONCLUSIONS: The ANTERION SS-OCT allows for high-resolution central and peripheral assessment of FR in scleral lens wear. With increased technology available for scleral lens customization, this imaging modality can assist in more detailed assessment in quadrant-specific scleral lens designs.

Comparative Contralateral Randomized Clinical Trial of Standard (3 mW/cm2) Versus Accelerated (9 mW/cm2) CXL in Patients With Down Syndrome: 3-Year Results.

PURPOSE: To compare the long-term results of accelerated corneal cross-linking (CXL) (9 mW/cm2, 10 min) with standard CXL (3 mW/cm2, 30 min) in patients with Down syndrome who had keratoconus. METHODS: In this contralateral randomized clinical trial, 27 patients with Down syndrome aged 15.78 ± 2.46 years (range: 10 to 19 years) were enrolled. CXL was performed using the KXL System (Avedro, Inc) under general anesthesia, and patients were followed up for 3 years. The main outcome measure was a change in average keratometry in the 3-mm zone around the steepest point (zonal Kmax-3mm). Secondary outcomes were changes in Corvis ST (Oculus Optikgeräte GmbH) biomechanical parameters and vision, refraction, and corneal tomography measurements. RESULTS: Mean 3-year changes in zonal Kmax-3mm were not significantly different between the accelerated and standard groups (-0.06 ± 0.75 and -0.35 ± 0.94 diopters [D], respectively, P = .727). Despite the contralateral design of the study, based on most baseline biomechanical indices, corneas in the standard group were weaker before treatment. The standard group also showed significantly fewer 3-year changes in the stress-strain index (-0.11 ± 0.21 vs -0.30 ± 0.32), integrated radius (+0.99 ± 3.48 vs +3.14 ± 2.84), and deformation amplitude ratio-2mm (-1.38 ± 1.33 vs +0.30 ± 1.75) (all P < .0167). Corneal stiffness in the accelerated group was stable for 2 years, and the decline mainly occurred during the third year. CONCLUSIONS: In young patients with Down syndrome who had keratoconus, accelerated and standard CXL showed a similar flattening effect. Standard CXL is better able to maintain corneal stiffness in weaker corneas. With accelerated CXL, despite stable results for 2 years, there was decreased corneal stiffness in the third year. Longer follow-up periods are warranted to study the decreased efficacy on keratoconus progression. [J Refract Surg. 2022;38(6):381-388.].

Biomechanical Evaluation of Topographically and Tomographically Normal Fellow Eyes of Patients With Keratoconus.

PURPOSE: To determine the effectiveness of parameters and indices based on biomechanical measures at discriminating fellow eyes with topographically and tomographically normal corneas in patients with keratoconus from normal control corneas. METHODS: The study included 47 keratoconus suspect eyes, defined as the topographically and tomographically normal fellow eyes of patients with frank keratoconus in the other eye. Eyes were imaged using the Pentacam HR and Corvis ST (both Oculus Optikgeräte GmbH). Fellow eyes were then categorized as topographically/tomographically normal fellow eyes (TNF) and topographically/tomographically borderline fellow eyes (TBF). The ability of each of the Corvis Biomechanical Index (CBI), Tomographic and Biomechanical Index (TBI), stiffness parameter at applanation 1 (SP-A1), and stress-strain index (SSI) at discriminating between normal controls and keratoconus suspects was assessed. RESULTS: The TBI had the best discriminative ability with the greatest area under the receiver operating characteristic (AUROC) curve value of 0.946 for normal controls versus TBF eyes, and 0.824 for normal controls versus TNF eyes. Compared to the TBI AUROC curves, SP-A1 and CBI had AUROC curve values of 0.833 (P = .09) and 0.822 (P = .01) for normal controls versus TBF eyes, respectively, and AUROC curve values of 0.822 (P = .96) and 0.550 (P = .0002) for normal controls versus TNF eyes, respectively. The TBI had the best positive predictive value for TNF and TBF eyes, followed by CBI and SP-A1. CONCLUSIONS: The TBI and the purely biomechanical parameter SP-A1 were of moderate utility in distinguishing between normal and keratoconus suspect eyes. In the absence of topographic/tomographic evidence of keratectasia, an independently abnormal biomechanical parameter may suggest an increased risk of ectasia. [J Refract Surg. 2022;38(5):318-325.].