Subclinical Keratoconus Detection and Characterization Using Motion-Tracking Brillouin Microscopy.

PURPOSE: To characterize focal biomechanical alterations in subclinical keratoconus (SKC) using motion-tracking (MT) Brillouin microscopy and evaluate the ability of MT Brillouin metrics to differentiate eyes with SKC from normal control eyes. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Thirty eyes from 30 patients were evaluated, including 15 eyes from 15 bilaterally normal patients and 15 eyes with SKC from 15 patients. METHODS: All patients underwent Scheimpflug tomography and MT Brillouin microscopy using a custom-built device. Mean and minimum MT Brillouin values within the anterior plateau region and anterior 150 µm were generated. Scheimpflug metrics evaluated included inferior-superior (IS) value, maximum keratometry (Kmax), thinnest corneal thickness, asymmetry indices, Belin/Ambrosio display total deviation, and Ambrosio relational thickness. Receiver operating characteristic (ROC) curves were generated for all Scheimpflug and MT Brillouin metrics evaluated to determine the area under the ROC curve (AUC), sensitivity, and specificity for each variable. MAIN OUTCOME MEASURES: Discriminative performance based on AUC, sensitivity, and specificity. RESULTS: No significant differences were found between groups for age, sex, manifest refraction spherical equivalent, corrected distance visual acuity, Kmax, or KISA% index. Among Scheimpflug metrics, significant differences were found between groups for thinnest corneal thickness (556 µm vs. 522 µm; P < 0.001), IS value (0.29 diopter [D] vs. 1.05 D; P < 0.001), index of vertical asymmetry (IVA; 0.10 vs. 0.19; P < 0.001), and keratoconus index (1.01 vs. 1.05; P < 0.001), and no significant differences were found for any other Scheimpflug metric. Among MT Brillouin metrics, clear differences were found between control eyes and eyes with SKC for mean plateau (5.71 GHz vs. 5.68 GHz; P < 0.0001), minimum plateau (5.69 GHz vs. 5.65 GHz; P < 0.0001), mean anterior 150 µm (5.72 GHz vs. 5.68 GHz; P < 0.0001), and minimum anterior 150 µm (5.70 GHz vs. 5.66 GHz; P < 0.001). All MT Brillouin plateau and anterior 150 µm mean and minimum metrics fully differentiated groups (AUC, 1.0 for each), whereas the best performing Scheimpflug metrics were keratoconus index (AUC, 0.91), IS value (AUC, 0.89), and IVA (AUC, 0.88). CONCLUSIONS: Motion-tracking Brillouin microscopy metrics effectively characterize focal corneal biomechanical alterations in eyes with SKC and clearly differentiated these eyes from control eyes, including eyes that were not differentiated accurately using Scheimpflug metrics. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Motion-Tracking Brillouin Microscopy Evaluation of Normal, Keratoconic, and Post-Laser Vision Correction Corneas.

PURPOSE: To characterize focal biomechanical differences between normal, keratoconic, and post-laser vision correction (LVC) corneas using motion-tracking Brillouin microscopy. DESIGN: Prospective cross-sectional study. METHODS: Thirty eyes from 30 patients (10 normal controls [Controls], 10 post-LVC, and 10 stage I or II keratoconus [KC]) had Scheimpflug and motion-tracking Brillouin microscopy imaging using a custom-built device. Mean, maximum (max) and minimum (min) Brillouin shift, spatial standard deviation, and max-min values were compared. Min values were correlated with local Brillouin values at multiple Scheimpflug imaging locations. RESULTS: Mean (P < .0003), min (P < .00001), spatial standard deviation (P < .01), and max-min (P < .001) were significantly different between the groups. In post hoc pairwise comparisons, the best differentiators for group comparisons were mean (P = .0004) and min (P = .000002) for Controls vs KC, min (P = .0022) and max-min (P = .002) for Controls vs LVC, and mean (P = .0037) and min (P = .0043) for LVC vs KC. Min (area under the receiver operating characteristic = 1.0) and mean (area under the receiver operating characteristic =  0.96) performed well in differentiating Control and KC eyes. Min values correlated best with Brillouin shift values at the thinnest corneal point (r2 = 0.871, P = .001) and maximum keratometry value identified in the tangential curvature map (r2 = 0.840, P = .002). CONCLUSIONS: Motion-tracking Brillouin microscopy effectively characterized focal corneal biomechanical alterations in LVC and KC and clearly differentiated these groups from Controls. Primary motion-tracking Brillouin metrics performed well in differentiating groups as compared with basic Scheimpflug metrics, in contrast to previous Brillouin studies, and identified focal changes after LVC where prior Brillouin studies did not.

Long-term results of hyperopic ablations using alcohol-assisted PRK and FS-LASIK: comparative study.

PURPOSE: To evaluate the long-term visual and refractive outcomes of hyperopic excimer ablation using alcohol-assisted photorefractive keratectomy (PRK) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). SETTING: American University of Beirut Medical Center, Beirut, Lebanon. DESIGN: Retrospective, matched comparative study. METHODS: Eyes that underwent alcohol-assisted PRK were compared to matched eyes that underwent FS-LASIK. All patients were followed up for at least 3 years after surgery. The refractive and visual outcomes of each group were compared at different postoperative time points. The main outcome measures were spherical equivalent deviation from target (SEDT), manifest refraction, and visual acuity. RESULTS: 83 eyes underwent alcohol-assisted PRK and 83 matched eyes underwent FS-LASIK. Preoperative manifest refraction spherical equivalent was 2.44 ± 1.18 diopters (D) and 2.20 ± 0.87 D ( P = .133) in the PRK and FS-LASIK groups, respectively. Preoperative manifest cylinder was -0.77 ± 0.89 D and -0.61 ± 0.59 D ( P = .175) for the PRK and LASIK groups, respectively. 3 years postoperatively, SEDT was 0.28 ± 0.66 D and 0.40 ± 0.56 D for the PRK and LASIK groups, respectively ( P = .222), whereas manifest cylinder was -0.55 ± 0.49 D and -0.30 ± 0.34 D for PRK and LASIK, respectively ( P < .001). The mean difference vector was 0.59 ± 0.46 for PRK and 0.38 ± 0.32 for LASIK ( P < .001). 13.3% of PRK eyes and 0% of LASIK eyes had >1 D of manifest cylinder ( P = .003). CONCLUSIONS: Both alcohol-assisted PRK and FS-LASIK are safe and effective for the treatment of hyperopia. PRK induces slightly more postoperative astigmatism than LASIK. Larger optical zones and recently introduced ablation profiles that lead to a smoother ablation surface might improve the clinical results of hyperopic PRK.

The Most Cited Articles and Authors in Refractive Surgery.

PURPOSE: To provide a comprehensive analysis of the most highly cited articles and authors in refractive surgery. METHODS: The Scopus database was searched for articles pertaining to refractive surgery using multiple search terms to identify the top 100 most cited articles in refractive surgery. A publicly available database of more than 100,000 scientists that provides standardized information on multiple variables resulting in a composite indicator (C score) was searched to identify refractive surgery authors. A refractive surgery-specific composite score was created using only the authors' publications that were directly related to refractive surgery. RESULTS: The 100 most cited articles and 40 refractive surgery authors with the highest ranked C score were identified. The article with the most citations by Trokel et al has garnered nearly 800 citations to date. All articles included in the top 100 had 200 or more citations. The peak publication years were 1998 to 2001. Laser in situ keratomileusis (22), photorefractive keratectomy (18), and postoperative corneal ectasia and/or corneal biomechanics (16) were the most represented topics. Emory University generated the most articles (7) and the majority of publications (48%) originated in the United States. Steven E. Wilson, MD, had the highest refractive C score and Jorge L. Alió, MD, PhD, had the most refractive surgery articles and citations. Among all authors listed, the average number of refractive surgery publications was 97, with 35% of the group having more than 100 refractive surgery articles published. All authors on the list had more than 2,000 citations for their refractive surgery articles, whereas 38% had 4,000 or more citations. CONCLUSIONS: This list provides a comprehensive assessment of the most cited articles and authors in refractive surgery and demonstrates key focuses and trends in the field over time. [J Refract Surg. 2023;39(2):78-88.].

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.].

Determining the Utility of Epithelial Thickness Mapping in Refractive Surgery Evaluations.

PURPOSE: To determine the impact of corneal epithelial thickness maps on screening for refractive surgery candidacy in a single refractive surgical practice. DESIGN: Comparison of screening methods. METHODS: A total of 100 consecutive patients who presented for refractive surgery screening were evaluated. For each patient, screening based on Scheimpflug tomography, clinical data, and patient history was performed and a decision on eligibility for laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE)was independently made by 2 masked examiners. Examiners were then shown patients' epithelial thickness maps derived from optical coherence tomography (OCT). The percentage of screenings that changed after evaluating the epithelial thickness maps, with regard to candidacy for surgery, and ranking of surgical procedures from most to least favorable was determined. RESULTS: Candidacy for corneal refractive surgery changed in 16% of patients after evaluation of the epithelial thickness maps, with 10% of patients screened in and 6% screened out. Surgery of choice changed for 16% of patients, and the ranking of surgical procedures from most to least favorable changed for 25% of patients. A total of 11% of patients gained eligibility for LASIK, whereas 8% lost eligibility for LASIK. No significant difference was found between the evaluations of the 2 examiners. CONCLUSIONS: Epithelial thickness mapping derived from optical coherence tomography imaging of the cornea altered candidacy for corneal refractive surgery, as well as choice of surgery, in a substantial percentage of patients in our practice, and was thus a valuable tool for screening evaluations. Overall, the use of epithelial thickness maps resulted in screening in a slightly larger percentage of patients for corneal refractive surgery.

Motion-tracking Brillouin microscopy for in-vivo corneal biomechanics mapping.

Corneal biomechanics play a critical role in maintaining corneal shape and thereby directly influence visual acuity. However, direct corneal biomechanical measurement in-vivo with sufficient accuracy and a high spatial resolution remains an open need. Here, we developed a three-dimensional (3D) motion-tracking Brillouin microscope for in-vivo corneal biomechanics mapping. The axial tracking utilized optical coherence tomography, which provided a tracking accuracy better than 3 µm. Meanwhile, 10 µm lateral tracking was achieved by tracking pupils with digital image processing. The 3D tracking enabled reconstruction of depth-dependent Brillouin distribution with a high spatial resolution. This superior technical performance enabled the capture of high-quality mechanical mapping in vivo even while the subject was breathing normally. Importantly, we improved Brillouin spectral measurements to achieve relative accuracy better than 0.07% verified by rubidium absorption frequencies, with 0.12% stability over 2000 seconds. These specifications finally yield the Brillouin measurement sensitivity that is required to detect ophthalmology-relevant corneal biomechanical properties.

Repeatability of Zone Averages Compared to Single-Point Measurements of Maximal Curvature in Keratoconus.

PURPOSE: To evaluate the repeatability of curvature zone averages centered on the point of maximum curvature (Kmax) compared to that of the single-point Kmax. DESIGN: Comparative reliability analysis. METHODS: Setting: American University of Beirut Medical Center, Beirut, Lebanon. STUDY POPULATION: Sixty-five eyes of 65 adult keratoconus patients. Patients with other ocular disease, history of ocular surgery or trauma, and contact lens wear within 2 weeks of image acquisition were excluded. OBSERVATION PROCEDURES: Eyes were evaluated with 3 consecutive scans using the Galilei dual Scheimpflug-Placido system. MAIN OUTCOME MEASURES: Repeatability of axial and instantaneous Kmax single points, and zone averages with radii of 0.1-2.0 mm, centered on them. Repeatability was assessed by within-subject standard deviations, repeatability limits (r), and intraclass correlation coefficients. RESULTS: Axial curvature zone averaging yielded clinically acceptable repeatability only in eyes with Kmax ≤50 diopters (D), for radii of 1.5 mm and 2.0 mm (r = 0.87 D and r = 0.76, respectively, vs r = 0.91 for the single-point axial Kmax). Compared to instantaneous Kmax, clinically acceptable repeatability was achieved with instantaneous zone averages of at least 1.5 mm radius in eyes with Kmax ≤50 D (r = 0.99 D and r = 0.70 D, respectively) and 2.0 mm radius in eyes with Kmax >50 D (r = 2.28 D and r = 0.87 D, respectively). For all eyes, the repeatability limit of the location of Kmax was 0.82 mm and 0.80 mm for axial and instantaneous curvature, respectively. CONCLUSIONS: Instantaneous curvature zone averages centered on Kmax yielded a greater improvement in repeatability than axial zone averages and reached clinical adequacy with radii of at least 1.5 mm, for eyes with Kmax ≤50 D, and with a 2.0 mm radius for eyes with Kmax >50 D.