Unilateral Granular Type 2 Corneal Dystrophy With Exacerbation After LASIK.

PURPOSE: The aim of this study was to report a case of unilateral granular corneal dystrophy type 2 (GCD2) with exacerbation after bilateral laser in situ keratomileusis (LASIK). METHODS: Clinical evaluation, Scheimpflug imaging, anterior segment optical coherence tomography (AS-OCT), cytology, and genetic testing were used to confirm the diagnosis of unilateral GCD2 with exacerbation after bilateral LASIK. Detailed literature review for possible unilateral GCD2 presentations was performed. RESULTS: A 54-year-old White woman presented with blurred vision in her left eye and a history of bilateral LASIK performed 8 years before. Examination revealed dense opacities in the left cornea only, which were confirmed to be confined to the LASIK interface and adjacent corneal stromal tissue, as determined by AS-OCT. The patient underwent flap lift, interface debris removal, and stromal bed phototherapeutic keratectomy. Cytological analysis showed eosinophilic corneal stromal deposits that stained with trichrome stain and were congophilic on Congo red stain. Genetic testing was positive for heterozygous GCD2 transforming growth factor ß-induced gene ( TGFBI ), c.371G>A, p.R124H mutation. There were no opacities identifiable in the right eye on serial slit-lamp examination, Scheimpflug imaging, or OCT imaging at 4 or 8 years after bilateral LASIK. Literature review failed to identify any previous reports of unilateral GCD2. CONCLUSIONS: This is the first known reported case of unilateral granular corneal dystrophy type 2. LASIK is contraindicated in eyes with corneal stromal dystrophies related to mutations in TGFBI as both flap creation and laser ablation can exacerbate visually significant opacity formation. Scheimpflug and AS-OCT imaging are useful to identify opacities in GCD2.

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.

Cataract surgery following refractive surgery: Principles to achieve optical success and patient satisfaction.

A growing number of patients with prior refractive surgery are now presenting for cataract surgery. Surgeons face a number of unique challenges in this patient population that tends to be highly motivated to retain or regain functional uncorrected acuity postoperatively. Primary challenges include recognition of the specific type of prior surgery, use of appropriate intraocular lens (IOL) power calculation formulas, matching IOL style with spherical aberration profile, the recognition of corneal imaging patterns that are and are not compatible with toric and/or presbyopia-correcting lens implantation, and surgical technique modifications, which are particularly relevant in eyes with prior radial keratotomy or phakic IOL implantation. Despite advancements in IOL power formulae, corneal imaging, and IOL options that have improved our ability to achieve targeted postoperative refractive outcomes, accuracy and predictability remain inferior to eyes that undergo cataract surgery without a history of corneal refractive surgery. Thus, preoperative evaluation of patients who will and will not be candidates for postoperative refractive surgical enhancements is also paramount. We provide an overview of the specific challenges in this population and offer evidence-based strategies and considerations for optimizing surgical outcomes.

The Most Cited Modern Articles in Refractive Surgery (2010-2020).

PURPOSE: To provide a comprehensive analysis of the most highly cited modern articles in refractive surgery, those published between 2010 and 2020, and compare these results to a list of the most highly cited articles in refractive surgery from all timepoints. 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 published between 2010 and 2020. Articles were reviewed for relevance and ranked based on total citations accrued. RESULTS: The 100 most cited modern articles in refractive surgery were identified. The article with the most citations by Sekundo et al has garnered nearly 600 citations to date. Almost all articles (88%) included in the top 100 had 200 or more citations. Intraocular lens (34 articles), keratorefractive lenticule extraction (ie, small incision lenticule extraction) (27 articles), and laser in situ keratomileusis (17 articles) were the predominant topics. Aarhus University in Denmark generated the most articles (5), whereas numerous articles originated from multiple countries, including the United States (16), United Kingdom (10), France (8), Spain (8), China (7), and Germany (7). CONCLUSIONS: This list provides a comprehensive assessment of the most cited modern articles in refractive surgery and demonstrates key focuses and trends in the field over the past decade. Intraocular lens and keratorefractive lenticule extraction were the primary topics. There was a broader representation of procedures, topics, authors, and country of origin as compared to prior work. [J Refract Surg. 2023;39(11):784-790.].

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.

Quantifying Corneal Topographic Astigmatism (CorT Total) in Keratoconic Eyes.

PURPOSE: To determine optimal corneal regions from which to derive corneal topographic astigmatism (CorT) in kerato-conic eyes. METHODS: In this retrospective study, potential measures of corneal astigmatism are calculated from raw total corneal power data (179 eyes from 124 patients) from a corneal tomographer. The measures are derived from annular corneal regions varying in both extent and center position, and evaluated according to the variability of the ocular residual astigmatism (ORA) in the cohort. This variability is quantified by the ORArms, which is the root-mean-squared distance of the ORAs from their summated vector mean in double angle space. The lower the ORArms, the better the corneal astigmatism measure corresponds to manifest refractive cylinder. RESULTS: Corneal astigmatism measures derived from regions centered on corneal vertex had ORArms values (mild: 1.07 diopters [D], moderate: 1.61 D, severe: 2.65 D) as low or lower than other measures derived from regions centered on thinnest point, corneal apex (front or back), or pupil center. Corneal astigmatism measures derived from a region centered 30% of the way toward thinnest point from corneal vertex appeared to have even lower ORArms values (mild: 1.05 D, moderate: 1.45 D, severe: 2.56 D). None of the corneal astigmatism measures corresponded closely with manifest refractive cylinder for severe keratoconus (ORArms > 2.50 D). CONCLUSIONS: For keratoconic eyes, the CorT should be derived from an annular region centered 30% of the way toward thinnest point from corneal vertex, although when the keratoconus is mild, a standard corneal-vertex-centered CorT performs just as well. [J Refract Surg. 2023;39(3):206-213.].

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.].

The Impact of Repetitive and Prolonged Eye Rubbing on Corneal Biomechanics.

PURPOSE: To evaluate the effect of simulated repetitive eye rubbing on the corneal biomechanics of porcine eyes using an ex vivo model system. METHODS: The average rubbing force that patients with keratoconus apply to their eyelids was previously determined. Fresh porcine eyes with eyelids were either exposed to 10,500 rub cycles from a custom-built eye rubbing machine that rubbed with a similar force to knuckle human eye rubbing (n = 33) or no rubbing at all (control; n = 37). A total of 10,500 rubs are equivalent to 1 year of rubbing six times daily, five movements per rub. The corneal biomechanical properties of these eyes were then tested by measuring the elastic modulus of 5-mm strips. RESULTS: The elastic modulus at the range of 1% and 5% of strain was 1.219 ± 0.284 and 1.218 ± 0.304 N/mm2 in the eye rubbing group and the no-rub control group, respectively. Corneal stiffness was similar in both groups (P = .984). CONCLUSIONS: The threshold to induce biomechanical changes (purely by eye rubbing) must be higher than 10,500 rubbing movements, suggesting that occasional eye rubbing may not affect corneal biomechanics in normal eyes, and likely only triggers keratoconus progression in predisposed corneas. Further in vivo studies assessing the impact eye rubbing has on inflammatory activity and the biomechanical properties of weakened corneas is warranted. [J Refract Surg. 2022;38(9):610-616.].

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.

IOL power calculations after LASIK or PRK: Barrett True-K biometer-only calculation strategy yields equivalent outcomes as a multiple formula approach.

PURPOSE: To compare the accuracy of intraocular lens (IOL) power calculations performed using the biometer-embedded Barrett True-K formula vs a multiple formula approach using the ASCRS postrefractive calculator in eyes with previous myopic or hyperopic refractive surgery. SETTING: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. DESIGN: Retrospective, consecutive case series. METHODS: Patients who underwent cataract surgery with a history of corneal refractive surgery were included. For each formula, the IOL prediction error and refractive prediction error was calculated. Main outcome measures included mean absolute error (MAE) and the percentage of eyes within ±0.25 diopters (D), ±0.50 D, and ±1.00 D. RESULTS: 96 postmyopic eyes and 47 posthyperopic eyes were analyzed. In the postmyopic cohort, the Barrett True-K formula had the lowest MAE (0.36 D), followed by the Haigis-L formula (0.41 D). The Barrett True-K formula had a significantly higher percentage (44.8%) of eyes within ±0.25 D in comparison with the Haigis-L formula (34.4%), which had the second highest percentage ( P < .01). In the posthyperopic cohort, the Barrett True-K formula had the lowest MAE (0.41 D), followed by the ASCRS-mean (0.46). The Barrett True-K and ASCRS-mean formulas had the highest percentage of eyes within ±0.25 D (42.6% vs 38.3%, P = .16). CONCLUSIONS: The Barrett True-K formula built into the biometer performed equivalently to a multiple formula approach on the ASCRS online calculator in both postmyopic and posthyperopic eyes. This approach reduces the potential for transcription error from data entry for lens power calculation approaches that require manual data entry.

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.

Cogan syndrome masquerading as corneal ectasia.

PURPOSE: To report a case of Cogan syndrome that presented with the appearance of bilateral asymmetric corneal ectasia on Scheimpflug tomography. METHODS: Case Report and Literature Review. RESULTS: A 43-year-old woman previously diagnosed with keratoconjunctivitis sicca and presumed keratoconus presented with seven months of episodic eye pain and progressive bilateral blurry vision with new onset bilateral monocular diplopia. Review of symptoms were significant for tinnitus, vertigo, and sensorineural hearing loss that began many months after her initial presentation for visual symptoms. Scheimpflug tomography showed asymmetric focal steepening on anterior curvature with corresponding focal total corneal thinning, focal posterior elevation, and abnormal ARTMax (205 OD, 103 OS) and BAD-D (2.75 OD, 5.6 OS) values. Clinical examination was notable only for faint anterior corneal stromal inflammation without neovascularization, but there was significant corresponding focal hyperreflectivity on anterior segment optical coherence tomography (OCT) examination with focal epithelial hypertrophy rather than thinning. Given the combined findings of interstitial keratitis and sensorineural hearing loss the patient was diagnosed with Cogan syndrome. She responded well to topical steroids and systemic immunosuppressive therapy, with near resolution of her abnormal topographic and tomographic findings and resolution of monocular diplopia in both eyes. CONCLUSIONS: Cogan syndrome should be suspected for any patient with corneal stromal findings and associated with vertigo and/or hearing loss. Anterior segment optical coherence tomography (OCT) can distinguish between ectatic and inflammatory diseases and may help make the appropriate diagnosis in subtle cases.

High-Fluence Accelerated Epithelium-Off Corneal Cross-Linking Protocol Provides Dresden Protocol-Like Corneal Strengthening.

Purpose: To assess whether optimized technical settings for accelerated epithelium-off corneal cross-linking may lead to increases in biomechanical stiffness similar to the benchmark 30-minute epithelium-off Dresden protocol. Methods: Three-hundred porcine eyes were divided equally into six groups for analysis. All samples underwent epithelial debridement and soaking with 0.1% iso-osmolar riboflavin solution for 20 minutes. Corneal cross-linking (CXL) was performed using epithelium-off protocols varying in acceleration and total fluence (intensity in mW/cm² * time in minutes, total fluence in J/cm²): standard (S)-CXL (3*30, 5.4), accelerated (A)-CXL (9*10, 5.4), A-CXL (9*13'20″, 7.2), A-CXL (18*6'40″, 7.2), and A-CXL (18*9'15″, 10). Control corneas were not irradiated. The elastic modulus of 5-mm wide corneal strips was measured as an indicator of corneal stiffness. Results: All irradiated groups had significantly higher elastic modulus than controls (P < 0.05), with a stiffening effect of 133% S-CXL (3*30, 5.4), 122% A-CXL (9*10, 5.4), 120% A-CXL (9*13'20″, 7.2), 114% A-CXL (18*6'40″, 7.2) and 149% A-CXL (18*9'15″, 10). The high-fluence accelerated epithelium-off protocol (18*9'15″, 10) showed the highest stiffening effect. Elastic modulus at 5% strain (1%-5% strain) showed significant differences between A-CXL (18*9'15″, 7.2) and three other accelerated protocols: A-CXL (9*10, 5.4; P = 0.01), A-CXL (9*13'20″, 7.2; P = 0.003), and A-CXL (18*6'40″, 10; P = 0.0001). Conclusions: An accelerated high-fluence epithelium-off CXL protocol (18 mW/cm² for 9'15″) was identified to provide a significantly greater stiffening effect than any other accelerated protocols and is indistinguishable from the Dresden protocol, with accelerating irradiation times ranging from 30 to 9 minutes; by combining gentle acceleration with higher fluence, such a protocol does not require supplemental oxygen. Translational Relevance: This A-CXL (18*9'15″, 10) protocol has the potential to become a new standard in epithelium-off CXL, delivering Dresden protocol-like strengthening over a shorter period.