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PURPOSE: To formulate an Epithelial Modulation index to differentiate between eyes with contact lens warpage and keratoconus. METHODS: Normal eyes and eyes with either contact lens warpage or keratoconus were scanned by a Fourier-domain optical coherence tomography (OCT) system. Maps of epithelial thickness and anterior surface mean curvature were generated and converted to deviation maps by subtracting the average maps from a healthy population. The Epithelial Modulation index was defined as the covariance between the two types of deviation maps. A logistic regression model was used to classify eyes as non-keratoconus (normal or warp-age) or keratoconus (manifest, subclinical, or forme fruste). RESULTS: The average Epithelial Modulation index value for normal eyes was −0.6 ± 1.0 µm/m. Eyes with keratoconus were characterized by coincident high anterior surface mean curvature and low epithelial thickness, resulting in a high Epithelial Modulation index (manifest: 103.0 ± 82.9 µm/m, subclinical: 37.0 ± 23.0 µm/m, forme fruste: 7.3 ± 13.2 µm/m). The Epithelial Modulation index was closer to normal for eyes with warpage (−1.9 ± 4.0 µm/m). The classification accuracy of the Epithelial Modulation index during five-fold cross-validation of the logistic regression model was 100 ± 0% for normal eyes and 99.0 ± 2.0% for eyes with warpage. The accuracy was 100 ± 0%, 100 ± 0%, and 53.1 ± 1.5% for the manifest, subclinical, and forme fruste keratoconus groups, respectively. CONCLUSIONS: The Epithelial Modulation index is useful in distinguishing eyes with secondary epithelial modulation (keratoconus) from those with primary epithelial deformation (contact lens–related warpage). [ J Refract Surg . 2022;38(2):112–119.]

PURPOSE: To quantify the abnormal corneal thinning and posterior surface steepening that is observed in keratoconus with an Ectasia Index. METHODS: Optical coherence tomography (OCT) was used to image the corneas of normal individuals and patients with varying stages of keratoconus (manifest, subclinical, and forme fruste). Maps of corneal pachymetry and posterior surface mean curvature were generated, and an Ectasia Index was calculated by multiplying Gaussian fits obtained from the two types of maps. Repeated five-fold cross-validation was used to evaluate the ability of the Ectasia Index to differentiate between normal and keratoconic eyes. The classification performance of the Ectasia Index was compared to minimum pachymetry and maximum posterior mean curvature. RESULTS: Thirty-two eyes from 16 normal individuals, 89 eyes from 63 patients with manifest keratoconus, 16 eyes from 15 patients with subclinical keratoconus, and 26 eyes from 26 patients with forme fruste keratoconus were included in the study. During cross-validation, 100% of the eyes with manifest (89 of 89) and subclinical (16 of 16) keratoconus were correctly classified by the Ectasia Index. The average classification accuracy for the forme fruste keratoconus group was 63 ± 21% (16.4 of 26). The specificity for the normal group was 91 ± 10% (29.1 of 32). The Ectasia Index had a higher sensitivity for keratoconus detection and similar specificity in comparison to minimum pachymetry and maximum posterior mean curvature. CONCLUSIONS: The Ectasia Index could be a valuable additional metric for clinicians to consider when screening for keratoconus. [ J Refract Surg . 2022;38(8):502–510.]

Purpose To describe the intraoperative and early postoperative complications using preloaded Descemet membrane endothelial keratoplasty (DMEK) grafts with intraocular injection of the graft in Optisol-GS and omission of trypan blue restaining. Methods This is a retrospective case series of 132 consecutive eyes with Fuchs endothelial dystrophy or endothelial failure who underwent DMEK using preloaded donor tissue prepared as previously described. The graft was not restained with trypan blue by the surgeon, and Optisol-GS was injected with the graft into the eye instead of being rinsed from the injector. Early postoperative complications (0-8 wk) including intraoperative fibrin formation, intraocular inflammation, elevated intraocular pressure, partial graft detachment requiring rebubble, and early graft failure were recorded. Results No eyes developed intraoperative fibrin formation or postoperative inflammation (such as toxic anterior segment syndrome) or elevated intraocular pressure. For eyes with Fuchs corneal dystrophy, our rebubble rate was 21% (22/106 eyes). Early graft failure was noted in 2% (3/132 eyes), which is similar to previous reports. Conclusions Our results suggest that injection of Optisol-GS into the anterior chamber during DMEK graft injection does not lead to increases in intraoperative or early postoperative complications. Trypan blue restaining is not necessary for intraoperative visualization. This simplification can reduce graft manipulation and save time and resources for this procedure.

To compare changes in corneal power measurements after Descemet membrane endothelial keratoplasty (DMEK) vs. ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK).Hospital centers DESIGN: : Post-hoc sub-analysis of the randomized controlled DETECT Trial METHODS: : 50 eyes (38 patients) with endothelial dysfunction from Fuchs' endothelial dystrophy or pseudophakic bullous keratopathy were randomized to DMEK or UT-DSAEK 1 to 2 days prior to surgery. Total Corneal Refractive Power (TCRP) and anterior/posterior simulated keratometry were obtained using Scheimpflug imaging preoperatively (baseline) and postoperatively at 3, 6, 12, and 24 months. Spectacle refractions were performed at 6, 12, and 24 months after surgery.Mean hyperopic shift of TCRP from baseline to 12 months was 0.80±1.1 (p=0.002) in the DMEK group and 0.69±0.84 (p0.001) in the UT-DSAEK group. Posterior corneal curvature (Km) steepened (more negative dioptric power) by 0.42±0.10 (p0.001) in DMEK and 0.54±0.09 (p0.001) in UT-DSAEK. Mean change in TCRP and posterior corneal curvature did not differ between DMEK and UT-DSAEK (TCRP, p=0.71; posterior Km, p=0.36).Sustained steepening in posterior corneal curvature with loss in total corneal power contributes to hyperopic shifts after endothelial keratoplasty. Changes in corneal measurements do not differ between DMEK and UT-DSAEK.

PURPOSE To examine the corneal transplant failure rates and associations with uveitic eye disease. METHODS The retrospective chart review identified 70 eyes from 42 patients with uveitis that underwent 40 primary transplants and 30 repeat transplants at 2 major academic centers over a 9-year period. The graft failure rate was calculated. Variables hypothesized to be associated with graft failure were analyzed as covariates using a Cox proportional hazards analysis clustered by the patients to determine their association with failure rates. RESULTS Of the 70 grafts, the mean duration of follow-up for patients was 40.6 months (range 4-90 months) and the median survival time was 24.1 months (interquartile range of 9-290 months). Twenty-two patients (52%) had graft failure. There was a higher rate of graft failure in patients with infectious uveitis as compared to those with noninfectious uveitis (hazard ratio 2.46, P = 0.031). Patients with successful grafts had their inflammation controlled for a longer period of time before transplantation as compared to those with failed grafts (38.6 vs. 13.6 months, P = 0.004). Worse preoperative visual acuities were significantly associated with graft failure (P < 0.001). CONCLUSIONS There is limited knowledge of corneal transplant outcomes in uveitic patients in the current literature. In our study, over half of the grafts failed. Infectious uveitis (especially viral) was a strong predictor of graft failure. A shorter period of inflammation control before transplantation, previously failed grafts, and worse preoperative visual acuity were also associated with graft failure.

To measure net corneal astigmatism using optical coherence tomography (OCT) (Avanti) in individuals with keratoconus and compare the repeatability and accuracy with those obtained using Scheimpflug imaging (Pentacam HR).Casey Eye Institute, Portland, Oregon.Prospective cross-sectional observational study.Net corneal astigmatism was calculated in keratoconic and normal eyes using OCT and Scheimpflug imaging with 4 settings-pupil or vertex centration settings with a 3 or 4 mm circular analytical zone. Corneal elevation maps were obtained from OCT images and fitted with the Zernike polynomials to obtain net corneal astigmatism. Manifest refraction astigmatism was used to evaluate the accuracy of net corneal astigmatism measurements. The coefficient of repeatability from 2 repeated measures was calculated.46 eyes with manifest or subclinical keratoconus and 52 normal control eyes were analyzed. For OCT measurements in keratoconus, better accuracy was achieved with pupil centration and 3 mm analytical zone; however, better repeatability was achieved with vertex centration and 4 mm analytical zone (coefficient of repeatability = 0.53 diopters, the Fligner-Killeen test with Bonferroni adjustment Pamp;lt; .0017). Agreement with manifest refraction was significantly better with OCT compared with that using Pentacam HR (generalized mixed-effect model with Bonferroni adjustment Pamp;lt; .00625). No statistically significant difference was found between instruments or settings in control eyes.OCT was able to measure net corneal astigmatism with better accuracy and precision in keratoconic eyes than the Pentacam HR. Measurements may be more accurate using pupil centration and a smaller analytical zone in patients with keratoconus.

Purpose To compare corneal higher-order aberrations (HOA) after ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). Design Patient- and outcome-masked randomized controlled clinical trial. Participants Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or pseudophakic bullous keratopathy who were good candidates for DMEK or ultrathin DSAEK. Methods Corneal anterior and posterior surface HOA were measured with Scheimpflug imaging before surgery and at 3, 6, and 12 months after surgery. HOA after ultrathin DSAEK and DMEK were compared; correlation was performed between best spectacle-corrected visual acuity (BSCVA) and HOA at each time point. Main Outcome Measures Higher-order aberrations of the anterior and posterior cornea, expressed as the root mean square deviation from a best fit sphere reference surface. Results At 3, 6, and 12 months after surgery, the posterior corneal surface had significantly less coma (P ≤ 0.003) and total HOA (P ≤ 0.001) in DMEK compared with ultrathin DSAEK (4.0- and 6.0-mm OZ). Posterior trefoil (P ≤ 0.034), secondary astigmatism (P ≤ 0.042), and tetrafoil (P ≤ 0.045) were lower in DMEK than ultrathin DSAEK at 3, 6, or 12 months (either 4.0- or 6.0-mm OZ). There were no significant differences in anterior surface HOA between DMEK and ultrathin DSAEK at any post-surgical time. Compared with baseline, total posterior HOA was increased (P ≤ 0.036) in ultrathin DSAEK at 3, 6, and 12 months, in contrast to DMEK, where it was decreased (P ≤ 0.044) at 6 and 12 months (4.0- or 6.0-mm OZ, or both). At 6 and 12 months, posterior corneal total HOA correlated with BSCVA (ρ ≤ 0.635, P ≤ 0.001; 4.0- and 6.0-mm OZ). There were no moderate or strong correlations between anterior or combined corneal surface HOA at any time point after surgery. Conclusions Descemet membrane endothelial keratoplasty results in less posterior corneal HOA compared with ultrathin DSAEK. Descemet membrane endothelial keratoplasty decreases and ultrathin DSAEK increases posterior corneal HOA compared with presurgical values. Total posterior corneal HOA correlates with 6- and 12-month postoperative visual acuity and may account for the better visual acuity observed after DMEK.

Purpose of review A survey of the recent literature of deep anterior lamellar keratoplasty using femtosecond laser technology. Recent findings There are several recent reports in the literature assessing technique and outcomes of deep anterior lamellar keratoplasty done with a femtosecond laser trephination. Most of these reports are laboratory studies and small case series with short-term outcomes. The laser technology is expensive and may not produce better results than conventional manual techniques. However, there are several theoretical advantages to femtosecond laser incisions in deep anterior lamellar keratoplasty that should be explored, including possible increased success of Descemet's membrane separation from stroma during surgery as well as postsurgical astigmatism benefits, earlier suture removal, and increased wound strength and healing. Summary Femtosecond laser trephination in the setting of DALK may improve the technique by decreasing the number of descemet's membrane ruptures and improving short-term and long-term outcomes as compared with manual techniques. However, there is no consensus on a standardized approach for wound design or postoperative management. The literature would benefit from a prospective randomized controlled trial.

Purpose To compare clinical outcomes of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) in the treatment of corneal endothelial dysfunction. Design Patient and outcome-masked, randomized controlled clinical trial. Participants Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or pseudophakic bullous keratopathy who were considered good candidates for DMEK or UT-DSAEK. Methods Study eyes were randomized by the eye bank to UT-DSAEK or DMEK 1 to 2 days before surgery. Main Outcome Measures The primary outcome of the trial was best spectacle-corrected visual acuity (BSCVA) at 6 months. Secondary outcomes included 3- and 12-month BSCVA; 3-, 6-, and 12-month endothelial cell counts; intraoperative and postoperative complications; and change in pachymetry. Results A total of 216 patients with endothelial dysfunction were screened, and 50 eyes of 38 patients were enrolled by 2 surgeons at Casey Eye Institute at Oregon Health & Science University in Portland, Oregon, and at Byers Eye Institute at Stanford University in Palo Alto, California. Overall, we found DMEK to have better visual acuity outcomes compared with UT-DSAEK after correcting for baseline visual acuity: compared with UT-DSAEK, those randomized to DMEK had 1.5 lines better BSCVA at 3 months (95% confidence interval [CI], 2.5–0.6 lines better; P = 0.002), 1.8 lines better BSCVA at 6 months (95% CI, 2.8–1.0 lines better; P Conclusions Descemet membrane endothelial keratoplasty had superior visual acuity results compared with UT-DSAEK at 3, 6, and 12 months in patients with isolated endothelial dysfunction with similar complication rates.

Purpose: To report 3 cases of corneal protein deposition occurring in association with systemic disease, with one case demonstrating a novel technique for clearing corneal deposits. Observations: Three patients presented with corneal deposits associated with systemic disease. Corneal involvement was noted prior to diagnosis of systemic disease in two patients, leading to subsequent diagnosis of multiple myeloma or monoclonal gammopathy of undetermined significance. OCT revealed protein deposition at various corneal levels, including at different stromal depths in the two cases of multiple myeloma. A novel technique of posterior endothelial scraping was performed in one case with deep stromal deposits, leading to significant corneal clearing. Conclusions and Importance: This case series demonstrates that recognition of corneal deposits may precede the diagnosis of systemic disease. It incorporates the use of anterior segment OCT to characterize corneal deposits, and demonstrates a novel surgical technique for clearing certain types corneal deposits. Keywords: Crystalline keratopathy, Deposition keratopathy, Paraproteinemia, Corneal pathology, Anterior segment optical coherence tomography, Multiple myeloma

Purpose The purpose of this study was to report a case of acute corneal epithelial rejection of living-related conjunctival limbal allograft (LR-CLAL) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Observations A 27-year-old woman developed acute epithelial rejection of LR-CLAL 2 weeks after receiving the SARS-CoV-2 vaccine. She received the LR-CLAL transplant 4 years and 7 months previously and had a stable clinical course with no history of rejection. She had an ABO blood group and human leukocyte antigen compatible donor, no systemic comorbidities, and no rejection risk factors. Conclusions The novel SARS-CoV-2 vaccine upregulates the immune system to produce an adaptive immune response. The SARS-CoV-2 vaccine may potentially be associated with increased risk of rejection in those with ocular surface transplants.

Deep anterior lamellar keratoplasty is a partial-thickness corneal graft technique void of endothelium. DALK technique offers several advantages over penetrating keratoplasty such as it being an extraocular procedure, never entering into the anterior chamber. Additionally, there is no risk of endothelial rejection and reduced need for immunosuppressive medications. DALK has shown similar VA outcomes when compared to PKP. Femtosecond laser-assisted DALK offers a more accurately prepared and matched transplant incision. Patients should have been evaluated and deemed appropriate for such surgical intervention. Patients should have been educated about the risks and benefits of the procedure, including alternatives.

PURPOSE To determine which baseline characteristics are associated with vision-related quality of life (QOL) after endothelial keratoplasty. METHODS A patient- and outcome-masked randomized clinical trial. Consecutive patients presenting with isolated endothelial disease requiring endothelial keratoplasty at Oregon Health Sciences University and Stanford University. Study eyes randomized to one of the 2 types of endothelial keratoplasty were given the national eye institute vision function questionnaire 25 at baseline and 12 months. In this prespecified secondary outcome, we assessed the role of recipient and donor characteristics as predictors of the 12-month national eye institute vision function questionnaire 25 change score. RESULTS The mean vision function questionnaire (VFQ) score was 74 (SD 14) at baseline and increased to 82 (SD 12) at 3 months and 87 (SD 10) at 12 months. We were unable to find a difference in vision-related QOL in study participants who underwent Descemet membrane endothelial keratoplasty compared with ultrathin Descemet stripping endothelial keratoplasty [coef -0.98, 95% confidence interval (CI) -9.27 to 7.31; P = 0.82]. In multivariable analysis, patients who underwent endothelial keratoplasty in 2 eyes had approximately 8 points higher VFQ at 12 months after the second eye than those who had only one eye enrolled (95% CI 0.10-15.72; P = 0.047). Posterior densitometry produced an approximately 1-point increase each in the VFQ change score for each 1 grayscale unit increase at baseline (95% CI 0.26-1.81; P = 0.009). Although the sample size was small, a diagnosis of pseudophakic bullous keratopathy had approximately 19-points more improvement on average compared with Fuchs (95% CI 7.68-30.00; P = 0.001). CONCLUSIONS Bilateral endothelial keratoplasty resulted in higher vision-related QOL compared with unilateral. Baseline densitometry, objective measure of corneal haze that predicts vision-related QOL, may play a role in monitoring disease progression.

PURPOSE: To compare the degree of corneal light scatter as measured by densitometry in ultrathin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK) in the Descemet endothelial thickness comparison trial. METHODS: This was a prespecified secondary analysis of the Descemet endothelial thickness comparison trial, which was a prospective, randomized controlled trial. Subjects with isolated endothelial dysfunction were enrolled and were randomized to either UT-DSAEK or DMEK. Corneal opacity was quantitatively measured by Pentacam densitometry (OCULUS) at 3, 6, and 12 months. RESULTS: Fifty eyes of 38 patients were enrolled at the Casey Eye Institute at Oregon Health & Science University and the Byers Eye Institute at Stanford University. Corneal densitometry for the anterior and posterior layers improved in both UT-DSAEK and DMEK after surgery. The decrease was more pronounced in the posterior layer for both groups. However, there was no difference in the degree of corneal light scatter between UT-DSAEK and DMEK at postoperative month 12, and no difference in change in densitometry was observed between the 2 arms from baseline to month 12. CONCLUSIONS: Both UT-DSAEK and DMEK experience an improvement in the degree of corneal light scatter after surgery. However, there was no difference in densitometry between the 2 groups at month 12. Therefore, other factors such as higher order aberrations in the posterior cornea rather than stromal–stromal interface haze mediate the superior visual outcomes in DMEK compared with UT-DSAEK.

Purpose To detect keratoconus using optical coherence tomography (OCT) corneal map parameters and patterns. Setting Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA DESIGN:: Cross-sectional observational study. Methods A spectral-domain OCT was used to acquire corneal and epithelial thickness maps in normal, manifest keratoconic, subclinical keratoconic, and forme fruste keratoconic (FFK) eyes. A two-step decision tree was designed. An eye will be classified as keratoconus if both decision tree conditions are met: First, at least one of the four quantitative corneal thickness (minimum, minimum-maximum, superonasal-inferotemporal) and epithelial thickness (standard deviation) map parameters exceed cutoff values. Second, presence of both concentric thinning pattern on the epithelial thickness map and coincident thinning patterns on corneal and epithelial thickness maps by visual inspection. Results The study was compromised of 54 eyes from 29 normal participants, 91 manifest keratoconic eyes from 65 patients, 12 subclinical keratoconic eyes from 11 patients, and 19 FFK eyes from 19 patients. The decision tree correctly classified all normal eyes (100% specificity), and had good sensitivities for detecting manifest keratoconus (97.8%), subclinical keratoconus (100.0%), and FFK (73.7%). Conclusions The two-step decision tree provided a useful tool to detect keratoconus including cases at early disease stages (subclinical keratoconus and FFK). OCT corneal and epithelial thickness map parameters and patterns can be used in conjunction with topography to improve keratoconus screening.

Purpose A consecutive case series of patients with dupilumab-associated ocular surface disease (DAOSD) that describes common ocular symptoms and signs, proposes a symptom disease severity grading system, and describes treatment strategies of DAOSD patients was evaluated. Methods A retrospective chart review of patients with concomitant dupilumab-treated atopic dermatitis and DAOSD with ophthalmic evaluation between January 2014 and May 2019 was conducted. Results Twenty-nine patients (mean age 46 years, M/F: 12/17) with 57 ophthalmic exams were identified. The most common ocular symptoms included irritation/pain (n = 28, 97%), redness (n = 24, 83%), pruritus (n = 18, 62%), discharge (n = 18, 62%), and light sensitivity (n = 6, 21%). The most frequent signs included conjunctival injection (n = 18, 62%), superficial punctate keratitis (n = 16, 55%), and papillary reaction (n = 8, 28%). Topical corticosteroids (TCS) (n = 23, 79%), tacrolimus (n = 6, 21%), and artificial tears (n = 7, 24%) were the most commonly used therapies. Of those with follow-up documentation (n = 21), 20 were noted to have partial or complete response with TCS based on symptoms and reduction of signs. Using our proposed symptom-based grading scale, scaled 1 to 5 based on the presence of common symptoms listed above, 66% (n = 19) requiring topical immunomodulating therapy were found in the 'severe' group (≥3 symptoms) and 17% (n = 5) were found in the 'mild' group (≤2 symptoms). Conclusions This study provides insight into the commonly presenting ocular signs and symptoms associated with DAOSD and highlights the efficacy of TCS and other immunomodulators in improving symptoms associated with DAOSD. Based on our findings, we propose a symptom-based grading system that can guide nonophthalmic physicians regarding ophthalmology consult.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Purpose:To map and measure the depths of corneal neovascularization (NV) using 3-dimensional optical coherence tomography angiography (OCTA) at 2 different wavelengths.Methods:Corneal NV of varying severity, distribution, and underlying etiology was examined. Average NV depth and vessel density were measured using 840-nm spectral-domain OCTA and 1050-nm swept-source OCTA. The OCTA results were compared with clinical slit-lamp estimation of NV depth.Results:Twelve eyes with corneal NV from 12 patients were imaged with OCTA. Clinically "superficial," "midstromal," and "deep" cases had an average vessel depth of 23%, 39%, and 66% on 1050-nm OCTA, respectively. Average vessel depth on OCTA followed a statistically significant ordinal trend according to the clinical classification of vessel depth (Jonckheere-Terpstra test, P < 0.001). In 8 cases where both 840-nm OCTA and 1050-nm OCTA were acquired, there was excellent agreement in the mean vessel depth between the 2 systems (concordance correlation coefficient = 0.94, P < 0.001). The average vessel density measured by 840-nm OCTA was higher (average 1.6-fold) than that measured by 1050-nm OCTA.Conclusions:Corneal OCTA was able to map corneal NV in 3 dimensions and measure vessel depth and density. The depth of corneal NV varied between different pathologies in a manner consistent with previous pathologic studies. The measured vessel density appeared to be affected by the interscan time, which affects blood flow velocity sensitivity, and the wavelength, which affects the ability to penetrate through opacity. These findings suggest possible clinical applications of OCTA for the diagnosis of corneal pathology and quantitative monitoring of therapeutic response in patients with corneal NV.

PURPOSE Evaluation of cumulative Descemet membrane endothelial keratoplasty endothelial cell loss (ECL) from preparation through injection using 2 different glass injectors. METHODS Eighteen Descemet membrane endothelial keratoplasty grafts with "S" stamps were prepared by eye bank technicians. Nine grafts were assigned to injection with a modified glass Jones tube injector with a 2.4-mm opening and 9 were assigned to injection with the DORC glass pipette injector (

To report on a new application of intraoperative optical coherence tomography (OCT) as a real-time imaging tool to help guide corneal biopsy.Single case report. After the negative result of a corneal biopsy, we used intraoperative OCT during repeat biopsy to assist in depth and acquisition of an anterior stromal opacity suspected to be immunoglobulin deposits.The use of intraoperative OCT is a novel tool, which assisted in successful identification and conservative biopsy of corneal immunoglobulin deposits.Intraoperative OCT is a novel tool that assists in the identification and location of corneal pathology for biopsy.

To analyze transepithelial phototherapeutic keratectomy (PTK) results using optical coherence tomography (OCT) and develop a model to guide the laser dioptric and depth settings.Casey Eye Institute, Portland, Oregon, USA.Prospective nonrandomized case series.Patients with superficial corneal opacities and irregularities had transepithelial PTK with a flying-spot excimer laser by combining wide-zone myopic and hyperopic astigmatic ablations. Optical coherence tomography was used to calculate corneal epithelial lenticular masking effects, guide refractive laser settings, and measure opacity removal. The laser ablation efficiency and the refractive outcome were investigated using multivariate linear regression models.Twenty-six eyes of 20 patients received PTK to remove opacities and irregular astigmatism due to scar, dystrophy, radial keratotomy, or previous corneal surgeries. The uncorrected distance visual acuity and corrected distance visual acuity were significantly improved (P .01) by 3.7 Snellen lines and 2.0 Snellen lines, respectively, to a mean of 20/41.2 and 20/22.0, respectively. Achieved laser ablation depths were 31.3% (myopic ablation) and 63.0% (hyperopic ablation) deeper than the manufacturer's nomogram. The spherical equivalent of the corneal epithelial lenticular masking effect was 0.73 diopter ± 0.61 (SD). The refractive outcome highly correlated to the laser settings and epithelial lenticular masking effect (Pearson R = 0.96, P .01). The ablation rate of granular dystrophy opacities appeared to be slower. Smoothing ablation under masking fluid was needed to prevent focal steep islands in these cases.The OCT-measured ablation depth efficiency could guide opacity removal. The corneal epithelial lenticular masking effect could refine the spherical refractive nomogram to achieve a better refractive outcome after transepithelial ablation.

Purpose To distinguish between corneal ectasia and contact lens–related warpage by characteristic patterns on corneal topography and optical coherence tomography (OCT) epithelial thickness maps. Setting Casey Eye Institute, Portland, Oregon, USA. Design Prospective and retrospective case series. Methods Axial and mean power maps were obtained on corneal topography systems. Epithelial thickness maps were generated using RTVue OCT. A sector divider was applied to all maps. The locations of the minimum epithelial thickness, maximum epithelial thickness, maximum axial power, and maximum mean power were determined based on sector averages. Agreement was defined as the extremums occurring in the same or adjacent sectors. Results Twenty-one eyes with keratoconus, 6 eyes with forme fruste keratoconus (better eye of asymmetric keratoconus), and 15 eyes with contact lens–related warpage were identified. The keratoconus and forme fruste keratoconus eyes had coincident topographic steepening with epithelial thinning. The locations of minimum epithelial thickness and maximum axial power agreed in 90% of the keratoconic eyes, while the minimum epithelial thickness and maximum mean power agreed in 95% of them. Conversely, the warpage eyes had coincident topographic steepening with epithelial thickening and normal pachymetry maps. The locations of maximum epithelial thickness and maximum axial power agreed in 93% of the warpage eyes, while the maximum epithelial thickness and maximum mean power agreed in all warpage eyes. Conclusion Results show that epithelial thickness maps and corneal topographic maps are powerful synergistic tools in evaluating eyes with abnormal topography and can help differentiate between keratoconus and nonectatic conditions.

Purpose Fuchs endothelial corneal dystrophy (FECD) might be managed by drug treatment before becoming severe enough to require surgery. For a clinical trial of such a drug, we hypothesize that selecting an adequate number of patients with FECD with only moderately compromised cell densities will be challenging. Thus, the purpose of the present study was to measure the prevalence of patients with FECD exhibiting moderately decreased corneal cell densities. Methods A retrospective data mining study (cross-sectional study) was performed on patient charts presenting at a large US northwestern academic health center by searching for diagnosis ICD-9 code 371.57 and Fuchs corneal dystrophies, including those with prior cataract surgeries and/or existing glaucoma. Patients with prior corneal transplants were excluded. Noncontact specular photomicroscopic data (Topcon 2000) were obtained from the central region whenever possible, and individual eyes were grouped according to cell density (cells/mm2): severe (1,500). Results The values for 98 eyes from 61 patients with FECD were as follows (mean ± SD): corneal thickness 573 ± 59 μm, cell size 627 ± 336 μm2/cell, coefficient of variation 23 ± 7, and density 1,883 ± 703 cells/mm2. The moderate subgroup with cell density values averaging 1,184 ± 212 (26) comprised 27% of the total FECD patient pool. Conclusions Only approximately 1 out of 4 patients with FECD will show moderately compromised corneal cell densities. A moderate level of damage may be optimal for clinical trials for testing topical drugs on endothelial cell viability. Thus, investigators will need to initially screen a fourfold excess of all patients with FECD.

PURPOSE The goals of this laboratory study were to evaluate the interface quality in laser-assisted lamellar anterior keratoplasty (LALAK) with microkeratome-cut grafts and achieve good graft-host apposition. METHODS Simulated LALAK surgeries were performed on 6 pairs of eye-bank corneoscleral discs. Anterior lamellar grafts were precut with microkeratomes. Deep femtosecond (FS) laser cuts were performed on host corneas followed by excimer laser smoothing. Different parameters of FS laser cuts and excimer laser smoothing were tested. Optical coherence tomography was used to measure corneal pachymetry and evaluate graft-host apposition. The interface quality was quantified in a masked fashion using a 5-point scale based on scanning electron microscopy images. RESULTS Deep FS laser cuts at 226 to 380 μm resulted in visible ridges on the host bed. Excimer laser smoothing with a central ablation depth of 29 μm and saline as a smoothing agent did not adequately reduce ridges (score = 4.0). Deeper excimer laser ablation of 58 μm and Optisol-GS as a smoothing agent smoothed ridges to an acceptable level (score = 2.1). Same sizing of the graft and host cut diameters with an approximately 50-μm deeper host side cut relative to the central graft thickness provided the best graft-host fit. CONCLUSIONS Deep excimer laser ablation with a viscous smoothing agent was needed to remove ridges after deep FS lamellar cuts. The host side cut should be deep enough to accommodate thicker graft peripheral thickness compared with the center. This LALAK design provides smooth lamellar interfaces, moderately thick grafts, and good graft-host fits.

Purpose To screen for subclinical keratoconus by analyzing corneal, epithelial, and stromal thickness map patterns with Fourier-domain optical coherence tomography (OCT). Setting Four centers in the United States. Design Cross-sectional observational study. Methods Eyes of normal subjects, subclinical keratoconus eyes, and the topographically normal eye of a unilateral keratoconus patient were studied. Corneas were scanned using a 26 000 Hz Fourier-domain OCT system (RTVue). Normal subjects were divided into training and evaluation groups. Corneal, epithelial, and stromal thickness maps and derived diagnostic indices, including pattern standard deviation (PSD) variables and pachymetric map–based keratoconus risk scores, were calculated from the OCT data. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the diagnostic accuracy of the indices. Results The study comprised 150 eyes of 83 normal subjects, 50 subclinical keratoconus eyes of 32 patients, and 1 topographically normal eye of a unilateral keratoconus patient. Subclinical keratoconus was characterized by inferotemporal thinning of the cornea, epithelium, and stroma. The PSD values for corneal ( P P P = .049) thickness maps were all significantly higher in subclinical keratoconic eyes than in the normal group. The diagnostic accuracy was significantly higher for PSD variables (pachymetric PSD, AUC = 0.941; epithelial PSD, AUC = 0.985; stromal PSD, AUC = 0.924) than for the pachymetric map–based keratoconus risk score (AUC = 0.735). Conclusions High-resolution Fourier-domain OCT could map corneal, epithelial, and stromal thicknesses. Corneal and sublayer thickness changes in subclinical keratoconus could be detected with high accuracy using PSD variables. These new diagnostic variables might be useful in the detection of early keratoconus. Financial Disclosures Oregon Health and Science University (OHSU) and Drs. Li, Tan, and Huang have a significant financial interest in Optovue, Inc. These potential conflicts have been reviewed and managed by OHSU. Dr. Brass receives research grants from Optovue, Inc. Drs. Chamberlain and Weiss have no financial or proprietary interest in any material or method mentioned.

To compare clinical outcomes of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) in the treatment of corneal endothelial dysfunction.Patient and outcome-masked, randomized controlled clinical trial.Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or pseudophakic bullous keratopathy who were considered good candidates for DMEK or UT-DSAEK.Study eyes were randomized by the eye bank to UT-DSAEK or DMEK 1 to 2 days before surgery.The primary outcome of the trial was best spectacle-corrected visual acuity (BSCVA) at 6 months. Secondary outcomes included 3- and 12-month BSCVA; 3-, 6-, and 12-month endothelial cell counts; intraoperative and postoperative complications; and change in pachymetry.A total of 216 patients with endothelial dysfunction were screened, and 50 eyes of 38 patients were enrolled by 2 surgeons at Casey Eye Institute at Oregon HealthScience University in Portland, Oregon, and at Byers Eye Institute at Stanford University in Palo Alto, California. Overall, we found DMEK to have better visual acuity outcomes compared with UT-DSAEK after correcting for baseline visual acuity: compared with UT-DSAEK, those randomized to DMEK had 1.5 lines better BSCVA at 3 months (95% confidence interval [CI], 2.5-0.6 lines better; P = 0.002), 1.8 lines better BSCVA at 6 months (95% CI, 2.8-1.0 lines better; P0.001), and 1.4 lines better BSCVA at 12 months (95% CI, 2.2-0.7 lines better; P0.001). Average endothelial cell counts were 1963 cells/mmDescemet membrane endothelial keratoplasty had superior visual acuity results compared with UT-DSAEK at 3, 6, and 12 months in patients with isolated endothelial dysfunction with similar complication rates.

Importance Electronic health record (EHR) systems have transformed the practice of medicine. However, physicians have raised concerns that EHR time requirements have negatively affected their productivity. Meanwhile, evolving approaches toward physician reimbursement will require additional documentation to measure quality and cost of care. To date, little quantitative analysis has rigorously studied these topics. Objective To examine ophthalmologist time requirements for EHR use. Design, Setting, and Participants A single-center cohort study was conducted between September 1, 2013, and December 31, 2016, among 27 stable departmental ophthalmologists (defined as attending ophthalmologists who worked at the study institution for ≥6 months before and after the study period). Ophthalmologists who did not have a standard clinical practice or who did not use the EHR were excluded. Exposures Time stamps from the medical record and EHR audit log were analyzed to measure the length of time required by ophthalmologists for EHR use. Ophthalmologists underwent manual time-motion observation to measure the length of time spent directly with patients on the following 3 activities: EHR use, conversation, and examination. Main Outcomes and Measures The study outcomes were time spent by ophthalmologists directly with patients on EHR use, conversation, and examination as well as total time required by ophthalmologists for EHR use. Results Among the 27 ophthalmologists in this study (10 women and 17 men; mean [SD] age, 47.3 [10.7] years [median, 44; range, 34-73 years]) the mean (SD) total ophthalmologist examination time was 11.2 (6.3) minutes per patient, of which 3.0 (1.8) minutes (27% of the examination time) were spent on EHR use, 4.7 (4.2) minutes (42%) on conversation, and 3.5 (2.3) minutes (31%) on examination. Mean (SD) total ophthalmologist time spent using the EHR was 10.8 (5.0) minutes per encounter (range, 5.8-28.6 minutes). The typical ophthalmologist spent 3.7 hours using the EHR for a full day of clinic: 2.1 hours during examinations and 1.6 hours outside the clinic session. Linear mixed effects models showed a positive association between EHR use and billing level and a negative association between EHR use per encounter and clinic volume. Each additional encounter per clinic was associated with a decrease of 1.7 minutes (95% CI, -4.3 to 1.0) of EHR use time per encounter for ophthalmologists with high mean billing levels (adjustedR2 = 0.42;P = .01). Conclusions and Relevance Ophthalmologists have limited time with patients during office visits, and EHR use requires a substantial portion of that time. There is variability in EHR use patterns among ophthalmologists.

Objective Outpatient clinics lack guidance for tackling modern efficiency and productivity demands. Workflow studies require large amounts of timing data that are prohibitively expensive to collect through observation or tracking devices. Electronic health records (EHRs) contain a vast amount of timing data – timestamps collected during regular use – that can be mapped to workflow steps. This study validates using EHR timestamp data to predict outpatient ophthalmology clinic workflow timings at Oregon Health and Science University and demonstrates their usefulness in 3 different studies. Materials and Methods Four outpatient ophthalmology clinics were observed to determine their workflows and to time each workflow step. EHR timestamps were mapped to the workflow steps and validated against the observed timings. Results The EHR timestamp analysis produced times that were within 3 min of the observed times for >80% of the appointments. EHR use patterns affected the accuracy of using EHR timestamps to predict workflow times. Discussion EHR timestamps provided a reasonable approximation of workflow and can be used for workflow studies. They can be used to create simulation models, analyze EHR use, and quantify the impact of trainees on workflow. Conclusion The secondary use of EHR timestamp data is a valuable resource for clinical workflow studies. Sample timestamp data files and algorithms for processing them are provided and can be used as a template for more studies in other clinical specialties and settings.

PURPOSE To report a case of local transmission of invasive lobular carcinoma from a donor to a recipient in a keratolimbal allograft after cessation of systemic immunosuppressive therapy. METHODS This is a case report including the clinicopathologic findings. Sections of the donor breast tumor and recipient conjunctival lesions were stained with hematoxylin and eosin. Immunohistochemical studies were performed using pancytokeratin, CK7, CK20, CAM 5.2, CD138, TTF1, estrogen receptor, progesterone receptor, GATA-3, GCDFP-15, and mammaglobin. Polymerase chain reaction-based DNA profiling of tumor cells was performed. RESULTS Histopathologic examination revealed an infiltrate of atypical cells with large hyperchromatic nuclei consistent with carcinoma. Immunohistochemical analysis showed pancytokeratin, CK7, CAM 5.2, GATA-3, and estrogen receptor positivity and progesterone receptor absence, consistent with the previously determined phenotype of the donor's breast carcinoma. Results of polymerase chain reaction analysis were also consistent with the donor's tumor. After reduced dosing of tacrolimus and mycophenolate mofetil, 2 limbal tumors occurred in the recipient. The immunosuppressive treatment had been stopped completely before the appearance of the third lesion. The recipient had no history of malignancy, and she had routine screenings for breast cancer. CONCLUSIONS We report a case of donor-derived breast carcinoma in a keratolimbal allograft recipient. The grafted tissue harbored donor-derived tumor cells for more than 4 years after surgery even after systemic immunosuppression was discontinued. Although no similar reports of tumor transfer could be found in the literature, this case suggests the need for increased stringency in donor selection and heightened surveillance for such tumor transmission.

Clinicians today face increased patient loads, decreased reimbursements and potential negative productivity impacts of using electronic health records (EHR), but have little guidance on how to improve clinic efficiency. Discrete event simulation models are powerful tools for evaluating clinical workflow and improving efficiency, particularly when they are built from secondary EHR timing data. The purpose of this study is to demonstrate that these simulation models can be used for resource allocation decision making as well as for evaluating novel scheduling strategies in outpatient ophthalmology clinics. Key findings from this study are that: 1) secondary use of EHR timestamp data in simulation models represents clinic workflow, 2) simulations provide insight into the best allocation of resources in a clinic, 3) simulations provide critical information for schedule creation and decision making by clinic managers, and 4) simulation models built from EHR data are potentially generalizable.

Deep anterior lamellar keratoplasty is a partial thickness corneal graft technique void of endothelium. DALK technique offers several advantages over penetrating keratoplasty such as it being an extraocular procedure, never entering into the anterior chamber. Additionally, there is no risk of endothelial rejection, and no need for immunosuppressive medications. DALK has shown similar VA outcomes when compared to PKP. IntraLase-enabled DALK offers a more accurately prepared and matched transplant. Patients should have been evaluated and deemed appropriate for such surgical intervention. Patients should have been educated about the risks and benefits of the procedure, including alternatives.

To improve accuracy and efficiency in quantifying the endothelial cell loss (ECL) in eye bank preparation of corneal endothelial grafts.Eight cadaveric corneas were subjected to Descemet Membrane Endothelial Keratoplasty (DMEK) preparation. The endothelial surfaces were stained with a viability stain, calcein AM dye (CAM) and then captured by a digital camera. The ECL rates were quantified in these images by three separate readers using trainable segmentation, a plug-in feature from the imaging software, Fiji. Images were also analyzed by Adobe Photoshop for comparison. Mean times required to process the images were measured between the two modalities.The mean ECL (with standard deviation) as analyzed by Fiji was 22.5% (6.5%) and Adobe was 18.7% (7.0%; p = 0.04). The mean time required to process the images through the two different imaging methods was 19.9 min (7.5) for Fiji and 23.4 min (12.9) for Adobe (p = 0.17).Establishing an accurate, efficient and reproducible means of quantifying ECL in graft preparation and surgical techniques can provide insight to the safety, long-term potential of the graft tissues as well as provide a quality control measure for eye banks and surgeons. Trainable segmentation in Fiji software using CAM is a novel approach to measuring ECL that captured a statistically significantly higher percentage of ECL comparable to Adobe and was more accurate in standardized testing. Interestingly, ECL as determined using both methods in eye bank-prepared DMEK grafts exceeded 18% on average.

PURPOSE To report on a patient with a welding flash burn with subsequent scarring and edema who twice underwent femtosecond laser-assisted keratoplasty (FLAK). Both grafts failed due to endothelial decompensation. He subsequently underwent successful Descemet stripping automated endothelial keratoplasty (DSAEK) under the second FLAK graft to decrease rejection risk and prevent further full-thickness keratoplasty. METHODS A 51-year-old man with a history of 2 FLAK procedures with subsequent graft failures likely from noncompliance with postoperative medications had diffuse microcystic edema with a visual acuity of counting fingers at 5 feet. The patient underwent DSAEK procedure 4 months after the second FLAK procedure. RESULTS No dehiscence occurred during second laser trephination of cornea. Sections of mild misalignment between the first and second FLAK graft trephinations were noted on optical coherence tomography. Post-DSAEK, the patient had a rapidly clearing, well-attached graft with mild temporal overlap of the graft-host interface. All sutures were removed from the overlying FLAK graft by 3 months after DSAEK (7 months after repeat FLAK). At 9 months post-DSAEK, the patient's uncorrected visual acuity was 20/40 and best spectacle-corrected visual acuity was 20/30. CONCLUSIONS Early secondary femtosecond laser trephination after first FLAK is possible even if the second graft is misaligned. A crescent remnant of the original graft was well-healed into the host cornea 7.5 months after the original surgery. The 3-month-old second FLAK graft was able to support a DSAEK surgery and rapid postoperative visual recovery. All sutures were removed from the cornea by 7 months after the second FLAK surgery.