Vision health perspectives on Breaking Bad: Ophthalmic sequelae of methamphetamine use disorder.

Methamphetamine use has become a rampant public health issue that not only causes devastating consequences to the user but also poses a burden to surrounding communities. A spectrum of ophthalmic sequelae is associated with methamphetamine use and includes episcleritis, scleritis, corneal ulceration, panophthalmitis, endophthalmitis, retinal vasculitis, and retinopathy. In many instances, prompt recognition of the condition and associated infectious process and early initiation of antimicrobial therapy are crucial steps to preventing vision loss. In this review, we summarize the reported ocular complications that may result from methamphetamine use in addition to several postulated mechanisms regarding the ocular toxicity of methamphetamine. The increasing prevalence of methamphetamine use as a public health threat highlights the need for continued investigation of this ophthalmologic issue.

Hydralazine Revives Cellular and Ocular Lens Health-Span by Ameliorating the Aging and Oxidative-Dependent Loss of the Nrf2-Activated Cellular Stress Response.

A major hallmark of aging-associated diseases is the inability to evoke cellular defense responses. Transcriptional protein Nrf2 (nuclear factor erythroid-derived 2-related factor) plays a pivotal role in the oxidative stress response, cellular homeostasis, and health span. Nrf2's activation has been identified as a therapeutic target to restore antioxidant defense in aging. Here, we demonstrated that FDA-approved drug, hydralazine (Hyd), was a reactivator of the Nrf2/ARE (antioxidant response element) pathway in various ages and types of mouse (m) or human (h) lens epithelial cells (LECs) and mice lenses in-vitro/in-vivo. This led to Hyd-driven abatement of carbonyls, reduced reactive oxygen species (ROS), and reduced 4-HNE/MDA-adducts with cytoprotection, and extended lens healthspan by delaying/preventing lens opacity against aging/oxidative stress. We elucidated that Hyd activated the protective signaling by inducing Nrf2 to traverse from the cytoplasm to the nucleus and potentiated the ARE response by direct interaction of Nrf2 and ARE sequences of the promoter. Loss-of-function study and cotreatment of Hyd and antioxidant, N-acetyl cysteine (NAC) or Peroxiredoxin (Prdx)6, specified that Nrf2/ARE-driven increase in the promoter activity was Hyd-dependent. Our study provides proof-of concept evidence and, thereby, paves the way to repurposing Hyd as a therapeutic agent to delay/prevent aging and oxidative-related disorders.

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.

Ophthalmic complications associated with methamphetamine use disorder.

Purpose: To describe the devastating ophthalmic sequelae of methamphetamine use disorder in two patients who developed vision loss from ocular complications, including keratitis and endophthalmitis. Observations: Case 1 is a 26-year-old male with hepatitis C, poorly controlled type 1 diabetes, and chronic methamphetamine use who presented with a corneal ulcer in the left eye. Corneal culture grew Staphylococcus aureus and Streptococcus viridans, prompting antibiotic therapy. Follow-up exam showed peripheral corneal ulceration OD and diffusely vascularized and scarred cornea OS, although nonadherence was reported. Vision eventually worsened to hand motions OD and light perception OS.Case 2 is a 44-year-old woman with hepatitis C, acute myeloid leukemia, dry eye syndrome secondary to chronic graft-versus-host disease (GVHD), and chronic methamphetamine use who presented with a diffuse corneal infiltrate and hypopyon. She underwent emergent corneal transplantation, vitrectomy, and broad-spectrum intravitreal and intravenous antibiotics. Vitreous cultures were positive for Streptococcus pyogenes. However, progressive disease eventually required enucleation despite initial globe salvaging measures. Conclusions and importance: These two patient cases highlight the risk of vision loss or blindness due to the detrimental effects of chronic methamphetamine use on the eye, including the potential for keratitis and endophthalmitis. Given the increasing prevalence of methamphetamine use disorder in the United States, further understanding of these toxicities and preventive strategies are needed.

The Dynamic History of the Ophthalmology Residency Matching Program.

Background The ophthalmology residency matching program is the first successful medical specialty match, dating back to 1979. This article reviews the impetus for starting the match and the roles that ophthalmologists Bruce Spivey, MD, and August Colenbrander, MD, PhD, played in establishing the match and developing the machinery to make it possible. Challenges to the match's operations over the years have improved the process. Objective This article aims to research the roles of key individuals and institutions in establishing and maintaining the ophthalmology residency matching program. Methods Oral and written interviews with key participants in establishing and maintaining the match were conducted. Primary and secondary written materials were reviewed. Results Two physicians played key roles in establishing the ophthalmology residency matching program. Bruce Spivey, MD, spearheaded the drive to persuade the Association of University Professors of Ophthalmology (AUPO) to support and sponsor the match. August Colenbrander, MD, PhD, created the original match algorithm and single-handedly ran the match process in the early years. Obstacles were overcome, including resistance from the Association of American Medical College's National Resident Matching Program, a challenge to the validity of the algorithm, and the threat that antitrust laws might prohibit all graduate medical education residency match programs. The ophthalmology match evolved over time to become a more formal entity, the San Francisco Matching Program (SF Match). With continued support of the AUPO, the process of matching applicants to residency programs has flourished despite contemporary challenges related to electronic applications and social media. Conclusion The ophthalmology residency matching program has benefited applicants and teaching programs for more than four decades due to visionary founders, ongoing support of the AUPO, and strong leadership within SF Match.

Quality of life and satisfaction among physicians after wavefront-optimized vs topography-guided laser vision correction.

PURPOSE: To assess satisfaction, quality of life, occupational impact, and clinical outcomes of physicians who have undergone laser vision correction (LVC) using either wavefront-optimized (WFO) or topography-guided (TG) excimer laser ablation profile with femtosecond laser flap creation. SETTING: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. DESIGN: Retrospective survey study. METHODS: A 12-question survey was sent to all physicians who underwent laser in situ keratomileusis or photorefractive keratectomy at the Cole Eye Institute between 2011 and 2018 on the WaveLight Allegretto Wave Eye-Q Laser (Alcon Laboratories, Inc.). Visual outcomes were obtained from patient charts. RESULTS: Two hundred thirty-five physicians (454 eyes) met the study's inclusion criteria, including 181 physicians (353 eyes) who underwent WFO LVC and 54 physicians (101 eyes) who underwent TG LVC. One hundred seventeen physicians (49.8%) responded to the survey and reported an overall satisfaction rate of 98.3% among all physicians receiving LVC with 96.6% reporting they would have the procedure again. Visual outcomes showed a high level of surgical predictability, efficacy, and safety among WFO and TG eyes, with a higher percentage of eyes that received TG ablation achieving 20/10 vision (22% vs 4%, P < .0001) and 20/15 vision (87% vs 69%, P < .01) when compared with WFO eyes. CONCLUSIONS: Physicians who had undergone LVC with either WFO or TG excimer laser ablation reported high satisfaction and quality-of-life improvements. Both groups achieved excellent visual outcomes, with a higher percentage of TG eyes achieving 20/10 and 20/15 vision.

Topography-Guided Refractive Astigmatism Outcomes: Predictions Comparing Three Different Programming Methods.

PURPOSE: To identify the laser programming strategy that will achieve optimal refractive outcomes of LASIK with a topography-guided laser for eyes with a disparity between cylinder measured by manifest refraction and cylinder measured by topography. SETTING: Six surgeons at 5 clinical sites in the USA. DESIGN: Retrospective data review. METHODS: Preoperative, treatment, and postoperative data on 52 eyes that underwent topography-guided LASIK with the WaveLight EX500 Contoura® Vision excimer laser ablation profile in which the vectors representing the preoperative refractive cylinder and the cylinder measured by the WaveLight® Topolyzer™ VARIO Diagnostic Device (Vario cylinder) differed by >/= 0.50D and/or >/= 10 degrees of orientation were analyzed retrospectively. Data were contributed by six surgeons using the laser at 5 different clinical sites. Vector analysis of postoperative cylindrical refractive error and the actual laser programming strategy was used to calculate the cylindrical correction that would, theoretically, have completely eliminated postoperative refractive cylinder. This was compared to expected results using the preoperative manifest cylinder, the topographic cylinder, and the Phorcides Analytic Engine (Phorcides LLC, North Oaks MN; Phorcides). For analysis, subjects were stratified on the basis of the vector difference between Manifest and Topo cylinder (High, >0.75 D; and Low, ≤0.75 D). RESULTS: The poorest calculated theoretical outcomes were obtained with the manifest refraction (centroid: -0.43, 0.22; mean calculated error vector: 0.56 ± 0.42 D; p=ns). Better outcomes were obtained with the topographically measured refraction (centroid: 0.37, 0.02; mean calculated error vector: 0.47 ± 0.33 D; p=ns). The best outcomes were obtained with Phorcides (centroid: -0.15, 0.06; mean calculated error vector: 0.39 ± 0.28 D; p=ns). The mean error vector magnitude in the Phorcides Low group was significantly lower than for the Manifest and Topo Low groups (0.26 D vs 0.48 D and 0.33 D; p<0.01). The mean error magnitude in the Phorcides High group was nearly 0.25 D lower than for the Manifest High group (0.48 D vs 0.70 D; p<0.01), but was the same as for the Topo High group (0.48 D vs 0.48 D). CONCLUSION: Our study suggests that using the topographically measured cylinder or the cylinder selected by Phorcides will produce more desirable refractive outcomes than entry of the preoperative refractive cylinder as the basis for correction of myopia and myopic astigmatism with the WaveLight Contoura Vision excimer laser.

Analysis of planning strategies in primary eyes gaining a line or more of visual acuity after topography-guided laser in situ keratomileusis.

PURPOSE: To analyze planning strategies for eyes that gained 1 or more lines of corrected distance visual acuity (CDVA) after topography-guided custom treatment (TCAT). SETTING: Refractive Surgery Clinic, Cleveland Clinic, Ohio, USA. DESIGN: Retrospective case series. METHODS: Eyes having TCAT by the same surgeon between February 2016 and June 2017 were enrolled. The corneal shape was captured with the Wavelight Allegretto Topolyzer diagnostic device coupled with refraction, generating an ablation profile. The cylinder magnitude and axis of laser entry were decided by the surgeon based on the manifest and measured values, assisted by additional data from the Pentacam Scheimpflug tomographer and Ladarwave ocular wavefront aberrometer. RESULTS: The study comprised 256 eyes. At 3 months, uncorrected distance visual acuity was 20/20 or better in 95.7% and 20/15 or better in 81.4%; 25.6% gained 1 or more lines of CDVA. The measured and manifest axes differed by less than 15 degrees in 59%, between 15 degrees and 30 degrees in 18%, and by more than 30 degrees in 23%. When it differed by at least 5 degrees, the measured axis was treated in 79%, 75%, and 73% of eyes, respectively. In eyes with higher measured cylinder, 75% were treated between the manifest and measured values, with 7% at full measured value. When the manifest value was greater, 60% were treated at the total measured value and 40% in between. Whole-eye aberrometry showed a small increase in coma, spherical aberration and the total root mean square (all P < .001). CONCLUSIONS: The TCAT procedure achieved visual acuity better than the preoperative CDVA in more than 25.0% of eyes. Tomography and wavefront aberrometry assisted in the selection process to achieve optimum visual outcomes.

Bilaterally Asymmetric Corneal Ectasia Following SMILE With Asymmetrically Reduced Stromal Molecular Markers.

PURPOSE: To evaluate extracellular matrix regulators and inflammatory factors in a patient who developed ectasia after small incision lenticule extraction (SMILE) despite normal preoperative tomographic and biomechanical evaluation. METHODS: The SMILE lenticules from both eyes of the patient with ectasia and three control patients (5 eyes) matched for age, sex, and duration of follow-up were used for gene expression analysis of lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), collagen types I alpha 1 (COLIA1) and IV alpha 1 chain (COLIVA1), transforming growth factor-beta (TGF-beta), bone morphogenetic protein 7 (BMP7), interleukin-6 (IL-6), cathepsin K, cluster of differentiation 68, integrin beta-1, and tissue inhibitor of metalloproteinase-1 (TIMP1). Furthermore, the functional role of LOX was assessed in vitro by studying the collagen gel contraction efficiency of LOX overexpressing in primary human corneal fibroblast cells. RESULTS: Preoperatively, manifest refraction was -9.25 diopters (D) in the right eye and -10.00 D in the left eye. Corneal thickness, Pentacam (OCULUS Optikgeräte GmbH, Wetzlar, Germany) tomography, and Corvis biomechanical indices (OCULUS Optikgeräte GmbH) were normal. The ectatic eye lenticule (left) had reduced expression of LOX and COLIA1 compared to controls without ectasia. Increased mRNA fold change expression of TGF-beta, BMP7, IL-6, cathepsin K, and integrin beta-1 was noted in the ectatic left eye compared to controls; however, MMP9 and TIMP1 levels were not altered. Ectopic LOX expression in human corneal fibroblast induced significantly more collagen gel contraction, confirming the role of LOX in strengthening the corneal stroma. CONCLUSIONS: Reduced preexisting LOX and collagen levels may predispose clinically healthy eyes undergoing refractive surgery to ectasia, presumably by corneal stromal weakening via inadequately cross-linked collagen. Preoperative molecular testing may reveal ectasia susceptibility in the absence of tomographic or biomechanical risk factors. [J Refract Surg. 2019;35(1):6-14.].

The Incidence and Natural History of Subjectively and Objectively Determined Metrics of Light Scattering in Femtosecond Laser-Assisted In Situ Keratomileusis.

Purpose: To assess the incidence and long-term persistence of both subjective (rainbow glare phenomenon) and objective metrics of light scattering (stray light measurement) in femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Settings: Cleveland Clinic Foundation, Cole Eye Institute. Design: Prospective, contralateral eye study in which 54 myopic eyes of 27 patients underwent LASIK using the ALLEGRETTO® Eye-Q excimer laser. Flap creation was created by IntraLASE FS60 (IL) in one eye and Wave Light FS200 (FS) in the contralateral eye. Rainbow glare and stray light measurements (C-Quant, Oculus Inc, Lynnwood, WA) were obtained preoperatively, and at 1 week, 1, 3, and 9 months postoperatively. Manifest and wavefront refractions were performed at each postoperative visit. Results: Stray light measurements in both IL and FS groups peaked at 1 week postoperatively (log 1.28 ± 0.16, p = 0.02 and log 1.26 ± 0.12, p = 0.039, respectively) with statistically significant improvement at 3 months (log 1.12 ± 0.35, p = 0.007 and log 1.20 ± 0.15, p = 0.04) and 9 months (log 1.11 ± 0.17, p = 0.008 and log 1.15 ± 0.14, p = 0.011). No statistically significant differences were found between IL and FS eyes at all time points. 11 patients reported postoperative rainbow glare at 1 week (42%), which decreased to 6 patients at 9 months (33%) in the IL treated eye. 14 patients reported postoperative rainbow glare at 1 week (54%), which decreased to 7 patients at 9 months (39%) in the FS treated eye. Conclusion: Both rainbow glare and objective light scatter were greatest at 1 week and were significantly reduced by 1 to 3 months postoperatively. Rainbow glare is a mild optical side effect of femtosecond laser LASIK that improves with time.

A review of small incision lenticule extraction complications.

PURPOSE OF REVIEW: As a flapless procedure, SMILE brings benefits to refractive surgery, such as lower corneal biomechanical impact, less dry eye risk and less stromal bed exposure. However, the longer learning curve can be a risk factor for complications. This article aims to discuss SMILE complications and proposes a categorized analysis of occurrences, dividing into two groups: intraoperative and postoperative complications. Among intraoperative, we also suggest a subdivision between those related to the laser (lenticule construction), tissue separation (lenticule dissection) and tissue removal (lenticule extraction). RECENT FINDINGS: The majority of SMILE complications are related to surgeon inexperience and reversible if precociously diagnosed and correctly managed. Intraoperative complications related to lenticule creation such as suction loss, opaque bubble layer and black spots, are correlated with later difficulties during lenticule dissection and removal, and may lead to unwanted situations, such as cap perforation, lenticule tear and cap-lenticule adhesion. Postoperative complications as dry eye, keratitis and ectasia should not be underestimated. SUMMARY: Analyzing what has been reported as major or unique among the complications with SMILE, and dividing them into subgroups, we aim to help refractive surgeons in becoming familiar with the things that can go wrong during SMILE. Early recognition and correct management will be fundamental for optimizing the final visual result.

Laser Vision Correction in Treating Myopia.

Myopia is a generally benign refractive error with an increasing prevalence worldwide. It can be corrected temporarily with glasses and contact lenses and permanently with laser vision correction. The 2 main procedures currently being performed for myopia correction are photorefractive keratectomy and laser-assisted in situ keratomileusis. Each technique has its advantages, but they appear to yield similar visual outcomes 1 year after surgery. Laser vision correction for myopia was considered a paradigm shift because healthy eyes could now undergo a surgical procedure to permanently and safely correct the error by altering the center of the cornea, which was previously off limits because of the potential for loss of transparency. Customized ablation using wavefront aberrometry and its optimized profiles were created to correct higher-order aberrations and give more vision quality to patients. Topography-guided ablation, initially used for complex retreatments, shows potential to make vision even better than glasses and contact lenses in a recent study on previously untreated eyes. One major concern is to identify corneas that are at risk of developing ectasia after the procedure. Topographic and tomographic screening indices have been implemented clinically, but there is still much to learn about corneal biomechanics. A more recently developed procedure for myopia correction is small-incision lenticule extraction, in which a lenticule is created in the cornea's stroma with a femtosecond laser and extracted through a small corneal incision. Long-term outcomes and new complication risks need to be better understood as this procedure develops.

Comparison of Patient-Specific Computational Modeling Predictions and Clinical Outcomes of LASIK for Myopia.

Purpose: To assess the predictive accuracy of simulation-based LASIK outcomes. Methods: Preoperative and 3-month post-LASIK tomographic data from 20 eyes of 12 patients who underwent wavefront-optimized LASIK for myopia were obtained retrospectively. Patient-specific finite element models were created and case-specific treatment settings were simulated. Simulated keratometry (SimK) values and the mean tangential curvature of the central 3 mm (Kmean) were obtained from the anterior surfaces of the clinical tomographies, and computational models were compared. Correlations between Kmean prediction error and patient age, preoperative corneal hysteresis (CH), and corneal resistance factor (CRF) were assessed. Results: The mean difference for Kmean between simulated and actual post-LASIK cases was not statistically significant (-0.13 ± 0.36 diopters [D], P = 0.1). The mean difference between the surgically induced clinical change in Kmean and the model-predicted change was -0.11 ± 0.34 D (P = 0.2). Kmean prediction error was correlated to CH, CRF, and patient age (r = 0.63, 0.53, and 0.5, respectively, P < 0.02), and incorporation of CH values into predictions as a linear offset increased their accuracy. Simulated changes in Kmean accounted for 97% of the variance in actual spherical equivalent refractive change. Conclusions: Clinically feasible computational simulations predicted corneal curvature and manifest refraction outcomes with a level of accuracy in myopic LASIK cases that approached the limits of measurement error. Readily available preoperative biomechanical measures enhanced simulation accuracy. Patient-specific simulation may be a useful tool for clinical guidance in de novo LASIK cases.

Advances in Refractive Surgery: June 2014 to July 2015.

PURPOSE: The objective of this study was to review the advances in the field of refractive surgery as reported in the peer-reviewed literature during the previous year. DESIGN: A literature review. METHODS: In this review, we highlight the most pertinent articles in the field from June 2014 to the end of July 2015. RESULTS: This past year has seen a growing body of research on small-incision lenticule extraction, presbyopic inlays, and phakic intraocular lenses, as more clinicians are adopting these techniques into their armamentarium. CONCLUSIONS: Laser-assisted in situ keratomileusis and photorefractive keratectomy continue to dominate the keratorefractive literature, as they remain the most frequently performed refractive surgeries.

Early post-LASIK flap amputation in the treatment of aggressive, branching keratitis: a case report.

Infectious keratitis is rare following laser vision correction. We present a case of aggressive fungal keratitis caused by Aspergillus flavus, following laser in situ keratomileusis (LASIK) in the setting of a unique environmental risk factor. We describe the key features of the acute case presentation, which guided empirical medical and surgical treatment, resulting in the most favorable outcome found in the literature, to date.

Early post-LASIK flap amputation in the treatment of aggressive, branching keratitis: a case report / Amputação precoce de pedículo de LASIK para o tratamento de ceratite ramificada agressiva: relato de caso

ABSTRACT Infectious keratitis is rare following laser vision correction. We present a case of aggressive fungal keratitis caused by Aspergillus flavus, following laser in situ keratomileusis (LASIK) in the setting of a unique environmental risk factor. We describe the key features of the acute case presentation, which guided empirical medical and surgical treatment, resulting in the most favorable outcome found in the literature, to date.

RESUMO Ceratites infecciosas são raras após a correção da visão a laser. Apresentamos um relato de caso de uma ceratite fúngica agressivo por Aspergillus flavus, após ceratomileuse a laser "in situ" (LASIK) em situação peculiar de fator de risco ambiental. Nós descrevemos as principais características da apresentação caso agudo, que orientou tratamento médico e cirúrgico empírico, demonstrando resultado mais favorável do que o encontrado na literatura até o momento.