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Kenneth A Beckman1,2 1Comprehensive EyeCare of Central Ohio, Westerville, OH, USA; 2The Ohio State University, Columbus, OH, USACorrespondence: Kenneth A BeckmanComprehensive EyeCare of Central Ohio, 450 Alkyre Run Dr #100, Westerville, OH, 43082, USATel +1 614 890-5692Email submissiondrbeckman@gmail.comIntroduction: Epithelium-off cross-linking (epi-off CXL) has long been established as the gold standard treatment for progressive keratoconus. Several protocols for epithelium-on (epi-on) CXL have been proposed to help reduce post-operative pain and facilitate visual recovery, but there is no epi-on treatment approach that is currently approved in the United States. The hydrophilic and macromolecular characteristics of conventional epi-off riboflavin formulations may create clinical challenges for absorption through an intact epithelium. This study investigates the clinical efficacy of a dextran-free hypotonic riboflavin ophthalmic solution (Photrexa, Glaukos, Burlington, MA, USA), approved for epi-off CXL, in a novel epi-on CXL protocol.Methods: Twenty-five eyes of 17 patients were treated in this prospective, single-arm study using a hypotonic riboflavin formulation without dextran and low irradiance UVA (3mW/cm2) for epi-on CXL. Visual acuity, as well as refractive and keratometry outcomes, were observed over 12 months.Results: At 12 months, Kmax was stable with no clinically or statistically significant change from a mean pre-op of 55.4D to 55.9D (p=0.13). Uncorrected and best corrected logMAR visual acuity significantly improved from 0.77 to 0.62 and from 0.17 to 0.12, respectively. There were no significant adverse safety events.Conclusion: Patients who underwent epi-on CXL with dextran-free hypotonic riboflavin demonstrated improvements in uncorrected and best corrected visual acuity with stable keratometry at 12 months post-operatively. The efficacy is consistent with other epi-on studies to date but remains lower than standard epi-off CXL. New technologies, including supplemental oxygen and transepithelial riboflavin ophthalmic solutions, are currently under clinical evaluation and may offer a path forward for epi-on CXL in the USA.Keywords: epithelium-on, cross-linking, CXL, dextran-free, photrexa

Elizabeth Yeu,1 Damien F Goldberg,2 Francis S Mah,3 Kenneth A Beckman,4,5 Jodi I Luchs,6,7 Jonathan D Solomon,8 Darrell E White,9 Preeya K Gupta101Eastern Virginia Medical School, Virginia Eye Consultants, Norfolk, VA, USA; 2Wolstan & Goldberg Eye Associates, Torrance, CA, USA; 3Scripps Clinic Torrey Pines, La Jolla, CA, USA; 4Ohio State University, Columbus, OH, USA; 5Comprehensive Eye Care of Central Ohio, Westerville, OH, USA; 6Hofstra Northwell School of Medicine, Hempstead, NY, USA; 7South Shore Eye Care, Wantagh, NY, USA; 8Bowie Vision Institute, Bowie, MD, USA; 9Skyvision Centers, Westlake, OH, USA; 10Duke University Eye Center, Durham, NC, USAPurpose: Evaluate the safety and efficacy of cryopreserved amniotic cytokine extract (ACE) in the treatment of subjects with dry eye disease (DED).Patients and methods: This was a retrospective, multicenter, chart review of adult patients with DED that instilled cryopreserved ACE drops twice-daily for 4 or 12 weeks. Patients had corneal fluorescein staining (0–20 range) and/or a lissamine green conjunctival staining score (0–18 range) of ≥3 and ≤9 in at least 1 eye and a score ≥40 (0–100 range) of eye dryness/irritation on a visual analog scale (VAS). Following completion of a treatment course, medical records were reviewed from the initiation of therapy (baseline), and at post-treatment visits (4 weeks, 8 weeks, and 12 weeks). Patient records for visual acuity, adverse events, corneal fluorescein staining, conjunctival lissamine green staining, and symptom scores of ocular dryness/irritation were reviewed for each visit, as available. Safety and tolerability were assessed through the evaluation of patient-reported adverse events recorded in the medical records.Results: A total of 54 eligible patients were identified at 7 clinical sites; 16 patients administered ACE drops for 4-weeks, and 38 patients instilled ACE drops for 12 weeks. Significant improvements in the mean changes from baseline were observed for corneal fluorescein staining, lissamine green staining, visual acuity (LogMar) and VAS ocular symptom scores at the 4-week post-treatment visit (p

Kenneth A Beckman,1,2 Jodi Luchs,3,4 Mark S Milner5,6 1Comprehensive EyeCare of Central Ohio, Westerville, OH, 2The Ohio State University, Columbus, OH, 3Hofstra University School of Medicine, Hempstead, NY, 4South Shore Eye Care, Wantagh, NY, 5The Eye Center of Southern Connecticut, PC, Hamden, CT, 6Yale University School of Medicine, New Haven, CT, USA Abstract: Sjögren’s syndrome (SS) is a chronic and progressive systemic autoimmune disease that often presents initially with symptoms of dry eye and dry mouth. Symptoms are often non-specific and develop gradually, making diagnosis difficult. Patients with dry eye complaints warrant a step-wise evaluation for possible SS. Initial evaluation requires establishment of a dry eye diagnosis using a combination of patient questionnaires and objective ocular tests, including inflammatory biomarker testing. Additional work-up using the Schirmer test and tear film break-up time can differentiate between aqueous-deficient dry eye (ADDE) and evaporative dry eye. The presence of ADDE should trigger further work-up to differentiate between SS-ADDE and non-SS-ADDE. There are numerous non-ocular manifestations of SS, and monitoring for SS-related comorbid findings can aid in diagnosis, ideally in collaboration with a rheumatologist. The clinical work-up of SS can involve a variety of tests, including tear function tests, serological tests for autoantibody biomarkers, minor salivary gland and lacrimal gland biopsies. Examination of classic SS biomarkers (SS-A/Ro, SS-B/La, antinuclear antibody, and rheumatoid factor) is a convenient and non-invasive way of evaluating patients for the presence of SS, even years prior to confirmed diagnosis, although not all SS patients will test positive, particularly those with early disease. Recently, newer biomarkers have been identified, including autoantibodies to salivary gland protein-1, parotid secretory protein, and carbonic anhydrase VI, and may allow for earlier diagnosis of SS. A diagnostic test kit is commercially available (Sjö®), incorporating these new biomarkers along with the classic autoantibodies. This advanced test has been shown to identify SS patients who previously tested negative against traditional biomarkers only. All patients with clinically significant ADDE should be considered for serological assessment for SS, given the availability of new serological diagnostic tests and the potentially serious consequences of missing the diagnosis. Keywords: dry eye, Sjögren’s syndrome, evaporative dry eye, aqueous-deficient dry eye, biomarkers, Sjö test

The Dietary Guidelines for Americans (DGA) provides science-based advice on dietary intake to promote health, reduce risk of chronic disease, and meet nutrient needs. It is jointly published by the United States Departments of Health and Human Services and Agriculture (USDA) every 5 y. As chronic diseases continue to rise to pervasive levels, helping the United States population follow the DGA is especially important for improving the health of our nation. The DGA is developed using a rigorous and transparent scientific process, and with the advice of an independent, external committee of leading scientists. Career federal nutrition scientists who manage the process ensure that the methods used to develop the DGA remain state of the art. Unfortunately, misinformation about the scientific basis, transparency, and relevance of the DGA for the United States population threatens its credibility. The main objective of this article is to correct this misinformation with factual information about the process used to develop the DGA. The DGA provides guidelines for the general public, and its primary audience includes policymakers and nutrition and health professionals who help individuals and families consume a healthy dietary pattern. Providing accurate information may bolster trust in the recommendations among these audiences while improving implementation across sectors to promote better adherence to the DGA, thereby improving diet quality among the United States population., (Published by Elsevier Inc.)

Pain and inflammation are common experiences following ocular surgery and, if uncontrolled, can compromise patients' vision, functioning and quality of life. Corticosteroid drugs are available to manage inflammation and discomfort but have limitations in penetrating the ocular mucus barrier to reach the target ocular tissues. KPI-121 1% (INVELTYS ® ) is a novel formulation of loteprednol etabonate that employs innovative proprietary technology to deliver nanoparticle-sized mucus-penetrating particles to the cornea. Results from clinical trials demonstrate that KPI-121 1% is effective and well tolerated. KPI-121 1% uses mucopenetrative technology for ophthalmic use and is the only US FDA-approved twice-daily ocular corticosteroid indicated for the treatment of inflammation and pain after ocular surgery.

Over the past 2 decades, posterior lamellar keratoplasty (PLK) has emerged as an alternative to penetrating keratoplasty in the treatment of corneal endothelial disorders. The reasons for this trend include the search for a safer procedure to replace diseased endothelium that provides faster and better visual rehabilitation and reduces the need for postoperative care. Different surgical techniques, surgical instruments, devices, and lasers have been introduced to overcome technical difficulties, thus improving clinical outcomes. Yet, surgeons and eye banks must address the complications and limitations that arise during the transition to these new techniques. This review discusses the most significant aspects of the evolution of PLK, including a detailed description of current techniques and the direction of future treatment for corneal endothelial disease with the use of laser-assisted surgery, bioengineered corneas, cell therapy, and new pharmacologic therapy., (Copyright © 2021 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

The endothelial cell is a critical structure within the cornea and is responsible for maintaining corneal clarity through its pump function. Endothelial cells are lost over time naturally but can be injured medically, surgically, or as a part of various dystrophies. Monitoring of endothelial cells can be performed clinically or more formally with specular microscopy. In cases of significant compromise, endothelial cells can be transplanted by various endothelial keratoplasty techniques. The future pipeline is bright for possible endothelial cell regeneration and rehabilitation. This article reviews these topics in depth to provide a comprehensive look at the structure and function of the endothelial cell, etiologies of endothelial cell damage, detailed review of iatrogenic causes of endothelial cell loss, and management strategies., (Copyright © 2021 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: To evaluate the extent to which rebound tonometry affects corneal surface properties and preoperative corneal measurements., Setting: Four cornea specialty private practices., Design: Prospective case series., Methods: Visual acuity testing, corneal topography, keratometry, and grading of corneal staining were performed on both eyes of 60 randomly selected, previously scheduled patients. Technicians then performed rebound tonometry on one randomly selected eye only. Immediately following, intraocular pressure measurement, corneal topography, keratometry, and corneal staining were repeated on both eyes., Results: None of the 60 study eyes developed increased staining scores following intraocular pressure testing with the Icare ic100. For corneal staining, mean keratometry, and total corneal cylinder, no statistically significant difference was found from the first measurement to the second measurement between the study eyes and control eyes., Conclusion: Rebound tonometry with the Icare ic100 may be used on any patient at any time during the exam without affecting the results of other tests, allowing clinicians to test intraocular pressure prior to preoperative cataract or refractive surgery measurements on the same day. This may allow for significant improvement in patient flow in the office and save patients from the cost and time of extra visits., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2020.)

Members of the ASCRS Cornea Clinical Committee performed a review of the current literature on the corneal crosslinking (CXL) procedure for treating corneal ectasia. The members explored the data on the techniques currently in use and under investigation, including their advantages, safety profiles, risks, and cost analyses, compared with data on corneal transplantation. They concluded that CXL limits the progression of keratoconus, thus reducing the need for transplantation. They also found that compared with permitting the disease to progress naturally, CXL techniques carry significant and long-term cost and safety benefits, primarily by reducing the need for corneal transplantation. Studies of various CXL techniques (eg, epithelium-on treatment, changes in ultraviolet light parameters, riboflavin composition) continue with the ultimate goal of improving the procedure's safety and efficacy., (Copyright © 2019 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Any ocular surface disease (OSD), but most commonly, dry-eye disease (DED), can reduce visual quality and quantity and adversely affect refractive measurements before keratorefractive and phacorefractive surgeries. In addition, ocular surgery can exacerbate or induce OSD, leading to worsened vision, increased symptoms, and overall dissatisfaction postoperatively. Although most respondents of the recent annual American Society of Cataract and Refractive Surgery (ASCRS) Clinical Survey recognized the importance of DED on surgical outcomes, many were unaware of the current guidelines and most were not using modern diagnostic tests and advanced treatments. To address these educational gaps, the ASCRS Cornea Clinical Committee developed a new consensus-based practical diagnostic OSD algorithm to aid surgeons in efficiently diagnosing and treating visually significant OSD before any form of refractive surgery is performed. By treating OSD preoperatively, postoperative visual outcomes and patient satisfaction can be significantly improved., (Copyright © 2019 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Sjögren's syndrome (SS) is a chronic and progressive multisystem autoimmune disease typically managed by rheumatologists. Diagnostic delays are common, due in large part to the non-specific and variable nature of SS symptoms and the slow progression of disease. The hallmark characteristics of SS are dry eye and dry mouth, but there are a broad range of other possible symptoms such as joint and muscle pain, skin rashes, chronic dry cough, vaginal dryness, extremity numbness or tingling, and disabling fatigue. Given that dry eye and dry mouth are typically the earliest presenting complaints, eye care clinicians and dental professionals are often the first point of medical contact and can provide critical collaboration with rheumatologists to facilitate both timely diagnosis and ongoing care of patients with SS. Current diagnostic criteria advocated by the American College of Rheumatology are predicated on the presence of signs/symptoms suggestive of SS along with at least two objective factors such as traditional biomarker positivity, salivary gland biopsy findings, and/or presence of keratoconjunctivitis sicca. Traditional biomarkers for SS include the autoantibodies anti-Sjögren's syndrome-related antigen A (SS-A/Ro), anti-Sjögren's syndrome-related antigen B (SS-B/La), antinuclear antibody (ANA) titers, and rheumatoid factor (RF). While diagnostically useful, these biomarkers have low specificity for SS and are not always positive, especially in early cases of SS. Several newly-identified biomarkers for SS include autoantibodies to proteins specific to the salivary and lacrimal glands [SP-1 (salivary gland protein-1), PSP (parotid secretory protein), CA-6 (carbonic anhydrase VI)]. Data suggest that these novel biomarkers may appear earlier in the course of disease and are often identified in cases that test negative to traditional biomarkers. The Sjö ® test is a commercially available diagnostic panel that incorporates testing for traditional SS biomarkers (anti-SS-A/Ro, anti-SS-B/La, ANA, and RF), as well as three novel, proprietary early biomarkers (antibodies to SP-1, PSP, and CA-6) which provide greater sensitivity and specificity than traditional biomarker testing alone. Timely diagnosis of SS requires appropriate clinical vigilance for potential SS symptoms, referral and collaborative communication among rheumatology, ophthalmology, and oral care professions, and proactive differential work-up that includes both physical and laboratory evaluations.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

Purpose: The purpose of this case series was to report the detection of early markers for Sjögren syndrome (SS) in 3 patients with chronic dry eye who previously tested negative for classic SS autoantibodies., Methods: Cases of 3 patients with a history of dry eye are described. Current assessments in a cornea/ocular surface specialist clinical setting and an ocular medical history review are presented in conjunction with laboratory testing for the presence of novel autoantibody markers linked to the early stages of SS., Results: All 3 dry eye patients described in this case series tested negative for the classic autoantibody markers [Sjögren syndrome type A (SS-A) and Sjögren syndrome type B (SS-B)]. However, autoantibodies were detected in these patients indicating a likely diagnosis of early-stage SS. All patients were referred to a rheumatologist for further evaluation and treatment., Conclusions: Patients with a history of dry eye signs/symptoms that persist despite treatment (male and female patients) may benefit from a serological evaluation for SS that is capable of detecting not only the traditional SS-A and SS-B markers, but also the recently identified autoantibodies.

Purpose: The purpose of this investigation was to assess the presence and relative severity of dry eye evaluated by a panel of diagnostic methods in diabetic patients as compared with that in nondiabetic patients., Methods: Patients (≥40 years of age) scheduled for a routine eye examination at the clinical site were recruited for the study. Exclusion criteria included current use of topical medication for glaucoma or prior ocular surgery if the patient was within the postoperative recovery period (3 months). Study endpoints included tear film break-up time, tear film osmolarity, corneal fluorescein and conjunctival lissamine green staining, Schirmer strip testing, Ocular Surface Disease Index questionnaire, and Dry Eye International Task Force severity ranking., Results: Sixty-three patients were enrolled in this study, 38 in the diabetic group and 25 in the nondiabetic group. All enrolled patients scored at least a 1 on the International Task Force ranking scale. A significantly higher mean tear film osmolarity was observed in the nondiabetic patient group, 312 versus 303 mOsm/L (P = 0.02). The mean conjunctival staining scores were significantly higher in the diabetic patient group, 2.72 versus 2.11 (P = 0.034). No statistically significant differences were observed between patient groups for corneal staining, tear film break-up time, Schirmer strip, or Ocular Surface Disease Index scores., Conclusions: The overall presence and severity of dry eye was found to be similar in the diabetic and nondiabetic patient groups. However, significant differences were observed between groups with regard to individual diagnostic assessments (lissamine green staining and tear film osmolarity).

We provide evidence from comparisons of populations of Drosophila that evolutionary correlations between longevity and stress resistance break down over the course of laboratory evolution. Using 15 distinct evolutionary regimes, we created 75 populations that were differentiated for early fecundity, longevity, starvation resistance, desiccation resistance, and developmental time. In earlier experiments, selection for postponed aging produced increases in stress resistance, whereas selection for increased stress resistance produced increases in longevity. Direct estimates of correlations also indicated an antagonistic relationship between early fecundity on one hand and longevity or stress resistance on the other. Laboratory evolution of extreme values of stress resistance, however, led to a breakdown in these evolutionary relationships. There was no evidence that these significant changes in correlation resulted from genotype-by-environment interactions or inbreeding. These findings suggest that correlations between functional characters are not necessarily durable features of a species, and that short-term evolutionary responses cannot be extrapolated reliably to longer-term evolutionary patterns.

We trace the evolutionary correlation between stress resistance and longevity in populations of Drosophila melanogaster selected for stress resistance over many generations. Females selected for desiccation resistance and both females and males selected for increasing starvation resistance initially show concurrent increases in longevity, but then begin to decrease in longevity, even as stress resistance continues to increase. We demonstrate that the correlation between two fitness traits can change and that this change is due to sustained selection rather than a genotype-by-environment interaction or inbreeding depression. The breakdown in evolutionary correlation we report underscores the difficulty of extrapolating the results from short-term selection experiments to predictions of long-term evolution.

Purpose: We studied two clinical cases that demonstrated an association between topical beta-blocker therapy and lichen planus., Methods: Two patients developed skin lesions while on topical beta-blocker therapy for open-angle glaucoma. They underwent skin biopsies to determine the origin of the lesions. They were subsequently treated and followed up clinically., Results: Skin biopsy specimens from each patient demonstrated infiltrates consistent with a lichenoid drug reaction. The symptoms resolved after discontinuation of the topical beta-blocker therapy. Neither patient developed a recurrence., Conclusion: We suggest that lichen planus is a possible side effect of topical beta-blocker therapy.

Previous studies, both in animals and humans, have demonstrated that the intravenous or intraventricular administration of endogenous opioids and opiates produce dose dependent increases in plasma concentrations of prolactin. Notably, in humans, intravenous infusion of centrally active cholinomimetic drugs, such as physostigmine or arecoline, may produce significant increases in plasma concentrations of prolactin and beta-endorphin immunoreactivity. In three separate studies, conducted collaboratively between the National Institute of Mental Health and the University of California at San Diego, physostigmine and arecoline associated increases in plasma concentrations of beta-endorphin immunoreactivity were highly correlated with increases in plasma prolactin concentrations. These results are of interest because centrally active cholinomimetic drugs have been variously reported either to have no effect, to increase, or to inhibit anterior pituitary prolactin release. We propose that cholinergic stimulation of hypothalamic beta-endorphin may represent an interesting example of peptidergic modulation of primary neurochemical effects on hypothalamic-pituitary hormonal regulation.