Members Esen Akpek, MD Herbert S. Baraf, MD, MACR Richard Brasington, MD, FACR Michael Brennan, DDS, MHS Steven E. Carsons, MD* Troy Daniels, DDS, MS* Denise L. Faustman, MD, PhD H. Kenneth Fisher, MD, FACP, FCCP Gary Foulks, MD, FACS Theresa Lawrence Ford, MD S. Lance Forstot, MD Philip C. Fox, DDS* Robert I. Fox, MD, PhD, FACP* Tara Mardigan, MS, MPH, RD Austin Mircheff, PhD John Daniel Nelson, MD, FACS Kelly Nichols, OD Athena Papas, DMD, PhD Ann Parke, MD Andres Pinto, DMD Nelson Rhodus, DMD, MPH Vidya Sankar, DMD, MHS Daniel Small, MD, FACP Neil Stahl, MD Frederick B. Vivino, MD, FACR Jeffrey Wilson, MD, FACR

Members Esen Akpek, MD Herbert S. Baraf, MD, MACR Richard Brasington, MD, FACR Michael Brennan, DDS, MHS Steven E. Carsons, MD* Troy Daniels, DDS, MS* Denise L. Faustman, MD, PhD H. Kenneth Fisher, MD, FACP, FCCP Gary Foulks, MD, FACS Theresa Lawrence Ford, MD S. Lance Forstot, MD Philip C. Fox, DDS* Robert I. Fox, MD, PhD, FACP* Tara Mardigan, MS, MPH, RD Austin Mircheff, PhD John Daniel Nelson, MD, FACS Kelly Nichols, OD Athena Papas, DMD, PhD Ann Parke, MD Andres Pinto, DMD Nelson Rhodus, DMD, MPH Vidya Sankar, DMD, MHS Daniel Small, MD, FACP Neil Stahl, MD Frederick B. Vivino, MD, FACR Jeffrey Wilson, MD, FACR

Members Richard Brasington, MD, FACR Michael Brennan, DDS, MHS Steven E. Carsons, MD* Troy Daniels, DDS, MS* H. Kenneth Fisher, MD, FACP, FCCP Gary Foulks, MD, FACS Theresa Lawrence Ford, MD Philip C. Fox, DDS* Tara Mardigan, MS, MPH, RD Austin Mircheff, PhD John Daniel Nelson, MD, FACS Kelly Nichols, OD Athena Papas, DMD, PhD Ann Parke, MD Andres Pinto, DMD Nelson Rhodus, DMD, MPH Daniel Small, MD, FACP Neil Stahl, MD Pamela Stratton, MD Frederick B. Vivino, MD, FACR

Members Richard Brasington, MD, FACR Steven E. Carsons, MD* Troy Daniels, DDS, MS* H. Kenneth Fisher, MD, FACP, FCCP Gary Foulks, MD, FACS Philip C. Fox, DDS* Tara Mardigan, MS, MPH, RD Austin Mircheff, PhD John Daniel Nelson, MD, FACS Kelly Nichols, OD Athena Papas, DMD, PhD Ann Parke, MD Andres Pinto, DMD Nelson Rhodus, DMD, MPH Daniel Small, MD, FACP Neil Stahl, MD Pamela Stratton, MD Frederick B. Vivino, MD, FACR

Purpose: To describe a patient with a history of epithelial basement membrane dystrophy who developed symptomatic corneal verticillata after vandetanib therapy for anaplastic astrocytoma. Methods: Retrospective interventional case report. Results: A 48-year-old female patient with a history of anaplastic astrocytoma status post resection, external beam radiation, and chemotherapy presented with glare symptoms, decreased contrast sensitivity, and increased lacrimation after approximately 12 months of therapy with the anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor receptor 2 protein tyrosine kinase inhibitor, vandetanib. Ophthalmic examination revealed diffuse corneal verticillata and fine subepithelial opacities. Schirmer 1 testing was normal bilaterally. Therapy with carboxymethylcellulose, 5% sodium chloride ointment, and a decrease in the dose of vandetanib led to an improvement in the patient's ophthalmic symptoms despite persistence of the corneal findings. The patient remained under surveillance for tumor recurrence. Conclusions: Vandetanib (ZD6474), a protein tyrosine kinase inhibitor with dual anti-EGFR and anti-vascular endothelial growth factor receptor 2 action, may have contributed to the formation of corneal verticillata in our patient. Inhibition of EGFR, which is involved with corneal epithelial cell migration and wound healing, may play a role in the pathogenesis underlying corneal vortex keratopathy and ocular surface conditions with significant epithelial turnover.

The last 2 years in dry eye research have been memorable; in fact, they have been a culmination of over a decade of effort by a growing group of passionate and steadfast individuals in the clinical and research dry eye community. Some of the fruits of these efforts are reflected in this special dry eye issue of Optometry and Vision Science (OVS), and represent several of the initiatives and recommendations found in the recently published report(s) of the International Dry Eye Work Shop (DEWS).1–6 The recent growth of our knowledge in the field of dry eye can be assessed by comparing the DEWS reports to what is arguably the most read and cited article in the field of dry eye research, the 1995 NEI/ Industry report on clinical trials in dry eye.7 The NEI/Industry report is 12 pages in length, including references. At the time it was published, it represented the significant effort put forth by researchers in defining the disease, classifying the condition, and defining future research directions. The current DEWS report (an entire journal issue, 125 pages in length) demonstrates the significant advances in the field over time, and like its predecessor, provides a dry eye research road map for the next generation of tear film and ocular surface clinicians and researchers. Who has Dry Eye and How is it Defined? It is exciting to see that many of the articles contained in this OVS issue seek to address cutting-edge areas mentioned within the DEWS report, as well as to provide new information, which will continue to fill gaps in our knowledge of the condition. In 1995, there was minimal knowledge of the prevalence, incidence or risk factors associated with the disease.7 In this OVS issue, the 10-year incidence of dry eye in an older population is presented. This is a group of patients likely to be seen in clinical practice, and as this study demonstrates, one which will continue to grow over in the upcoming decades. Although we have greatly increased our knowledge of the patient characteristics in dry eye, our understanding of the natural history of the condition is limited. In some regards this challenges researchers to define dry eye patients consistently in clinical trials, as well as creates an environment of cat-and-mouse in drug development for new therapeutics for the condition. Dry eye is often discussed as a symptom-based disease, yet, there is some disagreement as to what symptom instrument should be accepted to classify dry eye, as well as to track changes over time or with treatment. In this OVS issue, symptoms are used in the diagnosis paradigm for classification in several studies, and several dry eye surveys are discussed. Several of the available surveys can be utilized in the diagnosis, or possibly management of the condition. Of particular interest, related to symptomatology, is the impact on quality of life. Compelling data on the impact of dry eye on every day life symptom survey is presented here, which attempts to emphasize the impact of the condition on a patient's daily quality of life. The impact of the dry eye condition on the day to day activities in a patient's life will continue to garner clinical and research interest, as we struggle to define appropriate endpoints for clinical trials. Core Mechanisms The DEWS definition and classification report highlights four “core mechanisms” in the etiology of this multifactorial condition: tear instability, tear hyperosmolarity, association with inflammatory pathways, and ocular surface damage. It is unclear how the core mechanisms result in the symptoms reported by patients, but a better understanding of the inter-relation of these mechanisms is needed. For example, the role of inflammation in dry eye is a very hotly debated topic at the forefront of the field. Unfortunately, research in this area has been limited in the past, and several researchers are making significant contributions in this area. In this OVS issue, two articles highlight the evaluation of biochemical tear components, including inflammatory mediators such as cytokines, and predominant tear proteins lipocalin and lysozyme. This type of research is a challenge in that tear samples, especially those collected in dry eye patients, may be insufficient in volume for many of the commonly utilized techniques for protein analysis, thereby requiring sensitive, not widely-available instrumentation. We expect more cutting edge research like this over the next few years as these techniques become more widely accepted and available. Contact Lens Dry Eye Four articles in this OVS issue discuss contact lens related dry eye, and while it can be debated as to whether contact lens dry eye is a separate entity, readership of this journal is well aware of the frequent symptoms and clinical characteristics of this patient group for whom which we care. Of specific interest in the contact lens research community is the impact of materials and care solutions on dryness symptoms, tear component changes, and ocular surface damage, as well as improvement in the condition with changes in any of the previously mentioned parameters. In the evaluation of factors associated with contact lens discontinuation, patient-reported dryness drives contact lens discontinuation8; therefore, a better understanding of the role of these factors in lens-related dry eye is a step in preventing contact lens drop-out. Meibomian Gland Disease Recently, an international task force used the Delphi technique to delineate diagnosis and treatment algorithms for dry eye.9 Of notable interest, lid disease (anterior and posterior blepharitis) was considered separate from dry eye, but still under the umbrella of “dysfunctional tear syndrome.” In contrast, the DEWS report includes “meibomian oil deficiency” as a subcategory of evaporative dry eye, and the recommended management of this condition is part of the overall DEWS dry eye management scheme. Several articles presented in this OVS issue discuss treatment of meibomian gland disease, and it is our expectation that this area (classification, diagnosis, etiology, and management of meibomian gland-related conditions) will be the new “dry eye.” It is possible that the vast majority of mild dry eye patients may have low-grade lid disease, warranting future clinical, and basic science research in this area. The Future is Bright We realize that there is a vast array of topical information covered in this Optometry and Vision Science issue, which we feel reflects the complex, multifactorial nature of dry eye disease. As dry eye clinicians and researchers, we are proud of the content of this issue and of the recent advances in our field. As Albert Einstein once said, “We can't solve problems by using the same kind of thinking we used when we created them.” With a wave of new clinicians and researchers interested in dry eye and new technology to support these efforts, it is clear that the field of dry eye is moving forward with innovation and creativity. With luck and effort, a new way of thinking is within reach. Kelly K. Nichols Columbus, Ohio Gary N. Foulks Louisville, Kentucky Debra A. Schaumberg Boston, Massachusetts Janine A. Smith Bethesda, Maryland

Purpose. This study was to investigate the role of the upper meniscus in tear film formation and blinking. Methods. One microliter of 2% fluorescein was instilled under the upper lid of 15 dry eye (DE) and 15 control subjects. Subjects were instructed to blink partially and hold the eye open as long as possible, and analysis of tear breakup dynamics was used to quantify the area of breakup. This procedure was repeated following a full blink. Meniscus height was measured from digital videos. Results. Both menisci were significantly decreased in DE compared with controls (p < 0.02, t test). Tear breakup dynamics analysis showed that significantly greater areas of breakup occurred with full compared with incomplete blinks in DE (p < 0.003 Mann Whitney U test), but not in controls. Conclusions. A stable tear film can be deposited by the upper meniscus alone following a partial blink, without contribution from the lower meniscus. The increased tear stability of partial blinks in DE may be due to less stretching of the already fragile tear film compared with a full blink, which covers more surface area.

Two Northern African brothers presented to the National Institutes of Health for evaluation of severe damage to sun-exposed areas of the skin, eyes, and mucosae; multiple skin cancers; a tongue mass; and photophobia with loss of vision.

Purpose: To describe a patient with cone dystrophy who presented with acute hydrops and perforation, leading to the diagnosis of keratoconus. Methods: Case report and literature review. Results: A 21 -year-old male patient with a history of cone dystrophy presented with a flat anterior chamber, diffuse corneal stromal edema with an intrastromal cleft, and ruptured Descemet membrane, findings consistent with acute hydrops with corneal perforation. After bandage contact lens placement and instillation of a cycloplegic agent, the anterior chamber reformed within 24 hours. Over the next week, conservative management with a bandage lens, pressure patching, topical fluoroquinolone antibiotic, and topical cycloplegic led to the reformation and maintenance of anterior chamber stability. Corneal topography of the unaffected eye showed global corneal thinning and steep sim K readings suspicious for early keratoconus. Conclusions: Although the association between keratoconus and cone dystrophy is extremely rare, our patient's vision-threatening complication of acute hydrops with corneal perforation highlights the importance of corneal evaluation including topography in cone dystrophy. Conservative management was successful in the restoration of anatomic integrity in this situation.

Journal of Women's HealthVol. 16, No. 3 Conversation with the ExpertsToward Optimal Health: Janine A. Smith, M.D., Discusses Vision Impairment in WomenJodi R. GodfreyJodi R. GodfreySearch for more papers by this authorPublished Online:17 Apr 2007https://doi.org/10.1089/jwh.2007.C073AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetails Volume 16Issue 3Apr 2007 InformationMary Ann Liebert, Inc.To cite this article:Jodi R. Godfrey.Toward Optimal Health: Janine A. Smith, M.D., Discusses Vision Impairment in Women.Journal of Women's Health.Apr 2007.293-298.http://doi.org/10.1089/jwh.2007.C073Published in Volume: 16 Issue 3: April 17, 2007PDF download

The report of the Epidemiology Subcommittee of the 2007 Dry Eye WorkShop summarizes current knowledge on the epidemiology of dry eye disease, providing prevalence and incidence data from various populations. It stresses the need to expand epidemiological studies to additional geographic regions, to incorporate multiple races and ethnicities in future studies, and to build a consensus on dry eye diagnostic criteria for epidemiological studies. Recommendations are made regarding several characteristics of dry eye questionnaires that might be suitable for use in epidemiological studies and randomized controlled clinical trials. Risk factors for dry eye and morbidity of the disease are identified, and the impact of dry eye disease on quality of life and visual function are outlined. Suggestions are made for further prospective research that would lead to improvement of both eye and general public health.

Graft-vs-host disease (GVHD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Indications for HSCT have greatly expanded, and more patients are undergoing HSCT today than ever before. In addition, the options for immunosuppressive therapy for both prevention and treatment of GVHD have also expanded. These changes have in turn altered the landscape of this disease. We have reviewed the current literature on this subject and presented an update on this disease with a particular emphasis on mucosal manifestations.

PURPOSE:The aim of this study was to compare the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, doxycycline, and artificial tears for the treatment of ocular surface damage in the Botulinum toxin B (BTX-B)-induced mouse model of dry eye.METHODS:CBA/J mice were randomized into 2 experimental groups of 35 animals each. The control group received a transconjunctival injection of 0.05 mL of saline into the left lacrimal gland, and another group was injected with 0.05 mL of 20 milliunits BTX-B solution (SPSS, Inc., Chicago, IL). Three (3) days after intralacrimal gland injections, each group was equally randomized into 7 subgroups (n=5 each) to receive treatment unilaterally into their left eyes with topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, 0.4% ketorolac, 0.09% bromfenac, 0.1% diclofenac, or 0.025% doxycycline. Tear volume, ocular surface changes, and spontaneous blink rate were evaluated in each of the 14 experimental subgroups.RESULTS:Topical fluorometholone, nepafenac, and doxycycline significantly improved corneal surface staining in the BTX-B-injected mice within 2 weeks of treatment. Topical ketorolac, diclofenac, and bromfenac, applied twice-daily, partially reduce corneal staining, and did so more slowly by the 4-week time point. In comparison, topical artificial tear-treated mice did not demonstrate significant improvement of the corneal surface at any time point. Aqueous tear production in the BTX-B-injected fluorometholone-treated group started to return to baseline level within 2 weeks, although not significantly. Meanwhile, BTX-B-injected mice treated with artificial tears, topical NSAIDs, and doxycycline still exhibited a reduction in tear production up to 4 weeks. No significant differences in blink rate between the control and study groups undergoing the various treatments were noted at all time points.CONCLUSIONS:This study suggests the potential usefulness of topical NSAIDs, corticosteroid, and doxycycline for the clinical treatment of ocular surface epithelial disorders associated with dry eye.