Ocular Surface Disease: Supplement April 2018 Accurately Diagnose & Effectively Treat Your Surgical Patients

Supported by an unrestricted educational grant from Ocular Surface Disease: Accurately Diagnose & Effectively Treat Your Surgical Patients

Prevalence of Ocular Surface Disease and Its Impact on Surgical Outcomes Accurate diagnosis of dry disease is critical before or refractive surgery By Elisabeth M. Messmer, MD

ry eye is a common disease, but it may remain EPIDEMIOLOGY OF undetected. If it is not treated before cataract or 1-4 refractive surgery, patients may have suboptimal visual AFTER outcomes from their procedures. D l Very limited data available, mostly small descriptive/

IMPACT ON CATARACT SURGERY non-randomised studies There are a number of triggering factors for dry eye (Figure 1). l 10-20% of patients: DED induced or worsened after Cataract surgery worsens or causes dry eye in approximately uncomplicated cataract surgery 10% to 20% of patients (Figure 2).1-4 l In all studies: of dry eye In a study of 136 patients with a mean age of 71 years who increase after surgery were having cataract surgery, 22% had a prior diagnosis of dry eye that was not treated.5 Thirty-one percent complained l In most studies: gradual improvement of signs and of stinging, burning or other symptoms of dry eye when asked symptoms of dry eye within 3 months about their symptoms, and 41% reported a foreign body l In some studies: signs and symptoms persist > 3 months sensation. When the patients were examined, 77% had corneal staining and 50% had central staining. Figure 2 Denervation is probably the most important factor in the pathogenesis of dry eye after cataract surgery. A corneal incision Research comparing femtosecond laser-assisted cataract in the temporal area leads to decreased corneal sensation, but this surgery (FLACS) vs. conventional surgery also occurs in other parts of the , such as the incision site showed an increase in dry eye symptoms and ocular surface for the second port.6 The central cornea also showed decreased staining in both groups.4 However, in the FLACS group, ocular sensation on day 1, day 7 and day 15 after cataract surgery. surface staining increased significantly 1 day, 1 week and 1 month after surgery. However, approximately 50% of the study population had preexisting dry eye. The incidence of dry eye Cataract surgery worsens or causes increased to approximately 70% at 1 week and approximately 60% at 1 month. In the FLACS group, there was more severe dry dry eye in approximately 10% to eye in patients with pre-existing dry eye. 20% of patients – Elisabeth M. Messmer, MD This clearly shows that our cataract surgery patients will have pre-existing dry eye that will worsen after surgery. We also need to consider that dry eye can affect intraocular After cataract surgery, the meniscus may decrease, and we (IOL) calculations. Epitropoulos et al. reported that dry may find a decreased Schirmer’s test and tear film breakup eye and increased tear hyperosmolarity were associated with time, as well as ocular surface staining.2 more variability in average K readings and anterior corneal The incidence of meibomian gland dysfunction may increase .7 As a result, there were significant differences in after cataract surgery. A prospective, observational case series of IOL power calculations. 58 of 48 patients showed changes in lid margin abnormalities In a study by Szakáts et al., examining factors associated with after cataract surgery.3 This population already has a high incidence patient satisfaction, 50% were satisfied with their cataract of meibomian gland dysfunction at baseline, before surgery, and surgery and 50% were dissatisfied.8 The following factors were meibomian gland dysfunction increases after surgery. associated with dissatisfaction: decreased tear film stability, changes in the ocular surface disease index and the visual function index and worse results on the anxiety questionnaire. TRIGGERING FACTORS FOR DRY EYE When Woodward et al. examined patient dissatisfaction after multifocal IOL implantation, dry eye especially played a major role.9 INTRINSIC EXTRINSIC IMPACT ON CORNEAL REFRACTIVE SURGERY l Age l Local environment (low humidity, windy conditions, Jabbur et al. reported that dry eye was one of the major reasons l Gender 10 seasonal influences) patients were not satisfied after refractive surgery. l Hormones In a study of SMILE vs. LASIK, there was a high incidence of l Dietary imbalance in (esp. menopause and mild to moderate dry eye 1 month after both procedures, but it omega 3/6 intake reduced androgen levels) remained significantly higher in the LASIK group vs. the SMILE l 11 l Autoimmune disorders Use of video display group 6 months after surgery. One month after surgery, (rheumatoid arthritis, l Contact lens use corneal sensitivity was better in patients who had SMILE vs. systemic erythematosus, LASIK, but it was normal at 6 months in both groups. l Exposure to medications/ thyroid disease) Pre-existing dry eye is a risk factor for postoperative dry preservatives l Inflammatory bowel disease eye; therefore, it is important to identify patients at risk l Ocular surgery before surgery. Ophthalmologists should identify risk factors, l Dermatological disorders ask patients about their symptoms and diagnose dry eye by (Rosacea, psoriasis, , pemphigoid etc.) performing a comprehensive examination. It is important to inform patients about the possibility of postoperative dry eye Figure 1 before refractive surgery.

1 Ocular Surface Disease: Accurately Diagnose & Effectively Treat Your Surgical Patients

CONCLUSION small-incision cataract surgery or phacoemulsification. Cornea. Although preoperative dry eye is common, may 2008; 27 (suppl 1):S13-18. overlook signs and symptoms when preparing a patient for 7. Epitropoulos AT, et al. Effect of tear osmolarity on repeatability of ocular surgery. Consequently, patients may be dissatisfied with keratometry for cataract surgery planning. J Cataract Refract Surg. their surgical outcomes. Therefore, it is important to treat dry 2015; 41:1672-1677. eye before surgery because it may affect IOL calculations and 8. Szakáts I, et al. Dry eye symptoms, patient-reported visual postoperative outcomes. Treatment of preoperative dry eye is functioning, and health anxiety influencing patient satisfaction after cataract surgery. Curr Eye Res 2017; 42:832-836. particularly important in patients receiving premium IOLs. 9. Woodward MA, Randleman JB, Stulting RD. Dissatisfaction after REFERENCES multifocal implantation. J Cataract Refract Surg. 2009; 35:992–997. 1. Kasetsuwan N, et al. Incidence and pattern of dry eye after cataract 10. Jabbur NS, et al. Survey of complications and recommendations for surgery. PLoS One. 2013; 8:e78657. management in dissatisfied patients seeking a consultation after 2. Li XM, et al. Investigation of dry and analysis of the refractive surgery. J Cataract Refract Surg. 2004; 30:1867-1874. pathogenic factors in patients after cataract surgery. Cornea. 11. Denoyer A, et al. Dry eye disease after refractive surgery: 2007; 26(9 Suppl 1):S16-20. comparative outcomes of small incision lenticule extraction versus 3. Han KE, et al. Evaluation of dry eye and meibomian gland dysfunction LASIK. . 2015; 122:669-676. after cataract surgery. Am J Ophthalmol. 2014; 157:1144-1150. 4. Yu Y, et al. Evaluation of dry eye after femtosecond laser-assisted Dr. Messmer is professor of ophthalmology, Ludwig Maximilian cataract surgery. J Cataract Refract Surg. 2015; 41:2614-2623. University, Munich, Germany. She may be reached at Elisabeth. 5. Trattler WB, et al. The Prospective Health Assessment of Cataract [email protected]. Patients’ Ocular Surface (PHACO) study: the effect of dry eye. Dr. Messmer is a speaker or adviser for the following companies: Clin Ophthalmol. 2017; 11:1423-1430. Alcon Pharma GmbH, Dompé, Pharm-Allergan GmbH, Santen GmbH, 6. Sitompul R, et al. Sensitivity change in cornea and tear layer due Shire, Théa Pharma GmbH, TRB-Chemedica, Ursapharm Arzneimittel to incision difference on cataract surgery with either manual GmbH, and Visufarma.

Understanding of Physiopathology: Diagnosing and Treating OSD based on DEWS II International workshop offers new insights in defining and managing dry eye disease Christophe Baudouin, MD, PhD, FARVO

he International Dry Eye Workshop (DEWS) II gathered 150 members from 23 countries, bringing new The new definition still includes concepts, definitions, and aetiological approaches to hyperosmolarity and inflammation, but it also T dry eye disease, as well as the concept of the vicious circle of dry eye disease that I introduced during the first Dry Eye introduced neural sensory abnormalities… Workshop (DEWS I).1,2 The workshop also covered neuropathic – Christophe Baudouin, MD, PhD, FARVO pain, iatrogenic dry eye, new diagnostic technologies, and new etiology-based therapies. That workshop also defined the role of hyperosmolarity and DEFINING THE DISEASE inflammation in dry eye. A decade ago, DEWS I introduced new concepts in dry eye, The second workshop changed the definition to a certain defining it as a disease of the tears and ocular surface (rather than extent. Dry eye is a disease of the ocular surface resulting from as a syndrome) that causes symptoms and visual disturbances. loss of homeostasis (Figures 1 to 3). It is a question of regulation of the ocular surface in contact with the environment, a concept that is more useful in understanding dry eye. The new definition still includes hyperosmolarity and inflammation, but it also introduced neurosensory abnormalities, which are important. However, I am disappointed that the new definition no longer describes the influence of dry eye on vision. Dry eye is not only a stinging or irritated eye. Its impact on quality of vision is also very important, especially when a patient is having refractive or cataract surgery.3

CLASSIFYING DRY EYE Although we classify dry eye as aqueous-deficient vs. evaporative dry eye and quality vs. quantity of tears, we still do not know why so many different diseases cause many different manifestations. I proposed the concept of the vicious circle to explain this. Figure 1. Severe tear film instability It begins with tear deficiency or tear abnormalities, leading to

2 Ocular Surface Disease: Accurately Diagnose & Effectively Treat Your Surgical Patients

Carlos Belmonte MD, PhD, described very complex nerve systems in the cornea that are connected to the brain stem and that peripheral pain can become central neuropathic pain, and some receptors can be activated in a noxious way.4 Therefore, they can cause pain, irritation, or discomfort. Another interesting concept is iatrogenic dry eye, which can result from eyedrops or refractive or surgeries.5 If dry eye is caused by preservatives, and the clinician treats dry eye but continues treating the patient with antibiotics because of slight corneal staining or nonsteroidal drops for chronic inflammation, it will induce dry eye and toxicity. If we do not remove the cause, dry eye will not improve. Therefore, when the cornea does not heal and the patient’s discomfort does not lessen, we need to search for the cause. If long-term eyedrops are causing dry eye, for example, we should consider an alternative. Twenty percent of people in the general population have dry eye, but 50% of patients with have dry eye. Glaucoma Figure 2. Severe alone does not increase the incidence of dry eye. The treatment can cause dry eye.

DIAGNOSING DRY EYE New technologies allow clinicians to perform measurements, visualise glands, evaluate markers and perform other assessments. To manage dry eye, we begin by obtaining information from the patient, perform assessments with advanced diagnostics and treat the case based on the cause of dry eye. I propose examining the vicious circle of dry eye disease for diagnosis. In a series of events, we can control each event individually. We can control the environment. We can use tear substitutes or insert punctal plugs to keep tears in the eye. We can control meibomian gland disease with lid hygiene and tetracyclines. We can target dry eye at its source. If we understand dry eye disease well, we have a range of techniques we can use to identify the cause of dry eye and effectively treat it. Figure 3. Lissamine green staining of the REFERENCES 1. Report of the Definition and Classification Subcommittee of the International Dry Eye Workshop. Ocul Surf. 2007; 5:75-92. hyperosmolarity via tissue damage to neurogenic inflammation 2. Nelson JD, et al. TFOS DEWS II: Introduction. Ocul Surf. 2017; that destroys goblet cells and leads to further tear film 15:269-275. abnormalities. 3. Benitez-Del-Castillo J, et al. and quality of life in dry eye The same type of concept applies to meibomian gland disease: Proceedings of the OCEAN group meeting. Ocul Surf. 2017; disease, but it is a double vicious circle – with one involving the 15:169-178. and one related to the tear film. Patients enter the circle 4. Belmonte C, et al. What causes eye pain? Curr Ophthalmol Rep. with different risk factors or an acute stress. 2015; 3:111-121. You may understand why an acute stress may cause a patient 5. Gomes JAP, et al. TFOS DEWS II iatrogenic report. Ocul Surf. 2017; to enter the circle. It also may help you understand why, when 15:511e538. the cause of stress is removed (for example, time has passed since the surgery), the patient still experiences discomfort Dr. Baudouin is professor and chair of ophthalmology, Quinze-Vingts National Ophthalmology Hospital, and Vision Institute, University Paris because the consequence is disconnected from the cause. 6, Paris, France. He may be reached at [email protected]. DEWS II introduced neuropathic dry eye. Patients with He has received consultant and research fees from Allergan, Alcon, neuropathic pain have symptoms but no signs of dry eye. Dompé, Horus Pharma, Santen, Shire, and Thea.

3 Ocular Surface Disease: Accurately Diagnose & Effectively Treat Your Surgical Patients

Exploring OSD Diagnostic Testing: From Simple to Sophisticated Techniques Range of tests can help surgeons pinpoint dry eye preoperatively By Béatrice Cochener, MD, PhD

he ocular surface plays a key role in visual outcomes after refractive surgery, so it is important to accurately Refractive surgery has driven the progress diagnose ocular surface disease (OSD) preoperatively. of ocular surface research and investments T Surgeons have access to a range of diagnostic tests to accomplish this task, ranging from simple tests to increasingly by industry – Béatrice Cochener, MD, PhD sophisticated techniques.

IMPACT OF OSD ON SURGICAL OUTCOMES Refractive surgery has driven the progress of ocular surface includes checking each area of the cornea, limbus, research and investments by industry. We recognise that conjunctiva, eyelids and tear film. by improving the ocular surface, we can improve refractive Meibomian gland dysfunction is the most common cause of surgery outcomes. evaporative dry eye. We express the meibomian glands, and OSD is the main after cataract and refractive we can use a transilluminator or meibography to quantify the surgery. Most cases of severe postoperative dry eye can be disorder. We also need to look for signs of inflammation, with attributed to preoperative dry eye that was underestimated anterior , telangiectasias and other abnormalities. previously. It is important to keep in mind that most patients Everyone should consider how much we can learn from who seek refractive surgery are doing so because they cannot properly instilling one drop of fluorescein. Tear breakup time tolerate their contact lenses, a potential sign of dry eye. demonstrates tear film stability (Figure 2).2 Although a score As with other medical conditions, we know it is more effective less than 5 is considered abnormal, it is very subjective. It to prevent OSD than to treat it. can be highlighted with a yellow filter (Figure 3). Fluorescein also is used to check for epithelial lesions, which are graded OSD DIAGNOSTICS conventionally on the Oxford scale. In diagnosing dry eye preoperatively, we need to identify Lissamine green 1% stains membrane-damaged and risk factors, such as allergies, contact lens intolerance, devitalised epithelial cells. It may be useful where there is a loss medications, autoimmune disease, hormonal changes and of mucin in the tear film and it may be more sensitive for milder age (combining many of these factors). By examining the forms of dry eye. eyelids and the skin, we also can find useful information about For the last several years, there has been controversy over the conditions such as lupus or meibomian gland disease with use of Schirmer’s test, but it provides a quantitative analysis of rosacea (Figure 1). reflex tear secretion. The patient We are moving to point-of-care tests because despite the questionnaire, such value of traditional tests, they have shown low specificity, they as the OSDI, SPEED are subjective, and they have some limitations, particularly if and others, is an they are not performed correctly. In addition, traditional tests important screening quite commonly are not correlated to clinical findings. tool to evaluate dry If the ocular surface is unstable, the quality of vision is eye and document the unstable. Decreased central visual acuity from tear film patient’s response to instability can induce higher-order aberrations, 1 treatment over time. 3 Figure 1. The routine examination should and ocular fatigue. These complaints are related to ocular include evaluation of gland expression and A comprehensive surface abnormalities and not the surgery itself. quality of the meibum examination If the decrease in tear film thickness is uniform, it modestly affects refraction, but if there are irregular variations, there are more power variations. This is why it is important to focus on the quality of blinking.4 A number of qualitative tests used to evaluate surface stability are already in routine practice, such as Placido topography and elevation topography. We can also quantify the ocular surface with advanced optical coherence tomography.5 We can measure the height of the meniscus and tear film thickness and perform epithelial mapping. Eyelid dynamics and the lipid layer are important, including the frequency and time of blink, meibography, and automated tear breakup time. Aberrometry allows us to examine the entire optical system, from the tear film to the . We can use these technologies, but we need to know where the abnormalities are originating. Among aberrometers, the double-pass aberrometer (OQAS) provides a specific index – ocular scatter index – which reflects, when greater than 2, an alteration of light diffusion in the eye. Figure 2. Irregularities of the tear film can be seen as a decrease in tear breakup This may be related to OSD if the lens and retina are normal. time and dry spots on the cornea

4 Ocular Surface Disease: Accurately Diagnose & Effectively Treat Your Surgical Patients

CHARACTERISING THE OCULAR SURFACE When characterising the ocular surface, we need to define thresholds, as well as the specificity, repeatability and sustainability of our new measurements. Hyperosmolarity, biomarkers, automated conjunctival prints and meibography (interferometry) all play a role in characterizing the ocular surface.6,7 With the point-of-care test for hyperosmolarity, if osmolarity is greater than 308 mOsm/L, the patient is considered to have dry eye. This platform has evolved into another technology that integrates testing of tear fluid biomarkers using fluorescent immunoassay detection technology, testing for osmolarity and inflammation (MMP-9 and IL-1Ra). Lactoferrin – a glycoprotein secreted by the lacrimal gland – could be a new test. Low levels of lactoferrin occur when patients have aqueous-deficient dry eye. It is a sign of lacrimal gland dysfunction, and in these cases, there is a high suspicion for Sjögren’s syndrome. Interferometry enables us to quantify and qualify the lipid layer and evaluate the meibomian glands. Dynamic meibomian gland imaging allows us to check the Figure 3. The yellow filter emphasises the point of rupture of the tear film functionality of the meibomian glands, and using different light sources, we can take multiple images and combine them. 3. Koh S. Mechanisms of visual disturbance in dry eye. Cornea 2016; CONCLUSION 35(suppl 1):S83-88. Examining and treating the ocular surface before surgery helps 4. Montés-Micó R. Role of the tear film in the optical quality of the improve surgical outcomes from refractive surgery and decrease . J Cataract Refract Surg. 2007; 33:1631-1635. the number of unhappy patients. The diagnosis of OSD does not 5. Shen M, et al. Upper and lower tear menisci in the diagnosis of dry contraindicate surgery but guides the in choosing the eye. Invest Ophthalmol Vis Sci. 2009; 50:2722-2726. procedure, preparing the eye for operation, and informing the 6. Sullivan BD, et al. An objective approach to dry eye disease severity. patient about this specific risk. We know that in medicine, it is Invest Ophthalmol Vis Sci. 2010; 51:6125-6130. always better to prevent than to cure. 7. Chotikavanich S, et al. Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional REFERENCES tear syndrome. Invest Ophthalmol Vis Sci. 2009; 50:3203-3209. 1. Ngo W, et al. Psychometric properties and validation of the standard Dr. Cochener is chair and professor of the Ophthalmology patient evaluation of eye dryness questionnaire. Cornea. 2013; Department at Brest University Hospital, France, general secretary 32:1204-1210. of EuCornea, and president-elect of ESCRS. She may be reached at 2. Abelson M., et al. Alternative reference values for tear film break [email protected]. Dr. Cochener has financial up time in normal and dry eye populations. Adv Exp Med Biol. 2002; interests in Alcon, Zeiss, Johnson & Johnson Vision, PhysIOL, RVO, 506(Part B):1121--1125. Staar, Thea, Santen, and Cutting Edge.

Management of Ocular Surface in the Context of Surgery The field of dry eye treatments continues to expand José M. Benitez del Castillo, MD

o manage ocular surface disease before refractive or cataract surgery, ophthalmologists have a range of We now have intelligent artificial tears T treatment options to consider. with osmoprotectants because the tear TEAR SUBSTITUTES film in dry eye is hyperosmolar Tear substitutes include artificial tears, dissolvable inserts and combination medications.1 We now have intelligent – José M. Benitez del Castillo, MD artificial tears with osmoprotectants because the tear film in dry eye is hyperosmolar. such as acetylcysteine, vitamin A, quercetin, frequent cause of evaporative dry eye, there is a role for lipid gallic acid and selenoprotein P play a role because there is supplementation. oxidative stress in dry eye. Autologous serum has anti-inflammatory effects and It is important to consider the inactive agents, such as stimulates nerve regeneration. When we cannot use autologous buffers and electrolytes. If phosphate levels are too high, they serum, we can use adult allogenic serum, umbilical cord serum, can cause calcic keratopathy. and platelet preparations. Because meibomian gland dysfunction is the most We have mucolytics for patients with mucus strands. We can

5 Ocular Surface Disease: Accurately Diagnose & Effectively Treat Your Surgical Patients

TOPICAL SECRETAGOGUES CASE REPORT A 65-year-old woman was referred by her ophthalmologist. l Aqueous l Lipid She originally sought medical help for poor near vision - Diquafosol - ILG-1 after a premium intraocular lens was implanted. She had- - Lacritin - Topical testosterone cataract surgery in her right eye 5 months previously with l Mucin l Oral no complications. She used unpreserved artificial tears. - Rebamipide l Nasal neurostimulation Her distance visual acuity was 0.7 and near visual acuity - Galectin-3 (TrueTear®) J5. Corneal sensitivity (Cochet-Bonnet aesthesiometer) - MMF was 5 cm (central). Other results were as follows: Schirmer l TRPM8 stimulation - NGF test: 5 mm; tear film break-up time: 1 second; corneal staining (Oxford score): 3 (central localisation); and corneal topography: central irregularity. Slit lamp examination use oral preparations, such as ambroxol and bromhexine, and showed central corneal epithelial irregularity and no acetylcysteine topical drops. conjunctival hyperemia (Figure 2). For patients with symptoms but no signs of ocular She was treated with preservative-free artificial tear surface disease, we studied TRPVI receptor antagonist, which gel in the afternoon and at night, as well as cyclosporine reduced discomfort.2 0.1% drops once a day. ADDITIONAL STEPS Patient satisfaction improved after 2 months of To help preserve tears in aqueous-deficient dry eye, we can use treatment. Superficial punctate keratopathy healed and punctal plugs or perform surgical punctal occlusion. We can her near visual acuity was J2. also decrease evaporation with moisture chamber spectacles and humidifiers. It also is helpful to avoid drying medications, desiccating Topical secretagogues can increase the production of conditions, and pollutants. In addition, we need to manage the aqueous, mucin and lipids; however, topical aqueous and psychological aspects of the disease because these patients mucin secretogogues are not available in Europe or the United are more likely to have and anxiety. States (Figure 1). Nasal neurostimulation also can increase tear In patients with dry eye, cataract surgery and refractive production. We are also studying TRPM8 stimulation. surgery produce aqueous-deficient and evaporative dry eye There are a number of treatments for lid abnormalities. Lid resulting from the use of speculums and medications, and many hygiene is very important to reduce bacteria, and tea tree oil and patients have lower lid , altering the relationship between ivermectin are used to treat Demodex. Warm compresses help the puncta and . These patients have decreased tear liquefy the lipids of the meibomian glands, thermal pulsation clearance and a greater likelihood of evaporative dry eye. facilitates meibomian gland expression and debridement scaling helps remove debris. Patients also may benefit from CONCLUSION wearing contact lenses to prevent tear evaporation. Management of dry eye disease is still an art. Patients with symptoms but no signs have neuropathic pain, and patients Management of dry eye disease with signs but no symptoms have neuropathic keratopathy. is still an art – José M. Benitez del Castillo, MD REFERENCES 1. Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev 2016; 2:CD009729 To treat inflammation, which is a main component of dry eye, 2. Benitez-Del-Castillo JM, et al. Safety and efficacy clinical trials for we can use short-term unpreserved steroids and cyclosporine. syl1001, a novel short interfering RNA for the treatment of dry eye Lubricin, a biologic agent, helps reduce friction of the eyelid disease. Invest Ophthalmol Vis Sci. 2016; 57:6447-6454. against the globe, and other biologics are being studied. 3. Ng SM, Lindsley K, Akpek EK. Omega-3 and omega-6 polyunsaturated Lifitegrast 5% is a new approach to dry eye. It binds to fatty acids for dry eye syndrome (Protocol). Cochrane Database Syst integrin receptor LFA-1 and blocks interaction between LFA-1 Rev 2014; 3:CD011016. with ICAM-1 that signals the start of the inflammatory cycle. Dr. Benitez-del-Castillo, MD, is chairman of ophthalmology UCM, It may inhibit T-cell activation, T-cell migration and secretion of Hospital Clinico San Carlos, Clinica Rementeria, Madrid, Spain. He may inflammatory cytokines. Lifitegrast treats signs and symptoms be reached at [email protected]. He has financial interests of dry eye. The onset of action is as early as 2 weeks. It can be in Allergan, Santen, Bausch + Lomb, Abbvie, Angelini, Farmamix, Horus, used in combination with cyclosporine. Alcon, Thea, Esteve, Dompé, Novartis, Sylentis, and Brill. Surgical approaches include tarsorrhaphy, surgery for , botulinum toxin, treatment for dermatochalasis, amniotic membrane grafts, dacryoreservoirs and salivary gland transplantation. Dietary modifications, including improved hydration, lactoferrin, calorie restriction for weight reduction and omega 3, 6, and 3 + 6, also may be useful.3

6 Supplement April 2018

Supported by an unrestricted educational grant from Shire, Novartis & TearLab