Dry eye is a common yet under diagnosed cause of ocular morbidity such as decreased vision and ocular discomfort. Though common predisposing factors include female gender and autoimmune aetiology, cases with post LASIK dryness and computer vision syndrome are on the rise. This Live Lecture discusses the disease definitions to understand the aetiology and construct the management algorithms for dry eye disease.

Lecturer: Dr. Aravind Roy

Transcript

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DR ROY: Hello, everybody. We’ll start the discussion today on the diagnosis and management of dry eyes. So when we start this lecture, could you please state your position? Okay. So while we await the poll results, let us start off with today’s talk. The healthy ocular surface includes the cornea, conjunctiva, lacrimal glands, and eyelids. A normal tear film is required to maintain ocular health. The tear film serves to provide ocular surface comfort, mechanical and environmental immune protection, maintain epithelial cellular health, and provide a smooth and powerful refracting surface for clear vision. There are several factors which are responsible for the wound healing, epithelial healing, cell proliferation, et cetera. So what are the layers of the tear film from the surface downwards? Okay. So… Let’s have the poll. Okay. So there are two concepts. One,

the three-layer model, the air-liquid interface, the aqueous, which consisted of 90% of the tear film, and the mucus layer. The new concept consists of a decreasing mucus-aqueous gel, which gradually decreases in concentration until one reaches the superficial lipid layer. So there is a mixture of lipids which are secreted by the meibomian glands, the lipids, and a uniform spread of the tear film, which provides the smooth refractive surface. The mucin component of the glycocalyx gel consists of a group of glycoproteins that promote attachment of the matrix to the corneal epithelium, provide viscosity and low surface tension, that aids uniform coverage of the ocular surface. So central to this mechanism is the elevated tear osmolality. The tear dysfunction leads to increased osmolality, sodium function, and this is related to ocular surface damage. In a meta-analysis, they found a total value of 316 milliosmoles per liters, which appears to provide acceptable sensitivity and specificity for the diagnosis of keratoconjunctivitis sicca. The specificity was 94%. The definition of the dry eyes has undergone several modifications. The latest is what I referred to. There are several components to this. It is a multifactorial disease of the tear and ocular surface that results in symptoms of discomfort, visual disturbance, tear film instability, and potential damage to the ocular surface. It’s accompanied by increased osmolality of the tear film and inflammation of the ocular surface. So dry eye can be classified into aqueous deficient and evaporative dry eye. Aqueous deficient may be Sjogren’s or non-Sjogren’s. Sjogren’s can be associated with any other autoimmune disorder. But disorders that can be associated with it are… I’m sorry. There are several… I’m sorry. Just a minute. There are several dry eye syndromes, which includes lacrimal gland deficiency, lacrimal gland duct obstruction, reflex block, and systemic drugs. The other types can be intrinsic and extrinsic. We will be discussing that. Sjogren’s is a very common cause of dry eyes. So we’ll take this poll. What is true of Sjogren’s, except? Okay. So there are a set of criteria which help classify Sjogren’s. These are the criteria for the manifestation of Sjogren’s syndrome. They include categories such as the ocular symptoms, a positive response for at least one of the questions, such as daily persistent troublesome dry eye for more than three months, recurrent sensation of sand or gravel in the eyes, made to use tear substitutes more than three times a day, oral symptoms, such as daily feeling of dry mouth for more than three months, recurrently or persistently swollen salivary glands, need for aids to help swallowing of dry food. Positive signs include rose bengal signs. Flow being less than 1.5 milliliters, and delayed uptake with reduced concentration. The autoantibodies are also positive in the test for Sjogren’s. These include antibodies to Ro and La, SSA and SSB antigens, or both. The aqueous deficient dry eye can also be a non-Sjogren’s variety. The non-Sjogren’s variety can be due to lacrimal gland failure or lacrimal gland deficiency, lacrimal gland obstruction in certain conditions, reflex block, which can be due to reflex-induced lacrimal deficiency, and there can be a reflex sensory block. Which is common in diabetics. And it’s also in neurotrophic keratitis caused by herpes simplex virus. Some systemic medications can also lead to such a condition. Evaporative dry eye results from the ocular surface losing water in the presence of normal lacrimal gland function. It can be extrinsic or intrinsic. Intrinsic causes include ocular surface disease, such as allergic conjunctivitis, contact lens wear, and components of common ophthalmic formulations. The most common culprit is benzalkonium chloride. This causes surface epithelial damage, punctate keratitis, and interferes with surface wettability. The other common group is patients who have been treated for years on (inaudible) medications. Contact lenses are extremely liable to cause dry eyes. It has been found that contact lens wearers are 12 times more likely than emmetropes to report dry eye symptoms and 5 times more likely than spectacle wearers to have dry eyes. So in a nutshell, the aggravating factors include hot climate, exposure to chemicals, dust, smoke, prolonged use of computers, or reading. The features in addition one should look for, in a patient with dry eye, are features of blepharitis and meibomitis. Mucous debris or discharge, conjunctiva is lusterless, keratinization, superficial keratitis, et cetera. So it’s quite common to see, and yet very commonly overlooked in the clinic — are obstructed meibomian gland orifices, and some expression of a milky fluid, when one gently presses the lid margin. There may be some scales, which are in the eyelashes. These can be signs of blepharitis. And there might be some notching of the margin, which suggests an epithelial problem. So you need to look at the ocular adnexa when evaluating dry eye patients. So central to this is the blepharitis and meibomitis, and very commonly, one should also look for signs of obstruction of the meibomian gland orifices, with some whitish or foamy material. So when the patient has a chronic dry eye, there may be sequelae, such as corneal thinning, there may be perforation, they may be secondarily infected. Treatment of these conditions are crucial and need to be treated as well as the cause. There is a battery of diagnostic tests that are available in dry eye. These could be Schirmer’s, tear film breakup time, ocular surface staining, questionnaires, impression cytology, measurement of tear film meniscus, et cetera. So what is the hallmark of dry eye disease? Okay. So the hallmark is raised osmolarity of tears. There are several common tests, which are performed in dry eye disease. So the most common and the most familiar, first of all, is the Schirmer’s. It’s a common office procedure. There is a wide variability under different testing conditions. The wetting of the Schirmer strips may be from 8 to 33 millimeters. And in severe dry eyes, values below 5 milliliters are of significance. The other common test that is used in the office procedure is the tear film breakup time. We don’t exactly know the mechanism of that. That is probably a break in the mucus layer. Which allows the aqueous to reach the surface, causing dry spots, which are shown in the video below. They appear as prominent areas, where the tear film starts breaking up and as you can see here, that is a dry spot that is slowly appearing. Where it starts breaking up. So again, there is a wide variability of results. Less than 10 seconds suggests tear film instability, and less than 5 seconds suggests definite dry eyes. There are several patterns of ocular surface staining that is also noticed in dry eyes. 6 areas of the conjunctiva and 5 areas of the cornea are traditionally graded, as per the industry workshop guidelines. The several grading schemes, in addition to the NEI, are the Van Bijsterveld and the Oxford scheme. They have a maximum score of 9, 15 for the cornea, and 18 for the conjunctiva. Different ocular stains are also available to look at the degree of ocular surface damage. They include fluorescein, rose bengal, and lissamine green. Fluorescein shows where tight junctions are absent. Rose bengal stains dead devitalized cells and causes burning and stinging. Lissamine also stains dead/devitalized cells, but without stinging or affecting the viability of cells. So the dry eye or the dysfunctional tear syndrome panel have proposed different staining patterns of fluorescein in patients with dry eyes or those who have a dysfunctional tear syndrome, which includes dry eye as part of the pathology. So in severe keratoconjunctivitis sicca, there is this pattern of staining. Whereas in blepharitis exposure, there is an inferior staining. Medication toxicity is typically here. And contact lens is typically like this. Similarly, these are the patterns of rose bengal staining. Where moderate or severe keratoconjunctivitis can have this pattern of staining. Here the surface is stained superiorly and inferiorly. In addition, it is used to administer an ocular disease index questionnaire. So it is important to ask the patient about symptoms of dry eye, whether the eyes are sensitive to light, whether they are gritty, painful, sore, blurring of vision, or poor vision. And how often the patient experiences these symptoms. Whether it is sometimes or whether it is all the time. And then the subtotal of all is given in this score. Which is one part of this questionnaire. The other parts include whether there are problems with some tasks, such as reading, driving, working with the computer or bank machine, poor vision, and whether the eyes are uncomfortable in any particular situation. Such as windy conditions, low humidity, air conditioned areas… One needs to add up all the scores, A, B, and C, and then obtain a total score. And then also look at the number of questions that are answered by the subject. When there is a standard scale, where the number of questions and the sum total of all the scores are graded, and then it is calculated as the sum of scores times 25, divided by the number of questions answered, which gives the total score of the ocular surface disease index. Another useful tool is the OCT, which provides accurate measurements of the tear height, with acceptable sensitivity and specificity. And it is a reproducible test. Ocular surface scraping can show keratinized epithelial cells. Note the keratin granules that would be seen in dry eyes, in keratoconjunctivitis or exposure conjunctivitis. Or other allergic processes. Osmolarity is the hallmark of dry eye. And preferably, the test for osmolarity needs to be done before any other tests are administered, so that one can get the tear film, which is not affected by instillation of different drops or stains into the eye. The tear sample can easily be collected. Esthesiometry is again helpful to know the state of the corneal sensation, assess the blink rate, and find the stability of the cornea. This can be done with a Cochet-Bonnet esthesiometer. Corneal topography is also useful, where measurement of the mires from the tear film can identify tear film irregularities and tear film quality. In addition, the meibomian glands are also well displayed, and any dilatation, dropoff, or distortion can show issues with the health of the meibomian glands. Risk factors include older age, female gender, connective tissue disorders, refractive surgery, radiation therapy — it’s an extensive list. But these are the conditions which are the most common and which are the most consistent risk factors for dry eye disease. Dry eye disease severity can also be graded from mild to severe, based on the discomfort, visual symptoms, conjunctival injection, staining, corneal and tear signs, lid/meibomian gland conditions, the TBUT, the tear film breakup type, and Schirmer scores. So when there is unstable tear film, it’s important… It’s important to look for the tear meniscus height and the result of the Schirmer test. And then categorize whether you are dealing with aqueous tear deficiency or aqueous-normal condition. So if there is a level 1 aqueous tear deficiency, one needs to use the lubricating drops, hydrate it, or use punctal plugs. With more acute aqueous deficiency, use antiinflammatory agents, protease, steroids, cyclosporine, azathioprines, or serum/albumin. In addition, punctal occlusion and PROSE are useful in treatment of severe dry eyes. In aqueous normal conditions, one needs to look into meibomian gland disease, which needs to be treated with artificial tears, expression of the meibomian gland secretions by warm compresses and lid massage, and in case of blepharitis, or meibomitis, one needs to treat with tetracycline or erythromycin. Any other conditions, such as conjunctival calluses, lagophthalmos, or exposure — then one needs to treat as per etiology. So which lubricants are best for alleviating symptoms of dry eye? So prescribing patterns differ in most ophthalmologists. There is an interesting Cochrane study on this. And the researchers found that the artificial teardrops for dry eyes are a safe and effective means of treating dry eyes. However, the literature indicates that the majority of artificial tears have similar efficacy. Thus, artificial tears can lubricate the ocular surface and reduce the osmolarity of the tear film. Protect the ocular surface from desiccation. However, there is no distinct advantage in ocular surface protection that has been found with any particular brand. The decision is based on preference and the preservative. The common preservative in artificial tears is benzalkonium chloride. However, this is something which causes a lot of ocular surface toxicity. It is such that the epithelial tight junctions accelerate the desquamation of epithelial cells, causes apoptosis in low concentration, and necrosis in high concentration. It’s worst in aqueous deficient dry eye, especially in the presence of punctal plugs, as the osmolality is increased. Alternatives include sodium perborate or unit doses which are preservative-free. Autologous serum is another alternative, which contains mediators that support the proliferation, differentiation, and maturation of the normal ocular surface epithelium. This is attributed to presence of EGF, vitamin A, lysozyme, fibronectin, and TGF-beta. So there is another Cochrane study… Where the investigators reported inconsistency in possible benefits of autologous serum for improving the signs and symptoms of dry eye. There may be some short-term benefits of using… Of using autologous serum. However, there is no evidence of a beneficial effect of autologous serum over artificial tears after two weeks of therapy. Punctal occlusion is another way of preserving the tears in a patient with dry eyes. So there are several mechanisms by which one can do that. One can do dissolvable intracanalicular plugs that are placed into the canaliculus on a trial basis. Or permanent punctal occlusion. The techniques include surgical, thermal, or tamponade. So thermal punctal occlusion may be by laser, which shrinks the canalicular walls. Tamponade methods are popular, because no surgery is involved, and it is commonly performed as an outpatient procedure. Absorbable inserts such as HPMC, collagen, collagen implants can also be used. HPMC stays for 18 hours. Whereas collagen implants can last for as long as two weeks. It reduces the outflow by 60% to 80%. Non-absorbable materials include silicone, hydroxyethyl methacrylate, and teflon. They are usually placed under topical anesthesia, and the puncta are also dilated. There are two general styles of punctal plugs. One is the arrow or the umbrella variety. Where there is a vertical portion, a collar or ring on the top of the plug, with a narrow length, and it facilitates remembered grade plug removal and decreases the risk of plug migration. The other is the fluted funnel or golf tee. So this is the arrow variety. You can see there is a collar and a ring, which sits on top of the lacrimal puncta. It needs to be introduced as an office procedure, under topical anesthesia, after dilation of the puncta. However, punctal plugs can have a lot of complications. These include irritation of the conjunctiva, cornea, pruritus and discomfort, rupture of the punctal ring, suppurative canaliculitis, canalicular stenosis, and bacterial cystitis. The plugs may also be extruded or they may promote the biofilm formation. Punctal occlusion for dry eyes — we don’t really have a lot of literature, and there is very limited data, which has found that it may be of limited benefit in dry eye disease. Antiinflammatory therapy, as an adjunct for dry eye disease, includes cyclosporine, corticosteroids, tetracycline, azathioprine, erythromycin, and fatty acids. Cyclosporine prevents T-cell activation, and has been found to increase the density of mucus goblet cells. It’s administered in twice daily dosing. Corticosteroids are potent immunosuppressors, which control the ocular surface inflammation. However, one should use low potency steroids, such as fluorometholone, Low-Dex, loteprednol, to avoid raised IOP. Tetracyclines have an antiinflammatory effect, and it stabilizes the tear film, decreases meibomian gland dysfunction and rosacea. Azithromycin has an antibacterial effect on common agents of anterior blepharitis, including staphylococcus. A number of studies have shown improvement with azithromycin. Essential fatty acids have also been found to improve the symptoms and signs of dry eye disease. Some secretagogues, such as pilocarpine, also stimulate exocrine glands and improves corneal staining. Less toxic agents include Cevimeline, which are used as secretagogues in dysfunctional tear syndrome or dry eye disease. Contact lenses, such as PROSE, is also useful in patients with severe dry eye. These are basically fluid-filled reservoirs which hydrate the cornea and shield it from blink trauma, noxious environmental stimuli, and inflammatory mediators. So when the ocular surface is damaged, with a distorted cornea, the scleral PROSE device actually acts as a reservoir which sits on the cornea and promotes rehydration and prevents noxious environmental stimuli from irritating the ocular surface. This is a patient — excuse me. This is a patient with Steven-Johnson’s syndrome, who has a lot of ocular surface discomfort. So you can see the PROSE, which is a very large lens, that sits on the anterior surface of the cornea and the anterior part of the sclera, and it keeps the tear film stable and helps alleviate the symptoms of dry eye. In conclusion, the ocular surface is important for the health of the eye, and for the vision. The paradigm shifts of… The muco… The mucin… Aqueous glycocalyx gel… The elevated tear film osmolarity is the central mechanism for ocular surface damage. And dry eye can be categorized into aqueous deficient or evaporative dry eye. So when there is an unstable tear film, one needs to categorize it as if it is… Aqueous deficient dry eye or evaporative dry eye. And then one needs to treat as per the etiology and the severity of this condition. I would like to acknowledge the leads who have helped with the materials used in this topic for discussion today. Thank you, and we can take questions now.>> So, Dr. Roy, you can stop sharing your screen.

DR ROY: Okay.

>> And it looks like we have one question, if you want to open that up.

DR ROY: Okay. Thank you, Lawrence. So… Tacrolimus is mostly an immunomodulator. It has been used for dry eye. We use cyclosporine. I personally use tacrolimus mostly to treat normal keratoconjunctivitis. But in dry eye, I have very limited experience of tacrolimus.

>> So, Dr. Roy, maybe you can stay on for a few more minutes, and we’ll see if more questions come in.

DR ROY: Okay. Azathioprine or tetracycline is used mostly as ointments, and yes, they are available commercially. What is PF lubricants? I’m not sure I understand what the question is. Could you please elaborate? This is a very interesting question. What is the role of surgery in the management of dry eyes? Okay. So… One needs to stabilize the ocular surface before one undertakes any surgery, such as cataract surgery. It is very common to have patients to have dry eyes, as well as a visually significant cataract. So it’s important to find out the cause of the dry eye, treat the cause, give supportive management, allow the ocular surface to stabilize, and then go for surgery. Preservative-free lubricants… Yes. Those are useful, when one needs to chronically use these medications, and the patient is sensitive to preservatives like benzalkonium chloride. Chloramphenicol is useful if there is an active blepharitis or meibomitis. And it is also used as a mild bacteriostatic in the setting of a poor ocular surface disease, like Stevens-Johnson’s, or when there is a graft or a drug toxicity, and one needs to stop all the antibiotics. How does the ocular surface disease index affect the management? It is another investigative tool that is used to quantify the degree of discomfort that the patient has due to dry eye. Punctal occlusion… Can be done with various methods. The permanent punctal occlusion can be done when you want to completely block the punctal orifices. The temporary punctal plugs are used for a period of a couple of days to two to three weeks. When do we select… What is the treatment plan for dry eye in young children? Very rare. But supportive treatment and treat the cause. Certain type of sunglasses? No, not aware of those. Which cases do we select drops or gels? Whenever you want the eye to be protected for a longer period of time, but the patient is not able to use the drop, then use the gel, which stays on the ocular surface for a longer period of time. Sjogren’s… Treat the cause and also give supportive treatment. With ocular lubricants. And also give immunomodulators such as steroids and cyclosporine. Look for exposure and then treat accordingly, if it is there. But most important is to treat the cause. No, dry eye is not implicated in the pathogenesis of pterygium. Pterygium is mostly due to exposure to ultraviolet rays in sunny, tropical climates. Paradoxical tearing is a neuro-related condition. Better management of dry eye problems in people using computers? Computer vision syndrome is a new entity, due to different working conditions, where people need to use a lot of time before computer monitors. So traditionally, or classically, they tended to blink less frequently. So it would be advisable for them to actually take breaks frequently, if possible, within an hour. Avoid sitting directly in front of the draft of air from the air conditioners, because air conditioners tend to be very dry and tend to dry out the ocular surface very fast. And use any artificial tears, whenever there is discomfort. Cause-effect relationship between dry eyes and pterygium. None that I am aware of.

>> So we have about 15 minutes left, if more people want to submit questions.

DR ROY: Dry eye is very common in the setting of refractive surgery, and patients often tend to have episodes of discomfort and dryness, irritation, and burning, almost more than 3 to 6 months after the surgery. Treatment options for computer vision syndrome I discussed. Take breaks, blink often, blink consciously, use artificial tears. Esthesiometry is a test which is done to test for the corneal sensation. The commonest way of doing it is allowing the patient to look straight ahead and then stand by the side of the patient and then use a wisp of cotton to touch different areas of the cornea. It is done first for one eye and then for the other. And see how quickly the eyelids blink. However, this could be done quantitatively, using the different esthesiometers. The worst damaging effect of dry eye is thinning. Perforation. And secondary infection, if in a patient with a poor ocular surface due to dry eye. Can be very difficult to manage, because these patients usually do not do well. They may need a corneal transplant. Or the therapeutic transplant is done for a non-dissolving corneal infection. (inaudible) causes lagophthalmos. But one can also tape the lids together and use a lot of lubricant. Treatment options for computer vision syndrome. I have answered it twice. It’s using artificial tears, blinking, and taking breaks frequently. And avoiding sitting directly under air conditioner. Draft of air, basically. So the conjunctiva has a lateral and medial area. Upper lateral and upper medial. Zone. And the lower lateral and lower medial zone. The cornea is divided into five zones. Central, superior, inferior, radial, and lateral. How long should you use cyclosporine? You use until the surface is stable and the surface doesn’t show a lot of staining patterns. With either fluorescein or with rose bengal or lissamine green. The test results usually come after two to three months. The best results. Any drug which contains preservatives and used for a long time — the most common clinical scenario is the antiglaucoma medications. They typically cause dry eyes. Systemic drugs like Accutane can also cause dry eyes. Topical cyclosporine is available as 0.05 or 0.01% concentration. So computer vision syndrome, again… Take breaks. Blink consciously. Use artificial tears. And avoid dry air. Yeah, if the climate is very dry, and the patient is symptomatic, then maybe you can use artificial tears. Okay… I think this is the favorite question of the evening. Computer vision syndrome. So… Okay. Use a lot of artificial tears. Blink frequently. How long you use lubricants? Well, as long as it’s necessary. Yeah. Someone has answered the computer vision syndrome also. Antibiotics — there is no role of antibiotics. In dry eye. And we use lubricants as long as the patient is stable. Antibiotics are used in the setting of blepharitis or meibomitis. To treat the attendant ocular adnexal pathology. Best lubricants — there is a Cochrane study showing that no lubricant is superior to other. All had similar efficacy. Vitamin drops? Again, these are anecdotal evidence. Not really definite, whether they have any beneficial effect.

>> So we have about 10 minutes left, if people want to keep submitting questions. The role of eyeglasses in the management of computer vision syndrome? None that I am aware of. If the patient has dry eyes and needs to have a cataract surgery done, then one needs to manage the dry eye, look at the extent of damage to the ocular surface, treat, stabilize the ocular surface, and then go ahead for cataract surgery. So this can take about a month or six weeks or three months before the surface is stable and one can go ahead and plan for cataract. Maybe we should treat the dry eye, and of course… Also treat the cause. Due to which the patient is experiencing dry eye. Change in postoperative dry eyes after advent of phaco? I’m not aware of that. People can have dry eyes due to other causes too, in addition to the surgical incision. So a minimal surgical incision can have a very limited effect on the ocular surface and it also disturbs the ocular surface to the minimum.

>> So we have about five minutes left for any last questions for Dr. Roy.

DR ROY: Not sure I understand this last question. Do you mean hydration? Not aware of the effect of drinking water. Quickest method of diagnosis? Not really sure. Omega-3… They are being promoted to help in the adjunctive management of dry eyes. There is no definitive evidence, there is no harm in having them, also. They have other benefits. But not really sure. About how it may help the patient with dry eyes. There is some evidence that they may have a beneficial effect in patients with dry eyes. Possible to prevent? Well, if you can prevent the cause, then definitely can prevent the effect also. Dietary preferences? Nothing in particular. But then there are so many vitamins, multivitamins, Omega-3 fatty acids, essential fatty acids, that are promoted. There are several natural sources of that. One can explore those options. Use as long as possible. Or as long as the patient can afford. There is no definitive evidence of the beneficial effect or the harmful effect of dietary nutrients. So no particular dietary preferences, and again, the… Omega-3 fatty acids can be used.

>> So that looks like all the questions, Dr. Roy. So it looks like we’re almost out of time. So thank you, Dr. Roy.

DR ROY: Thank you very much. Have a nice day.

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March 31, 2017

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