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Clinical & Refractive Optometry Online VOLUME 26, NUMBER 1, 2015

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Clinical & Refractive Optometry Online Editorial Board • Volume 26, Number 1, 2015

Editor-in-Chief

Associate Editor

Yvon Rhéaume, OD Montreal, Quebec

Richard Maharaj, OD Toronto, Ontario

Leonid Skorin, Jr., OD, DO, MS Albert Lea, Minnesota

Editors Emeriti John Jantzi, OD Vancouver, British Columbia

Brad Almond, OD Calgary, Alberta

Barbara Caffery, OD Toronto, Ontario

Contributing Editors Jean Bélanger, OD Montreal, Quebec

Paul Dame, OD Calgary, Alberta

Gerald Komarnicky, OD Vancouver, British Columbia

Rodger Pace, OD Waterloo, Ontario

Scott D. Brisbin, OD Edmonton, Alberta

Danielle DeGuise, OD Montreal, Quebec

Bart McRoberts, OD Vancouver, British Columbia

Maynard Pohl, OD Bellevue, Washington

Lorance Bumgarner, OD Pinehurst, North Carolina

Pierre Forcier, OD Montreal, Quebec

Ron Melton, OD Charlotte, North Carolina

Barbara Robinson, OD Waterloo, Ontario

Louis Catania, OD Philadelphia, Pennsylvania

Guy Julien, OD Montreal, Quebec

Langis Michaud, OD Montreal, Quebec

Jacob Sivak, OD, PhD Waterloo, Ontario Randall Thomas, OD Concord, North Carolina

Publication Staff Publisher Lawrence Goldstein

Managing Editor Mary Di Lemme

Senior Medical Editor Evra Taylor

Layout Editor Colin MacPherson

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Mission Statement Clinical & Refractive Optometry Online is a peer-reviewed professional journal dedicated to the publishing and disseminating of COPE approved CE credit scientific articles. The contents of each issue are composed of a mixture of original: state-of-the-art/technical, therapeutic/clinical, or practice management articles which are of particular interest to and use by practicing optometrists. Participants achieving 70% or more on the questionnaires that accompany each of the articles in the journal, will receive a course credit certificate.

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Clinical

&Refractive Optometry Online

Contents • Volume 26, Number 1, 2015 CLINICAL PRESENTATION

The Role of Ointments in Clinical Practice Paul M. Karpecki, OD, FAAO INTRODUCTION: Ophthalmic ointments have a long history dating back to ancient times and yet are still evolving with recent approvals involving technologies that allow the medication to be preservative-free. The understanding of the use, positive characteristics and side effects has also evolved to better help us position these products to most assist our patients with ocular diseases. New products of the future, may further change how ophthalmic ointments are utilized and help in treating some of the most common as well as most severe ocular pathologies we face.

CE CREDIT ARTICLES

Mechanism of Action of Oral Omega-3 rTG in Meibomian Gland Dysfunction, Simplified Theory of Dry Eye, and Integrating Omega-3 into Clinical Practice S. Gregory Smith, MD INTRODUCTION: Dr. Smith began his presentation by recounting what has occurred in his patients being seen with Dry Eye Disease over the past 30 years, recognizing it as Meibomian Gland Dysfunction.

Blink Mechanics: Viscoadaptive Technology for the Ocular Surface Richard Maharaj, OD INTRODUCTION: While the body of Dr. Maharaj’s work is in Meibomian Gland Dysfunction, he noted that this presentation topic was focused on blink metrics in mild to moderate dry eye patients.

Ophthalmic Complications of Coronary Revascularization: A Review of Literature Eva Lau, OD; Pauline F. Ilsen, OD ABSTRACT: Coronary heart disease (CHD) occurs when plaque builds up within the coronary arteries. Over time, this leads to symptoms and complications such as fatigue, shortness of breath, general weakness, angina, and myocardial infarction. Coronary angiography, coronary artery bypass grafting and percutaneous coronary intervention are common surgical procedures related to the diagnosis and treatment of CHD. Ischemic optic neuropathy, retinal artery occlusion, cortical blindness, Horner’s syndrome, and cranial nerve paralysis are some of the potential ophthalmic complications that may occur in patients undergoing coronary revascularization.

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COVER: A patient with significant scarring secondary to longstanding nocturnal lagophthalmos being treated with ointments overnight. Courtesy of: Dr. Paul M. Karpecki

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CLICK HERE TO PRINT THIS ARTICLE

The Role of Ointments in Clinical Practice Paul M. Karpecki, OD, FAAO

INTRODUCTION Ophthalmic ointments have a long history dating back to ancient times and yet are still evolving with recent approvals involving technologies that allow the medication to be preservative-free. The understanding of the use, positive characteristics and side effects has also evolved to better help us position these products to most assist our patients with ocular diseases. New products of the future, may further change how ophthalmic ointments are utilized and help in treating some of the most common as well as most severe ocular pathologies we face.

considered the bottle or droppers. Petroleum jelly, the precursor to most ointments used today, was first patented in 1872 (U.S. Patent 127,568). But it was not until the early 1900’s that tear substitutes like sodium chloride were introduced to make eye ointments and drops more similar to our natural tears.2 And in the 1930’s viscosity agents like gelatin and methylcellulose were introduced.2 Today, ophthalmic ointments are a mainstay and a key vehicle for the management of various ocular conditions.

ADVANTAGES AND DISADVANTAGES OF OINTMENTS THE HISTORY OF OPHTHALMIC OINTMENTS In Egypt in 1500 BC, the first notations of something that might resemble an ophthalmic ointment was noted. A thick eye paste consisting of antimony or the soot from incense and oil applied to the brow and lid margins was used to protect the eye from sun glare and infections.1 Castor seeds or ricinus communis, were found in Egyptian tombs dating back to 4000 BC so ointments could have gone back even further, but there is no specific evidence the oils were used for the eye. They were likely also used in India since they are indigenous to that location. Even natural made ointments (from plants for example) were documented in Egypt in ancient times. Collyrium, which means eyewash, is found in Hippocratic books dating back about 2000 years. Romans specifically documented the term collyriums that involved the use of eye salves, pastes and ointments from 31 BC to 312 AD.1 Although they may have used the word collyrium to refer to the vehicles that held the ointments that today may be

P. M. Karpecki — Cornea Services and Clinical Research Director, Koffler Vision Group, Lexington, Kentucky Correspondence to: Dr. Paul M. Karpecki, Koffler Vision Group, 120 N. Eagle Creek Drive, Suite 431, Lexington, KY 40509; E-mail: paul@karpecki.com Dr. Karpecki is a consultant to Bausch & Lomb, Allergan, Alcon, AMO, OcuSoft, Shire, Akorn, Focus Laboratories. This article has been peer-reviewed.

Clinical & Refractive Optometry Online 26:1, 2015

Benefits of ointments include an increased contact time and the potential to provide an added barrier or protection to the ocular surface. Increased contact time allows for the drug to reside longer in the vehicle and be available for absorption.3 Studies have shown a higher concentration of fluoromethalone in the anterior chamber when an ointment vehicle is used compared to that of the same drug in a suspension.4 Another advantage is that ointments are easier for patients to apply compared to instilling drops. In one particular study involving post-cataract surgery patients not only was patient satisfaction higher with a ‘bandage ointment’ (meaning a thick ointment coverage of the eye) over drops, but patients described significantly less postoperative pain and discomfort — especially in the first 10 hours after the procedure.5 Studies have also found ophthalmic ointments to be as good or superior to pressure patching when comfort and healing was measured in patients with traumatic corneal abrasions.6 In one particular study comparing relatively similar abrasion sizes, the group receiving ophthalmic ointments had significantly less pain and faster epithelial healing than the pressure patched group at all time points measured.7 Disadvantages of ointments include blurred vision and tear film instability. In a study involving the use of day time artificial tears for dry eye sufferers, patients using artificial tear ointments had a much lower level of compliance than those using artificial tears in the drop formulation.8 This is likely due to blurring of vision that may occur with more viscous ointments.9 For that reason

Fig. 1 Exposure keratopathy in a 52-year-old patient with an incomplete blink secondary to Bell’s palsy.

Fig. 2 A patient with significant scarring secondary to longstanding nocturnal lagophthalmos being treated with ointments overnight.

many clinicians recommend artificial tear ointments at night in less severe ocular surface disease conditions. That provides greater coverage during sleep and may serve a protective role in patients with lagophthalmos.10 Patients may report that ointments can be messy if too much is applied and may get on their pillows or in their hair, so appropriate instructions as to the proper amount of ointment to be applied is imperative. Patients should apply the ointment into the lower fornix not overfill the fornix. Typically about a 1/4 inch strip or one line of ointment from the dispenser is recommended into the lower fornix and sometimes a 1/2 inch strip for more significant ocular diseases. Also the use of ophthalmic ointments will not work well in patients wearing contact lenses such as with a bandage lens as it may coat the lens or dislodge it.11 Ointments, because of the increased contact time, could result in an allergic or toxic reaction, especially for those preserved with benzalkonium chloride when used longterm.12 And long-term use of steroid ointments can lead to thinning of the epidermis of the skin tissue.13 Finally ointments should not be injected into the anterior segment after a surgical procedure for example, as the vehicle may result in toxic anterior segment syndrome.14 As an example, ophthalmic ointments can cover or protect the cornea in cases of exposure keratopathy/ lagophthalmos, trauma, infection, eyelid tumors, incomplete blink or a whole host of other contributing conditions (Fig. 1).15,16 Ointments have been particularly effective for patients suffering from nocturnal lagophthalmos because of their residence time in protecting the inferior cornea during sleep (Fig. 2).15 Ophthalmic ointments are routinely used after various surgical procedures,17 and in neonatal applications.18 The most common surgical procedure that involve

ophthalmic ointments are typically those performed by oculoplastic surgeons, such as a blepharoplasty. The ointments, which are more typically antibiotic ointments like erythromycin, but may include OTC ointments like lacrilube, help in lubricating the skin tissues and may decrease the irritation and dryness surrounding the incisions. The antibiotic ointments of course serve a prophylactic role in preventing an infection. Neonatal applications of ophthalmic ointments date back to a need that was discovered in the late 1800s. Although antibiotics were not invented until the mid1900’s, the incidence of ophthalmic neonatorum (ON) was about 10% at that time resulting in corneal damage to 20% of those infected and blindness to 3%.19 The cause of ON was found to be the bacteria, nisseria gonorrhea. At that time silver nitrate 2% was introduced to prevent ON and turned out to be effective against gonorrhea resulting in a significant decrease in the incidence of ON.19,20 Topical tetracycline ointment was also used extensively in other parts of the world with good efficacy.20 However currently Chlamydia is the most common cause of ON and was resistant to silver nitrate. With the invention of antibiotics in the mid 1900’s, erythryomycin ointment became the traditional method of prophylaxis at birth. It had advantages in that it prevented ON from chlamydia and was not as toxic or uncomfortable as silver nitrate.21 It is still used today on almost every birth in Canada and the US. Perhaps one of the most common uses of ophthalmic ointment is for lid diseases such as blepharitis.22 Blepharitis can be divided into anterior and posterior forms. Although ophthalmic ointments may work for both forms, it can also cause blurring of vision if used in the eye such as for posterior blepharitis or meibomian gland dysfunction (MGD). Thus for anterior blepharitis, it holds

The Role of Ointments in Clinical Practice — Karpecki

Fig. 3 Anterior Staphylococcal blepharitis.

Fig. 4 Demodex blepharitis.

numerous advantages including effectiveness, contact time and benefits against multiple forms of the disease. The most common cause of blepharitis is from staphylococcus (Fig. 3) and many ointments including bacitracin, tobramycin and erythromycin are effective against gram positive pathogens. Although clinicians should be cognizant of multi-resistant staphylococcus such as MRSA/MRSE as an occasional culprit and thus culturing non-responsive cases may be prudent.23 In these cases none of the aforementioned antibiotics would likely treat the condition.24 Compounded vancomycin or polytrim or other medications known to be effective against MRSA and MRSE would be required. One particular study in 2007 showed that of 915 ocular disease cases involving Staphylococcus aureus isolates, that 88 were MRSA. Of this group the most common ocular condition was blepharoconjunctivitis with 78% of the group that had MRSA, manifesting this ocular condition involving blepharitis.25 Also combination agents such as tobramycin dexamethasone ointment have been shown to be effective in blepharitis.26 In one study on 148 patients randomized to tobramycin dexamethasone ointment versus placebo, the group actively treated had a statistically significant improvement in both signs and symptoms even though both groups used warm compresses, mechanical washing of the eyelids and artificial tears. However it is important to note that the group treated with tobramycin dexamethasone had a significant elevation in IOP was 3.7% compared to 1.5% in the placebo group.26 Patients known to have significant demodex (Fig. 4) have a very high association with blepharitis.27 Although this condition often requires tea tree oil to achieve an effective cure, there is some thought that ointment can play a secondary role in suffocation of the nits associated with the disease. Likewise although even more rare, pediculosis caused by

pubic lice on the eyelashes requires a bland ointment to assist in suffocating the eggs that are present.28 Other areas of application may include allergic eye diseases including giant papillary conjunctivitis,29 vernal keratoconjunctivitis,30 atopic keratoconjunctivitis,31 and even more severe forms of seasonal allergic conjunctivitis.32 Finally corneal conditions (Fig. 5) are a major area of treatment given the contact time and protection of ointments. Conditions where ointments have been shown to be effective include filamentary keratitis,33 keratoconjunctivitis sicca,34 corneal staining and corneal abrasions.35

Clinical & Refractive Optometry Online 26:1, 2015

MOST COMMON USES OF OPHTHALMIC OINTMENTS AND POTENTIAL APPLICATIONS One of the most common applications for ophthalmic ointments is that of blepharitis, although new understanding and research in the field of lid margin disease is now changing our treatment paradigms. For acute cases of blepharitis, often presenting as blepharoconjunctivitis, a pure antibiotic ointment is often sufficient to treat most bacterial pathogens. Variance of this include angular blepharitis and once again were effectively treated with an antibiotic ointment. Combination ointments were primarily used in conditions that involved both an infectious process combined with inflammation. This was often prescribed for conditions such as anterior blepharitis. But overuse and greater contact times could lead to bacterial resistance.36 As new understanding has developed in the role of meibomian gland dysfunction or posterior blepharitis and the role of inflammation, a shift to steroid only â&#x20AC;&#x201D; monotherapy ointments is occurring. For example, patients with morning symptoms and a diagnosis of MGD tend to find their symptoms improve significantly with an overnight steroid ointment. Other novel application include

Fig. 5 Severe exposure keratopathy resulting in epithelial erosion.

Fig. 6 Peripheral synechia in a patient with anterior uveitis secondary to Crohnâ&#x20AC;&#x2122;s Disease.

the use of steroid ointments for the treatment of noninfectious anterior uveitis. In the past, steroid drops were primarily used aggressively, with dosing of Q2H or Q1H being typical, but then no treatment was administered overnight. The corollary to anterior uveitis on the infectious side would be a keratitis/corneal ulcer. As clinicians we always consider overnight drops or ointments in the management of a bacterial ulcer. Likewise it makes sense to apply an ointment overnight combined with steroid drops Q1H or Q2H during the day in the management of anterior uveitis. Since incorporating this into my clinic, which has a large uveitis population, I have seen a dramatic improvement in the resolutions of anterior chamber cell and flare as well as breaking of synechiae over the last 3 to 4 years (Fig. 6). Future study is warranted but the improved treatment results of the addition of a steroid ointment are unmistakable.

(p<0.0001) and fewer required rescue medications compared to the placebo group. The most common adverse events included anterior chamber inflammation, photophobia, corneal edema, conjunctival hyperemia, eye pain and iritis. Four patients had an increase in IOP more than 10 mmHg of which three of the patients were in the LE-ointment group and one was in the placebo group. Perhaps the reason for such a low IOP rise in over 400 patients may be due to the fact that loteprednol is an ester based steroid. Ester-based steroids (loteprednol) unlike ketone-based steroids (prednisolone, fluoromethalone, dexamethasone), can have their metabolites broken down by the naturally occurring esterases.37 I think this is established because these metabolites do not remain, they are less likely to reach receptors that could result in increased intraocular pressure or be likely to create a Schiff base that could result in posterior sub capsular cataract development.38 Studies comparing ester based steroids to ketone based steroids showed half the incidence of significant IOL elevation.39 Another study comparing healthy adults showed a 7.48% incidence of IOP rise greater than 10 mmHg for patients on dexamethasone, compared to 1.95% for patients on loteprednol, but yet the efficacy of each drug in controlling inflammation was found to be the same.40 A multicenter, randomized, parallel-group, clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis. LE-ointment has also shown a very favorable safety profile consistent with previous studies on loteprednol suspension. It has been shown to be effective and well tolerated by patients for the treatment of ocular inflammation following cataract surgery.41

NEW DEVELOPMENTS IN OPHTHALMIC OINTMENTS Just recently LotemaxÂŽ ointment (Bausch + Lomb, Vaughan, ON) was approved in Canada, which is the first new ophthalmic ointment approved in over a decade. Safety and efficacy was conducted comparing loteprednol etabonate ophthalmic ointment 0.5% (LE ointment) to the vehicle for the treatment of inflammation and pain following cataract surgery in 805 patients. Efficacy outcomes included the proportion of patients with complete resolution of anterior chamber inflammation and the proportion of patients with no (grade 0) pain at postoperative day 8. Safety outcomes looked at adverse events, ocular symptoms, intraocular pressure changes and visual acuity (VA). Significantly more LE ointment treated patients than vehicle treated patients had complete resolution of ACI and zero pain at day 8 (p<0.0001 for both). Fewer Lotemax patients had ocular adverse events

The Role of Ointments in Clinical Practice â&#x20AC;&#x201D; Karpecki

Table I Ocular conditions and their recommended treatment agents Acute blepharoconjunctivits: Antibiotic ung applied to eyelid and eyelashes QHS or BID for 10-14 days. Chronic blepharitis: Antibiotic/steroid combination ointment applied to eyelid/eyelash area QHS or BID x 10-14 days, if further treatment is required for inflammation, consider a steroid ung QHS. Nocturnal lagophthalmos: Bland ointment QHS (Ocunox as an effective preservative-free example) with or without eyelid taping indefinitely. Anterior non-infectious uveitis: Prednisolone Forte Q1H or Q2H during the day + cycloplegia + overnight steroid ointment (Lotemax ung preferred) QHS. Taper slowly as improvement in anterior chamber cell and flare or breaking of synechiae occurs. Severe MGD/meibomitis: Commercial warm compress QD x 10 minutes, lid hygiene QD, combination drops BID and steroid ung QHS x 10-14 days then taper steroid options and maintain warm compresses and lid hygiene + artificial tears.

with calcium and may impair your vision. This can also be applied to the eyelid margins if conditions such as seborrheic blepharitis where dry or chaffing skin is present.

CONCLUSION Although it is critically important for eye care practitioners to be aware of the various therapeutic agents available to them, it is also equally important to understand the vehicle that the drug resides in (Table I). It is important to have a protocol for knowing when to use drops versus ointments depending on the condition and how to best educate patients. Being aware of new ointments, understanding their advantages and disadvantages, can assist in making good clinical decisions. â??

REFERENCES 1. 2.

PRESERVATIVE-FREE INNOVATIONS Lotemax ointment is noted as being preservative-free even though it is not in a unit dose vial. This is possible because non-aqueous formulations cannot support microbial growth. A certain level of water, based on a ratio of vapor pressure of water in product to vapor pressure of pure water at the same temperature (known as aw) must be present for microorganisms to grow.25 Lotemax ointment does not reach that ratio. Microorganisms have been categorized with respect to their capacity to grow and produce metabolites in various conditions based on the aw ratio.25 Bausch + Lomb also conducted its own safety study were several lots of lotemax ointment were inoculated with various microorganisms including staphylococcus aureus, pseudomonas aeruginosa, e-coli, fusarium solani, serratia marcescens, stenotrophomonas maltophilia and bipolaris australiensis.42 The units were stared at 20-25 C and samples were tested at 7, 14 and 28 days post-inoculation by plating serial dilutions of sample aliquots on appropriate growth media and counting colony forming units (CFUs) following incubation. Results showed that growth of the microorganisms was not supported in any of the Lotemax ointment lots tested during all three time periods.26 Another innovation in preservative-free ointments is that of OcunoxTM (CandorVision, Montreal, QC). This product is meant for dry eye disease management as an overnight treatment. The formulation contains retinol palmitate or vitamin A, a natural component of tears that allows for better integration with a patients existing tear film. It also comes in a tube, not a vial, and was also created preservative-free. Furthermore, the formulation is phosphorous-free which can be especially important in post-traumatic cases such as post-surgical dry eye where calcium has been shown sometimes be released. Insoluble crystals can be formed due to the reaction of phosphorous

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14.

Hirschberg, J. (1982). The History of Ophthalmology, Vol. 1: Antiquity. Bonn: Verlag J. P. Wayenborgh Caffery B. The history of dry eye diagnosis and management. Contact Lens Spectrum. January 1, 2000. Available at: http://www.clspectrum.com/printarticle.aspx?articleID= 11752. Accessed January 3, 2015 Scruggs J, Wallace T, Hanna C. et al. Route of absorption of drug and ointment after application to the eye. Ann Ophthalmol 1978; 10(3): 267-271. Sieg JW, Robinson JR. Vehicle effects on ocular drug bioavailability i: evaluation of fluorometholone. J Pharm Sci 1975; 64(6): 931-936. Sipos E1, Stifter E, Menapace R. Patient satisfaction and postoperative pain with different postoperative therapy regimens after standardized cataract surgery: a randomized intraindividual comparison. Int Ophthalmol 2011; 31(6): 453-460. Menghini M, Knecht PB, Kaufmann C. Treatment of traumatic corneal abrasions: a three-arm, prospective, randomized study. Ophthalmic Res 2013; 50(1): 13-18. Le Sage N, Verreault R, Rochette L. Efficacy of eye patching for traumatic corneal abrasions: a controlled clinical trial. Ann Emerg Med 2001; 38(2): 129-134. Swanson M. Compliance with and typical usage of artificial tears in dry eye conditions. J Am Optom Assoc 1998; 69(10): 649-655. Hiraoka T, Yamamoto T, Okamoto F et al. Tie course of changes in ocular wavefront aberration after administration of eye ointment. Eye 2012; 26(10): 1310-1317. Pereira MV, Gloria AL. Lagophthalmos. Semin Ophthalmol 2010; 25(3): 72-78. Donnenfeld ED1, Selkin BA, Perry HD et al. Controlled evaluation of a bandage contact lens and a topical nonsteroidal anti-inflammatory drug in treating traumatic corneal abrasions. Ophthalmology 1995; 102(6): 979-984. Tu EY. Balancing antimicrobial efficacy and toxicity of currently available topical ophthalmic preservatives. Saudi J Ophthalmol 2014; 28(3): 182-187. Shlivko IL, Kamensky VA, Donchenko EV, Agrba P. Morphological changes in skin of different phototypes under the action of topical corticosteroid therapy and tacrolimus. Skin Res Technol 2014; 20(2): 136-140. Werner L, Sher JH, Taylor JR et al. Toxic anterior segment syndrome and possible association with ointment in the anterior chamber following cataract surgery. J Cataract Refract Surg 2006; 32(2): 227-235.

15. Katz J, Kaufman HE. Corneal exposure during sleep (nocturnal lagophthalmos). Arch Ophthalmol 1977; 95(3): 449-453. 16. Smith MF, Goode RL. Eye protection in the paralyzed face. Laryngoscope 1979; 89(3): 435-442. 17. Trussler AP, Rohrich RJ. Blepharoplasty. Plast Reconstr Surg. MOC-PSSM CME article: 2008; 121(1 Suppl): 1-10. 18. Faucher MA, Jackson G. Pharmaceutical preparations. A review of drugs commonly used during the neonatal period. J Nurse Midwifery 1992; 37(2 Suppl): 74S-86S. 19. Klauss V, Schwartz EC. Other conditions of the outer eye. In: Johnson GJ, Minassian DC, Weale R, eds. The epidemiology of eye disease. London, Chapman & Hall, 1998. 20. Laga M, Meheus A, Piot P. Epidemiology and control of gonococcal ophthalmia neonatorum. Bull World Health Organ 1989; 67(5): 471-477. 21. Darling EK, McDonald H. A meta-analysis of the efficacy of ocular prophylactic agents used for the prevention of gonococcal and chlamydial ophthalmia neonatorum. J Midwifery Womens Health 2010; 55(4): 319-327. 22. Remitz A, Virtanen HM, Reitamo S, Kari O. Tacrolimus ointment in atopic blepharoconjunctivitis does not seem to elevate intraocular pressure. Acta Ophthalmol 2010. Jan 8 23. Khan JA, Hoover D, Ide CH. Methicillin-resistant Staphylococcus epidermidis blepharitis. Am J Ophthalmol 1984; 98(5): 562-565. 24. Kejela T1, Bacha K. Prevalence and antibiotic susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA) among primary school children and prisoners in Jimma Town, Southwest Ethiopia. Ann Clin Microbiol Antimicrob 2013; 12: 11. 25. Freidlin JL, Acharya N, Lietman TM. et al. Spectrum of eye disease caused by methicillin-resistant Staphylococcus aureus. Am J Ophthalmol 2007; 144(2): 313-315. 26. Yan XM1, Sun XG, Xie et al. Effects of tobramycin dexamethasone eye ointment for blepharitis: multi-center clinical trial. Zhonghua Yan Ke Za Zhi. 2013; 49(1): 16-21. 27. Zhao YE1, Wu LP, Hu L. Association of blepharitis with Demodex: a meta-analysis. Ophthalmic Epidemiol 2012; 19(2): 95-102. 28. Couch JM, Green WR, Hirst LW, de la Cruz ZC. Diagnosing and treating Phthirus pubis palpebrarum. Surv Ophthalmol 1982; 26(4): 219-225.

29. Kymionis GD, Goldman D, Ide T et al. Tacrolimus ointment 0.03% in the eye for treatment of giant papillary conjunctivitis. 30. Vichyanond P, tantimongkolsuk C, Dumrongkigchaiporn P. Vernal keratoconjunctivitis: Result of a novel therapy with 0.1% topical ophthalmic FK-506 ointment. J Allergy Clin Immunol 2004; 113(2): 355-358. 31. Nivenius E, van der Ploeg I, Jung K et al. Tacrolimus ointment vs steroid ointment for eyelid dermatitis in patients with atopic keratoconjunctivitis. Eye (Lond) 2007; 21(7): 968-975. Epub 2006 May 5. 32. Kari O, Saari KM. Updates in the treatment of ocular allergies. J Asthma Allergy 2010; 24; 3: 149-158. 33. Diller R, Sant S. A case report and review of filamentary keratitis. Optometry 2005; 76(1): 30-36. 34. Williams DL. A comparative approach to topical cyclosporine therapy. Eye (Lond) 1997; 11(Pt 4): 453-464. 35. Comstock TL, Paterno MR, Singh A. Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery. Clin Ophthalmol 2011; 5: 177-186. Epub 2011 Feb 10. 36. Noah S. A primer on topical antibiotics for the skin and eyes. J Drugs Dermatol 2008; 7(4): 409-415. 37. Druzgala P, Wu WM, Bodor N. Ocular absorption and distribution of loteprednol etabonate, a soft steroid, in rabbit eyes. Curr Eye Res 1991; 10(10): 933-937. 38. Comstock TL, Decory HH. Advances in corticosteroid therapy for ocular inflammation: loteprednol etabonate. Int J Inflam. 2012; 2012: 789623. Epub 2012 Mar 28 39. Chen M, Gong L, Sun X et al. A multicenter, randomized, parallel-group, clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis. Curr Med Res Opin 2012; 28(3): 385-394. 40. Holland EJ, Bartlett JD, Paterno MR, Effects of loteprednol/ tobramycin versus dexamethasone/tobramycin on intraocular pressure in healthy volunteers. Cornea 2008; 27(1): 50-55. 41. Troller JA. Trends in research related to the influence of “water activity” on microorganisms in food. Adv Exp Med Biol 1991; 302: 305-313. 42. Bausch & Lomb Inc. protocol #7066-R0498-LSG-041911-A

The Role of Ointments in Clinical Practice — Karpecki

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Clinical & Refractive Optometry Online is pleased to present this continuing education (CE) article based on a presentation given by Dr. S. Gregory Smith at the CRO 2014 Meeting in Vancouver, BC in which he discussed the treatment of meibomian gland dysfunction and dry eye with Omega 3s in the re-esterified triglyceride (rTG) form. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 14 for complete instructions.

Mechanism of Action of Oral Omega-3 rTG in Meibomian Gland Dysfunction, Simplified Theory of Dry Eye, and Integrating Omega-3 into Clinical Practice S. Gregory Smith, MD

INTRODUCTION Dr. Smith began his presentation by recounting what has occurred in his patients being seen with Dry Eye Disease (DED) over the past 30 years, recognizing it as Meibomian Gland Dysfunction (MGD). He reported that these patients showed an estimated improvement of 5% during that time. While patients did improve with his other modes of treatment, the results were markedly better with a daily dose of PRN’s (Physician Recommended Nutriceuticals) Omega-3s (EPA and DHA) in the re-esterified triglyceride (rTG) form. It is the first Omega-3 product proven to address a root cause of posterior blepharitis/MGD, in a purified triglyceride form for maximum absorption.

MEIBOMIAN GLAND DYSFUNCTION AND DRY EYE DISEASE Dr. Smith described his theory that in cases of MGD, the meibomian gland is inflamed and the content of the meibum secretions is a pro-inflammatory Omega-6 so when people blink they have tears consisting of a pro-inflammatory lipid containing inflammatory mediators washing over the ocular surface. The Omega-3s change the content of the meibum therefore the tear composition does not contain the pro-inflammatory mediators, but, rather, contain soothing anti-inflammatory Omega-3s. He conducted a pilot study comprising 20 patients with dry eye/MGD complaints taking oral Omega-3s (EPA/DHA) in the re-esterified triglyceride form and did a number of analyses to examine the types of results that would ensue. The purpose of the study was to evaluate the effect of oral re-esterified Omega-3s (EPA/DHA) on the composition of meibum in patients with MGD. S.G. Smith — Attending Surgeon, Wills Eye Hospital, Philadelphia, PA Correspondence to: Dr. Gregory Smith, Delaware Eye Surgeons, 2710 Centerville Road, Suite 102, Wilmington, DE 19808; E-mail: sgsmith@deeyesurgeons.com

Clinical & Refractive Optometry Online 26:1, 2015

Dr. Smith specified that the only Omega-3s that are useful to the body for anti-inflammatory purposes are EPA and DHA. Alphalinoleic acid (ALA), an Omega-3 available in both nuts and flaxseed oil, among other substances, cannot be converted in the body to EPA and DHA and, therefore, has no value in reaching Omega-3 therapeutic levels necessary to produce healthy meibum. Of the various Omega-6s, the most important in this context is arachidonic acid, which is a direct precursor to prostaglandins. Omega-6s are acted on by cyclooxygenase. In this study, Dr. Smith’s patients were asked to complete a standardized questionnaire, the Ocular Surface Disease Index. In addition, the patient’s primary complaint, dry eye symptoms, tear osmolarity, TBUT, corneal staining and an Omega-Index blood test indicating the level of EPA and DHA on the red blood cell membrane were evaluated. Dr. Smith wanted to ensure that these patients were being compliant: with oral administration, increases in blood omega-3 levels should be evident. Initially, he extracted baseline meibum from the meibomian glands with a Maskin probe, followed by extraction with a Mastroda paddle at two months. The dosage was 2668 mg daily of the re-esterified triglyceride form of Omega-3s (PRN’s Dry Eye Omega Benefits). Dr. Smith explained that ocean fish contain Omega-3s in the triglyceride form. However, they also contain mercury, PCBs and other heavy metals. Ethyl alcohol is used to remove the toxins from the processed oil. During this distillation process the addition of alcohol creates a chemical bond with the triglyceride oil producing an ethyl ester oil, which is a synthetic substance to the body and much less absorbable when ingested.

PRN: DISTINGUISHING FACTORS After purification, PRN takes the extra step of re-esterifying the Omega-3s. This allows the ester to be removed producing a purified, concentrated re-esterified triglyceride (rTG) Omega-3 oil, which is how the body is programmed to receive the Omega-3s (EPA and DHA), greatly increasing the body’s ability to absorb it. The first group of 20 patients was shown to be compliant. Their EPA and DHA rose significantly, while

Table I Favorable blood level indices with PRN’s rTG Omega-3s administration • All patients were compliant • EPA (eicosapentaenoic acid) increased significantly p < 0.00000 0.8% to 3.2% at 8 weeks • DHA (docosahexaenoic acid) increased significantly p < 0.00349 3.3% to 4.1% at 8 weeks • AA (arachidonic acid) decreased significantly p < 0.000004 12.2% to 10.3%

the arachidonic acid levels in their blood decreased greatly (Table I). One patient rose from 4 percent to 8 percent, which is the target level for clinical outcomes for Omega-3s. Dr. Smith noted that Omega-3s are somewhat analogous to an antibiotic like penicillin. With one capsule per day, patients are receiving only 250 mg of penicillin, and a study might therefore suggest that penicillin is not a good antibiotic. If, however, they’re given four capsules a day, the study would suggest that a therapeutic level has been achieved; the bacteria have been eliminated, with the conclusion that it is a good antibiotic. The same thing occurs with Omega-3s. One needs to examine what form the Omega-3s are in and whether or not patients actually received a therapeutic level. All 20 patients in this study reported a reduction in their primary complaint and 14 of them actually said that it was completely resolved; they no longer suffered from dry eye.

TEAR OSMOLARITY AND TBUT Tear osmolarity decreased on average roughly 17 percent after two months. There wasn’t a specific number that was significant — there were wide ranges on either side — but the net result was an average decrease of 17 percent. In addition, corneal staining improved, which was expected, and the lid margins also appeared to get better. Most importantly, stated Dr. Smith, the tear breakup time (TBUT) improved significantly. He reiterated his belief that blepharitis, MGD, and Dry Eye Disease are primarily diseases of the meibum. If the meibomian gland is not working well, the TBUT is abnormal. With these types of patients, they blink and within a second there are large clumps of oil floating on the ocular surface.

ATTAINING THERAPEUTIC LEVELS AND ABSORPTION With regard to the meibum analysis, only seven of the first 13 samples were adequate. The results showed that oleic acid formed the bulk of the meibum (Table II). Bacterial fatty acids were present at a 10 percent to 15 percent level and there was an absence of Omega-3s. At eight weeks, 14 of the 20 samples were analyzable. All 14 had Omega-3 present in the form of DHA. In this

Table II Meibum analysis • At baseline 13 samples were inadequate for analysis • Of the 7 available: • Oleic acid 18:1w9c comprised 34% to 60 % • Bacterial fatty acids comprised 10% to 15% • No omega 3 was found

initial study, Dr. Smith took patients with dry eyes, blepharitis, and meibomian gland dysfunction and put them on Omega-3s in a re-esterified triglyceride form. He found that he had now changed their meibum; it now had Omega-3s present. Concerning the literature on the topic, Dr. Marian Macsai was the first to propose that Omega-3s can be used to treat Dry Eye Disease. However, using flaxseed oil (ALA), she didn’t find any change in the meibum.

HISTORY AND EVOLUTION OF OMEGA-3S Dr. Jorn Dyerberg was the physician who basically discovered Omega-3s. In fact, he wrote the very first three papers on Omega-3s and since then there have been approximately 23,000 papers written on the subject. He did a study for the company that manufactures Lovaza, an Omega-3 in the ethyl-ester form, using three patient groups: one with Omega-3s in the re-esterified triglyceride form; another with Lovaza, a concentrated ethyl ester (much more concentrated than what patients would get at the store); and a third using unprocessed fish oil. The clinicians administered these to volunteers and measured the three absorption levels. The subjects taking unprocessed fish oil had a 100 percent bioavailability. The Lovaza level was only 72 percent bioavailability while the Omega-3s in the re-esterified triglyceride form had much greater bioavailability at 124 percent. Overall, the absorption level of the re-esterified form was roughly 98 percent, meaning that if you take 1000 mg of Omega-3s in this form by mouth, you are going to get 980 mg into your blood. However, with Lovaza, one might absorb only 540 mg into the blood, a significant difference. An over-the-counter ethyl-ester form would run at roughly 30 percent bioavailability. In light of this, said Dr. Smith, patients are receiving very limited benefits. Labels for Omega-3 products are difficult to decipher: it may state 1000 mg of fish oil, but on closer examination, the product may contain only 200 mg of Omega-3s in an ethyl-ester form of which only 30 percent is absorbed into the bloodstream; that means the patient would only get 60 mg of Omega-3s into their blood out of the 1000 mg of fish oil. That is why, Dr. Smith continued, it is essential to do the math for yourself and figure out whether or not patients are receiving the recommended therapeutic level of 2000 mg to 3000 mg of EPA/DHA per day.

Treatment of MGD and Dry Eye with Omega-3s rTG — Smith

Table III Study results: total Omega-3 (eicosapentaenoic acid [EPA] / docosahexaenoic acid [DHA])

A B C #2 #3 #5 #6 #7 #8 #9 #10 #11 #12 #13 #14 #15 #16 #17 #18 #19

Baseline

Week 8

.04 .08 .02 .03 .15 .05 .85 .16 .23 1.08 .17 .08 .13 .06 .11 .08 .12 .64 .05 lost

.31 .09 .22 .09 .23 .36 .20 .16 .34 .45 .11 .19 .32 .27 ---.18 .63 .20 .15 ----

Baseline up 7x -------up 10x up 3x up 2x up 7x down 4x --------up 3/4x down ½ down 2/5 up 2x up 3x up 4x up 2x up 5x down 3x up 3x

As flaxseed (ALA) has roughly a 3 percent conversion rate, the ALA does not get converted into EPA and DHA, which may be part of the reason why, in the Macsai and Wojtowicz studies, that they didn’t find any quantifiable change in meibum composition. However, Omega-3s in the re-esterified triglyceride form as used in this study, achieve much higher blood levels. Dr. Smith explained that the Sherlock system is a system of analysis designed to examine bacteria by identifying and typing bacterial fatty acids. However, in this case, there was an issue with calibration, prompting him to conduct another study with a different lab in order to verify the results. The improvement in symptoms, TBUT and osmolarity correlated with the findings of Macsai. However, Dr. Smith pointed out that bacterial components are also at play in patients with meibomian gland dysfunction. In 70 percent of patients in Dr. Smith’s study, the administration of oral Omega-3s in the rTG form resulted in the presence of Omega-3s in the meibum. In the repeat study comprising 21 patients, meibum was also sampled before and after administration of a daily dose of 2668 mg of Omega-3 rTG by mouth. The patients returned for follow-up at eight weeks. In his first study, Dr. Smith had noted poor meibum pretreatment collection rates and he had questions regarding the accuracy of the Sherlock system and therefore meibum composition. In this second trial group, he used the Mastroda paddle for collection and the OmegaQuant lab for analysis of the meibum.

Table IV Study results: Omega-6 (arachidonic acid [AA])

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A B C #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 #12 #13 #14 #15 #16 #17 #18

.34 .07 .07 .07 .22 .87 .04 .33 .08 .23 1.09 .03 .23 .09 .02 .05 .08 .11 .65 .04

Week 8 .11 .03 .04 .02 .05 ---.14 .02 .07 .13 .05 .03 .18 .27 .07 -----.08 .04 .04 .02

down 3x down 2x down 2x down 3x down 4x up 4x down 16x ------down 2x down 20x --------down ¼ up 3x up 3x --------down 3x down 18x down 2x

Table III illustrates the results, with the first column indicating the baseline Omega-3s level in their meibum, the second column at the eight-week follow-up, and the last column showing increase and decrease. Twelve of the 15 (80 percent) show an increase in their Omega-3s, a nearly five-fold increase. Several samples were contaminated and excluded from the calculation. Table IV illustrates the arachidonic acid results in which 12 of 18 showed a decrease; three of 18 had an increase; and three showed no change. The three contaminated specimens also had high arachidonic acid levels which dropped dramatically after treatment. The average decrease was two-and-a-half fold. Dr. Smith summarized his findings by pointing out that administering oral Omega-3s in the rTG form resulted in a nearly five-fold increase in anti-inflammatory Omega-3s and a two-and-a-half-fold decrease in proinflammatory Omega-6s in the meibum of at least 67 percent of patients. This correlated well to the first study he conducted in which 70 percent of patients had complete resolution of their symptoms and 70 percent of patients also had Omega-3s in their meibum after eight weeks of treatment. Other studies, such as those by Sullivan and Butovich, looked at meibum analysis and found nothing in terms of Omega-3s. They saw a pattern shift, but this didn’t identify anything specific. For essentially the first time, said Dr. Smith, his study found Omega-3s in the meibum — increasing — and arachidonic acid decreasing. The trial also identified bacterial cell wall products.

Meibomian Gland Dysfunction Compositon

Rheology

High in arachidonic acid

Irregular oil production

Phosolipases cyclooxygenase Prostaglandins

INFLAMMATION ON THE OCULAR SURFACE

Clumps of oil

Gaps in coverage

Irregular tear film Oil adherence to cornea

Evaporation

FOREIGN BODY SENSATION

Fig. 1 Composition and rheology of meibomian gland dysfunction.

Dr. Smith described the mechanism of action in the presence of arachidonic acid, an immediate precursor to prostaglandin (Fig. 1). The corneal surface becomes dried out because the oils are not working well. The oil leaves gaps in coverage allowing evaporation. The cells and the cell wall become injured, liberating phospholipase and therefore cyclooxygenase. With each blink, arachidonic acid is bathing the eye. The cyclooxygenase acts on the arachidonic acid to create prostaglandins on the surface of the patient’s eye, so it’s no wonder that they’re uncomfortable. Cyclooxygenase also works on Omega-3s. It converts Omega-3s through an anti-inflammatory cascade with a corresponding eicosanoid for each prostaglandin. In addition, Omega-3s produce resolvins, protectins and maresins. Resolvins are potent at the nanomolar level. Some references indicate that resolvins may be more powerful than steroids. Omega-6s have no counterpart to this. One can conclude that there are definite anti-inflammatory mechanisms relating to Omega-3s.

A NEW APPROACH TO DRY EYE TREATMENT Dr. Smith highlighted that in terms of the causes of dry eye symptoms, the inflammatory mediators are coming from an inflammatory meibum. When the meibomian glands are not functioning properly, the result is abnormal rheology — rheology is how an oil functions, including clumps, gaps and evaporation, resulting in foreign body sensation and the release of phospholipases. In these patients, the composition of the meibum is affected, producing high arachidonic acid blinks and release of prostaglandins on the surface. Clearly, he stated, giving these patients artificial tears is not going to have a long-term result, and it will produce

no change in the composition of the meibum. With an inflammatory meibum, every time the patient blinks there is another wave of arachidonic acid coming down over the surface of the eye. Each subsequent blink floods the corneal surface with Omega-6s, arachidonic acid specifically, creating inflammation. Dr. Smith’s protocol involves the administration of Omega-3s in a cleaned re-esterified triglyceride form, at a dosage of four capsules per day (2668 mg EPA/DHA). He has put approximately 1200 patients on this regimen, with improvement in 70 percent of them. If they do not improve on that regimen, he gives them a course of a topical azithromycin or oral doxycycline which works on the bacterial components of the meibum. If there is no subsequent improvement, he performs LipiFlow, which typically achieves an additional 20 percent improvement. All of this represents a tremendous shift, from a 5 percent cure rate to a 70 percent cure rate — and extremely satisfied patients.

CONCLUSION Dr. Smith concluded his presentation by describing the treatment process with an rTG Omega-3 for Meibomian Gland Dysfunction. Prior to treatment, the meibum contains inflammatory substrate arachidonic acid. Following treatment with oral Omega-3s in rTG form, the meibum is not only changed towards less inflammatory but it becomes inflammation resolving. With each blink, the ocular surface is bathed with Omega-3s which the same enzymes convert to anti-inflammatory agents, yielding extremely positive results for patients whose disturbing symptoms of dry eye had been previously treated with less than favorable, long-lasting results. ❏

Treatment of MGD and Dry Eye with Omega-3s rTG — Smith

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Registration for this CE credit course questionnaire has been made available by an unrestricted medical education grant from Physician Recommended Nutriceuticals (PRN). This course is valid for 1 hour of COPE-approved CE credit provided that it is submitted for receipt by CRO Online no later than December 1, 2017. Please do not submit after this date. In order to obtain CE credit, please follow these steps: • Fill in the identification section and answer the 10 multiple choice questions in this CE credit application form • Mail your completed CE credit application form to the Journal at: Mediconcept, 3484 Sources Blvd, Suite 518, Dollard des Ormeaux, Quebec H9B 1Z9 Canada If you score 70% or more, a COPE-approved CE Credit Certificate will be forwarded to you by your preference of either e-mail or regular mail.

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QUESTIONNAIRE Mechanism of Action of Oral Omega-3 rTG in Meibomian Gland Dysfunction, Simplified theory of Dry Eye, and Integrating Omega-3 into Clinical Practice S. Gregory Smith, MD 1. ❑ ❑ ❑ ❑

In Dr. Smith’s practice, what estimated percentage of patients with Dry Eye Disease (DED) have shown improvement over the course of three decades? 5% 10% 15% 20%

2. ❑ ❑ ❑ ❑

All of the following describe the results of Dr. Smith’s pilot study, EXCEPT: EPA increased significantly at 8 weeks DHA increased significantly at 8 weeks EPA showed a modest increase at 8 weeks AA decreased significantly

3. ❑ ❑ ❑ ❑

What is the target blood level for clinical outcomes for Omega-3s? 5% 8% 10% 12%

Clinical & Refractive Optometry Online 26:1, 2015

COPE-APPROVED CE CREDIT APPLICATION FORM

26:1, 15

4. ❑ ❑ ❑ ❑

In Dr. Smith’s pilot study, what percentage of patients reported a reduction in their primary complaint? 20% 50% 75% 100%

5. ❑ ❑ ❑ ❑

In Dr. Smith’s pilot study, what was the average decrease shown in tear osmolarity after two months? 5% 10% 13% 17%

6. ❑ ❑ ❑ ❑

In Dr. Dyerberg’s study, what was the level of bioavailability for Lovaza? 40% 55% 72% 75%

7. ❑ ❑ ❑ ❑

What is the estimated level of bioavailability for an over-the-counter ethyl-ester form of Omega-3? 30% 35% 40% 50%

8. ❑ ❑ ❑ ❑

Which of the following is the recommended therapeutic level for EPA/DHA per day? 500 mg to 1000 mg 1000 mg to 2000 mg 2000 mg to 3000 mg 3000 mg to 3500 mg

9. ❑ ❑ ❑ ❑

What is the conversion rate of flaxseed (ALA) into EPA and DHA? 3% 5% 10% 15%

10. In Dr. Smith’s repeat study, which of the following describes the approximate increase of Omega-3s in patients’ meibum? ❑ Two-fold ❑ Three-fold ❑ Four-fold ❑ Five-fold

Treatment of MGD and Dry Eye with Omega-3s rTG — Smith

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Clinical & Refractive Optometry Online is pleased to present this continuing education (CE) article based on a presentation given by Dr. Richard Maharaj at the CRO 2014 Meeting in Vancouver, BC in which he discussed the mechanics of blinking and viscoadapative technologies for the treatment of dry eye. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 21 for complete instructions.

Blink Mechanics: Viscoadaptive Technology for the Ocular Surface Richard Maharaj, OD, FAAO

INTRODUCTION While the body of Dr. Maharaj’s work is in Meibomian Gland Dysfunction, he noted that this presentation topic was focused on blink metrics in mild to moderate dry eye patients. There are two components in the discussion of the mechanics of blinking and viscoadaptive technologies. The first is what the eyelid does on a given blink. The second is the microanatomy involved in the blink at the inner and outer eyelid surface. Dr. Maharaj has observed that a blanket approach to treatment with artificial tears isn’t an effective model of care for the multifactorial dry eye patient. Following the artificial tear evolution and consideration of the chemical properties of various artificial tear products, industry has moved toward meibomian gland driven therapies with specific focus on lipid layer supplementation.

BLINK MECHANICS AND VISCOADAPTIVE DEVICES In a normal functioning eye, the eyelid closes as the superior eyelid comes down and meets the bottom eyelid, grabs onto the lipid layer and the oil film rises with the upper lid to coat the tear film. This is clearly shown on video imaging with the Oculus keratograph 5M and looks very clear under slit lamp. The human body has evolved in such a way that this mechanism of action is responsible for achieving comfort, and in fact can be the source of discomfort, said Dr. Maharaj. He noted that one of the current focuses of the Tear Film & Ocular Surface Society (TFOS) is the mechanics and metrics of blinking. Computer vision syndrome is not surprisingly on the rise. A common at home tip for patients involves blinking 20 times every 20 seconds by looking 20 feet away or the

R. Maharaj — Clinic Director, eyeLABS, Brampton, Ontario; Staff Optometrist, Humber River Regional Hospital - York/Finch Eye Associates, Toronto, Ontario Correspondence to: Dr. Richard Maharaj, 7900 Hurontario, Suite 406 Brampton, ON L6Y0P6; E-mail: rmaharaj@eyelabs.ca

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20-20-20 rule. When one looks at dry eye and ocular |surface disease, one realizes the role that the blink plays in it. Dr. Maharaj stated that understanding blink mechanics makes it easier to understand the mechanisms involved in the development of the dry eye.

MECHANICS OF DRY EYE DISEASE Dr. Maharaj described rheology, the behavior of fluids in response to applied forces, which is different from Newtonian physics; fluids respond differently than solids. An appreciation of this difference is crucial in reviewing viscoadaptive technology and pseudoelastic viscoadaptive tears. While dry eye is a chronic condition for which there is no cure, ECPs can manage it. Dr. Maharaj counsels patients that they can be treated and progress to a point where they are more comfortable, where they may not notice their eyes on any given day or any given week, but by no means is it a cure. According to various worldwide studies over the past decade, the prevalence of dry eye ranges from 7 percent up to close to 50 percent, depending on the study. In Dr. Maharaj’s dry eye clinic, more than 90 percent of patients actually exhibit the condition in itself; however, in general eye care practices, dry eye as a condition is second only to cataracts. Pre-identification of the dry eye patient undergoing surgery and pretreatment is far more likely to result in patients having a better postoperative experience. When considering sending a 65-year-old patient to a cataract surgeon for cataract surgery, for instance, preparing the patient’s ocular surface has been shown to contribute to their postoperative success. Patients that lack preoperative treatment have a four times greater risk of their dry eye worsening following surgery. In the next two to ten years, stated Dr. Maharaj, practitioners will see their role in the perioperative arena growing, and rightfully so. Based on current trends, he predicted greater discussion and use of triglyceride omega 3s for added systemic impact on meibomian gland disease. Dr. Maharaj discussed osmolarity as a dry eye metric that is important to understand in a general setting. Tear osmolarity is a valuable tool, relative to the Ocular Surface Disease Index (OSDI), corneal staining and Schirmer tear test and has been shown to be more sensitive and more specific than these other measures.

Fig. 1 Mechanics of blinking.

Fig. 2 Breakdown of blinking process.

When examining the correlation to the severity of the condition, osmolarity has the strongest correlation. To identify existing dry eye patients in a general practice, it is extremely relevant for patients that may not be symptomatic but are silently suffering. Those are the ones who may, in fact, have a hyperosmolar tear film, which means that they do have a higher component of salt and proteins like MMP-9 and other inflammatory cytokines in their tear film. If this inflammation is elevated and the patient is not symptomatic, the chronic inflammatory environment will eventually produce symptoms.

together, the gland orifice isn’t receiving any negative pressure to draw oil out of it, and if it’s not used, obstruction begins, prompting a cascade of events. Figure 2 depicts a breakdown of the blinking process, showing a superior component and a torsional component of the upper eyelid moving mainly up and down and slightly, with a minor rotation. However, the inner eyelid barely moves vertically; it actually has a nasal movement. This is an extremely complex movement with the forces being applied to the cornea and to the ocular surface, in addition to the forces being applied to the fluid between the eyelid and the cornea. Dr. Maharaj expressed his opinion that there are some more effective solutions for dry eye than artificial tears. Regardless of ethnicity or the shape of the eye, there is slight vertical movement on the superior eyelid; there is nasal and torsional movement of the superior eyelid; the inferior eyelid margin typically makes lateral movements. This produces a type of shearing force. What occurs is that rather than the front surface closing, it is the posterior lid margin that closes. The mucocutaneous junction otherwise known as the Line of Marx (LOM) forms a ridge that is not meeting up. There’s no seal of the superior and inferior LOM on lid. A quick test for this is the light test using a transilluminator (Fig. 3). With retroillumination similar to what is being depicted in the figure, a slight gap becomes apparent. Even in those patients who, under a microscope, appear to be blinking completely, they may, in fact, have inadequate lid seal which will exacerbate the condition. This will lead to increased friction, causing the lid wiper to become inflamed. In this case, the posterior lid surface is in direct opposition to the cornea with a thin pre-corneal tear film acting as a buffer between the two surfaces. The result is tissue with repetitive microtrauma causing eventual, epitheliopathy and lid inflammation. The meibomian glands are very closely associated to the lid wiper and this

BLINK MECHANICS Under a slit lamp, it is quite common for the lower eyelid to hang slightly lower than the iris, which is very common and produces infrequent, incomplete blinking. There are, however, some patients who don’t have this characteristic; they have a neat palpebral fissure, but the eyelid still doesn’t drop all the way down. In terms of blink mechanics, said Dr. Maharaj, what most patients think happens is that their lower eyelid and upper eyelid come together, touch and then move away. However, when one starts to examine the mechanics of a blink, one sees that this is, in fact, the opposite of what occurs (Fig. 1). The lower eyelid makes very little vertical movement; however, the superior eyelid does most of the travel and there’s actually a torsional component to it. That’s not even taking into consideration ethnicity, the thickness of the tear, the inner eyelid surface, or the lid wiper itself, the band of tissue that also impacts the way eyelids move. In Dr. Maharaj’s experience, examining the asymmetry between one eye and the other, one often sees anatomical and morphological changes in the meibomian gland of the eye that has a decreased blink rate and decreased blink completeness. In patients whose eyelids come together, there is a correlation with meibomian gland atrophy or truncation: if the eyelids are not coming completely

Blink Mechanics: Viscoadaptive Technology for the Ocular Surface — Maharaj

Fig. 3 Transilluminator test.

Fig. 4 Components of the TFOS DEWS algorithm.

is where Meibomian Gland Dysfunction (MGD) can start in some patients. Dr. Maharaj stated that while it is important to distinguish between aqueous deficiency and evaporative dry eye, he does not view the situation as one or the other. This condition is very much a spectrum disease. At some point, MGD will lead to up-regulation of the lacrimal gland, eventually causing it to become inflamed, resulting in aqueous deficiency. All dry eye patients appear at some point on this spectrum.

forces previously discussed, and whether or not it stabilizes the tear film.

MECHANICS OF DYSFUNCTIONAL BLINKING In terms of the MGD cycle, Dr. Maharaj stated that the TFOS DEWS algorithm is extremely complex; therefore, he has extracted some of the elements he feels are most relevant (Fig. 4). He suggests that practitioners examine the eyelid aperture of the blink first, looking for the lid seal. When the blink becomes dysfunctional, it results in lid wiper microtrauma due to friction. The resulting symptoms can include extreme pain, mild to severe contact lens intolerance and visual instability. This will lead to hyperosmolarity with an up-regulation in MMP-9 (Matrix metallopeptidase 9), salts and other proteins. Tear hyperosmolarity drives the tear solutes toward the lid margin and meibomian glands and thus the evaporative and aqueous cycle begins. This process applies to the vast majority of mild to moderate dry eye patients and is therefore a good starting point in determining the goal of an artificial tear. Looking at the problems created by that cycle, the first thing that occurs is decreased blink rate and poor closure. Therefore, said Dr. Maharaj, the goal in tear film therapeutics should be aimed at increased residence time on the cornea with minimal effect on vision stability. Examining the attributes of a topical treatment that allows it to last longer on the eye is essential. For instance, how it interacts with the eyelid surfaces with the shearing

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CURRENT DRY EYE TREATMENTS The goal of therapy is long-term stability, which is a very important part of the tear chemistry — an essential element. As an immunomodulator — a targeted antiinflammatory therapy — Restasis® (cyclosporine ophthalmic emulsion, Allergan Canada, Markham, ON), is extremely effective, noted Dr. Maharaj, at addressing aqueous deficient dry eye. At the 2011 MGD workshop, MGD became defined as perhaps the leading cause of dry eye disease around the globe. With this, replacing the lipid layer became the utmost priority. The term “viscoadaptive” was introduced; Dr. Maharaj remarked that it appears to be a confusing term. When doctors refer to the viscosity of a solution, they know what it means in terms of thicker or thinner. Intraoperatively, it has a different meaning than viscoadaptive on the external eye. In rheology, the study of forces on fluids is very different when compared to forces on solids because fluids are very much like air; the forces are more or less Newtonian. One can pass one’s hands through it without resistance. However, with a fluid like glass, the forces that need to be applied to get it to move like a liquid are very, very high. The three tenets are understanding viscosity, understanding elasticity, and then examining the cohesive and dispersive nature of fluids. Dr. Maharaj stated that there are four patterns of rheometric behavior of fluids (Fig. 5); namely Newtonian, pseudoplastic, plastic and dilatant. In Figure 5 the further to the left on the x axis, the lower the shear forces being applied; the further to the right, the higher the shear force. The y axis relates to viscosity. The solution can be a

Rheometric Patterns of Fluid Behaviour: Viscosity

Intraocular OVD Pseudoplasticity Curves

Fig. 5 Variations in applied force.

Fig. 6 Pseudoplastic curves of viscoelastic devices.

liquid which will be lower down on the graph or, it can behave like glass or a fractureable solid which will appear higher on the graph.

of this type of fluid is hyaluronic acid (HA). In order to make it a dispersive substance, one can add a short-chain branched molecule that is not bound to the HA that can actually separate from the HA by force. What happens with an artificial tear with HA and a short-chain branched polymer is exposed to blink forces, the HA separates — it binds with the water found in the aqueous component of tears — and it excludes the short branched polymer present. A hyaluronate and glycerin solution during the blinking process will almost behave like a contact lens — a fractureable solid — in the eye when the eyelid closes because it is applying a high amount of shear force. When the eyelid opens, the solution returns to a fluid state. In terms of applying these forces to an artificial tear, consideration needs to be given to the way the eyelid moves with a HA-based eye drop compared to a Newtonian solution like methylcellulose, for example. In the surgical context, the pseudoplastic curves of some of the ophthalmic viscoadaptive devices used in intraocular surgery are shown in Figure 6. The curves vary depending on the device used. Dr. Maharaj noted that some examples currently used in surgery were actually used to derive hyaluronic-based eye drops. Healon® 5 (sodium hyaluronate, AMO, Markham, ON) and iVisc® (sodium hyaluronate, I-Med Pharma, Montreal, QC), for instance, are commonly used. Depending on the shear forces applied, the liquid will eventually reach a certain viscosity and not go past that point. Artificial tears such as Tears Naturale® (ocular lubricant, Alcon Canada, Mississauga, ON), Systane® (lubricant eye drops, Alcon Canada, Mississauga, ON), GenTeal® (lubricant eye drops, Alcon Canada, Mississauga, ON), all have a very simple linear Newtonian movement on the eye regardless of the eye’s blink mechanics.

NEWTONIAN TEAR SOLUTIONS Many fluids are pseudo-Newtonian; they’re not quite Newtonian; however, they possess more or less these same characteristics. On the other hand, plastics when exposed to a great force can carry liquid-like characteristics. As shown in Figure 5, fluid-like behaviors or low viscosity behaviors at a certain force will become more viscous. The term for this is zero shear rate. Past the zero shear rate it becomes a fractureable solid. The zero shear rate of a pseudoplastic material is important in surgery (intraoperative surgery is really where it all evolved from) because there has to be a point at which it doesn’t become more viscous. If it did, it would harden in the anterior chamber making surgery very difficult. Pseudoplastics have evolved and have been adapted to the ocular surface specifically because of this fact. Dr. Maharaj stated that this is particularly important when considering artificial tears: The eyelid moves around and applies shear forces. Viscous solutions that still have Newtonian-like behavior with long and short branched polymers behave in more or less a Newtonian fashion. Pseudoplastic or viscoadaptive solutions will behave differently to the various moments in a blink.

NON-NEWTONIAN TEAR SOLUTIONS Regarding blink forces, instead of a tear solution progressing from a cohesive fluid to a hard solid, it actually moves from a cohesive fluid to an elastic material. In the process of blinking, the eyelid comes down and compresses. It squeezes the material down. One example

Blink Mechanics: Viscoadaptive Technology for the Ocular Surface — Maharaj

FEATURES OF PSEUDOPLASTIC ELASTOVICOUS TEARS The first Canadian pseudoplastic elastoviscous tear is known as i-drop® (I-Med Pharma, Montreal, QC). It is distinguished by its high molecular weight sodium hyaluronate combined with a short-chain branched polymer, glycerin. The interesting feature of HA is that all the cells in the body, including those of the cornea, have hyaluronic binding sites. The HA in the eye drop binds to these binding sites, anchoring the tear onto the ocular surface. The HA actually combines with the water found in the tears. It excludes the glycerin which rises to the surface as the eyelid blinks. The glycerin provides a lubricating surface to the blink, decreasing friction on the ocular surface. Once the eyelid reaches down to the bottom, and the eyelid comes up and the solution returns to its original low viscosity. As a result of this process, the residence time is high. The tear mimics all three layers of the tear film simply by virtue of its physical properties. Dr. Maharaj uses this approach in his general patients, in order to prolong residence time, decrease evaporation and create visual stability. A high molecular weight hyaluronic-based drop allows this. From a rheological perspective, pseudoplastic elastoviscous tears, or PETs, produce the desired effect, mimicking naturally occurring tears. The problem of decreased blink rate and closure requires that a topical tear increases the residence time on the eye, which i-drop achieves. This is accomplished through decreasing friction on the ocular surface with unbound glycerin and stabilization of the tear film via HA. This decreases evaporation and stabilizes the tear film, providing patients substantially greater comfort. Dr. Maharaj stated that the last benefit of some of the new drops coming to market, i-drop being one of them, is that they are packaged in a multi-dose, non-preserved bottle. He views the lack of preservatives as an important

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benefit. The bottle form may make it more convenient for patients. The first clinical study of hyaluronan eye drops was undertaken in 1982. At the time, HA was found to have a much longer residence time. This led to the Hylan™ Surgical Shield (Elastoviscous Hylan Surgical Shield, 0.45%) which surgeons were using during surgery to coat and protect the ocular surface. Dr. Maharaj suggested that when addressing the ocular surface, practitioners ought to carefully consider the true etiology of the condition and all available solutions. With an abundance of products on the market and patients not knowing which to choose, Dr. Maharaj suggested that eye care professionals make very specific patient recommendations. It is now known that patients are blinking less frequently and less completely, which Dr. Maharaj noted are facts that need to be addressed when weighing treatment options for dry eye. He stated that the best way to achieve this is to provide patients the most successful available products, rather than simply telling them to modify their blink behavior and to use the nearest artificial tear. In Dr. Maharaj’s Dry Eye Clinic, a very discrete and direct protocol is used. He instructs his patients, “Follow my specific instructions or you won’t feel better. That’s why I’m being specific.” He takes this approach because if one tells patients to use any artificial tear, they will. This leaves the decision of choosing the topical up to the patient. As a health provider is it imperative to educate patients to make an informed decision.

CONCLUSION Dr. Maharaj concluded his presentation by emphasizing the importance of providing patients a specific recommendation to their individual dry eye problem. The tear film ought to be addressed as a mechanism, as opposed to an element that must be supplemented. ❏

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QUESTIONNAIRE Blink Mechanics: Viscoadaptive Technology for the Ocular Surface Richard Maharaj, OD, FAAO

1. ❑ ❑ ❑ ❑

According to worldwide studies, what is the estimated prevalence of dry eye? 7 percent to 20 percent 7 percent to 30 percent 7 percent to 40 percent 7 percent to 50 percent

2. ❑ ❑ ❑ ❑

What is the rate of risk for patients who lack preoperative treatment having their dry eye worsen following surgery? Two times greater Three times greater Four times greater Five times greater

3. ❑ ❑ ❑ ❑

Which of the following is a risk factor for dry eye? Dysfunctional blink Patient age Blink rate Heredity

Blink Mechanics: Viscoadaptive Technology for the Ocular Surface — Maharaj

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4. ❑ ❑ ❑ ❑

How common is the phenomenon of the lower eyelid hanging slightly lower than the iris? Rare Very common More common in the Asian population Occurs in approximately 50 percent of the overall population

5. ❑ ❑ ❑ ❑

All of the following can affect blink mechanics, EXCEPT: Recent episode of conjunctivitis Thickness of the tear The inner eyelid surface Ethnicity

6. ❑ ❑ ❑ ❑

All of the following statements regarding blink mechanics are false, EXCEPT: Blink frequency and completeness have not changed over the last decade People are blinking less frequently and less completely People are blinking more frequently due to computer vision syndrome People are blinking more frequently and less completely

7. ❑ ❑ ❑ ❑

All of the following are clinical signs/symptoms of dysfunctional blinking, EXCEPT: Extreme ocular pain Visual instability Foreign body sensation Contact lens intolerance

8. ❑ ❑ ❑ ❑

In Dr. Maharaj’s dry eye clinic, what percentage of patients exhibit dry eye? 25% 50% 70% 90%

9. ❑ ❑ ❑ ❑

All of the following statements about dry eye are false, EXCEPT: It can be managed but not cured In the earliest stage of the disease, it can be cured Various studies have shown cure rates of 5 percent to 20 percent It can be cured if patients comply with strict medication protocols

10. ❑ ❑ ❑ ❑

Which of the following is the most accurate measure of dry eye severity? Schirmer tear test Ocular Surface Disease Index (OSDI) Tear osmolarity Corneal staining

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Clinical & Refractive Optometry Online is pleased to present this continuing education (CE) article by Dr. Eva Lau and Dr. Pauline F. Ilsen entitled Ophthalmic Complications of Coronary Revascularization: A Review of Literature. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 29 for complete instructions.

Ophthalmic Complications of Coronary Revascularization: A Review of Literature Eva Lau, OD; Pauline F. Ilsen, OD

ABSTRACT Background: Coronary heart disease (CHD) occurs when plaque builds up within the coronary arteries. Over time, this leads to symptoms and complications such as fatigue, shortness of breath, general weakness, angina, and myocardial infarction. Coronary angiography, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) (also known as coronary angioplasty) are common surgical procedures related to the diagnosis and treatment of CHD. Ischemic optic neuropathy, retinal artery occlusion, cortical blindness, Horner’s syndrome, and cranial nerve paralysis are some of the potential ophthalmic complications that may occur in patients undergoing coronary revascularization. Unfortunately, the risk for ophthalmic complications is often not discussed with patients prior to surgery. Conclusions: The risks and complications for patients undergoing coronary revascularization may range from transient and benign to permanent and visually devastating. Patients who anticipate undergoing surgery should be aware that potential risks could involve their vision and ocular health. It is important for both the patients and their health care providers to seek ocular care if signs or symptoms of ophthalmic complications present themselves.

INTRODUCTION Coronary heart disease (CHD) occurs when atherosclerotic lesions build up within the coronary arteries. Over time this leads to symptoms and complications such as fatigue, chest pain, shortness of breath, arrhythmia, angina, or E. Lau — Former Resident, West Los Angeles VA Healthcare Center, Los Angeles, CA; P.F. Ilsen — Professor, Southern California College of Optometry, Los Angeles, CA Correspondence to: Dr. Pauline F. Ilsen, Southern California College of Optometry, West Los Angeles Veterans Affairs Healthcare Center, Optometry Clinic (123) Bldg. 304, Room 2-123, 11301 Wilshire Blvd., Los Angeles, CA 90073; E-mail: Pauline.Ilsen@va.gov This article has been peer reviewed.

myocardial infarction.1-4 Over 16 million people in the United States are affected with CHD; of this total, approximately 9 million have angina pectoris and 7.9 million have experienced a myocardial infarction.5,6 Diagnosis of CHD involves a thorough medical history, a physical examination, and diagnostic testing such as laboratory tests, electrocardiogram (EKG), echocardiography (ECG), computed tomography (CT) scan, stress testing, or angiography.2,4,6,7 Laboratory tests for CHD risk factors may include a lipid profile and homocysteine level for metabolic disease; creatine kinase or other markers for ischemia or necrosis; activated protein C resistance, protein C deficiency, plasminogen, antiphospholipid antibodies, von Wille-brand factor, etc. for coagulation; C-reactive protein or myeloperoxidase for inflammation; Cystatin C for renal dysfunction and other conditions as indicated.8 Coronary angiography is currently considered the gold standard for confirming the presence and determining the severity of CHD (Table I).2,5,6 Coronary angiography is a procedure that detects areas of coronary vessel blockage and helps to diagnose CHD.2,5,6,9 The patient is first injected with local anesthesia, then a catheter is inserted through the femoral or radial artery and guided toward the coronary arteries. This process is also known as cardiac catheterization. Once the catheter is in place, a contrast dye is released, which becomes visible on x-ray imaging. The contrast dye flows through the arteries and allows for any narrowed or blocked vessels to be visualized. If indicated, percutaneous coronary intervention (coronary angioplasty) can be performed immediately after the angiography.10, 11 There are two main methods for coronary revascularization: coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), also known as coronary angioplasty.2,6 Coronary artery bypass graft is the most common type of open-heart surgery and is usually performed for several reasons, including 3-vessel disease (blockage of 3 major arteries to the heart), left main coronary artery disease, and 3-vessel disease in diabetics.6,7,12,13 Coronary artery bypass graft is the preferred and most effective method of revascularization in patients with chronic total occlusions and several complex lesions.6,12,14

Ophthalmic Complications of Coronary Revascularization — Lau, Ilsen

Table I Diagnosis and surgical intervention for CHD

Table II Ophthalmic complications of coronary revascularization

Diagnostic Testing for CHD • Complete medical history • Physical examination • Laboratory testing ◆ Lipid profile ◆ Homocysteine ◆ Creatine kinase ◆ Activated protein C resistance ◆ Protein C deficiency ◆ Plasminogen ◆ Antiphospholipid antibodies ◆ Von Willebrand Factor ◆ C-Reactive Protein ◆ Myeloperoxidase ◆ Cystatin C • Electrocardiogram (EKG) • Echocardiography (ECG) • Computed Tomography (CT) scan • Stress testing • Coronary angiography

Optic Nerve • Perioperative ischemic optic neuropathy

Surgical Intervention for CHD • Coronary artery bypass grafting (CABG) ◆ On-Pump CABG ◆ Off-Pump CABG ◆ MIDCAB • Percutaneous coronary intervention (PCI)/coronary angioplasty

During CABG surgery, a healthy artery or vein is grafted so that blood flow is able to bypass an occluded coronary artery. Traditional on-pump CABG involves a large incision along the sternum to open the chest wall and using a cardiopulmonary bypass machine which functions in place of the heart while the heart is stopped with medication. The newer, off-pump method does not use the cardiopulmonary bypass and allows the heart to beat during the surgery. The challenge of grafting a vessel on a dynamically beating heart involves the use of devices that can stabilize the parts of the heart needed for suturing. A third method, called the Minimally Invasive Direct Coronary Artery Bypass (MIDCAB), has been used for revascularization that is focused on the anterior location of the heart. MIDCAB is typically performed by making a smaller incision in the sternum without the use of a cardiopulmonary bypass.2,7,15-17 While each type of surgery poses its own set of risks and complications, one particular method has not shown to be superior to another.15,18-20 Percutaneous coronary intervention is indicated in patients who do not fulfill the criteria for CABG or who have atherosclerotic lesions that can be alleviated by angioplasty alone. Similar to coronary angiography, a balloon-tipped catheter is inserted from the femoral or radial artery and travels to reach the blocked artery in the heart. The balloon catheter transverses the blockage in

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Retina • Asymptomatic microemboli • Cotton wool spots • Superficial hemorrhages • Branch retinal artery occlusion • Central retinal artery occlusion Neuro-ophthalmic • Cortical blindness • Horner’s syndrome • Internuclear ophthalmoplegia • Cranial nerve paralysis

the artery and is then inflated to allow passage for blood flow. A bare metal or drug eluting stent is often placed at the site to maintain patency of the newly revascularized artery.7,21 Systemic risks and complications of coronary revascularization are greater in CABG procedures than the non-invasive technique of PCI. Such complications include increased postoperative atrial fibrillation, perioperative stroke, neurological injury, infection, bleeding and transfusion, longer in-hospital recovery, and a slower return to normal daily activities.6,21-24 Unfortunately, ophthalmic complications are often not discussed with patients prior to surgery. The following will be a review of ophthalmic complications that can result from coronary revascularization.

DISCUSSION Several ophthalmic complications arising from coronary revascularization have been reported in the literature. These complications tend to manifest in the immediate postoperative period (Table II). Optic Nerve Complications Perioperative ischemic optic neuropathy (ION) is the most common type of vision loss experienced after cardiac surgery. The reported incidence ranges from 0.06% to 0.113% of cases.25-27 Anterior ION has been more common than posterior ION after CABG25,27,28 and cases have been more frequent in men than women.26,29 Risk factors for perioperative ischemic optic neuropathy include vascular diseases such as diabetes mellitus, hypertension, and hyperlipidemia. Smoking, hyperglycemia, anemia, prolonged duration of being on the cardiopulmonary bypass, hypotension during surgery, small optic nerve cup-to-disc ratio (or a “disc at risk”), arrhythmias, hypocoagulability, tissue edema, lower

hematocrit levels, intraoperative blood loss, and perioperative weight gain are also important risk factors.25-27,29-32 Anterior ION has been described as an infarction to the lamina cribrosa and prelaminar region of the optic nerve, which is supplied by the posterior ciliary arteries.25,29,33-35 Defective autoregulation of blood flow through the optic nerve head and its association with increased intraocular pressure is said to be part of the pathogenesis for anterior ION during CABG.29,34 In contrast, posterior ION is an infarction of the optic nerve posterior to the lamina cribrosa. While the exact mechanism of posterior ION is not well-understood, hemodynamic parameters and patient susceptibility play significant roles. Visual prognosis is poor after posterior ION, usually resulting in finger-counting vision or worse.27,30 Common signs and symptoms in anterior ION include sudden subjective vision loss, acute disc edema, optic atrophy, positive relative afferent pupillary defect, and visual field loss (most commonly altitudinal defects and nasal steps).36 Anterior ION is more commonly a unilateral finding after CABG surgery,26 while it is more often bilateral after spinal surgery.30 Retinal Complications Retinal ischemia in various forms is another potential complication following coronary revascularization. Findings may include microembolisms, cotton wool spots, hemorrhages, branch retinal artery occlusion (BRAO), and central retinal artery occlusion (CRAO). Asymptomatic microembolisms are commonplace after cardiac catheterization and transcranial Doppler (TCD) ultrasonography studies have shown that most are gaseous rather than particulate in origin.37,38 The reported incidence of new microemboli localized specifically to the retina after heart catheterization procedures has ranged from 0% to 15%.39-43 Although the source of retinal emboli is usually unknown, it is often expected to be from either an atheroma that was dislodged from the aortic arch or a thrombus formed by movement of the catheter.38,41,44,45 Retinal emboli are worrisome because of their ability to obstruct retinal arteries causing a decrease in blood supply to either a portion of the retina (BRAO) or the entire retina (CRAO). Symptoms of an artery occlusion may include unilateral vision loss, a positive afferent pupillary defect, whitening of a portion or entire retinal, a cherry red macula (CRAO), attenuated arterioles, and cotton wool spots.32 Several cases of both BRAO44-49 as well as CRAO50-52 have been documented following cardiac catheterization. Cotton wool spots and superficial hemorrhages are also noted to be a retinal complication.53,54 Kinoshita et al studied a group of 30 patients diagnosed with acute myocardial infarction. After undergoing PCI, 57% of these patients had cotton wool spots and 41% had superficial hemorrhages, most of which resolved within 3 months.53

Compared to catheterization needed for both coronary angiography and angioplasty, the CABG procedure also poses similar risks to the retina. Unlike embolization from catheterization, sources of emboli during CABG are related to aortic cross-clamping and left ventricular clots.25,28,55 Similar to catheterization, CABG procedures can also lead to vascular retinopathies involving cotton wool spots, superficial hemorrhages, BRAOs, and CRAOs.27,56 While the off-pump and minimally invasive techniques have not been shown to be superior to the traditional on-pump method, some studies have shown lower rates of cerebral and/or retinal embolization with the newer techniques.20,57,58 Neuro-Ophthalmic Complications Coronary revascularization can lead to neuro-ophthalmic complications, including cortical blindness and Hornerâ&#x20AC;&#x2122;s syndrome. Internuclear ophthalmoplegia and cranial nerve paralysis have also been rare findings following surgery. Cortical blindness is visual impairment due to a lesion in the posterior visual pathway or occipital lobe. Visual symptoms range from decreased visual acuity, general visual loss, paracentral or central scotomas, homonymous hemianopsias, or complete blindness. In these cases, pupillary response, eye motility, and ocular health are normal, while imaging may reveal the causative lesion and location.59-61 Cortical blindness has been associated with CABG surgery, as well as coronary angiography and angioplasty. Shaw et al found the incidence of cortical blindness after CABG surgery to be approximately 5% in their study of 312 patients.62 The pathophysiology of cortical blindness is not completely understood. Cerebral embolization during surgery is believed to be a major cause.63 Cerebral hypoperfusion and occipital lobe ischemia between the middle and posterior cerebral arteries are also thought to be a source of visual impairment.64,65 Hypertension, diabetes, renal disease, and other systemic issues that affect the vertebrobasilar vascular system can increase the patientâ&#x20AC;&#x2122;s risk.66 The prognosis for visual recovery is better for healthier patients, while those who experience cortical blindness along with other focal neurological signs can expect prolonged or minimal visual recovery.59 Cortical blindness following coronary angiography has also been reported in the literature. While more common after cerebral and vertebral angiography, cortical blindness is considered rare after cardiac angiography.60,67-70 The pathophysiology of cerebral injury by contrast agents is still unknown, but it is believed that the contrast dye used for imaging blood flow penetrates the blood brain barrier in the occipital lobe, causing a neuro-toxic effect upon brain parenchyma.61,67-73 The occipital lobe is especially vulnerable to penetration of the contrast agent

Ophthalmic Complications of Coronary Revascularization â&#x20AC;&#x201D; Lau, Ilsen

due to reduced sympathetic innervation of the vertebrobasilar system. This lack of protective sympathetic vasoconstriction during hypertension triggers the breakdown of the blood brain barrier.67,72 All types of contrast agents (ionic, non-ionic, isotonic, high and low osmolality) have been associated with transient cortical blindness and it is not volume dependent.61,68,69,72 Computed tomography (CT) scans may show marked extravasation of contrast into the occipital lobes immediately after the procedure with resolution on subsequent scans.60,61 Prognosis is therefore excellent, since cortical blindness following angiography is transient, usually resolving within 24-48 hours.69,72,73 Horner’s syndrome results from a lesion in the neuroophthalmic sympathetic pathway leading to the classic triad of eyelid ptosis, pupillary miosis, and facial anhydrosis. Lesions due to coronary artery bypass surgery are often iatrogenic due to surgical trauma near the pleural apex of the lung, causing damage to nearby sympathetic fibers.74,75 It has been proposed that Horner’s syndrome may also be due to ischemic injury of related sympathetic neurons, especially in patients with increased risk factors of diabetes and hypertension.76 The frequency of acquired Horner’s syndrome in patients after coronary artery bypass surgery has been found to be between 0.2% and 7.6%.76,77 Clinical features of ptosis and/or miosis may be transient or persistent. Imamaki et al presented a case of a patient diagnosed with Horner’s syndrome one week after an off-pump coronary artery bypass, but signs resolved after one month.77 Barbut et al presented a study of 19 patients with Horner’s syndrome after coronary bypass surgery, 47% of whom showed resolution after 6 months.77,78 Lesser-known neuro-ophthalmological complications such as internuclear ophthalmoplegia (INO) after PCI and cranial nerve paralysis have been associated with coronary revascularization. Eggenberger et al performed a retrospective chart review on 110 patients with INO; 4.5% of these patients demonstrated an INO in the perioperative period after catheterization, angioplasty or stent placement. The small vessels supplying the medial longitudinal fasciculus (MLF) were thought to be vulnerable to microemboli following cardiac catheterization, thus causing the INO. All patients exhibiting INO showed resolution of diplopia after a mean of 82 days.79 A case report by Kocabay et al described a 58-year-old woman with hypertension and diabetes who underwent coronary angioplasty, who developed perioperative left eyelid ptosis and diplopia. Her ocular examination revealed a left partial third nerve paralysis, which persisted for 2 months.80 Another case report by Drummond et al described a 61-year-old woman who underwent coronary angioplasty and developed diplopia from a partial right third nerve palsy along with a left fourth nerve palsy. Partial resolution occurred over seven months of follow-up.81 Microembolic ischemia was thought to be the contributing cause in both cases.80,81

Clinical & Refractive Optometry Online 26:1, 2015

MANAGEMENT Urgent ophthalmologic consultation may be in order if a patient has had a recent coronary revascularization procedure and develops perioperative ocular signs or symptoms of complications. Both ophthalmic and systemic investigative testing is indicated to rule out differential diagnoses. Pre- and post-surgical patient education is also crucial. Once the primary eye care provider has diagnosed the patient with a visual complication resulting from the patient’s surgery, it is important that the patient be managed appropriately depending on the complication. For example, patients with cotton wool spots and/or superficial hemorrhages should be followed in approximately 3 months to monitor for resolution. Patients with permanent cortical blindness can be provided with assistance in managing their field loss or directed to mobility and/or low vision services if necessary. Proper management should be considered on a case-bycase basis.

CONCLUSION The list of risks and complications for patients undergoing coronary revascularization may range from transient and benign to permanent and visually devastating. Patients who plan to undergo surgery should be aware that potential risks could involve their vision and ocular health. While having a comprehensive eye exam after coronary revascularization may not be the standard of care today, it is important for both patients and their health care providers to seek eye care once signs or symptoms of ophthalmic complications present themselves. ❏

REFERENCES 1.

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25. Nuttall GA, Garrity JA, Dearani JA, et al. Risk factors for ischemic optic neuropathy after cardiopulmonary bypass: a matched case/control study. Anesth Analg 2001; 93: 1410-1416. 26. Kalyani SD, Miller NR, Dong LM, et al. Incidence of and risk factors for perioperative optic neuropathy after cardiac surgery. Ann Thorac Surg 2004; 78: 34-37. 27. Newman NJ. Perioperative visual loss after nonocular surgeries. Am J Ophthalmol 2008; 145(4): 604-610. 28. Trethowan BA, Gilliland H, Popov AF, et al. A case report and brief review of the literature on bilateral retinal infarction following cardiopulmonary bypass for coronary artery bypass grafting. Journal of Cardiothoracic Surgery 2011; 6: 154. 29. Shapira OM, Kimmel WA, Lindsey P, Shahian DM. Anterior ischemic optic neuropathy after open heart operations. Ann Thorac Surg 1996; 61: 660-666. 30. Buono LM, Foroozan R. Perioperative posterior ischemic optic neuropathy: review of the literature. Survey of Ophthalmology 2005; 50(1): 15-26. 31. Mansour AM, Awwad ST, Najjar DM, et al. Anterior ischaemic optic neuropathy after coronary artery bypass graft: the role of anaemia in diabetics. Eye 2006; 20: 706-711. 32. Grover VK, Jangra K. Perioperative vision loss: a complication to watch out. J Anaesthesiol Clin Pharmacol 2012; 28(1): 11-16. 33. Hayreh SS. Anterior ischemic optic neuropathy. Arch Neurol 1981; 38: 675-678. 34. Larkin DFP, Wood AE, Neligan M. Eustache. Ischaemic optic neuropathy complicating cardiopulmonary bypass. British Journal of Ophthalmology 1987; 71: 344-347. 35. Sha’aban RI, Asfour WM. Visual loss after coronary artery bypass surgery. Neurosciences 2000; 5(1): 74-76. 36. Hayreh SS. Visual field abnormalities in nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol 2005; 123: 1554-1562. 37. Leclercq F, Kassnasrallah S, Cesari JB, et al. Transcranial doppler detection of cerebral microemboli during left heart catheterization. Cerebrovascular Diseases 2001; 12(1): 59-65. 38. Bladin CF, Bingham L, Grigg L, et al. Transcranial doppler detection of microemboli during percutaneous transluminal coronary angioplasty. Stroke 1998; 29(11): 2367-2370. 39. Thyer I, Kovoor P, Wang JJ, et al. Coronary catheterisation does not lead to retinal artery emboli in short-term followup of cardiac patients. Stroke 2007; 38(8): 2370-2372. 40. Wilentz JR, Chati Z, Krafft V, Amor M. Retinal embolization during carotid angioplasty and stenting: mechanisms and role of cerebral protection systems. Catheter Cardiovasc Interv 2002; 56(3): 320-327. 41. Kreis AJ, Nguyen T, Rogers S, et al. Acute retinal arteriolar emboli after cardiac catheterization. Stroke 2008; 39(11): 3086-3087. 42. Vos JA, van Werkum MH, Bistervels JH, et al. Retinal embolization during carotid angioplasty and stenting: periprocedural data and follow-up. Cardiovascular and Interventional Radiology 2010; 33(4): 714-719. 43. Blauth CI, Arnold JV, Schulenberg WE, et al. Cerebral microembolism during cardiopulmonary bypass: retinal microvascular studies in vivo with fluorescein angiography. J Thorac Cardiovasc Surg 1988: 95(4): 668-676. 44. O’Connor J, Kiernan TJ. Branch retinal artery occlusion following elective percutaneous coronary intervention. Heart 2011; 97(8): 640.

Ophthalmic Complications of Coronary Revascularization — Lau, Ilsen

45. Kymionis GD, Tsilimbaris MK, Christodoulakis EB, Pallikaris IG. Late onset branch retinal artery occlusion following coronary angiography. Acta Ophthalmol Scand 2005; 83(1): 122-123. 46. Bucci FA Jr, Dimitsopulos TM, Krohel GB. Branch retinal artery occlusion secondary to percutaneous transluminal coronary angioplasty. Br J Ophthalmol 1989; 73(4):309-10. 47. Filatov V, Tom D, Alexandrakis G, et al. Branch retinal artery occlusion associated with directional coronary artherectomy after percutaneous transluminal coronary angioplasty. Am J Ophthalmol 1995; 120(3): 391-393. 48. O’Neill MD, Akerele T, Dancy M. Branch retinal artery occlusion during coronary angiography. Postgrad Med J 2005; 81: 710. 49. Chan KC, Wu DJ, Ueng KC, et al. Branch retinal artery occlusion after diagnostic cardiac catheterization. Jpn Heart J 2002; 43: 193-196. 50. Stefansson E, Coin JT, Lewis WR 3rd, et al. Central retinal artery occlusion during cardiac catheterization. Am J Ophthalmol 1985; 99(5): 586-589. 51. Selton J, Maalouf T, Olivier A, et al. Central Retinal artery occlusion following coronary angiography: a case report. J Fr Ophthalmol 2011; 34(3): 181-215. 52. Krasnicki P, Proniewska-Skretek E, Mariak Z, et al. Embolic central retinal artery occlusion as a complication of percutaneous coronary arngioplasty—case report. Klin Oczna 2008; 110 (1-3): 64-66. 53. Kinoshita N, Kakehashi A, Yasu T, et al. A new form of retinopathy associated with myocardial infarction treated with percutaneous coronary intervention. Br J Ophthalmol 2004; 88(4): 494-496. 54. Shaw PJ, Bates D, Cartlidge NE, et al. Early neurological complications of coronary artery bypass surgery. Br Med J 1985; 291: 1384-1387. 55. Lund PE, Madsen K. Bilateral blindness after cardiopulmonary bypass. Journal of Cardiothoracic and Vascular Anesthesia1994; 8(4): 448-450. 56. Barash PG, Cullen, BF, Stoelting RK, Cahalan MK, Stock MC. Retinal Ischemia. Clinical Anesthesia. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009. 1341-342. 57. Ascione R, Ghosh A, Reeves BC, et al. Retinal and cerebral microembolization During coronary artery bypass surgery. Circulation 2005; 112(25): 3833-3838. 58. Rimpilainen R, Hautala N, Koskenkari JK, et al. Minimized cardio-pulmonary bypass reduces retinal microembolization: a randomized clinical study using fluorescein angiography. Ann Thorac Surg 2011; 91(1): 16-22. 59. Miller R, Eriksson LI, Fleisher LA, et al. Cortical Blindness. Miller’s Anesthesia. Edinburgh: Churchill Livingstone, 2009;2835-37. 60. Yazici M, Ozhan H, Kinay O, et al. Transient cortical blindness after cardiac catheterization with Iobitridol. Texas Heart Institute Journal. 2007; 34: 373-75. 61. Gellen B, Remp T, Mayer T, et al. Cortical blindness: a rare but dramatic complication following coronary angiography. Cardiology 2003;99:57-59.

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62. Shaw PJ, Bates D, Cartidge NEC, et al. Neurologic and neuropsychological morbidity following major surgery: comparison of coronary artery bypass and peripheral vascular surgery. Stroke. 1987; 18: 700-707. 63. Hogue CW, Sundt TM 3rd, Goldberg M, et al. Neurological complications of cardiac surgery: the need for new paradigms in prevention and treatment. Semin Thorac Cardiovasc Surg 1999; 11(2): 105-115. 64. Bagheri J, Mandegar MH, Sarzaeem MR, Chitsaz S. Transient bilateral cortical visual loss after coronary artery bypass grafting in a normotensive risk-free patient. The Heart Surgery Forum. 2008;11(4): E248-E251. 65. Shahian DM, Speert PK. Symptomatic visual deficits after open heart operations. Ann Thorac Surg 1989; 48: 275-279. 66. Movahedi N, Shirani S, Soltanzadeh S, Yazdanifard P. Transient cortical blindness following coronary artery Bypass graft: a case report. The Heart Surgery Forum 2009; 12(5): E303-304. 67. Merchut MP, Bunnie R. Transient visuospatial disorder from angiographic contrast. Arch Neurol 2002; 59: 851-854. 68. Borghi C, Saia F, Marzocchi A, Branzi A. The conundrum of transient cortical blindness following coronary angiography. Italian Federation of Cardiology 2008; 1063-1065. 69. Lim KK, Radford DJ. Transient cortical blindness related to coronary angiography and graft study. Med J Aust 2002; 177: 43-44. 70. Zwicker JC, Sila C. MRI findings in a case of transient cortical blindness after cardiac catheterization. Catheterization and Cardiovascular Interventions 2002; 57: 47-49. 71. Lantos G. Cortical blindness due to osmotic disruption of the blood-brain barrier by angiographic contrast material: CT and MRI studies. Neurology 1989; 39(4): 567-571. 72. Danenberg HD, Lotan C. Nonrecurring transient cortical blindness after coronary angiography: a role for hypoventilation and hypercarbia? Catheterization and Cardiovascular Interventions 2006; 67: 384-385. 73. Sticherling C, Berkefeld J, Auch-Schwelk W, Lanfermann, H. Transient bilateral cortical blindness after coronary angiography. Lancet 1998; 351(9102): 570. 74. Walton KA, Buono LM. Horner syndrome. Curr Opin Ophthalmol 2003; 14: 357-363. 75. Allen AY, Meyer DR. Neck procedures resulting in Horner syndrome. Ophthal Plast Reconstr Surg 2009; 25: 16-18. 76. Barbut D, Gold JP, Heinemann MH, et al. Horner’s syndrome after coronary artery bypass surgery. Neurology 1996; 46: 181-184. 77. Imamaki M, Ishida A, Shimura H, et al. A case complicated with Horner’s syndrome after off-pump coronary artery bypass. Ann Thorac Cardiovasc Surg 2006; 12: 113-115. 78. Patel S, Ilsen PF. Acquired Horner’s syndrome: clinical review. Optometry. 2003;74:245-56. 79. Eggenberger ER, Desai NP, Kaufman DI, Pless M. Internuclear ophthalmoplegia after coronary artery catheterization and percutaneous transluminal coronary balloon angioplasty. J Neuroophthalmol 2000; 20(2): 123-126. 80. Kocabay G, Bayram T. Unilateral isolated partioal oculomotor nerve paralysis after percutaneous intervention. Angiology 2009; 60(3): 385-386. 81. Drummond GT, Wuebbolt G. Bilateral ophthalmoplegia during percutaneous transluminal coronary angioplasty. Canadian Journal of Ophthalmology 1990; 25(3): 152-155.

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QUESTIONNAIRE Ophthalmic Complications of Coronary Revascularization: A Review of Literature Eva Lau, OD; Pauline F. Ilsen, OD 1. ❑ ❑ ❑ ❑

All of the following are symptoms and complications of coronary heart disease (CHD), EXCEPT: Fatigue Chest pain Dizziness Angina

2. ❑ ❑ ❑ ❑

All of the following are diagnostic tests for CHD, EXCEPT: Creatine kinase Lipid profile Transcranial Doppler (TCD) ultrasonography Stress testing

3. ❑ ❑ ❑ ❑

All of the following are systemic risks and complications of coronary revascularization, EXCEPT: Infection Bleeding and transfusion Neurological injury Necrosis

Ophthalmic Complications of Coronary Revascularization — Lau, Ilsen

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4. ❑ ❑ ❑ ❑

All of the following are risk factors for perioperative ischemic optic neuropathy (ION), EXCEPT: Prolonged alcohol abuse Tissue edema Anemia Hyperglycemia

5. ❑ ❑ ❑ ❑

All of the following are common signs and symptoms of perioperative ION, EXCEPT: Low intraocular pressure Acute disc edema Optic atrophy Visual field loss

6. ❑ ❑ ❑ ❑

All of the following are symptoms of cortical blindness, EXCEPT: Complete blindness General visual loss Night blindness Unaffected eye motility

7. ❑ ❑ ❑ ❑

According to Shaw et al, what was the approximate incidence of cortical blindness after CABG surgery? 5% 10% 15% 20%

8. ❑ ❑ ❑ ❑

In Kinoshita’s study, patients who received percutaneous coronary intervention mostly resolved their complication of cotton wool spots and/or superficial hemorrhages within: 1 month 6 weeks 2 months 3 months

9. ❑ ❑ ❑ ❑

All of the following are neuro-ophthalmic complications of coronary revascularization, EXCEPT: Papilledema Horner’s syndrome Cranial nerve paralysis Cortical blindness

10. ❑ ❑ ❑ ❑

All of the following statements about cortical blindness following angiography are true, EXCEPT: Its prognosis is excellent All types of contrast agent have been associated with it It occurs in 40% of cases Its incidence is rare

Clinical & Refractive Optometry Online 26:1, 2015

Book Review

Diagnostic Procedures in Ophthalmology, 2nd Edition by HV Nema and Nitin Nema. Hard cover with colored illustrations. Jaypee Brothers Medical Publishers (P) LTD, 2009; ISBN: 978-81-8448-595-0; US$60. Diagnostic Procedures in Ophthalmology is a well written manuscript covering both basic and complex procedures done in the eye clinic. The book is hard covered and is a lengthy twenty-eight chapters with a total of 470 pages. Throughout the book there are colored photographs to help the reader visualize what the writer has described. The book would be best used as a reference. I did not find any errors in the book and I felt that the book was written for both the novice and the experienced. My favorite chapters in the book included Chapter 1 on Visual Acuity, Chapter 2 on Color Vision and Color Blindness and Chapter 4 on Corneal Topography. I found the first chapter to be appropriate because it covered visual acuity which is the first procedure done on every patient. I really liked the summary table towards the end of the chapter which included the ranges of vision associated with the visual ability aspects and social/economic aspects of that degree of vision. Chapter 2 on Color Vision and Color Blindness was probably my favorite chapter in the book followed closely by Chapter 4. Chapter 2 is probably the best comprehensive look at color vision I have read confined to one chapter. I not only liked that the authors covered the procedures for the different color vision tests, but they also explained in great detail the theories of color vision, the anatomy of color vision, and the anomalies of color vision. I also really enjoyed Chapter 4 on Corneal Topography. The authors did a good job in describing the different topography displays (i.e., Axial Map, Local Tangential Curvature Map, Refractive Map, Elevation Map, Difference Map, Relative Map, and Irregularity Map). The other part I liked about the

chapter was that the authors included clinical applications on various corneal topographies. These examples included small writes-ups on keratoconus, pellucid marginal degeneration, keratoglobus, Terrienâ&#x20AC;&#x2122;s Marginal Degeneration, pterygium, postoperative cornea in refractive surgery, postradial keratotomy, postastigmatic keratotomy, postphotorefractive keratotomy, postlaser in situ keratomileusis, postlaser thermal keratoplasty, postintrastromal corneal rings implantation, postkeratoplasty, and contact lensinduced corneal warpage or molding. Finally, the colored topography examples which are found in this chapter were of exceptional quality. The book has many well written chapters, but these three chapters stood out the most to me. My least favorite chapter in the book was Chapter 5 on Confocal Microscopy. Even though this is a very interesting ophthalmic imaging technology, I feel that the procedure would be more useful in research rather than in clinic. Therefore, it was not as relevant to me as other chapters in the book. I also did not like the photographs in Chapter 28 on Neurological Disorders of Pupil. It was very difficult to distinguish the pupil in the photographs, and therefore, it was difficult to understand what the author was trying to describe. It would have been nice to use a light colored iris (i.e., blue or green) to allow visualization of the pupil with the examples the authors were trying to convey. The last thing I would have liked to see in the book would have been more examples of visual field defects on different diseases (i.e., glaucoma visual field defects and other neurological examples). Another thing I really enjoyed about the book was that individual chapters were written by various authors thereby giving insight from numerous people who know that chapterâ&#x20AC;&#x2122;s topic the best. I also found the bullet chart in Chapter 10 on Ophthalmoscopy to be a good reference for fundus drawings, and I liked the multiple colored photographs in Chapter 8 on Optic Disk Assessment in Glaucoma. Diagnostic Procedures in Ophthalmology is a well written and easy to read book covering some of the basic procedures done in the eye clinic. It covers procedures that we do on all of our patients to those procedures that are only required in special circumstances. I really enjoyed Chapters 1, 2 and 4 and the multiple colored photographs throughout the book. I would recommend this book to optometrists and ophthalmologists that would like a reference in the office for the various diagnostic procedures performed in the eye clinic. This book can also serve as an excellent teaching resource for optometry students and ophthalmology residents who need to learn to utilize these procedures and instruments. Reviewed by: Tyler Heuer, OD Avera Marshall Southwest Ophthalmology Marshall, MN

Book Review

News and Notes Launch of the 1st World Optometry Congress Founding Member of Optometry Giving Sight, The World Council of Optometry (WCO), and La Federación Colombiana de Optómetras (FEDOPTO) are delighted to announce the launch of the 1st World Congress of Optometry. This is the first global optometry conference and a unique opportunity for anyone in the eye health sector including community and hospital practitioners, researchers, academics and students. From August 14 to 16, 2015 the world’s leading eye health experts will be gathered in Medellín, Colombia to share the latest ideas, research, knowledge and ideas from across the optometry sector. Delegates will have the opportunity to: • learn more about differing approaches to optometry in a wide range of countries • maintain and develop their professional and clinical knowledge and skills • network with colleagues to share ideas and discuss key themes and topics The three-day programme will include more than 50 presentations, lectures and seminars led by world-renowned experts and arranged into two programmes: clinical, and educational. Lectures and clinical workshops will be accredited by UK GOC CET and US COPE and there will be simultaneous translation into Spanish and English. There will be a poster and video display, with abstracts submitted from students, academics and professionals worldwide. There will also be an exhibition bringing together the world’s leading service and equipment providers to present and discuss the latest products and advancements within the industry. For additional information, visit http://worldcongressof optometry.org/ LSU Health New Orleans Discovers Retina Protein That May Help Conquer Blindness Research led by Nicolas Bazan, MD, PhD, Boyd Professor and Director of the LSU Health New Orleans Neuroscience Center of Excellence, discovered a protein in the retina that is crucial for vision. The paper reports, for the first time, the key molecular mechanisms leading to visual degeneration and blindness. The research reveals events that may be harnessed for prevention, as well as to slow down progression of retinal degenerative diseases. The paper is published in the March 4, 2015, issue of Nature Communications. There is growing evidence of the significance of the essential omega-3 fatty acid family member, docosahexaenoic acid (DHA), for photoreceptor function and in retinal degenerative diseases, but not much understanding about what governs it. The research team found that the protein receptor for adiponectin, a hormone that promotes insulin sensitivity and is involved in the metabolic syndrome, has a heretofore unrecognized function. The receptor also regulates DHA retention and conservation in cells in the eye and is necessary for photoreceptor cell function. “This is the first time that such an integral membrane protein has been localized in the photoreceptor cells and shown to have the capacity to support sight,” notes Dr. Bazan, the paper’s corresponding author.

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