JANUARY/FEBRUARY 2019

CORNEAL SURGERY REVIEW OF CORNEA ISSUE & CONTACT LENSES

Discover how long to monitor and treat symptoms before considering surgical interventions, PAGE 16

• GPs: A Reliable Post-PK Option, PAGE 8

• The Art of Corneal Transplantation, PAGE 20

• Post-cataract Surgery Infl ammation: A Toxin or a Bug?, PAGE 26

• Transplantation for Limbal Stem Cell Defi ciency, PAGE 30 (earn 1 CE credit)

ALSO:Also: new lensesAcanthamoeba for 2019 • myopia keratitis: control A • Disease CYL advice in • Disguise,anterior staphyloma p. 36 RCCL2019_Contamac.indd 1 2/5/19 11:14 AM contents Review of Cornea & Contact Lenses | January/February 2019

departments features

4 News Review New Lenses for a New Year Highlights in 2019 will include toric Myopia Research Advances; CLs multifocals, a photochromic contact and MGD: a Mixed Bag lens and more. By Jane Cole, contributing editor 7 My Perspective 10 Perfecting the Art of Practice By Joseph P. Shovlin, OD Keratoplasty: When and Why 8 The GP Experts Discover how long to monitor and A Reliable Post-PK Option treat symptoms before considering surgical interventions. By Robert Ensley, OD, and Heidi Miller, OD 16 By James Esposito, OD 36 Corneal Consult The Art of Corneal Was it a Failure or Rejection? Transplantation By Aaron Bronner, OD Optometrists have several options when it comes to keratoplasties, each Fitting Challenges of which has its own pros, cons and 38 management guidelines. Depth Charge 20 By Andrew Steele, OD By Vivian P. Shibayama, OD Post-cataract Surgery 40 Practice Progress Infl ammation: A Toxin Don’t be Nearsighted About Myopia or a Bug? By Andrew Fischer, OD, Mile Brujic, OD, Although rare, TASS and and David Kading, OD endophthalmitis are possible 26 complications, and clinicians must be able to recognizing the diff erence. 42 The Big Picture By Barbara J. Fluder, OD Singing the Blues By Christine W. Sindt, OD CE — Transplantation for Limbal Stem Cell Defi ciency When severe disease 30 calls for surgery, here’s how you can be prepared for the pre- and post-op care. By Cecelia Koetting, OD

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IN BRIEF ■ Researchers recently found that Afri- Myopia Research Advances can Americans have fi ve times higher odds of developing infectious uveitis wo recent studies shed more UK, researchers analyzed a subset and 1.5 higher odds of developing light on the pathogene- of the Twins Early Development non-infectious uveitis compared with Caucasians. The study used data from Tsis of this growing ocular Study, a longitudinal evaluation of the National Inpatient Sample (NIS) condition: 1,991 subjects recruited at birth and collected patient’s age, sex, race, between 1994 and 1996. Subjective median household income, payer status and ocular complications. Medicare pa- MYOPIA BIOMARKER refraction was obtained from the tients have double the odds of having A group of European researchers twins’ optometrists, with myopia complications from infectious uveitis recently found conjunctival ultravi- defi ned as mean spherical equiva- compared with those with private ≤ insurance, and Medicaid patients have olet autofl uorescence (CUVAF) can lent -0.75 diopters. Mean age of a 1.7 higher risk. Medicare and Medicaid show clinicians how much time pa- subjects was 16.3 years.2 patients also have twice the odds of tients spend outdoors, and that can The team used a ‘life-course having complications from non-infec- tious uveitis compared with those with translate into a myopia monitoring epidemiology’ approach, which private insurance. tool. They assert their study, pub- considers the infl uence of gesta- Chauhan K, Scaife S, Rosenbaum JT. Uveitis lished in Clinical and Experimental tional and early childhood factors and health disparities: results from the National Inpatient Sample. Br J Ophthalmol. December 21, Optometry, shows that the smaller on long-term development, to 2018. [Epub ahead of print]. a patient’s area of CUVAF, the more appropriately weight myopia risk ■ A new eye drop shows promise for time they spend outdoors.1 factors during critical periods of eye reducing corneal scarring after Pseudo- “These fi ndings suggest that growth. Adjusted odds ratios (ORs) monas aeruginosa infection, compared with traditional treatment. Developed CUVAF measures are a useful, for myopia were estimated at each by researchers from the University of non-invasive biomarker of the time life stage.2 Birmingham, the eye drop consists spent outdoors in adults in northern Factors signifi cantly associated of a fl uid gel that includes decorin, a naturally occurring protein that binds hemisphere populations,” the study with myopia included level of ma- to collagen in the corneal stroma and reads.1 ternal education (OR 1.33), fertility regulates cell proliferation, survival and To determine that, the team treatment (OR 0.63), summer birth diff erentiation by modulating numerous growth factors. The drop acts similar to looked at 54 patients (24 with my- (OR 1.93) and hours spent play- a therapeutic bandage, creating a barri- opia and 30 without) and examined ing computer games (OR 1.03). er that protects the ocular surface from their CUVAF as well as self-re- In addition, the researchers noted further damage caused by blinking. Researchers found the eye drop result- ported sun exposure preferences. associations with socioeconomic ed in reduced corneal opacity within They also took the patients’ blood status, educational attainment, 16 days. Adding human recombinant samples to assess their vitamin D3 reading enjoyment and certain cog- decorin helped restore corneal epithelial integrity with minimal stromal opacity. concentrations. While they found nitive variable (particularly verbal Hill LJ, Moakes RJA, Vareechon C, et al. Sustained no signifi cant association between cognition) at multiple points over release of decorin to the surface of the eye 2 enables scarless corneal regeneration. NPJ Regen sun exposure preferences or serum the life course. Med. 2018;3:23. concentration of vitamin D3 and re- “A greater understanding of ■ Researchers examined the benefi ts fractive status, they did fi nd that, in contemporaneous, early life factors of toric contact lenses vs. sphericals on nearly every case, CUVAF area was associated with myopia risk is objective measures of visual perfor- negatively associated with myopia.1 urgently required, particularly in mance for patients with low-to-moder- ate astigmatism. High- and low-contrast The researchers concluded that younger-onset myopia,” the au- visual acuities signifi cantly improved the less cumulative ultraviolet B thors wrote in their study, “as this with toric lenses compared with spher- exposure from sunlight, the more correlates with higher severity and ical lenses at both fi tting and follow-up. 1 Electromyography recordings showed likely patients were to be myopic. increased complications in adult less orbicularis muscle activity, correlat- life.”2 ing with less eyestrain, with toric lenses PHYSIOLOGIC FACTORS compared with spherical lenses; howev- 1. Kearney S, O’Donoghue L, Pourshahidi L, et al. er, the diff erence was only diff erent at A second study found a mix of en- Conjunctival ultraviolet autofl uorescence area, but not intensity, is associated with myopia. Clin Exp the fi tting visit. vironmental and physiologic factors Optom. 2019;102(1):43-50. Berntsen DA, Cox SM, Bickle KM, et al. A give rise to myopia, some of them 2. Williams KM, Kraphol E, Yonova-Doing E, et al. randomized trial to evaluate the eff ect of toric 2 Early life factors for myopia in the British Twins Ear- versus spherical contact lenses on vision and quite surprising. ly Development Study. Br J Ophthalmol. November eyestrain. Eye Contact Lens. 2019;45(1)28-33. In a new study conducted in the 6, 2018. [Epub ahead of print].

4 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 RRCCLCCL REVIEW OF CORNEA & CONTACT LENSES

11 Campus Blvd., Suite 100 Newtown Square, PA 19073 Telephone (610) 492-1000 Fax (610) 492-1049 Editorial inquiries: (610) 492-1006 CLs and MGD: a Mixed Bag Advertising inquiries: (610) 492-1011 Email: [email protected] esearch now shows silicone mian glands due to silicone hydrogel EDITORIAL STAFF EDITOR-IN-CHIEF hydrogel contact lens (CL) CL wear, some of which could help Jack Persico [email protected] Rmaterials don’t cause cy- clinicians detect early MGD.2 MANAGING EDITOR Rebecca Hepp [email protected] tokine-driven infl ammation for Researchers examined 173 eyes ASSOCIATE EDITOR patients with meibomian gland of 87 soft CL wearers and 103 eyes Catherine Manthorp [email protected] ASSOCIATE EDITOR dysfunction (MGD), but they can of 55 controls, grouping them based Mark De Leon [email protected] affect morphological and functional on duration of wear: less than three CLINICAL EDITOR Joseph P. Shovlin, OD, [email protected] changes to the meibomian glands. years, between three and seven years ASSOCIATE CLINICAL EDITOR One study evaluated MGD and more than seven years.2 Christine W. Sindt, OD, [email protected] EXECUTIVE EDITOR patients who had worn CLs for They found signifi cantly higher Arthur B. Epstein, OD, [email protected] at least six months and found upper and lower eyelid meiboscores CONSULTING EDITOR Milton M. Hom, OD, [email protected] silicone hydrogel CLs didn’t cause in the CL wearers compared with GRAPHIC DESIGNER cytokine-driven ocular surface controls, as well as higher mean Ashley Schmouder [email protected] AD PRODUCTION MANAGER infl ammation, but they may impact OSDI scores, corneal staining Scott Tobin [email protected] tear function, which could still lead scores, percentage of gland loss and BUSINESS STAFF to symptoms of dry eye disease percentage of thickened and curled PUBLISHER (DED).1 meibomian glands in the upper and James Henne [email protected] REGIONAL SALES MANAGER The researchers found the mean lower lids. Both the mean TBUT Michele Barrett [email protected] cytokine concentrations of CL wear- and meibomian gland expressibility REGIONAL SALES MANAGER Michael Hoster [email protected] ers were not statistically signifi cant were lower in CL wearers compared VICE PRESIDENT, OPERATIONS compared with those of healthy with the control groups.2 Casey Foster [email protected] controls. Even the concentrations The study also found duration of EXECUTIVE STAFF of those with and without MGD wear was important, considering CEO, INFORMATION SERVICES GROUP Marc Ferrara [email protected] didn’t show statistically signifi cant meiboscores were higher in patients SENIOR VICE PRESIDENT, OPERATIONS variation.1 who wore CLs for more than three Jeff Levitz [email protected] SENIOR VICE PRESIDENT, According to the research team, years compared with those wear- HUMAN RESOURCES the TBUT and ocular surface stain- ing lenses for less than three years. Tammy Garcia [email protected] VICE PRESIDENT, ing in CL wearers with MGD were The earliest change the researchers CREATIVE SERVICES & PRODUCTION Monica Tettamanzi [email protected] signifi cantly worse compared with documented was meibomian gland VICE PRESIDENT, CIRCULATION controls, but they did not correlate thickening in the upper eyelid—be- Emelda Barea [email protected] CORPORATE PRODUCTION MANAGER with tear cytokine levels, suggest- fore deterioration of meiboscores or John Caggiano [email protected] ing other factors are to blame for increase in gland dropout, the study EDITORIAL REVIEW BOARD the symptoms. “The abnormal says. This was the only fi nding that Mark B. Abelson, MD interaction between the meibomian had the highest diagnostic ability for James V. Aquavella, MD 2 RCCL Edward S. Bennett, OD lipids and the contact lens surface MGD, they noted. Aaron Bronner, OD is thought to result in thinning of Brian Chou, OD 1. Yucekul B, Mocan M, Mehmet C, et al. Evaluation Kenneth Daniels, OD the tear lipid layer, accelerated tear of long-term silicone hydrogel use on ocular surface S. Barry Eiden, OD infl ammation and tear function in patients with Desmond Fonn, Dip Optom, M Optom evaporation and dewetting as a and without meibomian gland dysfunction. Eye & Gary Gerber, OD Contact Lens. 2019:45(1):61–6. Robert M. Grohe, OD result of the increased lens-surface Susan Gromacki, OD hydrophobicity,” the report reads. 2. Uçakhan Ö, Arslanturk-Eren M. The role of soft Patricia Keech, OD contact lens wear on meibomian gland morphology Bruce Koffler, MD “These changes are likely to be and function. Eye Contact Lens. 2018 December 28, Pete Kollbaum, OD, PhD 2018. [Epub ahead of print]. Jeffrey Charles Krohn, OD the underlying causes for reduced Kenneth A. Lebow, OD Jerry Legerton, OD TBUT, higher ocular surface staining Kelly Nichols, OD as well as higher OSDI scores previ- Advertiser Index Robert Ryan, OD 1 Jack Schaeffer, OD ously reported in CL wearers.” Art Optical ...... Cover 3 Charles B. Slonim, MD Kirk Smick, OD A second study recently docu- CooperVision ...... Cover 2 Mary Jo Stiegemeier, OD mented several morphological and Loretta B. Szczotka, OD Menicon ...... Cover 4 Michael A. Ward, FCLSA functional changes to the meibo- Barry M. Weiner, OD Barry Weissman, OD

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 5 Earn up to NEWNEEW TTECHNOLOGIES 2019 & TTREATMENTS IN 18-28 CE Credits* 9 EyeEyyeeGVCE CCaCarearearree REVIEW’S COMMITMENT TO CONTINUING EDUCATION Join us for our 2019 MEETINGS

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GVCE **16th Annual Education Symposium REVIEW’S COMMITMENT TO CONTINUING EDUCATION *Approval pending Joint Meeting with NT&T in Eye Care RGVCE partners with Salus University for those ODs who are licensed in states that require university credit. See www.reviewsce.com/events for any meeting schedule changes or updates. My Perspective By Joseph P. Shovlin, OD

Perfecting the Art of Practice These seven steps might help you start off your new year on the right foot.

o you have a New know you plan on addressing each practitioners become somewhat Years’ resolution? I’m concern or complaint to the best of hardened from our daily routine; we fairly certain some of your ability in the future. see so much pathology and visual you will have already 3. Assess the patient’s response loss that we run the risk of forget- Dmade and broken to illness and suffering. We must ting how devastating it can be. Dr. one for the new year by the time provide a precise diagnosis when- Egnew highlights the need for being you read this. If so, make a new ever possible. Dr. Egnew says that explicit in your understanding of one! And if you haven’t yet made patients suffer in ways other than a patient’s problem; in doing so, a New Year’s resolution, here is a experiencing physical pain. We it actually allows them to be more suggestion. encounter patients with anterior open in sharing both personal and I came across a fascinating article and posterior segment anomalies clinically important information. about a year ago by Thomas Egnew, that may not be painful physically EdD. It deals directly with what we but cause suffering from visual CHECK IN do daily in clinical practice—caring compromise. One way to incorporate these skills for patients. I hope you fi nd the 4. Communicate to foster heal- is to keep a list of patients you’ve highlights striking enough to make ing. Carl Rogers notes that anyone seen over the past week who might a new resolution to replace the one who counsels patients needs to benefi t from a phone call to check you didn’t adhere to already, or to display congruence (being authen- on their progress. I’ve done this add to your list of resolutions. tic), acceptance (valuing the patient for years, and patients are always even if you don’t agree with their amazed that you have taken the THE MAGNIFICENT SEVEN actions) and understanding (being time to call and are grateful for Here are the seven skills for mastery sensitive to what they are experi- your concern. It goes a long way in of practice that the author refers to encing). However, on occasion, we saying, “I really care about you.” Of as “the magnifi cent seven:1 are forced into confrontation. For course, there’s some risk that it may 1. Take a moment to focus before example, “You have thyroid eye get you more than you bargained you enter the examination room. disease—you must stop smoking!” for, but the pluses seem to always It’s important to clear your mind 5. Use the power of touch. Of outweigh the minuses. from the last encounter or recharge course, we do not recommend any- Many of these seven skills may after the morning’s tribulations. thing that can be misconstrued as seem straightforward and even Then, it’s time to focus on the next an unwanted gesture, but this article obvious, but I fi nd it always good patient. As Dr. Egnew stresses, be- recommends a warm handshake. to refl ect on how your patients coming mindful of the details of the If you get the sense that a patient and their families might perceive next patient outside the consultation is uncomfortable with any touch you. Carefully refl ecting on each of room is a precursor to being mind- because of their cultural or religious these areas should serve us all well ful inside the examination room. beliefs, avoid it. to be better care providers. I thank 2. Establish a connection with the 6. Laugh a little. “Humor can Dr. Egnew for his seven skills to patient, develop rapport and agree be helpful in establishing rapport, promote mastery in clinical practice. on an agenda. This initial interac- relieving anxiety, communicating a I hope you also fi nd them helpful. tion gives you a chance to connect message that you care, enhancing And if this is one New Year’s reso- with the patient interpersonally healing and providing an acceptable lution you can adopt—an attempt and intellectually. Spending a small outlet for any anger and frustra- to master the art of practice—I hope amount of time socializing and lis- tion.” Gentle self-deprecation also it’s one you keep for the remainder tening is a worthy investment. Also, has worked well for all of us from of your career. Wishing all a happy set an agenda. You don’t need to time to time. and healthy New Year! RCCL

address all of their concerns on the 7. Show some empathy. This 1. Egnew TR. The art of medicine: seven skills that pro- fi rst visit, but be certain that they is seldom practiced, especially as mote mastery. Fam Pract Mangag. 2014;21(4):25-30.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBURARY 2019 7 The GP Experts By Robert Ensley, OD, and Heidi Miller, OD

A Reliable Post-PK Option Scleral lenses are growing in popularity, but GPs have long been a mainstay in managing the complex corneas of these patients.

ince 2005, the annual topography will help number of penetrat- dictate the proper ing keratoplasty (PK) contact lens fi t. procedures performed Regular astigmatism in the United States has two principal me- S 1 has decreased by 56%. When ridians perpendicular transplantation is required, more to each other in a bow- selective procedures, such as tie pattern. Depending anterior lamellar keratoplasty and on the power of each endothelial keratoplasty, have half of the bowtie, reg- contributed to the reduced need ular astigmatism can for full-thickness grafts. However, be classifi ed further as PKs are still performed in cases symmetrical or asym- of advanced corneal disease or Post-PK, the cornea can take on a steep-to-fl at metrical. When the opacifi cation. pattern where the graft is tilted. cornea is non-uniform A full-thickness PK replaces all or principal meridians layers of the cornea with a donor may be minimized, careful observa- are not 90 degrees apart, the astig- button, typically 7.5mm to 8.5mm tion for signs of hypoxia is critical. matism is considered irregular, with in diameter, sutured in place to Scleral lenses are made with highly several pattern subtypes.7 Irregular the host tissue.2 Newer surgical oxygen permeable (DK) materi- astigmatism is the most common techniques such as using a femto- als, but they must also take into indication for fi tting GP lenses second laser to create the donor account the diffusion of oxygen post-transplantation.8 button have improved postopera- through the post-lens tear layer. If Corneal shape is typically tive wound stability and reduced excessive hypoxic stress is placed classifi ed into three basic pat- healing time.3 However, refrac- on the endothelium, corneal edema terns: prolate, oblate and mixed. tive outcomes are still variable, may occur and increase the risk of Prolate-shaped corneas are steeper and are largely impacted by the rejection. Smaller-diameter corneal centrally and fl atter in the periph- amount of astigmatism that the GP lenses use the same high DK ery, while oblate-shaped corneas graft produces. High amounts materials and also benefi t from a are fl atter centrally and steeper of astigmatism are not uncom- greater tear exchange beneath the in the periphery. Mixed-shape mon, with one large cohort study lens. This improves oxygen tension features both prolate and oblate reporting at least fi ve diopters of and is suggested to play a role in areas of the cornea. Post-PK, the astigmatism in 20% of grafts.4 the lower risk of microbial keratitis cornea can also take on a steep- If spectacles do not provide a with GP lenses.5,6 to-fl at pattern where the graft is successful visual outcome, contact tilted, steep on one side and fl atter lenses, specifi cally gas permeable THE CORNEAL PROFILE towards the other side.7,9 (GP) lenses, may be required for The goal of fi tting GP lenses is to vision rehabilitation. align the lens’s back surface to the FITTING STRATEGY anterior curvature of the cornea. A well-fi t GP lens will minimize LENS CONSIDERATIONS With a normal cornea, eyelid posi- mechanical trauma to the graft, Because of their ability to vault tioning and keratometry measure- optimize vision and be comfortable over the corneal surface, scleral ments are used to select diameter to the patient. Maintaining proper lenses are becoming an increasingly and base curve. For PK patients, centration and distributing weight popular lens choice for post PK analyzing astigmatism and corne- equally on the cornea can achieve patients. While mechanical stress al shape with the aid of corneal these objectives.

8 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 201908 In general, larger-diameter in- alignment. If the graft is tilted, a post-surgical corneas. The tralimbal lenses (10mm to 12mm) GP lens will tend to center over SynergEyes UltraHealth lens is are preferred because their back the steepest part of the cornea. designed using a hyper DK reverse optical zone diameter will extend Larger-diameter lenses help with geometry GP lens and a high DK beyond the graft-host junction.9,10 centration, although in these cases SiHy skirt. The GP lens vaults over If small-diameter lenses must be scleral lenses may indeed be the the cornea with minimal touch used, care must be taken to avoid preferred choice. and the soft skirt maintains centra- heavy bearing, especially on the tion with minimal movement. junction. OTHER OPTIONS Choosing a back surface design Discomfort and decentration can he versatility of scleral lenses for the lens is dependent on the potentially derail the success of GP Tmakes them a popular choice corneal profi le. Prolate corneas lenses. A piggyback system may for the post-PK patient; however, with regular astigmatism and a be an effective option to correct they are not without risk. If a graft normal eccentricity can often still both complications. A soft sili- patient cannot tolerate or afford be fi t in a conventional spherical cone hydrogel (SiHy) lens can be a scleral lens, they have options. lens. If the regular astigmatism is placed under the GP lens to reduce Don’t be afraid to put your GP 2.5D or more, a bitoric design can friction on the cornea. The power fi tting skills to the test! RCCL be fi t to avoid lens rocking and ar- profi le of the soft lens can help 1. Eye Bank Association of America. 2016 Eye eas of heavy touch. When the graft manipulate centration. A high my- Banking Statistical Report. restoresight.org/ wp-content/uploads/2017/04/2016_Statistical_ is steeper, a keratoconic design, opic powered soft lens will act as Report-Final-040717.pdf. Accessed December which typically has a steeper base a carrier for the GP lens to rest on, 23, 2018. curve and smaller optic zone size, while a high plus lens may “fi ll in” 2. Richard JM, Paton D, Gasset AR. A Comparison 10 of penetrating keratoplasty and lamellar kerato- can be used. Proud grafts that pro- an oblate cornea. In a piggyback plasty in the surgical management of keratoco- trude more from the host cornea design, the soft lens will provide nus. AM J Ophthalmol. 1978;86(6):807-11. 3.Farid M, Pirouzian A, Steinert RF. Femtosec- may require a quadrant specifi c only 20% of the total optical ond laser keratoplasty. Int Ophthalomol Clin. peripheral curve design if there is power of the system.11 Because 2013;53(1):55-64. excessive edge lift. A reverse ge- oxygen must now diffuse through 4. Kelly TL, Williams KA, Coster DJ. Corneal trans- plantation for keratoconus: A registry study. Arch ometry lens, in which one or more two lenses, careful monitoring for Ophthalmol. 2011; 129(6):691-7. peripheral curves are steeper than corneal hypoxia is warranted. 5. Weissman BA. Corneal oxygen: 2015. CL Spec- the optical zone curvature, can Contemporary hybrid lens trum. 2015;30:25-29,55. 9 6. Fleiszig SM. The pathogenesis of con- also reduce peripheral edge lift. designs are also available for tact lens-related keratitis. Optom Vis Sci. Reverse geometry lenses 2006;83:E866-73. 7. Karabatsas CH, Cook SD, Sparrow JM. Proosed are also useful for oblate classifi cation for topographic patterns seen corneas. A conventional after penetrating keratoplasty. BR J Ophthalmol. GP would exhibit excessive 1999;83:403-9 8. Wietharn BE, Driebe WT Jr. Fitting contact central clearance, at risk lenses for visual rehabilitation after penetrat- for bubble formation, ing keratoplasty. Eye & Contact Lens 2004; 30(1):31–33. mid-peripheral bearing and 9. Szczotka LB, Lindsay RG. Contact lens fi tting edge lift. Flattening the base following corneal graft surgery. Clin Exp Optom. curve to match the central 2003;86(4):244-9. 10. Louie DJ, Kawulok E, Kauff man M, Epstein A. cornea and steepening Postsurgical contact lens fi tting. In: Bennett ES, the peripheral curves Henry VA, eds. Clinical Manual of Contact Lenses. 4th Ed. Philadelphia, PA: Lippincott, Williams & will better match corneal Wilkins; 2014:578-608. contour, with a fl uorescein 11. Woo M, Weissman B. Eff ective optics of A well-fi t GP lens will minimize mechanical piggyback soft contact lenses. CL Spectrum. pattern appearing to be in trauma to the graft. 2011;26(11):50.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 9 New Lenses for a Highlights in 2019 will include toric multifocals, a photochromic contact lens and more. New Year

By Jane Cole, Contributing Editor

ot too long ago, the SUN PROTECTION them from the sun’s brightness contact lens marketplace For the fi rst time, photochromic without carrying sunglasses has seemed a bit stagnant. technology is coming to the con- been on patients’ minds for some NPractitioners had a sta- tact lens platform, with a new lens time. Specifi cally, at least once a ble line-up of offerings that served under the Transitions banner from month for as long as I have been patients well, but it was essentially Johnson & Johnson Vision (JJV) in practice, I’ve gotten the ques- the same product lines year in slated to hit the market in the fi rst tion about photochromic contact and year out with some incremen- half of this year. Formally named lenses. There is clearly a desire, tal updates. For 2019, however, Acuvue Oasys with Transitions and I am excited to answer ‘yes’ to industry has some ambitious new Light Intelligent Technology, the this question several times a year, ideas to debut. Here, we offer a lens is a two-week reusable prod- and possibly more, as awareness sneak peek of what’s expected in uct that continuously adapts from increases once the product is the coming months, and optome- clear to dark and back, according available.” trists weigh in on how these new to the company. The lenses might fi t into what’s cur- lenses become dark rently available. in 45 seconds when “In general, the lenses will be exposed to UV or a stab at what doctors and pa- HEV light and fade tients have been asking for over back to clear within the last several years,” says David 90 seconds in dark- Anderson, OD, of Miamisburg, er lighting. The lens Ohio. “We will see toric mul- also provides 100% tifocals, lenses to treat medical protection against UVB conditions and lenses that change rays, JJV says. The lens color like Transitions glasses. For is the result of a joint the longest time, the lens advanc- partnership between es have been all health driven, JJV and Transitions addressing compliance with daily Optical. disposables or more oxygen with “This lens has been silicone hydrogel lenses. Now, the long awaited for,” Fig. 1. and Fig. 2. The Acuvue Oasys with Transitions Light Intelligent Technology lenses companies are making an effort to says Dr. Anderson. become dark in 45 seconds when exposed to focus on the cosmetic and medical “The idea of both bright light and fade back to clear within 90 arenas to help solve some needs protecting your eyes seconds in darker lighting, according to the that patients have had for years.” from UV and shielding company.

10 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 Mile Brujic, OD, of Bowling an increase in astigmatism as Are CL Developments Green, Ohio, likens this new lens they age, which alone can cause Meeting ODs’ Needs? option to a “sunglass contact dropout,” Dr. Anderson adds. We asked experts from the Centre lens.” Although it doesn’t provide “This is the fi rst time we’ve for Ocular Research & Education ocular tissue protection, athletes had access to a toric contact (CORE) at the University of who may not be able to wear lens that has presbyopia-cor- Waterloo to weigh in on wheth- sunglasses, for example, will be recting options available in our er the new contact lenses being able to see comfortably in this offi ce without having to special- developed are bridging doctor and new lens. “In my mind, that’s the ty order them,” says Dr. Brujic. patient needs. bigger thing than the actual pro- While a multifocal for astig- At a basic level, contact lenses tective factors of the potential UV matism has existed for many need to enable patients to see protection in the lens.” years, it is a custom-fi t lens, clearly, with all-day comfort, while maintaining the health of the Adds Glenda Secor, OD, of which presents myriad clinical wearer’s eye, they say. For practi- Huntington Beach, CA, “This and logistical barriers. “The tioners, lenses need to be quick and lens should be great. Patients are process is lengthy because it is a predictable to fi t. “Many changes in anxious to try them.” made-to-order lens,” says Justin contact lens design and technology Bazan, OD, of Park Slope Eye over the last few years have helped NEW PRESBYOPIC OPTIONS in Brooklyn, NY. “It can take us move closer to being able to Last fall, Alcon launched its a couple of weeks just to get provide those basics for a greater monthly replacement Air Optix the fi rst trial lenses. More times number of patients,” they say. plus HydraGlyde Multifocal than not, a second or third For example, silicone hydrogel contact lens, giving the company a trial is needed, adding several materials provide the cornea with new monthly option to round out weeks to complete the fi t. This suffi cient oxygen for daily wear, and, in many cases, adequate its multifocal product line. The drawn-out process often leads oxygen for overnight wear also. HydraGlyde component is said to to frustration and many patients Materials have been engineered to improve moisture retention and are lost to follow-up.” try and maintain comfort through- thus contact lens comfort, accord- Also, the fi tting process for out the day, and choice of design to ing to the company. custom lenses is complicated correct astigmatic and presbyopic Other companies are also plan- and the visual outcome isn’t prescriptions has increased. ning new multifocal offerings for always satisfactory, Dr. Bazan Yet, there are still improvements this patient population: says. “For me, the complication to be gained in delivering enhanced Astigmatism. Bausch + Lomb is stems from numerous add pow- comfort for the many patients who gearing up to debut a multifocal ers and power designs. It’s rare experience contact lens-related toric lens, the Ultra Multifocal to get a patient who is happy dryness, they add. “We need to understand more about the interac- for Astigmatism. The monthly with their visual outcome.” tion of contact lenses with both the replacement silicone hydrogel The forthcoming lens from tear fi lm and contact lens solutions, lens can correct near or distance B+L may help to resolve these and we would benefi t from technol- vision, astigmatism and presby- issues, Dr. Bazan says. “It com- ogy which enables the incidence of opia and has an expected release bines technology that has been both microbial keratitis and corneal of mid-2019. proven successful, it is easy to infi ltrative events to be reduced.” This lens may help patients with fi t and will be available on the Acquisitions of instrument and uncorrected astigmatism stay in spot in an in-offi ce fi tting kit. therapeutic device intellectual contact lenses because they won’t From our spherical presbyopic property by some of the major need to wear readers over their patients, we have learned that vision care companies over the past distance vision contacts or rely multifocal contact lenses are the few years demonstrate the focus that exists in this area, they add. “A on monovision to help with near preferred way to handle pres- better understanding of the tear vision, says Dr. Anderson. “A byopia, and now we are fi nally fi lm and how it interacts with the multifocal option to also correct able to offer it to our astigmatic contact lens should lead to new astigmatism offers an opportunity presbyopic patients.” technology and treatments which to help more patients as they lose “It will be like fi tting a spher- can help maintain, or even enhance, their near vision, and provides ical multifocal lens, and the ocular surface health,” the CORE an option as many patients have Ultra material is a comfortable researchers explain.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 11 NEW LENSES FOR A NEW YEAR

platform,” Dr. Brujic adds. “This pathway for their innovation. An line extensions added correction is one I’m excited about.” accommodating contact lens still for astigmatism and presbyopia. Dynamic refraction. Presbyopic appears to be on Alcon’s product The company also has a non-SiHy patients may one day have ac- roadmap, too, according to public workhorse lens in the Dailies Aqua cess to a self-powered smart lens documents. Comfort Plus product line. designed to dynamically change Though a product launch won’t In 2019 or perhaps 2020, look focus. The subject of much spec- make it into 2019, clinicians may for the company to add a third ulation for years, this concept be able to hear more about these category in between those two, is being pursued by at least two technologies as plans proceed at reportedly to be called Precision1. companies, Alcon and JJV. Both both companies. Few details are available, but the have publicly discussed their plans company expects the silicone hy- to develop a lens that adjusts its A MID-TIER SiHy LENS drogel contact lens to use what it shape to change the refractive Back in 2011, Alcon planted a fl ag calls ‘advanced aqueous extraction index as needed. JJV says it has at the high end of the daily dis- and surface treatment,’ which it overcome many technical hurdles, posable market with the launch of believes will help the contact lens including onboard battery tech- its DailiesTotal1 silicone hydrogel compete with other mainstream nology, and it is working closely (SiHy) lens, using a water gradient silicone hydrogel options currently with the FDA on the regulatory lens matrix. Subsequent product on the market. Happy 20th, Silicone Hydrogels! By Lyndon Jones, PhD, DSc, FCOptom, Jill Woods, BSc (Hons), MCOptom, Karen Walsh, BSc (Hons), MCOptom, and Doerte Luensmann, PhD, Dipl. Ing. In 2018, silicone hydrogel (SiHy) contact lenses cele- epithelial microcysts, limbal hyperemia and corneal brated their 20th birthday. Now that these lenses have neovascularization were signifi cantly reduced. However, been available for two decades, we at CORE off er a mechanical complications arose from the combination walk down memory lane. Here is a look at SiHy’s mile- of increased modulus and original base curve designs. stones and challenges, from balancing properties for These included contact lens induced papillary conjunc- comfortable daily wear to increased understanding of tivitis, mucin balls, epithelial splits and discomfort. how the lenses interact with the ocular surface and tear fi lm, plus a glimpse into the future: ELEMENTARY YEARS: 2004-2009 This was a period of great advancements for SiHy with INFANT/TODDLER YEARS: 1998-2003 the launch of the fi rst reusable SiHy lens with a daily Prior to SiHy lenses, frequent replacement soft hydro- wear-only indication. This material, galyfi lcon A, had gel lenses were available, but hypoxia-related compli- a bound internal wetting agent to achieve wettability. cations existed with full-time daily and extended wear. Further innovation saw the release of comfi lcon A, an The potential benefi ts of silicone were known, but inherently wettable material. Practitioners had access researchers and manufacturers faced signifi cant tech- to an increased choice of spherical lenses, along with nical challenges when incorporating the hydrophobic the addition of toric and multifocal options across a element into a lens. The fi rst generation of SiHy lenses number of new materials for both extended and daily

were balafi lcon A, with a plasma ox- Photo: Jeffrey Sonsino, OD, and Shachar Tauber, MD wear. The fi rst daily disposable SiHy idation surface treatment that cre- lens, narafi lcon A, was launched in ated silicate “islands’ on the surface 2008-2009. of the lens, and lotrafi lcon A with Balancing the material properties a plasma coating. Both required of oxygen transmissibility, modulus, surface modifi cation to create a coeffi cient of friction and wetta- suitably hydrophilic surface. bility was a focus through these The fi rst years of the SiHy era years to drive increased comfort for delivered both a leap forward in daily wear. Packaging solutions also oxygen delivery and some initial received attention, with comfort-en- Researchers are investigating contact physiological challenges. Hypoxic lens materials that may reduce the hancing agents added to the blister responses, such as corneal striae, incidence of microbial keratitis. pack of several SiHy materials.

12 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 In statements to fi nancial ana- also see an advance that builds professor and university research lysts, the company said Precision1 upon the Dailies Total1 lens matrix chair, and includes Jill Woods, “will be a daily disposable, SiHy technology. Investor presentations BSc (Hons), MCOptom, clinical contact lens intended to compete note a “next generation water research manager and senior clin- within the mainstream subcatego- gradient” material in the works, ical scientist at CORE; and Karen ry of the global daily disposable though no release date is specifi ed. Walsh, BSc (Hons), MCOptom, contact lens market” and it “will CORE clinical scientist. be engineered for the highest INNOVATION ON Myopia. They predict an visual clarity of any contact lens in THE HORIZON expansion of myopia control its class.” Positioned between the Researchers from the Centre for designs, including the MiSight high-end Dailies Total1 and the Ocular Research & Education (CooperVision) design they have non-SiHy Dailies Aqua Comfort (CORE) at the School of been working with in clinical tri- Plus, this new, mid-tier lens could Optometry & Vision Science at the als. This soft lens for myopia con- strike a balance between perfor- University of Waterloo offer their trol has been available in Canada mance and cost that helps grow insights on what’s ahead on the for a year and even longer in some the daily disposable category as a contact lens horizon. This research East Asian and European markets. mass-market product. team is led by Lyndon Jones, PhD, “It will be interesting to see the im- Further down the road, we may DSc, FCOptom, CORE director, pact of this lens in the US market

However, adverse reactions still occurred, including tions remain and are the subject of ongoing research. the potentially sight-threatening complication of micro- Hopefully innovation will result in lenses with reduced bial keratitis. Additionally, reusable SiHys were found to complication rates and improved all-day comfort. be two times more likely to result in corneal infi ltrative events compared with hydrogel lenses.1-4 COLLEGE YEARS: 2018 AND BEYOND Today, researchers are looking into the development of HIGH SCHOOL: 2010-2017 materials to reduce the incidence of infective (microbial New research and development resulted in an in- keratitis) and infl ammatory (corneal infi ltrative) events. creased understanding of the interaction of SiHys This may involve the addition of antimicrobial coatings with the tear fi lm. This included establishing protein to contact lens materials. In addition, improving com- and lipid deposition profi les, and the relevance of the fortable wear times is another goal, and researchers conformational state of those tear components once are studying the controlled interaction with the tear adsorbed onto, and absorbed into, the contact lens. fi lm, which would encourage uptake of “good” proteins Further investigations also explored other variables and lipids while resisting deposition of “bad” tear fi lm that may impact comfort, such as the eff ect of contact components. Investigators believe the conformational lens wear on the ocular infl ammatory response and state of deposits is important, with materials ideally the interactions that occur between SiHy materials and being able to minimize the denaturation of proteins and contact lens care systems. oxidation of lipids. Further comfort enhancements may Key milestones during this era included a new lens also involve diff erential deposition on the front vs. the material, delefi lcon A, with a silicone core and a hydro- back of the lens and the delivery of comfort enhancing gel-like surface, updated designs from the original 1998 components that could help to stabilize the tear fi lm lenses, and the emergence of color SiHys. By the end of and enhance wettability. 2017, more than 40 SiHys were available in all prescrip- Although an important area of development, no myo- tions and modalities, including daily disposables for pia-control designs are available in SiHy materials, but astigmatism and presbyopia. By 2017, two-thirds of all researchers expect this to change. They also anticipate soft fi ts were SiHys, with the greatest use of this mate- innovation for presbyopia with the addition of novel rial occurring with reusable contact lenses.5 optical designs for multifocal contact lenses. While understanding SiHy materials and their ocular With 20 years of lens advancements, the future looks interactions increased during this time, some ques- promising for SiHy lenses.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 13 NEW LENSES FOR A NEW YEAR

once it gains the necessary FDA Sensimed’s Triggerfi sh, a contact approvals to launch,” the CORE lens designed to evaluate changes team says. in intraocular pressure, is commer- Another new soft myopia cially available in Europe and has control lens that could hit the US FDA clearance. market in the future is NaturalVue “Biosensing technologies are a (Visioneering Technologies), which focus for many manufacturers and was available in some global mar- research institutions,” the CORE kets in 2018. researchers say. “Parties are ac- “Given the worldwide recogni- tively exploring the possibilities of tion of the myopia epidemic, and this technology in a contact lens, the real sight-threatening pathol- as well as with other ocular and ogy associated with high myopia, systemic applications, including the focus on myopia control is detection of cancer markers, blood Fig. 3. Patients with astigmatism now crucial. We are excited by the rate pressure monitoring, measuring have a monthly replacement silicone hydrogel lens option in the form of at which our collective knowledge tear fi lm osmolarity and markers Bausch + Lomb’s new Ultra Multifocal grows in this area and the fact of dry eye disease.” While biosens- for Astigmatism, which is designed that optical designs really do seem ing contact lenses are an exciting to provide stable, consistently clear to have an impact,” CORE says. possibility, most technologies are vision and spherical aberration “While it is true that there is much still quite a few years away from control in both axes to help reduce halos and glare. we don’t understand, this is a fast being commercially available, the moving area of research, with new CORE team adds. Developers evidence being generated, and new have several hurdles to overcome through the approval process, contact lens and spectacle designs before bringing anything to mar- optometrists still hope additional being tested and released with ket. In November 2018, Verily advances will help to fulfi ll their increasing regularity.” (Alphabet) and Alcon announced patient needs. In addition to these products, that they shelved development of a “A daily disposable toric multi- the group is aware of alternate diabetes-monitoring contact lens, focal lens is next on my wish list,” myopia management approaches citing diffi culties with obtaining Dr. Anderson says. “I have more via the use of orthokeratology, consistent measures of glucose than 65% of my patients wearing pharmaceutical treatments and the levels in tears. daily disposable lenses. The next future potential of combination Drug delivery. The CORE area needed is the daily toric mul- therapies that may bring together researchers also see growth in tifocal lens.” contact lens optical designs and drug-delivering contact lenses to There are still two key areas drug delivery. treat specifi c conditions, including where patient needs could be Light moderation. Light man- glaucoma, infl ammation, allergy better met, the CORE team says. agement will be of interest in and to aid ocular surface healing. “First are the rates of infection 2019, the CORE team says. In One such product in the pipeline and infl ammatory events.” Daily addition to the photochromic is a JJV contact lens that includes disposables are the best way to lens on the way from JJV, there the medication ketotifen fumarate. minimize risk of these adverse is much interest around eyestrain This drug-eluting contact lens is events, they say, but reusable con- from digital device use. designed to help patients with tact lenses could benefi t from the “This has led to modifi cations to itchy eyes due to ocular allergies, addition of antimicrobial proper- the optical designs of some contact according to the company. JJV ties to help reduce the incidence of lenses, targeted to reduce digital says it is on track to bring the these complications. “Secondly, we eyestrain. It is also possible that product to market within fi ve are striving to minimize dryness/ the digital light management tech- years. discomfort, which remains the nology offered in certain spectacle main reason for ceasing contact designs may translate into the CONTACT LENS WISH LISTS lens wear. New technologies that contact lens market,” they add. Even though several new contact can enhance the comfort of the Biosensing. A growth in special- lenses are set to launch this year contact lens, such as release of ty medical lenses is also expected. and others are working their way tear-fi lm type components when

14 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 Earn up to NEWNEW TTECHNOLOGIES 18 CE 2019 & TTREATMENTS IN

Credits* 9 EyeEyyeeGVCE Care Carer REVIEW’S COMMITMENT TO worn, would be welcome,” the CONTINUING EDUCATION CORE team says. One example is the Tangible Hydra-PEG coating (Tangible Science), which recently gained FDA approval for use on daily disposable silicone hydrogel lenses. This coating is designed to im- prove wettability, increase surface water retention and lubricity, and minimize lens deposits. Tangible Science had previously licensed its technology for use with Bausch + Lomb’s rigid gas permeable and Nashville scleral contact lenses. “We have a standing order with our gas permeable lenses right MAY 17-19, 2019 now to put Tangible on every- Join Review’s New Technologies & Treatments in Eye thing,” Dr. Brujic says. “That’s Care on May 17-19, 2019 in Nashville, TN. how good it’s actually been.” This meeting provides up to 18* COPE CE credits Additionally, while research ** continues in the area of myopia including interactive workshops! control, new lens options for GAYLORD OPRYLAND this patient population would be 2800 Opryland Drive welcome sooner rather than later, doctors say. “Myopia manage- Nashville, Tennessee 37214 † ment is a hot topic in optometry,” DISCOUNTED RATE: $209/night Dr. Bazan says. “I would like to PROGRAM CHAIR: see more contact lens companies develop options to help with the myopia epidemic.”

hile everyone waits for their Wcontact lens dreams to come Paul M. Karpecki, OD, FAAO true, ODs are looking forward trying several new lenses this year FACULTY: and sharing them with patients. RCCL Ben Gaddie, OD, FAAO Jay M. Haynie, OD, FAAO 1. Szczotka-Flynn L, Diaz M. Risk of corneal infl am- matory events with silicone hydrogel and low dk hydrogel extended contact lens wear: a meta-anal- ysis. Optom Vis Sci. 2007;84(4):247-56. 2. Radford CF, Minassian D, Dart JK, et al. Risk THREE WAYS TO REGISTER factors for nonulcerative contact lens complica- tions in an ophthalmic accident and emergency department: a case-control study. Ophthalmology. ONLINE: www.reviewsce.com/nashville2019 2009;116(3):385-92. 3. Chalmers RL, Wagner H, Mitchell GL, et al. Age EMAIL: [email protected] and other risk factors for corneal infi ltrative and infl ammatory events in young soft contact lens wearers from the Contact Lens Assessment in CALL: 866-658-1772 Youth (CLAY) study. Invest Ophthalmol Vis Sci. 2011;52(9):6690-6. 4. Chalmers RL, Keay L, McNally J, Kern J. Multi- Administered by center case-control study of the role of lens mate- rials and care products on the development of cor- GVCE REVIEW’S COMMITMENT TO neal infi ltrates. Optom Vis Sci. 2012;89(3):316-25. CONTINUING EDUCATION *Approval pending 5. Morgan PB, Woods C, Tranoudis I, et al. In- ternational contact lens prescribing in 2017. CL Partially supported by an unrestricted Spectrum. 2018;33(January):28-33. educational grant from Bausch & Lomb

**Subject to change, separateREVIEW registration OF CORNEA required. & CONTACT See LENSES event website| JANUARY/FEBRUARY for complete details. 2019 †Rooms 15 limited. RGVCE partners with Salus University for those ODs who are licensed in states that require university credit. Visit www.reviewsce.com/events for any meeting changes or updates. KERATOPLASTY: WHEN AND WHY

Discover how long to monitor and treat symptoms before considering surgical interventions. By James Esposito, OD

urgeons perform corneal history and clinical exam are nec- keratoplasty. Questioning a patient graft surgery for a wide essary before referring patients for on their visual symptoms is a crucial variety of indications, in- cataract surgery. The next two most fi rst step. Scluding stromal opacifi ca- common pathologies for corneal • Blurred or variable vision tion, corneal ectasias and persistent graft surgery are repeat graft surgery associated with corneal edema often corneal edema due to endothelial after failure and keratoconus.3 has a diurnal nature—worse upon failure. Worldwide, four-and-a-half Currently, the United States has waking and improved later in the million individuals have moder- the highest rate of corneal trans- day. This is due to prolonged eyelid ate to severe vision impairment plants per capita.4 In the 2016 EBAA closure and a relatively hypotonic secondary to the loss of corneal report, endothelial keratoplasty tear fi lm, which reverses throughout clarity and more than 200 million (EK) compromised 57% of surgeries the day with greater exposure. are visually impaired.1 Corneal performed in the United States, and Symptoms of photophobia, glare, disease is the fi fth leading cause of full-thickness penetrating keratoplas- redness, tearing, pain or foreign- blindness after cataract, uncorrect- ty (PK) was performed in 38% of pa- body sensation are also commonly ed refractive error, glaucoma and tients.3 Anterior lamellar keratoplasty associated with corneal edema. macular degeneration.1 Here we (ALK) and deep anterior lamellar • Most conditions associated with review common graft indications keratoplasty (DALK) procedures corneal edema present gradually in the United States, clinical pearls accounted for the small portion of over weeks, months or even years. for a timely and correct diagnosis remaining surgeries. Symptoms may be so gradual at and recommendations on when to Since EK’s introduction in 1999, times that the patient is able to func- obtain an initial surgical consult there has been an impressive growth tion surprisingly well and at a much for keratoplasty. in the number of surgeries and litera- higher level than would be expected ture publications, supplanting PK as based on a slit-lamp biomicroscopy COMMON INDICATIONS the mainstay.5,6 In contrast, ALK and exam. Exceptions to this general rule AND PROCEDURES DALK surgeries were fi rst introduced would be edema caused by acutely The Eye Bank Association of in 1959, but their popularity has elevated intraocular pressure (IOP), America’s (EBAA) 2016 report waned, primarily due to the lack of ABOUT THE AUTHOR revealed that the most common indi- properly trained ophthalmic sur- cation for any corneal graft surgery geons.7 ALK and DALK also require Dr. Esposito is an attending provider and in the US is endothelial cell failure a more prolonged operating room clinical researcher at the secondary to either Fuchs’ endotheli- time and carry a high risk of perfora- New Mexico Veterans Administration Health al dystrophy or cataract surgery [e.g., tion in older patients. Care System Eye pseudophakic bullous keratopathy Clinic in Albuquerque, New Mexico. He is an (PBK)]. Be aware that a signifi cant CASE HISTORY PEARLS adjunct clinical professor portion of PBK patients also have Many factors come into play when at the University of Houston College of Optometry, the Pacifi c University undiagnosed Fuchs’ endothelial monitoring patients for corneal College of Optometry and the New dystrophy.2 Therefore, a detailed case edema and considering referral for England College of Optometry.

16 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 testing may not be during initial examination. • A differential diagnosis of corne- al edema or opacifi cation can be nar- rowed after noting the following: (1) unilateral or bilateral signs, (2) dif- fuse or localized edema, (3) primarily epithelial or stromal edema, (4) stromal infi ltration, striae, thinning, scarring or vascularization and (5) endothelial guttae, Descemet’s tears At left, this patient has severe corneal edema associated with complicated cataract surgery. At right, the same patient’s corneal epithelium and or detachments, endothelial vesicles, irregularity can be easily seen with the sodium fl uorescein dye pattern. keratic precipitates and peripheral anterior synechiae. moderate corneal or intraocular • A number of systemic diseases • Clinicians can use various slit- infl ammation or hydrops associ- and medications are associated with lamp techniques such as sclerotic ated with corneal ectasias, such as corneal opacifi cation. These include scatter, specular refl ection or indirect keratoconus. metabolic/hereditary disorders illumination to evaluate all layers • Certain factors or special situ- such as mucopolysaccharidosis; of the cornea. When performing a ations can also modify a patient’s immune-mediated diseases careful iris examination, note the quality of vision and affect the sur- such as rheumatoid arthritis, shape of the pupil, as it is often evi- gery referral timeline. Low humidity Stevens-Johnson syndrome dence of past trauma, infl ammation and modest air movement may lead and ocular mucous membrane or complicated intraocular surgery. to visual improvement, where- pemphigoid; and hematologic IOP measurement by Goldmann as endothelial dysfunction from disorders such as monoclonal applanation tonometry is somewhat humid days or after a long shower gammopathies and malabsorption unreliable in abnormal corneas, so can exacerbate corneal edema. A syndromes, usually following use alternative devices in concert, dehumidifi er can be used as a trial colon resection. Amiodarone, such as a pneumatonometer, a Tono- and this may even help patients with dietary calcium supplementation, pen device (Reichert) or a dynamic concurrent ocular allergy. Visual periocular radiation and various contour tonometer. Consider go- acuity and function may not neces- chemotherapeutic agents have all nioscopy to rule out retained nuclear sarily correlate well together when also been reported as causative fragments, occult foreign bodies and considering disabling glare during agents for opacifi cation.14-17 secondary glaucomas that could driving at night or other activities of cause elevated pressure and corneal daily living. EXAMINATION PEARLS decompensation. • Clinicians should always obtain After recording a detailed history, a a detailed medical history and cur- comprehensive examination of the ANCILLARY TESTING rent list of medications, as infl am- eye and adnexa is key to determining Other tests can augment the clinical matory conditions associated with the etiology of most cases of corneal observations from the slit lamp uveitis (anklosing spondylitis, sar- edema. exam. coidosis) may also cause corneal ede- • Clinicians should test visual • A potential acuity meter or pin- ma. Amantadine, for example, helps acuity with the lights on and off hole vision using an illuminated near treat Parkinson’s disease and other and compare to produce a qualita- card in a darkened room can assess neurologic diseases but may cause tive assessment of the individual’s potential acuity in an effort to bypass reversible corneal edema if used for functional status. When performing anterior segment pathology. a short period of time. Long-term the external examination, pay careful • Disruption of the central or use may cause permanent damage.8,9 attention to lid abnormalities, facial paracentral ocular surface due Inadvertent exposure of the cornea asymmetry and evidence of trauma. to corneal edema or scarring can to topical chlorhexidine preparation, Slit-lamp biomicroscopy is exceed- have a surprising impact on vision. commonly used during cosmetic fa- ingly important, especially because Obtain best-corrected vision with cial surgery, may predispose a cornea it is universally available to ophthal- spectacles and a rigid gas permeable to endothelial failure.10-13 mic providers, and other ancillary (RGP) contact lens over-refraction.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 17 KERATOPLASTY: WHEN AND WHY

clinical practice; however, most large MANAGEMENT studies report AS-OCT pachyme- Treatment for corneal edema try measurements to be lower than or opacifi cation may be optical, ultrasound by between 7µm and medical, surgical or a combination, 26µm.19,20 depending on the etiology, nature • Scheimpfl ug imaging systems can and severity of the opacity. The assess the topographic characteristics needs, desires and health status of of both the anterior and posterior the patient also play a part. corneal surfaces in addition to cor- The medical agents used to control neal thickness measurements. These corneal edema include all ocular systems have improved the ability to hypotensive agents except two drug diagnose forme fruste keratoconus classes. Prostaglandin analogs should The presence of stromal edema and other corneal ectasias immense- be avoided in patients for whom in- and linear folds of Descemet’s membrane can help you narrow down ly. They can also assess the depth of fl ammation is a possible contributing a diagonsis. corneal opacifi cation, which pro- factor—any history of graft rejection vides useful information for surgical or uveitis.22 Also, when endothelial This can quickly be done in- planning. disease is a possible contributing offi ce by obtaining keratometry • AS-OCT provides high factor, avoid carbonic anhydrase measurements and then fi tting an resolution, cross-sectional images inhibitors as the fi rst line of therapy RGP lens slightly fl atter than the of the cornea, angle and anterior because of their potential to interfere average keratometry reading. Be sure chamber. Measurement tools to with the endothelial pump.23 Use to note the mire pattern to correlate document and follow changes in topical corticosteroids when infl am- directly with the amount of anterior corneal thickness, angle and anterior mation is present and infection has surface irregularity. chamber are standard with all been ruled out. Although hyper- • Corneal pachymetry has models. Currently, AS-OCT has the osmotic agents or hairdryers are become more readily available in greatest utility for imaging deep and commonly suggested treatment rou- ophthalmic offi ces and is important retrocorneal structures, such as a tines, there are no studies that have for quantifying corneal thickness large detached Descemet’s membrane determined the optimal routines of and change over time. Ultrasonic and a retrocorneal membrane. These either of these modalities. pachymeters provide information conditions may arise with trauma, Topical antibiotics and therapeu- about a single spot on the cornea, after EK surgery or acute corneal tic contact lenses can be used in and their range is often limited to edema associated with keratoconic conjunction with bullae rupture in between 200µm and 1,000µm. hydrops. Ultrasound biomicroscopy PBK to reduce the risk of infection With careful positioning and utility is similar to AS-OCT but and help control discomfort or pain. probe angulation, an interobserver is more useful when dealing with Although many different lenses standard deviation of 12µm is the extremely opaque corneas and may be used, thin lenses with high best to be expected.18 imaging deeper anterior segment water content and a high Dk are • If precision and peripheral mea- structures. thought to have the greatest advan- surements are important, anterior • Endothelial cell count (ECC) is tages.24 Ideally, use bandage contact segment optical coherence tomog- comparable using both specular and lenses for a fi nite treatment period; raphy (AS-OCT) and Scheimpfl ug confocal microscopy.21 Confocal however, longer-term use may be re- imaging systems provide greater microscopy provides an advantage quired in many cases, with periodic accuracy. Since both of these tech- over specular when imaging the cor- exchange of the lens. niques use light instead of sound, neal endothelium in cases of corneal Patients with corneal edema and each one’s accuracy decreases as edema. This is particularly useful persistent discomfort but limited stromal opacifi cation worsens. in cases of unilateral corneal edema visual potential are better candidates • The ultrasound biomicroscope where the preoperative diagnosis for a conjunctival fl ap, amniotic provides the most accurate mea- may be undetermined. Special cases membrane or one of many scarifi ca- surements when signifi cant stromal like iridocorneal endothelial syn- tion procedures. While less common, edema is present. Keep in mind that drome or posterior polymorphous a patient with good visual potential measurements with different devices corneal dystrophy have distinctive may opt for one of these procedures are not directly comparable in confocal appearances. when extenuating circumstances

18 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 4. Gain P, Jullienne R, He Z. Global survey of corneal affecting general health or follow-up activities of daily living to prompt an transplantation and eye banking. JAMA Ophthalmol. care/transportation become issues. early referral for EK. Once subep- 2016;134:167-73. 5. Melles GR, Lander F, Beekhuis WH. Posterior Timely referral of patients with ithelial scarring has occurred with lamellar keratoplasty for a case of pseudopha- kic bullous keratopathy. Am J Ophthalmol. endothelial dysfunction is extremely chronic PBK, an early referral is 1999;127:340-1. important because patients with less important, since PK will be the 6. Terry MA, Ousley PJ. Endothelial replacement without surface corneal incisions or sutures: topog- chronic PBK often develop a layer preferred surgical technique. raphy of the deep lamellar endothelial keratoplasty of subepithelial fi brosis. If a patient Prior to 2000, virtually all corneal procedure. Cornea. 2001;20:14-8. 7. Hallermann W. Some remarks on keratoplas- already has considerable subepithe- transplant candidates with decom- ty. Klin Monbl Augenheilkd Augenarztl Fortbild. lial scarring, this will prevent a good pensated corneas underwent PK. 1959;135:252-9. 8. Jeng BH, Galor A, Lee MS. Amantadine-associ- visual outcome following an EK. However, according to the 2011 ated corneal edema potentially irreversible even after cessation of the medication. Ophthalmology. They would instead need full-thick- EBAA report, approximately 75% 2008;115:1540-4. ness PK or a superfi cial keratectomy of patients with corneal edema 9. Naumann GO, Schlotzer-Schrehardt U. Amanta- dine-associated corneal edema. Ophthalmology. 26 combined with EK. are now managed with EK. This 2009;116:1230-1. For patients with endothelial broad acceptance of EK is due to its 10. Phinney RB, Mondino BJ, Hofbauer JD. Corneal edema related to accidental Hibiclens exposure. Am dysfunction, it is important to ad- rapid visual recovery, its signifi cantly J Ophthalmol. 1988;106:210-5. 11. Van Rij G, Beekhuis VH, Eggink CA, et al. Toxic dress considerations beyond visual greater optical (both astigmatic and keratopathy due to the accidental use of chlor- acuity assessment. EK as a combined refractive) predictability, the presence hexidine, cetrimide and cialit. Doc Ophthalmol. 1995;90:7-14. procedure should be considered in of greater wound strength and its 12. Ohguro N, Matsuda M, Kinoshita S. The eff ects of the context of a visually signifi cant lesser risk for rejection with a greater denatured sodium hyaluronate on the corneal endo- thelium in cats. Am J Ophthalmol. 1991;112:424-30. 26 cataract and even early cataracts long-term survival rate. 13. Varley GA, Meisler DM, Benes SC. Hibiclens ker- atopathy: a clinicopathologic case report. Cornea. with the presence of corneal edema. For patients with corneal 1990;9:341-6. Ultrasound pachymetry measurement subepithelial or stromal scarring, 14. Kaplan LJ, Cappaert WE. Amiodarone kera- topathy. Correlation to dosage and duration. Arch in excess of 640µm or the presence of the procedure of choice will be PK, Ophthalmol. 1982;100:601-2. epithelial edema suggest the cornea and, therefore, early consultation for 15. Jhanji V, Rapuano CJ, Vajpayee RB. Corneal calcifi c band keratopathy. Curr Opin Ophthalmol. may decompensate with intraocular graft surgery is less important. These 2011;22:283-9. surgery.25 patients may benefi t more from 16. Jeganathan VS, Wirth A, MacManus MP. Ocular risks from orbital and periorbital radiation therapy: An ECC below 800 has also been initially improving ocular surface a critical review. Int J Radiat Oncol Biol Phys. suggested as predictive of poor en- health (addressing tear fi lm stability, 2011;79:650-9. 17. Van Meter WS. Central corneal opacifi cation dothelial cell function post-cataract lid function and hygiene), controlling resulting from recent chemotherapy in corneal do- surgery. Confl uence of guttae, even IOP in the setting of glaucoma nors. Trans Am Ophthalmol Soc. 2007;105:207-13. 18. Miglior S, Albe E, Guareschi M. Intraobserver and in the absence of stromal or epithe- and stabilizing glycemic control in interobserver reproducibility in the evalutation of ultrasonic pachymetry measurements of central cor- lial edema, can reduce visual acuity, diabetic populations. neal thickness. Br J Ophthalmol 2004;88:174-7. contrast sensitivity and increase 19. Wirbelauer C, Scholz C, Hoerauf H. Noncon- 25 tact corneal pachymetry with slit lamp-adapted symptomatic glare for patients. s corneal graft surgery evolves, optical coherence tomography. Am J Ophthalmol. Consider these criteria along with Aso do our pre-op considerations. 2002;133:444-50. 20. Zhao PS, Wong TY, Wong WL. Comparison of New surgical techniques make deci- central corneal thickness measurements by visante anterior segment optical coherence tomography sions regarding your patient all the with ultrasound pachymetry. Am J Ophthalmol more important, as each case may 2007;143:1047-9. 21. Mustonen RK, McDonald MB, Srivannaboon S, et do better with one procedure over al. In vivo confocal microcsopy of Fuchs’ endothelial another. Practitioners must remain dystrophy. Cornea. 1998;17:493-503. 22. Aydin S, Ozcura F. Corneal edema and acute vigilant when observing patients for anterior uveitis after two doses of travoprost. Acta signs of edema and know when the Ophthalmol Scand 2007;85:693-4. 23. Wirtitsch MG, Findl O, Heinzl H, Drexler W. Eff ect time is right to refer them for kerato- of dorzolamide hydrochloride on central corneal thickness in humans with corneal guttata. Arch plasty. RCCL Ophthalmol. 2007;125:1345-50. 24. Foulks GN, Harvey T, Raj CV. Therapeutic con- 1. Flaxman SR, Bourne RRA, Resnikoff S. tact lenses: the role of high-Dk lenses. Ophthalmol Global causes of blindness and distance vision Clin North Am 2003;16:455-61. impairment 1990-2020: a systematic review and 25. Seitzman GD, Gottsch JD, Stark WJ. Cataract meta-analysis. Lancet Glob Health. 2017;5:e1221-34. surgery in patients with Fuchs’ corneal dystrophy: 2. Eye Bank Association of America. 2016 Eye Bank- expanding recommendations for cataract surgery ing Statistical Report. Washington DC: Eye Bank without simultaneous keratoplasty. Ophthalmology. In this patient with Fuchs’ endothelial Association of America; 2017. 2005;112:441-6. 3. Afshari NA, Pittard AB, Siddiqui A. Clinical Study 26. Wu El, Ritterband DC, Yu G. Graft rejection dystrophy and central stromal edema, of Fuchs corneal endothelial dystrophy leading to following descemet stripping automated endothelial note the light dots along the posterior penetrating keratoplasty: a 30-year experience. keratoplasty: features, risk factors, and outcomes. aspect of the corneal light beam. Arch Ophthalmol. 2006;124:777-80. Am J Ophthalmol. 2012;153:949-57.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 19 THETHE ARTART OFOF CORNEALCORNEAL TRANSPLANTATION TRANSPLANTATION

Optometrists have several options when it comes to keratoplasties, each of which has its own pros, cons and management guidelines. By Andrew Steele, OD

orneal transplantation in rare cases, cosmetic needs. involving the stroma and endo- has changed dramati- Patients who have a signifi cant- thelium still require full-thickness cally since Eduard Zirm ly reduced best-corrected visual grafts. However, pathology involv- Cperformed the fi rst one acuity (BCVA) from a corneal ing 85% to 95% of the cornea, on a human just over a century pathology usually benefi t from a sparing Descemet’s membrane ago. As an avascular tissue lacking graft. Occasionally, transplanta- (DM) and the endothelium, may lymphatic vessels, the cornea tion is required to save an altered be best suited for a partial-thick- enjoys immune privilege, resulting corneal structure from perforation ness graft or a deep anterior lamel- in it being associated with one of or thinning. Pain management for lar keratoplasty (DALK). the lowest rejection rates of all bullous keratopathy and non-heal- Corneal ectasias, stromal human organs.1 In recent years, ing ulcers can also be a primary dystrophies and scarring from a the evolution of techniques and therapeutic indication. Cosmetic previous infection often qualify technologies has substantially reasons for surgery in eyes without for a DALK, which has major improved outcomes and enabled a visual potential remain contro- advantages over a PKP. The risks shift toward replacement of only versial and are considered weak of infection, hemorrhage and the diseased layers. The differ- indications. traumatic wound dehiscence asso- ent transplant types can be a bit ciated with “open sky” procedures disorienting, but understanding FULL- VS. are considerably reduced. DALKs their indications and knowing PARTIAL-THICKNESS also avoid the most common and how to perform perioperative care Historically, full-thickness pene- serious type of rejection—endo- can make a world of difference for trating keratoplasties (PKP) have thelial—and cause signifi cantly optometrists and their patients. been the primary approach to corneal transplantation, during ABOUT THE AUTHOR KERATOPLASTY which all layers are replaced. The Dr. Steele practices INDICATIONS technique is standardized and consultative, medical The two main categories of ker- familiar to most corneal surgeons. and surgical optometry at Bennett & Bloom Eye atoplasties are full-thickness and However, complications are Centers in Louisville, partial-thickness. As the latter relatively common, and recovery KY. He is also an American Academy procedures only remove one or can be painstaking and take up of Optometry fellow, an more selected layers of the cornea, to a year to stabilize. Vision may adjunct professor at the Indiana University and the University they are also referred to as lamel- actually be worse at fi rst and not of Alabama-Birmingham schools of lar. These keratoplasties can be improve for six months or longer, optometry, an attending for forth- year interns and ocular disease further classifi ed as either anterior partially due to the unpredictabil- residents and a lecturer for continuing education courses. He graduated with or posterior. The indications for ity of the cornea’s toricity, and honors from the Ohio State University transplantation are numerous often requires rigid contact lens College of Optometry and completed resident training in ocular disease with and include optical, tectonic and correction. Penetrating trauma, Bennett & Bloom. reconstructive, therapeutic and, corneal hydrops and diseases

20 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 Photo: Lawrence Tenkman, MD THE (a decrease of 1.3% since 2016), ENDOTHELIAL while EK numbers increased by ROUTE 2.6% to 28,993, largely due to Since 2011, the the 18.1% increase in DMEK number of endothelial procedures.5 keratoplasties (EK) in The most common indication the United States has for an EK is Fuchs’ endothelial surpassed full-thick- dystrophy (FED).6 Others include ness grafts.4 For pos- pathologies confi ned to the endo- terior corneal disease, thelium and DM, such as posterior an EK is superior to polymorphous dystrophy and a PKP or a DALK in some cases of pseudophakic bul- nearly every aspect lous keratopathy. FED is usually and is associated with inherited as an autosomal domi- a better visual acuity, nant condition that causes endo- Ten months after a full-thickness PKP, a 68-year- a faster recovery time thelial cells to die off faster than old white female developed methicillin-resistant and a lower rejec- normal. Female patients common- Staphylococcus aureus keratitis at the graft-host tion rate. There are ly suffer from a more debilitating junction and early endothelial rejection after suture removal. She was treated with fortifi ed antibiotics, two primary types version of the disease. steroids and an intrastromal injection. After a week, of EKs: a Descemet’s The hallmark beaten-metal only a small scar remained. stripping automated appearance we refer to as guttata endothelial kerato- starts to appear during a patient’s less endothelial cell loss than plasty (DSAEK) and a Descemet’s third decade. Using a specular PKPs.2 Patients who receive a membrane endothelial keratoplas- refl ection technique when ex- DALK stabilize more rapidly, ty (DMEK). A DSAEK graft in- amining guttata with a slit lamp allowing for earlier suture removal cludes some posterior stroma, DM may produce the best results. and tapering of topical steroids. and the corneal endothelium and Retroillumination of the iris or The surgery itself, however, is comprises about 100µm to 200µm fundus is helpful if the beam width more challenging. While using of tissue. A DMEK graft does not is moderately narrow, allowing for the Anwar big-bubble technique contain any stroma and may only the appropriate contrast. Newer to detach DM from the stromal be 10µm to 15µm in thickness. In technologies provide endothelial layers aids in a faster and overall 2017, the number of PKP grafts cell counts via specular microsco- safer approach, it also increases in the United States was 18,346 py. The AC and corneal thickness surgical complexity and introduces other risks. Intraoperative DM Image: Eye Bank Association of America tears may result in DM detach- Domestic Surgery Use of US-supplied ment, which is also called a double Intermediate-Term Preserved Tissue anterior chamber (AC).3 45,000 Postoperative management is 40,000 similar to that of a full-thickness 35,000 keratoplasty and requires a long 30,000 course of topical steroids. Half 25,000 of PKP patients end up with at 20,000 least four diopters of astigmatism, 15,000 which is often irregular and could 10,000 produce signifi cant anisometropia 5,000 and aniseikonia. Unfortunately, 0 the likelihood of high astigmatism 2005 2006 20072008 20092010 20112012 2013 2014 2015 2016 is not lessened in a DALK, and PK EK ALK KLA satisfactory visual rehabilitation with rigid gas permeable lenses is Improvements in surgical technique have allowed endothelial keratoplasties to often still required. thrive in recent years, eclipsing full-thickness procedures.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 21 THE ART OF CORNEAL TRANSPLANTATION

can now be visualized EK, which is key for with anterior segment unfolding, can cause OCT. Occasionally, gut- the vitreous to pro- tata deposition may be lapse through a large so confl uent that it has a capsulotomy. whitish plaque appear- Patients who have ance. Some corneal haze undergone a vitrectomy represents permanent are usually not good fi brosis. candidates for an EK. In Ideally, an EK should some cases, the AC will be performed before any not shallow when fl uid is stromal scarring appears. let out of the wound; the Patients who notice iris sags posteriorly like morning worsening of a hammock while the their vision have started High magnifi cation image of endothelial corneal guttata by eye softens and wrinkles. their descent toward cor- specular refl ection. This is problematic be- neal endothelial decom- cause the forward move- pensation. Concentrated tions. It is a challenge to keep air ment of the iris is needed sodium chloride ophthalmic drops in these eyes, which makes attach- to hold the donor tissue partially may help symptoms temporarily, ment so diffi cult. open long enough for the surgeon but patients should be closely Injecting sulfur hexafl uoride to put in the initial bubble. monitored, and transplantation gas in place of air into the AC, a New techniques, especially in should be seriously considered, technique used in vitrectomies, the arena of donor preparation, especially if epithelial edema de- is favorable due to its extended have made complex, delicate and velops. Many cases, unfortunately, duration—about four to seven sometimes frustrating DMEK sur- progress rapidly, with corneal bul- days of gas support on the do- geries more manageable. Corneal lae into dense subepithelial haze, nor—compared with air, which surgeons have slowly adopted possibly eliminating a patient’s dissipates more rapidly.7 Due DMEKs in part because of diffi - candidacy for an EK. to risks of pupillary block from culties encountered with donor either bubble type, one or more preparations and concerns about NEW AND IMPROVED peripheral iridotomies (PIs) should the potential loss of donor tissue. TECHNIQUES be placed inferiorly preoperatively Early adopters reported tissue Educating patients on surgical with a YAG laser, as the bubble wastage and a failure rate of one expectations and the necessity will block a superior PI when the in three during donor peeling.9 of close monitoring postopera- patient is upright. Some choose to Lawrence Tenkman, MD, a tively is crucial. Candidates must create a surgical PI intraoperative- corneal surgeon out of Louisville, understand that their vision will ly, which does not come without KY, has modifi ed the Giebel 2008 be blurry for the fi rst few days due risks. Surgical PIs can bleed, SCUBA (submerged cornea using to the intraoperative air bubble in- sometimes in delayed fashion.8 If backgrounds away) technique jected into the AC during surgery. blood is present in the AC, clots with impressive success, reporting Successful donor adhesion requires and fi brin may form. only one tissue failure in over 600 faithful supine positioning for the Given the fragility of the tissue, DMEK cases. Scored with a blunt fi rst 72 hours. Patients may sit manipulating the donor graft Y-hook, the donor edge is stained up to eat, use the bathroom and can be the most challenging part with VisionBlue, lifted with a glide bathe but are typically required to of performing a successful EK, technique and peeled by corridors, spend 45 to 50 minutes of every especially a DMEK. The graft is minimizing tension. This ground- hour with their heads fl at and susceptible to expulsion from an breaking method provides guid- chins elevated about 30 degrees. incision wound and may invert. If ance in handling excessive sepa- Maintaining the proper gas fi ll is the patient is pseudophakic with ration resistance and small breaks critical for success, which is why posterior opacifi cation, consider that form during peeling that Dr. tubes, aphakia and major iris delaying the YAG. Tenkman refers to as “horseshoe defects are relative contraindica- The fl attening of the AC in an tears.”10

22 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 Other improvements facilitat- to acute angle-closure glaucoma and drop scheduling should be ing the rise of DMEK procedures and requires immediate action. reemphasized to the patient. By include instrumentation, such as Surprisingly, some patients with day three or four, there should be the Straiko Modifi ed Jones Tube, this issue may experience symp- much less corneal edema, and the and Eye Bank stamping of an “S” toms of nausea but not eye pain. air bubble should only fi ll about (signifying “stroma”) on the donor The initial and least invasive ap- 25% of the AC. Generally, more tissue to prevent inverted grafts proach involves putting the patient air time is needed if there is focal (iatrogenic graft failure can occur in a full supine position, parallel edema from the DM separation when a surgeon mistakenly places to the ground, and instructing that is signifi cant enough to cause the endothelium in contact with them to look in the extreme supe- blurry vision, in which case, the stroma).11 rior gaze. This technique moves patient instructions should favor the bubble inferiorly in the AC, positions that allow the bubble POST-OP MANAGEMENT occasionally with enough force to to press as directly against the On day one of the postoperative break the adhesion between the dehisced zone as possible. At this period, mild to moderate corneal iris and the cornea. If a closed PI point, the patient may not need to edema with folds is expected. A is present, attempt to reopen it via adhere to the supine position. bandage contact lens may have YAG laser. After one week, the bandage been placed in the operating room. Sometimes, supine positioning lens can be removed, and if a The patient should be reassured is not enough, and performing a single suture is present, it can be that blurry vision is normal due to paracentesis is necessary. Sterile taken out. The use of topical anti- the bubble. conditions must be prioritized, biotics can be discontinued three The goal is an attached DMEK preferably with betadine 5% and days after the suture is removed. donor and a deep AC with air antibiotic drops to the ocular sur- It is appropriate to order anterior fi lling 50% to 70% of the cham- face. Attached to a 1mL syringe, a segment OCT imaging and/or en- ber. It is also imperative to ensure 30-gauge needle should be injected dothelial cell counts at this stage. there is not an air-induced pupil- at the limbus and parallel to the Beginning to slowly taper the lary block, which pushes the pupil iris to avoid the DMEK graft. The steroid is not suggested until three back against the lens and seals needle should be inserted into the to four months after surgery. Some it to prevent the anterior fl ow of bubble, and the plunger should be surgeons recommend complete fl uid. If the inferior PI is not func- slowly withdrawn to let enough discontinuation by six months, tioning, the aqueous produced by air out so the eye is no longer fi rm. but most experts agree that a daily the ciliary body cannot fl ow into Sometimes, re-bubbling is neces- dose of a topical steroid should be the AC, and the iris bulges for- sary to ensure proper peripheral used indefi nitely to reduce the risk ward. Functionally, this is similar donor attachment, especially in of rejection.12 cases of a The learning curve is steep, but total graft in most cases, outcomes from a detachment. DMEK are superior to those from If the graft is a DSAEK, which is largely due not detached to the problems that arise from by more than the stroma-to-stroma interface of a third or DSAEK grafts.13 A tissue with a a fl uid cleft certain radius of curvature con- is present, fi ning itself to a smaller radius of it may only curvature results in micro-irreg- require ularities. Bare stroma cannot be observation. avoided in these cases, leading to Even if edema and a signifi cantly longer postopera- healing time. Eight percent to 10% tive fi ndings of DSAEK grafts are rejected, ac- are normal, cording to recent studies.14 DMEK This is an example of the bubble that can be seen in the positioning, grafts, on the other hand, enjoy a supine position one day after DMEK surgery. restrictions rate of just above 1%.14

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 23 THE ART OF CORNEAL TRANSPLANTATION

covery with a single the perioperative care of corneal procedure. Phakic transplantation. Working together patients over 50 with cornea surgeons will allow years old who have for fl uid comanagement and moderate guttata undoubtedly better outcomes for may even benefi t our patients, as the ultimate goal from a proactive of any keratoplasty is to improve approach. We quality of life through increased know endothelial vision and/or comfort. RCCL cell loss accelerates 1. Amouzegar A, Chauhan SK, Dana R. Alloimmunity following cataract and tolerance in corneal transplantation. J Immunol. surgery, which 2016;196(10):3983-91. 2. Huang A, Bogucki J, Sheybani A. Faculty of 1000 could turn a mild evaluation for Endothelial cell loss and visual outcome of deep anterior lamellar keratoplasty versus pene- FED case into a se- trating keratoplasty: a randomized multicenter clinical vere case requiring trial. F1000Prime. December 2011. Ideal donor attachment from DMEK surgery looks like 3. Daneshgar F, Fallahtafti M. ‘Expanding bubble’ this one-week postoperatively. an EK. modifi cation of ‘big-bubble’ technique for performing maximum-depth anterior lamellar keratoplasty. Eye (Lond). 2011;25(6):803-8. Postoperative stability following LOOKING TOWARD 4. 2016 eye banking statistical report. Eye Bank Asso- a DSAEK may take four to six THE FUTURE ciation of America. 2017:5. 5. 2017 eye banking statistical report. Eye Bank Asso- months and delay a prescription The future of lamellar kerato- ciation of America. 2018:9. update until then. In contrast, plasties is bright. Since 2006, 6. Le R, Yucel N, Khattak S, et al. Current indications and surgical approaches to corneal transplants at the a DMEK mimics normal anat- femtosecond lasers have been used University of Toronto: a clinical-pathological study. Can J Ophthalmol. 2017;52(1):74-9. omy and is essentially refrac- to produce custom trephination 7. Von Marchtaler PV, Weller JM, Kruse FE, et al. Air tive-neutral, creating a negligible patterns. Femtosecond laser-en- versus sulfur hexafl uoride gas tamponade in Descem- et membrane endothelial keratoplasty: a fellow eye hyperopic shift of only about abled keratoplasty has been comparison. Cornea. 2018;37(1):15-9. +0.25D compared with a +1.00D praised for achieving better donor 8. Hlinomazová Z, Horácková M, Pirnerová L. DMEK (Descemet membrane endothelial keratoplasty)—ear- to +1.50D shift in a DSAEK. alignment, resistance to leakage, ly and late postoperative complications. Cesk Slov Oftalmol. 2011;67:75-9. DMEK patients may be ready for faster healing and less postopera- 9. Lie JT, Birbal R, Ham L, et al. Donor tissue prepara- an updated prescription in one tive astigmatism. With the emer- tion for Descemet membrane endothelial keratoplasty. J Cataract Refract Surg. 2008;34(9):1578-83. to three months. Nearly 50% of gence of femtosecond technology, 10. Tenkman LR, Price FW, Price MO. Descemet DMEK patients achieve 20/20 six improvement in descemetorhexis membrane endothelial keratoplasty donor prepara- tion: navigating challenges and improving effi ciency. months postoperatively, and some is being examined and may prove Cornea. 2014;33(3):319-25. 14 11. Veldman PB, Dye PK, Holiman JD, et al. Stamping surgeons boast a higher rate. to be a useful adjunct in DMEK an S on DMEK donor tissue to prevent upside-down A much smaller percentage of and DSAEK cases.17 Pre-DMEK grafts: laboratory validation and detailed preparation technique description. Cornea. 2015;34(9):1175-8. patients who have had a DSAEK procedures, which are thought 12. Price MO, Scanameo A, Feng MT, et al. Descemet’s achieve 20/20, and they only do to include Dua’s layer, are being membrane endothelial keratoplasty: risk of immuno- logic rejection episodes after discontinuing topical so when very thin tissue is used. seriously studied now. At 25µm to corticosteroids. Ophthalmology. 2016;123(6):1232-6. More often than not, patients end 30µm in thickness, these kerato- 13. Marques RE, Guerra PS, Sousa DC, et al. DMEK versus DSAEK for Fuchs’ endothelial dystrophy: a up with a BCVA ranging from plasties have an advantage over meta-analysis. Eur J Ophthalmol. April 1, 2018. [Epub 15 ahead of print]. 20/20 to 20/60. the ultra-thin 10µm to 15µm 14. Deng SX, Lee WB, Hammersmith KM, et al. Unfortunately, astigmatism cre- DMEK donors.18 Descemet membrane endothelial keratoplasty: safety and outcomes: a report by the American Academy of ated by a DSAEK is posterior and Ophthalmology. Ophthalmology. 2018;125(2):295-310. not easily measurable and, there- ur role as optometrists goes 15. Guerra FP, Anshu A, Price MO, et al. Descemet’s membrane endothelial keratoplasty: prospective fore, limits combined cataract pro- Owell beyond visual rehabil- study of one-year visual outcomes, graft survival and endothelial cell loss. Ophthalmology. 2011;118:2368-73. cedures to implant a non-toric in- itation. From surgical consulta- 16. Schoenberg ED, Price FW Jr., Miller J, et al. traocular lens (IOL). But, DMEK tion and preoperative YAG PI to Refractive outcomes of Descemet membrane en- dothelial keratoplasty triple procedures (combined patients are far more predictable. paracentesis and suture removal, with cataract surgery). J Cataract Refract Surg. Using a slightly adjusted myopic optometrists across the country 2015;41(6):1182-9. 17. Mckee HD, Jhanji V. Femtosecond laser-assisted target, toric IOLs can be success- are learning how to do more. graft preparation for Descemet membrane endothelial fully used.16 Commonly, EKs are Education expansion and pro- keratoplasty. Cornea. 2018;37(10):1342-4. 18. Narang P. Pre-Descemet’s endothelial keratoplasty. combined with cataract surgery gressive legislation has allowed Management of PHACO Complications: Newer Tech- for convenience and a quicker re- many to play an integral role in niques. 2014:110-4.

24 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 Earn up to NEW TECHNOLOGIES 2019 28 CE & TREATMENTS IN Eye Care Credits* GVCE OPTOMETRIC CORNEA, CATARACT REVIEW’S COMMITMENT TO CONTINUING EDUCATION AND REFRACTIVE SOCIETY SAN DIEGO APRILAPRIL 1111-14, -14, 14 2012019 9

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Three Ways to Register A limited number of rooms have been Online: www.reviewsce.com/sandiego2019 reserved at $269 plus tax per night. Please make reservations with the hotel Call: 866-658-1772 • E-mail: [email protected] directly at 1-888-421-1442. For group rate, mention “Review’s New Technologies and Convenient opportunities to register for one or both meetings.** Treatments in Eye Care”.

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**Additional registration fees if attending both meetings. Agenda subject to change. RGVCE partners with Salus University for those ODs who are licensed in states that require university credit. See www.reviewsce.com/events for any meeting changes or updates. POST-CATARACT SURGERY INFLAMMATION: A Toxin OR A Bug?

Although rare, TASS and endophthalmitis are possible complications, and clinicians must be able to recognizing the difference.

By Barbara J. Fluder, OD

hile cataract ? toxic substances break down surgery has the corneal endothelial become an junctions, causing the viable Wincredibly remaining cells to spread safe outpatient procedure, out over the damaged area it’s still surgery, and more in an effort to maintain than 738,000 surgical site the endothelial pumping infections occur every year system. If the remaining involving outpatient surgery functional cells are unable patients in the United States.1 to compensate for the loss, With the aging baby boomer it can cause permanent generation, the number of corneal edema. Due to cataract surgeries is expected its inability to regenerate to rise, and clinicians must and replace dead cells, the be prepared to handle Diff use limbus-to-limbus corneal edema and anterior corneal endothelium is often segment infl ammation noted in a patient with TASS. the possible increased Reprinted with permission from Deschênes J.11 the most damaged structure. prevalence of complications. If the trabecular meshwork Two in particular—toxic anterior treatment paths—one of which is damaged as well, it can cause segment syndrome (TASS) and requires swift changes to the surgical decreased aqueous outfl ow, endophthalmitis—are often protocol and prompt reporting to peripheral anterior synechiae and confused and pose signifi cant risk if state and local health departments. increased intraocular pressure.2 they arise. Four situations can lead to TASS:2 Both can present early in the A TOXIC SITUATION post-op period and share similar TASS occurs when toxic substances Inadequate sterilization of symptoms such as decreased visual enter the anterior chamber and 1instruments. To avoid this acuity, redness and pain. The pain cause a sterile, noninfectious concern, manufacturers of reusable is usually mild with TASS but postoperative infl ammatory handpieces recommend the is often a deep ocular pain with response. Signs and symptoms of instruments be fl ushed with 120cc endophthalmitis. Signs can be TASS present within 12 to 24 hours of sterile de-ionized or distilled similar as well, including hypopyon, of cataract or refractive surgery water. anterior chamber reaction such as and can include hypopyon, fi brin fi brin formation and corneal edema. formation in the anterior chamber, ABOUT THE AUTHOR Endophthalmitis may show a vitritis corneal edema, irregular pupil, and loss of red refl ex. decreased visual acuity, mild pain Dr. Fluder practices at While they can present with and redness. Cellular necrosis and Williams Eye Institute in similar signs and symptoms, apoptosis occur, resulting in acute Merrillville, IN. they have different etiologies and postoperative infl ammation. The

26 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 Enzymes and detergents remain salt solutions. Any changes in pH, epinephrine is preferred, although 2on cleaned instruments. This osmolarity or ionic composition corneas exposed to 0.05% sodium can be especially problematic with of balanced salt solutions can also bisulfi te have not shown any multi-specialty surgical centers cause infl ammation and damage to functional or structural damage to that use enzymes and detergents the corneal endothelium.3 the corneal endothelium.4 generously to clean off tissue left on In 2005, seven surgery centers surgical instruments from several TALES OF CONTAMINATION across six states experienced a TASS types of surgery. Any residue that Several products containing outbreak related to a balanced remains on the instruments from preservatives and other additives salt solution contamination.5 this cleaning process can cause have been linked to TASS: Of 112 patients diagnosed with infl ammation. Better education can In December 2017, the American TASS from July 19, 2005 through help multispecialty surgical centers Society of Cataract and Refractive November 28, 2005, 89% had and hospitals understand that Surgery (ASCRS) published a been exposed to a single brand ophthalmic surgery rarely leaves clinical alert regarding intraocular of balanced salt solution, AMO tissue on instruments, and the use of use of epinephrine to maintain Endosol, manufactured by Cytosol these detergents and enzymes, which mydriasis during cataract surgery. Laboratories and distributed by can be a cause of infl ammation, may According to the alert, in January Advanced Medical Optics.5 No not be necessary.2 2017 PAR Pharmaceutical began signifi cant breaks in sterile technique shipping a new formulation of or instrument reprocessing occurred. Endotoxin contamination epinephrine that contained 0.457mg Fourteen balanced salt solution lots 3during instrument sterilization. of sodium metabisulfi te and 2.25mg were tested and fi ve had elevated Even though gram-negative bacteria, of tartaric acid per ml. While there levels of endotoxin. The product which can reside in water baths is no published data or experience was recalled, effectively containing and autoclave reservoirs, are killed with intracameral administration the outbreak.5 during autoclaving, heat-resistant of solutions containing tartaric Another uptick of TASS occurred endotoxins from the bacteria can acid, ASCRS had become aware of in October 2006 at a 25-bed remain on instruments. The water several reports of TASS associated community hospital in Maine.6 used for these cleaning procedures with inadvertent use of the PAR The facility’s ophthalmologist must be changed regularly to avoid epinephrine.3 noted increased infl ammation this complication. Since then, the indication of and decreased visual acuity in use and maintenance of mydriasis eight out of 10 cataract surgery Preservatives from products during intraocular surgery has patients in one day.6 To prevent 4and medications. Products been removed from the product’s further cases, the surgical team used during intraocular surgery, and prescribing information. The 30ml suspended surgery and implemented intracameral drugs and balanced bottles of epinephrine salt solutions used in the anterior are clearly labeled chamber, must all be preservative- “not for ophthalmic free.2 Preservatives or stabilizing use,” although the agents used in ophthalmic solutions 1ml single-use vials can be toxic to the corneal are not.4 endothelium, leading to TASS. Some products The most common preservative is contain 0.1% benzalkonium chloride. While this bisulfi te, which is product is relatively safe when used used to improve on the ocular surface, it can cause stability by delaying corneal edema and endothelial cell the oxidation of the damage when it enters the anterior active substance. chamber. Stabilizing agents such This agent can cause as bisulfate are also toxic to the damage to the corneal corneal endothelium if it enters the endothelium. Ideally, anterior chamber. This agent is often preservative-free and Anterior chamber infl ammation with hypopyon. found in epinephrine and balanced bisulfi te-free (PFBF) Reprinted with permission from Chaudhry IA, et al.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 27 POST-CATARACT SURGERY INFLAMMATION: A TOXIN OR A BUG? Photo: Nick Mamalis, MD CONTROL AND REPORT BEWARE THE BUGS Once an infectious etiology Endophthalmitis is an infl ammatory has been ruled out, patients reaction of the intraocular should start aggressive topical fl uid and tissues as a result of anti-infl ammatory therapy with a microbial organism entering prednisolone 1% or similar steroid the eye. Once bacteria enter every hour, with daily monitoring the eye, they proliferate rapidly for resolution of anterior chamber because the vitreous acts as an infl ammation, corneal edema and excellent medium, and initiates the intraocular pressure control. infl ammatory cascade.1 In mild cases, patients usually Over an eight-year period from improve quickly with no 1994 to 2001, there were 1,026 This patients has corneal striae and permanent damage. Moderate presumed endophthalmitis cases out folds associated with TASS. cases usually resolve within of 477,627 cataract surgeries—an three to six weeks with possible incidence rate of 2.15 per 1,000.7 these changes: switched the residual corneal edema or damage. Signs and symptoms usually begin epinephrine to a preservative- Severe cases can cause permanent two to 10 days postoperatively and free formulation; began changing damage leading to corneal include decreased visual acuity, the ultrasonic bath solution used transplant, cystoid macular edema, deep ocular pain and redness. The to clean surgical instruments permanently dilated pupil and average acute onset is between 72 twice a day instead of once; used glaucoma due to damage to the and 96 hours after surgery. Delayed- medications with different lot trabecular meshwork.2 onset endophthalmitis generally numbers for future surgeries; used TASS outbreaks should be occurs greater than six weeks after personnel with more experience reported to both state and local surgery. Slit lamp examination with the ophthalmologist; had the health departments. Outbreak often reveals lid edema, hyperemia, manufacturer inspect the autoclave investigation assistance can be corneal edema, anterior chamber to ensure it was functioning obtained from the Centers for cells and fl are, keratic precipitates, normally; changed the topical Disease Control and Prevention’s hypopyon, fi brin formation, vitritis iodine antiseptic to single-use Division of Healthcare Quality and loss of red refl ex.1 vials; and began using a new Promotion. The Intermountain Acute-onset endophthalmitis phacoemulsifi cation tip with each Ocular Research Center at the is usually caused by coagulase- new patient.6 University of Utah and Emory negative gram-positive species such With these changes in place, University Eye Center can both as Staphylococcus epidermidis, the ophthalmologist performed assist with prevention and Staphylococcus aureus, cataract surgery on four patients treatment. TASS cases associated Streptococci, Enterococcus, and the following week—and all with a certain product can be about 25% of all cases are caused four developed TASS. The team reported to the Food and Drug by gram-negative species such as suspended cataract surgery again Administration’s Medwatch Pseudomonas aeruginosa. Delayed and made further adjustments to Program.2 onset endophthalmitis is usually the protocol: new cannulas for each procedure; a new lot of balanced salt Avoiding Preservatives solution; rinsing equipment removed Currently, only a few manufacturers produce PFBF epinephrine. from the ultrasonic cleaning bath Belcher Pharmaceutical, a small company in Largo, Fla., produces with sterile distilled water instead of PFBF, and Imprimis Pharmaceuticals makes a non-preserved, tap water; and discontinuing use of methylparaben-free epinephrine. Compounding 1.5% phenylephrine enzymatic cleaner in the ultrasonic with 1.0% lidocaine without bisulfi te is also an option. Omidria bath. In addition, they performed (Omeros) contains 1% phenylephrine and 0.3% ketorolac once an endotoxin test on the solution diluted and helps to maintain mydriasis. Although American Regent from the ultrasonic bath, which changed their epinephrine formulation in 2012 to contain bisulfi te, came back positive. Patients who they planned to re-released the PFBF formulation in May 2018 after underwent surgery following these ASCRS reached out to stress the need for such a formulation.4 changes all had successful surgery.6 There has been no update by American Regent as of August 2018.

28 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 caused by Propionibacterium Concomitant steroid use to randomized study would help to acnes, coagulase-negative and decrease infl ammation remains determine the effi cacy of newer Corynebacterium species.1 controversial.9 systemic and topical medications Many of these organisms are part The presenting visual acuity in the treatment of postoperative of the natural eyelid and nasal fl ora, is a good predictor of fi nal endophthalmitis.8 and conditions such as blepharitis visual outcome and often aids in and nasolacrimal infections can determining the best course of ptometrists are comanaging increase the risk of endophthalmitis. treatment: Omore cataract surgery patients Patients with systemic infections, • Hand motion or better. as baby boomers continue to age. diabetes and immunocompromise Treatment usually consists of Although both are rarities, TASS are also at a higher risk for a vitreous tap and injection of and endophthalmitis are possible infection. Bacteria can enter the eye intravitreal antibiotics. The vitreous complications every OD must be via breaks in the sterile fi eld from fl uid is sent for a gram stain and prepared to diagnose and manage events such as improper draping culture. If the vitreous is too dense should it arise. Their similar and prepping of the surgical area, and consists of infl ammatory presenting signs and symptoms complex and prolonged surgeries, fi brin, an aqueous sample may be may cause initial confusion, and and inadequate sterilization of obtained via an anterior chamber recognizing and understanding surgical equipment.7 paracentesis. Vitreous tap cultures the differences between the two Postoperatively, delayed are positive 56% to 70% of the conditions is the key to initiating wound healing can also lead to time, while an anterior chamber timely and appropriate treatment endophthalmitis. Posterior capsular paracentesis is positive in about and referral to save our patients’ 8 tears, wound leaks, contaminated 40% of cases. vision. RCCL irrigation solutions and IOLs, • Light perception. Treatment 1. Progressive Surgical Solutions, LLC. TASS surgeon experience, incision size consists of a PPV with injection and Endophthalmitis. 2013. and angle can all be risk factors for of intravitreal antibiotics. The 2. Sabbagh MD, Omar Mekari. Update on endophthalmitis.8 vitrectomy allows for removal of Toxic Anterior Segment Syndrome. Rev Ophthalmol. March 16, 2007. the organism, reduction of vitreous 3. American Academy of Ophthalmology. THE NEEDLE AND KNIFE fi brin and membranes that could TASS etiology. www.aao.org/ Endophthalmitis treatment is guided lead to subsequent tractional focalpointssnippetdetail.aspx?id=35b758bf- 71a0-4264-bdb6-62d4a7f5be12. Accessed by the Endophthalmitis Vitrectomy retinal detachment and improved January 14, 2018. Study (EVS), which recommends an penetration of the antibiotics. 4. American Society of Cataract and Refractive Surgery. Clinical Alert: Intraocular injection of intravitreal antibiotics Samples of the vitreous at the time use of epinephrine to maintain mydriasis along with either a vitreous biopsy of the vitrectomy are sent for gram during cataract surgery. December 13, 2017. or PPV. The injections pass the stain and culture. 5. Kutty PK, Forster TS, Wood-Koob C, et al. Multistate outbreak of toxic anterior blood-retinal barrier and often Patients with no improvement segment syndrome 2005. J Cataract Refract achieve successful therapeutic from a vitreous tap and injection Surg. 2008;34(4):585-90. drug levels. Typically, treatment should have a vitrectomy followed 6. CDC MMWR Weekly. Toxic anterior segment syndrome after cataract surgery- involves vancomycin (1mg/0.1cc) by repeated intravitreal antibiotic Maine. 2006;56(25):629-30. and ceftazidime (2.25mg/.01cc). injection.8 7. West ES, Ashley Behrens A, McDonnell PJ, et al. The incidence of endophthalmitis after Photo: Nick Mamalis, MD The EVS shows that systemic cataract surgery among the U.S. Medicare antibiotic treatment has no benefi t. population increased between 1994 and While the antibiotics used in the 2001. Ophthalmology. 2005;112(8):1388-94. 8. Abelson MB, Kennedy K, Lilyestrom L. study, ceftazidime and amikacin, Unraveling the mystery of endophthalmitis. have limited gram-positive Rev Ophthalmol. January 24, 2008. coverage, newer fourth-generation 9. Tewari A, Shah GK. Cataract complications: the retinal perspective. Rev fl uoroquinolones have better Ophthalmol. August 16, 2006. effi cacy and broader coverage 10. Chaudhry IA, Al-Dhibi H, Al-Rashed W, et al. Endophthalmitis: experience from a when given systemically. Oral tertiary eye care center. IntechOpen. May 8, moxifl oxacin, for example, can 2013. achieve therapeutic levels in the 11. Deschênes J. Toxic Anterior Segment Syndrome (TASS). Medscape. May 3, TASS can cause both corneal edema aqueous and vitreous in a non- 2017. https://emedicine.medscape.com/ and stromal haze, as seen here. infl amed human eye. A large article/1190343. Accessed January 8, 2019.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 29 1 CE Credit (COPE APPROVED)

Transplantation for Limbal Stem Cell Defi ciency When severe disease calls for surgery, here’s how you can be prepared for the pre- and post-op care. By Cecelia Koetting, OD

orneal diseases, and our are important for the regeneration Acquired LSCD can occur from understanding of them, of the entire corneal epithelium.1 trauma due to alkaline and acidic have advanced signifi - The limbal stem cells produce the injuries, contact lens wear, ther- Ccantly over the last 15 basal cell layer of the epithelium.1 mal injury or iatrogenic causes.4 to 20 years. One such disorder is These basal cells migrate towards Infl ammatory issues such as chron- limbal stem cell defi ciency (LSCD). the center of the cornea in the ic limbitis and bullous keratopathy Diagnosis of patients with LSCD basal layer, moving up to become and neurotrophic keratopathy has greatly increased with techno- wing cells and then to become from trigeminal neuralgia, diabetes logical advancements of corneal surface cells, allowing for the con- mellitus, herpes simplex or herpes topography/tomography and tinued rejuvenation of the corneal zoster may also lead to LSCD.4,5 anterior segment optical coherence surface.1 This process of corneal Acquired LSCD can also be related tomography (AS-OCT). This has epithelium turnover takes approxi- to autoimmune disorders such as led to the need to improve treat- mately seven days.1 Stevens-Johnson syndrome and ment options for LSCD. Not only are the limbal stem mucous membrane pemphigoid.4 As optometrists, we are more cells responsible for the regener- familiar with non-surgical treat- ation of the corneal epithelium, DIAGNOSIS ment options for LSCD, but it is but they also create a barrier to Patients with LSCD present with also important for us to under- prevent conjunctival epithelial varying degrees of ocular signs, stand the surgical treatments and cells from migrating to the corneal depending on the severity and level how to care for these patients surface.2 of corneal conjunctivalization. postoperatively. As you can imagine, damage Symptoms may include decreased to or dysfunction of these limbal vision, photophobia, tearing, HOW LSCD OCCURS stem cells can be devastating to the blepharospasm and recurrent The cornea is comprised of six health and function of the cornea. pain.6 They may present with layers: epithelium, Bowman’s lay- In LSCD, the poorly functioning superfi cial punctate late fl uoresce- er, stroma, Descemet’s membrane, limbal stem cells are unable to in stippled staining at the limbus, Dua’s layer and the endothelium. properly regenerate the epithelial whorl-like epitheliopathy (Figure The epithelium—the outermost layer, resulting in replacement by 1), progressive ingrowth of opaque 3 layer of the cornea—is only fi ve to conjunctival goblet cells. ABOUT THE AUTHOR seven cells thick (about 50µm).1 Peripherally, the cornea is con- UNDERLYING CAUSES Dr. Koetting is the referral optometric care and tinuous with the conjunctiva and Limbal stem cell defi ciency can be externship program sclera with a 0.5mm to 1mm band either congenital or acquired, al- coordinator at Virginia Eye Consultants in Norfolk, of limbal stem cells at the corneo- though it is most often considered VA. She is a fellow of the scleral junction. an acquired condition. Congenital American Academy of Optometry and a trustee Limbal stem cells, which are causes of LSCD include aniridia of the Virginia Optometric continually shed into the tear fi lm, and ectodermal dysplasia.4 Association.

30 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 epithelium and superfi cial neovas- cularization.7 The conjunctivalized corneal surface stains abnormally because the conjunctival epitheli- um that has grown on the cornea is more permeable to the stain than true corneal epithelium.6 Patients with more severe dis- ease may present with recurrent or non-healing epithelial defects, stromal scarring, or melting.7 As the cornea decompensates, the pa- tient may experience more intense Fig. 1. At left, corneal staining in patient with early LSCD. Note the stippled, pain and loss of vision. elongated, almost pill like shape to the areas of staining. Middle, traditional whorl pattern staining with fl uorescein. Note that the pattern starts at the NON-SURGICAL TREATMENT limbus and begins to circle towards the apex of the cornea. At right, subtle The overall goal in managing pa- late staining inferior and temporal with fl uorescein of conjunctival cells on cornea in patient with LSCD. tients is to prevent disease progres- sion. So, regardless of what stage ally take patients off of these, if Both of these options have the of LSCD the patient presents with, possible. Concurrently, the patient potential to stop or reverse early management begins with address- can be started on long-term use of acquired LSCD.11,12 ing the underlying etiology, which ocular cyclosporine, which may is most often infl ammatory in help stabilize LSCD symptoms.8,9 SURGICAL TREATMENT nature. Many ocular medications Use of amniotic membrane grafts, The surgical journey of stem cell and over-the-counter artifi cial or long-term amniotic membrane transplantation started in 1984 tears contain preservatives, such as drops, helps to restore the func- with keratoepithelioplasty using benzalkonium chloride, which can tion of limbal stem cells that may cadaver corneas in an allograft cause or exacerbate infl ammation. only be “stunned” in patients with procedure, which was also used Removing these offending agents mild to moderate LSCD.10 later in 1994 in a variation of and replacing them with preser- Discontinuation of contact lens keratolimbal allograft.13,14 This vative-free alternatives is a good wear or refi tting patients into was followed shortly thereafter start to treating these patients. scleral lenses, which minimize in 1989 with limbal autograft Immediate use of topical trauma to the limbal area, can transplantation, which involved steroids can calm the reaction, help eliminate mechanical rubbing harvesting conjunctival and limbal although the intent is to eventu- and further corneal damage.11,12 tissue from the patient’s unaffected

Release Date: February 15, 2019 is jointly accredited by the Accreditation Council for Continuing Expiration Date: February 15, 2022 Medical Education, the Accreditation Council for Pharmacy Education, Estimated time to complete activity: 1 hour and the American Nurses Credentialing Center, to provide continuing Jointly provided by Postgraduate Institute for TM education for the healthcare team. Postgraduate Institute for Medicine and RGVCE JOINTLY ACCREDITED PROVIDER INTERPROFESSIONAL CONTINUING EDUCATION Medicine is accredited by COPE to provide continuing education to Educational Objectives: After completing this optometrists. activity, the participant should be better able to: • Discuss the needs and reasons for stem cell replacement. Faculty/Editorial Board: Cecelia Koetting, OD, referral optometric • Identify appropriate candidates for limbal stem cell transplantation. care and externship program coordinator at Virginia Eye • Describe the current process (and a bit of the history) of harvesting and growing limbal stem cells. Consultants in Norfolk, VA. • Recognize the pathophysiology of limbal stem cell diseases. Credit Statement: This course is COPE approved for 1 hour of CE • Explain the most up-to-date procedure(s) for limbal stem cell transplantation. credit. Course ID is 60687-PO. Check with your local state licensing • Discuss the comanagement of patients who received limbal stem board to see if this counts toward your CE requirement for relicensure. cell allograft. Disclosure Statements: Target Audience: This activity is intended for optometrists engaged in the care of patients with limbal stem cell diseases. Dr. Koetting: Nothing to disclose. Managers and Editorial Staff : The PIM planners and managers have Accreditation Statement: In support of improving patient care, this activity has been planned and implemented by the Postgraduate nothing to disclose. The RGVCE planners, managers and editorial staff Institute for Medicine and RGVCE. Postgraduate Institute for Medicine have nothing to disclose.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 31 TRANSPLANTATION FOR LIMBAL STEM CELL DEFICIENCY

eye.13,15 By 1995, an early version and Stevens-Johnson syndrome, of the living-related conjunctival can be treated with KLAL but Clinical Pearl limbal allograft technique used do- require that the eye remain con- Corneal punctate staining in nor limbal and conjunctival grafts trolled and quiet for at least a year patients with dry eye disease from any living relative.13,16 prior to surgery. (DED) appears diff erently from Here are the common surgical Conjunctival limbal autograft the punctate staining found in transplantation methods, in order (CLAU) makes use of the conjunc- LSCD patients. The staining in LSCD appears more elongated of their development: tiva and limbus from the unaffect- and pill shaped. Early on, the Keratolimbal allograft (KLAL) ed eye of a patient with LSCD. staining will be concentrated uses allogeneic limbal tissue Up to 40% of the stem cells can more peripheral near the limbal attached to a corneoscleral carrier be harvested from the donor eye area. As the disease progresses from a cadaveric donor. This without risk, and no systemic im- and worsens, the staining will procedure can be indicated for munosuppression is needed.13,18 spread centrally and become patients who have either bilateral This procedure is overall more diff use. As the natural LSCD without a related donor or extremely successful at 80% to migration of the epithelial cells a unilateral LSCD whose contra- 100% with between 25% and to the center, the whorl-like pattern will be noted spiraling lateral eye is not a viable donor.17 100% improvement in visual acu- from the limbus centrally to the 12,13 KLAL can be used in patients with ity. The rejection rate of these apex of the cornea. LSCD caused by aniridia, contact grafts is minimal, with 76% at lens wear or iatrogenic event with three years and 62% at six years primarily limbal damage. Severe after surgery.13,18 tiva is available that is lacking in conjunctival involvement decreas- Living-related conjunctival KLAL alone and increased limbal es the likelihood of success. For limbal allograft (LR-CLAL) uses tissue that is lacking in LR-CLAL instance, conjunctiva that has harvested limbal and conjunctival alone. Patients whose condition is chronic infl ammation or scarring tissue from the patient’s living severe enough to require C-KLAL will have decreased mucin and tear relative.13 It can be used in patients may also need restoration of the production, creating an increased with both unilateral and bilateral conjunctival fornices and possi- likelihood for keratinization of the LSCD, harvesting up to 40% of ble mucous membrane grafting. ocular surface.13,14 the donor’s limbal tissue with no Because of this, these patients are Other etiologies of LSCD, such risk to the donor (Figures 2 and often evaluated by oculoplastic as mucous membrane pemphigoid 3).13 This procedure harvests con- specialists before proceeding. siderable amounts of con- Cultured limbal epithelial junctiva along with the lim- transplantation (CLET) is the bal tissue and is well-suited most commonly used ex vivo for patients with signifi cant method for limbal stem cell trans- conjunctival defi ciency such plantation. Cultivated limbal stem as Stevens-Johnson syn- cells are harvested and grown on drome, mucous membrane a substrate to be later implanted pemphigoid and chemical into the patient’s cornea.4 The injuries.13 Failure risk is stem cells are harvested from higher in this procedure either the patient’s fellow eye, a since it is an allograft, so it cadaver or a living relative.4 Oral requires long-term systemic mucosa may also be used as a immunosuppression.13 tissue source. Combined conjunctival In autologous CLET, a limbal and KLAL (C-CL/ 2mmx2mm piece of limbal KLAL or C-KLAL) uses ca- stem cell tissue is excised from daveric keratolimbal tissue the superior limbus in the Fig. 2. A moderate LSCD patient pre- with LR-CLAL, helping to patient’s healthy eye, 1mm from operative for Ir-CLAL. Note the dullness and irregularity of the central cornea where the treat severe LSCD pa- either side of the corneoscleral 4,13 4,13,18 epithelium has begun to be replaced with tients. By combining the junction. The limbal tissue conjunctival cells. procedures, more conjunc- is then immediately cultured and

32 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 we must not only recognize the di- agnosis early but also understand how it can be surgically treated and managed in severe stages. RCCL

1. Remington LA. Clinical Anatomy of the Visual System. 2nd ed. St. Louis, MO: Elsevier; 2005 2. Dua HS, Azuara-Blanco A. Limbal stem cells of the corneal epithelium. Surv Ophthalmol. 2000;44(5):415-25. 3. Biber JM, Holland EJ, Neff KD. Management of ocular stem cell disease. Int Ophthalmol Clin. 2010;50(3):25-34. 4. Mannis MJ, Holland EJ. Cornea: Fundamentals, Diagnosis and Management. 4th ed. Philadelphia: Fig. 3. Same patient from Figure 4, one week postoperative after Ir-CLAL. You Elsevier; 2017. can see the recessed conjunctiva superior and inferior along the limbus. The 5. Atallah MR, Palioura S, Perez VL, Amescua G. Limbal stem cell transplantation: current perspec- patient’s central cornea has stain pooling as it continues to re-epithelialize, tives. Clin Ophthalmol. 2016 Apr 1;10:593-602. but there is no peripheral late staining. 6. Dua HS, Saini JS, Azuara-Blanco A, Gupta P. Limbal stem cell defi ciency: concept, aetiology, clinical presentation, diagnosis and management. seeded in one of multiple culture currence of LSCD, which can be Indian J Ophthalmol. 2000;48(2):83-92. mediums.4,13,18 After the cell-seeded treated with a repeat SLET.18 7. Kim BY, Riaz KM, Bakhtiari P, et al. Medically re- versible limbal stem cell disease: clinical features culture plates are allowed to and management strategies. Ophthalmology. grow for two to three weeks, the LONG-TERM MANAGEMENT 2014;121(10):2053-8. 8. Baradaran-Rafi i A, Javadi MA, Rezaei Kanavi M, surgeon then implants two to three Immunosuppression and control et al. Limbal stem cell defi ciency in chronic and delayed-onset mustard gas keratopathy. Ophthal- sheets of the cells in the patient’s of infl ammation both pre- and mology. 2010;117(2):246-52. diseased eye.4,13 postoperatively is key to achieving 9. Jadidi K, Ebrahimi A, Panahi Y, et al. Topi- cal cyclosporine A for mustard gas induced Studies of eyes having under- successful outcomes. Following the ocular surface disorders. J Ophthalmic Vis Res. gone CLET have reported success current Cincinnati Eye Institute 2015;10(1):21-5. 10. Zhao Y, Ma L. Systematic review and rates between 67% and 77%, and protocol, prior to surgery patients meta-analysis on transplantation of ex vivo cultivated limbal epithelial stem cell on amniotic yielded visual acuity improve- are prescribed oral prednisone membrane in limbal stem cell defi ciency. Cornea. ment results in 51% to 75% of 1mg/kg/day and tapered over one 2015;34(5):592-600. 11. Schornack MM. Limbal stem cell disease: patients.10,18-21 Patients undergoing to three months, oral valganciclo- management with scleral lenses. Clin Exp Optom. allografts vs. autografts had com- vir 225mg QD, trimethoprim/sul- 2011;94(6):592-4. 12. Jeng BH, Halfpenny CP, Meisler DM, Stock EL. parable success rates.19,20 Overall, famethoxazole (TMP/SMX) every Management of focal limbal stem cell defi ciency associated with soft contact lens wear. Cornea. CLET has a low complication rate, MWF, oral tacrolimus 4mg BID, 2011;30(1):18-23. with living donor grafts having the and oral mycophenolate mofetil 13. Holland EJ. Management of limbal stem cell defi ciency: A historical perspective, past, present, highest safety.18 (MMF) 1g BID.22 Valganciclovir and future. Cornea. 2015;34(Suppl 10):S9-15. 14. Thoft RA. Keratoepithelioplasty. Am J Ophthal- Simple limbal epithelial trans- and TMP/SMX are stopped at 12 mol. 1984;97(1):1-6. 22 plantation (SLET) is a newer months. Tacrolimus is tapered 15. Kenyon KR, Tseng SC. Limbal autograft trans- plantation for ocular surface disorders. Ophthal- technique fi rst reported in 2012 to after six months and MMF after mology. 1989;96(5):709-22. treat unilateral LSCD. In SLET, a 12 months.22 16. Kwitko S, Marinho D, Barcaro S, et al. Allograft conjunctival transplantation for bilat- 2mm-by-2mm donor limbal tissue All medications are discontin- eral ocular surface disorders. Ophthalmology. is divided into eight to 15 small ued at approximately three years, 1995;102(7):1020-5. 17. Cheung AY, Holland EJ. Keratolimbal allograft. pieces and then distributed evenly but patients should continue to Curr Opin Ophthalmol. 2017;28(4):377-81. over an amniotic membrane glued be monitored closely for possible 18. Yin J, Jurkunas U. Limbal stem cell transplan- tation and complications. Semin Ophthalmol. to the recipient’s cornea.18 Reports rejection.22 This systemic protocol 2018;33(1):134-41. 19. Baylis O, Figueiredo F, Henein C, et al. 13 years show success rates at anywhere used over the last 10 years has of cultured limbal epithelial cell therapy: a review from 50% to 100% with up to shown to be safe and effective of the outcomes. J Cell Biochem. 2011;112(4):993- 1002. 75% improvement in two-line with minimal side effects and se- 20. Shortt AJ, Secker GA, Notara MD, et al. Trans- 18 plantation of ex vivo cultured limbal epithelial visual acuity. Failure rate is low vere adverse events in only about stem cells: a review of techniques and clinical and tends to occur within the fi rst 1.5% of the treated population.22 results. Surv Ophthalmol. 2007;52(5):483-502. 21. Haagdorens M, Van Acker SI, Van Gerwen V, et six months in higher risk patients Although LSCD has been recog- al. Limbal stem cell defi ciency: Current treatment (i.e., pre-existing symblepharon or nized as a corneal disease process options and emerging therapies. Stem Cells Int. 2016;2016:9798374. 18 penetrating keratoplasty). The for quite some time, it is becom- 22. Holland EJ, Mogilishetty G, Skeens HM, et al. Systemic immunosuppression in ocular surface most common complication after ing diagnosed and treated with stem cell transplantation: results of a 10-year the procedure is localized reoc- increasing frequency. As clinicians, experience. Cornea. 2012;31(6):655-61.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 33 CE TEST ~ JANUARY/FEBRUARY 2019 1. Where are limbal stem cells located? c. Stevens-Johnson syndrome. 8. Cultured limbal epithelial transplantation (CLET) a. Central cornea. d. Aniridia. can be performed with limbal stem cells harvested all the following except: b. Corneoscleral junction. a. Cadavers. c. Conjunctiva. 5. The fi rst limbal stem cell transplant was: b. Living relatives. d. Midperipheral cornea. a. Cadaver tissue. b. Mucosal tissue. c. The patient’s healthy eye. d. Living non-relatives. 2. In limbal stem cell defi ciency (LSCD), the limbal c. Living relative tissue. stem cells are unable to regenerate which corneal d. Tissue from the patient’s unaff ected eye. layer? 9. In simple limbal epithelial transplantation (SLET), donor tissue is: a. Stroma. 6. All of the following procedures can be performed b. Dua’s. for bilateral LSCD transplants except: a. Distributed over an amniotic membrane on the recipient’s cornea. c. Epithelium. a. Keratolimbal allograft (KLAL). b. Grown in a culture medium prior to d. Bowman’s. b. Conjunctival limbal autograft (CLAU). implantation. c. Living-related conjunctival limbal allograft (LR- c. Implanted directly into the recipient’s eye. CLAL). 3. Which common corneal fi nding is associated with d. Not used in this procedure. LSCD? d. Combined conjunctival limbal and KLAL a. Guttata. (C-KLAL). 10. Providing immunosuppression in stem cell b. Vogt striae. transplantation is: c. Whorl-like epitheliopathy. 7. How much living donor limbal tissue can be harvested without risk to corneal function? a. Not necessary. d. Amyloid deposits. a. 20%. b. Used only prior to surgery. b. 40%. c. Performed both pre- and postoperatively for 4. All of the following can cause acquired LSCD one month. c. 60%. except: d. Performed both pre- and postoperatively for up a. Chemical injury. d. 70%. to three years. b. Contact lens overwear.

EXAMINATION ANSWER SHEET Mail to: Jobson Healthcare Information, LLC, Attn.: CE Processing, 395 Hudson Street, 3rd Floor New York, New York 10014 Transplantation for Limbal Stem Cell Deficiency Valid for credit through February 15, 2022 Payment: Remit $20 with this exam. Make check payable to: Jobson Healthcare Information, LLC. Online: This exam can also be taken online at www.reviewsce.com. Upon passing the Credit: This lesson is approved for 1 hour of CE credit. Course ID is 60687-PO. exam, you can view your results immediately and download a real-time CE ceriticate. Jointly provided by Postgraduate Institute for Medicine and RGVCE. You can also view your test history at any time from the website. Salus University has sponsored the review and approval of this activity. Directions: Select one answer for each question in the exam and completely darken the appropriate circle. A minimum score of 70% is required to earn credit. Processing: There is a four-week processing time for this exam.

Answers to CE exam: Post-activity evaluation questions: Rate how well the activity supported your achievement of these learning objectives: 1. A B C D 1=Poor, 2=Fair, 3=Neutral, 4=Good, 5=Excellent 2. A B C D 11. Discuss the needs and reasons for stem cell replacement. 1 2 3 4 5 3. A B C D 12. Identify appropriate candidates for limbal stem cell transplantation. 1 2 3 4 5 4. A B C D 13. Describe the current process (and a bit of the history) of harvesting and growing limbal stem cells. 1 2 3 4 5 A B C D 5. 14. Recognize the pathophysiology of limbal stem cell diseases. 1 2 3 4 5 6. A B C D 15. Explain the most up-to-date procedure(s) for limbal stem cell transplantation. 1 2 3 4 5 7. A B C D 16. Discuss the comanagement of patients who received limbal stem cell allograft. 1 2 3 4 5 20. Based upon your participation in this activity, do you intend to change your practice behavior? (choose only one of the following options) 8. A B C D A I do plan to implement changes in my practice based on the information presented. 9. A B C D B My current practice has been reinforced by the information presented. 10. A B C D C I need more information before I will change my practice. 21. Thinking about how your participation in this activity will influence your patient care, how many of your patients are likely to benefit? Rate the quality of the (please use a number) material provided: 22. If you plan to change your practice behavior, what type of changes do you plan to implement? (check all that apply) 1=Strongly disagree A Apply latest guidelines B Change in pharmaceutical therapy C Choice of treatment/management approach 2=Somewhat disagree D Change in current practice referral E Change in non-pharmaceutical therapy F Change in differential diagnostics 3=Neutral G Change in diagnostic testing H Other, please specify: 4=Somewhat Agree 23. How confident are you that you will be able to make your intended changes? 5=Strongly agree A very confident B somewhat confident C unsure D not confident 24. Which of the following do you anticipate will be the Identifying information (please print clearly): 17. The content was evidence- primary barrier to implementing these changes? based. First Name A Formulary restrictions 1 2 3 4 5 Last Name B Time constraints Email C System constraints 18. The content was balanced D Insurance/financial issues The following is your: Home Address Business Address and free of bias. E Lack of interprofessional team support Business Name 1 2 3 4 5 F Treatment related adverse events Address G Patient adherence/compliance 19. The presentation was clear City State H Other, please specify: and effective. ZIP

1 2 3 4 5 Telephone # - - Fax # - -

25. Additional comments on this course: By submitting this answer sheet, I certify that I have read the lesson in its entirety and completed the self-assessment exam personally based on the material presented. I have not obtained the answers to this exam by fraudulent or improper means.

Signature: ______Date: ______Please retain a copy for your records. LESSON 117640, RO-RCCL-0219

34 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 Earn up to NEWNEW TTECHNOLOGIES

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**Separate registration required. RGVCE partners with Salus University for those ODs who are licensed in states that require university credit. See event websitebsite for cocompletemplp ete dedetails.taita ls. Administered by Partially supported by an GVCE unrestricted educational grant from REVIEW’S COMMITMENT TO CONTINUING EDUCATION *Approval pending Bausch & Lomb

Photos Courtesy of Disneyisney GrGroupoup MkMarkMarketingetinti g Corneal Consult By Aaron Bronner, OD

Was it a Failure or Rejection? Identifying the right diff erential in a troubled transplant patient makes a world of diff erence when determining corrective action.

59-year-old male presented to the clinic complaining of reduced vision in his Aright eye. He de- scribed his vision loss as generally painless (though he noted increas- ing photophobia) and occurring slowly over the last month. He stated, however, that his right eye is his poorer-sighted eye and said it was possible he had been experi- encing reduced acuity over a longer period of time.

OBTAIN OCULAR HISTORY We used retroillumination to highlight signifi cant epithelial edema in this The patient had a corneal trans- patient with a history of edematous PK. plant on his right eye 20 years ago due to keratoconus and then on counting on the left. Due to ante- ing to light. Examining the left eye his left eye three years later. His rior media opacity, an intraocular showed normal anterior segment postoperative course was unre- pressure (IOP) evaluation was structures, with the exception of a markable, though he noted that postponed until after the slit lamp PK. The interface had mild vascu- high levels of astigmatism limited exam. larization but was otherwise clear the vision in his right eye. At the The slit lamp exam of the right and compact. IOPs were 23mm Hg time he presented, the patient was eye showed normal lids. Injection, OD and 14mm Hg OS. not using any medicated drops but which was greatest nasally and was wearing glasses to see. interpalpebrally, was noted at 1+ DETERMINE THE PROBLEM to 2+ levels. The cornea showed Though we could not rule out CONDUCT PRELIMINARY a central penetrating keratoplasty corneal graft rejection, we made a TESTING (PK) with inferior vascularization primary diagnosis of endothelial Entrance testing showed the pa- to the graft-host junction of the graft failure. To rule out rejection, tient’s habitually corrected vision transplant, though the vessels did the patient was instructed to use to be hand motion on the right eye not bridge onto the transplant. The Pred Forte on his right eye every without improvement on pinhole graft was edematous with 3+ to two hours for a week. A baseline and 20/40 on the left, improving 4+ epithelial and stromal edema, pachymetry was gathered (1057µm to 20/25 through pinhole. It was though the peripheral cornea re- OD and 712µm OS) to assess the not possible to assess the patient’s mained clear. patient’s treatment response. He pupillary response in his right eye Views of the deep cornea and was sent home and asked to return due to a poor view of his iris, but anterior chamber (AC) were in a week. his left eye showed brisk direct extremely poor, though no keratic and consensual responses. Full and precipitates (KPs) were seen, and REASSESS AT FOLLOW-UP confrontation visual fi elds, which the AC appeared to be quiet and After a week, the patient’s exam could only be grossly assessed on absent of cells. The iris detail was results had not changed. Vision, the right eye, were full to motion poor, but with magnifi cation of the IOP and pachymetry were stable. on the right and full to fi nger slit lamp, the pupil was seen react- The slit lamp exam on the right eye

36 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 showed no reduction in edema and failing, their average life expectan- more permanent the damage to the still no visible KPs or intraocular cy is 10 to 20 years. Endothelial transplant and the higher the risk injections. At this point, the diag- graft failure manifests as corne- of failure due to endothelial cell nosis was confi rmed, and we gave al edema, which is often mixed density loss. In cases where there the patient the option of a repeat stromal edema (stromal pleats is no resolution of edema with PK or a Descemet’s membrane and Descemet’s membrane folds) steroid use, the patient likely has endothelial keratoplasty (DMEK) and epithelial edema (microcystic underlying graft failure and needs behind the primary transplant. He corneal edema). It tends to occur an endothelial re-transplant, either elected to pursue the DMEK route. slowly and without infl ammation, via a DSAEK, DMEK or repeat The patient underwent surgery though if bullae form, pain can PK. uneventfully a month later. By develop. The current standard practice is the six-month postoperative visit, On the other side of our differ- to perform a lamellar transplant, spectacle corrected visual acuity ential is endothelial graft rejection. as repeat PKs are more prone to (VA) was limited to 20/60 minus, Though rejection is most likely complications and failure than though the patient was pleased to occur in the fi rst year postop- are original PKs and secondary with the outcome. eratively, later cases of rejection DMEKs and DSAEKs. There are do occur. Signs of this process are cases where a repeat PK, however, DISCUSSION keratic precipitates on the graft is worth considering. A patient presenting with signifi - and increasingly prominent corneal The patient noted that the vision cant corneal edema without appar- edema. Extracorneal infl ammation in his right eye had never been as ent corneal or AC infl ammation may also be present but should be good as the vision in his left, owing has a relatively straightforward relatively mild. In some cases of to astigmatism. Though second- differential diagnosis: viral endo- rejection, the corneal edema may ary DMEKs and DSAEKs have a theliitis, acute IOP spike (though be too profound to visualize KPs. more preferable safety profi le than we expect patients with a high In this case, it can be impossible to secondary PKs, do not expect these enough IOP to generate pain, this clearly distinguish rejection from posterior lamellar surgeries to is a trend and not a rule), hypox- failure on exam. improve anterior corneal irregu- ia from contact lens use, corneal In an eye with an endothelial larities caused by an original PK. transplant rejection and native or graft and signifi cant recent-onset A repeat PK may be able to do transplanted endothelium decom- corneal edema, use a high-dose just that. When we reviewed the pensation. In this case, we can im- steroid to differentiate failure from course and recovery of all avail- mediately rule out IOP and contact rejection. A few cases I thought able options, however, the patient lens infl uences. While viral endo- for certain were cases of failed felt his acuity prior to graft failure theliitis remains on the differential, grafts showed improved edema was strong enough to function in this patient with a history of PK and subsequent underlying KPs. and knew he would be happy if he but no history of viral eye disease, In cases where edema clears, make could get back to that level, so a it is more appropriate to consider a diagnosis of rejection. At this DMEK was settled on. endothelial graft rejection or fail- point, the patient should be very ure as the most likely suspects. slowly tapered on the steroid (over hen dealing with any new Note that all corneal transplants six to 12 months) but should also Wonset corneal edema in a involving the endothelium—PK, be indefi nitely maintained on a transplant setting, it is important to DMEK and Descemet’s stripping steroid dose greater than what arrive at the right differential and automated endothelial keratoplasty was in effect when the rejection understand the diagnosis to effec- (DSAEK)—fail eventually. Though episode occurred. The longer a tively shape short- and long-term some transplants last longer before rejection episode goes on for, the patient care. RCCL

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 37 Fitting Challenges By Vivian P. Shibayama, OD

Depth Charge Undercorrected cylinder hindered the binocularity of this athlete. Here’s how pushing the CYL took care of it.

n optometry were placed on the school, we are patient and evaluated: trained to refract • 8.6/-1.00-0.75 patients to 20/20 x165 (VA of 20/15) Iand undercorrect, OD rather than over- • 8.4 (VA of 20/15) correct, cylinder in OS contact lens prescrip- The patient was tions. However, in extremely happy with patients with higher the in-offi ce perfor- visual demands, such mance of the trial as athletes, this may lenses, so they were lead to subpar visual dispensed. performance. If so, it’s time to challenge FOLLOW-UP our assumptions. The patient returned a week later and report- THE CASE This soft toric lens aligns at 6 o’clock. ed clearer vision and A 21-year-old male better binocularity. presented for an eye exam com- • -1.00 (VA of 20/15) OS The fi t was fi nalized. plaining that the vision in his right The patient’s slit lamp exam eye was blurry with contact lenses. revealed clear lids, lashes and con- DISCUSSION He went through several iterations junctiva with deep and quiet ante- Because each sport has its own with his previous optometrist but rior chambers OU. His cornea, lids unique demands, certain athletes said his vision never seemed right. and irises were clear and normal have more visual demands than He played collegiate golf, so his OU. His intraocular pressures others. When assessing small balls vision and depth perception were were 10mm Hg OD and 11mm that move at high speeds, VA and very important to his performance Hg OS. The undilated posterior contrast can have a large impact and ability to follow the small, segment evaluation was within on a golfer’s performance, which high-velocity balls. However, he normal limits. His autokeratom- can be negatively affected by axis was having trouble fi nding his golf etry readings were 43.00/43.50 mislocation, poor centration and balls, and he said his depth percep- @173 OD and 43.00/43.25 @162 imprecise cylinder correction.1,2 tion seemed off at close distances. OS. Some patients are more sensi- His presenting visual acuities I explained to the patient that tive to cylinder than others. We (VAs) were 20/25- OD and 20/15 the uncorrected astigmatism in know this because we all have OS, and he was wearing Acuvue his contact lens was affecting his those patients who can confi dently Oasys (Johnson & Johnson) with visual acuity and discussed further choose one or two even though a prescription of 8.4 -1.25 over-re- options with him, one of which in- we are making the most minute fraction plano OD and 8.4 -1.00 volved over-correcting the cylinder adjustments to check cylinder, over-refraction plano OS. with a soft toric lens. He was on whereas others hem and haw and board and wanted to give it a try. can’t decide. Patients with low- CONTACT LENS EVALUATION er power-to-cylinder ratios are Manifest refraction revealed: CONTACT LENS FITTING typically more sensitive to cylinder • -1.75 +0.50x070 (VA of 20/15) AND DISPENSING changes than those with higher OD The following Acuvue Oasys lenses ratios. For example, a -1.00D

38 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 Earn up to NEW TECHNOLOGIEST 2019 & TTREATMENTS IN 18 CE Credits* 9 EyeEyyeeGVCE Care CCaare REVIEW’S COMMITMENT TO CONTINUING EDUCATION

patient with 0.75D of cylinder will most likely see a difference with spherical contact lenses compared with glasses while a -6.00D with 0.75D of cylinder may not notice a difference. Sensitivity to changes in cylinder rotation is one of the reasons we BALTIMORE, MD are taught to undercorrect cylinder in contact lenses; the higher the cylinder, the more sensitive the NOVEMBER 1-3, 2019 patient will be to lens rotation, which causes blur.2 Some patients prefer constant slight blur over variable clarity, which makes Join Review’s New Technologies & Treatments in us more likely to undercorrect Eye Care November 1-3, 2019, at the Renaissance cylinder than to overcorrect it. In Baltimore Harborplace. this case, however, an overcorrec- tion of cylinder gave the patient two additional lines of acuity and Renaissance Baltimore Harborplace improved his visual performance. Located on coastal Inner Harbor, home to the National Aquarium. Luckily, we have several choices 202 E. Pratt Street when correcting cylinder. Planned Baltimore, MD 21202 replacement lenses are usually 410-547-1200 available in high oxygen mate- Discounted Room Rate: $169/night† rials and more cost-effi cient for patients. However, they are only Program Chair available in limited parameters, and it’s the practitioner’s job to decide if customization is need- ed. In this case, if a soft planned replacement toric hadn’t worked for this patient, a custom-ordered Paul M. Karpecki, OD, FAAO soft lens would have been the next step. If the patient is sensitive to See event website for additional information and faculty. axis rotation, rigid gas permeable, scleral or hybrid lenses would be worth looking into since the per- THREE WAYS TO REGISTER formances of these lenses do not ONLINE: www.reviewsce.com/baltimore2019 depend on rotational stability. CCL EMAIL: [email protected] 1. Kirschen DG, Laby DM. Contact lenses for sports: a new ball game. Cont Lens Spec. CALL: 866-658-1772 December 1, 2006. [Epub ahead of print]. 2. Bennet ES, Henry VA. Correction of astig- matism. Clinical Manual of Contact Lenses. 3rd edition. Philadelphia. 2009. Administered by Partially supported by an GVCE unrestricted educational grant from REVIEW’S COMMITMENT TO Bausch & Lomb CONTINUING EDUCATION *Approval pending

RGVCE partners with Salus University for those ODs who are licensed in states that require university credit. See www.reviewsce.com/events for any meeting schedule changes or updates.†Rooms limited. Practice Progress By Andrew Fischer, OD, Mile Brujic, OD, and David Kading, OD

Don’t be Nearsighted About Myopia With the groundbreaking new resources available, there’s no excuse not to take advantage of myopia management.

e often welcome IDENTIFY AND TREAT peripheral defocus and provide each year by Many additive factors contribute to adequate central vision. Inducing refl ecting on the development and progression of peripheral defocus decreases eye the preceding myopia, including genetics, mini- elongation and slows myopic W12 months to mal time spent outdoors, increased progression. identify changes we can make to near demand and binocular vision enhance our lives, personally and characteristics.5 ORTHO-K LENSES professionally. Instead of looking Emmetropia typically occurs While ortho-K has been shown to backwards, though, let’s shift our when a patient is six to eight years slow axial length (AL) progression focus forward to 2019 to pinpoint old. Any amount of myopia pre- by 52% and is the primary myopia what opportunities we can capi- ceding this age range is outside the management technique for many talize on to enrich the lives of our norm and increases the likelihood of practitioners, it may not be success- patients. With the myopia pan- a higher myopic prescription later ful in every patient.7 Patients with demic continuing to worsen—the on.5,6 It is important to monitor ex- greater than -4.00D of myopia, prevalence in the United States has isting myopes for changes of -0.50D -1.75D of with-the-rule astigmatism increased by 66% from the 1970s or more over a one-year span, as or -1.00D of against-the-rule astig- to the early 2000s, and by 2050 these indicate myopic progression. matism tend to be more diffi cult half of the world’s population will Treatment should be initiated at the fi ts. When working outside of these be myopic—this year is the perfect onset of myopia, regardless of the parameters, however, experienced time for optometrists to implement patient’s age. The most effective and ortho-K fi tters regularly achieve myopia management into their widely used forms of myopia man- great fi ts. practices.1,2 agement include orthokeratology Despite having limited experi- It’s time to rethink myopia. For (ortho-K) lenses, center-distance soft ence, new fi tters have also shown decades, we’ve thought of myopia multifocal contact lenses and topical impressive success rates. With the as a refractive error and failed to ac- atropine eye drops. help of empirical fi tting techniques, knowledge the extent of the impact When a myopic eye is corrected optometrists who have no previous the condition can have on patients. with spectacles or single-vision con- ortho-K experience achieved 80% Myopes face an economic burden tact lenses, central rays are focused success on the fi rst ordered lens.8 to satisfy their visual correction on the fovea, while peripheral rays If they were unsuccessful with one needs, experience a reduced quality are focused behind the eye. This lens, 95% were successful after one of life and are at increased risk for peripheral hyperopic defocus is lens change and 99.5% after two ocular health conditions.3,4 While thought to stimulate axial elonga- lens changes.8 our priorities tend to gravitate tion. While the mechanism by which A successful ortho-K fi t has been toward higher levels of myopia, it is atropine slows myopic progression described as having good centra- important to recognize that even a is not yet fully -1.00D prescription doubles the risk understood, of glaucoma and triples the risk of we know retinal detachment (Table 1).4 that the We must see myopia for what it goals of is: a progressive disease associated ortho-k and with long-term risks. With the mul- multifo- titude of technology, tools, research cals are to and information available to us, it address and would be a shame not to dive in to correct for Table 1. Odds ratios of diff erent ocular health risks associated myopia management. hyperopic with increasing myopia.4

40 REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 Pacific University College of Optometry Photo: Randy Kojima and Patrick Caroline, ATROPINE DROPS Topical atropine has been shown to reduce the progres- sion of myopia in children, with one study fi nding that 1% atropine had a 77% reduction in refractive progression and prevented AL progression after two years.11 As expected, Centrally, this patient has an irregular however, 1% atropine had sig- treatment zone with an optical zone Note the centration of the lens, bull’s-eye nifi cant side effects, including that is too large and would not provide pattern and textbook “V” pattern of AL near blur and photophobia.11 adequate “plus in the pupil.” The change in this ideal ortho-k fi t. Another study compared the optical zone parameters were switched from 6.0mm to 5.4mm for a better fi t. tion over the pupil, a bull’s-eye effects of various concentrations of fl uorescein pattern when the lens is atropine on myopia progression and steps to limit its progression, our on the eye, a bull’s-eye topographic concluded that a once-daily dose patients can enjoy a lifestyle free, pattern and acuities of 20/25 or of 0.01% atropine had the most for the most part, of the ocular risks better. Limiting myopic progression signifi cant effect on slowing myopia associated with high myopia. RCCL has been shown to be dependent progression.12 1. Vitale S, Sperduto RD, Ferris III FL. Increased preva- on the relationship between the Currently, many clinicians have lence of myopia in the United States between 1971-1972 pupil size and the optic zone of the accepted 0.01% atropine as the and 1999-2004. Arch Ophthalmol. 2009;127(12):1632-9. 2. Holden BA, Fricke TR, Wilson DA, et al. Global ortho-K lens—if the optic zone is standard dosage for myopia man- prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. much larger than the pupil, the pe- agement. Some argue that since 2016;123(5):1036-42. ripheral hyperopic defocus may not the second study mentioned above 3. Resnikoff S, Pascolini D, Mariotti SP, et al. Global magnitude of visual impairment caused by uncorrected be adequately corrected, making it reported a decrease in refractive refractive errors in 2004. Bulletin of the World Health important to maximize “plus in the progression rather than AL pro- Organization. 2008;86:63-70. 9 4. Flitcroft DI. The complex interactions of retinal, opti- pupil.” gression, 0.01% atropine should cal and environmental factors in myopia aetiology. Prog not actually be the concentration of Retin Eye Res. 2012;31(6):622-60. 5. Giff ord K. Preparing your practice for the myopia con- SOFT MULTIFOCALS choice. In reality, long-term use of a trol stampede. Cont Lens Spec. 2016;31:20-3, 25, 55. Similar to ortho-K, studies inves- higher concentration may stave off 6. Flitcroft DI. Emmetropisation and the aetiology of refractive errors. Eye (Lond). 2014;28(2):169-79. 13 tigating the effectiveness of mul- AL progression more effectively. 7. Chen C, Cheung SW, Cho P. Myopia control using toric orthokeratology (TO-SEE Study). Invest Ophthalmol Vis tifocals in managing myopia have Sci. 2013;54:6510-7. shown a reduced AL progression of hen presenting myopia man- 8. Davis RL, Eiden SB, Bennett ES, et al. Stabilizing myo- 10 pia by accelerating reshaping technique (SMART)-study up to 49%. These lenses are ideal Wagement options to patients three year outcomes and overview. Adv Ophthalmol Vis for patients who present with high and their parents, it is important to Syst. 2015;2(3). 9. Chen Z, Biu L, Xue F, et al. Impact of pupil diameter refractive errors. In our clinic, we set realistic goals and expectations. on axial growth in orthokeratology. Optom Vis Sci. use a center-distance daily dispos- Be open and honest by acknowledg- 2012;89(11):1636-40. 10. Anstice NS, Phillips JR. Eff ect of dual-focus soft con- able soft multifocal with a gradi- ing that, while we do everything we tact lens wear on axial myopia progression in children. ent +3.00 add. For patients with can to decrease AL progression, it is Ophthalmology. 2011;118(6):1152-61. 11. Chua W, Balakrishnan V, Chan YH, et al. Atropine for excess cylinder, spectacles can be not always possible to stop myopia the treatment of childhood myopia. Ophthalmology. worn over multifocals to provide in its tracks. As optometrists, we 2006;113(12):2285-91. 12. Chia A, Lu QS, Tan D. Five-year clinical trial on improved clarity. This treatment pledge to maintain or enhance the atropine for the treatment of myopia 2: myopia control with atropine 0.01% eye drops. Ophthalmology. option can be easily integrated into general health of our patients. By 2016;123(2):391-9. a practice already familiar with soft recognizing myopia as an ocular 13. Yam JCS, Jiang Y, Tang SM, et al. Low-concentration atropine for myopia progression (LAMP) study. Ophthal- contact lenses. disease and taking the necessary mology. 2019;126(1):113-24.

REVIEW OF CORNEA & CONTACT LENSES | JANUARY/FEBRUARY 2019 41 The Big Picture By Christine W. Sindt, OD

Singing the Blues A patient’s complicated ocular history results in an anterior staphyloma, leaving him few treatment options.

his 18-year-old male veloped a worsening anterior staphy- al course of action in staphyloma, has an ocular history loma and was referred for a patch it was contraindicated in this case of congenital Marfan’s graft consult and vision assessment. because of the size of the thinned syndrome and Axenfeld- Staphylomas result from intraocu- area and the risk of intraocular Rieger syndrome with lar pressure pushing the uvea into an bleeding. Surprisingly, however, he T 1 bilateral dislocated lenses and iris ectatic sclera. This causes the sclera pinholed to his baseline visual acu- hypoplasia. At age nine he suffered to have a bluish or even blackish ap- ity. Refraction yielded lower plus a large retinal tear, underwent a pars pearance as the underlying pigment- power with a signifi cant increase in plana vitrectomy (PPV) repair and ed tissue becomes visible through astigmatism, providing him 20/80 subsequently developed aphakic the thinning scleral tissue. While vision. glaucoma. In the right eye, he was posterior staphylomas are generally While a contact lens correction, treated for lattice degeneration with congenital, anterior staphylomas including the option of a scleral lens a 360-degree laser, providing him develop in response to trauma, such fi t, would likely yield better optics, good vision in that eye at 20/30. as surgery, or infection, as with it is contraindicated in this case Recently, he developed a choroi- fungal ulcers.1,2 Anterior staphylo- secondary to the risk of perforation. dal neovascular membrane in the mas are generally located over the Safety goggles were prescribed. RCCL

right eye and began treatments with ciliary body (ciliary staphyloma) or 1. (Corneal) Staphyloma, Anterior. Am J Neurora- Avastin (bevacizumab, Genentech). between the ciliary body and the diol. www.ajnr.org/ajnr-case-collections-diagnosis/ corneal-staphyloma-anterior. Accessed January He subsequently developed a limbus (intercalary staphyloma). 30, 2019. non-clearing vitreal hemorrhage Although reinforcement surgery 2. Grieser EJ, Tuli SS, Chabi A, et al. Blueberry eye: acquired total anterior staphyloma after a fungal requiring PPV. Unfortunately, he de- with a scleral patch graft is the usu- corneal ulcer. Cornea. 2009;28(2):231-2.

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