1. Explain why interest in lamellar keratoplasty has been renewed.

2. Describe the role of fibrin and cyanoacrylate glues in corneal surface ablation procedures.

3. List ways in which the risk for ectasia and other complications can be reduced.

4. Compare the advantages and disadvantages of the different methods of surface ablation.

5. Discuss the rationale for using riboflavin and an ultraviolet laser to enhance corneal strength.

Lamellar Keratoplasty
Herbert E. Kaufman, MD, Boyd Professor Emeritus of Ophthalmology, Pharmacology, and Microbiology, Louisiana State University School of Medicine, New Orleans

Background: avoid penetrating endothelial keratoplasty whenever possible; corneal transplants usually fail within 20 yr, so young person who undergoes transplantation probably will need at least one replacement; odds of success fall with each repeat transplant; lamellar keratoplasty fell out of favor due to poor results associated with rough corneal surface; interest revitalized with ability to make surface smooth; transplanted tissue need not be new or alive, as long as patient’s own endothelium good; can use “almost anything” as long as collagen matrix intact; endothelial rejection rare without penetrating keratoplasty; even vascularized corneas eligible; epithelium regenerates, even if keratocytes dead; intact collagen matrix is only requirement

Pearls: with scars and damage, anterior irregularities usually decrease visual acuity more than stromal haze; never graft translucent or partial scar without contact lens refraction; surgical procedure—de-epithelialization unnecessary if globe fresh; speaker uses 200-µ plate with 8.5-mm ring and free cap; leave corneal stroma 250 µ thick; eye banks can provide precut donor for anterior as well as posterior lamellar keratoplasty; phototherapeutic keratectomy (PTK) adequate for superficial opacities; fibrin glue (Tisseal)—minimal tensile strength; essentially “a blood clot”; good for adhesion of amnion or free conjunctival grafts after pterygium; completely biocompatible; eventually dissipates, with no effect on optical clarity; not recommended if anything pulls on tissue; residual scars—anterior optical coherence tomography helps determine scar depth; if scar remains, make another pass with microkeratome, then suture; laser in situ keratomileusis (LASIK)—fibrin glue secures flap, prevents epithelial or recurrent ingrowth; can be squirted under flap; cyanoacrylate tissue adhesive—not tissue biocompatible; can be used on surface, not under tissue; good tensile strength; can seal cataract wounds; forms thin relatively nonirritating coat that comes off; inexpensive (available in drugstores); can bind skin as well as sutures, without irritation or need for removal

Femtosecond laser (IntraLase): microkeratome has sloping edges and can slide off, making glue necessary; risk for poor outcome increases if epithelium not intact; with laser, can shape cyanoacrylate glue differently, “like a peg in hole”; will not slide; fibrin glue often not necessary; vision excellent with any lamellar procedure; if remaining stroma sufficient to support cornea, patient will do well

Deep anterior lamellar keratoplasty (DALK): useful for full-thickness scars, keratoconus, or any other condition requiring replacement of anterior cornea; can go down to Descemet’s membrane leaving smooth surface; resulting vision comparable to that achieved with penetrating keratoplasty, without entering eye or presenting risk for rejection; patient must have good endothelium; drawback—residual astigmatism similar to that associated with penetrating keratoplasty

Photorefractive Keratectomy (PRK) and LASIK
Mark S. Milner, MD, Associate Clinical Professor of Ophthalmology, Yale University School of Medicine, New Haven, CT

Major problems associated with laser vision correction: ectasia, halos or glare, dry eye symptoms; improve outcomes by detecting and preventing ectasia, maximizing tear film, preventing infection, and implementing appropriate procedural methods (eg, technology, maximizing tear film, postoperative healing)

Preoperative risk factors for ectasia

Ectasia: no single factor identifies patients at risk; best screening tool is multiple risk assessment; rare but possible after surface ablation; average time to presentation 12 to 19 mo; most cases evident by 36 mo; risk factors— include abnormal topography; low corneal or residual stromal bed thickness on pachymetry; age (inverse correlation with risk; speaker will not perform procedure on patients <21 yr of age); high myopia; history of atopic disease; enhancements

Pachymetry: central corneal thickness <500 µ; residual stromal bed thickness <250 µ (somewhat arbitrary; best data confirm risk definitely decreases when thickness >300 µ); risk highest when thinnest point of cornea coincides with steepest point

Topography: contraindications include keratoconus, pellucid marginal degeneration, keratoglobus; check carefully for forme fruste ectasia and corneal warpage; 19% of normal patients may have inferior steepening; asymmetric bow tie with skewed radial axis seen in 0.5% of normal patients; pellucid marginal degeneration—characterized by inferior steepening, “crab claw” or “dripping mustache” appearance; new developments—elevation-based topography; determines how much cornea deviates from reference shape (eg, Best Fit Sphere); examines anterior and posterior elevations, but posterior more important (+20 considered suspicious); compare to pachymetry of whole cornea

Pearls: forme fruste ectasia contraindicates laser vision correction (makes cornea thinner); when in doubt, do surface ablation; counsel patients with abnormal topography and obtain signed informed consent; do not perform LASIK if patient has inferior steepening, K >48, pachymetry <500 µ, stromal bed thickness <300 µ

Maximizing tear film: dry eye most common complaint after LASIK; may last 6 to 12 mo; underappreciated cause of other postoperative problems (halos, glare, vision fluctuation [“dysfunctional tear syndrome until proven otherwise”], poor vision quality, difference in refraction from intended result, vision regression [often caused by dry eye–induced inflammation], haze from surface ablation); management—diagnose dysfunctional tear syndrome promptly; obtain patient’s consent acknowledging discussion of risks; treat before vision correction

Treating causes of dysfunctional tear syndrome

Blepharitis and Meibomian gland disease: speaker recommends aggressive treatment with punctal plugs before and after LASIK; anti-inflammatory treatment (topical cyclosporine [Restasis]); consider surface ablation; to spare corneal nerves, consider nasal hinges instead of superior hinges; large hinges, thin flaps; candidates for topical cyclosporine—any patient with a low Schirmer’s score, blepharitis, history of contact lens intolerance, preoperative corneal staining, or dry eye symptoms

Innovative treatments: Vitamin A ointment (retinoic acid; replenishes goblet cells); hormones (medroxyprogesterone and topical androgens have anti-inflammatory effects); autologous serum; flaxseed oil; topical azithromycin (Azasite) and metronidazole for Meibomian gland disease; amniotic membrane bandage (ProKera); diquafosol tetrasodium (uridine nucleotide analogue P2Y; not yet approved by Food and Drug Administration)

Prevention of infection: lid hygiene critical; proper equipment sterilization (avoid cold sterilization); spore testing; use of disposable instruments; prophylactic use of broad-spectrum fluoroquinolones (gatifloxacin [Tequin], moxifloxacin [Vigamox]) starting 3 days preoperatively; emerging anti-infectives—daptomycin, linezolid (Zyvox), tygecycline (Tygacil)

Procedure

PRK: removal of epithelium with alcohol, Amoils brush, or transepithelial laser; easiest, least expensive of surface ablation methods, but speed of re-epithelialization questionable

Laser epithelial keratomileusis (LASEK): epithelium denatured with alcohol; laser procedure performed, epithelium replaced; may reduce postoperative haze; associated with less discomfort than PRK and LASIK; however, re-epithelialization takes longer due to denaturing

Epi-LASIK: uses epikeratome to remove epithelium; has advantages of LASEK plus preservation of viable epithelium; more expensive; main problem is rare risk of stromal incursion, with possibility of scarring

New developments in haze prevention: use of 0.02% mitomycin for myopes of -3 to -6 D or more (formerly reserved for at least -6 D), and 50 to 75 µ (formerly used only with thicknesses >80 µ); 12- to 30-sec application recommended, 2 min for retreatment; candidates include patients with history of radial keratotomy, PRK, LASIK, or penetrating keratoplasty; irrigation with chilled balanced salt solution (BSS) or application of frozen BSS “popsicles” (prevents keratocyte activation); 1000 mg vitamin C daily for 6 mo; use of ultraviolet-blocking sunglasses for 3 to 6 mo; autologous serum

New developments in flap creation: sub-Bowman’s LASIK—uses 100-µ flap; associated with less risk for ectasia and dry eye; femtosecond laser—associated with fewer complications (buttonholes, incomplete flaps) and more reproducible 100-µ flaps than with blade or keratome; better able to treat flat or steep corneas and narrow fissures; marketing advantage of “bladeless LASIK”; keratome—advantages include lower cost and less space

Custom vs conventional treatment: custom based on wavefront analysis, which requires wavefront analyzer; measures and treats some higher-order as well as lower-order aberrations; tailors treatment to each patient; lower-order aberrations are sphere or cylinder; most important higher-order aberrations (HOAs) are spherical and coma (most often responsible for halos and glare)

LASIK: advantages—easy to perform; less expensive than other procedures; removes less corneal tissue; does not cause “opposite corneal aberrations”; disadvantages—induces more higher-order aberrations than other procedures, with possible decreased quality of vision, higher risk for glare; not individualized; custom (wavefront) LASIK associated with less induced HOA, decreased risk for glare; more time-consuming, complicated, and expensive; removes more corneal tissue, requiring thicker cornea to start; new development—custom-optimized treatment; developed with idea that spherical aberration causes glare; wavefront-guided treatment reduces amount of induced HOA; custom-optimized treatment addresses lower-order aberrations plus custom HOA treatment based on individual K reading; involves use of WaveLight laser originally developed by Allegretto, now owned by Alcon

New developments: faster lasers, topographically guided lasers, presbyopia laser treatment (presbyLASIK)

PresbyLASIK: increases depth of focus, and low and moderate hyperopia

Pearls for improving outcomes: be selective (turn away poor candidates); be thorough (double-check every refraction); check for forme fruste ectasia; be open to new techniques; ask for help when necessary; be honest with patients, document discussions, and obtain informed consent

Ectasia and Healing: Cross-linking
Dr. Kaufman

Observations: edematous corneas thick but no stronger than normal; scars may be compact; cornea may appear thin, but “they’re tough as nails and they don’t become ectatic”; still no good way to measure corneal strength definitively

Cross-linking: contributes to strength; refers to bridges that hold collagen fibers together and make them strong; differences in amount of cross-linkage may figure in glaucoma as well as keratoconus and pellucid modular degeneration because optic nerve “gives”; cross-linking with riboflavin (vitamin B2 ) and ultraviolet (UV) light, hook fibers together to make strong nondeformable cornea

Procedure: remove or disrupt epithelium to increase permeability; add 2 drops riboflavin every 5 min for 25 min; then apply 370-nm UV laser for 30 min; activates groups on riboflavin molecule to hook proteins together, cross-linking collagen fibrils; also apply riboflavin every 5 min during irradiation; procedure kills all keratocytes and nerves in cross-linked area to depth of 300 to 350 µ; if cornea thin, endothelium obliterated (repopulates over several months)

Complications: persistent corneal edema; occasional melting, infection due to loss of sensation, and reduced tear flow; persistent stromal haze (rare); increase in measured intraocular pressure (IOP) relative to true IOP due to toughening of cornea; increased corneal hysteresis

Efficacy: keratoconus usually reversed (persists for ≥3 yr); possible improvement in topography; increased resistance to melting; improvement of any type of ectasia (eg, post-LASIK, pellucid marginal degeneration); suggested as possible treatment for corneal edema, due to increased resistance to corneal swelling

Stimulating healing: in rabbit experiments, speaker has found that even after removal, corneal sutures impart strength not seen otherwise; due to scars that “weld” cornea together; may explain why deep transplants seldom associated with ectasia, unlike procedures not involving sutures; however, growth factors (eg, TGF- β) or irritants such as talc applied to wound edge, may achieve similar result with LASIK flap, impart more tectonic strength, and “get rid of LASIK ectasia forever”