CLINICOPATHOLOGIC REPORTS, CASE REPORTS, AND SMALL CASE SERIES

SECTION EDITOR: W. RICHARD GREEN, MD

duce corneal ectasia. Because the flap ever, intrastromal corneal ring (ICR) Histopathological Analysis produced by LASIK never com- segments have shown promise as an of Post–Laser-Assisted In pletely heals, the residual bed likely alternative surgical option.3 We de- Situ Keratomileusis Corneal provides most of the support to scribe a unique case of visually sig- Ectasia With Intrastromal maintain corneal shape and func- nificant post-LASIK corneal ectasia Corneal Ring Segments tion, and keratectasia occurs when initially managed with ICR seg- the residual bed is unable to pro- ments that subsequently pro- Keratectasia, an acquired, nonin- vide this support. The 2 main risk gressed, thus requiring penetrating flammatory, outward bulging of the factors for post-LASIK keratectasia keratoplasty. , is associated with a progres- are a residual corneal bed of 250 µm 1 2 sive myopic shift in refraction, ir- or less and . Report of a Case. A 40-year-old regular , corneal thin- Although post-LASIK corneal ec- man underwent bilateral LASIK for ning, and scarring. It generally tasia may be managed conserva- a preoperative of occurs in the thinnest portions of the tively with rigid gas-permeable −1.50ϩ 2.25ϫ 090° OD and cornea, with a central or inferona- lenses, this nonsurgical treatment −1.75ϩ 2.50ϫ 090° OS, with sal paracentral predilection; how- option may fail or may represent an topographies that showed sym- ever, it may occur elsewhere. Ocu- unacceptable alternative for pa- metrical astigmatism in both eyes lar surgical procedures, particularly tients who underwent refractive sur- (Figure 1A). After myopic regres- lamellar refractive surgery (eg, laser- gery. In such cases, penetrating kera- sion, an enhancement was per- assisted in situ keratomileusis toplasty has been the principal formed to the patient’s right eye by [LASIK]), have been known to in- surgical treatment. Recently, how- relifting the flap 8 months after the

A B

47.0 Power: 44.8 D 49.0 Power: 45.6 D Radius: 7.53 mm Radius: 7.41 mm 46.5 105 90 75 48.0 105 90 75 46.0 From Vertex: 120 60 47.0 From Vertex: 120 60 Distance 0.00 mm Distance 0.00 mm 135 45 135 45 45.5 S-merid 0° 46.0 S-merid 0° 45.0 45.0 From : 150 30 From Pupil: 150 30 44.5 Distance 0.31 mm 44.0 Distance 0.24 mm 44.0 S-merid 316° 165 15 43.0 S-merid 306° 165 15 43.5 Simulated Keratometer: 42.0 Simulated Keratometer: 180 0 180 0 43.0 45.75 D (7.38 mm) @98 41.0 43.87 D (7.69 mm) @96 43.25 D (7.80 mm) @8 43.00 D (7.85 mm) @6 42.5 40.0 195 345 195 345 42.0 Astigmatism: 2.50 D 39.0 Astigmatism: 0.87 D 41.5 CIM: 0.64 210 330 38.0 CIM: 2.44 210 330 Shape Factor: 0.46 Shape Factor: 0.79 Diopter 225 315 Diopter 225 315 Pupil Size: 2.91 mm Pupil Size: 3.10 mm OD 240 300 OD 240 300 255 270 285 255 270 285 Extrapolated 1 mm Extrapolated 1 mm

C D

53.5 Power: 49.4 D 51.5 Power: 50.9 D Radius: 6.83 mm Radius: 6.63 mm 90 52.0 105 90 75 50.0 105 75 50.5 From Vertex: 120 60 48.5 From Vertex: 120 60 Distance 0.00 mm 135 45 47.0 Distance 0.00 mm 135 45 49.0 S-merid 0° S-merid 0° 47.5 150 30 45.5 150 30 From Pupil: From Pupil: 46.0 Distance 0.22 mm 44.0 Distance 0.00 mm 165 165 15 44.5 S-merid 294° 15 42.5 S-merid 0° 43.0 Simulated Keratometer: 41.0 Simulated Keratometer: 180 0 180 0 41.5 45.62 D (7.40 mm) @110 39.5 47.12 D (7.16 mm) @114 44.87 D (7.52 mm) @20 42.62 D (7.92 mm) @24 40.0 38.0 195 345 195 345 38.5 Astigmatism: 0.75 D 36.5 Astigmatism: 4.50 D 37.0 CIM: 4.39 210 330 35.0 CIM: 4.61 210 330 Shape Factor: 0.99 Shape Factor: 0.12 Diopter 225 315 Diopter 225 315 Pupil Size: 3.17 mm 240 300 Pupil Size: 1.81 mm 240 300 OD OD 255 270 285 255 270 285 Extrapolated 1 mm Extrapolated 1 mm

Figure 1. Corneal topographies of the right eye preoperatively (A), 1 year after enhancement (B), 2 years after enhancement (C), and 9 months after intrastromal corneal ring segment implantation (D).

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©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 first procedure. One month after en- hancement, uncorrected visual acu- ity (UCVA) was 20/25 OD and 20/20 OS, and best-corrected visual acu- ity (BCVA) was plano=20/25 OD and plano ϩ0.50ϫ180°=20/20 OS. The refractive correction was stable 1 year postoperatively, although some asymmetrical astigmatism was shown on topographies (Figure 1B). Fifteen months after enhancement, the patient began to complain of blurred, uncorrected vision in the right eye. This was found to be ow- ing to high irregular astigmatism that progressively worsened over the next 8 months. Twenty-three months af- ter enhancement, UCVA was 20/80 OD and 20/60 OS, and BCVA was −1.75ϩ4.75ϫ143°=20/30 OD and Figure 2. Clinical photograph of the right eye 1 day after the inferior intrastromal corneal ring segment −1.75ϩ2.00ϫ085°=20/20 OS. Ul- was implanted. Arrow indicates crystalline deposits around the intrastromal corneal ring segment; trasound pachymetry measured a arrowheads, incision. Inset, Higher magnification of the crystalline deposits. central thickness of 477 µm OD and 492 µm OS. Topography was sug- A gestive of corneal ectasia in the right eye (Figure 1C) and was unremark- able in the left eye. After discussing the options of rigid gas-permeable contact lenses, insertion of ICR seg- ments, or corneal transplantation, contact lenses were tried without success. The patient then elected to have 2 0.35-mm ICR segments placed in the right cornea in di- B vided sessions (Figure 2). The su- perior ring was placed using a con- ventional technique (ie, mechanical dissection), and 8 months later, the inferior ring was inserted using a femtosecond laser-created chan- nel. Although UCVA initially im- proved to 20/60 and BCVA im- ϩ ϩ ϫ proved to 1.00 1.50 045°=20/ C 25, ectasia progressed throughout the next year (Figure 1D). Ulti- mately, the patient’s UCVA deterio- rated to 20/100 with a BCVA of −3.25ϩ4.50ϫ125°=20/50. When the patient again proved intolerant to rigid gas-permeable contact lenses, a penetrating keratoplasty was performed. Gross examination of the 8.0- mm-diameter corneal button Figure 3. Photomicrographs from light microscopy of the central portion of the button, showing the inconspicuous laser-assisted in situ keratomileusis flap. Arrows indicate the laser-assisted in situ showed 2 ICR segments, one placed keratomileusis wound and the ectatic residual corneal bed. A few focal breaks were found in the Bowman superiorly and the other placed in- layer. The specimens were stained with hematoxylin-eosin (original magnification ϫ25) (A), periodic feriorly, with a 7.0-mm optical zone. acid–Schiff (original magnification ϫ25) (B), and toluidine blue (original magnification ϫ25) (C). The cornea was bisected for conven- tional histological analysis and trans- tions in the Bowman layer, and pe- lar LASIK scar was present along the mission electron microscopy. Light ripheral focal thickened areas where interface below the LASIK flap, microscopy showed a centrally the ICR segments were placed. A pe- which left a 218-µm residual stro- thinned cornea with focal disrup- riodic acid–Schiff–positive lamel- mal corneal bed (Figure 3A-C).

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©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 gen lamellae (Figure 4A and B). A The stroma around the ICR seg- ments stained more intensely with periodic acid–Schiff than normal corneal stroma do, and on transmis- sion electron microscopy, the stroma contained deposits of electron- dense granular material with inter- spersed empty spaces (Figure 4C). There was no histological or ultra- structural difference between the mechanically created vs the femto- B second laser-created intrastromal channels. Overlying the ICR seg- ments, a small area of epithelial hy- poplasia was present. Inside this area was a zone of epithelial hyperplasia that tapered centrally to normal mor- phology and thickness (Figure 4A).

Comment.Approvedforthetreatment of 1.0 to 3.0 diopters (D) of withupto1Dofastigmatism,4 ICRseg- ments correct refractive errors by act- ingasaspacerbetweencollagenlamel- lae. This induces a shortening of the corneal arc length with peripheral cor- neal steepening over the region of ICR segments and central corneal flatten- ing between segments.5,6 Because ICR segments induce a refractive correc- tion without removing corneal tissue C and may potentially reinforce the cor- neal stroma owing to the addition of material, they have been suggested as a reversible surgical option in patients withcornealectasia,especiallyinthose with keratoconus7 or post-LASIK cor- neal ectasia.8 Prospective results from 1-year follow-up in post-LASIK cor- neal ectasia cases suggest that ICR seg- ments can sometimes acutely reduce corneal steepening and astigmatism, thereby improving UCVA, BCVA, and topographic regularity.8 Our case is unique because it is one of only a few human histopathologi- cal specimens obtained from a cornea managed with ICR segments, and be- cause the ectasia progressed over the Figure 4. Photomicrographs from light microscopy of the midperipheral cornea stained with toluidine first year despite ICR segment implan- blue at original magnification ϫ10 (A) and original magnification ϫ25 (B), showing where the tation. It is also unique in that one ring intrastromal corneal ring segment had been implanted. Asterisks indicate silhouette of hexagonal segment. The distance from the anterior border of the segment to the anterior corneal surface measures was implanted using conventional 384 µm. Notice the laser-assisted in situ keratomileusis wound (arrows) above the implant. B, The techniques and the other using a fem- adjacent displaced collagen lamellae (arrowheads) are above and below the implant. The rectangle tosecond laser. Previous animal stud- indicates the area that was analyzed by transmission electron microscopy. C, On low-magnification ies5,9,10 that looked at the intrastromal transmission electron microscopy of the area inside the intrastromal corneal ring segment silhouette (asterisk), notice that wound healing around the implant consists of electron-dense granular material insertion of polymethyl methacrylate deposits intermixed with extracellular empty spaces (arrowheads) and persistently activated keratocytes prosthetic materials show keratocyte (arrows) (original magnification ϫ4750). activation, new collagen formation, andlipiddepositsinthecornealstroma Hexagonal silhouettes were pres- placed, with anterior and posterior around the implant. Our human his- ent where the ICR segments were displacement of the adjacent colla- topathological findings of electron-

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©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 densedepositscontaininginterspersed TE. A geometric model to predict the change proliferative sickle cell is in corneal curvature from the intrastromal cor- collagen fibrils, extracellular empty neal ring (ICR). Invest Ophthalmol Vis Sci. 1994; characterized clinically by a con- spaces (likely clefts formed from lipid 35(suppl):2023. cave tractional retinal elevation, reti- removal during processing), and per- 7. Colin J, Cochener B, Savary G, Malet F. Cor- recting keratoconus with intracorneal rings. nal nonperfusion, inner-layer breaks, sistentlyactivatedkeratocytesaresimi- J Refract Surg. 2000;26:1117-1122. absorption of laser by the outer layer, lar to these animal findings. The ex- 8. Kymionis GD, Siganos CS, Kounis G, Asty- and a split pattern on optical coher- rakakis N, Kalyvianaki MI, Pallikaris IG. tracellular lipid collections, which Management of post-LASIK corneal ectasia with ence tomography. Two cases of reti- likely correspond to the crystalline de- Intacs inserts: 1-year results. Arch Ophthalmol. nal schisis are described herein, both posits seen clinically, probably arise 2003;121:322-326. 3 9. Twa MD, Ruckhofer J, Kash RL, Costello M, featuring the conjunctival sickle sign from chronic mechanical irritation to Schanzlin DJ. Histologic evaluation of corneal and both eventually complicated by keratocytes that continually strive to stroma in rabbits after intrastromal corneal ring outer-layer breaks and retinal detach- heal the stromal wound. implantation. Cornea. 2003;22:146-152. 10. Rodrigues MM, McCarey BE, Waring GO III, ment that possibly might have been The breaks in the Bowman layer Hidayat AA, Kruth HS. Lipid deposits posterior prevented by timely laser treatment. could correspond to predisposition toimpermeableintracorneallensesinrhesusmon- keys: clinical, histochemical, and ultrastructural to keratoconus and ectasia. Al- studies. Refract Corneal Surg. 1990;6:32-37. Report of Cases. Case 1. A 44-year- though the reinforced stromal bed old African American woman com- was not strong enough to prevent plained that in recent months the vi- further ectasia from developing in sual acuity in her left eye had been this case, longitudinal studies have Schisis in Sickle Cell decreasing as a result of what she de- not yet addressed the overall long- Retinopathy scribed as “a moving veil.” She had term success or stability of ICR seg- been diagnosed with sickle cell dis- ments for corneal ectasia beyond 1 Retinal schisis is a rare but poten- ease, type SS, 17 years earlier. She had year postoperatively. These studies tially serious of sickle a history of multiple pulmonary em- are necessary to address whether the cell retinopathy.1 It is related to boli complicated by pulmonary hy- natural history of the ectasia changes chronic low-grade ischemia of the in- pertension, which had necessitated after ICR segment implantation. ner nuclear layer, which houses the placement of an aortic umbrella 2 Marc J. Spirn, MD Muellerian glia, the structural back- years earlier. She took warfarin so- Daniel G. Dawson, MD bone of the .2 Schisis as part of dium and folic acid. Her visual acu- Roy S. Rubinfeld, MD Christine Burris, OD A B Jonathan Talamo, MD Henry F. Edelhauser, PhD Hans E. Grossniklaus, MD

Correspondence: Dr Grossniklaus, BT428 Emory Eye Center, 1365 Clifton Rd NE, Atlanta, GA 30322 ([email protected]). C D Financial Disclosure: None. Funding/Support: This study was supported in part by grants RO1- EY-00933 and P30-EY-006360 from the National Eye Institute, Bethesda, Md, and an unrestricted grant from Research to Prevent Blindness, Inc, New York, NY. 1. Seiler T, Koufala K, Richter G. Iatrogenic kera- tectasia after laser in situ keratomileusis. J Re- E F fract Surg. 1998;14:312-317. 2. Randleman JB, Russell B, Ward MA, Thomp- son KP, Stulting RD. Risk factors and progno- sis for corneal ectasia after LASIK. . 2003;110:267-275. 3. Lovisolo CF, Fleming JF. Intracorneal ring seg- ments for iatrogenic keratectasia after laser in situ keratomileusis or photorefractive keratectomy. J Refract Surg. 2002;18:535-541. 4. Rapuano CJ, Sugar A, Koch DD, et al. Intrastro- mal corneal ring segments for low myopia: a re- portbytheAmericanAcademyofOphthalmology. Ophthalmology. 2001;108:1922-1928. 5. Fleming JF, Reynold AE, Kilmer L, Burris TE, Figure 1. Funduscopy, angiography, and optical coherence tomography results in patient 1. A, Drawing Abbott RA, Schanzlin DJ. The intrastromal cor- of the fundus showing the extent of schisis (hatched lines). B, Ocular coherence tomogram of the left neal ring: 2 cases in rabbits. J Refract Surg. 1987; macula. The Muellerian pillars indicate schisis. Photographs of the fundus of the left eye showing 3:227-232. neovascularization of the disc (C) and temporal retinal elevation (D). Fluorescein angiogram of the 6. Silvestrini TA, Mathis ML, Loomas BE, Burris arteriovenous phase focused on the fovea (E) and vessels of retinal elevation (F).

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