Terrien's marginal degeneration is a progressive bilateral peripheral corneal disorder that primarily affects the superior cornea, causing irregular astigmatism or ectasia in most cases.1,2 The typical findings include: corneal thinning and the presence of yellowish-white small stromal opacities in the superior-nasal quadrant, neovascularization, scarring, and lipid deposits at the edges of the area of thinning. Some variant forms even show prominent inflammatory signs. Terrien's marginal degeneration appears associated with pseudo-pterygium in 20% of cases, whereas it presents with spontaneous or small traumatic corneal perforation in 15%.2–5
The management of corneal ectasias, such as Terrien's marginal degeneration, is challenging due to severe corneal thinning that mainly occurs in the periphery. In addition, there are no definitive guidelines to correct these corneal disorders. Peripheral keratoplasty techniques have shown the most lasting effect and have been proposed for the treatment of sight-threatening complications, such as corneal perforation.1 However, these surgical techniques often require the use of large diameter grafts, which are more difficult to suture, entail a higher risk of intraoperative complications, such as Descemet's membrane perforation, and possess an increased chance of rejection.1,6 Moreover, recurrence of the original disease can complicate the long-term outcomes. Therefore, there is a need for finding new therapeutic options that can provide safe and effective treatment for these patients.
The effectiveness of corneal cross-linking (CXL) has been widely reported for the treatment of ectatic diseases, such as keratoconus and post-LASIK corneal ectasia,4,5,7 and also in infectious and non-infectious corneal melting.6 However, little has been published on the use of CXL for other ectatic disorders.1,8 We report the long-term outcomes of a patient with Terrien's marginal degeneration who underwent successful peripheral CXL in both eyes.
A 28-year-old man presented to our hospital in January 2008 complaining of a 5-year history of progressive reduction of visual acuity and increased astigmatism in the right eye. The patient did not present any significant systemic disorders. Slit-lamp examination and topography imaging (Orbscan; Bausch & Lomb, New York) confirmed the presence of bilateral Terrien's marginal degeneration, at a moderate stage in the right eye and at an earlier stage in the left eye (Figure A, available in the online version of this article). Further examination of the right eye showed uncorrected distance visual acuity (UDVA) of 0.05 decimal (20/400 Snellen), corrected distance visual acuity (CDVA) of 0.8 decimal (20/25 Snellen), with −14.00 diopters (D) (@ 95°) cylinder and +3.00 D sphere (Table 1). The left eye presented with UDVA of 0.45 decimal (20/44.4 Snellen) and CDVA of 0.9 decimal (20/22.2 Snellen), with −2.25 D (@ 85°) cylinder only. The patient did not tolerate his contact lenses and the high astigmatism forced him to wear glasses with fewer diopters than required. The topographical average keratometry (SimK) in the right eye was 10.50 D (@ 16°), the maximum keratometry (Kmax) was 51.80 D, and the minimum keratometry (Kmin) was 41.20 D (Table 1, Figure B, available in the online version of this article). In the left eye, SimK was 2.00 D (@ 2°), Kmax was 43.80 D, and Kmin was 41.90 D. Ultrasound pachymetry (Corneo-Gage; Sonogage, Inc., Cleveland, OH) showed a thinnest point of 443 μm in the peripheral superior right cornea and of 663 μm in the same area of the left eye. The thinnest point measured with the Orbscan was 483 μm in both eyes (Table 1). Anterior segment optical coherence tomography (AS-OCT) (Visante; Carl Zeiss Meditec, Oberkochen, Germany) corroborated these measurements (Figure 1). Based on these findings, together with the apparent rate of progression and the low risk of perforation due to sufficient corneal thickness,7,9 we decided to perform a prophylactic treatment with peripheral CXL in the right eye, aiming to treat the area of thinning.
(A–C) Images of the right eye showing the superior thinning of the cornea 4 years after corneal cross-linking. (D–E) Images of the left eye showing a slight decrease of the corneal thickness in the superior quadrants. Notice the slight increase of the pannus at the same level, especially in the right eye.
Comparison of Visual Acuity and Topographic Changes
Preoperative corneal topography showing the increased against-the-rule astigmatism and the anterior and posterior elevation of the cornea in the superior quadrants. (Top) Right eye, 2008. (Bottom) Left eye, 2012.
(A) Anterior segment tomography confirms the decrease in corneal thickness in the right eye, compared to (B) the left eye.
The treatment was performed according to the standard Dresden protocol (Table 2).10 Briefly, the corneal epithelium was removed with a golf blade after a 1-minute exposure to 20% ethanol, which delaminates the epithelial basement membrane,11 and a conjunctival peritomy of the invading superior limbus was performed. To focus the CXL treatment in the affected area only, an eccentric epithelium-off CXL procedure was designed by decentering the irradiation zone over the area of thinning in the superior periphery of the cornea. Direct exposure to the limbus was avoided by using a customized 4 × 5 mm arch-shaped opaque plastic mask. After the exposure, the conjunctiva was repositioned with four interrupted sutures of 10-0 nylon (Ethilon Nylon Suture; Ethicon, Somerville, NJ).
The postoperative drug regimen included ofloxacin 0.3% w/v (Exocin Ophthalmic Solution; Allergan, Inc., Irvine, CA) and dexamethasone 0.1% (Maxidex; Alcon Laboratories, Inc., Fort Worth, TX) eye drops every 2 hours during daytime for 3 days, until complete restoration of the corneal epithelium. Once the epithelium had healed, the antibiotic eye drops were stopped completely and the steroid drops were tapered down in a weekly fashion. The conjunctival sutures were removed at the 15th day follow-up visit.
Twenty days after surgery (Figure 2), visual acuity and refraction improved significantly, with UDVA of 0.3 decimal (20/66.7 Snellen) and CDVA of 0.7 decimal (20/28.6 Snellen), with −7.00 D (@ 100°) cylinder and +0.50 D sphere. Corneal topography also started showing clinically significant changes: SimK decreased to 9.10 D (@ 18°), with Kmax of 49.40 D and Kmin of 40.30 D.
Twenty days after corneal cross-linking, the right eye shows (A, B) the persistence of the superior thinning of the cornea, confirmed by (C) the anterior segment optical coherence tomography images. Despite this marked thinning, the visual acuity and the astigmatism improved significantly.
Ten months after the procedure, slit-lamp examination showed no signs of complications in either eye. In the right eye, the UDVA improved to 0.3 decimal (20/66.7 Snellen) and the CDVA reached 0.85 decimal (20/23.5 Snellen) with −4.00 D (105°) cylinder and +1.00 D sphere. These results correlated well with the topographic changes: SimK decreased further to 3.50 D (@ 16°), Kmax improved to 45.90 D, Kmin changed to 42.40 D, and the thinnest point remained stable at 482 μm. In the left eye, CDVA had not changed (0.9 decimal; 20/22.2 Snellen). However, we observed small changes in the topography: SimK increased from 2.00 to 2.80 D (@ 157°), Kmax increased from 43.80 to 44.10 D, and Kmin changed from 41.90 to 41.30 D, suggesting a slow progression of the disease. Thus, based on the initial good results from the CXL in the right eye, we recommended the same treatment for the left eye, but the patient decided to postpone the procedure.
The patient returned 4 years later (in 2012), with a marked increase in the peripheral thinning of the left eye (Figure 3). The UDVA had decreased to 0.1 decimal (20/200 Snellen), although the CDVA was excellent (1.2 decimal; 20/16.7 Snellen). However, there was a significant increase in the astigmatism, with −6.00 D (@ 85°) cylinder and +2.00 D sphere (Table 1). This worsening of the astigmatism was also corroborated with the topography. The SimK and Kmax increased to 5.60 D (@ 180°) and 46.20 D, respectively, and the Kmin decreased to 40.60 D (Table 1). The thinnest point measured by Orbscan had not changed (481 μm), but the ultrasound pachymetry did show a decrease in the central thickness (618 μm) (Table 1). The Ocular Response Analyzer (ORA; Ametek Reichert Technologies, Depew, NY) in the left eye revealed corneal hysteresis of 10.5 and corneal response factor of 9 (Table 1). The right eye did not show any significant clinical or topographical changes since the previous follow-up (CDVA = 0.9 decimal, 20/22.2 Snellen) (Figure 3).
(A–B) Slit-lamp images showing a stabilization of the disease in the right eye 4 years after treatment with corneal cross-linking. However, (C–D) the left eye presented with an increase in the superior corneal thinning, confirmed by (E) the anterior segment optical coherence tomography images.
Based on the findings in the left eye, which indicated a progression of the Terrien's marginal degeneration, we performed the same treatment with CXL as previously done for the right eye (see above). We also performed a small biopsy in the affected corneal area, which later confirmed the clinical diagnosis of Terrien's marginal degeneration. One month after surgery, the left eye presented UDVA of 0.35 decimal (20/57 Snellen) and CDVA of 1.2 decimal (20/16.7 Snellen), with −4.00 D (@ 95°) cylinder and +0.75 D sphere. The topography showed only small changes from preoperative values: SimK was 3.80 D (@ 6°), Kmax was 46.20 D, and Kmin was 42.40 D.
One year after the procedure in the left eye (in 2013; 5 years after surgery in the right eye), slit-lamp examination did not show any significant signs of complications in either eye. Compared to the preoperative data, in the left eye the UDVA had increased from 0.1 decimal (20/200 Snellen) to 0.5 decimal (20/40 Snellen), the CDVA remained at 1.2 decimal (20/16.7 Snellen), but the cylinder and the sphere decreased from −6.00 to −2.50 D, and from +2.00 to +0.50 D, respectively. Topography also showed an improvement in SimK (from 5.60 to 2.00 D @ 2°), Kmax (from 44.10 to 45.20 D), and Kmin (from 40.60 to 43.20 D). In the right eye, the UDVA improved from 0.05 decimal (20/400 Snellen) to 0.25 decimal (20/80 Snellen and the CDVA changed from 0.8 decimal (20/25 Snellen) to 1.2 decimal (20/16.7 Snellen). Similarly, the SimK decreased from 10.50 to 3.50 D (@ 9°), the Kmax also improved from 51.80 to 46.20 D, and the Kmin remained stable (from 41.20 to 42.70 D).
At the last follow-up visit (in February 2017; 10 years after CXL in the right eye and 5 years after CXL in the left eye), the patient was happy with the significant improvement in his vision. The slit-lamp examination showed a stable thinning on the superior peripheral cornea in both eyes, with no signs of neovascularization or punctate stromal opacities (Figures C–D, available in the online version of this article). The complete comparison between the preoperative situation and the situation at the last follow-up for the right and left eyes is shown in Table 1. The patient is now wearing spectacles comfortably, which provide him with an excellent visual acuity.
At the last follow-up visit, (A, B) 10 years after corneal cross-linking in the right eye and (C, D) 5 years after corneal cross-linking in the left eye, slit-lamp examination showed a stable thinning of the superior peripheral cornea in both eyes, with no signs of progression of the disease.
Postoperative corneal topography in 2017 showing the significant reduction in simulated, maximum, and minimum keratometry values in both eyes after corneal cross-linking. (Top) Right eye. (Bottom) Left eye.
In our case, epithelium-off CXL treatment not only provided sustained morphological stabilization of the disease, but also induced an important regularization of the corneal astigmatism (reaching an 11.00 D correction in the right eye), with a corresponding improvement in CDVA in both eyes. Slit-lamp examination and pachymetry also showed stabilization of the thinning on the superior peripheral cornea with no signs of progression of the disease after 10 years. In addition, there were no significant changes in corneal hysteresis and corneal resistance factor. These results confirm the efficacy of CXL in treating early and moderate stages of Terrien's marginal degeneration, when the cornea still retains a decent thickness, and correlate well with the findings of a previous report in which CXL also arrested the progression of Terrien's marginal degeneration.8
The efficacy and safety of CXL therapies in preventing progression of keratoconus at early stages has extended its use.1,12 However, there is currently little evidence regarding the efficacy and safety of CXL in other ectatic corneal disorders, such as Terrien's marginal degeneration. Herein, we observed an effective result in both eyes in a patient with established Terrien's marginal degeneration, which enabled the patient to recover a good visual function and reduce his visual disability. Previous studies have demonstrated the ability of CXL to stabilize visual and topographical changes due to an increase in resistance to enzymatic digestion.13–16 However, no changes in corneal morphology and elasticity have been evidenced before.17
Although further data are needed to confirm its safety and efficacy, and a clinical study needs to be conducted to confirm our findings, the data presented herein suggest that peripheral CXL appears to be a safe and effective therapeutic alternative to improve long-term visual acuity and normalize corneal topography in patients with Terrien's marginal degeneration.
- Maharana PK, Dubey A, Jhanji V, Sharma N, Das S, Vajpayee RB. Management of advanced corneal ectasias. Br J Ophthalmol. 2016;100:34–40. doi:10.1136/bjophthalmol-2015-307059 [CrossRef]
- Barraquer RI, Toledo MC, Torres E. Distrofias y Degeneraciones Corneales: Atlas y Texto. Barcelona: ESPAXS Publicaciones Médicas; 2004.
- Ashenhurst M, Slomovic A. Corneal hydrops in Terrien's marginal degeneration: an unusual complication. Can J Ophthalmol. 1987;22:328–330.
- Huang T, Wang Y, Ji J, Gao N, Chen J. Evaluation of different types of lamellar keratoplasty for treatment of peripheral corneal perforation. Graefes Arch Clin Exp Ophthalmol. 2008;246:1123–1131. doi:10.1007/s00417-008-0812-9 [CrossRef]
- Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen cross-linking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg. 2008;34:796–801. doi:10.1016/j.jcrs.2007.12.039 [CrossRef]
- Schnitzler E, Spörl E, Seiler T. Irradiation of cornea with ultraviolet light and riboflavin administration as a new treatment for erosive corneal processes, preliminary results in four patients [article in German]. Klin Monbl Augenheilkd. 2000;217:190–193. doi:10.1055/s-2000-10344 [CrossRef]
- Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg. 2009;35:1358–1362. doi:10.1016/j.jcrs.2009.03.035 [CrossRef]
- Hafezi F, Gatzioufas Z, Seiler TG, Seiler T. Corneal collagen cross-linking for Terrien marginal degeneration. J Refract Surg. 2014;30:498–500. doi:10.3928/1081597X-20140527-02 [CrossRef]
- Caporossi A, Mazzotta C, Baiocchi S, Caporossi T. Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena Eye Cross Study. Am J Ophthalmol. 2010;149:585–593. doi:10.1016/j.ajo.2009.10.021 [CrossRef]
- Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–627. doi:10.1016/S0002-9394(02)02220-1 [CrossRef]
- Browning AC, Shah S, Dua HS, Maharajan SV, Gray T, Bragheeth MA. Alcohol debridement of the corneal epithelium in PRK and LASEK: an electron microscopic study. Invest Ophthalmol Vis Sci. 2003;44:510–513. doi:10.1167/iovs.02-0488 [CrossRef]
- Richoz O, Mavrakanas N, Pajic B, Hafezi F. Corneal collagen cross-linking for ectasia after LASIK and photorefractive keratectomy: long-term results. Ophthalmology. 2013;120:1354–1359. doi:10.1016/j.ophtha.2012.12.027 [CrossRef]
- Hayes S, Kamma-Lorger CS, Boote C, et al. The effect of riboflavin UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal. PLoS One. 2013;8:e52860. doi:10.1371/journal.pone.0052860 [CrossRef]
- Spoerl E, Wollensak G, Seiler T. Increased resistance of cross-linked against enzymatic digestion. Curr Eye Res. 2004;29:35–40. doi:10.1080/02713680490513182 [CrossRef]
- Soong HK, Fitzgerald J, Boruchoff SA, Sugar A, Meyer RF, Gabel MG. Corneal hydrops in Terrien's marginal degeneration. Ophthalmology. 1986;93:340–343. doi:10.1016/S0161-6420(86)33737-0 [CrossRef]
- Zhang Y, Mao X, Schwend T, Littlechild S, Conrad GW. Resistance of corneal RFUVA-cross-linked collagens and small leucine-rich proteoglycans to degradation by matrix metalloproteinases. Invest Ophthalmol Vis Sci. 2013;54:1014–1025. doi:10.1167/iovs.12-11277 [CrossRef]
- Beauchamp GR. Terrien's marginal corneal degeneration. J Pediatric Ophthalmol Strabismus. 1982;19:97–99.
Comparison of Visual Acuity and Topographic Changes
|Parameter||Right Eye||Left Eye|
|Preoperative||9 Years Postoperative||Preoperative||5 Years Postoperative|
|UDVA (decimal/Snellen)||0.05 (20/400)||0.3 (20/66.6)||0.1 (20/200)||0.2 (20/100)|
|CDVA (decimal/Snellen)||0.8 (20/25)||1.2 (20/16)||1.2 (20/16)||1.25 (20/16)|
|Spherical equivalent (D)||−4.00||−1.50||1.00||−1.35|
|SimK (D) @ steep axis||10.50 @ 16°||3.70 @ 11°||5.60 @ 180°||3.30 @ 3°|
|Orbscan thinnest pachymetry (μm)||483||469||481||486|
|Ultrasound pachymetry (μm)||443||410||481||486|
|Corneal resistance factor||8.8||7.7||9||9.3|
|Treatment target||Peripheral ectasia|
|Fluence (total) (J/cm2)||5.4|
|Soak time and interval (minutes)||30(q2)|
|Treatment time (minutes)||30|
|Light source||CCL-365 (Peschke Corneal Cross-linking)|
|Protocol modification||Eccentric on superior periphery|
|Protocol abbreviation in manuscript||CXL|