The Clinical Manifestations and Prognostic Factors of Autoimmune-Related Peripheral Corneal Ulcers

Dae Joong Ma; Hyuk Jin Choi; Mee Kum Kim; Won Ryang Wee

doi:10.3341/jkos.2011.52.8.936

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Ma, Choi, Kim, and Wee: The Clinical Manifestations and Prognostic Factors of Autoimmune-Related Peripheral Corneal Ulcers

Original Article

J Korean Ophthalmol Soc 2011;52(8):936-942.

Published online: 7 September 2011

DOI: https://doi.org/10.3341/jkos.2011.52.8.936

The Clinical Manifestations and Prognostic Factors of Autoimmune-Related Peripheral Corneal Ulcers

Dae Joong Ma, MD¹, Hyuk Jin Choi, MD^1,², Mee Kum Kim, MD, PhD^1,², Won Ryang Wee, MD, PhD^1,²

¹Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea

²Laboratory of Corneal Regenerative Medicine and Ocular Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, Korea

Address reprint requests to Mee Kum Kim, MD, PhD Department of Ophthalmology, Seoul National University Hospital #28 Yeongeon-dong, Jongno-gu, Seoul 110-744, Korea Tel: 82-2-2072-2438, Fax: 82-2-741-3187, E-mail: kmk9@snu.ac.kr

Received 19 November 2010 Revised 20 January 2011 Accepted 6 May 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To investigate clinical manifestations and prognostic factors of autoimmune-related peripheral corneal ulcers.

Methods

Nineteen eyes in 18 patients who were diagnosed with autoimmune-related peripheral corneal ulcer from November 1999 to August 2010 were enrolled in the present study. Clinical manifestations and treatment results were investigated retrospectively.

Results

The average age at presentation was 64.6 years with female (66.7%) and unilateral (94.4%) dominance. The main etiologies were Mooren's ulcer (53.6%) and rheumatoid arthritis (26.3%). The ulcer depth was greater than 75% of the corneal thickness in more than half of the cases (57.9%) and the mean extent of the ulcer was 69.5°. There were no significant improvements in visual acuity after treatment (p = 0.789) and no significant differences in treatment outcomes among etiologies or treatment modalities. The patients who underwent ulcer recurrence (p = 0.048) or treatment failure (p = 0.005) had poorer final visual acuity than those patients who did not. The ulcer depth correlated with treatment failure (p = 0.037). The final visual acuity showed positive correlations with visual acuity at presentation (p = 0.031) and negative correlations with the number of recurrences (p = 0.042).

Conclusions

The visual acuity at presentation and ulcer depths were significant prognostic factors. These factors appeared to be helpful in the treatment of marginal keratitis depending on the depth of the ulcer.

Keywords: Autoimmune, Connective tissue disease, Mooren's ulcer, Peripheral corneal ulcer, Recurrence, Treatment failure

References

1. Mondino BJ. Inflammatory diseases of the peripheral cornea. Ophthalmology. 1988; 95:463–72.

2. Allansmith MR, McClellan BH. Immunoglobulins in the human cornea. Am J Ophthalmol. 1975; 80:123–32.

3. Lewallen S, Courtright P. Problems with current concepts of the epidemiology of Mooren's corneal ulcer. Ann Ophthalmol. 1990; 22:52–5.

4. Chow CY, Foster CS. Mooren's ulcer. Int Ophthalmol Clin. 1996; 36:1–13.

5. Messmer EM, Foster CS. Vasculitic peripheral ulcerative keratitis. Surv Ophthalmol. 1999; 43:379–96.

6. Ladas JG, Mondino BJ. Systemic disorders associated with peripheral corneal ulceration. Curr Opin Ophthalmol. 2000; 11:468–71.

7. Malik R, Culinane AB, Tole DM, Cook SD. Rheumatoid keratol-ysis: a series of 40 eyes. Eur J Ophthalmol. 2006; 16:791–7.

8. Chen KH, Hsu WM, Liang CK. Relapsing Mooren's ulcer after amniotic membrane transplantation combined with conjunctival autografting. Ophthalmology. 2004; 111:792–5.

9. Wood TO, Kaufman HE. Mooren's ulcer. Am J Ophthalmol. 1971; 71:417–22.

10. Chen J, Xie H, Wang Z, et al. Mooren's ulcer in China: a study of clinical characteristics and treatment. Br J Ophthalmol. 2000; 84:1244–9.

11. Woo SJ, Wee WR, Lee JH. The clinical manifestations of Mooren's ulcer. J Korean Ophthalmol Soc. 2002; 43:1388–96.

12. Kim DG, Kim BJ. A peripheral corneal ulcer in rheumatoid arthritis. J Korean Ophthalmol Soc. 1987; 28:1083–7.

13. Kervick GN, Pflugfelder SC, Haimovici R, et al. Paracentral rheumatoid corneal ulceration. Clinical features and cyclosporine therapy. Ophthalmology. 1992; 99:80–8.

14. Bernauer W, Ficker LA, Watson PG, Dart JK. The management of corneal perforations associated with rheumatoid arthritis. An analysis of 32 eyes. Ophthalmology. 1995; 102:1325–37.

15. Messmer EM, Foster CS. Destructive corneal and scleral disease associated with rheumatoid arthritis. Medical and surgical management. Cornea. 1995; 14:408–17.

16. Tauber J, Sainz de la Maza M, Hoang-Xuan T, Foster CS. An analysis of therapeutic decision making regarding immunosuppressive chemotherapy for peripheral ulcerative keratitis. Cornea. 1990; 9:66–73.

17. Gottsch JD, Liu SH, Minkovitz JB, et al. Autoimmunity to a cornea-associated stromal antigen in patients with Mooren's ulcer. Invest Ophthalmol Vis Sc. 1995; 36:1541–7.

18. Dana MR, Qian Y, Hamrah P. Twenty-five-year panorama of corneal immunology: emerging concepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection. Cornea. 2000; 19:625–43.

19. Feder RS, Krachmer JH. Conjunctival resection for the treatment of the rheumatoid corneal ulceration. Ophthalmology. 1984; 91:111–5.

20. Fogle JA, Kenyon KR, Foster CS. Tissue adhesive arrests stromal melting in the human cornea. Am J Ophthalmol. 1980; 89:795–802.

21. Bessant DA, Dart JK. Lamellar keratoplasty in the management of inflammatory corneal ulceration and perforation. Eye. 1994; 8:22–8.

22. Raizman MB, Sainz de la Maza M, Foster CS. Tectonic keratoplastyaccommodative for peripheral ulcerative keratitis. Cornea. 1991; 10:312–6.

Figure 1.

Corneal ulcer extent. The angle between the two margins of the corneal ulcer (degree).

Figure 2.

Comparison of final acuity for recurrence or treatment failure. Statistics were analyzed by Mann-Whitney U-test. ^* p = 0.048; ^† p = 0.005.

Table 1.

Clinical features of autoimmune related peripheral corneal ulcer

Patient age (yr)		64.6 (22.00)
Mean follow up (mon)		25.5 (24.4)
Sex (F:M)		12 (66.7%):6 (33.3%)
Unilateral:bilateral		17 (94.4%):1 (5.6%)
Right:left		10 (52.6%):9 (47.3%)
Visual acuity at presentation (log MAR)		−0.53 (0.42)
Presenting symptom		
Redness		16 (84.3%)
Ocular pain		14 (73.7%)
Perforation		7 (36.8%)
Etiologies		
Mooren's ulcer		10 (53.6%)
Conective tissue disease related		
Rheumatoid arthritis		5 (26.3%)
Wegener's granulomatosis		1 (5.3%)
Juvenile rheumatoid arthritis		1 (5.3%)
Others		2 (10.5%)
Ulcer characteristics		
Location of ulcer	Nasal	6 (31.6%)
	Superior	6 (31.6%)
	Inferior	6 (31.6%)
Onset of ulcer	Temporal	1 (5.2%)
	Acute	6 (31.6%)
	Chronic	13 (68.4%)
Depth of ulcer	Mild	7 (36.8%)
	Severe	12 (63.2%)
Extent of corneal neovascularization	Mild	6 (31.6%)
	Severe	13 (68.4%)
Extent of ulcer (degree)		69.5 (46.5)

Table 2.

Range of the treatment used

Variable	Operation	No. (%) of patients
Surgical treatment (n = 22)	Amniotic membrane transplantation	14 (48.3%)
	Glue application	6 (20.7%)
	Corneal limbal transplantation	5 (17.2%)
	Scleral patch graft	2 (6.9%)
	Conjunctival recession	2 (6.9%)
	Total	29^*
Topical immune-suppressive treatment (n = 20)	Steroid	20 (60.6%)
	Cyclosporin A	10 (30.3%)
	Interferon-α	2 (6.1%)
	Taclolimus	1 (3.0%)
	Total	33^*
Systemic immune-suppressive treatment (n = 19)	Steroid	19 (59.4%)
	Cyclosporin A	7 (18.6%)
	Mycophenolate mofetil	4 (12.5%)
	Cyclophosphamide	1 (3.9%)
	Infliximab	1 (3.9%)
	Total	32^*

^* Some patients underwent more than one treatment.

Table 3.

The comparison of treatment outcomes between treatment modalities

Variable	Surgical and medical treatment (n = 7)	Medical treatment only (n = 7)	p-value	Total (n = 15^*)
Visual acuity at presentation (log MAR)	−0.63 (0.26)	−0.37 (0.59)	0.038	−0.50 (0.44)
Final visual acuity (log MAR)	−0.98 (−1.18)	−0.18 (0.08)	0.073	−0.56 (0.88)
p-value	0.335	0.371		0.789
Duration of treatment (mon)	2.02 (1.50)	0.88 (0.58)	0.165	1.42 (1.20)
Number of recurrence	0.43 (0.79)	0.00 (0.00)	0.383	0.27 (0.59)
Number of treatment failure	1.43 (1.27)	0.00 (0.00)	0.026	0.67 (1.11)
Visually improved after treatment:not improved	4 (57.1%):3 (42.9%)	5 (71.4%):2 (28.6%)	0.296	6 (42.9%):8 (57.1%)

Statistics were analyzed by Mann-Whitney U-test and Fisher's exact test.

^* One patient, who underwent an additional medical treatment after the relapse was added.

Table 4.

Comparison of treatment outcomes between etiologies

Variable	Mooren's ulcer (n = 8)	Connective tissue disease related (n = 7)	p-value
Final visual acuity (log MAR)	−0.61 (0.88)	−1.05 (1.31)	0.546
p-value	0.483	0.093	
Duration of treatment (mon)	1.44 (1.12)	1.39 (1.38)	0.694
Number of recurrence	0.13 (0.35)	0.4286 (0.79)	0.613
Number of treatment failure	0.88 (1.36)	0.4286 (0.79)	0.779
Visually improved after treatment:not improved	5 (62.5%):3 (37.5%)	2 (28.6%):5 (71.4%)	0.214

Statistics were analyzed by Mann-Whitney U-test and Fisher's exact test.

Connective tissue disease related: Rheumatoid arthritis, Wegener's granulomatosis, Juvenile rheumatoid arthritis, other autoimmune disease.

Table 5.

Comparison of treatment outcome for clinical characteristics

	Site of ulcer				Onset of ulcer			New vessel ingrowth^*			Sign of inflammation^*			Ulcer depth
	Nasal (n = 5)	Superior (n = 5)	Inferior (n = 5)	p	Acute (n = 5)	Chronic (n = 10)	p	Mild^†(n = 6)	Severe^†(n = 8)	p	Mild^‡(n = 7)	Severe^‡(n = 5)	p	Mild^§(n = 7)	Severe^§(n = 8)	p
Final visual acuity (log MAR)	−0.29(0.24)	−0.66(1.14)	−0.72(1.10)	0.641	−0.70(1.12)	−0.49(0.80)	0.679	−1.03 (1.29)	−0.26(1.88)	1.000	−0.53 (0.96)	−0.31 (0.24)	0.639	−0.18(0.86)	−0.89(1.13)	0.072
Number of recurrence	0.00 (0.00)	0.60(0.89)	0.20(0.45)	0.291	0.60(0.89)	0.10(0.32)	0.371	0.50 (0.84)	0.13(0.35)	0.491	0.43(0.79)	0.00(0.00)	0.432	0.00(0.00)	0.50 (0.76)	0.232
Number of treatment failure	0.80 (1.30)	0.40(0.89)	0.80(1.30)	0.766	0.40 (0.89)	0.80(1.23)	0.594	0.83(1.33)	0.63(1.06)	0.950	0.71(1.25)	0.40(0.55)	1.000	0.00 (0.00)	1.25(1.28)	0.040

Statistics were analyzed by Mann-Whitney U-test.

^* Patients were excluded from the statistical analysis if medical records were insufficient

^† Mild: new vessel ingrowth from the corneal limbus < 1 mm, severe: ≥ 1 mm

^‡ Mild: The degree of injection and/or swelling of the bulbar conjunctiva, episclera or sclera belongs to the mild half of cases, severe: belongs to the severe half of cases

^§ Mild: corneal ulceration < 75% of the corneal thickness, severe: ≥ 75% of the corneal thickness include perforations.

Table 6.

Associations of final visual acuity with clinical characteristics by linear regression analysis

Variables	Β ± SE (mean ± SD)	Partial R²	p-value (multivariate)
Age at presentation (yr)	−0.008 ± 0.013	0.024	0.553
Visual acuity at presentation (log MAR)	−1.228 ± 0.563	0.229	0.045 (0.031)
Extent of ulcer (degree)	−0.002 ± 0.007	0.006	0.775
Number of recurrence	−1.426 ± 0.293	0.856	0.008 (0.042)
Number of treatment failure	−0.552 ± 0.158	0.485	0.004 (0.786)
Duration of treatment	−0.643 ± 0.099	0.766	0.000 (0.092)

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