BAND KERATOPATHY

Signs and Symptoms

Band keratopathy can afflict any patient regardless of age, sex or race. Early in the course of the disease, individuals tend to be asymptomatic. Glare, photophobia, foreign body sensation, ocular surface dryness and surface erosions gradually develop over time, and may evolve so as to cause significant pain. At this stage, patients are often visually symptomatic with acuity reduction, possibly to a level of 20/400 or worse. Fortunately, the majority of patients will maintain acuity in the 20/40 to 20/200 range.1

On biomicroscopic evaluation, patients with band keratopathy display a dense, opaque white accumulation of calcific material in the superficial cornea, usually within the interpalpebral zone.2 The appearance has been described as that of frosted, ground glass. Typically, the band begins in the limbal region and progresses centrally from both the nasal and temporal periphery; as such, the calcific material appears most dense near the limbus. Initially, there will be a sharp demarcation with a small band of normal cornea separating the peripheral edge of the keratopathy from the limbus.3

The key diagnostic feature is the presence of areas where clear cornea shows through the calcific opalescence. This has been described as a “Swiss cheese” appearance, and represents areas where corneal nerves penetrate Bowman’s membrane.1,2

The majority of cases of band keratopathy are idiopathic.1 However, there are also a great number of underlying conditions, both systemic and ocular, which can contribute to the development of band keratopathy. Systemically induced band keratopathy tends to be bilateral, whereas ocularly-induced or idiopathic forms are typically unilateral.1 Often, there is a history of chronic, recurrent anterior uveitis, corneal ulceration, corneal burn or other ocular inflammatory disease.2 The presence of uveitis and band keratopathy concurrently in a young person is highly indicative of juvenile idiopathic arthritis (JIA).1,2,4-9 Systemic conditions that cause increased blood calcium levels can also lead to the development of band keratopathy. Thus, there is often a history of hyperparathyroidism in these patients.10-12

Other systemic conditions associated with band keratopathy development include renal failure, gout and sarcoidosis.10,13-15 Other ocular conditions that have been seen in association with band keratopathy include chronic glaucoma and use of older glaucoma medications (e.g., pilocarpine), interstitial keratitis, dry eye, corneal exposure and intraocular silicone oil tamponade.2,7,16,17 Chronic corneal edema is a common cause of band keratopathy.1 In addition, there is a recognized hereditary component and a form of the disease known as familial band keratopathy.18,19

Pathophysiology

Band keratopathy represents a deposition of calcium salts into the anterior corneal stroma and Bowman’s layer. The precise mechanism appears to be multifactorial, but chronic inflammation and a modification of the ocular surface pH almost certainly play a role. Evaporation of tears increases the tonicity/osmolarity of the tear film, allowing for the potential of ionic salt precipitation.20 Elevated serum calcium or phosphate can enhance this activity, as can increased alkalinity of the tear film (as seen in chronic dry eye states).

Interestingly, this type of tissue pH shift can also be seen in chronically inflamed eyes. Ultimately, the changes induce degeneration and abnormal cellular metabolism within the cornea, leading to the pathological changes in band keratopathy.21,22 Histological evaluation shows elevated peaks of calcium and phosphorus within the area of granular deposits, as well as dense material consistent with extracellular calcospherites.21

Hypercalcemia from systemic hyperparathyroidism is a common cause of band keratopathy.10-12 Hyperparathyroidism results from excessive production of parathormone, usually due to parathyroid adenoma, but also from ectopic parathormone production related to pulmonary or renal cancer.23 Band keratopathy is also frequently found in association with JIA, presumably due to the chronicity of anterior uveitis in this condition.4-9

Management

All patients with band keratopathy should be evaluated for abnormal calcium metabolism. Referral to an endocrinologist for evaluation and parathyroid function testing is indicated. If the patient is of younger age, or particularly if there is concurrent cataract and uveitis, referral to a rheumatologist to evaluate for JIA is appropriate. It should be remembered that malignant disease can also cause abnormal calcium metabolism. Cases demonstrating unusual laboratory findings may merit evaluation by an oncologist.

Initially, band keratopathy should be managed with topical lubricants, particularly if tear dysfunction is evident. Eventually, however, more aggressive management is generally necessary. When the calcium plaque is thick, it can be debrided from the superficial cornea using a forceps, burr or foreign body spud. Chelation with 3% ethylenediaminetetraacetic acid (EDTA) has been a procedure of choice since it was described in the 1950s and will generally resolve band keratopathy.1,24

In this procedure, the anesthetized epithelium is gently debrided with either a cotton-tipped applicator soaked in topical anesthetic or with a foreign body removal instrument. Next, a cotton-tipped applicator or wick sponge soaked in EDTA is brushed across the calcium-deposited cornea from five to 45 minutes, depending upon the thickness of the plaque. The eye is then bandaged with a soft contact lens and prophylactic topical antibiotics are prescribed QID until re-epithelialization is achieved. In these cases, the epithelium is slower to heal than for a similarly sized traumatic corneal abrasion as the abnormal corneal metabolism retards efficient repair.1

Other, newer therapeutic modalities have also been explored. Surgical intervention via lamellar keratoplasty has been shown to help patients achieve both visual and structural success.25,26 Phototherapeutic keratectomy using the excimer laser has also demonstrated high rates of visual and structural improvement, and can be considered a safe, front-line therapy for band keratopathy.27-29 The adjunctive use of amniotic membrane transplantation to promote epithelial healing, reduce inflammation and scarring, and provide a stable ocular surface has improved the success of the other treatment options.26,30-32

Clinical Pearls

The combination of band keratopathy, uveitis and cataract in juvenile idiopathic arthritis is termed Still’s Triad.33

Band keratopathy in patients under 16 years of age is highly suggestive of JIA.

Visual prognosis is guarded in patients with band keratopathy, as the underlying condition that promoted calcium deposition often causes recurrence.

Band keratopathy can signal malignant processes and may indicate the need for evaluation in that area.

1. Najjar DM, Cohen EJ, Rapuano CJ, et al. EDTA chelation for calcific band keratopathy: results and long-term follow-up. Am J Ophthalmol. 2004;137(6):1056-64.

2. Jhanji V, Rapuano CJ, Vajpayee RB. Corneal calcific band keratopathy. Curr Opin Ophthalmol. 2011;22(4):283-9.

3. Kwon YS, Song YS, Kim JC. New treatment for band keratopathy: superficial lamellar keratectomy, EDTA chelation and amniotic membrane transplantation. J Korean Med Sci. 2004;19(4):611-5.

4. Heiligenhaus A, Niewerth M, Mingels A, et al. Epidemiology of uveitis in juvenile idiopathic arthritis from a national paediatric rheumatologic and ophthalmologic database. Klin Monatsbl Augenheilkd. 2005;222(12):993-1001.

5. Carvounis PE, Herman DC, Cha S, et al. Incidence and outcomes of uveitis in juvenile rheumatoid arthritis, a synthesis of the literature. Graefes Arch Clin Exp Ophthalmol. 2006;244(3):281-90.

6. Mahdaviani S, Higgins GC, Kerr NC. Orbital pseudotumor in a child with juvenile rheumatoid arthritis. J Pediatr Ophthalmol Strabismus. 2005;42(3):185-8.

7. Rosenberg KD, Feuer WJ, Davis JL. Ocular complications of pediatric uveitis. Ophthalmology. 2004;111(12):2299-306.

8. Paroli MP, Speranza S, Marino M, et al. Prognosis of juvenile rheumatoid arthritis-associated uveitis. Eur J Ophthalmol. 2003;13(7):616-21.

9. Zak M, Fledelius H, Pedersen FK. Ocular complications and visual outcome in juvenile chronic arthritis: a 25-year follow-up study. Acta Ophthalmol Scand. 2003;81(3):211-5.

10. Galor A, Leder HA, Thorne JE, Dunn JP. Transient band keratopathy associated with ocular inflammation and systemic hypercalcemia. Clin Ophthalmol. 2008;2(3):645-7.

11. Canellos HM, Cooper J, Paek A, Chien J. Multiple calcified deposits along the eyelid margins secondary to chronic renal failure and hyperparathyroidism. Optometry. 2005;76(3):181-4.

12. Abeysiri P, Sinha A. An unusual pattern of corneal calcification in tertiary hyperparathyroidism. Arch Ophthalmol. 2006;124(1):138-9.

13. Mullaem G, Rosner MH. Ocular problems in the patient with end-stage renal disease. Semin Dial. 2012;25(4):403-7.

14. Lo WR, Broocker G, Grossniklaus HE. Histopathologic examination of conjunctival tophi in gouty arthritis. Am J Ophthalmol. 2005;140(6):1152-4.

15. Johnston RL, Stanford MR, Verma S, et al. Resolution of calcific band keratopathy after lowering elevated serum calcium in a patient with sarcoidosis. Br J Ophthalmol. 1995;79(11):1050.

16. Pavicić-Astalos J, Lacmanović-Loncar V, Petric-Vicković I, et al. Eye drops preservative as the cause of corneal band keratopathy in long-term pilocarpine hydrochloride treatment. Acta Clin Croat. 2012;51(1):107-11.

17. Sharma N, Mannan R, Sinha R, et al. Excimer laser phototherapeutic keratectomy for the treatment of silicone oil-induced band-shaped keratopathy. Eye Contact Lens. 2011;37(5):282-5.

18. Schmid E, Lisch W, Philipp W, et al. A new, X-linked endothelial corneal dystrophy. Am J Ophthalmol. 2006;141(3):478-87.

19. Arora R, Shroff D, Kapoor S, et al. Familial calcific band-shaped keratopathy: report of two new cases with early recurrence. Indian J Ophthalmol. 2007;55(1):55-7.

20. Liu H, Begley C, Chen M, et al. A link between tear instability and hyperosmolarity in dry eye. Invest Ophthalmol Vis Sci. 2009;50(8):3671-9.

21. Mihara E, Miyata H, Inoue Y, et al. Application of energy-dispersive X-ray microanalysis on the diagnosis of atypical calcific band keratopathy. Okajimas Folia Anat Jpn. 2005;82(1):19-24.

22. Doostdar N, Manrique CJ, Hamill MB, Barron AR. Synthesis of calcium-silica composites: a route toward an in vitro model system for calcific band keratopathy precipitates. J Biomed Mater Res A. 2011;99(2):173-83.

23. Cordellat IM. Hyperparathyroidism: primary or secondary disease? Reumatol Clin. 2012;8(5):287-91.

24. Breinin GM, Devoe AG. Chelation of calcium with edathamil calcium-disodium in band keratopathy and corneal calcium affections. AMA Arch Ophthalmol. 1954;52(6):846-51.

25. Saini JS, Jain AK, Sukhija J, et al. Indications and outcome of optical partial thickness lamellar keratoplasty. Cornea. 2003;22(2):111-3.

26. Kwon YS, Song YS, Kim JC. New treatment for band keratopathy: superficial lamellar keratectomy, EDTA chelation and amniotic membrane transplantation. J Korean Med Sci. 2004;19(4):611-5.

27. Najjar DM. Management of band keratopathy with excimer phototherapeutic keratectomy. Eye. 2006;20(2):252.

28. Moniz N, Fernandez ST. Efficacy of phototherapeutic keratectomy in various superficial corneal pathologies. J Refract Surg. 2003;19(2 Suppl):S243-6.

29. Stewart OG, Morrell AJ. Management of band keratopathy with excimer phototherapeutic keratectomy: visual, refractive, and symptomatic outcome. Eye. 2003;17(2):233-7.

30. Anderson DF, Prabhasawat P, Alfonso E, Tseng SC. Amniotic membrane transplantation after the primary surgical management of band keratopathy. Cornea. 2001;20(4):354-61.

31. Esquenazi S, Rand W, Velazquez G, Grunstein L. Novel therapeutic approach in the management of band keratopathy using amniotic membrane transplantation with fibrin glue. Ophthalmic Surg Lasers Imaging. 2008;39(5):418-21.

32. Im SK, Lee KH, Yoon KC. Combined ethylenediaminetetraacetic acid chelation, phototherapeutic keratectomy and amniotic membrane transplantation for treatment of band keratopathy. Korean J Ophthalmol. 2010;24(2):73-7.

33. Multack RF, Genge MR, Skorin L, Jr. Juvenile rheumatoid arthritis. In: Onofrey BE, Skorin L, Jr., Holdeman NR, ed. Ocular Therapeutics Handbook: A Clinical Manual, 2nd Edition. Philadelphia: Lippincott Williams & Wilkins;2005:255-8.