Atypical presentation of calcific band keratopathy: A case report and literature review

Lee Goren; Fani Segev

doi:10.4103/IJO.IJO_2683_22

CASE REPORT

Year : 2023 | Volume : 3 | Issue : 2 | Page : 274-277

Atypical presentation of calcific band keratopathy: A case report and literature review

Lee Goren¹, Fani Segev²
¹ Department of Ophthalmology, Rabin Medical Center, Petah Tikva, Israel
² Department of Ophthalmology, Sheba Tel HaShomer Medical Center, Ramat Gan, Israel

Date of Submission	13-Oct-2022
Date of Acceptance	06-Feb-2023
Date of Web Publication	28-Apr-2023

Correspondence Address:
Lee Goren
Department of Ophthalmology, Rabin Medical Center, Petah Tikva, 39 Jabotinsky St. 49100
Israel

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJO.IJO_2683_22

Abstract

To report an unusual presentation of calcific band keratopathy and to hypothesize what causes this presentation, as well as its management with ethylenediaminetetraacetic acid (EDTA) chelation using dipotassium-ethylenediaminetetraacetic acid (K2-EDTA). We have conducted a review of the literature on the pathogenesis and treatment of calcific band keratopathy while focusing on the role of hypercalcemia, dry eyes, and corneal exposure. A 53-year-old patient developed an atypical calcific band keratopathy attributed to her ocular and medical history, which included end-stage renal disease (ESRD), hypercalcemia, glaucoma, dry eyes, and chronic use of eye drops. Within two months after starting the administration of oral vitamin D supplements, white/grey opacities appeared on the patient's cornea, as well as hypercalcemia. The patient was instructed to desist vitamin D supplements. Superficial epithelial keratectomy with EDTA chelation using K2-EDTA was performed while abstaining from the limbal opacities. After a 30-day period, the patient's cornea remained clear, and no recurrence of corneal opacities was observed. To the best of our knowledge, this is the first published case that reports this type of unique presentation of calcific band keratopathy. The hypothesis for the reason of the unique clinical presentation of our case will be discussed.

Keywords: Calcific band keratopathy, corneal exposure, corneal opacities, dry eye, EDTA chelation

How to cite this article:
Goren L, Segev F. Atypical presentation of calcific band keratopathy: A case report and literature review. Indian J Ophthalmol Case Rep 2023;3:274-7

How to cite this URL:
Goren L, Segev F. Atypical presentation of calcific band keratopathy: A case report and literature review. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 5];3:274-7. Available from: https://www.ijoreports.in/text.asp?2023/3/2/274/374970

Calcific band keratopathy is a non-specific corneal condition, mainly characterized by the deposition of white/grey opacities in the superficial layers of the cornea. Such opacities are commonly located at the exposed areas of the cornea, i.e. the interpalpebral zone.^[1] Calcific band keratopathy is a chronic and degenerative condition that typically develops slowly and may vary from a period of a few months to a longer period of a few years.^[2] These opacities are deposits composed of calcium hydroxyapatite and non-crystalline forms of phosphate, and carbonate salts of calcium.^[3] Calcific band keratopathy may be a result of a variety of systemic and ocular conditions. While the most common ocular conditions are chronic inflammation and chronic uveitis, the most common systemic condition is hypercalcemia.^[1],[2] Other conditions associated with calcific band keratopathy are corneal chemical burns, intraocular silicone oil, and phthisic eyes after multiple surgeries.^[1],[2]

A recent study showed that patients with an end-stage renal disease (ESRD) may be at significantly higher risk to develop band keratopathy,^[4] and may suffer from a variety of systemic and ocular complications, where the most common and serious complications include elevation of serum phosphate, secondary renal hyperparathyroidism, and the consequent elevated serum calcium levels.^[4],[5] In addition, ESRD patients may develop other ocular conditions such as increased intraocular pressure and irritated red eyes requiring long-term use of eye drops which is also associated with band keratopathy.^[4]

The mechanism of calcium deposition in the cornea is currently unknown but as deposition occurs primarily in the exposed area of the cornea, it is assumed to be associated with corneal exposure. The assumption is that band keratopathy may result from precipitation left as tears evaporate from the ocular surface, or as a result of changes in pH in this region, effecting the solubility of the calcium-phosphate complex.^[1],[3] Calcium deposition may occur with an alteration in tear osmolality, elevation of the pH from corneal tissue metabolism due to the increased evaporation of carbon dioxide, increase in the concentration of either calcium or phosphate in the serum, or in patients with dry eyes, further suggesting a role for tear evaporation in the pathogenesis of this process.^[6]

The most common treatment for this condition is ethylenediaminetetraacetic acid (EDTA) chelation,^[2] which is a simple procedure that removes the calcium opacities from the cornea with minimal damage to the corneal tissue. The most common agent used in EDTA chelation treatments is disodium ethylenediaminetetraacetic acid (Na2-EDTA), despite its high price and low availability. A recent study found that the use of dipotassium-ethylenediaminetetraacetic acid (K2-EDTA) is as affective.^[7] It has been demonstrated that after this procedure, a quick and significant relief was noted, as well as an improvement in visual acuity.^[1],[2] Other treatments include mechanical debridement and phototherapeutic keratectomy.^[8],[9],[10] The main objective of this treatment is to restore a smooth ocular surface by way of removing the calcium opacities from the ocular corneal surface.^[1]

We hereby report a case of an atypical presentation of band keratopathy in an ESRD patient suffering from multiple ocular conditions. The band keratopathy developed over the course of solely three months and was presented in an unusual location. We also review the literature on the rapid progression and pathogenesis of calcific band keratopathy and further discuss the different etiologies causing band keratopathy.

Case Report

A 53-year-old woman was referred to our clinic due to vision diminution, intermittent ocular pain, and white/gray opacities mainly in her right eye, which were blocking the visual axis. The initial diagnosis made by the referral physician was herpes zoster keratitis. The patient had an extensive past ocular history, including proliferative diabetic retinopathy (PDR) for which she went through several anti-vascular endothelial growth factors (VEGFs) intravitreal injections and pan-retinal photocoagulation laser (PRP) in her left eye, neovascular glaucoma (NVG) that required Ahmed glaucoma valve (AGV) transplant in both eyes, trabeculectomy (TRAB) and needling in her left eye, and diabetic macular edema (DME) in her left eye. In addition, the patient has been suffering from dry eyes for many years and was recently evaluated for thyroid eye disease (TED) due to proptosis (the later diagnosis was ruled out). The patient's medical history included hypertension, diabetes mellitus, ESRD refusing dialysis treatment, vitamin D deficiency, and consequently hyperparathyroidism, for which she received vitamin D supplements in an extensive amount (50,000 units per week) for a period of two months before her ophthalmic complaints. As a result, her calcium levels rose gradually (maximum levels reached 13.2 mg/dl), and she has been hospitalized for treatment. In addition, she developed hyperphosphatemia.

Initial examination at the cornea clinic showed marked proptosis and inferior scleral show in both eyes [Figure 1]a, a finding that was described years before her recent complaints, and after further investigation that included pictures of her and her siblings from childhood was determined as a congenital familial trait. Intraocular pressure was 19/17 mmHg. There were extensive white/grey opacities on the patient's right eye blocking the entire inferior half of the cornea including the limbus, and the nasal temporal and inferior bulbar conjunctiva [Figure 1]b, [Figure 1]c. The patient's left eye showed similar but less extensive findings [Figure 1]d, [Figure 1]e. Fluorescein dye did not reveal any erosion or dendrite. No keratic precipitates (KPs) were noted. It is important to note that on an ocular examination performed three months before this visit, both corneas were clear with no other ocular surface involvement.

Figure 1: (a) Proptosis and scleral show in both eyes. (b and c) (black arrows): Right eye, A white/grey superficial corneal opacity that involves the inferior half of the cornea, with opacities scattered in the conjunctiva. The arrows point at the conjunctival opacity. (d and e) Left eye, A white/grey superficial corneal opacity that mainly involves the limbus of the inferior half of the cornea and the adjacent cornea, with opacities scattered in the conjunctiva

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An anterior segment optical coherence tomography (AS-OCT) imaging was performed and is presented in [Figure 2]. On the patient's right eye, there was a hyper-reflective segment located at the sub-epithelial layer of the cornea, which blocked the rest of the corneal structures in a “shadowing effect.” This finding correlates to the location of the corneal opacity. As expected, the left eye showed a similar, but to a lesser extent. The hyper-reflective sub-epithelial segment was located solely at the limbus and adjacent cornea.

Figure 2: (a) Anterior segment optical coherence tomography (AS-OCT) imaging of the right eye. Hyper-reflective segment located at the sub-epithelial layer of the cornea, which blocked the rest of the corneal structures in a “shadowing effect.” (b) AS-OCT (imaging of the left eye). The hyper-reflective sub-epithelial segment was located at the limbus and adjacent inferior cornea

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The clinical appearance of the corneal opacity distribution was not compatible with the traditional presentation of calcific band keratopathy regarding its corneal location and conjunctival involvement.

The patient was instructed to desist vitamin D supplements and to continue a close follow-up until the calcium levels normalize, as well as, to continue her regular ophthalmic treatment, emphasizing the importance of frequent preservative-free lubricating drops, and lubricant ointment at bedtime.

After the normalization of calcium blood levels, the patient underwent EDTA chelation in her right eye using K2-EDTA following Lee ME et al.^[7] protocol. The patient's surgical outcome at the one-month follow-up is presented in [Figure 3]. To avoid damage to the corneal limbal stem cells and jeopardize the corneal healing process, it was decided to abstain from the limbal opacities. The last follow-up visit was one year after the surgery, with no change regarding the corneal opacities.

Figure 3: (a and b) Right eye at one-month post band keratopathy chelation

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Discussion

Rapid deposition of calcium in the cornea is an unusual presentation of calcific band keratopathy. Previous reports described rapid calcification in patients with glaucoma treated with pilocarpine drops containing organic mercurial preservatives, a phenomenon attributed to the direct toxic effect of mercury on stromal collagen.^[4],[7] In addition, patients with severe dry eye and chronic epithelial defects,^[6],[11] and patients with significant corneal pathology treated with steroid–phosphate drops,^[1],[2] are also at high risk of developing a rapid calcification. Since calcium and phosphate are normally present in tears in concentrations that approach their solubility constant, in the cases mentioned, these changes create a local chemical environment that causes their precipitation.^[2],[9] Since the concentrations of calcium and phosphate at the ocular surface are close to their solubility constant, any environmental change may drive the chemical reaction towards precipitation.^[9] In dry eyes for instance, while the tear osmolality is increased causing a more alkaline pH, the use of phosphate-containing drops may increase the phosphate and calcium concentration. It is important to note that the pH at the interpalpebral zone is regularly higher than that of the rest of the ocular surface due to the evaporation of carbon dioxide.^[1],[6] In an experimental model, rabbits were induced with ocular inflammation and were administered with high doses of vitamin D. The animals were then divided into two groups. In the first group, the eyelids could be open, and in the second group, the eyelids were kept closed. Calcified band keratopathy developed only in the first group, further suggesting the importance of tear evaporation and pH changes in the pathogenesis of calcific band keratopathy.^[11]

Previous reports deduced that there is a connection between ESRD and red eyes resulting from calcific deposits in the conjunctivae or in the corneas.^[4] To this day, a few pathogenic mechanisms for the formation of calcific band keratopathy in ESRD patients were suggested. These include hyperparathyroidism and its consequence increased serum calcium levels, and long-term eye drops used in cases of long-standing glaucoma or irritated red eyes. As the serum levels of phosphate and calcium become high enough to result in calcium phosphate salt precipitation, ESRD patients are prone to develop deposition of calcium phosphate salts in the form of microcrystalline hydroxyapatite and consequently band keratopathy.^[4] To prevent band keratopathy in ESRD patients, elevated levels of phosphate or calcium must be aggressively controlled.

Our patient presented with atypical band keratopathy characterized by rapid deposition of calcium in both corneas and an unusual corneal opacity distribution of the inferior cornea and limbus without the characteristic corneal clear zone adjacent to the limbus. In addition, the left eye was affected to a lesser degree and showed calcified opacity of the inferior limbus and adjacent cornea suggesting that the keratopathy climbed up the cornea, and not in the usual degenerative process, which initially begins near the limbus in the nasal and temporal zones and progresses towards the center. In addition, the inferior and interpalpebral bulbar conjunctiva was involved, something that can easily lead to a misdiagnosis. This unusual presentation was attributed to her systemic condition, which included ESRD, hypercalcemia and hyperphosphatemia, and her ocular background (long-standing glaucoma, chronic eye drop use, and structural proptosis with prominent lower inferior scleral show, and on the other hand, ptosis of the upper eyelids).

Conclusion

Our case illustrates that acute formation of calcific band keratopathy is possible and that the clinical presentation is dependent not only on the multifactorial factors but apparently also upon the extent of corneal exposure resulting in an unusual band keratopathy configuration.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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