Journal of Refractive Surgery

Report Supplemental Data

Bilateral, Asymmetric Keratoconus Induced by Thyrotoxicosis With Long-term Stability After Corneal Cross-linking

Ramon Lee, MD; Ahmed El-Massry, MD; Youssef El-Massry, MD; J. Bradley Randleman, MD

Abstract

PURPOSE:

To present a case of bilateral, asymmetric keratoconus presenting unilaterally after partial thyroidectomy with delayed presentation in the second eye after thyrotoxicosis, with disease stabilization following corneal cross-linking (CXL).

METHODS:

Case report and literature review.

RESULTS:

A 17-year-old girl with a history of Graves' disease underwent partial thyroidectomy without thyroid hormone replacement therapy with normal baseline ophthalmic examination of corrected distance visual acuity (CDVA) of 20/20 and no manifest astigmatism in either eye. At age 29 years, keratoconus manifested in the right eye and standard protocol CXL was performed. At age 40 years, the right eye remained stable after CXL, but keratoconus manifested in the left eye and epithelium-off accelerated CXL was performed with subsequent disease stabilization.

CONCLUSIONS:

This case demonstrates the association between thyrotoxicosis and keratoconus and the bilateral nature of keratoconus, and highlights the potentially asymmetric presentation of thyroid-induced keratoconus. CXL had a long-term stabilizing effect over 10 years despite the ongoing effects of thyroid gland dysfunction.

[J Refract Surg. 2018;34(5):354–356.]

Abstract

PURPOSE:

To present a case of bilateral, asymmetric keratoconus presenting unilaterally after partial thyroidectomy with delayed presentation in the second eye after thyrotoxicosis, with disease stabilization following corneal cross-linking (CXL).

METHODS:

Case report and literature review.

RESULTS:

A 17-year-old girl with a history of Graves' disease underwent partial thyroidectomy without thyroid hormone replacement therapy with normal baseline ophthalmic examination of corrected distance visual acuity (CDVA) of 20/20 and no manifest astigmatism in either eye. At age 29 years, keratoconus manifested in the right eye and standard protocol CXL was performed. At age 40 years, the right eye remained stable after CXL, but keratoconus manifested in the left eye and epithelium-off accelerated CXL was performed with subsequent disease stabilization.

CONCLUSIONS:

This case demonstrates the association between thyrotoxicosis and keratoconus and the bilateral nature of keratoconus, and highlights the potentially asymmetric presentation of thyroid-induced keratoconus. CXL had a long-term stabilizing effect over 10 years despite the ongoing effects of thyroid gland dysfunction.

[J Refract Surg. 2018;34(5):354–356.]

The association between thyroid gland dysfunction and keratoconus is being increasingly recognized and has been previously reported.1–5 These previous reports have shown keratoconus associated with thyroid gland dysfunction in the setting of hyperthyroidism, euthyroidism, hypothyroidism, and after thyroidectomy. Due to the scarcity of identified cases, much is still unknown about the disease process and its treatment options. As more cases are identified and studied, a greater understanding of the condition is being obtained.

We present a case of bilateral, asymmetric keratoconus presenting after partial thyroidectomy in one eye and after thyrotoxicosis in the other eye, with disease stabilization following corneal cross-linking (CXL).

Report

A 17-year-old girl presented in 1995 with a history of Graves' disease and thyroid-associated orbitopathy. She had undergone partial thyroidectomy. She was observed closely every 3 months after the partial thyroidectomy for 1 year. She had normal serum triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels and did not require thyroid hormone replacement therapy. Her baseline ophthalmic examination prior to the partial thyroidectomy was normal and consisted of corrected distance visual acuity (CDVA) of 20/20 in both eyes with a manifest refraction of +1.00 diopters (D) sphere in both eyes. She was noted to have recurrent chalazia and was given a spectacle prescription.

Routine ophthalmic evaluation revealed stable CDVA and manifest refraction from her baseline examination until 2004 (9 years). The patient then presented again in 2007 at the age of 29 years with decreased visual acuity in the right eye. CDVA was 20/30 in the right eye and 20/20 in the left eye. Her manifest astigmatism increased from no astigmatism in either eye to +2.50 D in the right eye and +1.50 D in the left eye. Corneal topography revealed significant irregular, asymmetric astigmatism with inferior steepening (maximum keratometry = 46.50 D) indicative of keratoconus in the right eye, and regular symmetric astigmatism in the left eye (Figure 1).

Corneal topography in 2007 of the (A) right eye demonstrating focal anterior curvature steepening inferiorly and (B) left eye demonstrating regular astigmatism without focal steepening

Figure 1.

Corneal topography in 2007 of the (A) right eye demonstrating focal anterior curvature steepening inferiorly and (B) left eye demonstrating regular astigmatism without focal steepening

The right eye underwent CXL using the standard CXL protocol (Table 1). The procedure was tolerated without complications. At the 1-year follow-up visit in 2008, CDVA was 20/20 with manifest astigmatism of +1.25 D in the right eye and stable corneal topography in the left eye, whereas CDVA, manifest astigmatism, and corneal topography remained stable (Figure A, available in the online version of this article).

CXL Methods

Table 1:

CXL Methods

Corneal topography in 2008 of the (A) right eye demonstrating stable anterior curvature of focal steepening 1 year after corneal cross-linking and (B) left eye demonstrating stable regular astigmatism without focal steepening.

Figure A.

Corneal topography in 2008 of the (A) right eye demonstrating stable anterior curvature of focal steepening 1 year after corneal cross-linking and (B) left eye demonstrating stable regular astigmatism without focal steepening.

In 2016, at the age of 39 years, routine follow-up evaluation revealed CDVA of 20/20 in both eyes and mild changes in manifest refraction with +2.00 +1.75 × 155° in the right eye and +3.00 +2.50 × 30° in the left eye. Corneal tomography was stable in the right eye, but there was mild steepening and corneal thinning in the left eye that was worse than the 2009 examination. No intervention was pursued due to the mild change in refraction and tomography.

One year later in 2017, the patient obtained screening serum thyroid hormone levels in anticipation of surgical removal of bilateral ovarian cysts and was found to have free T3 (3.950 pg/mL) and free T4 (1.610 ng/dL) levels that were within the normal range; however, the TSH level was markedly decreased (0.014 uIu/mL; normal range: 0.400 to 4.200 uIu/mL). She was evaluated by her endocrinologist, who obtained a thyroid ultrasound that noted bilateral enlargement of thyroid lobes that was causing her hyperthyroid state. She was subsequently prescribed oral carbimazole 5 mg daily and radioactive iodine therapy was planned. Her ophthalmic examination at that time showed CDVA of 20/30 in the right eye and 20/60 in the left eye with an increase in manifest astigmatism to 2.50 D in the right eye and 5.00 D in the left eye.

Pentacam imaging (Oculus Optikgeräte, Wetzlar, Germany) demonstrated stable findings in the right eye but progressed inferior steepening (maximum keratometry = 45.50 D) and inferior corneal thinning of 482 microns (Figure 2). Given the dramatic change in CDVA, manifest astigmatism, and increase in corneal thinning, accelerated epithelium-off CXL was performed in the left eye without complications (Table 1).

Scheimpflug tomography in 2017 of the (A) right eye in 2012 demonstrating stability compared to the 2009 examination and (B) the left eye demonstrating progression of focal steepening and thinning.

Figure 2.

Scheimpflug tomography in 2017 of the (A) right eye in 2012 demonstrating stability compared to the 2009 examination and (B) the left eye demonstrating progression of focal steepening and thinning.

Discussion

This case highlights the integral relationship between acute thyroid hormone alterations and the development of keratoconus and further supports the commonly held belief that keratoconus is a bilateral disease process even when presentation is highly asymmetric and progression in the less affected eye is significantly delayed.

Previous case reports have highlighted the association between thyrotoxicosis and keratoconus,1–5 and various studies have evaluated the possible pathophysiology in the disease process. Patients with thyroid gland dysfunction have elevated levels of thyroxine in both the tear film and the aqueous humor, which may cause biomechanical changes in the corneal stroma due to thyroxine-receptor interactions.6–8

Additionally, studies have demonstrated the importance of thyroxine in corneal dehydration and transparency, as well as the natural development of corneal epithelium and endothelium.9,10 Also, hormonal changes affecting corneal biomechanics and topography during pregnancy could be related to the thyroid. Dysthyroidism may directly influence corneal biomechanics.11 This case demonstrates the long-term stabilizing effects of CXL for thyroid-induced keratoconus, even when a second inciting event occurred that significantly altered thyroid hormone levels. Long-term data have shown that CXL for progressive keratoconus is stable for at least 10 years.12 As stated previously, the pathophysiology of this disease process is not completely known, but it is presumed that the corneal biochemical changes caused by thyroid gland dysfunction are ongoing. Thus, our case demonstrates that standard protocol CXL is robust enough to withstand the ongoing effects of thyroid gland dysfunction for at least 10 years.

This case presents further evidence of the association between acute alterations in thyroid hormone levels and the manifestation of keratoconus, the bilateral nature of the disease even when presentation is asymmetric and delayed, and the ability of CXL using the standard protocol to stabilize thyroid-induced keratoconus even when subjected to a second thyrotoxicosis. Endocrinologists should be informed to send patients with thyroid gland dysfunction for corneal screening to exclude keratoconus.

References

  1. King E. Keratoconus following thyroidectomy. Trans Ophthal Soc U K. 1953;(73):31–39.
  2. Howard S, Raine J, Dattani M. Corneal rupture in a child with Down syndrome and hyperthyroidism. BMJ Case Rep. 2009;2009. doi:10.1136/bcr.08.2008.0842 [CrossRef]
  3. Gatzioufas Z, Thanos S. Acute keratoconus induced by hypothyroxinemia during pregnancy. J Endocrinol Invest. 2008;31:262–266. doi:10.1007/BF03345600 [CrossRef]
  4. Koçak Altintas AG, Gül U, Duman S. Bilateral keratoconus associated with Hashimoto's disease, alopecia areata and atopic keratoconjunctivitis. Eur J Ophthalmol. 1999;9:130–133. doi:10.1177/112067219900900210 [CrossRef]
  5. Lang GE, Naumann GO. Keratoconus in Alagille syndrome [article in German]. Klin Monbl Augenheilkd. 1991;198:555–557. doi:10.1055/s-2008-1046031 [CrossRef]
  6. Stachon T, Stachon A, Hartmann U, Seitz B, Langenbucher A, Szentmáry N. Urea, uric acid, prolactin and ft4 concentrations in aqueous humor of keratoconus patients. Curr Eye Res. 2017;42:842–846. doi:10.1080/02713683.2016.1256413 [CrossRef]
  7. Thanos S, Oellers P, Meyer Zu Hörste M, et al. Role of thyroxine in the development of keratoconus. Cornea. 2016;35:1338–1346. doi:10.1097/ICO.0000000000000988 [CrossRef]
  8. Kahán IL, Varsányi-Nagy M, Tóth M, Nádrai A. The possible role of tear fluid thyroxine in keratoconus development. Exp Eye Res. 1990;50:339–343. doi:10.1016/0014-4835(90)90134-G [CrossRef]
  9. Coulombre AJ, Coulombre JL. Corneal development: 3. The role of the thyroid in dehydration and the development of transparency. Exp Eye Res. 1964;3:105–114. doi:10.1016/S0014-4835(64)80024-5 [CrossRef]
  10. Masterson E, Edelhauser HF, Van Horn DL. The role of thyroid hormone in the development of the chick corneal endothelium and epithelium. Invest Ophthalmol Vis Sci. 1977;16:105–115.
  11. Tabibian D, de Tejada B, Gatzioufas Z, et al. Pregnancy-induced changes in corneal biomechanics and topography are thyroid hormone related. Am J Ophthalmol. 2017;184:129–136. doi:10.1016/j.ajo.2017.10.001 [CrossRef]
  12. Raiskup F, Theuring A, Pillunat LE, Spoerl E. Corneal collagen c 176 crosslinking with riboflavin 181 and ultraviolet-A light in progressive keratoconus: ten-year results. J Cataract Refract Surg. 2015;41:41–46.

CXL Methods

ParameterVariable for First Eye CXLVariable for Second Eye CXL
Treatment targetKeratoconusKeratoconus
Fluence (total) (J/cm2)5.45.4
Soak time (minutes)3030
Intensity (mW)318
Treatment time (minutes)305
Epithelium statusOff – 9-mm removalOff – 9-mm removal
Chromophore0.15% riboflavin (Peschke D)0.10% riboflavin (Peschke D)
Light sourceUV-X1000 (IROC)CCL-VARIO (Peschke)
Irradiation modeContinuousContinuous
Authors

From the Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California (RL, JBR); the Department of Ophthalmology, Faculty of Medicine, Alexandria University, Alexandria, Egypt (AE, YE); and University of Southern California Roski Eye Institute, Los Angeles, California (JBR).

The authors have no financial or proprietary interest in the materials presented herein.

Dr. Randleman did not participate in the editorial review of this manuscript.

Supported in part by an unrestricted departmental grant from Research to Prevent Blindness, Inc. to the USC Roski Eye Institute, Los Angeles, California.

AUTHOR CONTRIBUTIONS

Study concept and design (RL, AE, YE, JBR); data collection (AE, JBR); analysis and interpretation of data (RL, YE, JBR); writing the manuscript (RL, YE, JBR); critical revision of the manuscript (RL, AE, YE, JBR); supervision (AE, JBR)

Correspondence: Ahmed El-Massry, MD, Alexandria University Faculty of Medicine, Alexandria, Egypt. E-mail: ahmad.elmassry@gmail.com

Received: December 07, 2017
Accepted: February 16, 2018

10.3928/1081597X-20180301-02

Sign up to receive

Journal E-contents