July 2019

CORNEA

Presentation Spotlight
Study links late-onset ectatic progression with estrogenic hormones


by Stefanie Petrou Binder, MD EyeWorld Contributing Writer


Figure 1. Scheimpflug image showing progression of keratoconus until stable after approximately 4 months using tibolone

Figure 2. Scheimpflug image showing large bilateral flattening after CXL
Source: Emilio Torres-Netto, MD

 

A published case report,1 presented at the 23rd European Society of Cataract and Refractive Surgeons Winter Meeting, suggests that female keratoconus patients on tibolone (selective tissue estrogenic activity regulator [STEAR] therapy) need to be closely monitored. The report describes an association of rapid progression of keratoconus with STEAR therapy in the case of a 49-year-old woman.

Ectasia worse despite increased age

The patient began STEAR therapy for endometriosis. Roughly 4 months after initiating STEAR and 3 months after an ovariectomy, ectasia was increased in the eyes of the previously stable patient.
According to Emilio Torres-Netto, MD, who presented on behalf of his colleagues, estrogen may be one of the factors decreasing corneal biomechanical stability, along with pregnancy and hypothyroidism. Factors having the opposite effect include increasing age and tobacco smoking.
“Although some of the evidence is weak for the effect that a number of these factors have on corneal biomechanics, we all agree on the effect of age,” Dr. Torres-Netto said. “As the cornea gets older, it gets stiffer and that’s what makes our case interesting. We have a 49-year-old woman with bilateral stable keratoconus for 10 years, long-term stable BCVA and refraction, whose ectasia got worse, and was receiving no systemic or topical medications.”
After oral use of tibolone (2.5 mg/day) for 28 days and bilateral ovariectomies 17 days before, Scheimpflug image revealed a change in the corneal topography. Dr. Torres-Netto observed a flattening of the cornea, with Kmax 2.5 D lower in the patient’s left eye. The right eye experienced a flattening of 1.2 D.
Three months later, the patient complained about blurry vision. Her right eye had 20/20 but the left had 20/50 visual acuity. Dr. Torres-Netto noted a steepening of both corneas of up to almost 4 D. The Kmax was increased by 2.7 D in the right eye and by 3.8 D in the patient’s left eye (Figure 1).

Treating the ectasia

The team decided to handle the corneal modifications observed in both eyes with the use of epithelium-off accelerated corneal crosslinking, 9 mW/cm2 for 10 minutes (total fluence 5.4 J/cm2). Six months after bilateral crosslinking, the right eye Kmax was lowered by 5.5 D with 20/16 visual acuity, and the left sided Kmax was lowered by 6.1 D with 20/16 visual acuity.
“There is a strong similarity between tibolone, a selective estrogen activity regulator, and estrogen,” Dr. Torres-Netto explained. “It is not only similar in the chemical structure but also as a result of metabolism is rapidly converted into components with estrogenic effects, such as 3alpha-hydroxy-tibolone and 3beta-hydroxy-tibolone. Although there was nothing published on tibolone specifically, it has been shown that estrogen receptors are present in the corneal stroma.”
Estrogen receptors are thought to modify collagen and glycosaminoglycans biosynthesis. Such components play a central role in corneal composition and therefore in biomechanics. More evidence is needed, however, to prove the effects of estrogen on these molecules and to demonstrate how other factors like pregnancy, hypothyroidism, age, and smoking affect the cornea and the eye overall.
According to an unrelated in vitro study on the subject, estrogen was seen to reduce corneal stiffness by 36%.2 The authors noted that the significance of hormone status and its influence on the biomechanical stability of the cornea were largely underestimated.2 Another investigation demonstrated clinical evidence that hormonal changes occurring during gestation had an impact on keratoconus progression.3 In yet another study, a stable patient experienced corneal steepening following both of her pregnancies, despite the corneal stabilization from CXL that was performed after the first pregnancy.4
“Usually we expected to find a remodeling effect around 2 D, according to the Dresden protocol, which is the most effective protocol for corneal crosslinking. Accelerated CXL normally has a lower stiffening effect and is less effective than the Dresden protocol. In our case, however, it flattened the corneas up to 6 D, up to 9 months post-CXL [Figure 2],” Dr. Torres-Netto said.

About the doctor

Emilio Torres-Netto, MD
Center for Applied Biotechnology and Molecular Medicine
Ocular Cell Biology Group
University of Zurich
Zurich, Switzerland

Contact information

Torres-Netto: emilioatorres@me.com

References

1. Torres-Netto EA, et al. Late-onset progression of keratoconus after therapy with selective tissue estrogenic activity regulator. J Cataract Refract Surg. 2019;45:101–104.
2. Spoerl E, et al. Oestrogen-induced changes in biomechanics in the cornea as a possible reason for keratectasia. Br J Ophthalmol. 2007;91:1547–50.
3. Hoogewoud F, et al. Transitory topographical variations in keratoconus during pregnancy. J Refract Surg. 2013;29:144–6.
4. Hafezi F, Iseli H. Pregnancy-related exacerbation of iatrogenic keratectasia despite corneal collagen crosslinking. J Cataract Refract Surg. 2008;34:1219–21.

Financial interests

Torres-Netto: None

Study links late-onset ectatic progression with estrogenic hormones Study links late-onset ectatic progression with estrogenic hormones
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