C
LINICALS
CIENCEPregnancy-induced Progression of Keratoconus
Kamil Bilgihan, MD,* Ahmet Hondur, MD,* Sabahattin Sul, MD,* and Sertac Ozturk, MD†
Purpose:To report eyes with keratoconus that progressed during pregnancy.
Methods:Seven eyes of 4 patients with progression of keratoconus during pregnancy were included in this study. The mean age of patients and the mean follow-up duration were 29.3 years and 39 months, respectively. Progressive keratoconus was documented with changes in refraction, corneal topography, and rigid gas-permeable lens fitting pattern. Patients with accompanying systemic and ocular diseases associated with keratoconus, uncontrolled atopic disease, and eye rubbing were excluded.
Results: Mean increase in spherical equivalent refraction and simulated keratometry values were 1.4 6 1.1 and 1.1 6 0.8 diopters, respectively. In eyes wearing rigid gas-permeable lenses, increase in corneal apical touch and decrease in the base curve radius of the best-fitting contact lens were observed.
Conclusions: Hormonal changes during pregnancy may affect corneal biomechanics negatively, and pregnancy may be a previously unrecognized risk factor for progression of keratoconus. To our knowledge, this is the first study showing pregnancy-induced keratoconus progression in patients with no accompanying disease. Key Words: keratoconus, pregnancy, progression, corneal topography (Cornea 2011;30:991–994)
K
eratoconus is characterized by progressive corneal ectasia and thinning, an increase in myopia and irregular astigmatism, eventual corneal scarring, and loss of vision. The pathological processes underlying keratoconus have not been fully understood, despite extensive research. Keratoconus is accepted to be a clinical condition in which multifactorial etiological factors lead to corneal conical protrusion. Eye rubbing and corneal refractive surgery are common factors, which can aggravate progression of keratoconus.The effect of pregnancy on the clinical course of keratoconus is mostly unknown. Only 2 cases of pregnancy-induced progression of post–laser in situ keratomileusis (LASIK) ectasia and a single case of acute corneal hydrops induced by hypothyroxinemia during pregnancy have been reported.1–3
In this study, we report 4 cases of keratoconus without any accompanying disease that progressed during pregnancy.
MATERIALS AND METHODS
Patients with pregnancy-induced progression of kerato-conus were included in the study. Medical records of these patients were reviewed for accompanying systemic and ocular diseases, predisposing factors, and clinical findings. All patients underwent a detailed clinical examination, including corneal topography and ultrasound pachymetry. To avoid any lens-induced changes in corneal curvature, corneal topographic examinations were performed 2 weeks after the removal of rigid gas-permeable (RGP) lenses.
Inclusion criteria were topographically documented progression of keratoconus, change in RGP contact lens fitting pattern, or change in refraction. Progression of keratoconus was confirmed if at least 1 or more of the following criteria were met: an increase of at least 1 diopter (D) in the steep or mean simulated keratometry (SimK) value in corneal topography, a 0.1-mm or more decrease in the base curve radius of the best fitting contact lens with minimal apical clearance, an increase of at least 1.0 D in astigmatism, or an increase of at least 0.5 D in manifest spherical equivalent refraction. Exclusion criteria were any accompanying systemic diseases associated with keratoconus, uncontrolled atopic disease, and eye rubbing.
RESULTS
Pregnancy-related progression of keratoconus was observed in 7 eyes of 4 patients. The mean age of patients was 29.3 years (range: 22–43 years) at the time keratoconus progression was detected, and the mean follow-up duration was 39 months (range: 4–108 months) (Table 1). No predisposing factors, accompanying systemic, and ocular disease associated with keratoconus were noted.
Two of the patients reported a recent decrease in their visual acuity. The other 2 patients did not have any visual symptoms, they were wearing RGP lenses, and progression was detected during their regular visits (Table 1). These patients had not changed their lens-wearing habits.
The mean changes in spherical equivalent refraction and astigmatism were 1.4 6 1.1 D and 0.8 6 0.6 D, respectively
Received for publication June 6, 2010; revision received November 7, 2010; accepted November 9, 2010.
From the *Department of Ophthalmology, Gazi University Medical School, Ankara, Turkey; and †Department of Ophthalmology, Ufuk University Medical School, Ankara, Turkey.
None of the authors have financial or proprietary interest in any method or material mentioned. Also, no funding was received.
Reprints: Ahmet Hondur, Gazi Universitesi Hastanesi Goz Hastaliklari AD, 13. Kat, Besevler, Ankara 06500, Turkey (e-mail: ahondur@gazi.edu.tr). CopyrightÓ 2011 by Lippincott Williams & Wilkins
(Table 2). Topographically, progression of keratometric values was noted (Table 2; Figs. 1A and 1B). Mean increases in the steep and mean SimK values were 1.0 6 0.9 D (range: 20.2 to 2.5 D) and 1.1 6 0.8 D (range: 0.3–2.4 D), respectively.
In patients wearing RGP lenses, marked corneal apical contact was observed, which was beyond the minimal apical contact—or no apical contact with minimal apical clearance—of these lenses at previous visits. The mean decrease in the base curve radius of the best-fitting lens in 3 eyes (patient 1, OU; patient 3, OS) was 0.3 6 0.1 mm (range: 0.2–0.4 mm).
Progression was also documented in an eye with stable topography for 7 years after anterior lamellar keratoplasty (patient 2, OS). Stopping of progression after pregnancy was documented in 1 patient (patient 1; Figs. 1B and 1C). The other 2 patients (patients 2 and 3) have not completed adequate follow-up to document stabilization of keratoconus, and the last patient (patient 4) was treated with corneal cross-linking.
DISCUSSION
In this study, we report 4 keratoconus patients in whom the disease has progressed during pregnancy. Progression was documented with changes in corneal topography, RGP lens-fitting pattern, and refraction.
Stability of keratoconus before pregnancy, its progression during pregnancy, and its stabilization after pregnancy have been completely documented in patient 1 (Figs. 1A, 1B, and 1C). Patients 2 and 3 have not completed adequate follow-up to document stabilization of keratoconus. However, patient 2 had
stable refraction and corneal topography for 7 years before progression was noted, and patient 3 demonstrated apparent progression in a brief period of only 4 months. Another interesting point was that progression in the last patient occurred at age 43, which is an age when keratoconus is expected to be mostly stable. The clinical features of these patients indicate that progression occurred during pregnancy.
Recently, the influence of hormone status on the severity and progression of keratoconus has been reported by the Collaborative Longitudinal Evaluation of Keratoconus Study Group.4
They could not disclose any influence of hormone status on keratoconus, which seems to be contradictory to our results. However, the Collaborative Longitudinal Evaluation of Keratoconus Study did not include any pregnant patients. Instead, the study involved patients 48 to 59 years old and evaluated the effects of menopause and external hormone replacement therapy. The study group also admitted that the slow progression of keratoconus in their particular age group represented a limitation.
Contrary to the Collaborative Longitudinal Evaluation of Keratoconus Study, there have been a few reports of corneal ectasia progression during pregnancy. Gatzioufas and Thanos3 have reported a case of hypothyroxinemia-induced acute corneal hydrops during pregnancy. The authors suggested that the progression was related to thyroid gland dysfunction because the deterioration of keratoconus coincided with the lowest plasma thyroxine level. In the context of studies indicating a possible link between thyroid gland dysfunction and keratoconus, and rapid recovery of their patients with
TABLE 1. Clinical Features of the Patients Patient/
Age (yr) Symptom
Duration of Stability Before Progression Time Point of Progression Documentation Time Course of Progression (mo) Total Follow-up (mo) RGP Lens Wear Duration Additional Feature 1/22 None 7 mo Sixth month of pregnancy 11 30 3 years, OU None 2/28 VA decrease 84 mo 3 months after delivery 7 108 — LK (OD) 3/24 None NA Sixth month of pregnancy 4 4 3 years, OS None 4/43 VA decrease NA Sixth month of pregnancy 12 12 — Second pregnancy
LK, lamellar keratoplasty; NA, not available; VA, visual acuity; mo, months; RGP, rigid gas-permeable.
TABLE 2. Corneal Topography, Refraction, and Pachymetry Data of Patients Patient/ Eye Baseline SimK SimK After Progression Baseline Refraction (D) Baseline BSCVA Refraction After Progression (D) BSCVA After Progression Baseline Pachymetry (mm) 1/OD 45.7/48.7 47.6/50.6 22.0 3 60 20/32 (20/20 with RGP lenses) 22.0–3.5 3 65 20/40 (20/20 with RGP lenses) 450 1/OS 45.4/47.7 47.6/50.2 21.5 3 120 20/32 (20/20 with RGP lenses) 22.0–3.0 3 120 20/40 (20/20 with RGP lenses) 450 2/OD 45.5/50.2 45.8/51.0 20.5–2.5 3 35 20/20 23.5 3 30 20/20 495 2/OS 42.9/47.4 45.0/48.6 2.0–2.25 3 140 20/32 21.75 3 30 20/32 420 3*/OD 44.9/48.0 45.0/48.2 Plano 20/20 20.5 3 35 20/20 490 3/OS 45.3/49.9 46.1/49.7 23.5 3 145 20/32 (20/20 with RGP lenses) 20.5–3.0 3 140 20/32 (20/20 with RGP lenses) 470 4†/OD 45.9/50.8 46.6/51.4 24.0 3 25 20/32 21–4.0 3 25 20/32 470 4†/OS 45.6/50.7 45.9/51.1 24.5 3 170 20/32 20.75–5.0 3 180 20/32 483
BSCVA, best spectacle–corrected visual acuity; RGP, rigid gas-permeable; SimK, simulated keratometry (in diopters); D, diopters. *No marked progression; †Treated with collagen cross-linking.
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| www.corneajrnl.com q2011 Lippincott Williams & Wilkinsthyroxine supplementation, they suggested a possible link between progression of keratoconus and thyroid disease in pregnancy.3
Post-LASIK ectasia is accepted to be similar to keratoconus in clinical behavior. In most instances, it is actually exacerbation of preexisting subclinical keratoconus after LASIK. Hafezi and Iseli1
reported a case of bilateral iatrogenic keratectasia 26 months after LASIK, which developed during pregnancy. This patient was successfully treated with corneal cross-linking, which provided regression in keratometric values. However, the patient demonstrated exacerbation of ectasia in 1 eye during her second pregnancy.1 Similarly, Padmanabhan et al2reported a case of post-LASIK ectasia developing during pregnancy. However, this patient was found to have a high risk for ectasia before LASIK. In contrary to previous studies,1–3
none of the patients in our study had any associated disease or predisposing factor.
Recent studies have suggested that changes in estrogen levels may play a role in corneal ectasia. Estrogen receptors have been identified in cornea,5–7
and a significant stiffness-reducing effect of estrogen on cornea has been shown in an experimental study, which suggests that high estrogen states—such as pregnancy—may predispose biomechanically weak corneas to ectasia development or progression.8
Various studies have demonstrated elevated levels of collagenolytic and gelatinolytic activities in keratoconic corneas.9–13
Matrix metalloproteinase (MMP) levels are in-creased, whereas tissue inhibitors of MMPs (TIMPs) are decreased in the keratoconic corneas.13–15Therefore, it has been suggested that proteinases (collagenases and MMPs) may play an important role in the pathogenesis of keratoconus.16 Similarly, proteinase enzymes play key roles in various points of pregnancy. Proteinases contribute to extracellular matrix
remodeling required for follicular development and ovulation, loosening of the collagen framework of the endometrium for implantation, growth and softening of the cervix, and relaxation of the pelvic bones for delivery.17–20In addition, various studies have demonstrated that serum levels of MMPs are increased and serum levels of TIMPs are decreased during pregnancy.21–24 This implies that increased levels of proteolytic enzymes and decreased levels of their inhibitors during pregnancy are important for the progression of keratoconus during pregnancy. An important molecule that plays key roles in pregnancy is relaxin. Relaxin was discovered in 1926 by Hisaw25
, who noted relaxation of the pubic ligament in virgin guinea pigs after injection of serum from pregnant guinea pigs. The most consistent biological effect of relaxin is its ability to stimulate the breakdown of collagen. It increases the synthesis of the collagen-degrading enzymes and MMPs and decreases the synthesis of TIMPs.26 Therefore, relaxin may also play a role in the progression of keratoconus during pregnancy through MMPs and TIMPs.
The major implication of our study is that hormonal changes during pregnancy may affect corneal biomechanics negatively, and pregnancy may be a previously unrecognized or underestimated risk factor for progression of keratoconus. Currently, corneal cross-linking is available as an effective treatment to stop keratoconus progression. If further studies demonstrate a significant risk of keratoconus progression during pregnancy, then corneal cross-linking may be more extensively applied in patients with keratoconus considering pregnancy.
In conclusion, our data imply that pregnancy may be an unrecognized risk factor for progression of keratoconus. To the best of our knowledge, this study is the first report of pregnancy-induced keratoconus progression. Further studies are required to elucidate the clinical correlation of keratoconus and pregnancy.
FIGURE 1. A, Corneal topography of an eye before pregnancy (patient 1, right eye). B, Progression in keratometric values and size of the cone were noted about 11 months later, at the sixth month of pregnancy in the same eye. C, No further progression was observed 11 months later, at 8 months after delivery.
q2011 Lippincott Williams & Wilkins www.corneajrnl.com |
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