|Year : 2019 | Volume
| Issue : 3 | Page : 221-224
Brittle cornea syndrome
Rani Menon, Sharika S Menon
Consultant Ophthalmologist, Dr. Rani Menon's Eye Clinic, Thrissur, Kerala, India
|Date of Web Publication||31-Dec-2019|
Dr. Rani Menon
Dr. Rani Menon's Eye Clinic, Thrissur, Kerala
Source of Support: None, Conflict of Interest: None
Brittle cornea syndrome is a rare generalized connective tissue disorder associated with extreme corneal thinning and other features such as blue sclera, keratoconus, keratoglobus, and high myopia. In this report, the mother and both the children had blue sclera of varying intensity along with corneal thinning in the children which was measurable only in the elder sibling.
Keywords: Blue sclera, brittle cornea, keratoconus, keratoglobus
|How to cite this article:|
Menon R, Menon SS. Brittle cornea syndrome. Kerala J Ophthalmol 2019;31:221-4
| Introduction|| |
Blue sclera with corneal fragility is an underrecognized ocular disorder. This case is reported due to its rarity and also to increase awareness to screen for associations at an early age and warn the patients about impending ocular risks.
Brittle cornea syndrome (BCS) is a rare autosomal recessive connective tissue disorder that presents with corneal thinning and fragility. Due to corneal thinning, they are predisposed to develop keratoglobus, keratoconus, high myopia, and irregular astigmatism. Furthermore, in the later stages, they are prone to spontaneous corneal rupture, which leads to scarring and loss of vision in almost all of them affected by BCS.
| Case reports|| |
This is the case report of two siblings, sibling 1 is a 10-year-old girl and sibling 2 is a 4-year-old boy born of a nonconsanguineous marriage.
Case 1 (Sibling 1 – 10-year-old girl)
She was wearing glasses from the age of 6 years, for progressive defective vision. On examination, unaided visual acuity was 4/60 in the right eye and 2/60 in the left eye with best-corrected visual acuity of 6/36 in the right eye 6/18 in the left. Refraction readings were −3.75 sph − 5.75 cyl@13*(OD) and −6.5sph −1.25 cyl@169*(OS). Slit-lamp examination showed bluish discoloration of the sclera with globular cornea with extreme corneal thinning and protrusion both eyes. Corneal diameter was 12 mm both eyes.
The sclera was moderately blue [Figure 1].
Corneal topography by pentacam showed [Figure 2] extreme corneal thinning all around with thinnest pacymetry reading of 294 μm (OD) and 290 μm (OS).
|Figure 2: Corneal topography by pentacam showed extreme corneal thinning all around with thinnest pachymetry reading of 294 μm (OD) and 290 μm (OS)|
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Fundus examination was normal with a cup disc ratio of 0.4 both eyes. Periphery was also normal.
Intraocular pressures (IOPs) by Goldmann applanation tonometry at 2 pm was 20 mm in both eyes. Corrected IOP (after central corneal thickness [CCT]) was 32.5 mmHg (OD) and 32.75 mmHg (OS).
Optical coherence tomography (OCT) disc was normal with normal neuroretinal rim. OCT macula [Figure 3] showed normal foveal contour with macular thickness within normal limits.
|Figure 3: Optical coherence tomography disc was normal with normal neuroretinal rim. Optical coherence tomography macula showed normal foveal contour with macular thickness within normal limits|
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B scan was done to assess Retino Choroido Scleral (RCS) thickness and revealed RCS = 1.1 mm close to optic disc in both eyes, which was reduced.
Systemic examination was within normal limits for her age. No evidence of joint hyperextensibility or hearing loss.
Case 2 (Sibling 2 – 4-year-old boy)
He was brought for evaluation along with the elder sibling. Refraction −1.00 sph −2.5 cyl@15*(OD) and +2.00 sph −4.5cyl@163*(OS). Slit-lamp examination and fundus were within normal limits. Gross corneal thinning as in the elder sibling was not observed, but bluish discoloration of the sclera was more marked. [Figure 4] IOPs and topography could not obtained.
B scan shows RCS thickness = 1.13 mm
Parents –The mother has mild bluish discoloration of the sclera. [Figure 5] Corneal topography results were within normal limits. OCT disc and macula was also normal with corrected IOPs of 16 mm both eyes.
The mother denies any similar history in her two sisters and her parents. The father has no sclera discoloration, and CCT was also within normal limits.
| Discussion|| |
BCS is a rare generalized connective tissue disorder associated with extreme corneal thinning and other features such as blue sclera, keratoconus, keratoglobus, and high myopia. Extraocular manifestations include deafness, joint hypermobility, skin hyperelasticity, and developmental dysplasia of the hip.
BCS results from mutation in one of the two genes, ZNF469, encoding zinc finger protein 469 and second PRMD5, encoding PR domain-containing protein 5. Immunohistochemistry in eyes with BCS also found PRDM5 localisation in Bruch's membrane of retina apart from the corneal epithelium. Mutations in the ZNF469 gene are causative for BCS Type 1 and BCS Type 2 is caused by mutations in the PRDM5 gene., Mutations in ZNF469 gene are thought to be associated with changes in CCT. Recent researches also confirmed that ZNF469 also plays an important role in anterior segment development and hence in the pathogenesis of ocular disorders such as glaucoma., PRDM5 is found to be associated with extracellular matrix physiology.
- Thin cornea (CCT often <400 μm); BCS corneas are unable to withstand normal biomechanical stresses and hence cannot maintain their structural integrity and shape, hence resulting in early-onset progressive keratoconus and/or keratoglobus, later leading onto corneal perforation and scarring
- Blue sclerae are usually present in those affected by BCS, but this is not universal, may disappear over time, is also present in many individuals identified to be heterozygous carriers for BCS-associated mutations
- Secondary glaucoma has been reported in many affected patients, particularly those with extensive corneal damage following rupture
- Retinal detatchments have also been identified in few according to previous literature.
Auditory features are less pronounced, but one-third of the patients have been found to have mixed sensineural and conductive hearing loss.
Other musculoskeletal features observed were developmental dysplasia of hip, scoliosis, and small joint hypermobility and skin hyperelasticity.
If there are no obvious extraocular features, extreme corneal thinning or spontaneous ocular rupture should be highly suspected for suspecting BCS.
Moreover, there exist some other diseases associated with brittle cornea and blue sclera such as the Ehlers–Danlos syndrome, osteogenesis imperfecta, and the Marfan syndrome.,
However, patients with these diseases frequently have more pronounced generalized connective tissue manifestations as compared to more of ocular manifestations in BCS.
Mainstay includes early diagnosis, preventing ocular rupture, and optimizing visual function. Providing protective polycarbonate spectacles can be beneficial to some extent in preventing direct trauma and rupture.
In cases of progressive BCS, epikeratoplasty (a partial thickness corneal graft) has been used in prevention of corneal rupture, which aims to increase the thickness of limbus to limbus and allow a penetrating keratoplasty subsequently  because of the extreme thinning and frailty, the corneas in BCS patients were not suitable for a corneal cross-linking procedure.
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 initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]