Woman presents with worsening blurry vision and glare
Both eyes exhibited central corneal branching lesions.
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A 53-year-old woman was referred by her general ophthalmologist for cornea evaluation due to glare and blurry vision that started in her 30s and progressively worsened.
She also reported difficulty with driving, especially at night, because of glare, as well as difficulty working in front of her computer. Her medical history was significant for diabetes and skin cancer; her family history was unremarkable. No one from her family had experienced any similar vision problems. The patient did not have any facial dysmorphisms.
Examination
On initial examination, the patient’s visual acuities were 20/80 in the right eye with improvement with pinhole to 20/50 and 20/40 in the left eye without improvement with pinhole. Pupils were equal, round and reactive without an afferent pupillary defect. Extraocular movements were full, and confrontational visual fields were intact to finger counting in both eyes. IOPs were also within normal limits. Eyelid exam did not show any lagophthalmos or dermatochalasis. Anterior segment examination is shown in Figure 1. The right eye cornea exhibited central corneal branching lesions measuring 8 mm vertically and 9 mm horizontally. The left eye cornea exhibited central corneal branching lesions measuring 5.5 mm vertically and 5.5 mm horizontally. These lesions did not stain with fluorescein in either eye. The limbus was not involved in either eye. Posterior segment examination was unremarkable.
Source: Eleni Konstantinou, MD, and Naveen K. Rao, MD
Anterior segment OCT was subsequently obtained to define the depth of these corneal lesions. As seen in Figure 2, the lesions started in the epithelium and extended into the anterior stroma. Additionally, there was Bowman’s layer atrophy.
What is your diagnosis?
See answer below.
Corneal epithelial and stromal lesions
The patient was found to have bilateral corneal epithelial and stromal lesions that per report started in her 30s and progressively increased in number and size, leading to glare and blurry vision.
The differential diagnosis for bilateral progressively worsening corneal epithelial and stromal lesions includes corneal epithelial-stromal dystrophies and stromal dystrophies. Amongst these, lattice corneal dystrophy type 1 (classic), familial amyloidosis or Meretoja syndrome (previously known as lattice corneal dystrophy type 2), granular corneal dystrophy type 1 (classic), granular corneal dystrophy type 2 (also known as Avellino corneal dystrophy) and macular corneal dystrophy are conditions that could present in a similar way. Familial amyloidosis is a systemic disease whose amyloid deposition in the cornea starts in the periphery and spreads to the center, whereas in lattice corneal dystrophy type 1, it starts centrally, and the periphery is usually spared. Patients also have characteristic dermatochalasis, lagophthalmos, and cranial and peripheral nerve palsies. In granular corneal dystrophy type 1, the deposits are also found in the epithelium and anterior stroma, but they are circular and not linear. Granular corneal dystrophy type 2 is a combination of granular and lattice-like deposits. In macular corneal dystrophy, the entire cornea is involved, and cornea between the deposits appears cloudy. Macular corneal dystrophy also generally presents at a younger age.
Clinical course
Given the distinct clinical appearance of the patient’s corneal deposits and the absence of systemic manifestations, our patient was diagnosed with lattice corneal dystrophy type 1. Her daughters were in their late 20s, and upon examination, they did not have any corneal lesions. Due to the patient’s significant symptoms, surgery was recommended. Deep anterior lamellar keratoplasty was initially planned for the right eye, but due to intraoperative Descemet’s membrane perforation, the surgery was converted to penetrating keratoplasty. Histopathology of the corneal button showed amyloid deposits in the corneal stroma, which confirmed our diagnosis of lattice corneal dystrophy type 1 (Figure 3). At the postoperative day 1 follow-up visit, the patient’s visual acuity was 20/200; at her 1-week follow-up, it was 20/100, and a month later, it was 20/100. At her most recent visit, 10 months after surgery, after most of the sutures were removed, her visual acuity was 20/50 (Figure 4).
Discussion
Corneal dystrophies are symmetric and bilateral conditions that affect the cornea due to a genetic aberration. The diagnosis is generally clinical, based on pattern recognition of the specific deposits in the different corneal layers, and can be confirmed by histopathological analysis.
Lattice corneal dystrophy type 1 (LCD1), also known as Biber-Haab-Dimmer disease, is a relatively common type of corneal dystrophy. It is inherited in an autosomal dominant pattern; the responsible mutation is in the 5q31 chromosome locus with a defective TGFBI gene. Its end product is a defective keratoepithelin protein.
The corneal deposits in LCD1 are made of amyloid. Clinically, they appear as lattice-like filamentous lines. They start in the subepithelium and extend deeper into the anterior stroma over time. Mainly the center of the cornea is involved, and the corneal limbus and the periphery are typically spared. Initially the spaces between the lesions are clear, but with time, the stroma between the deposits takes on a “ground-glass” appearance.
Patients may present with symptoms at a young age, as early as childhood, and these symptoms become more prominent later in life as the condition progresses. Epithelial erosions occur frequently due to the location of the deposits in the anterior cornea and may cause recurrent pain. Vision can diminish as soon as the patient’s 20s to 30s due to stromal haze and irregular astigmatism.
LCD1 is characterized by atrophy of the corneal epithelium under light microscopy, with basal epithelial cell degeneration and thinning of Bowman’s layer over time. The amyloid material deposits between the basement membrane of the epithelium and Bowman’s layer, which disrupts the architecture of the corneal stroma. These amyloid deposits stain with Congo red stain, periodic acid-Schiff stain and Masson’s trichrome stain. They also stain metachromatically with crystal violet. Under polarized light, they demonstrate apple-green birefringence, and they fluoresce with thioflavin-T stain.
Recurrent erosions in LCD1 are treated in the typical manner with lubrication and bandage contact lenses, phototherapeutic keratectomy and superficial keratectomy. In more progressed stages, as the deposits become more confluent and the haze denser, causing vision decline, surgery is the definitive treatment. Due to preservation of the corneal endothelium in DALK, and thus decreased risk for rejection and fewer intraocular complications, it is generally preferred over PK. On the other hand, PK can offer more immediate improvement in visual acuity.
Even after surgery, the risk for recurrence of deposits in LCD1 is high.
- References:
- Basic and Clinical Sciences Course. Section 8: External disease and cornea. American Academy of Ophthalmology. 2017;133-135, 145-151, 187.
- Cheng J, et al. Ophthalmology. 2013;doi:10.1016/j.ophtha.2012.07.037.
- Friedhofer H, et al. Aesthet Surg J. 2017;doi:10.1093/asj/sjx172.
- Klintworth GK. Orphanet J Rare Dis. 2009;doi:10.1186/1750-1172-4-7.
- Munier FL, et al. Nat Genet. 1997;doi:10.1038/ng0397-247.
- Weiss JS, et al. Cornea. 2015;doi:10.1097/ICO.0000000000000307.
- For more information:
- Eleni Konstantinou, MD, and Naveen K. Rao, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Christine Benador-Shen, MD, and Malgorzata Dymerska Peterson, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.