This article is more than 5 years old. Information may no longer be current.
Young woman presents with long-standing bilateral photophobia and blurry vision
Click Here to Manage Email Alerts
A 24-year-old woman was referred to the cornea service for evaluation of bilateral corneal opacities resulting in decreased vision and painful light sensitivity.
The patient had been followed by an ophthalmologist since adolescence. Initially she suffered mostly from foreign body sensation. Over the ensuing years, her vision and photophobia gradually worsened. She found minimal relief from a trial with bandage contact lenses. At the time of her exam at the New England Eye Center, she reported constant blurry vision and sharp pain, especially in bright light, which she described as debilitating, given that her job required many hours working at the computer.
Her medical history and review of systems were unremarkable. Her ocular history otherwise included only refractive error. She had no allergies, and the only medication she took was an oral contraceptive. She knew of no eye conditions that ran in her family, although she admitted that her knowledge was limited because her father was estranged. She denied abuse of alcohol or illicit substances.
On examination, best corrected visual acuity was 20/30 in each eye. Pupils were round, equal and reactive to light. Significant photophobia was noted during pupillary exam. Confrontation visual field testing and extraocular motility were full. IOP was within normal limits. The conjunctiva was white and quiet. The corneal epithelium was clear and smooth with no staining.
Figure 1. Slit lamp photographs of the right and left eyes demonstrating symmetric rings of dense, white anterior stromal opacities with limbus-to-limbus diffuse stromal haze.
Images: Lewen M, Raizman MB
Figure 2. Slit lamp photographs of the right and left eyes with higher magnification view of the small, round deep stromal opacities.
Figure 3. Corneal topography of the right and left eyes demonstrates with-the-rule astigmatism but is otherwise unremarkable.
Anterior segment exam was remarkable for prominent round, irregular, patchy opacities arranged in a ring in the paracentral cornea and located at the level of the anterior stroma in both eyes. Diffuse corneal stromal haze was present, leaving no clear cornea between the lesions. The diffuse haze extended to the limbus. Smaller opacities were noted in the deep stroma, and these extended to the limbus bilaterally. There were no guttae or keratic precipitates. No anterior chamber reaction was present. The iris was normal with a clear lens in both eyes. Funduscopic exam was unremarkable.
What is your diagnosis?
Photophobia, blurry vision
The history and presentation of this patient with long-standing bilateral corneal opacities is highly suggestive of corneal dystrophy. While degenerative, infectious, inflammatory and environmental conditions can cause corneal opacification with subsequent photophobia and decreased vision, the chronicity and lack of evidence of active or prior inflammation make these conditions far less likely.
Corneal dystrophies have classically been delineated based upon the anatomic corneal layer most affected. Many of the dystrophies may involve multiple layers of the cornea, especially in advanced cases. For the present discussion, epithelial-stromal and stromal dystrophies are the most pertinent.
Epithelial-stromal dystrophies consist of multiple, distinct conditions that have all been linked to defects in the TGFB1 gene. The list includes Reis-Bücklers, Thiel-Behnke, lattice (multiple variants) and granular (type 1 and type 2) corneal dystrophies. The onset of symptoms tends to occur in childhood. The clinical course involves recurrent, painful corneal erosions and characteristic patterns of corneal opacification. For example, Reis-Bücklers corneal dystrophy demonstrates confluent, irregular geographic-like opacities, whereas granular corneal dystrophy presents discrete, sharp-edged granules that have been likened to breadcrumbs.
The list of stromal corneal dystrophies includes macular corneal dystrophy, Schnyder crystalline corneal dystrophy, congenital stromal dystrophy, fleck dystrophy, posterior amorphous corneal dystrophy, central cloudy dystrophy of François and pre-Descemet’s corneal dystrophies. Patients with these dystrophies tend to have smooth corneal epithelium that does not recurrently erode. However, they may have significant photophobia due to pronounced glare. Additionally, macular corneal dystrophy is unique in that it follows an autosomal recessive inheritance pattern, whereas the overwhelming majority of the aforementioned dystrophies are autosomal dominant.
Diagnosis and management
The absence of epithelial changes or erosions made a stromal corneal dystrophy more likely than an epithelial-stromal dystrophy. One particular finding on slit lamp examination was helpful in narrowing the differential diagnosis: the limbus-to-limbus stromal haze. Out of the long list of corneal dystrophies, there are only a few that are classically described as extending from limbus to limbus. This short list is comprised of Meesmann corneal dystrophy (an epithelial dystrophy), Reis-Bücklers corneal dystrophy (epithelial-stromal), macular corneal dystrophy (stromal) and Fleck corneal dystrophy (stromal).
As previously mentioned, Reis-Bücklers typically presents with confluent geographic opacification, and Fleck corneal dystrophy classically demonstrates dandruff-like stromal opacities. Neither of these presentations fits our patient’s findings. Given her history and classic findings of stromal opacities with diffuse corneal haze extending from limbus to limbus, she was diagnosed with macular corneal dystrophy.
She was counseled extensively on the nature of her condition and the natural progression of macular corneal dystrophy. It was explained that there is no permanent treatment, and that her cornea and vision would progressively deteriorate, likely necessitating transplantation in the future. She was offered penetrating keratoplasty given her debilitating discomfort; however, she elected for conservative management with regular follow-up. She was offered genetic testing to confirm the diagnosis, but she deferred at that time.
Discussion
Macular corneal dystrophy is an autosomal recessively inherited disease that results from a defect in the CHST6 gene. This leads to the accumulation of glycosaminoglycans within Bowman’s layer, the stroma, Descemet’s membrane and the endothelium. The onset tends to occur within the first decade of life, and severe visual impairment may begin between 10 to 30 years of age. Clinically, patients demonstrate central irregular opacities within the stroma that extend to the limbus. As the disease progresses, stromal haze involves the entire cornea, leaving little to no clear cornea between the focal opacities, and guttate may develop as well. The epithelium usually remains smooth, and so phototherapeutic keratectomy offers little benefit. Severe visual impairment can be treated with corneal transplantation, although opacification can recur in the graft. Corneal tissue from a patient with macular corneal dystrophy stained with Hale colloidal iron or Alcian blue will demonstrate the accumulation of glycosaminoglycans.
Conclusion
Multiple recent studies have compared penetrating keratoplasty with deep anterior lamellar keratoplasty in the surgical management of patients with advanced macular corneal dystrophy. While no formal recommendation has been established, the reports tend to demonstrate equivalent best corrected visual acuity between the two procedures. Rates of recurrence or graft failure between the two approaches are mixed and inconclusive because these results are heavily dependent upon the viability of the endothelium before and after surgery. We favor penetrating keratoplasty because the recurrence of lesions in the interface after lamellar keratoplasty can be severe. While no therapy exists to delay or reverse progression in macular corneal dystrophy, advances in genetic analysis offer hope for possible gene therapy in the future.
References:
Cheng J, et al. Ophthalmology. 2013;doi:10.1016/j.ophtha.2012.07.037.Kawashima M, et al. Am J Ophthalmol. 2006;doi:10.1016/j.ajo.2006.03.057.
Patel AK, et al. Cornea. 2009;doi:10.1097/ICO.0b013e31818c2c74.
Shimazaki J, et al. Am J Ophthalmol. 2002;doi:10.1016/S0002-9394(02)01523-4.
Sogutlu SE, et al. Am J Ophthalmol. 2013;doi:10.1016/j.ajo.2013.03.007.
Weiss JS, et al. Cornea. 2015;doi:10.1097/ICO.0000000000000307.
For more information:
Michael Lewen, MD, and Michael B. Raizman, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.Edited by Gregory D. Lee, MD, and Nora W. Muakkassa, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.