Increasing myopia in a patient complaining of glare and photophobia

On examination, the corneas were significantly abnormal; fine anterior stromal haze was seen superiorly in the left eye, with some endothelial vesicles and bullae.

Issue: November 1, 2006

ByHelen K. Wu, MD

ByTom Hsu, MD

A 44-year-old man was referred to the cornea service at the New England Eye Center for the evaluation and management of decreasing vision in both eyes, left worse than right. Over the past few years he began experiencing greater difficulty focusing on objects at a distance. More specifically, he noted that his symptoms were exacerbated by bright light, which caused photophobia and disabling glare. He described a halo-like effect that combined with the photophobia and began to significantly affect his daily activities. He visited his local optometrist several times over the past few years, where his manifest refraction continued to change from visit to visit.

Shazia Ahmed

My Hanh T. Nguyen

He denied any ocular history other than progressive myopia. His medical history included end stage renal disease, onset in childhood, with a failing kidney transplant in 1991. He was currently on dialysis and was scheduled for a repeat renal transplant in the coming months. In addition, he had high-tone deafness, first detected in his high school years. He denied any family history of ocular disease and was not aware of any family history of kidney problems.

Examination

On examination, the patient’s best corrected visual acuity was 20/70 in both eyes. Manifest refraction was –15.75 D in the right eye and –17 D in the left. IOP by applanation was 15 mm Hg bilaterally. Pupils were equally reactive without afferent pupillary defect. Visual fields by confrontation were intact. On slit lamp examination, the conjunctiva was white and quiet bilaterally. The corneas were significantly abnormal, with changes much more pronounced in the left eye. There was a fine anterior stromal haze superiorly, with some endothelial vesicles and bullae (Figures 1 and 2). The anterior chambers were without cell or flare. The lenses showed approximately 1+ nuclear sclerotic cataracts, but more significantly, anterior greater than posterior lenticonus (Figure 2). There was a slight posterior subcapsular cataract present in both eyes. On retroillumination, a central white reflex could be seen at the level of the lens (Figure 3). The remainder of the exam was normal, including a dilated funduscopic exam, which showed a flat, attached retina without any lesions.

Color photograph of the left eye. Note the anterior stromal haze in the superior portion of the cornea with the set of parallel stromal bands centrally.

Slit beam view of the left cornea revealing endothelial vesicles and bullae around the edges of the beam. The anterior lens capsule demonstrates significant lenticonus.

Retroillumination of the left eyedemonstrating a central white opacity.

Images: Hsu T, Wu HK

What is your diagnosis?

Photophobia, glare

In light of the patient’s symptoms, the corneal changes can be considered to be either an isolated finding or part of a systemic picture. Certainly some diagnoses to be considered when looking at corneal haze include anterior basement membrane dystrophy, Fuchs’ endothelial dystrophy, posterior polymorphous membranous dystrophy, as well as a variety of infectious etiologies. With regards to infection, this can be considered less likely given the presence of a white, quiet eye as well as the bilateral and slowly progressive nature of the pathology. The corneal findings did not support the presence of Fuchs’ dystrophy, given the lack of guttae or stromal edema. Similarly, while anterior basement membrane dystrophy can certainly result in a geographic region of corneal haze, the lesions in this patient were primarily posterior and involved the endothelium.

Posterior polymorphous membranous dystrophy is a diagnosis with similar corneal findings. In this disease, vesicles or blisters are found adherent to the corneal endothelium. They are usually found in clusters, although isolated vesicles are frequently seen. Within the posterior stroma, there are often linear opacified bands and areas of stromal haze with an irregular scalloped edge. While this condition usually affects both eyes, there can be marked asymmetry in the severity of disease between eyes. Recalling Figures 1 and 2, our patient’s cornea bears a striking resemblance.

Stopping at the cornea would be an incomplete assessment of this patient. The corneal changes could certainly be the root cause of his complaints of glare and photophobia, but we need to account for the lenticular changes as well as his renal and cochlear disease. By Ockham’s razor, a unifying syndrome would be ideal for consideration. Usher’s syndrome, a disease of retinitis pigmentosa accompanied by varying degrees of deafness, can present with gradual decreasing vision, but we did not see any retinal findings suggestive of retinitis pigmentosa. Alstrom syndrome is a rare disease with elements of cone-rod dystrophy, deafness, obesity and juvenile diabetes often progressing to renal failure. Several of these key elements are missing in our patient, thereby excluding it as a diagnosis. Alport syndrome, on the other hand, is a disease often defined by the triad of early high-tone deafness, juvenile renal disease and specific ocular findings. It is this diagnosis that best describes our patient.

Discussion

Alport syndrome is a heterogeneous disease in terms of symptom severity secondary to the various modes of inheritance. It affects roughly one in 5,000 children, and about 85% of cases are X-linked. The remainder exhibit autosomal recessive and autosomal dominant patterns.

As with most X-linked diseases, male patients with X-linked Alport syndrome show the most severe forms of the disease. The defects in Alport syndrome are secondary to mutations in the alpha-chains of type IV collagen. Specifically, the classes of alpha-chains affected are found predominantly in the glomerular basement membrane, Descemet’s membrane of the cornea, Bruch’s membrane in the retina, the anterior lens capsule, lungs and cochlea. Not surprisingly, these represent some of the areas where Alport syndrome manifests its symptoms. With the damage to the glomerular basement membrane, hematuria tends to be the first presenting symptom, usually within the first few years of life. In female patients with the X-linked form, progression to renal failure is less likely.

High-tone deafness becomes significant in the late teens, with some cases progressing to deafness in the frequencies of the human conversational range. Ocular findings are never present congenitally; rather, they become apparent in late childhood. Because of the location of type IV collagen in the eyes, the classical ocular findings include posterior polymorphous membranous dystrophy, anterior lenticonus, rarely posterior lenticonus, posterior subcapsular cataracts and, in the retina, a dot and fleck retinopathy. All of these symptoms are attributable to disruptions in the associated collagen structures. With regards to the retinopathy, these lesions are postulated to be lipofuscin deposits secondary to an abnormal Bruch’s membrane. Similarly, anterior lenticonus is due to forward pressure on the weakened, thinnest portion of the anterior lens capsule.

In our patient, we felt that his symptoms were primarily due to the lenticonus and subcapsular cataract. An uncomplicated continuous curvilinear capsulorrhexis with phacoemulsification was performed, which alleviated much of his glare and unstable myopia.

For more information:

Tom Hsu, MD, and Helen K. Wu, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.

Edited by Shazia Ahmed, MD, and My Hanh T. Nguyen, MD. Drs. Ahmed and Nguyen can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Ahmed and Nguyen have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.

References:

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Pelit A, Oto S, Yilmaz G, Akova YA. Spontaneous rupture of the anterior lens capsule combined with macular hole in a child with Alport’s syndrome. J Pediatr Ophthalmol Strabismus. 2004;41(1):59-61.

Sukhija J, Saini JS, Jain AK. Phacoemulsification and intraocular lens implantation in an Alport’s syndrome patient with bilateral anterior and posterior lenticonus. J Cataract Refract Surg. 2003;29(9):1834-1836.

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