This article is from February 2011 and may contain outdated material.
Jose Martinez* is a 65-year-old Latino who presented to our clinic with concerns about his central vision, which had been deteriorating for about a year, especially in the left eye. He recalled having progressive night vision loss when he was a teenager, which was followed, a few years later, by some loss of daytime peripheral vision as well.
Mr. Martinez believes he was born after an uncomplicated birth and delivery, but he had hearing problems at an early age, which resulted in the use of hearing aids. He reported no vertigo or balance problems and no family history of visual or hearing loss. He takes tamsulosin for prostatic hypertrophy.
We Get a Look
His BCVA was 20/70 in the right eye and 20/200 in the left. The anterior segment examination was notable for moderate posterior subcapsular cataracts in the right (Fig. 1 and Fig. 2) and left eyes. We noted a cortical cataract in his left eye. IOP was 16 mmHg in both eyes. The dilated fundus examination showed perifoveal atrophy. Retinal periphery was notable for significant RPE pigmentary clumps (bone spicules) and atrophy (Fig. 3 and Fig. 4).
The potential acuity meter suggested that the worsening visual acuity was related to the developing cataract rather than the retinal pathology. Optical coherence tomography peripapillary nerve fiber layer (NFL) testing revealed thinning of the NFL in both eyes (Fig. 5).
At the Slit Lamp. We noted moderate posterior subcapsular cataract (Fig. 1), which was also evident with retroillumination (Fig. 2). Both photos are of the right eye.
Diagnosis and Treatment
Based on the retinal exam, Mr. Martinez was initially diagnosed with retinitis pigmentosa (RP). Eventually, the diagnosis of Usher syndrome type 2 was established based on finding the mutated gene USH2A on chromosome 1q41. Many other syndromes may exhibit signs similar to Usher syndrome, including Alport syndrome, Alström syndrome, spondyloepiphyseal dysplasia congenita, Norrie disease, osteopetrosis, Refsum disease and Zellweger syndrome.
The simplest approach to diagnosing Usher syndrome is to test for the characteristic chromosomal mutations. Another approach is electroretinography (ERG), but this is often disfavored for children, since its discomfort can make the results unreliable.
The patient underwent uneventful cataract extraction and IOL placement in the left eye, followed by the right eye two weeks later. The surgeries were completed under retrobulbar anesthesia, given the history of tamsulosin use and the risk of intraoperative floppy iris syndrome.
The follow-up exam revealed visual acuities of 20/60 in the right eye and 20/40 in the left. The anterior segment exam was notable for trace cell in the right anterior chamber and well centered posterior chamber IOLs (Fig. 6). IOP was 16 mmHg in the right eye and 14 mmHg in the left. The dilated fundus exam was unchanged.
Imaging. Dilated fundus photographs of the right (Fig. 3) and left (Fig. 4) eyes show dark pigmentary clumps in the midperiphery and perivenous areas (bone spicules), attenuated retinal vessels and waxy optic disc pallor. OCT nerve fiber analysis (Fig. 5) demonstrates thinning of the NFL in both eyes. A slit-lamp exam (Fig. 6) of the left eye postoperatively is showing a well-centered posterior capsule IOL.
Usher syndrome is a recessively inherited disorder, characterized by the combination of sensorineural hearing loss and RP. It has a worldwide prevalence of one in 16,000 to one in 50,000.1 The wide range of prevalence must depend on ethnicity. The prevalence is approximately one in 17,000 people in the United States.
In Usher syndrome, the ocular morbidity is explained by the progressive retinal degeneration (rod-cone dystrophies) caused by abnormal production of photoreceptor proteins, resulting in severe visual impairment.2
There are three types of Usher syndrome. Type 1 is the most severe, with fast-progressing symptoms in early life causing total deafness with no vestibular function. Type 2 is the most common (67 percent) and is characterized by partial deafness with normal vestibular function, and better vision than in type 1.3 Type 3 is the least severe, with slowly progressing symptoms that start later and include deafness, vestibular ataxia and psychosis.
Our patient was diagnosed with Usher syndrome type 2. In 74 to 90 percent of these cases the mutated gene is USH2A on chromosome 1q41. This gene encodes for an extracellular matrix protein called usherin, which is a basement membrane protein that interferes with the normal development and tissue homeostasis in the retina and inner ear. Hence, the development and maintenance of neurosensory cells in both retina and cochlea are compromised in Usher syndrome.4
Patients with Usher syndrome are more likely to develop cataracts compared with the general population. The condition has been associated with the development of posterior subcapsular cataract, which decreases central visual acuity in these patients earlier and more markedly than in patients without retinal problems.3When Usher syndrome patients are diagnosed with cataract, they should undergo surgery earlier rather than later because they need optimal contrast to attain best visual acuity in the presence of subnormal retinal function.
Walia and colleagues observed an abnormal thinning or increased thickness of peripapillary nerve fiber layer (NFL) on testing with Fourier-domain OCT in RP and Usher syndrome type 2. The observed NFL defects imply the presence of anatomic defects in anterior structures within the retina in a notable number of patients with RP.5 One theory of explanation entertains the possibility of some degree of anterograde injury to the inner retinal structures after profound loss of photoreceptors in RP.
Currently proposed therapies (like photoreceptor transplantation and retinal prostheses) are based on the premise that the inner retinal structures are relatively well retained, despite the profound loss of photoreceptors. This is supported by Oishi and colleagues who found no correlation between OCT-measured NFL thickness and visual acuity in RP.6
Mr. Martinez’s Case
Our patient’s OCT showed abnormal thinning of NFL in both eyes, which in combination with the photoreceptor injuries could explain the underlying visual acuity loss. However, the gradual worsening of the central vision was certainly related to the development of cataract. Hence, the visual acuity improved when the cataracts were removed.
* Patient name is fictitious.
1 Auslender, N. et al. Genet Test 2008;12:289–294.
2 Kaiserman, N. et al. Arch Ophthalmol 2007;125:219–224.
3 Sadeghi, A. M. et al. Acta Ophthalmol Scan 2006;84:537–544.
4 Van Wijk, E. et al. Am J Hum Genet 2004;74:738–744.
5 Walia, S. and G. A. Fishman. Invest Ophthalmol Vis Sci 2008;49:3525–3528.
6 Oishi, A. et al. Eye 2009;23:561–566.
Dr. Alasil is currently a research fellow at the Massachusetts Eye and Ear Infirmary in Boston. Mr. Knabb is the medical photographer, and Dr. Rauser is the director of the ophthalmology residency program at Loma Linda University, Loma Linda, Calif. The patient was seen and treated in Loma Linda University.