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Girl presents with lifelong history of poor vision in both eyes
Bilateral parafoveal pigmentary changes, mild vessel attenuation and pigmentary stippling in the periphery were noted on fundus exam.
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A 15-year-old girl presented to the eye clinic at the New England Eye Center for a second opinion regarding reduced vision in both eyes since infancy.
She was born at 36 weeks’ gestation with an unremarkable birth history. Her mother denied any history of perinatal infections or prolonged perinatal hospitalizations. During infancy, her mother noted the patient would close her eyes or fall asleep whenever outside during daylight hours and was more interactive at night. In early childhood, she was taken to an ophthalmologist and was documented to have poor vision at that time. She was enrolled in early intervention services given her visual deficits.
Over the years, she had been intermittently followed by various ophthalmologists and reportedly had no changes in vision or examination. She denied any ocular pain and felt her vision had been stable since early childhood. The mother denied any history of significant crossing of the eyes, nystagmus, eye poking or eye rubbing during childhood. She had reached all other milestones at appropriate ages.
On review of her family history, the patient’s sister was deaf and her younger brother had learning disabilities. Her parents were noted to be first cousins. The parents were nonsmokers, denied alcohol or drug use, and had no learning disabilities or hearing problems.
Examination
The patient’s best corrected visual acuity was 20/125 in the right eye and 20/125 in the left eye. The pupillary response in both eyes was mildly sluggish (3 mm to 2 mm) without an afferent pupillary defect. Extraocular movements were full with no latent nystagmus, but a small end-gaze nystagmus was noted. Alternate prism cover testing revealed an exophoria of 12 ∆D. Confrontation visual fields were normal. She could not read any of the 10 Ishihara color plates with either eye. IOP in both eyes was normal.
Anterior segment exam was normal in both eyes. The patient had no corneal abnormalities, transillumination defects, colobomas, anterior chamber inflammation or lens opacities. Cycloplegic retinoscopy revealed myopic measurements of –3 D of sphere with +3 D of cylinder at 90º in both eyes.
On posterior segment exam, the vitreous was clear, and fundus exam demonstrated a normal optic nerve with 0.15 cup-to-disc ratio in both eyes. She was noted to have bilateral parafoveal pigmentary changes, mild vessel attenuation, as well as pigmentary stippling in the periphery (Figure 1).
Figure 1. Color fundus photos of both eyes showing pigmentary changes of the macula parafoveally and mild attenuation of the retinal vessels.
Images: Lee GD, Strominger MB
Figure 2. Cirrus OCT macular cube showing diffusely thin retinal layers of both eyes.
Figure 3. Cirrus SD-OCT one-line raster scans of the right (a) and left (b, c) eyes with a hyporeflective area in the fovea between the external limiting membrane and the retinal pigment epitheliu.
Figure 4. ERG results. Mildly decreased amplitudes and normal latencies of scotopic (rod-predominant) waveforms with completely diminished or undetectable photopic (cone-predominant) waveforms.
On Cirrus optical coherence tomography (Carl Zeiss Meditec), the patient had diffusely thin retinal layers of both eyes (Figure 2) with a hyporeflective area in the fovea between the external limiting membrane and the retinal pigment epithelium corresponding to where the hyperreflective bands of the ellipsoid zone and interdigitation zones would normally be found (Figure 3). There was diffuse photoreceptor attenuation in both eyes on OCT.
Full-field electroretinogram (ERG) showed almost complete loss of cone response with a slightly diminished rod response in both eyes (Figure 4, Table).
Source:Lee GD, Strominger MB
What is your diagnosis?
Poor visual acuity
The differential diagnosis of bilateral early-onset pigmentary maculopathy with poor visual acuity includes retinitis pigmentosa, cone-rod dystrophy, Bardet-Biedl syndrome, spinocerebellar ataxia, Leber’s congenital amaurosis, Stargardt disease, blue rod monochromatism and achromatopsia.
Bardet-Biedl syndrome and spinocerebellar ataxia can be excluded from the differential in our patient because she lacked any other medical issues or syndromic findings. However, in a younger child, it would be imperative to pursue a thorough work-up to rule out these syndromic diseases. Leber’s congenital amaurosis is unlikely in our patient because these patients typically are very hyperopic and have nystagmus and very poor vision (20/400 or worse). Furthermore, ERG findings in Leber’s congenital amaurosis demonstrate an extinguished rod response in addition to an abnormal cone response, which was not present in our patient. In the absence of typical pisciform yellow flecks, Stargardt disease is less likely.
The ERG also helps differentiate between predominantly rod dystrophies, such as retinitis pigmentosa, and predominantly cone dystrophies, such as cone-rod dystrophy, achromatopsia and blue rod monochromatism. The predominantly abnormal cone response in our patient rules out retinitis pigmentosa. The ERG findings of our patient could be consistent with achromatopsia or blue rod monochromatism; however, the peripheral pigmentary changes and lack of nystagmus in our patient make these diagnoses less likely.
Given her clinical findings, OCT images and ERG results, the patient was diagnosed with cone-rod dystrophy. She was referred to genetics to undergo a formal work-up to determine which genetic mutation, if any, is responsible for her macular dystrophy.
Discussion
Cone-rod dystrophy is an inherited retinopathy with a prevalence of one in 40,000. It is characterized by loss of cone cells, with minimal to mild loss of rod cells in the retina. Genetic analyses have identified several genes that are predominately found in cone dystrophies, including ABCA4, CRX, GUCY2D, GUCA1A and RPGR. Autosomal dominant, autosomal recessive and X-linked inheritance patterns have all been described. Typically, patients present with photophobia, decreased visual acuity, dyschromatopsia and hemeralopia. Night blindness is rarely the chief complaint in cone-rod dystrophies, whereas it may be the presenting or predominant symptom in rod-cone dystrophies. Findings on examination include pigmentary retinopathy, macular atrophy that may present in a bull’s-eye pattern, vessel attenuation and temporal optic atrophy. Visual field testing typically shows a central scotoma with sparing of the peripheral field, consistent with the anatomic distribution of cones.
ERG is the gold standard in testing for cone-rod dystrophy, and findings include diminished cone response in the photopic and flicker waveforms. Rod responses usually remain normal or near normal. However, in later stages of disease, the rod response in the scotopic waveforms may diminish.
OCT findings in cone-rod dystrophy have been described in recent publications. Lima and colleagues analyzed OCT images of 24 eyes of 12 patients with cone-rod dystrophy. They found a complete loss of the interdigitation zone band in all eyes, as well as a loss of the foveal ellipsoid zone in 92% of eyes. Kim and colleagues reported similar findings with disruption of the ellipsoid band in a 13-year-old girl with cone-rod dystrophy. Emfietzoglou and colleagues reported total absence of the inner segment/outer segment junction and a hyporeflective area in the outer retina, similar to our patient’s OCT findings.
Conclusion
The patient was given a full cycloplegic refraction with red tint lenses in addition to sunglasses to help with photophobia. She is currently undergoing genetic evaluation. She was encouraged to follow up with her low vision specialist. Patients with visually significant retinal degenerations should be registered with the Commission for the Blind, if appropriate, and children should be enrolled in early intervention services. Our patient was fortunate to have had early intervention services in childhood as soon as the visual problems were identified and did not suffer any developmental or learning delays.