History of present illness
We present a case of a 34-year-old male patient with a chief report of long-standing photophobia associated with reduced visual acuity, myopia, and dyschromatopsia. His vision has never been perfect, although he states subjectively, “It’s pretty good.” He has been wearing a myopic correction most of his life with partial benefit to visual acuity. He denies night blindness or visual field loss, and he has never exhibited nystagmus.
Ocular examination findings
Best corrected visual acuity with a high myopic correction was 20/50 in the right eye and 20/64 in the left. Ocular motility was intact in all positions of gaze; there was no ptosis and no nystagmus. External and anterior segment examinations were unremarkable, with no evidence of corneal pannus, and there were no iris transillumination defects, evidence for ectropion uveae, or corectopia. Intraocular pressure was normal.
Dilated fundus examination ( Fig. 2.1 ) showed myopic findings with a mild posterior staphyloma involving both the macula and the peripapillary region, and blunting of the foveal reflexes with fine foveal mottling of the retinal pigment epithelium (RPE). The optic disc exhibited a sloped cup and mild temporal peripapillary atrophy (crescent-like). Retinal vasculature was normal, and there were no peripheral findings. There were no macular or peripheral pigmentary deposits or flecks, macular tapetal-like golden metallic sheen, or evidence for diffuse hypopigmentation. All findings were symmetrical between the two eyes.
Questions to ask
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Does the patient exhibit any systemic findings in association to the visual reports? It is important to ask a patient like this about any history of kidney problems, hearing loss, diabetes or prediabetes, heart problems (in particular, dilated cardiomyopathy or heart conduction defects), or extra digits on hands and/or feet (or other anomalies of the extremities). Both height and weight should be measured to check for short stature and/or obesity (body mass index > 30). Any one or more of these features may be associated with an eye problem as part of a syndromic condition.
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No
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What is the patient’s refractive error? Myopic refraction in a male patient who reports long-standing photophobia, poor visual acuity, and dyschromatopsia is far more common in X-linked conditions such as blue cone monochromacy (BCM), X-linked cone dystrophy (XL-COD), X-linked cone–rod dystrophy (XL-CORD), and Bornholm eye disease (BED) (a condition characterized by the triad of X-linked myopia, deuteranopia, and cone dysfunction), whereas a hypermetropic refraction is far more common in patients with achromatopsia (ACHM) or another X-linked disorder, type 2 (“incomplete”) congenital stationary night blindness (CSNB). Other conditions associated with photophobia, poor visual acuity, and dyschromatopsia are not known to be more typically associated with any particular type of refractive error.
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−6.75sph − 1.00 × 052 in the right eye and −6.75sph − 1.00 × 117 in the left eye
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Does the patient have a family history of ocular conditions, or is there consanguinity among his parents? A family history of a female sibling with similar reports in the absence of any other cases along the vertical family axis would suggest an autosomal recessive inheritance. Parental consanguinity would further support this possibility and would predict that any genetic etiology for the findings will be present in the homozygous state (same mutation inherited from each parent). A history of similar reports in his father would instead indicate male-to-male transmission and support an autosomal dominant inheritance pattern. If instead there were other male relatives affected with the same problem on the maternal side only and no instance of male-to-male transmission, with the mother being asymptomatic or exhibiting milder findings, this would suggest an X-linked recessive inheritance.
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No. In this case, family history was not contributory, leaving the door open to both autosomal recessive and X-linked recessive inheritance.
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Assessment
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This is a case of a 34-year-old male patient with a chief report of long-standing photophobia associated with reduced visual acuity, myopia, and dyschromatopsia, and with negative family history for other cases of similar reports in other relatives, who exhibits a largely normal fundus examination except for very clear foveal changes on macular spectral domain optical coherence tomography (SD-OCT).
Differential diagnosis
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XL-COD
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XL-CORD
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BCM
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BED
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X-linked CSNB
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X-linked ocular albinism
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Autosomal dominant cone dystrophy
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Autosomal dominant PAX6-associated disease
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Autosomal recessive ACHM
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Autosomal recessive ocular albinism
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Autosomal recessive cone dystrophy
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Autosomal recessive cone–rod dystrophy
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Autosomal recessive CSNB
Because of the noted association of the myopic refractive defect with conditions that have an X-linked inheritance pattern, X-linked diagnoses are to be considered higher on the differential, but autosomal recessive inheritance cannot be fully ruled out in this case. Autosomal dominant inheritance (which is well-known to be associated with instances of incomplete penetrance and/or highly variable disease expressivity) also cannot be technically excluded and could also be an uncommon case of a de novo mutation, but at this moment there is nothing to support this possibility.
Working diagnosis
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Based on the reports, the family history, and the refractive defect, the diagnoses XL-COD, XL-CORD, BCM, and BED are at this stage most and equally likely ones. Because there is no nystagmus, BCM (which is typically associated with it) is potentially the lowest on the differential at this stage.
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The possibility of a cone dystrophy–like variant of BCM, as they have been associated with particular genetic changes in the visual pigment locus control region, also exists and would be best compatible with the lack of nystagmus.
Multimodal testing and results
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SD-OCT
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Despite the blunted foveal reflexes, but in line with the foveal RPE mottling seen on dilated fundus examination, SD-OCT ( Fig. 2.2 ) showed a clearly identifiable and well-defined foveal pit in both eyes with an underlying area of focal loss of the ellipsoid zone (EZ), with hyporeflective EZ gaps (so-called cavitation lesions), and focal hypertransmission defects attributable to RPE loss. There were no intraretinal or subretinal hypo- or hyperreflective lesions, changes, or deposits. Despite the myopia, there was also no choroidal thinning. On horizontal SD-OCT scans, a downward slanting toward the disc of the retinal scan because of the staphyloma was also noticeable. Macular volume maps (not shown) were within normal limits.
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