What's Your Diagnosis?

Young man reports poor vision since childhood

A 25-year-old man presented with a history of poor vision since he was 12 years old. He reported no night vision problems, photophobia or peripheral field loss. He reported his color vision was normal.

Color photographs of the posterior pole of both eyes.
Source: Sherry J. Bass, OD, FAAO, FCOVD

Family history included a mother and brother with reduced vision of unknown etiology in both eyes. Systemic health history was normal. The patient had no other systemic or ocular history and used no medications.

Best-corrected visual acuities were 20/100 OD (-11.75 D -1.00 D x 65) and 20/80 OS (-9.25 D -0.75 D x 40). Pupils were equally round and reactive to light and accommodation. External examination of the eyes revealed clear corneas, clear lenses and deep and quiet anterior chambers. IOPs were 12 mm Hg in each eye.

Fundus autofluorescence of the posterior pole of both eyes.

Confrontation visual fields were full in each eye. Internal examination of the eyes through a dilated pupil revealed normal optic nerve head size and color with normal neuroretinal rim tissue. The retinal nerve fiber layer was full in both eyes. The maculas appeared normal in both eyes with no evidence of any pigmentary abnormalities or flecks. The vasculature was normal; retinal and arteriolar caliber appeared normal.

Fundus autofluorescence (FAF) is an imaging method that topographically maps lipofuscin in the retinal pigment epithelium (RPE). Hyperautofluorescence, or hyper AF, (bright white areas) occurs in areas where the RPE is under metabolic stress, accumulating lipofuscin. Hypoautofluorescence, or hypo-AF, (dark areas) occurs where there is degeneration or death of RPE cells and photoreceptors. In this patient, FAF appeared “iso-autofluorescent,” indicating that no autofluorescent abnormalities were noted. Fluorescein angiography revealed no abnormalities. A full-field electroretinogram (ERG) was normal under both photopic and scotopic conditions. Color vision tested with Ishihara plates was normal in each eye, tested separately.

What’s your diagnosis?
See answer on the next page.

Bilateral reduced visual acuity in a 12-year-old suggests a possible hereditary macular dystrophy, the most common of which is Stargardt disease.

OCT macular cube and GCA reveals normal retinal thickness in the fovea (A) and macula (B).

Stargardt disease typically affects individuals in their teenage years, and they often suffer a gradual loss of vision, usually in the 20/100 to 20/200 range. However, Stargardt disease is characterized by pigmentary changes in the macula often accompanied by yellowish fish-tailed flecks composed of lipofuscin. This patient had none of these findings. On fundus autofluorescence imaging (FAF), a patient with Stargardt disease would demonstrate hyper-AF and hypo-AF abnormalities consistent with macular atrophy and lipofuscin accumulation. This patient had no FAF abnormalities whatsoever. The OCT in Stargardt disease demonstrates macular thinning or atrophy or a bull’s eye type of thinning around the fovea. This patient’s OCT, however, only demonstrated disruption of the photoreceptors, indicated by a diffuse reflectivity of the ellipsoid zone (the interface between the inner and outer segments of the photoreceptors) noted by the red arrows in the accompanying figure. The RPE itself is intact, which is why the FAF looks completely normal. In addition, in Stargardt disease, the OCT ganglion cell analysis (GCA), which is dependent on normal retinal thickness, would be abnormal. In this patient, however, the GCA is completely normal, indicating no evidence of optic nerve dysfunction and normal retinal thickness.

Sherry J. Bass

The inheritance of Stargardt disease is autosomal recessive. Therefore, few family members are affected. This patient, however, has a mother and a brother with a similar history, which suggest a hereditary retinal autosomal dominant disease.

OCTs of the right (middle) and left eyes (bottom). Note the diffuse reflectivity of the ellipsoid zone (red arrows) representing photoreceptor disruption. There are no disruptions in the RPE. The top image is a normal OCT.

Visual field testing using the Octopus M program (Haag-Streit), which tests points 0.7 degrees apart in the central 4 degrees, reveals a central scotoma in both eyes, which corroborates, functionally, with the reduced visual acuity. In Stargardt disease, patients usually have superior eccentric fixation, resulting in superior paracentral scotomas, not the central scotomas seen in this patient.

Therefore, this patient does not have Stargardt disease. These findings indicate a rare macular dystrophy called occult macular dystrophy (OMD). This autosomal dominantly inherited condition causes reduced visual acuity in the early teenage years, like Stargardt disease, and affects multiple family members. Although inherited, it has variable effects on visual acuity and presentation within family members. It is considered “occult” because there are no abnormalities on ophthalmoscopy, color photography, fluorescein angiography or fundus autofluorescence. The only abnormality is the OCT, which demonstrates a well-defined disruption in the ellipsoid zone, affecting photoreceptor function only. The RPE is normal. This is unusual for hereditary dystrophies, which usually affect both the RPE and the photoreceptors. These two layers are intimately associated with one another, and RPE death and degeneration will eventually lead to photoreceptor degeneration. That is not the case in this dystrophy, characterized by disruption, not degeneration. The disease is, therefore, not progressive.

Octopus M central 10-degree visual fields reveal central scotomas in both eyes (red arrows).

A full-field ERG will be normal because this disease affects only the macula. A better test is a multifocal ERG, which tests macular function. The patient will be returning for this test, which we expect will be abnormal, because the patient demonstrates central scotomas on visual field testing.

Heterozygous mutations on the RP1L1 gene on chromosome 8 (8p23-p22) have been identified in affected pedigrees. This gene codes for a retina-specific protein that plays an essential role in rod outer segment morphogenesis and in photosensitivity. One can confirm OMD through genotype testing of RP1L1 and, in fact, this patient did test positive for a mutation on RP1L1.

There is no treatment for OMD. Visual function is stable over the lifetime of the individual, and they do well with low vision aids, as the disease affects only central function. Correct diagnosis of OMD is important to educate the patient about prognosis and for purposes of career decisions and family planning.

Disclosure: Bass is an investor in ArcticDx. Semes reports no relevant financial disclosures.

A 25-year-old man presented with a history of poor vision since he was 12 years old. He reported no night vision problems, photophobia or peripheral field loss. He reported his color vision was normal.

Color photographs of the posterior pole of both eyes.
Source: Sherry J. Bass, OD, FAAO, FCOVD

Family history included a mother and brother with reduced vision of unknown etiology in both eyes. Systemic health history was normal. The patient had no other systemic or ocular history and used no medications.

Best-corrected visual acuities were 20/100 OD (-11.75 D -1.00 D x 65) and 20/80 OS (-9.25 D -0.75 D x 40). Pupils were equally round and reactive to light and accommodation. External examination of the eyes revealed clear corneas, clear lenses and deep and quiet anterior chambers. IOPs were 12 mm Hg in each eye.

Fundus autofluorescence of the posterior pole of both eyes.

Confrontation visual fields were full in each eye. Internal examination of the eyes through a dilated pupil revealed normal optic nerve head size and color with normal neuroretinal rim tissue. The retinal nerve fiber layer was full in both eyes. The maculas appeared normal in both eyes with no evidence of any pigmentary abnormalities or flecks. The vasculature was normal; retinal and arteriolar caliber appeared normal.

Fundus autofluorescence (FAF) is an imaging method that topographically maps lipofuscin in the retinal pigment epithelium (RPE). Hyperautofluorescence, or hyper AF, (bright white areas) occurs in areas where the RPE is under metabolic stress, accumulating lipofuscin. Hypoautofluorescence, or hypo-AF, (dark areas) occurs where there is degeneration or death of RPE cells and photoreceptors. In this patient, FAF appeared “iso-autofluorescent,” indicating that no autofluorescent abnormalities were noted. Fluorescein angiography revealed no abnormalities. A full-field electroretinogram (ERG) was normal under both photopic and scotopic conditions. Color vision tested with Ishihara plates was normal in each eye, tested separately.

What’s your diagnosis?
See answer on the next page.

PAGE BREAK

Bilateral reduced visual acuity in a 12-year-old suggests a possible hereditary macular dystrophy, the most common of which is Stargardt disease.

OCT macular cube and GCA reveals normal retinal thickness in the fovea (A) and macula (B).

Stargardt disease typically affects individuals in their teenage years, and they often suffer a gradual loss of vision, usually in the 20/100 to 20/200 range. However, Stargardt disease is characterized by pigmentary changes in the macula often accompanied by yellowish fish-tailed flecks composed of lipofuscin. This patient had none of these findings. On fundus autofluorescence imaging (FAF), a patient with Stargardt disease would demonstrate hyper-AF and hypo-AF abnormalities consistent with macular atrophy and lipofuscin accumulation. This patient had no FAF abnormalities whatsoever. The OCT in Stargardt disease demonstrates macular thinning or atrophy or a bull’s eye type of thinning around the fovea. This patient’s OCT, however, only demonstrated disruption of the photoreceptors, indicated by a diffuse reflectivity of the ellipsoid zone (the interface between the inner and outer segments of the photoreceptors) noted by the red arrows in the accompanying figure. The RPE itself is intact, which is why the FAF looks completely normal. In addition, in Stargardt disease, the OCT ganglion cell analysis (GCA), which is dependent on normal retinal thickness, would be abnormal. In this patient, however, the GCA is completely normal, indicating no evidence of optic nerve dysfunction and normal retinal thickness.

Sherry J. Bass

The inheritance of Stargardt disease is autosomal recessive. Therefore, few family members are affected. This patient, however, has a mother and a brother with a similar history, which suggest a hereditary retinal autosomal dominant disease.

OCTs of the right (middle) and left eyes (bottom). Note the diffuse reflectivity of the ellipsoid zone (red arrows) representing photoreceptor disruption. There are no disruptions in the RPE. The top image is a normal OCT.

Visual field testing using the Octopus M program (Haag-Streit), which tests points 0.7 degrees apart in the central 4 degrees, reveals a central scotoma in both eyes, which corroborates, functionally, with the reduced visual acuity. In Stargardt disease, patients usually have superior eccentric fixation, resulting in superior paracentral scotomas, not the central scotomas seen in this patient.

Therefore, this patient does not have Stargardt disease. These findings indicate a rare macular dystrophy called occult macular dystrophy (OMD). This autosomal dominantly inherited condition causes reduced visual acuity in the early teenage years, like Stargardt disease, and affects multiple family members. Although inherited, it has variable effects on visual acuity and presentation within family members. It is considered “occult” because there are no abnormalities on ophthalmoscopy, color photography, fluorescein angiography or fundus autofluorescence. The only abnormality is the OCT, which demonstrates a well-defined disruption in the ellipsoid zone, affecting photoreceptor function only. The RPE is normal. This is unusual for hereditary dystrophies, which usually affect both the RPE and the photoreceptors. These two layers are intimately associated with one another, and RPE death and degeneration will eventually lead to photoreceptor degeneration. That is not the case in this dystrophy, characterized by disruption, not degeneration. The disease is, therefore, not progressive.

Octopus M central 10-degree visual fields reveal central scotomas in both eyes (red arrows).

A full-field ERG will be normal because this disease affects only the macula. A better test is a multifocal ERG, which tests macular function. The patient will be returning for this test, which we expect will be abnormal, because the patient demonstrates central scotomas on visual field testing.

Heterozygous mutations on the RP1L1 gene on chromosome 8 (8p23-p22) have been identified in affected pedigrees. This gene codes for a retina-specific protein that plays an essential role in rod outer segment morphogenesis and in photosensitivity. One can confirm OMD through genotype testing of RP1L1 and, in fact, this patient did test positive for a mutation on RP1L1.

There is no treatment for OMD. Visual function is stable over the lifetime of the individual, and they do well with low vision aids, as the disease affects only central function. Correct diagnosis of OMD is important to educate the patient about prognosis and for purposes of career decisions and family planning.

Disclosure: Bass is an investor in ArcticDx. Semes reports no relevant financial disclosures.