What's Your Diagnosis?

Routine exam reveals unusual retinal findings

Catherine Hogan
Jim WIlliamson

A 70-year-old Caucasian man presented for an updated spectacle prescription. Ocular history included cataracts, monovision RK performed in 1997 and “damage to the back of my right eye.” Medically, the patient reported only a history of prostate cancer 11 years prior, for which he received treatment. Medications included a multivitamin. He denied any current or past use of tobacco, alcohol or recreational drugs.

Entering distance visual acuities measured 20/20-2 OD and OS with his current distance-only glasses and 20/25 OU uncorrected at near. The manifest refraction (–0.75-1.00 x 088 OD; +2.25-1.75 x 067 OS) resulted in unchanged distance vision, but increased the near acuity to 20/20 with a +2.50 D add.

Pupils, extraocular motilities and confrontation visual fields were unremarkable. IOPs taken with Goldmann applanation tonometry were 19 mm Hg OD and 18 mm Hg OS. Biomicroscopy revealed the presence of radial corneal scars in both eyes consistent with the RK history and bilateral lens opacities of C1, NO2 and NC2 as graded with the LOCS III classification system.

The fundus photo of the right eye shows optic nerve findings of a nasal crescent and inferior vasculature that exits nasally before resuming a temporal course. The mean disc diameter (DD) to disc to macula (DM) ratio measured less than 3. The fundus photo of the right eye shows a staphyloma outside the posterior pole nasally. B-scan ultrasound using the 10 Mhz probe further highlighted the staphyloma. The left eye appeared unremarkable. Retinal nerve fiber layer (RNFL) scans of the right eye revealed thinning compared with the reference database in the area in which the device determined to be the temporal inferior (TI) quadrant. The Bruch’s membrane opening (BMO) to minimum rim width (MRW) scan resulted in measurements within norms of the reference database.

What’s your diagnosis?

See answer on next page.

We considered five differential diagnoses.

Temporal myopic crescents (malinserted optic disc) are commonly located temporally adjacent to the optic disc. This acquired condition results in attenuated retinal pigment epithelium (RPE) and choroid but is otherwise unremarkable.

Optic nerve hypoplasia is a small optic disc surrounded by a double ring sign, typically with abnormal organization/tortuosity of the retinal vasculature.

Fundus photo of the right eye demonstrates a nasal crescent and inferior vasculature that exits nasally.

Source: Jim Williamson, OD, FAAO, FORS

Nasally located staphyloma in the right eye.

Degenerative myopia is caused by the excessive axial elongation of the globe. This condition primarily presents with posterior staphyloma and different features of myopic maculopathy including chorioretinal atrophy, central pigment spot from myopic choroidal neovascularization (CNV; Fuch’s spot), lacquer cracks and choroidal atrophy approaching the optic disc.

Glaucoma is a progressive disease of the optic nerve with signs of RNFL thinning and ganglion cell complex loss in tandem with optic nerve head cupping as well as symptoms of visual field loss over time.

Tilted disc syndrome (TDS) is an inferonasally rotated disc in tandem with juxtapapillary changes and retinal vascular abnormalities.

This case is representative of TDS — a congenital anomaly resulting from malclosure of the embryonic optic fissure during the second month of gestation. It is classified under the spectrum of ocular coloboma.

TDS is an ocular condition that typically presents with inferonasally rotated discs in tandem with juxtapapillary changes and retinal vascular abnormalities. These include an adjacent inferonasal crescent or peripapillary atrophy (PPA), thinning or atrophy of the RPE and choroid, posterior staphyloma and situs inversus of the retinal vessels. Situs inversus is depicted as retinal vasculature that abnormally exits the optic disc nasally before appropriately bending temporally. This phenomenon is reported in about 70% of patients with TDS — a significant amount compared with only 5% in normal populations (Young et al.). Patients with TDS with these retinal abnormalities experience an increased risk for complications including CNV, polypoidal choroidal vasculopathy, peripapillary pseudocysts, foveal retinal detachment, retinoschisis, serous neurosensory retinal detachment, chorioretinal degeneration and chorioretinal folds. A frequent location for these complications is the upper edge of the staphyloma where the transition from a normal to abnormal curvature occurs.

Optic disc tilt refers to the apparent angle at which the optic nerve enters the eye, which creates a disparity in the surface elevation of the nerve margins. Torsion, however, represents a degree of rotation along the sagittal axis of the nerve. In contrast, “oblique insertion” of the optic disc refers to entrance of the nerve at an acute angle without the appearance of rotation. Optic disc tilt is visualized funduscopically in 3D as an oval-shaped optic nerve where the margins may not be simultaneously in focus to the viewer.

Clinical methods of analyzing the amount of optic disc tilt focus on studying the index of tilt combined with the degree of torsion. When assessing the optic disc, the clinician should note the direction of the tilt (vertical, horizontal or oblique) and the orientation of the depressed and elevated margins. Inferonasal rotation is the most common disc orientation in TDS, with a 65% incidence (Witmer et al.). However, clinicians should note that the optic disc can rotate in any direction. The optic disc rotation itself does not increase over time and, therefore, is considered nonprogressive.

The left eye appeared unremarkable.
BMO to MRW measurements were normal.

Associated disorders

Although nonprogressive, a tilted optic disc is strongly associated with other visual disorders including amblyopia, myopia, astigmatism, visual field defects and abnormal color vision. Amblyopia associated with TDS is most likely a result of induced anisometropia, potentially from unilateral increases in corneal astigmatism in young patients. There is a positive correlation between long axial length, the severity of myopia and the degree of optic disc tilt. The percentage of the population with tilted discs grows with an increase in the amount of astigmatism. Any amount of astigmatism is present in as many as 93% of patients with TDS. TDS population trends report less than 0.4% in eyes with less than 1.00 D of astigmatism and upward of 17.9% in eyes with greater than or equal to 5.00 D of astigmatism (Vongphanit et al.).

Visual fields defects in patients with TDS usually appear in the superior temporal quadrant (recall inferonasal is the most common disc rotation), with reports of up to 33%. However, visual field defects may occur in any quadrant, including paracentrally (Brazitikos et al., Gurlu et al.). Overall, patients with TDS experience a generalized reduction in retinal sensitivity in all four field quadrants compared with norms, with speculation regarding the impact of refractive and neurogenic aberrations on field testing. The location of field defects may also correspond to the area of retinal thinning due to the decrease in retinal ganglion cells and nerve fibers.

Small sample size studies have found a higher prevalence of color vision abnormalities in patients with TDS, with mixed defect as the most common (70% of eyes), and red-green defect in only 6% of eyes (Vuori et al.).

Differentiating the diagnosis

Clinicians should discern this congenital optic disc anomaly from other optic disc disorders, especially those that increase the risk for progressive vision loss.

Acquired myopic crescents are not caused by malformation of the embryonic ocular fissure but rather are a result of progressive mechanical elongation of the globe. Both TDS and myopic crescents result in attenuated RPE and choroid but are otherwise unremarkable. Ocular history offers the best differential between these conditions; myopic crescents increase in size over time, whereas TDS juxtapapillary thinning will remain stationary.

There is some overlap in clinical terminology of tilted discs and segmental optic nerve hypoplasia, especially in bilateral cases. However, this form of hypoplasia mostly refers to intrauterine injury to the retina, optic tract, chiasm or posterior visual pathway, which in turn causes an asymmetric loss of ganglion cell axons.

The intrinsic anatomic distortions of TDS can make its differential from glaucoma challenging. Measurements of IOP, central corneal thickness, RNFL thinning and visual field progression are the best clinical tools to assess for glaucomatous optic disc changes. Glaucomatous eyes will present with variations of RNFL thinning that will progress over time, whereas patients with TDS will show “false” RNFL thickening in nasal quadrants, from situs inversus of the retinal vessels, that remains constant over time. In this case, because of the disc tilt and situs inversus, the anatomical TI quadrant is shifted nasally, shown by the blue arrow in the figure on page 22. This places the RNFL TI “hump” in the nasal inferior (NI) quadrant, indicated by the red arrow, which produces false thickening of the NI RNFL and false thinning of the TI RNFL. BMO to MRW and ganglion cell measurements are useful, as those results should be unaffected by disc tilt, as they were in this case.

Visual field defects in glaucomatous patients will also progress over time, have a higher mean deviation than patients with TDS and are associated with more focal lamina cribrosa thinning. A visual field defect that respects the horizontal meridian largely rules out TDS, as this disc anomaly does not result in field patterns from nerve fiber layer disruption.

RNFL thinning of what the device measured as the TI quadrant.
B-scan ultrasound using the 10 Mhz probe highlighted the nasally located staphyloma. Shadowing of the optic nerve is seen to the left of the affected area.

Analyzing BMO, TDS

Analysis of BMO aids in cases where the neuroretinal rim appears thinned clinically. BMO marks the beginning of the optic nerve. Localizing this structure and correlating its position to the funduscopic appearance assists in determining whether true cupping exists.

Whether differentiating TDS from glaucoma or evaluating patients with TDS with glaucomatous clinical findings, analysis of RNFL and the visual field progression currently provides the strongest guidance for appropriate treatment and management.

Segmental elevation of the disc margin in TDS can mimic other causes of elevated disc margins, including optic disc drusen, compressive optic neuropathy, ischemic optic neuropathy, retinal vasculature occlusions, papillitis and papilledema from elevated intracranial pressure. Signs and symptoms should allow the clinician to differentiate TDS from these conditions, as TDS is usually an incidental finding on examination and only symptomatic when associated with macular pathology such as CNV. Patients with signs of papilledema should be assessed and worked up.

Anterior visual pathway neoplasms including optic nerve gliomas and meningiomas can potentially elevate the disc margin in an asymmetric pattern like TDS. These conditions will have more extensive visual loss, including progressive visual field abnormalities of enlarged blind spots and central scotomas. The optic nerve may appear pale in eyes with a glioma, and an afferent pupillary defect is commonly present in neoplastic ocular conditions. The physician must order appropriate neuroimaging when suspicious of neoplastic elevation of the disc margin.

TDS is a congenital anomaly that challenges the doctor to analyze the optic nerve structure and function beyond clinical appearance. Using the aforementioned technology, the clinician can better grasp the health of the optic nerve, monitor for stability and differentiate TDS from progressive neuropathies and even urgent or emergent optic nerve conditions.

References:

Apple DJ, et al. Surv Ophthalmol. 1982;doi:10.1016/0039-6257(82)90111-4.

Aung T, et al. Ophthalmology. 2001;doi:10.1016/S0161-6420(00)00497-8.

Brazitikos PD, et al. Arch Ophthalmol. 1990;doi:10.1001/archopht.1990.01070140052027.

Cohen S, et al. Retina. 2013;doi:10.1097/IAE.0b013e3182831364.

Gurlu VP, et al. Retina. 2002;doi:10.1097/00006982-200206000-00021.

Han SY, et al. Semin Ophthalmol. 2014;doi:10.3109/08820538.2013.839815.

Jonas JB, et al. Ophthalmology. 1997;doi:10.1016/S0161-6420(97)30004-9.

Kang S, et al. J Glaucoma. 2013;doi:10.1097/IJG.0b013e31829e1ba2.

Kwun Y, et al. J Glaucoma. 2016;doi:10.1097/IJG.0000000000000565.

Liu GT. Curr Opin Ophthalmol. 2006;doi:10.1097/01.icu.0000243016.90004.12.

Ohno-Matsui K, et al. Am J Ophthalmol. 2015; doi:10.1016/j.ajo.2015.01.022.

Tay E, et al. Am J Ophthalmol. 2005;doi:10.1016/j.ajo.2004.08.076.

Vongphanit J, et al. Am J Ophthalmol. 2002;doi:10.1016/S0002-9394(02)01339-9.

Vuori ML, et al. Acta Ophthalmol Scand. 2007;doi:10.1111/j.1600-0420.2007.00918.x.

Witmer MT, et al. Surv Ophthalmol. 2010;doi:10.1016/j.survophthal.2010.01.002.

Xu M, et al. Retina. 2017;doi:10.1097/IAE.0000000000001140.

Young SE, et al. Am J Ophthalmol. 1976;doi:10.1016/00002-9394(76)90658-9.

For more information:

Catherine Hogan, OD, FAAO, is a clinical instructor at the Southern College of Optometry, Memphis, Tenn.

Jim Williamson, OD, FAAO, FORS, is the residency supervisor at the Memphis VA Medical Center. He can be reached at: jim.williamson44@gmail.com.

Disclosures: Hogan and Williamson report no relevant financial disclosures.

Catherine Hogan
Jim WIlliamson

A 70-year-old Caucasian man presented for an updated spectacle prescription. Ocular history included cataracts, monovision RK performed in 1997 and “damage to the back of my right eye.” Medically, the patient reported only a history of prostate cancer 11 years prior, for which he received treatment. Medications included a multivitamin. He denied any current or past use of tobacco, alcohol or recreational drugs.

Entering distance visual acuities measured 20/20-2 OD and OS with his current distance-only glasses and 20/25 OU uncorrected at near. The manifest refraction (–0.75-1.00 x 088 OD; +2.25-1.75 x 067 OS) resulted in unchanged distance vision, but increased the near acuity to 20/20 with a +2.50 D add.

Pupils, extraocular motilities and confrontation visual fields were unremarkable. IOPs taken with Goldmann applanation tonometry were 19 mm Hg OD and 18 mm Hg OS. Biomicroscopy revealed the presence of radial corneal scars in both eyes consistent with the RK history and bilateral lens opacities of C1, NO2 and NC2 as graded with the LOCS III classification system.

The fundus photo of the right eye shows optic nerve findings of a nasal crescent and inferior vasculature that exits nasally before resuming a temporal course. The mean disc diameter (DD) to disc to macula (DM) ratio measured less than 3. The fundus photo of the right eye shows a staphyloma outside the posterior pole nasally. B-scan ultrasound using the 10 Mhz probe further highlighted the staphyloma. The left eye appeared unremarkable. Retinal nerve fiber layer (RNFL) scans of the right eye revealed thinning compared with the reference database in the area in which the device determined to be the temporal inferior (TI) quadrant. The Bruch’s membrane opening (BMO) to minimum rim width (MRW) scan resulted in measurements within norms of the reference database.

What’s your diagnosis?

See answer on next page.

PAGE BREAK

We considered five differential diagnoses.

Temporal myopic crescents (malinserted optic disc) are commonly located temporally adjacent to the optic disc. This acquired condition results in attenuated retinal pigment epithelium (RPE) and choroid but is otherwise unremarkable.

Optic nerve hypoplasia is a small optic disc surrounded by a double ring sign, typically with abnormal organization/tortuosity of the retinal vasculature.

Fundus photo of the right eye demonstrates a nasal crescent and inferior vasculature that exits nasally.

Source: Jim Williamson, OD, FAAO, FORS

Nasally located staphyloma in the right eye.

Degenerative myopia is caused by the excessive axial elongation of the globe. This condition primarily presents with posterior staphyloma and different features of myopic maculopathy including chorioretinal atrophy, central pigment spot from myopic choroidal neovascularization (CNV; Fuch’s spot), lacquer cracks and choroidal atrophy approaching the optic disc.

Glaucoma is a progressive disease of the optic nerve with signs of RNFL thinning and ganglion cell complex loss in tandem with optic nerve head cupping as well as symptoms of visual field loss over time.

Tilted disc syndrome (TDS) is an inferonasally rotated disc in tandem with juxtapapillary changes and retinal vascular abnormalities.

This case is representative of TDS — a congenital anomaly resulting from malclosure of the embryonic optic fissure during the second month of gestation. It is classified under the spectrum of ocular coloboma.

TDS is an ocular condition that typically presents with inferonasally rotated discs in tandem with juxtapapillary changes and retinal vascular abnormalities. These include an adjacent inferonasal crescent or peripapillary atrophy (PPA), thinning or atrophy of the RPE and choroid, posterior staphyloma and situs inversus of the retinal vessels. Situs inversus is depicted as retinal vasculature that abnormally exits the optic disc nasally before appropriately bending temporally. This phenomenon is reported in about 70% of patients with TDS — a significant amount compared with only 5% in normal populations (Young et al.). Patients with TDS with these retinal abnormalities experience an increased risk for complications including CNV, polypoidal choroidal vasculopathy, peripapillary pseudocysts, foveal retinal detachment, retinoschisis, serous neurosensory retinal detachment, chorioretinal degeneration and chorioretinal folds. A frequent location for these complications is the upper edge of the staphyloma where the transition from a normal to abnormal curvature occurs.

Optic disc tilt refers to the apparent angle at which the optic nerve enters the eye, which creates a disparity in the surface elevation of the nerve margins. Torsion, however, represents a degree of rotation along the sagittal axis of the nerve. In contrast, “oblique insertion” of the optic disc refers to entrance of the nerve at an acute angle without the appearance of rotation. Optic disc tilt is visualized funduscopically in 3D as an oval-shaped optic nerve where the margins may not be simultaneously in focus to the viewer.

PAGE BREAK

Clinical methods of analyzing the amount of optic disc tilt focus on studying the index of tilt combined with the degree of torsion. When assessing the optic disc, the clinician should note the direction of the tilt (vertical, horizontal or oblique) and the orientation of the depressed and elevated margins. Inferonasal rotation is the most common disc orientation in TDS, with a 65% incidence (Witmer et al.). However, clinicians should note that the optic disc can rotate in any direction. The optic disc rotation itself does not increase over time and, therefore, is considered nonprogressive.

The left eye appeared unremarkable.
BMO to MRW measurements were normal.

Associated disorders

Although nonprogressive, a tilted optic disc is strongly associated with other visual disorders including amblyopia, myopia, astigmatism, visual field defects and abnormal color vision. Amblyopia associated with TDS is most likely a result of induced anisometropia, potentially from unilateral increases in corneal astigmatism in young patients. There is a positive correlation between long axial length, the severity of myopia and the degree of optic disc tilt. The percentage of the population with tilted discs grows with an increase in the amount of astigmatism. Any amount of astigmatism is present in as many as 93% of patients with TDS. TDS population trends report less than 0.4% in eyes with less than 1.00 D of astigmatism and upward of 17.9% in eyes with greater than or equal to 5.00 D of astigmatism (Vongphanit et al.).

Visual fields defects in patients with TDS usually appear in the superior temporal quadrant (recall inferonasal is the most common disc rotation), with reports of up to 33%. However, visual field defects may occur in any quadrant, including paracentrally (Brazitikos et al., Gurlu et al.). Overall, patients with TDS experience a generalized reduction in retinal sensitivity in all four field quadrants compared with norms, with speculation regarding the impact of refractive and neurogenic aberrations on field testing. The location of field defects may also correspond to the area of retinal thinning due to the decrease in retinal ganglion cells and nerve fibers.

Small sample size studies have found a higher prevalence of color vision abnormalities in patients with TDS, with mixed defect as the most common (70% of eyes), and red-green defect in only 6% of eyes (Vuori et al.).

Differentiating the diagnosis

Clinicians should discern this congenital optic disc anomaly from other optic disc disorders, especially those that increase the risk for progressive vision loss.

Acquired myopic crescents are not caused by malformation of the embryonic ocular fissure but rather are a result of progressive mechanical elongation of the globe. Both TDS and myopic crescents result in attenuated RPE and choroid but are otherwise unremarkable. Ocular history offers the best differential between these conditions; myopic crescents increase in size over time, whereas TDS juxtapapillary thinning will remain stationary.

PAGE BREAK

There is some overlap in clinical terminology of tilted discs and segmental optic nerve hypoplasia, especially in bilateral cases. However, this form of hypoplasia mostly refers to intrauterine injury to the retina, optic tract, chiasm or posterior visual pathway, which in turn causes an asymmetric loss of ganglion cell axons.

The intrinsic anatomic distortions of TDS can make its differential from glaucoma challenging. Measurements of IOP, central corneal thickness, RNFL thinning and visual field progression are the best clinical tools to assess for glaucomatous optic disc changes. Glaucomatous eyes will present with variations of RNFL thinning that will progress over time, whereas patients with TDS will show “false” RNFL thickening in nasal quadrants, from situs inversus of the retinal vessels, that remains constant over time. In this case, because of the disc tilt and situs inversus, the anatomical TI quadrant is shifted nasally, shown by the blue arrow in the figure on page 22. This places the RNFL TI “hump” in the nasal inferior (NI) quadrant, indicated by the red arrow, which produces false thickening of the NI RNFL and false thinning of the TI RNFL. BMO to MRW and ganglion cell measurements are useful, as those results should be unaffected by disc tilt, as they were in this case.

Visual field defects in glaucomatous patients will also progress over time, have a higher mean deviation than patients with TDS and are associated with more focal lamina cribrosa thinning. A visual field defect that respects the horizontal meridian largely rules out TDS, as this disc anomaly does not result in field patterns from nerve fiber layer disruption.

RNFL thinning of what the device measured as the TI quadrant.
B-scan ultrasound using the 10 Mhz probe highlighted the nasally located staphyloma. Shadowing of the optic nerve is seen to the left of the affected area.

Analyzing BMO, TDS

Analysis of BMO aids in cases where the neuroretinal rim appears thinned clinically. BMO marks the beginning of the optic nerve. Localizing this structure and correlating its position to the funduscopic appearance assists in determining whether true cupping exists.

Whether differentiating TDS from glaucoma or evaluating patients with TDS with glaucomatous clinical findings, analysis of RNFL and the visual field progression currently provides the strongest guidance for appropriate treatment and management.

Segmental elevation of the disc margin in TDS can mimic other causes of elevated disc margins, including optic disc drusen, compressive optic neuropathy, ischemic optic neuropathy, retinal vasculature occlusions, papillitis and papilledema from elevated intracranial pressure. Signs and symptoms should allow the clinician to differentiate TDS from these conditions, as TDS is usually an incidental finding on examination and only symptomatic when associated with macular pathology such as CNV. Patients with signs of papilledema should be assessed and worked up.

Anterior visual pathway neoplasms including optic nerve gliomas and meningiomas can potentially elevate the disc margin in an asymmetric pattern like TDS. These conditions will have more extensive visual loss, including progressive visual field abnormalities of enlarged blind spots and central scotomas. The optic nerve may appear pale in eyes with a glioma, and an afferent pupillary defect is commonly present in neoplastic ocular conditions. The physician must order appropriate neuroimaging when suspicious of neoplastic elevation of the disc margin.

TDS is a congenital anomaly that challenges the doctor to analyze the optic nerve structure and function beyond clinical appearance. Using the aforementioned technology, the clinician can better grasp the health of the optic nerve, monitor for stability and differentiate TDS from progressive neuropathies and even urgent or emergent optic nerve conditions.

References:

Apple DJ, et al. Surv Ophthalmol. 1982;doi:10.1016/0039-6257(82)90111-4.

Aung T, et al. Ophthalmology. 2001;doi:10.1016/S0161-6420(00)00497-8.

Brazitikos PD, et al. Arch Ophthalmol. 1990;doi:10.1001/archopht.1990.01070140052027.

Cohen S, et al. Retina. 2013;doi:10.1097/IAE.0b013e3182831364.

Gurlu VP, et al. Retina. 2002;doi:10.1097/00006982-200206000-00021.

Han SY, et al. Semin Ophthalmol. 2014;doi:10.3109/08820538.2013.839815.

Jonas JB, et al. Ophthalmology. 1997;doi:10.1016/S0161-6420(97)30004-9.

Kang S, et al. J Glaucoma. 2013;doi:10.1097/IJG.0b013e31829e1ba2.

Kwun Y, et al. J Glaucoma. 2016;doi:10.1097/IJG.0000000000000565.

Liu GT. Curr Opin Ophthalmol. 2006;doi:10.1097/01.icu.0000243016.90004.12.

Ohno-Matsui K, et al. Am J Ophthalmol. 2015; doi:10.1016/j.ajo.2015.01.022.

Tay E, et al. Am J Ophthalmol. 2005;doi:10.1016/j.ajo.2004.08.076.

Vongphanit J, et al. Am J Ophthalmol. 2002;doi:10.1016/S0002-9394(02)01339-9.

Vuori ML, et al. Acta Ophthalmol Scand. 2007;doi:10.1111/j.1600-0420.2007.00918.x.

Witmer MT, et al. Surv Ophthalmol. 2010;doi:10.1016/j.survophthal.2010.01.002.

Xu M, et al. Retina. 2017;doi:10.1097/IAE.0000000000001140.

Young SE, et al. Am J Ophthalmol. 1976;doi:10.1016/00002-9394(76)90658-9.

For more information:

Catherine Hogan, OD, FAAO, is a clinical instructor at the Southern College of Optometry, Memphis, Tenn.

Jim Williamson, OD, FAAO, FORS, is the residency supervisor at the Memphis VA Medical Center. He can be reached at: jim.williamson44@gmail.com.

Disclosures: Hogan and Williamson report no relevant financial disclosures.