Superior Segmental Optic Nerve Hypoplasia (SSONH)

Key points at a glance

Key points of this disease

• A congenital hypoplasia localized to the superior part of the optic disc, also called “topless optic disc”.
• The prevalence in Japan is about 0.3%, with no sex difference. Most cases are asymptomatic and discovered incidentally.
• Two or more of four characteristic findings (superior vessel displacement, superior disc pallor, superior peripapillary halo, superior retinal nerve fiber layer thinning) are diagnostic criteria.
• The greatest risk factor is maternal diabetes, and glycemic control during pregnancy is considered important.
• OCT aids diagnosis, and differentiation from glaucoma is the most important clinical challenge.
• It is a non-progressive disease and generally does not require treatment, but regular follow-up is necessary due to the risk of glaucoma.
• Inappropriate use of eye drops or surgery to lower intraocular pressure should be avoided.

1. What is Superior Segmental Optic Nerve Hypoplasia (SSONH)?

Superior Segmental Optic Nerve Hypoplasia (SSONH) is a congenital condition characterized by a localized reduction of retinal ganglion cells (RGC) in the superior part of the optic disc. Because the superior portion of the optic disc is hypoplastic, giving the disc a “hatless” appearance, it is also called “topless optic disc”.

Optic nerve hypoplasia (ONH) overall is the most common group of congenital optic nerve abnormalities, and SSONH is a subcategory.

Historical background: In 1977, Petersen & Walton first reported 17 children born to diabetic mothers. In 1989, Kim et al. coined the term “SSONH” and systematically described four characteristic fundus findings [1,2].

Epidemiology:

• Prevalence in Japan: about 0.3% (approximately 1/10 of normal-tension glaucoma) [3]
• Prevalence in Korea: 0.08–0.24% (varies by study) [4]
• No sex difference
• It is said that many cases are undiagnosed due to subtle findings [1].

Q How is SSONH different from optic nerve hypoplasia (ONH)?

A

Optic nerve hypoplasia (ONH) refers to a group of diseases in which the entire optic disc is small. SSONH is a subcategory characterized by hypoplasia limited to the upper part of the optic disc. The distribution of fundus findings and visual field defects differs from ONH, where the lower part or the entire disc is uniformly affected.

2. Main symptoms and clinical findings

Subjective symptoms

In many cases, there are no symptoms, and it is often discovered incidentally during health checkups or examinations for other diseases.

• Visual acuity, intraocular pressure, pupillary function, color vision, eye position, and eye movements are usually within normal range.
• Even if typical visual field defects are present, they are mild and rarely interfere with daily life.
• Some reports indicate that visual field defects are found in only about half of the cases.

Clinical findings

Four characteristic fundus findings (definition by Kim et al., 1989):

Superior displacement of blood vessels

Superior entry of central retinal artery and vein: The origin of the vessels is displaced upward from the optic disc, emerging above the geometric center of the disc.

Pallor of the upper optic disc

Narrowing and pallor of the superior rim: The upper part of the optic disc rim becomes thin and pale, reflecting loss of neural tissue.

Superior Halo

Superior peripapillary scleral halo: A white ring appears above the optic disc (upper part of the double ring sign). This finding indicates hypoplasia.

RNFL Thinning

Superior retinal nerve fiber layer (RNFL) thinning: Thinning of nerve fibers originating from the upper part of the optic disc. Can be quantitatively assessed by OCT.

Often not all four findings are present; not all items are necessarily required. For diagnosis, a combination of at least two of the four findings and a non-progressive visual field defect is considered a guideline (though this criterion is debated) [1,5].

Characteristics of visual field defects:

• Typical cases show a fan-shaped defect that connects to the Mariotte blind spot (physiologic blind spot) and extends downward.
• Characteristically, sensitivity loss occurs more peripherally than the Bjerrum area affected in glaucoma.

Characteristics in Asians: Asians often do not show the four typical findings, and thinning of the superonasal retinal nerve fiber layer is often the main finding [5,6].

Q Does SSONH affect visual acuity?

A

Visual acuity, intraocular pressure, pupillary function, and color vision are usually normal, with little impact on daily life. Even when typical visual field defects are present, if glaucoma does not coexist, visual acuity and visual field often remain unchanged over time.

3. Causes and Risk Factors

Maternal diabetes is considered the greatest risk factor for SSONH [2,4,7]. The first report in 1977 also began with cases of children born to diabetic mothers. Animal experiments have confirmed abnormal ocular structural development and RGC death under hyperglycemia. However, cases have also been reported from mothers without diabetes, so maternal diabetes alone cannot explain the pathology.

Other risk factors:

• Female (the patient is female)
• Short gestational period (preterm birth)
• Low birth weight

Risks for optic nerve hypoplasia in general also include maternal use of certain medications (such as phenytoin, quinine, LSD) and alcohol consumption during pregnancy.

Developmental background: The optic nerve initially has about 3.7 million nerve fibers, but by 29 weeks of gestation, natural selection through apoptosis reduces this to about 1.1 million. Abnormalities in this process are thought to contribute to optic nerve hypoplasia.

Prevention and Daily Care

The greatest risk factor for SSONH is abnormal blood glucose levels during pregnancy. If you are planning a pregnancy or are pregnant, please work with your doctor to manage your blood glucose appropriately.

4. Diagnosis and Testing Methods

Fundus Examination and Diagnostic Criteria

A combination of two or more of the four characteristic findings along with non-progressive visual field defects is considered a diagnostic guideline. However, this criterion often does not apply to Asians. According to criteria proposed in 2008, visual field defect patterns on Goldmann perimetry and retinal nerve fiber layer defects should be emphasized over optic disc morphology.

DM/DD ratio (disc diameter to macula-disc distance ratio):

• Clinically, a ratio of 3 or more suggests optic nerve hypoplasia, and 4 or more indicates high likelihood.
• A ratio of 3.2 or more is also used for simple diagnosis of small optic disc.
• A peripapillary pigment ring (double ring sign) may be observed.

OCT (Optical Coherence Tomography)

OCT is the most useful test for diagnosing SSONH and differentiating it from glaucoma.

• Quantitative evaluation of retinal nerve fiber layer thickness: In SSONH, the superior retinal nerve fiber layer thickness is markedly thinned (Unoki et al. reported 56.7 µm in affected eyes vs. 127.3 µm in normal eyes for the superior quadrant) [8].
• Useful measurement segments: The 12, 1, and 2 o’clock directions are considered most useful for diagnosis [5].
• Involvement of all quadrants: Not only the superior quadrant but all quadrants are affected, suggesting widespread involvement of the entire retina [5,8].

SD-OCT: Overhang of the retinal pigment epithelium (RPE)/Bruch’s membrane (BM) complex above the optic disc is characteristic of SSONH, and the overhang at the nasal disc margin in affected eyes has been reported to be significantly longer than in healthy eyes [6].

OCTA (Optical Coherence Tomography Angiography): Decreased nasal peripapillary capillary vessel density (RPCVD) and increased inferior and temporal RPCVD are observed in SSONH, which is useful for differentiation from glaucoma [9].

Head MRI

Performed to evaluate systemic complications. Abnormalities of the pituitary infundibulum have been reported in approximately 15% of optic nerve hypoplasia cases, and further evaluation for endocrine disorders may be necessary. The association with de Morsier syndrome (septo-optic dysplasia: optic nerve hypoplasia + absent septum pellucidum + agenesis of corpus callosum + pituitary dysfunction) should also be considered. Even in unilateral cases, systemic evaluation is recommended at least once.

Differentiation from Glaucoma

SSONH and glaucoma have similar fundus and visual field findings, making differentiation the most important clinical challenge.

The main differentiating points between SSONH and glaucoma are shown below.

Differentiation Item	SSONH	Glaucoma
Course	Non-progressive	Progressive
Predilection sites of retinal nerve fiber layer defect	Superior and superonasal	Temporal (upper and lower poles)
Retinal pigment epithelium/BM protrusion	Present (superior)	Absent
Location of visual field defect	More peripheral than Bjerrum area	Bjerrum area

• The most important evidence supporting SSONH is the absence of progressive changes in visual field and optic disc morphology over time.
• Glaucomatous optic atrophy tends to occur slightly temporal, and visual field/RNFL defects progress over time [7].
• Some reports suggest that SSONH is prone to glaucoma comorbidity, requiring long-term follow-up [10].

Q How to differentiate SSONH from glaucoma?

A

The key point is the temporal stability of visual field and optic disc morphology. Since SSONH is non-progressive, if regular visual field tests and OCT show no changes, it provides evidence against glaucoma. Furthermore, the location of RNFL defects (superior/superonasal in SSONH, temporal in glaucoma), protrusion of the retinal pigment epithelium/BM complex (characteristic of SSONH), and capillary density distribution on OCTA are also useful for differentiation. See the “Diagnosis and Examination Methods” section for details.

5. Standard Treatment

SSONH is a non-progressive congenital condition and generally does not require treatment. Long-term follow-up studies have confirmed that visual field defects and optic disc morphology remain unchanged [1,7].

Principles of management:

• Observation is fundamental: Regular OCT and visual field testing should be continued to monitor for the presence of glaucoma.
• When detected in children: Attempt to improve remaining visual function by providing appropriate refractive correction.

Important considerations in treatment

SSONH is sometimes misdiagnosed as glaucoma, and in such cases there is a risk of unnecessary intraocular pressure-lowering treatment (eye drops, surgery). Hasty use of eye drops or surgery aimed at lowering intraocular pressure should be avoided. On the other hand, there are reports that glaucoma is often associated with SSONH, so regular follow-up is essential. The most important management point is to confirm whether progression is occurring through regular monitoring with visual field testing and OCT.

Q Is treatment necessary if diagnosed with SSONH?

A

Basically, treatment is not necessary. SSONH is a non-progressive congenital condition, and if glaucoma does not develop, vision and visual field remain stable. However, because there is a risk of glaucoma, regular follow-up with OCT and visual field testing should be continued. It is recommended to avoid hasty use of eye drops or surgery aimed at lowering intraocular pressure.

6. Pathophysiology and detailed pathogenesis

Basic pathological mechanism

The pathological essence of optic nerve hypoplasia is the developmental failure of retinal ganglion cells (RGCs) and their nerve fibers. Two mechanisms are considered: primary RGC reduction due to developmental abnormalities, and retrograde degeneration secondary to central (lateral geniculate body, visual cortex) developmental abnormalities. The RNFL thinning in SSONH directly reflects selective RGC loss in the superior region.

Developmental process and involvement of diabetes

Optic nerve fibers number approximately 3.7 million in early development, but are reduced to about 1.1 million by apoptosis (programmed cell death) by the 29th week of gestation. It is presumed that impairment of this normal developmental process (lack of initial formation or increased apoptosis) is involved in the pathogenesis of SSONH. A 1998 study showed increased apoptosis in retinal cells of diabetic patients, suggesting that maternal hyperglycemia may cause excessive RGC death.

Mechanism of superior selectivity

Why the damage is limited to the upper part of the optic disc has not been fully elucidated. It is known that signaling via ephrin B1/B2 (ligands) and EphB1-4 (receptors) is involved in dorsoventral patterning (differentiation of upper and lower regions) and RGC axon guidance at the optic disc, and abnormalities in this system have been proposed as a possible mechanism for creating the upper-lower boundary. However, while the clinically observed upper-lower boundary is very distinct, the ephrin/Eph signaling forms a gradual concentration gradient, so some argue that this explanation alone is insufficient. There is also discussion that selective cell death following local damage at the optic disc may be a more appropriate explanation [1].

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7. References

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2. Landau K, Bajka JD, Kirchschläger BM. Topless optic disks in children of mothers with type I diabetes mellitus. Am J Ophthalmol. 1998;125(5):605-611. PMID: 9625543.
3. Yamamoto T, Sato M, Iwase A. Superior segmental optic hypoplasia found in Tajimi Eye Health Care Project participants. Jpn J Ophthalmol. 2004;48(6):578-583. PMID: 15592784.
4. Seo S, Lee CE, Kim DW, et al. Prevalence and risk factors of superior segmental optic hypoplasia in a Korean population: the Korea National Health and Nutrition Examination Survey. BMC Ophthalmol. 2014;14:157. PMID: 25510911.
5. Yagasaki A, Sawada A, Manabe Y, Yamamoto T. Clinical features of superior segmental optic hypoplasia: hospital-based study. Jpn J Ophthalmol. 2019;63(1):34-39. PMID: 30367298.
6. Hayashi K, Tomidokoro A, Konno S, Mayama C, Aihara M, Araie M. Evaluation of optic nerve head configurations of superior segmental optic hypoplasia by spectral-domain optical coherence tomography. Br J Ophthalmol. 2010;94(6):768-772. PMID: 20508053.
7. Yamamoto T. Superior segmental optic hypoplasia as a differential diagnosis of glaucoma. Taiwan J Ophthalmol. 2019;9(2):63-66. PMID: 31198664.
8. Unoki K, Ohba N, Hoyt WF. Optical coherence tomography of superior segmental optic hypoplasia. Br J Ophthalmol. 2002;86(8):910-914. PMID: 12140214.
9. Abe M, Omodaka K, Kikawa T, Nakazawa T. Radial peripapillary capillary density in superior segmental optic hypoplasia measured with OCT angiography. BMC Ophthalmol. 2020;20(1):199. PMID: 32448227.
10. Yamazaki Y, Hayamizu F. Superior segmental optic nerve hypoplasia accompanied by progressive normal-tension glaucoma. Clin Ophthalmol. 2012;6:1713-1716. PMID: 23118522.