Abstract

Background: Coloboma or colobomatous cyst of the optic nerve coloboma (ONC) is a rare congenital anomaly commonly associated with microphthalmia or anophthalmia. Neurosurgeons usually treat orbital lesions surgically; however, in some centers, neuro-ophthalmologists and other surgical specialties may also be involved in these procedures. Given this context, neurosurgeons must be familiar with various intraorbital lesions, including ONC. Here, emphasizing the clinical, pathological, and radiological aspects, we report two uncommon pediatric cases of ONC to enhance neurosurgeons’ awareness and recognition of this condition.

Case Description: The first case involved a 2-year and 9-month-old boy who presented with proptosis, palpebral ptosis, visual impairment, and exotropia of the right eye. Magnetic resonance imaging (MRI) showed an intraorbital retrobulbar cystic lesion without microphthalmia. A right front-orbital craniotomy was performed with total removal of the cystic lesion and with improved proptosis, maintaining the visual deficit. The second case involved a 7-year-old and a 9-month-old girl with congenital exotropia and visual impairment in the right eye. MRI revealed a cystic optic nerve associated with microphthalmia. She underwent a cyst puncture and clinical and MRI follow-up. The histology studies confirmed ONC in both cases.

Conclusion: Although often unfamiliar to neurosurgeons, these two presentations of ONC (with and without microphthalmia) should be included in the differential diagnosis of retrobulbar lesions, especially in pediatric patients.

Keywords: Coloboma, Colobomatous cysts, Intraorbital optic nerve cyst, Microphthalmia, Orbital lesions

INTRODUCTION

The optic nerve coloboma (ONC) is a rare embryogenic malformation caused by an abnormal closure of the fetal optic fissure along the eye and optic nerve.[ 3 , 6 ] Their formation possibly results from impaired astrocyte differentiation during development.[ 16 ] The defects can affect any ocular structure from the cornea to the optic nerve, occurring hereditary or sporadically.[ 4 , 11 ] It has the same frequency in uni- or bilateral forms and is present in 0.5–2.4 children/10,000 live births.[ 2 , 12 , 14 ]

Clinically, it occurs as a cyst near the optic nerve, possibly invading the orbital cavity and displacing the eye into the orbit, leading to exophthalmos, strabismus, and visual deficits. It is often associated with microphthalmia or anophthalmia.[ 8 ] The severity of optic disc involvement correlates with the visual deficits caused by the defect.[ 10 ] The condition’s rarity, along with its variable presentation and potential for severe visual and ocular complications, emphasizes the importance of effective diagnostic and therapeutic approaches.

Resecting pure intraorbital tumors is challenging due to the presence of neural and vascular structures, particularly the optic apparatus. Neurosurgeons typically perform surgery on orbital tumors, but in some centers, neuro-ophthalmologists, head-and-neck surgeons, and craniomaxillofacial surgeons may also be involved.

Given this context, neurosurgeons must be familiar with various intraorbital lesions, including ONC. Here, by emphasizing the clinical, pathological, and radiological aspects, we present two uncommon pediatric cases of ONC to enhance neurosurgeons’ awareness and recognition of this condition.

CASE REPORTS

Case 1

A 2-year-and-9-month-old boy presented with palpebral ptosis on the right eye beginning 1 year before. He was admitted with exotropia, proptosis, and visual deficit (counting fingers). The retinography of the right eye reveals a tessellated background and a pale, colobomatous optic disc with a deep, dark excavation [ Figure 1 ]. Magnetic resonance imaging (MRI) showed intraorbital retrobulbar cystic formation, and the ocular globe axial length was 21 mm (without microphthalmia) [ Figures 2a and b ]. There were no systemic signs, and the systemic investigation did not show other organ abnormalities. The genetic investigation does not show any specific relation to a syndrome or a family history of the lesion.

Figure 1:

Case 1 – Retinography of the right eye: preoperative, showing a tessellated background and a pale colobomatous optic disc with deep, dark excavation.

Figure 2:

Case 1 – (a) Preoperative magnetic resonance imaging demonstrating a right intraorbital retrobulbar cystic lesion with proptosis on T2-weighted and (b) T1-weighted images.

A right front-orbital craniotomy with the removal of the orbital roof, followed by careful dissection of the intraorbital structures, exposed a light-gray cystic optic nerve mass with drainage and capsule resection [ Figure 3 ]. Histological examination demonstrated a fibrous structure in the cyst wall, without glial, retinal, choroidal, or inflammatory tissue, consistent with the diagnosis of ONC [ Figure 4 ].

Figure 3:

Case 1 – Perioperative photography showing the intraorbital retrobulbar cystic lesion. (arrow).

Figure 4:

Case 1 – Histopathological examination – hematoxylin and eosin staining showing fibrous tissue in the cyst wall, without glial, retinal, choroidal, or inflammation tissue at medium magnification (×40) (arrows).

The postoperative retinography of the right eye showed that the entire optical disc had become white, with the excavation having disappeared [ Figure 5 ]. Postoperative MRI showed a complete cyst resection, enophthalmia, and an ocular globe whose axial length was 23.6 mm [ Figure 6 ]. The postoperative course was uneventful. The patient has been well-maintained with previous exotropia, the visual deficit, and palpebral ptosis, along with a regression of the proptosis after 2 years of follow-up.

Figure 5:

Case 1 – Retinography of the right eye: postoperative, showing that the entire optical disc became white with the disappearance of the excavation.

Figure 6:

Case 1 – (a) Postoperative magnetic resonance imaging gradient echo sequence; (b) and T1-weighted sequence showing an enophthalmos and the complete resection of the intraorbital cystic lesion.

Case 2

A 7-year-old girl with congenital strabismus and a visual deficit in the right eye (counting fingers) associated with microphthalmia. The MRI revealed a multi-cystic, well-defined lesion in the right orbit, measuring 1.8 × 1.5 × 2.1 cm in the anteroposterior, lateral, and craniocaudal directions, respectively. This lesion compressed the ocular globe and displaced the optic nerve. The patient underwent a biopsy through cystic puncture at 1 year of age. On biomicroscopy, lens subluxation associated with subcapsular cataracts was observed in the right eye. In the fundus of the right eye, a colobomatous disc, posterior pole chorioretinitis scars, and vitreous opacities were noted. The axial length of the ocular globe was 20.3 mm in the right eye and 22.4 mm in the left eye. Retinography revealed the right eye’s coloboma of the optic nerve with associated chorioretinal scars and vitreous opacities [ Figure 7 ]. The postoperative MRI showed a cystic, septate, encapsulated, and well-defined lesion in the right orbit, compressing the posteromedial wall of the ocular globe and displacing the optic nerve inferiorly, with capsular contrast enhancement [ Figures 8a and b ]. The histopathological study of the material obtained by the previously described procedure confirmed the diagnosis of ONC [ Figure 9 ]. After 4 years of follow-up, she is undergoing annual MRI and clinical surveillance with stable lesion dimensions, and the patient and her family have no interest in pursuing esthetic surgical options.

Figure 7:

Case 2 – Retinography of the right eye (two views) revealed coloboma of the optic nerve with associated chorioretinal scars and vitreous opacities.

Figure 8:

Case 2 – (a) T1-weighted and (b) T2-weighted magnetic resonance imaging demonstrated a right intraorbital retrobulbar cystic lesion and associated microphthalmia.

Figure 9:

Case 2 – Photomicrograph showing fibrous tissue in the cyst wall, without glial, retinal, choroidal, or inflammation tissue (Hematoxylin and eosin, ×100) (arrows).

DISCUSSION

ONCs and colobomatous cysts are rare orbital anomalies, typically associated with genetic syndromes and often accompanied by microphthalmia, which facilitates diagnosis.[ 18 ] However, when these classic syndromic features are absent, as in our cases, the diagnosis becomes more challenging. This underscores the importance of a comprehensive diagnostic approach.[ 18 ] A thorough evaluation that combines clinical findings and imaging studies is necessary in such atypical cases where the affected eye maintains normal dimensions.

ONCs are classified as typical or atypical by their location and derivation.[ 20 ] Typical colobomas result from a variable lack of fusion of the fetal optic fissure, which extends inferonasally along the optic nerve and globe.[ 20 ] Atypical colobomas in the iris may result from abnormal secondary fetal fissures; they do not result from a defect in the fusion of the fetal optic fissure.[ 20 ] Furthermore, they are commonly associated with changes in ocular dimensions, such as microphthalmia or anophthalmia.[ 13 ]

In the first case described, despite several other associated ocular changes, the dimensions of the affected eye remained unchanged. The marked difference in the cycloplegia refractive examination observed after coloboma removal, from −7.5 to −14.5 spherical diopters, shows that there was a flattening caused by the cyst of the eye, which became more elongated after surgery, according to the comparative findings of the diameters in the pre-and post-operative MRIs. These atypical changes, not associated with microphthalmia or anophthalmia, may result from the structural interaction of the cyst with the globe.[ 5 ] Studies suggest larger cysts can mitigate orbital hypoplasia by maintaining orbital volume and improving cosmetic and functional outcomes. Orbital cysts can act as natural volume replacements, potentially promoting orbital development and symmetry.[ 5 ]

Optic disc coloboma may be diagnosed in children during routine ophthalmologic examinations or evaluations for other ocular problems, such as strabismus or amblyopia. Some cases[ 1 , 4 , 7 , 8 , 19 , 21 ] describe the presence of optic disc coloboma in children aged between 21 months and 12 years, correlating these epidemiological characteristics with our cases. In this age group, complications may include significant visual deficits, development of amblyopia, nystagmus, and strabismus. The diagnosis may occur later in adults, mainly if symptoms are mild or asymptomatic. However, complications in adults may include progressive visual loss, retinal detachment, cataract development, and glaucoma.[ 15 , 17 ]

Many cases in the literature are associated with genetic syndromes, such as Charge syndrome and renal coloboma syndrome[ 4 , 8 , 23 ] or paired box (PAX₂) gene mutations.[ 13 , 24 ] This association is significant because genetic syndromes often present with a broader spectrum of anomalies, influencing management and prognosis. Mutations in the PAX₂ gene are a common cause of renal coloboma syndrome, characterized by optic colobomas and renal abnormalities.[ 4 ] However, other genetic mutations, such as those found in the sperm antigen with calponin homology and coiled-coil domains 1-like (SPECC1L) gene in 22q11.2 duplication syndrome, may also be involved in the development of colobomas.[ 23 ] In addition, ONC has been reported in patients with tetraploidy, a rare chromosomal condition.[ 23 ] The genetic diversity underlying colobomas highlights the complexity of this malformation. Sporadic cases of colobomas may stem from low-penetrance genetic mutations, environmental insults during embryogenesis, or a combination of these factors.[ 24 ] However, in our case, neither patient presented with systemic signs that could indicate a genetic syndrome or a family history of the lesion, suggesting it was sporadic. However, patients presenting ONC should have a genetic study. The occurrence of bilateral involvement is more common,[ 21 ] although unilateral pathology has also been noted.[ 8 , 15 , 22 ]

Other intraorbital optic nerve cysts include: optic nerve glioma, meningioma, neurofibromatosis, empty sella syndrome, hemangioma of leptomeningeal origin, heterotopia glial, and arachnoid cyst.[ 9 ] Orbit and cranial MRI, along with ophthalmologic evaluation including fundoscopy, are important tools in cystic evaluation to define the conduct.

The treatment of colobomas associated with orbital cysts is multifaceted and must be tailored to each patient’s needs, requiring a multidisciplinary approach.[ 18 ] Options range from conservative management to invasive surgical interventions, depending on the cyst’s size, functional impact, and connection to the globe. Kim et al.[ 9 ] recommend puncture and aspiration of the cystic content followed by histopathological study. Excluding the tumor diagnosis, this procedure can avoid surgery for benign cysts, such as ONC, and decrease compression of the ocular globe and optic nerve, improving the patient’s visual prognosis, without a craniotomy. In children, devices such as orbital expanders can be used to promote symmetrical growth of the orbit.[ 9 ] The main goal of surgical intervention is the functional aspect of visual acuity and ocular movement, followed by esthetic reasons that include restoring orbital volume, preserving ocular structures to the greatest extent possible, and achieving optimal cosmetic outcomes.[ 17 ]

CONCLUSION

We present two rare cases of ONC with distinct presentations, highlighting the variability of this anomaly. Although ONC is frequently associated with syndromic features, its sporadic occurrence and atypical presentations, as observed here, increase diagnostic complexity. These cases reinforce the importance of including ONC in the differential diagnosis of intraorbital cystic lesions, especially in pediatric patients presenting with proptosis, visual deficits, or strabismus. This condition remains unfamiliar primarily to neurosurgeons, emphasizing the need for greater awareness and detailed clinical and imaging evaluations to achieve an accurate diagnosis.

Ethical approval:

The research/study approved by the Institutional Review Board at Health Science Center Ethics Committee at the Federal University of Espírito Santo, number 85925418.2.0000.5060, dated February 05, 2018.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

References

1. Beck KD, Harper CA. Bilateral optic nerve colobomas in infant with tetraploidy. Retin Cases Brief Rep. 2016. 10: 252-3

2. Bermejo E, Martínez-Frías ML. Congenital eye malformations: Clinical-epidemiological analysis of 1,124,654 consecutive births in Spain. Am J Med Genet. 1998. 75: 497-504

3. Chu Y, Hughes S, Chan-Ling T. Differentiation and migration of astrocyte precursor cells and astrocytes in human fetal retina: Relevance to optic nerve coloboma. FASEB J. 2001. 15: 2013-5

4. Chung GW, Edwards AO, Schimmenti LA, Manligas GS, Zhang YH, Ritter R. Renal-coloboma syndrome: Report of a novel PAX2 gene mutation. Am J Ophthalmol. 2001. 132: 910-4

5. Cui Y, Zhang Y, Chang Q, Xian J, Hou Z, Li D. Digital evaluation of orbital cyst associated with microphthalmos: Characteristics and their relationship with orbital volume. PLoS One. 2016. 11: e0157819

6. Elouarradi H, Bencherif MZ. Kyste colobomateux de l’orbite. Pan Afr Med J. 2014. 17: 159

7. Gopal L, Badrinath SS, Kumar KS, Doshi G, Biswas N. Optic disc in fundus coloboma. Ophthalmology. 1996. 103: 2120-6 discussion 2126-7

8. Guirgis MF, Lueder GT. Choroidal neovascular membrane associated with optic nerve coloboma in a patient with CHARGE association. Am J Ophthalmol. 2003. 135: 919-20

9. Kim KM, Kang SJ, Kim DS, Chi JG, Kim SM. Congenital intraorbital optic nerve cyst. Case report. J Neurosurg. 1999. 91: 325-7

10. Laasri K, El harras Y, Izi Z, El yousfi Z, El fenni J, En nafaa I. Congenital right optic nerve colobomatous cyst associated with microphthalmos. Radiol Case Rep. 2024. 19: 5346-9

11. Murphy BL, Griffin JF. Optic nerve coloboma (morning glory syndrome): CT findings. Radiology. 1994. 191: 59-61

12. Nakamura KM, Diehl NN, Mohney BG. Incidence, ocular findings, and systemic associations of ocular coloboma: A population-based study. Arch Ophthalmol. 2011. 129: 69-74

13. Pagon RA. Ocular coloboma. Surv Ophthalmol. 1981. 25: 223-36

14. Pollock S. The morning glory disc anomaly: Contractile movement, classification, and embryogenesis. Doc Ophthalmol. 1987. 65: 439-60

15. Salam A, Khan-Lim D, Luff AJ. Superior retinal detachment in an oil-filled eye with a colobomatous optic disc. Retin Cases Brief Rep. 2008. 2: 124-5

16. Savell J, Cook JR. Optic nerve colobomas of autosomal-dominant heredity. Arch Ophthalmol. 1976. 94: 395-400

17. Sels L, Dirven W, Devriendt K, Leys A. Severe case of renal coloboma syndrome in long-term follow-up. Retin Cases Brief Rep. 2020. 14: 77-81

18. Shields JA, Shields CL. Orbital cysts of childhood--classification, clinical features, and management. Surv Ophthalmol. 2004. 49: 281-99

19. Silva MW, Martins A, Medeiros AL, Vasconcelos A, Ventura CV. Ophthalmological manifestations of the SchuursHoeijmakers syndrome: A case report. Arq Bras Oftalmol. 2021. 85: 85-7

20. Simmons JD, LaMasters D, Char D. Computed tomography of ocular colobomas. AJR Am J Roentgenol. 1983. 141: 1223-6

21. Skriapa Manta A, Olsson M, Ek U, Wickström R, Teär Fahnehjelm K. Optic disc coloboma in children-prevalence, clinical characteristics and associated morbidity. Acta Ophthalmol. 2019. 97: 478-85

22. Sun Y, Ng JK, Gaynon MW. Pseudoduplication of the optic disk. Retin Cases Brief Rep. 2011. 5: 144-5

23. Valencia-Peña C, Jiménez-Sanchez P, Saldarriaga W, PayánGómez C. Optic nerve coloboma as an extension of the phenotype of 22q11.23 duplication syndrome: A case report. BMC Ophthalmol. 2020. 20: 333

24. Venincasa VD, Modi YS, Aziz HA, Ayres B, Zehetner C, Shi W. Clinical and echographic features of retinochoroidal and optic nerve colobomas. Invest Ophthalmol Vis Sci. 2015. 56: 3615-20