Optic Nerve Aplasia Research Articles

Unilateral optic nerve aplasia associated with microphthalmia: a rare cadaveric report

This case report describes the anatomical presentation of the anomalous optic nerve (cranial nerve II). Cranial nerve II developmental anomalies encompass both optic nerve hypoplasia and aplasia. While most studies on optic nerve anomalies rely on radiological imaging, anatomical presentation and nerve course are rarely described. The current case reveals a complete absence of the right optic nerve and its connection to the optic chiasma, resembling radiological presentation of optic nerve aplasia. In addition, the right-sided bony orbit and eyeball were smaller than the left, accompanied by a poorly developed cornea and iris with a calcified mass, resembling clinical presentation of microphthalmia. Having a thorough understanding of the gross anatomical presentation and course of optic nerve anomalies can facilitate precise diagnosis and management of visual impairments associated with these anomalies. Furthermore, such knowledge can provide valuable insights into the actual prevalence of optic nerve aplasia and further substantiate the literature.

Refractory Central Serous Retinal Detachment in the Presence of Optic Disc Pit – Case Report

Among congenital optic disc anomalies are megalopapilla, optic nerve aplasia and hypoplasia (de Morsier’s syndrome) and optic disc excavations. The latter are attributed to abnormal fetal fissure’s closure. There is a wide spectrum of these anomalies ranging from single optic disc pit, to multiple pits, to morning glory syndrome. Excavated defects of the optic disc are usually associated with retinal detachment in the macular region. It is usually confined to the macular region though a subtotal or total retinal detachment may occur. It requires treatment (a surgical approach in most cases) though a spontaneous resolution of the subretinal fluid within a short period of the detachment onset has been observed. We report a case of unilateral central serous retinal detachment in the presence of a bilateral optic disc pit refractory to primary treatment.

Optic nerve aplasia

Optic nerve aplasia (ONA) is a rare disorder. We report the second largest series including ophthalmologic, systemic, and genetic findings.

Optic Nerve Aplasia.

Optic nerve aplasia (ONA) is a rare ocular anomaly. We report ophthalmologic, systemic, and genetic findings in ONA. Patients were identified through an International Pediatric Ophthalmology listserv and from the practice of the senior author. Participating Listserv physicians completed a data collection sheet. Children of all ages were included. Neuroimaging findings were also recorded. Nine cases of ONA are reported. Patients' ages ranged from 10 days to 2 years (median 9 months). Seven cases were bilateral. All patients had absence of the optic nerve and retinal vessels in the affected eye or eyes. Ophthalmologic findings included glaucoma, microcornea, persistent pupillary membrane, iris coloboma, aniridia, retinal dysplasia, retinal atrophy, chorioretinal coloboma, and persistent fetal vasculature. Systemic findings included facial dysmorphism, cardiac, genitourinary, skeletal, and developmental defects. A BCOR mutation was found in one patient. One patient had rudimentary optic nerves and chiasm on imaging. ONA is a unilateral or bilateral condition that may be associated with anomalies of the anterior or posterior segment with or without systemic findings. Rudimentary optic nerve on neuroimaging in one case suggests that ONA is on the continuum of optic nerve hypoplasia.

Case report: Unilateral optic nerve aplasia and developmental hemi-chiasmal dysplasia with VEP misrouting

PurposeTo describe the trans-occipital asymmetries of pattern and flash visual evoked potentials (VEPs), in an infant with MRI findings of unilateral optic nerve aplasia and hemi-chiasm dysplasia.MethodsA child with suspected left cystic microphthalmia, left microcornea, left unilateral optic nerve aplasia, and hemi-chiasm underwent a multi-channel VEP assessment with pattern reversal, pattern onset, and flash stimulation at the age of 16 weeks.ResultsThere was no VEP evidence of any post-retinal visual pathway activation from left eye with optic nerve aplasia. The VEP trans-occipital distribution from the functional right eye was skewed markedly across the midline, in keeping with significant misrouting of optic nerve fibres at the chiasm. This was supported by the anatomical trajectory of the optic chiasm and tracts seen on MRI.ConclusionThis infant has chiasmal misrouting in association with unilateral optic nerve aplasia and unilateral microphthalmos. Chiasmal misrouting has not been found in patients with microphthalmos or anophthalmos, but has been reported after early eye loss in animal models. Our findings contribute to our understanding of the discrepancy between the visual pathway physiology of human unilateral microphthalmia and animal models.

The Atoh7 remote enhancer provides transcriptional robustness during retinal ganglion cell development

The retinal ganglion cell (RGC) competence factor ATOH7 is dynamically expressed during retinal histogenesis. ATOH7 transcription is controlled by a promoter-adjacent primary enhancer and a remote shadow enhancer (SE). Deletion of the ATOH7 human SE causes nonsyndromic congenital retinal nonattachment (NCRNA) disease, characterized by optic nerve aplasia and total blindness. We used genome editing to model NCRNA in mice. Deletion of the murine SE reduces Atoh7 messenger RNA (mRNA) fivefold but does not recapitulate optic nerve loss; however, SEdel/knockout (KO) trans heterozygotes have thin optic nerves. By analyzing Atoh7 mRNA and protein levels, RGC development and survival, and chromatin landscape effects, we show that the SE ensures robust Atoh7 transcriptional output. Combining SE deletion and KO and wild-type alleles in a genotypic series, we determined the amount of Atoh7 needed to produce a normal complement of adult RGCs, and the secondary consequences of graded reductions in Atoh7 dosage. Together, these data reveal the workings of an evolutionary fail-safe, a duplicate enhancer mechanism that is hard-wired in the machinery of vertebrate retinal ganglion cell genesis.

Unilateral optic nerve aplasia documented with optical coherence tomography—case report and literature review

Optic nerve aplasia is a rare nonhereditary developmental anomaly characterized by congenital absence of the optic nerve, retinal blood vessels, retinal ganglion cells, and optic nerve fibers in a unilaterally malformed eye of an otherwise healthy individual. We report the case of a 6-year-old girl with unilateral optic nerve aplasia documented by optical coherence tomography (OCT). She had no systemic or central nervous system anomalies. Her right eye had no light perception, total afferent pupillary defect, microcornea, variable strabismus, and enophthalmos. The fundus examination showed complete absence of the optic nerve and central retinal vessels characteristic of optic nerve aplasia in the right eye. Computerized tomography and magnetic resonance imaging showed unilateral absence of the optic nerve. Spectral domain OCT showed absence of normal foveal contour, severe atrophy of the retinal layers, extremely thin choroid, and absence of the optic nerve head.

Unilateral Optic Nerve Aplasia In An Otherwise Normally Developed Eye

We report a unique case of unilateral optic nerve aplasia in an otherwise normally developed child. It was an incidental finding in a preterm child who was being screened for retinopathy of prematurity. Anterior segment of the affected eye was normal. However pupillary light reflexes- direct and consensual were absent. Ultrasound B scan and MRI confirmed the absence of optic nerve, in an otherwise normally developed eye.

A Case of Septo-Optic Dysplasia Resulting in Central Diabetes Insipidus and Nonobstructive Bilateral Hydronephrosis

A 27-year-old male with nonobstructive hydronephrosis was referred from the urology department for polyuria evaluation and management. The patient was hospitalized for urinary tract infection and cystostomy was performed due to neurogenic bladder of unknown origin. The patient was of short stature and had visual impairment. From the interview, we discovered he had been suffering from polyuria and polydipsia for more than 20 years. Urine output was 13 L/day and urine osmolarity was 85 mOsm/kg. The results of a water deprivation test were consistent with central diabetes insipidus. Septo-optic dysplasia (SOD) was observed on brain magnetic resonance imaging (MRI). SOD is a very rare condition characterized by agenesis of the septum pellucidum or corpus callosum, which may cause optic nerve aplasia or hypoplasia, midbrain abnormalities and/or hypopituitarism. After desmopressin treatment, polyuria and hydronephrosis were improved. We report a case of a 27-year-old male diagnosed with SOD including diabetes insipidus, resulting in nonobstructive hydronephrosis. (Korean J Med 2014;87:209-214)

Optic Nerve Aplasia and Microphthalmos: A Case Report

Optic nerve aplasia is an extremely rare anomaly that is usually associated with microphthalmos as well as with other ocular and extraocular anomalies. In this case report we describe a case of an occasional finding of unilateral complete aplasia of the optic nerve in girl at the age of 42 days, in association only with microphthalmos.

ATOH7 mutations cause autosomal recessive persistent hyperplasia of the primary vitreous

The vertebrate basic helix-loop-helix (bHLH) transcription factor ATOH7 (Math5) is specifically expressed in the embryonic neural retina and is required for the genesis of retinal ganglion cells (RGCs) and optic nerves. In Atoh7 mutant mice, the absence of trophic factors secreted by RGCs prevents the development of the intrinsic retinal vasculature and the regression of fetal blood vessels, causing persistent hyperplasia of the primary vitreous (PHPV). We therefore screened patients with hereditary PHPV, as well as bilateral optic nerve aplasia (ONA) or hypoplasia (ONH), for mutations in ATOH7. We identified a homozygous ATOH7 mutation (N46H) in a large family with an autosomal recessive PHPV disease trait linked to 10q21, and a heterozygous variant (R65G, p.Arg65Gly) in one of five sporadic ONA patients. High-density single-nucleotide polymorphism analysis also revealed a CNTN4 duplication and an OTX2 deletion in the ONA cohort. Functional analysis of ATOH7 bHLH domain substitutions, by electrophoretic mobility shift and luciferase cotransfection assays, revealed that the N46H variant cannot bind DNA or activate transcription, consistent with structural modeling. The N46H variant also failed to rescue RGC development in mouse Atoh7-/- retinal explants. The R65G variant retains all of these activities, similar to wild-type human ATOH7. Our results strongly suggest that autosomal recessive persistent hyperplastic primary vitreous is caused by N46H and is etiologically related to nonsyndromic congenital retinal nonattachment. The R65G allele, however, cannot explain the ONA phenotype. Our study firmly establishes ATOH7 as a retinal disease gene and provides a functional basis to analyze new coding variants.

Congenital optic nerve aplasia

To delineate the phenotype associated with sporadic optic nerve (ON) aplasia.

Unilateral optic nerve aplasia associated with microphthalmos

Optic nerve aplasia is a rare developmental anomaly characterised by the congenital absence of the optic nerve, central retinal vessels and retinal ganglion cells that is seen most often in a unilaterally malformed eye. We reported a girl with a very rare anomaly of the eye, unilateral aplasia of the optic nerve and microphthalmia. We carried out a complete ophthalmological examination, A- and B-scan ultrasonography, magnetic resonance imaging (MRI) of the orbit and brain, pediatrician, neurological examinations and karyotype determination. The examined child was a third child from the third regular pregnancy, born at term (39 GS, BM 3100 g). Family ocular history was negative. The right corneal diameter was 7.5 mm and left 10 mm. On dilated fundus examination, the right eye showed the absence of op tic nerve and central retinal vessels. B-scan echography showed a small right globe (axial length 13.80 mm), normal size left globe (axial length 18.30 mm) and the absence of optic nerve on the right eye. Physical and neurological findings and karyotype was normal. MRI of the orbits and brain marked asymmetry of globe size and unilateral absence of the optic nerve. The patient is under the control of a competent ophthalmologist and prosthetic. Further aesthetic and functional development of a young person is the primary goal in tracking this rare congenital optic nerve anomalies in the malformed eye.

Unilateral congenital glaucoma in a child with optic nerve aplasia

Unilateral optic nerve aplasia is a rare, nonhereditary defect associated with anterior chamber malformations and other ocular malformations. We report the case of an 8½-week-old boy with unilateral optic nerve aplasia who was diagnosed with glaucoma on presentation with corneal edema and an intraocular pressure of 36 mm Hg. The cornea edema cleared after a trabeculotomy, and subsequent fundus examination revealed optic nerve aplasia that was confirmed with magnetic resonance imaging. Intraocular pressure remained well-controlled with 7½ months of follow-up. To our knowledge, this is the first documented case of optic nerve aplasia associated with glaucoma at presentation.

Unilateral optic nerve aplasia associated with rudimental retinal vasculature

Optic nerve aplasia (ONA) is a rare congenital malformation characterized by absence of optic disk, optic nerve, retinal ganglion cells, and central retina vessels. It is frequently associated with other ocular and central nervous system anomalies. In this paper, we describe a case of ONA associated with microphthalmos and a rudimental retinal vasculature in an otherwise healthy infant.

Optic nerve aplasia: A case report and literature review

To report a case of unilateral optic nerve aplasia with unusual presentation and to review the literature. Clinical and histopathological features of a 36-week-old gestation male infant were described with review of all cases of optic nerve aplasia in the literature. The unusual findings in this case are the systemic congenital anomalies. Twenty-nine out of forty-two cases reported in the literature are true cases of optic nerve aplasia; the others probably represent optic nerve hypoplasia. Out of four cases reported as bilateral, only one case could possibly represent bilateral optic nerve aplasia. Optic nerve aplasia is very rare anomaly. It is overdiagnosed entity in the literature. Bilateral cases are exceedingly rare.

Distinctive histopathologic features of canine optic nerve hypoplasia and aplasia: a retrospective review of 13 cases

Canine optic nerve hypoplasia (ONH) and aplasia (ONA) are significant neuro-ophthalmologic disorders that have been reported in several species. The purpose of this study was to describe the distinctive histopathologic features of ONH and ONA in canine patients identified from a collection of 20 000 ocular submissions at the comparative ocular pathology laboratory of Wisconsin from 1989 to 2006. The following information about ONH and ONA cases was collected: signalment, and clinical and gross findings, including unilateral vs. bilateral involvement. Microscopic evaluation was performed, with attention to optic nerve malformation, retinal ganglion cell (RGC) and nerve fiber layer (NFL) loss, and retinal disorganization. The distribution of retinal vasculature was recorded and a search for unusual findings of ONH and ONA was performed. Information and histologic documentation was available for 13 cases. Eight cases of ONH and five cases of ONA were identified. The average group age was 20.2 months and 16.1 months, respectively. The most common breed was the Shih Tzu (3/13). ONH usually presented bilaterally (7/8); all ONA cases presented as a unilateral disease (5/5). The morphologic findings in the optic nerve (ON) in ONH included variable degrees of ON hypoplasia and gliosis, as well as ectopic vestigial ON remnants within orbital nerves and connective tissues. The NFL was detected in the majority of the ONH cases; however, RGCs were rare or absent. Mild retinal disorganization was seen occasionally. Most cases of ONH were associated with regional peripheral retinal blood vessel extension into the vitreous, leaving the peripheral retina avascular. In ONA cases the retinal blood vessels, NFL and RGCs were totally absent and retinal disorganization was severe. Distinctive microscopic features encountered in ONA included anterior segment dysgenesis in some cases. The retina in these cases was stretched across the posterior lens capsule, never making contact with the posterior pole of the globe. The current study reviews the human and veterinary literature pertaining to ONH and ONA, compares ONH and ONA in dogs, and presents related ophthalmic histopathologic findings that have not been reported previously.

Genetic diseases of the optic nerve head: from embryogenesis to pathogenesis

Retinal ganglion cells converge to leave the eye through the optic nerve head (ONH). Numerous developmental steps contribute to its complex architecture and, as a corollary, many diseases affect both ONH structure and function. Patients with cavitary disc anomalies have been found to have mutations in PAX6 and PAX2, and although PAX6 mutations have also been associated with optic nerve aplasia and hypoplasia, these specific diseases can also be caused by mutations in other genes, such as SOX2 and OTX2. The genetic mechanisms for a range of diseases causing retinal ganglion cell loss, such as glaucoma or optic atrophy, have also been investigated and although substantial insight into the molecular underpinnings for a proportion of ONH diseases has been reached, much remains to be uncovered.

Retinal Dysplasia Mimicking Intraocular Tumor: MR Imaging Findings with Histopathologic Correlation

We report a 6-month-old boy who presented with unilateral leukocoria, retinal detachment, and a retrolental mass in a microphthalmic eye based on retinal dysplasia with concurrent optic nerve aplasia. Dysplastic retinal tissue, a rare congenital defect, may create a clinical and radiologic picture of an intraocular mass closely resembling tumor tissue. MR imaging findings with histopathologic correlation are presented to facilitate discrimination of the more common causes of leukocoria.

Proper patterning of the optic fissure requires the sequential activity of BMP7 and SHH

The optic disc develops at the interface between optic stalk and retina, and enables both the exit of visual fibres and the entrance of mesenchymal cells that will form the hyaloid artery. In spite of the importance of the optic disc for eye function, little is known about the mechanisms that control its development. Here, we show that in mouse embryos, retinal fissure precursors can be recognised by the expression of netrin 1 and the overlapping distribution of both optic stalk (Pax2, Vax1) and ventral neural retina markers (Vax2, Raldh3). We also show that in the absence of Bmp7, fissure formation is not initiated. This absence is associated with a reduced cell proliferation and apoptosis in the proximoventral quadrant of the optic cup, lack of the hyaloid artery, optic nerve aplasia, and intra-retinal misrouting of RGC axons. BMP7 addition to organotypic cultures of optic vesicles from Bmp7-/- embryos rescues Pax2 expression in the ventral region, while follistatin, a BMP7 antagonist, prevents it in early, but not in late, optic vesicle cultures from wild-type embryos. The presence of Pax2-positive cells in late optic cup is instead abolished by interfering with Shh signalling. Furthermore, SHH addition re-establishes Pax2 expression in late optic cups derived from ocular retardation (or) embryos, where optic disc development is impaired owing to the near absence of SHH-producing RGC. Collectively, these data indicate that BMP7 is required for retinal fissure formation and that its activity is needed, before SHH signalling, for the generation of PAX2-positive cells at the optic disc.