Atypical Coloboma Research Articles

Isolated Unilateral Temporal Coloboma of the Lens

Lens coloboma is a rare congenital anomaly that occurs due to failure of the foetal fissure to close completely causing an incomplete formation of the lens, so usually inferonasal. Temporal lens coloboma is extremely rare; reported cases were associated with ocular or systemic anomalies. We report a rare case of unilateral atypical temporal lens coloboma without any iris abnormality and posterior segment coloboma or any other ocular or systemic anomaly.
 An 18-year-old female presented with a gradually progressive painless diminution of vision in her left eye for two years. There was no history of trauma, and family history was non-contributory. The systemic examination was normal. Ocular examination revealed a vision of 6/6 in the right eye and 6/60 in the left eye improving to 6/24 with pinhole and unilateral atypical temporal coloboma of the crystalline lens in the left eye after dilatation. The rest of the anterior segment and fundus examination was normal. No abnormality was detected in the right eye. The best corrected visual acuity of 6/6 OD and 6/9 OS was achieved with spectacle correction at 6 months of follow-up. This case is a rare presentation of unilateral atypical coloboma located temporally without any iris abnormality and posterior segment coloboma or any other ocular or systemic anomaly. Early correction of refractive error and astigmatism results in good prognosis.

Aniridia cohort data from the Schwiete center

In congenital aniridia, there is malformation of almost all eye segments. In addition, endocrinologic, metabolic and central nervous systems diseases may be present. The most common ophthalmic signs in congenital aniridia are AAK, iris malformation, cataract and macular hypoplasia. Between 556 eyes of 286 subjects (20.1 ± 20.1 years; 45.5% males), there was nystagmus in 518 (93.7%) eyes, strabismus in 327 (58.8%) eyes. There was iris malformation with atypical coloboma in 34 eyes (6.1%), more than 6 clock hours of iris remnants in 61 eyes (10.9%), less than 6 clock hours of iris remnants in 96 eyes (17.2%), and complete aniridia in 320 (57.5%) eyes. The patients were graded according to the following aniridia‐associated keratopathy (AAK) stages: Stage 0 (96 eyes (17.2%), no keratopathy), Stage 1 (178 eyes (32.0%)), Stage 2 (107 eyes (19.2%)), Stage 3 (67 eyes (12.0%)), Stage 4 (62 eyes (11.1%)), Stage 5 (45 eyes (8.0%)). There was clear lens in 127 (22.8%), cataract in 224 (40.2%), subluxated lens in 9 (1.6%), pseudophakia in 129 (23.2%), aphakia in 32 (5.7%) eyes. There was secondary glaucoma in 307 (55.5%), macular hypoplasia in 395 (71.4%) and congenital optic nerve head pathology in 223 (40.3%) eyes. The iris malformation type may indicate future expression of AAK, cataract and glaucoma development and it is correlated with congenital optic nerve head and macular pathology. Our registry will support further detailed longitudinal analysis of ophthalmic and systemic diseases of aniridia subjects during long‐term follow‐up.

A Cross-sectional Analysis of 556 Eyes Entering the Homburg Aniridia Centre.

Congenital aniridia is a severe malformation of almost all eye segments. In addition, endocrinological, metabolic, and central nervous systems diseases may be present. In order to develop better treatment options for this rare disease, an aniridia center must be established. The purpose of this work is to summarize ophthalmic findings of aniridia subjects examined at the Department of Ophthalmology, Saarland University Medical Center in Homburg. Our retrospective single-center study included patients who underwent a comprehensive ophthalmic examination through the head of the KiOLoN ("Kinderophthalmologie", Orthoptics, Low Vision and Neuroophthalmology) Unit of the department between June 2003 and January 2022. Data at the first examination time point have been included. Of 286 subjects, 556 eyes of (20.1 ± 20.1 years; 45.5% males) were included. There was nystagmus in 518 (93.7%) eyes, and strabismus in 327 (58.8%) eyes. There were 436 (78.4%) eyes with age-appropriate axial length, 104 (18.7%) eyes with microphthalmos, and 13 (2.3%) eyes with buphthalmos. There was iris malformation with atypical coloboma in 34 eyes (6.1%), more than 6 clock hours of iris remnants in 61 eyes (10.9%), less than 6 clock hours of iris remnants in 96 eyes (17.2%), and complete aniridia in 320 (57.5%) eyes. The patients were graded according to the following aniridia-associated keratopathy (AAK) stages: Stage 0 (96 eyes [17.2%], no keratopathy), Stage 1 (178 eyes [32.0%]), Stage 2 (107 eyes [19.2%]), Stage 3 (67 eyes [12.0%]), Stage 4 (62 eyes [11.1%]), Stage 5 (45 eyes [8.0%]). There was secondary glaucoma in 307 (55.5%), macular hypoplasia in 395 (71.4%), and congenital optic nerve head pathology in 223 (40.3%) eyes. The iris malformation type was significantly positively correlated with AAK stage, lens properties, presence of glaucoma, congenital macular, and optic nerve head properties (p < 0.001 for all), while complete aniridia showed the most complications. At the Homburg Aniridia Center, the most common ophthalmic signs in congenital aniridia were AAK, iris malformation, cataract, and macular hypoplasia. The iris malformation type may indicate future expression of AAK, cataract, and glaucoma development and it is correlated with a congenital optic nerve head and macular pathology. Our registry will support further detailed longitudinal analysis of ophthalmic and systemic diseases of aniridia subjects during long-term follow-up.

Novel insights into chorioretinal and juxtapapillary colobomas by optical coherence tomography.

The purpose was to describe the in vivo microanatomy of typical and atypical chorioretinal and juxtapapillary colobomas in the dog. Three cross-breed dogs were found to be affected with colobomas. Two of the cases were NEHJ1homozygous and Collie Eye Anomaly (CEA) affected and had the typical optic nerve head colobomas seen with the disease. The third case had an unexpected atypical coloboma. In vivo retinal photography and non-invasive retinal imaging by confocal scanning laser ophthalmoscope (cSLO) and optical coherence tomography (OCT) were done, and the eye affected with the atypical coloboma was collected and processed for histopathological evaluation. The majority of the defining features within the CEA defects were similar, with the extent of change to the choroid being of note. Similar to the first two cases, the atypical coloboma demonstrated absent normal retina, RPE, and choroid within the coloboma. Prominent intercalary membranes and vitreal strands attached to the depth of the coloboma were also apparent in all affected eyes. However, unlike the CEA-associated colobomas, the atypical coloboma possessed normal choroid surrounding the lesion and the depth of the lesion was apparent throughout. Advanced retinal imaging enables the appreciation of microanatomical changes that occur in the living eye. The ability of OCT to enhance visualization of abnormal retinal structures and detect subtle neurosensory retinal defects has allowed for the in vivo characterization of features observed in typical and atypical colobomas, as well as the appreciation of some of the resulting structural changes not visible by ophthalmoscopy alone.

Pseudoduplication of the optic disc initially resembling a bifurcated optic nerve in a strabismus child: a case report

BackgroundPseudoduplication of the optic disc is a rare clinical condition that is characterized by a circumscribed, disc-like lesion with radiating vessels but only one normal optic nerve. We report a rare case that initially resembled a bifurcated optic nerve in a strabismus child.Case presentationA 6-year-old female child was initially referred to our hospital due to perceptual exotropia of 15 degrees with poor fixation of the left eye. The visual acuity of the left eye was 3/100 with a refraction of + 1.75/− 1.25 × 175. Fundus images of her left eye revealed a circumscribed and disc-like lesion located one disc diameter (DD) below the true optic disc that showed profound central cupping resembling a second optic disc with a vascular supply. B scan ultrasonography showed an optic nerve with a bifurcated weak-echo region, suggesting that two strands originated from the optic nerve. Optic coherence tomography (OCT) demonstrated a large crater-like depression of the lesion, indicating a colobomatous defect covered by a mysterious membranous structure, a disturbed nerve fibre layer and the absence of regular outer retinal layers. A perimetric examination revealed a relatively superior defect. Magnetic resonance imaging (MRI) revealed the left eye globe showed an abnormal morphology and that the optic nerve was abnormally shaped and shifted nasally in the left eye. Fundus fluorescein angiography (FFA) of the left eye revealed the absence of independent vascular vessels in the disc-like lesion. Hyperfluorescence with patchy fluorescence was evident in the inferotemporal area of the disc. Vascular loops surrounding the temporal region were evident in both eyes. Her right eye was normal except for the vascular loop. We proposed that this represented a case of pseudoduplication of the optic disc. The patient did not undergo any treatment, and her visual acuity remained stable during the follow-up period.ConclusionsOur patient presented with a deep and ectatic coloboma below the optic disc that communicated with the true optic nerve and was originally thought to indicate a bifurcated optic nerve. This case suggests that atypical ectatic colobomas should be considered before diagnosing malformations related to the optic nerve in double optic disc cases.

Progressive optic nerve changes in cavitary optic disc anomaly: integration of copy number alteration and cis-expression quantitative trait loci to assess disease etiology

BackgroundWe performed clinical and genetic characterization of a family with cavitary optic disc anomaly (CODA), an autosomal dominant condition that causes vision loss due to adult-onset maculopathy in the majority of cases. CODA is characterized by a variably excavated optic nerve appearance such as morning glory, optic pit, atypical coloboma, and severe optic nerve cupping.MethodsFour affected and fourteen unaffected family members of a multi-generation pedigree were phenotyped by visual acuity, intraocular pressure, dilated fundus examination, fundus photography, and optical coherence tomography. Genetic analysis was performed by breakpoint polymerase chain reaction (PCR), long range PCR, and direct Sanger sequencing. The functional relevance of the copy number alteration region was assessed by in silico analysis.ResultsWe found progressive optic nerve cupping in three affected members of a family with CODA. In one individual, an optic pit developed over time from a normal optic nerve. By two independent methods, we detected a previously described intergenic triplication that segregated with disease in all adults of the family. The copy number alteration was also detected in five children with normal optic nerves. eQTL analysis demonstrated that this CNA region regulates expression of up to 4 genes in cis.ConclusionsMorning glory, optic pit and atypical coloboma are currently considered congenital anomalies of the optic nerve, but our data indicate that in CODA, the excavated optic nerve appearance may develop after birth and into adulthood. In silico analysis of the CNA, may explain why vairable expressivity is observed in CODA.

Pathogenesis and Treatment of Maculopathy Associated With Cavitary Optic Disc Anomalies

To propose a unifying theory regarding the pathogenesis of maculopathy associated with cavitary optic disc anomalies and to describe a rational approach to achieving a permanent cure in affected eyes. Interpretive essay. Review and synthesis of selected literature, with interpretation and perspective in relating pathoanatomic features to pathogenesis and treatment. Congenital cavitary anomalies of the optic disc, including typical coloboma, optic pit (and other atypical colobomas), morning glory anomaly, and extrapapillary cavitation, are associated with an enigmatic maculopathy characterized by schisis-like thickening and serous detachment. The unifying anatomic theme of these anomalies is the presence of a scleral (or lamina cribrosa) defect permitting anomalous communications between intraocular and extraocular spaces. These communications enable the critical pathogenic mechanism responsible for the maculopathy, namely, dynamic fluctuations in the gradient between intraocular and intracranial pressures that direct the movement of fluid (vitreous humor or cerebrospinal fluid) into and under the retina. Vitreous traction does not seem to play a significant pathogenic role. Permanent cure of the maculopathy requires either elimination of the translaminar pressure gradient or closure of the pathway for fluid flow into the retina. We advocate carefully titrated juxtapapillary laser photocoagulation followed by vitrectomy with gas tamponade for creation of a permanent intraretinal and subretinal fluid barrier. The peculiar features of cavitary optic disc maculopathy can be explained only by considering the pressure gradients that develop along anomalous communications between intraocular and extraocular spaces. A permanent cure for this condition can be achieved by closing the pathway for fluid migration from the cavitary lesion into and under the retina.

Peripapillary Schisis with Serous Detachment in Advanced Glaucoma

To describe features associated with the development and resolution of peripapillary retinoschisis with an underlying serous detachment in a patient with primary open angle glaucoma. This presentation occurred in the absence of an observed optic nerve coloboma, congenital, or acquired optic nerve head pit. A patient with advanced glaucomatous optic nerve cupping developed a temporally localized peripapillary serous detachment in the right eye which spontaneously resolved. Optical coherence tomography demonstrated an area of retinoschisis with underlying serous detachment contiguous with the temporal disc margin. Although fluorescein angiography was not performed and the presence of a peripapillary subretinal neovascular membrane could not be ruled out, an atypical coloboma, optic nerve head pit, or peripapillary subretinal neovascular membrane was not observed during biomicroscopy or scanning laser ophthalmoscopy. The retinoschisis and detachment resolved without intervention. Peripapillary retinoschisis with an underlying serous detachment may develop in subjects with advanced glaucoma. Although the occurrence of the findings in this case may be unrelated to glaucomatous optic neuropathy, the likelihood that a pathogenic mechanism linked to advanced glaucoma may be responsible for the development of peripapillary schisis and serous detachment should alternatively be taken into consideration. This case documents its spontaneous resolution without intervention.

Torpedo Maculopathy: In-Vivo Histology Using Optical Coherence Tomography

Recent reports of torpedo maculopathy have disclosed underlying irregularities within the chorioretinal tissue that have not been shown to induce disturbances in visual function. Optical coherence tomography (OCT) provides a unique means of assessing the chorioretinal organization and integrity of torpedo lesions in an in vivo setting that has yet to be explored. In agreement with reported cases, torpedo maculopathy appears to be a benign, non-progressive condition that subtends the horizontal raphe in the juxtafoveal region and imparts no disturbance in visual function. Three cases of torpedo maculopathy were examined using Stratus OCT3 imaging (Carl Zeiss Meditec, Dublin, CA). OCT scans revealed intact, attenuated retinal layers with hyper-reflectivity of the retinal pigmented epithelium (RPE). The RPE subtending these lesions appears of normal thickness, yet, there is an abrupt transition between intact-organized and intact-disorganized retinal tissue in scans transitioning from normal retina to torpedo lesions. Our imaging studies revealed significant attenuation and disorganization of the inner and outer retinal layers overlying a hyper-reflective RPE, which was of normal thickness and devoid of any structural defects. An analysis of the OCT images collected suggests anomalies in retinal architecture. This finding implies that these lesions may represent atypical colobomas whereby retinal tissues are present but, perhaps, not fully developed. In light of these imaging studies, we propose that this uncommon condition may arise from deficits in cellular migration and/or organization.

Superior Lens Coloboma with Superior Rectus Palsy and Congenital Ptosis

A lens coloboma is characterized by the lens tissue's notching at the equator. It is usually inferior-nasal else it is called an atypical coloboma. We report a young male who presented with a superior lens coloboma, an elevation deficit and moderate ptosis, left eye. As superior rectus and levator muscles are derived from the neural crest cell we propose, genetically, there may be an association between the lens coloboma and the superior rectus/levator muscle underaction via an anomalous homeobox gene function.

Ophthalmic examination findings of Thoroughbred racehorses in Australia

To record the prevalence and document the types of eye disease in population of Thoroughbred racehorses in Victoria, Australia. Prospective study. Two hundred four Thoroughbred racehorses. All horses and both eyes were examined at four metropolitan and two country racing stable complexes. Ophthalmic exam was performed following dark adaptation with a transilluminator, biomicroscope, and direct ophthalmoscope. Intraocular pressures were measured when indicated. Both pupils were dilated with tropicamide when indicated. One hundred eighty-two (89.2%) flat-racing and 22 (10.8%) jump-racing (hurdle or steeple) horses were examined. Age range: 2-9 years (mean 3.7 years, median 3); 97 (47.5%) male-neuter, 74 (36. 3%) female, 33 (16.2%) male. Potential vision-threatening eye disease was present in 15 (7.4%) different horses: complete lenticular cataracts 3, posterior lens luxation and cataract 1, large peripapillary 'butterfly' inactive lesions 3, large peripapillary 'butterfly' active lesions 2, peripapillary focal inactive 'bullet hole' chorioretinal lesions (> 20) 5, optic nerve atrophy 1. Non-vision threatening eye disease was present in 117 (57.4%) different horses, involving one or more ocular structures: lower eyelid scars 3; periocular fibropapillomatous disease 1; third eyelid squamous cell carcinoma 1; corneal scars 6; corneal band opacity 2; anterior iris synechia 1; developmental cataracts 36 (17.2%); peripapillary focal inactive 'bullet hole' chorioretinal lesions (< 20) 103 (50.0%); linear peripapillary hyperpigmentation bands 16 (7.9%). Unusual variations of normal ocular anatomy and colobomata was recorded in 11 (5.4%) different horses: granular iridica hypoplasia 3, granular iridica hyperplasia 2, multilobular granular iridica cyst 1, microcornea 1, hyaloid remnant 1, rotated optic nerve head 1, coloboma of the lens 1, atypical coloboma of the retina 1. This survey demonstrates that the prevalence of vision-threatening eye disease in racing horses may be greater than previously perceived, and highlights the importance of ocular examination within any routine physical examination of horses.

De novo insG619 mutation in PAX2 gene in a Japanese patient with papillorenal syndrome

To describe a Japanese patient with papillorenal syndrome (PRS) and to identify the genetic defect responsible for the disease. Interventional case report. Complete ophthalmologic and systemic examinations were performed, and direct genomic sequencing of the PAX2 gene. Fundus examination of a 3-year-old Japanese girl showed atypical coloboma bilaterally. At 6 years of age, she presented with proteinuria, and renal ultrasonography showed hypoplastic kidneys bilaterally. Molecular genetic analysis of the PAX2 gene revealed a de novo heterozygous insertion of a G at position 619. Our findings suggest that an abnormal development of the optic stalk led to the optic disk dysplasia in PAX2-associated PRS. This indicates that we should consider renal abnormalities when an atypical round coloboma is present. Molecular genetic analysis of the PAX2 gene in combination with renal ultrasonography can help in making an earlier diagnosis of the disease.

Variable phenotype related to a novel PAX 6 mutation (IVS4+5G>C) in a family presenting congenital nystagmus and foveal hypoplasia

Several ocular defects have been identified as a consequence of the PAX6 gene mutations. With regard to the implication of this gene in unusual phenotypes, we report a family presenting with congenital nystagmus, foveal hypoplasia, and iris hypoplasia or atypical coloboma. Observational case report. The entire transcribed region of the PAX6 gene was submitted to mutation search at the DNA and mRNA levels in five affected members of a French family in test with 82 normal subjects. A novel heterozygous PAX6 gene splice mutation (IVS4 + 5G>C) was identified. The mutation is located in IVS4 within the consensus donor splice site. A mutant mRNA lacking exon 4 as the sole defect was evidenced. The resultant protein was predicted to contain a cryptic ATG initiation codon in exon 3 and a slightly altered paired-domain in an open reading frame extended by 13 amino acids. The association of anterior segment anomalies and foveal hypoplasia with one of the slightest alterations of the PAX6 protein described to date confirms the association of variant phenotypes with hypomorphic alleles. Mutation screening of the PAX6 gene could be useful in elucidating the origin of complex ocular malformations.

Pax6 heterozygous eyes show defects in chamber angle differentiation that are associated with a wide spectrum of other anterior eye segment abnormalities

The development of the chamber angle was studied in the eyes of heterozygous Pax6 lacZ/+ mutant mice (Nature 387 (1997) 406). Mutations in PAX6 cause aniridia, a condition that is frequently associated with glaucoma, a blinding disease that may be associated with chamber angle defects. Mesenchymal cells were seen in the chamber angle at P1–P5. In wild-type mice, these cells differentiated into typical trabecular meshwork (TM) cells next to Schlemm's canal. In Pax6 lacZ/+ mice, TM cells remained undifferentiated and Schlemm's canal was absent. From P1 to P4, staining for β-galactosidase and immunoreactivity for Pax6 were observed in chamber angle mesenchyme, but were absent later. Cultured murine TM cells expressed Pax6. The defects in chamber angle and TM differentiation were associated with a wide spectrum of other anterior eye defects, which included various degrees of iris hypoplasia and corneal haze, isolated iridocorneal adhesions and atypical coloboma, and a vascularized cornea in all adult animals. A third of the animals showed Peters' anomaly including corneal opacity and iridocorneal adhesions. The separation of the lens from the cornea was incomplete, and epithelial layers of lens and cornea were continuous. Pax6 activity is directly required for differentiation of the chamber angle. Variations in phenotype of Pax6 lacZ/+ mice appear not to involve direct dominant-negative or dose-dependent effects.

The equine fundus II: normal anatomical variants and colobomata

A wide range of fundic variants are encountered during routine ophthalmoscopic examination of visually normal horses, often causing the examiner difficulty in assessing their clinical significance. Many of these are anatomical variants having no significant effect on visual function, and lie within the limits of normality in the horse. This paper illustrates this range of variants and discusses their anatomical basis and physiological consequences. Colobomata are non-progressive discontinuities in the structure of the anatomic fundus, occasionally noted as incidental findings during ophthalmoscopy. This paper illustrates typical and atypical colobomata of the equine fundus, the latter occurring outside the embryonic optic fissure. The anatomical basis of these colobomata and their possible consequence on vision is discussed.

Atypical coloboma in the optic disc of a Beagle

An atypical coloboma was found during a routine ophthalmoscopical examination in an experimental Beagle dog and was studied histologically. This condition has only been reported once in Beagles and is the first case in several thousand Beagles which we have examined. Atypical colobomata may be symptomless and are not yet fully explained pathogenically; some of the theories advanced to explain these defects are reported.

The Pathogenesis of Some Atypical Colobomas of the Choroid

The Pathogenesis of Some Atypical Colobomas of the Choroid

Atypical coloboma of choroid with dysplasia of macula; report of a case.

A CASE of atypical coloboma of the choroid with dysplasia of the macula is presented. REPORT OF CASE A white woman aged 24 consulted one of us because of a minor injury to her left eye. The left eye was markedly divergent, with a deviation of approximately 30 degrees, and vision was reduced to perception of hand movements. Vision was increased to counting fingers at 6 feet (1.8 meters) when the eye was adducted. Retinoscopic studies of the left eye revealed the presence of compound hypermetropic astigmatism (+ 0.75 [unk] + 1.00 cyl., axis 165), but no improvement was obtained with lenses. The lids and lacrimal apparatus were normal, and the palpebral fissure was equal to that of the right eye. Gross inspection and slit-lamp studies of the anterior segment revealed no abnormality other than some stellate pigmentation of the anterior capsule of the lens; the vitreous was of normal transparency and structure.

The Genesis of Atypical Ocular Coloboma

After studying careful reconstructions of the optic vesicle of the human embryo, the author concludes that growth is by spurts, or waves of tissue energy, and that atypical colobomata have no relation to the closure of the fetal ocular cleft, but result from loss of this growth energy in the tissue at the site of the coloboma, the adjacent tissue growing forward, and connective tissue, if present, attempting to fill up the defect. The time when this lag in tissue growth occurs in the development of the eye determines whether the gap is shallow or deep, whether it involves the choroid and ciliary body or the iris only. From the Wilmer Ophthalmological Institute and the Carnegie Embryological Institute. Presented before the Association for Research in Ophthalmology, in Cleveland, June 12, 1934.

Anomalous Condition of Ocular Fundus

This case of probably congenital anomaly of the eye was presented at the Colorado Congress on Ophthalmology and Oto-Laryngology, August 4, 1919. It is of interest in connection with a paper of Dr. Gifford on Atypical Coloboma, see page 97.