Cavitación coroidea asociada a coloboma macular. Estudio multimodal. Imagen en face / Choroid cavitation associated with macular coloboma. Multimodal study. Image en face

La cavitación intracoroidea es un hallazgo identificado con OCT descrito inicialmente en pacientes miopes, pero también aparece en pacientes no miopes. Puede presentarse tanto en el área peripapilar como en el polo posterior. El coloboma macular es un defecto del desarrollo embrionario del polo posterior, y en la OCT estructural es imprescindible la ausencia del epitelio pigmentario de la retina y de los vasos coroideos para su diagnóstico. Este caso presenta la cavitación intracoroidea circunscribiendo el coloboma macular, en ausencia de membrana intercalar. La imagen en face permite valorar la relación entre ambas estructuras, así como la magnitud de las mismas. (AU)

Intrachoroidal cavitation is a finding identified with OCT initially described in myopic patients, it also appears in non-myopic patients. It can occur in both the peripapillary area and the posterior pole. Macular coloboma is a defect of embryonic development of the posterior pole, in structural OCT the absence of the retinal pigment epithelium and choroidal vessels is essential. In this case, intrachoroidal cavitation circumscribes the macular coloboma, in the absence of an intercalary membrane. The face image allows us to assess the relationship between the two structures as well as their magnitude. (AU)

PRPS1-associated retinopathy: a diagnostic odyssey.

PURPOSE: This study describes how the diagnosis of Usher syndrome was revised to PRPS1-associated retinopathy and Charcot-Marie-Tooth disease type 5. CASE REPORT: A 38-year-old female with bilaterally subnormal vision and non-congenital hearing loss was initially diagnosed with Usher syndrome, based on finding variants in three genes (MYO7A, USH2A, and PCDH15), was re-evaluated at the inherited retinal disorders clinic. She had asymmetric retinopathy and right macular pseudocoloboma. She was also found to have myopathic facies, poor grip strength and atrophy of the calf muscles. Whole exome sequencing including variants in PRPS1 showed a variant (NM_002764.4:c.287 G > A; p.Arg96Gln), which was not detected by targeted Sanger sequencing of the DNA from her mother and sister. CONCLUSION: The constellation of asymmetric retinopathy and non-congenital hearing impairment should prompt the clinician to search for other diagnoses that may not be covered by an Usher syndrome next generation sequencing panel. Interpretation of genetic testing results should be correlated with a detailed clinical phenotype.

Choroid cavitation associated with macular coloboma. Multimodal study. Image en face.

Intrachoroidal cavitation is a finding identified with OCT initially described in myopic patients, it also appears in non-myopic patients. It can occur in both the peripapillary area and the posterior pole. Macular coloboma is a defect of embryonic development of the posterior pole, in structural OCT the absence of the retinal pigment epithelium and choroidal vessels is essential. In this case, intrachoroidal cavitation circumscribes the macular coloboma, in the absence of an intercalary membrane. The en face image allows us to assess the relationship between the two structures as well as their magnitude.

Novel Compound Heterozygous Variations in MPDZ Gene Caused Isolated Bilateral Macular Coloboma in a Chinese Family.

Macular coloboma (MC) is a rare congenital retinochoroidal defect characterized by lesions of different sizes in the macular region. The pathological mechanism underlying congenital MC is unknown. Novel compound heterozygous variations, c.4301delA (p.Asp1434fs*3) and c.5255C>G (p.Ser1752Ter), in the multiple PDZ domain (MPDZ) proteins were identified via whole-exome analysis on the proband with isolated bilateral macular coloboma in a Chinese family. Segregation analysis revealed that each of the unaffected parents was heterozygous for one of the two variants. The results of the in silico and bioinformatics analysis were aligned with the experimental data. The knockdown of MPDZ in zebrafish caused a decrease in the ellipsoid zone, a destruction of the outer limiting membrane, and the subsequent RPE degeneration. Overall, the loss of MPDZ in zebrafish contributed to retinal development failure. These results indicate that MPDZ plays an essential role in the occurrence and maintenance of the macula, and the novel compound heterozygous variations were responsible for an autosomal recessive macular deficiency in this Chinese family.

Intercalary membrane break and detachment causes intrachoroidal cavitation in macular coloboma.

PURPOSE: To describe the clinical and imaging features in a series of patients diagnosed with macular coloboma (MC) and intrachoroidal cavitation (ICC). METHODS: Patients diagnosed with MC based on clinical examination between June 2017 and July 2021 were retrieved from the electronic medical record system and were included in the study. Colour fundus photographs, optical coherence tomography (OCT) and Multicolour® imaging scans of these patients were analysed. RESULTS: We identified 16 eyes of 11 patients with MC on fundus examination. Based on OCT imaging features, conforming variant of MC was seen in 9 (56%) eyes and non-conforming variant in 7 (44%) eyes. No eyes with MC in the study showed features of both conforming and non-conforming varieties simultaneously. In the non-conforming variety of MC with presence of intercalary membrane break, ICC was identified in 5 (71%) of these eyes. ICC in MC appeared as flat, dark greenish areas with or without an orange-coloured boundary abutting the margin of the coloboma on Multicolour® imaging. CONCLUSION: In 31% eyes, ICC was seen in non-conforming type of MC and was well-identified on Multicolour® imaging. It appears that presence of intercalary membrane break and detachment are prerequisites for developing ICC.

Optical Coherence Tomographic Finding in a Case of Congenital Macular Coloboma at King Abdulaziz University Hospital, Jeddah.

Macular coloboma is a rare eye condition that affects around 0.5-0.7/10,000 of live births. Macular coloboma appears as a well-demarcated atrophic lesions that could affect one eye or both eyes on fundus examination. This is a case of a 33-year-old male patient who presented to the outpatient clinic with a history of poor vision in the left eye since childhood. He had a history of strabismus surgery for sensory exotropia (XT) in the left eye. Anterior segment examination of both eyes was normal while the fundus examination of both eyes revealed bilateral chorioretinal lesions in the macula which was larger in the left eye (OS) than the right eye (OD), representing bilateral chorioretinal coloboma. Congenital coloboma is a rare eye condition that leads to non-progressive decrease in visual acuity. Optical coherence tomography (OCT) is the modality of choice in diagnosing and describing macular coloboma.

New Insights on the Genetic Basis Underlying SHILCA Syndrome: Characterization of the NMNAT1 Pathological Alterations Due to Compound Heterozygous Mutations and Identification of a Novel Alternative Isoform.

This study aims to genetically characterize a two-year-old patient suffering from multiple systemic abnormalities, including skeletal, nervous and developmental involvements and Leber congenital amaurosis (LCA). Genetic screening by next-generation sequencing identified two heterozygous pathogenic variants in nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) as the molecular cause of the disease: c.439+5G>T and c.299+526_*968dup.This splice variant has never been reported to date, whereas pathogenic duplication has recently been associated with cases displaying an autosomal recessive disorder that includes a severe form of spondylo-epiphyseal dysplasia, sensorineural hearing loss, intellectual disability and LCA (SHILCA), as well as some brain anomalies. Our patient presented clinical manifestations which correlated strongly with this reported syndrome. To further study the possible transcriptional alterations resulting from these mutations, mRNA expression assays were performed in the patient and her father. The obtained results detected aberrant alternative transcripts and unbalanced levels of expression, consistent with severe systemic involvement. Moreover, these analyses also detected a novel NMNAT1 isoform, which is variably expressed in healthy human tissues. Altogether, these findings represent new evidence of the correlation of NMNAT1 and SHILCA syndrome, and provide additional insights into the healthy and pathogenic expression of this gene.

A Systematic Review of the Clinical Manifestations and Diagnostic Methods for Macular Coloboma.

Objectives: To present the clinical features of and diagnostic methods used for macular coloboma (MC), and to analyze the factors associated with best-corrected visual acuity (BCVA) in patients with MC.Methods: A systematic review using the MEDLINE (PubMed), EMBASE, LILACS, and Cochrane databases was performed. The factors associated with BCVA were analyzed.Results: A total of 21 patients (mean age at diagnosis, 18.1 ± 14.6 years) with 36 eyes affected by MC (5 unilateral, 16 bilateral) were included in the study. All 21 patients (100%) had undergone a good-quality fundus examination. The size of the MC lesions ranged from 1.0 × 1.2 to 4.0 × 4.0 disc diameters (DD). Twenty-seven (73%) eyes had pigmented MC, seven (19%) had non-pigmented MC, and one (3%) had an unspecific type. The diagnosis was confirmed using spectral-domain optical coherence tomography (SD-OCT) in 16 (43.2%) eyes. A positive correlation was found between BCVA and the type of MC (ß = 0.876, p = .006) and abnormal eye movement (ß = 0.087, p = .018), and a negative correlation was found between BCVA and a contributory medical history of ventricular septal defect (ß = -0.327, p = .001).Conclusions: Pigmented MC was the most common type and had the highest possibility of causing impaired vision in the affected eyes. Additionally, joint examinations should be applied for diagnostic confirmation of MC. Furthermore, fundoscopy, electroretinogram, electrooculography, fundus fluorescein angiography, and SD-OCT are all critical for differential diagnosis of MC-like lesions.

Three cases of molecularly confirmed Knobloch syndrome.

Background: Knobloch syndrome (OMIM 267750) is a rare autosomal recessive disorder due to genetic defects in the COL18A1 gene. The triad of high myopia, occipital defect, vitreoretinal degeneration has been described as pathognomonic for this condition. Patients with Knobloch syndrome have also extraocular problems as brain and kidney malformations. High genetic and phenotypic variation has been reported in the affected patients.Materials and Methods: Here we provide detailed clinical description of 3 individuals with Knobloch syndrome. Ocular examination and fundus imaging have been performed. Detailed information about systemic conditions has been provided.Results: Mutations in COL18A1 were identified in all three patients. Patient 1 had congenital hip dislocation and patient 2 had renal atrophy, cardiac insufficiency and difficult skin healing.Conclusions: With this report we add to the clinical and genetic knowledge of this rare condition.

Familial non-syndromic macular pseudocoloboma secondary to homozygous CLDN19 mutation.

PURPOSE: The purpose of this study is to uncover the genetic cause for non-syndromic macular "coloboma" (pseudocoloboma) in three brothers from a consanguineous family. METHODS: Homozygosity mapping for the three affected brothers and whole-exome sequencing in one affected brother, followed by confirmatory Sanger sequencing and segregation analysis of the candidate gene for all immediate family members; molecular modeling of the candidate mutation; and review of clinical, imaging, and laboratory findings. RESULTS: Three otherwise-healthy brothers (age 10, 10, and 6 years) had macular pseudocoloboma. Both parents and the fourth brother were not affected. Parents were first cousins. A novel homozygous missense variant in claudin 19 (CLND19: NM_148960.2:c. 263T>A; p.Val88Glu) segregated with the phenotype, and molecular modeling predicts an unfavorable effect to protein function. All prior reported biallelic CLND19 mutations cause symptomatic hypomagnesemia with hypercalciuria and nephrocalcinosis, often with concurrent macular pseudocoloboma. However, general physical assessment, metabolic profile, and renal imaging for the three affected brothers were normal. CONCLUSIONS: A homozygous CLDN19 mutation can cause macular pseudocoloboma without evidence for systemic disease in children. This is the first reported family with CLDN19 mutations to have an ocular phenotype only; however, those identified to harbor biallelic CLDN19 mutations should be considered at risk for the extraocular manifestations that have previously been associated with mutations in the gene.

Ocular abnormalities in congenital Zika syndrome: a case report, and review of the literature.

BACKGROUND: As the number of children with Zika virus-related complications grows, the long-term developmental trajectory and its effects on families are unknown. We present the first known case of congenital Zika syndrome seen at our institution with significant fundus findings. CASE PRESENTATION: A 3-day-old Hispanic baby girl presented with severe microcephaly of 24 cm and temperature instability at birth. Her mother had traveled to Honduras early in pregnancy and testing of amniotic fluid was positive for Zika virus via polymerase chain reaction. A dilated fundus examination was significant for bilateral severe colobomatous chorioretinal atrophy of the macula and pigmentary changes. Neonatal magnetic resonance imaging revealed diffuse lissencephaly with decreased brain volume, atrophic corpus callosum and brainstem, periventricular calcifications, and ventriculomegaly of the lateral ventricles. CONCLUSIONS: Our patient, who presented with the first known case of congenital Zika syndrome in Northern Florida, demonstrated profound bilateral colobomatous chorioretinal atrophy of the macula. The ophthalmologic findings along with severe microcephaly emphasize the neurotropism of the Zika virus, and ultimately are indicative of poor developmental and visual prognosis for affected infants. With the increased prevalence of Zika virus, ophthalmologists should be aware of the associated findings and the importance of an eye-screening examination with a dilated fundus examination within 1 month of life of infants in which congenital Zika syndrome is suspected. A multidisciplinary care approach is essential for the care of affected infants and their families.

[Unilateral macular coloboma: about a case]. / Colobome maculaire unilatérale: à propos d'un cas.

Macular coloboma is a congenital condition characterized by failure of closure of the fetal intraocular fissure which may have a hereditary origin. Clinically, it is characterized by decreased visual acuity with macular excavated lesion characterized by missing or rudimentary retinal tissue and scleral ectasia. Macular OCT strongly supports the diagnosis and electrophysiology examination, if requested, is altered. Differential diagnosis includes pathologies causing atrophic and excavated macular lesion, in particular congenital toxoplasmosis.

Achondroplasia and Macular Coloboma.

Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia.

Optical Coherence Tomographic Finding in a Case of Macular Coloboma

PURPOSE: To report the optical coherence tomography (OCT) findings in a patient with unilateral macular coloboma. METHODS: A 12-year-old male was presented with macular coloboma in the left eye. The optical coherence tomography was performed with fluorescein angiography (FA). RESULTS: The OCT revealed the crater-like depression in the macula, demonstrating atrophic neurosensory retina, and an absence of retinal pigment epithelium and choroid in the lesion. FA showed hypofluorescence corresponding to the size of the lesion in both early and late frames without leakage of dye at any stage. CONCLUSIONS: The OCT can be beneficial to confirm the diagnosis of macular coloboma.

Two cases of congenital macular coloboma

Macular coloboma is a rare atypical form of choroidal coloboma which develop secondary to intrauterine infection or developmental abnormality of the eye. These are usually oval or round with well defined margin sized from less than 1 disc diameter to 10 disc diameters. The macular coloboma was classified into pigmented type, non-pigmented type, and type associated with presence of abnormal vessels. We experienced two cases of macular coloboma, without any family history or other associated physical abnormalities. The first case showed pigmented type in the right eye and intermediated type between pigmented and non-pigmented type in the left eye and the second case showed macular coloboma with abnormal vessels.