Couching of cataractous lens in microphthalmic eyes with irido-fundal coloboma: revisiting the historical technique.

PURPOSE: Cataract surgery in microphthalmic eyes is challenging due to anatomical restraints, hard bulky nucleus. This series aims to evaluate the safety and efficacy of couching of intraocular lens in irido-fundal coloboma with microphthalmos. SETTING: Tertiary care centre in South India. DESIGN: Retrospective non-comparative study in eyes with irido-fundal coloboma, corneal diameter < 7 mm and brown cataract. Visual acuity less than 6/60 in other eye. METHODS: Anterior chamber entry made, zonules broken and lens dislocated into the vitreous cavity in a controlled manner. Baseline Clinico-demographic details, corrected distance visual acuity (CDVA), Intra-ocular pressure (IOP), corneal diameter, axial length, lens status and post-surgery CDVA, IOP and complications recorded and followed up for atleast 6 months. RESULTS: Fifteen eyes of 15 subjects were evaluated with a mean age 49.4 ± 10.9 years. At baseline, mean IOP 14.5 ± 3.8 mmHg, mean axial length 19.3 ± 0.5 mm, mean corneal diameter was 6.5 ± 0.34 mm and CDVA 2 logMAR which improved to 1.5 logMAR at 3 months (p value 0.002). Transient spike in IOP in 33.3% subjects was medically managed with no significant difference in IOP (p > 0.05) at baseline (14.5 ± 3.8 mmHg), 3 months post-surgery (16 ± 2.8 mmHg) and 6 months post-surgery (14.9 ± 2.5 mmHg). One patient underwent re-couching. No other major complications were noted. CONCLUSION: Couching of cataractous lens is an effective and safe method in microphthalmic eyes with irido-fundal coloboma as last resort procedure, where no other surgical procedure may work. It provides an ambulatory gain of visual acuity in previously non-ambulatory subjects. Corneal measurements help in determining the subset of patients where couching offers viable option.

MIR204 n.37C>T variant as a cause of chorioretinal dystrophy variably associated with iris coloboma, early-onset cataracts and congenital glaucoma.

Four members of a three-generation Czech family with early-onset chorioretinal dystrophy were shown to be heterozygous carriers of the n.37C>T in MIR204. The identification of this previously reported pathogenic variant confirms the existence of a distinct clinical entity caused by a sequence change in MIR204. Chorioretinal dystrophy was variably associated with iris coloboma, congenital glaucoma, and premature cataracts extending the phenotypic range of the condition. In silico analysis of the n.37C>T variant revealed 713 novel targets. Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants. Haplotype analysis excluded relatedness with the original family reported to harbour the n.37C>T variant in MIR204. Identification of a second independent family confirms the existence of a distinct MIR204-associated clinical entity and suggests that the phenotype may also involve congenital glaucoma.

Insights Regarding Optometric Findings of CHARGE Syndrome in a Pediatric Low Vision Clinic.

SIGNIFICANCE: CHARGE, named for common findings-coloboma, heart defects, atresia of choanae, retardation of growth and development, genital hypoplasia, and ear anomalies-is a frequent etiology of deaf-blindness. A retrospective review in a pediatric low vision clinic presented the opportunity to investigate ocular findings in this syndrome with variable clinical presentations. PURPOSE: This retrospective study reviewed ocular findings and visual function measures from low vision evaluations of patients with CHARGE syndrome, which may influence their multidisciplinary management. METHODS: A retrospective chart review was conducted by three examiners of 60 patients presenting with CHARGE syndrome at a pediatric low vision clinic. Visual acuity and contrast sensitivity were obtained using standard measures. Ocular alignment and cycloplegic refractive error measurements were recorded. Refractive findings were analyzed using vector analysis. Anterior and posterior segment findings were recorded. RESULTS: Patients ranged in age from 1 to 29 years and were followed up for a mean of 4.3 years. Best-corrected visual acuity ranged from no light perception to 20/20 Snellen equivalent. Characteristics of strabismus, occurring in 82% of patients, were reported. Contrast sensitivity was reduced in 52% of patients. Chorioretinal colobomas were reported in 88% of patients. The most common ocular findings included nystagmus (43%), microphthalmia (27%), iris coloboma (27%), and facial nerve palsy (23%). Refractive vector analysis revealed significant myopic progression of the spherical equivalent with age and a tendency for with-the-rule astigmatism and minimal obliquity. CONCLUSIONS: This retrospective review of a relatively large sample size for this rare condition outlined the most common ocular manifestations of CHARGE syndrome. Decreased visual acuity, myopic refractive error, strabismus, and reduced contrast sensitivity were common. Thus, careful optometric evaluation in this population is required, as these findings must be considered in appropriate clinical and habilitative management.

Lunar lenses - Acquired lens colobomas.

Acquired lens colobomas secondary to ocular surgeries are scarcely described in the literature. We describe two cases of acquired lens coloboma in two infants with glaucoma who underwent ocular surgery. The coloboma in the first case was likely because of direct trauma to the lens zonules during an optical iridectomy with a vitrectomy cutter, resulting in localized loss of zonules and consequently localized lens coloboma. The coloboma in the second case was noticed during examination under anesthesia after scleral buckling and cryopexy for retinal detachment. The cause for coloboma development in this case could be disruption of the lens zonules because of stretching of the globe after scleral buckle surgery or because of injury to zonules during scleral buckling and the cryopexy procedure.

Coloboma Accompanying Microphthalmos With Orbital Cyst in a Mother and Child.

Microphtalmos with orbital cyst is a rare congenital abnormality of the eye and orbit that is caused by incomplete closure of the embryonic fissure. The cysts project through in a coloboma of the affected eye. It may be sporadic or genetic. Herein, the authors present a 32-year-old mother with unilateral and her 4-month-old daughter with bilateral microphtalmos and accompanying orbital cyst.

Orbital Cyst with Ependymal Differentiation Associated with Microphthalmia.

BackgroundOrbital cysts associated with microphthalmia are colobomatous lesions that typically present unilaterally and posterior to the globe. Case Report: A male infant had an orbital cyst associated with microphthalmia located anterior to the globe composed of a neuroglial wall, ependymal-like epithelial lining, with synaptophysin-positive cells resembling the retinal neuronal layer. Conclusion: This orbital cyst may represent a malformation of the eye rather than an encephalocele.

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.

Coloboma of the retina, choroid and iris co-existing with cardiac & Skeletal anomalies in a male Nigerian: A case of noonan syndrome.

A 19-year-old male undergraduate presented to the eye clinic with a history of poor vision in the left eye since childhood. The best-corrected visual acuity was 6/6 in the right eye and hand movement in the left eye respectively. Examination of the anterior segment of the right eye was essentially normal, whereas the anterior segment examination of the left eye revealed a small globe, microcornea, and an iris coloboma inferiorly at the 6 o'clock position. Binocular indirect ophthalmoscopy of the right eye revealed a pink disc, normal vessels and macula, lattice degeneration with retinal holes, and a flat retina. The left eye had a pink disc, normal macula and vessels with an inferior arc-shaped excavation with exposure of the sclera, which involved both the disc and macula and was in keeping with a retinochoroidal coloboma. Systemic examination revealed low-set ears with a left atrophic pinna, mild kyphoscoliosis, pectus excavatum, and an atrophic left lower limb with anomalies of the toes and talipes equinovarus. A pan-systolic murmur was present on cardiovascular examination.

Discovery of a novel CHD7 CHARGE syndrome variant by integrated omics analyses.

Chromodomain helicase DNA-binding protein 7 (CHD7) pathogenic variants are identified in more than 90% of infants and children with CHARGE (Coloboma of the iris, retina, and/or optic disk; congenital Heart defects, choanal Atresia, Retardation of growth and development, Genital hypoplasia, and characteristic outer and inner Ear anomalies and deafness) syndrome. Approximately, 10% of cases have no known genetic cause identified. We report a male child with clinical features of CHARGE syndrome and nondiagnostic genetic testing that included chromosomal microarray, CHD7 sequencing and deletion/duplication analysis, SEMA3E sequencing, and trio exome and whole-genome sequencing (WGS). We used a comprehensive clinical assessment, genome-wide methylation analysis (GMA), reanalysis of WGS data, and CHD7 RNA studies to discover a novel variant that causes CHD7 haploinsufficiency. The 7-year-old Hispanic male proband has typical phenotypic features of CHARGE syndrome. GMA revealed a CHD7-associated epigenetic signature. Reanalysis of the WGS data with focused bioinformatic analysis of CHD7 detected a novel, de novo 15 base pair deletion in Intron 4 of CHD7 (c.2239-20_2239-6delGTCTTGGGTTTTTGT [NM_017780.3]). Using proband RNA, we confirmed that this novel deletion causes CHD7 haploinsufficiency by disrupting the canonical 3' splice site and introducing a premature stop codon. Integrated genomic, epigenomic, and transcriptome analyses discovered a novel CHD7 variant that causes CHARGE syndrome.

Heterozygous recurrent HNF4A variant p.Arg85Trp causes Fanconi renotubular syndrome 4 with maturity onset diabetes of the young, an autosomal dominant phenocopy of Fanconi Bickel syndrome with colobomas.

Heterozygous pathogenic variants in HNF4A cause hyperinsulinism, maturity onset diabetes of the young type 1, and more rarely Fanconi renotubular syndrome. Specifically, the recurrent missense pathogenic variant c.253C>T (p.Arg85Trp) has been associated with a syndromic form of hyperinsulinism with additional features of macrosomia, renal tubular nephropathy, hypophosphatemic rickets, and liver involvement. We present an affected mother, who had been previously diagnosed clinically with the autosomal recessive Fanconi Bickel Syndrome, and her affected son. The son's presentation expands the clinical phenotype to include multiple congenital anomalies, including penile chordee with hypospadias and coloboma. This specific pathogenic variant should be considered in the differential diagnosis of Fanconi Bickel Syndrome when genetics are negative or the family history is suggestive of autosomal dominant inheritance. The inclusion of hyperinsulinism and maturity onset of the diabetes of the young changes the management of this syndrome and the recurrence risk is distinct. Additionally, this family also emphasizes the importance of genetic confirmation of clinical diagnoses, especially in adults who grew up in the premolecular era that are now coming to childbearing age. Finally, the expansion of the phenotype to include multiple congenital anomalies suggests that the full spectrum of HNF4A is likely unknown.

CHARGE syndrome without colobomas: Ophthalmic findings.

To report ophthalmic findings of patients without colobomas, and with a clinical and molecular diagnosis of CHARGE Syndrome. Retrospective study of ophthalmic findings in 67 CHARGE patients-clinically confirmed diagnosis with positive CHD7 mutation-seen in the Ophthalmology department of Cincinnati Children's Hospital Medical Center between January 1, 2008 through September 25, 2018. Criteria for inclusion in this study was absence of any form of a coloboma in either eye. In our cohort, all patients had a positive CHD7 mutation, in addition to a clinical diagnosis. 19.4% (13/67) of CHARGE patients did not have a coloboma in either eye. 69.2% (9/13) had strabismus, 76.9% (10/13) had a refractive error that warranted refractive correction, 23.1% (3/13) had amblyopia, 38.5% (5/13) had nasolacrimal duct obstruction, 30.8% (4/13) had dry eye syndrome and exposure keratopathy, 15.4% (2/13) had ptosis, 15.4% (2/13) had blepharitis, 15.4% (2/13) had Cortical Visual Impairment, 7.7% (1/13) of patients had optic nerve drusen, 7.7% (1/13) had Marcus Gunn Jaw Winking, and 7.7% (1/13) with an eyelid nevus. There are numerous ophthalmic findings in individuals with CHARGE Syndrome without colobomas. No study to date has evaluated the ophthalmic findings in CHD7 positive CHARGE patients without colobomas. These findings need to be assessed and treated to ensure optimal vision in the CHARGE patient population. Absence of coloboma does not rule out a diagnosis of CHARGE syndrome, and if there is a clinical suspicion, clinical confirmation then genetic testing would be warranted.

Expanding the phenotypic spectrum consequent upon de novo WDR37 missense variants.

Structural eye disorders are increasingly recognised as having a genetic basis, although current genetic testing is limited in its success. De novo missense variants in WDR37 are a recently described cause of a multisystemic syndromic disorder featuring ocular coloboma. This study characterises the phenotypic spectrum of this disorder and reports 2 de novo heterozygous variants (p.Thr115Ile, p.Ser119Tyr) in three unrelated Caucasian individuals. All had a clinical phenotype consisting of bilateral iris and retinal coloboma, developmental delay and additional, variable multisystem features. The variants fall within a highly conserved region upstream of the WD-repeat domains, within an apparent mutation cluster. Consistent with the literature, intellectual disability, structural eye disorders, epilepsy, congenital heart disease, genitorenal anomalies and dysmorphic facial features were observed. In addition, a broader developmental profile is reported with a more specific musculoskeletal phenotype described in association with the novel variant (p.Thr115Ile). We further expand the phenotypic spectrum of WDR37-related disorders to include those with milder developmental delay and strengthen the association of ocular coloboma and musculoskeletal features. We promote the inclusion of WDR37 on gene panels for intellectual disability, epilepsy and structural eye disorders.

A Syrian patient with Steel syndrome due to compound heterozygous COL27A1 mutations with colobomata of the eye.

The joint occurrence of short stature, congenital dislocation of the hip, carpal coalition, dislocation of the radial head, cavus deformity, scoliosis, and vertebral anomalies was first described in 1993 by Steel et al. (OMIM #615155) in 23 children from Puerto Rico. The condition is caused by a deficient matrix protein, collagen type XXVII alpha 1 chain, due to bi-allelic loss of function mutations in the gene COL27A1. Outside of Puerto Rico, only four families have been described, in three of which the patients also had hearing loss. However, structural eye defects have not yet been reported in conjunction with this rare autosomal recessive syndrome. Here, we describe a 9-year-old girl born to nonconsanguineous Syrian parents with the characteristic features of Steel syndrome, including short stature, massive malalignment of large joints, kyphoscoliosis, hearing loss, and typical facial dysmorphism. However, she was also born with bilateral colobomata of the irides and choroido-retinae with unilateral affection of the macula. Whole exome sequencing identified two pathogenic compound heterozygous variants in COL27A1: c.93del, p.(Phe32Leufs*71) and c.3075del, p.(Lys1026Argfs*33). There was no discernible alternative cause for the colobomata. Our findings might indicate an association of this exceptionally rare disorder caused by COL27A1 mutations with developmental defects of the eye from the anophthalmia/microphthalmia/coloboma spectrum.

Cataract surgery in eyes with congenital ocular coloboma.

PURPOSE: To assess the safety, efficacy, and complication rate of phacoemulsification and intraocular lens (IOL) implantation in patients with congenital uveal coloboma and to evaluate the role of pupilloplasty. METHODS: A retrospective review of 41 eyes (31 patients) with congenital coloboma that underwent phacoemulsification and IOL implantation between September 2012 and September 2018. Preoperative, intraoperative, and postoperative data were collected for analysis. RESULTS: The mean patient age at surgery was 53.9 years (range 15-82). The primary indication for surgery was cataract removal for visual improvement, and lens subluxation was additionally present in two eyes (5%) preoperatively. The mean preoperative corrected distance visual acuity (CDVA) was 0.90 LogMAR. Phacoemulsification surgery was performed in all cases and nine eyes (22%) had pupilloplasty for pupil reconstitution at the time of the procedure. Surgeon grade varied from trainee surgeon under supervision to consultant. Eight patients (19.5%) had posterior capsular rupture (PCR) with or without vitreous loss requiring anterior vitrectomy. Of these, 2 cases (5%) had dropped nuclear fragments requiring subsequent pars plana vitrectomy and lens fragment removal. The mean postoperative CDVA was 0.62 LogMAR (p = 0.0003). CONCLUSION: Patients with iridolenticular choroidal coloboma appear to be more at risk of complications, as were cases performed by non-consultant surgeons. Contrary, patients with phakodonesis, preoperative anterior chamber vitreous, dense cataracts, and cases were iris hooks used had no significant difference at PCR rate. The risk of postoperative glare and pupilloplasty needs to be considered in cases with good visual potential to avoid a possible second procedure.

Ocular coloboma combined with cleft lip and palate: a case report.

BACKGROUND: Ocular coloboma is an excavation of ocular structures that occurs due to abnormal fusion of the embryonic optic fissure. Further, cleft lip/palate (CL/P), a congenital midline abnormality, is caused by a defect in the fusion of the frontonasal, maxillary, and mandibular prominences. No study has reported the association between these two phenotypes in the absence of other systemic abnormalities. We present a case of ocular coloboma along with CL/P and without other neurological abnormalities. CASE PRESENTATION: A 5-year-old Asian boy presented with decreased visual acuity in his right eye. Physical examination revealed no abnormal findings except CL/P, which was surgically corrected at the age of 9 months. Best-corrected visual acuity was 20/60 in the right eye and 20/25 in the left eye. Anterior segment examination revealed iris coloboma in the inferior quadrant of his right eye as well as a large inferonasal optic disc and chorioretinal coloboma in the same eye. He was prescribed glasses based on his cycloplegic refractive errors and part-time occlusion of the left eye was recommended. After 3 months, best-corrected visual acuity improved to 20/30 in the right eye. CONCLUSION: The association of ocular coloboma should be kept in mind when encountering a patient with CL/P without other neurological or systemic abnormalities.

Lacrimal drainage system anomalies in microphthalmia anophthalmia coloboma complex.

Purpose: To study the prevalence and types of lacrimal drainage system (LDS) anomalies inchildren with congenital microphthalmia anophthalmia coloboma (MAC) complex.Methods: This is a prospective, consecutive, non-comparative, case series of LDS anomalies in 31 children presenting with MAC complex. Previously untreated children with MAC complex, enrolled for socket surface and volume expansion during the study period from January 2017 to April 2018 were included.Results: Thirty-one patients with MAC complex were evaluated for LDS anomalies. Incidence of LDS anomalies in children presenting with MAC complex was 68% (42 of 62 lacrimal systems evaluated). Mean age of the patients at the time of examination under anaesthesia was 27 ± 25 (median 15 months, range 3-108 months). Proximal bicanalicular block (BCB) was the commonest LDS anomaly, noted in 15 (48%) cases. In patients with unilateral ocular disease (n = 20), LDS was affected in 14 (70%) patients and in 9 (45%) patients ipsilateral side LDS was affected. In patients with bilateral ocular disease (n = 11), LDS was affected in 7 (64%) patients. Three patients with unilateral anophthalmos (25%) had an ipsilateral upper canalicular block and contralateral nasolacrimal duct obstruction, of which one patient had a single canalicular wall hypoplasia along with CNLDO. No patient had punctal anomalies.Conclusions: LDS anomalies are seen in nearly two-thirds (68%) of children with MAC complex. The lacrimal drainage system anomaly is not limited to the side of the MAC complex. Commonest LDS anomaly is proximal bicanalicular blocks while punctal anomalies are unusual.

OUTCOMES OF VITRECTOMY WITH SILICONE OIL TAMPONADE FOR MANAGEMENT OF RETINAL DETACHMENT IN EYES WITH CHORIORETINAL COLOBOMA.

PURPOSE: To estimate the outcomes of retinal detachment in eyes with chorioretinal coloboma managed by pars plana vitrectomy and silicone oil tamponade. METHODS: A retrospective chart review of 10 eyes (10 patients) who underwent pars plana vitrectomy for retinal detachment with chorioretinal coloboma. RESULTS: The average age at the time of the surgery was 29.8 ± 19.7 years. The mean follow-up period was 28.8 ± 28.4 months. The mean silicone oil tamponade duration was 9.8 ± 3.5 weeks. Of 10 eyes, 4 (40%) had retinal breaks outside the coloboma, 4 (40%) had breaks inside the coloboma, 1 (10%) had breaks inside and outside the coloboma, and in 1 eye (10%); the causative retinal break was not localized. Preoperatively, the mean visual acuity was 20/2,500 (n = 9), and 1 (10%) was recorded as "Not CSM." At the final examination, the mean visual acuity for the patients with measurable visual acuity was 20/200 (P = 0.06), and in the remaining eye was recorded as light perception. The retina was finally reattached in nine eyes (90%). Postoperative complications included cataract in three (30%), persistent elevated intraocular pressure in one (10%), band keratopathy in one (10%), and proliferative vitreoretinopathy in one (10%). CONCLUSION: Complete pars plana vitrectomy with or without lensectomy, laser photocoagulation around the peripheral retina, around all the peripheral breaks and around the colobomatous area, and silicone oil tamponade is effective for retinal detachment in eyes with chorioretinal coloboma. Silicone oil removal as early as possible did not increase the risk of redetachment and seems to reduce the incidence of oil-related complications in such cases.

A hybrid coloboma and optic disc pit associated with macular retinoschisis.

BACKGROUND: To report and describe an unusual case of a patient with optic disc pit in one eye and optic disc coloboma with a focal pit associated with macular retinoschisis in the other eye. CASE PRESENTATION: A 21-year-old woman presented with optic disc pit in the right eye and optic disc coloboma with a focal pit like excavation in the left eye. Macular spectral domain optical coherence tomography (SD-OCT) of the left eye revealed macular retinoschisis, without serous detachment. CONCLUSIONS: Proper monitoring of patients with disc anomalies associated with maculopathy is mandatory. The use of OCT imaging during follow-up can help to identify involvement of the fovea or enlargement of the retinoschisis area.

'Pai Syndrome' with anterior alveolar polyp: A variant of a rare clinical entity.

'Pai syndrome' (PS) is a rare congenital syndrome. Presented here, a new-born baby-girl who exhibited the characteristic features of having a midline nasal (septal) polyp, an anterior alveolar process polyp, and a pericallosal lipoma associated with corpus callosum dysgenesis of the brain. Both polyps were lined with stratified-squamous epithelium. The overall features were largely consistent with those described by Pai et al., in 1987. A midline cleft-lip (with or without cleft-alveolus) is one of the most common features of the syndrome which was however absent in this case. Instead, an anterior alveolar polyp is present, which is relatively rare.

RETINAL DETACHMENT AND RETROBULBAR CYSTS IN A LARGE COHORT OF OPTIC NERVE COLOBOMA.

PURPOSE: To examine the relationship between retinal detachment and retrobulbar cysts in patients with optic nerve coloboma (ONC) and Morning Glory syndrome (MGS). METHODS: Patients diagnosed with either ONC or MGS were identified through a search of the Sick Kids database. Seventy-one patients either agreed to come in for a B-scan or had an incidental orbital B-scan or magnetic resonance imaging or both. Eyes with orbital B-scan ultrasound and/or magnetic resonance imaging images were assessed independently by two ophthalmologists and a radiologist for the presence of retrobulbar cysts. Retinal detachment was identified clinically with either indirect ophthalmoscopy or from fundus photographs. RESULTS: Forty-five of 71 (63%) and 26/71 (37%) patients had ONC and MGS, respectively. Retinal detachment occurred significantly more often in eyes with MGS than with ONC (9/17 [53%] vs. 5/45 [11%], P = 0.03, respectively). Retrobulbar cysts were not detected more often in MGS than in ONC (11/45 [24%] vs. 7/26 [27%]; P = 1.0). Eyes with retrobulbar cysts were significantly more likely to be associated with retinal detachment than those without (7/18 [39%] vs. 7/53 [13%]; P = 0.04). CONCLUSION: Retinal detachment occurs more frequently in MGS than in ONC in a cohort of patients referred to a specialist children's retinal service. Eyes with retrobulbar cysts are more likely to be associated with retinal detachment.