Congenital Ocular Malformations Research Articles

The EFEMEREYE Study: prenatal medication exposure and ocular anomaly occurrence in EFEMERIS health database

PurposeTo describe ocular anomalies (OAs) in children and fetuses in a French general population, to estimate their prevalence, and to investigate a possible association between prenatal medication exposure and the occurrence of OA in utero or in early childhood. MethodsWe conducted a case-control study using the EFEMERIS cohort, a database containing pregnancies registered in Haute-Garonne and their outcomes. We collected OA descriptions of fetuses at the time of pregnancy termination or of children at birth and the results of eye examinations of children at 9 months and 2 years of age. ResultsThe prevalence of overall OAs was 2.13%, of which 0.04% were congenital ocular malformations (COMs). A total of 2,968 cases and 136,619 controls were selected for analysis. There was a significant difference between the two groups with regard to prenatal exposure to medications for the digestive tract and metabolism, the cardiovascular system, and the respiratory system. Multivariate analysis revealed an increased risk of OA in children of mothers exposed to magnesium during and 1 month before pregnancy (OR = 1.24; 95% CI, 1.11-1.38). ConclusionsThis first pharmaco-epidemiological study on OA in France suggests that OA may be associated with exposure to commonly used medications. Given the rarity of COM, larger, international studies are warranted.

Neuroimaging of Ocular Abnormalities in Children.

In this article, we will discuss the essential MR imaging protocol required for the assessment of ocular abnormalities including malignancies. Then we will describe relevant anatomy, ocular embryogenesis, and genetics to establish a profound understanding of pathophysiology of the congenital ocular malformations. Finally, we will discuss pediatric ocular malignancies, benign mimics, and the most common congenital ocular malformations with case examples and illustrations and give tips on how to distinguish these entities on neuroimaging.

Research progress of persistent hyperplastic primary vitreous with Peters anomaly

Persistent hyperplastic primary vitreous is a rare congenital ocular developmental malformation caused by the failure of regression of the primary vitreous during the embryonic development period. Peters anomaly is a monogenetic disease of congenital anterior segment dysgenesis. Recent studies have shown that these two diseases may occur concomitantly and be associated with a variety of systemic abnormalities. This review demonstrates the basis of ocular embryonic development, research status of molecular genetics, clinical manifestations, surgical objectives and progress of treatment of persistent hyperplastic primary vitreous with Peters anomaly, in order to provide guidance for clinical practice and research as well as to promote further progression of related gene detection.

Porcn is essential for growth and invagination of the mammalian optic cup.

Microphthalmia, anophthalmia, and coloboma (MAC) are congenital ocular malformations causing 25% of childhood blindness. The X-linked disorder Focal Dermal Hypoplasia (FDH) is frequently associated with MAC and results from mutations in Porcn, a membrane bound O-acyl transferase required for palmitoylation of Wnts to activate multiple Wnt-dependent pathways. Wnt/β-catenin signaling is suppressed in the anterior neural plate for initiation of eye formation and is subsequently required during differentiation of the retinal pigment epithelium (RPE). Non-canonical Wnts are critical for early eye formation in frog and zebrafish. However, it is unclear whether this also applies to mammals. We performed ubiquitous conditional inactivation of Porcn in mouse around the eye field stage. In Porcn CKO , optic vesicles (OV) arrest in growth and fail to form an optic cup. Ventral proliferation is significantly decreased in the mutant OV, with a concomitant increase in apoptotic cell death. While pan-ocular transcription factors such as PAX6, SIX3, LHX2, and PAX2 are present, indicative of maintenance of OV identity, regional expression of VSX2, MITF, OTX2, and NR2F2 is downregulated. Failure of RPE differentiation in Porcn CKO is consistent with downregulation of the Wnt/β-catenin effector LEF1, starting around 2.5days after inactivation. This suggests that Porcn inactivation affects signaling later than a potential requirement for Wnts to promote eye field formation. Altogether, our data shows a novel requirement for Porcn in regulating growth and morphogenesis of the OV, likely by controlling proliferation and survival. In FDH patients with ocular manifestations, growth deficiency during early ocular morphogenesis may be the underlying cause for microphthalmia.

EPHA2 biallelic disruption causes syndromic complex microphthalmia with iris hypoplasia

Disruption of any of the ocular development steps can result in ocular defects such as microphthalmia, coloboma and anterior segment dysgeneses including aniridia and cataract. All of these anomalies can be isolated or seen in association with each other. Except for aniridia (almost exclusively due to PAX6 mutations), most of these congenital ocular malformations are related to a wide genetic heterogeneity, as hundreds of genes are implied in ocular development. Here we describe a patient presenting with bilateral microphthalmia, congenital cataract, corneal dystrophy and iris hypoplasia, associated with extra-ocular features, who underwent an analysis of 119 ocular development related genes. Genetic testing revealed the presence of two truncating variants in the EPHA2 gene. While EPHA2 mutations are mainly known to be responsible for isolated dominant congenital cataract, we report here the first case of complex anterior segment dysgenesis caused by a biallelic EPHA2 mutation. This gene should be screened in case of aniridia with a negative PAX6 testing, as the ocular features of our patient clearly mimic those of PAX6 mutated patients. This observation enlarges the phenotype associated with EPHA2 variations and rise the insight of a possible PAX6-EPHA2 interaction that needs further investigations. Moreover, despite a great variability in ocular and extra-ocular phenotypes, mutations type and inheritance pattern, a possible genotype-phenotype correlation can also be drawn for this gene.

Bilateral Anophthalmia in Dog Associated with Congenital Penile Malformation

Background: Anophthalmia refers to the complete absence of an eyeball. It is a very rare congenital condition that affects all breeds of dogs, which may be unilateral or bilateral. Anophthalmia results from a severe developmental deficiency in the primitive forebrain, prior to the formation of the optic sulcus. This condition has a complex etiology, and chromosomal, monogenic, and environmental causes have already been identified. There might be an association between anophthalmia and other congenital abnormalities. This case report aimed to report the case of a male dog with bilateral anophthalmia associated with penile malformation. Case: A 3-year-old male mongrel dog was evaluated in a clinical consultation at the Veterinary Medical Teaching Hospital of the Federal University of Piauí (UFPI) - Teresina - Brazil, with signs of anemia and diarrhea. His vaccinations were not up to date (multiple and anti-rabies), presented ectoparasites (ticks), and showed inappetence. The owner reported that the animal was blind from birth, was already well adapted to its environment, had the company of other animals, and had no access to the street. On clinical examination, the animal had a good body score. The eyelids were bilaterally present with normally developed eyelashes. Both the head and face had a symmetrical appearance, without structural abnormalities, and the palpebral fissures were narrow. When opening the eyelids manually, the presence of the conjunctiva was observed bilaterally, the orbits were shallow, and neither orbit contained the eyeball. Further inspection with an ophthalmic clinical flashlight did not reveal any other ocular structures. The initial diagnosis was suggestive of bilateral anophthalmia. Ultrasound examination of the ocular region confirmed the presence of bilateral anophthalmia. A general physical examination revealed a malformed penis with a persistent penile frenulum. Regarding systemic clinical signs (apathy, inappetence, diarrhea, and anemia), clinical and laboratory examinations led to the suspicion of verminosis. Discussion: The dog in this report had a good body score; however, this type of malformation can generate non-viable puppies. Anophthalmia is an extremely rare congenital ocular malformation, both in humans and companion animals, in which there are no ocular structures in the orbits, and these structures (orbits) in affected individuals are generally small and shallow, as seen in the dog in this report. Ultrasonographic examination confirmed the bilateral anophthalmic condition, being the most accurate method of diagnosing this congenital condition. The animal in this report presented with anophthalmia associated with penile malformation. This type of association until this case report has only been described in humans and mice, and is probably caused by a mutation in the Sox2 gene, which is responsible for the protein of the same name, which makes the maturation of ocular tissues in the primitive forebrain. Thus, it is likely that such congenital alterations are the cause of the malformations observed in this animal. Maternal vitamin A deficiency, a factor known to cause ocular malformations, may also be involved in the etiology of congenital diseases. Nutritional imbalances in dogs are common in the animal’s region of origin The dog in this report had a normal life. Although it is a condition that causes blindness, dogs can have a normal life and welfare, even with bilateral anophthalmia. Keywords: canine, persistence penile frenulum, eye, congenital anomalies. Título: Bilateral Anophthalmia in Dog Associated with Congenital Penile Malformation. Descritores: canino, doenças animais, genética, anomalias congênitas.

Ocular Manifestations in Patients with Fanconi Anemia: A Single-Center Experience Including 106 Patients

To describe the prevalence of acquired ocular manifestations in patients with Fanconi anemia (FA) and to describe and correlate the congenital ocular malformations with the genetic subtypes of the disease. This is a cross-sectional observational study of 106 consecutive patients with confirmed diagnosis of FA who were followed at the Hematopoietic Stem Cell Transplantation (HSCT) Service at the Federal University of Paraná, Curitiba, Parana, Brazil. Participants underwent a complete ophthalmologic evaluation and 84 patients underwent ocular ultrasound examination. This study was conducted between November 2014 and August2017. The patients ranged in age from 6months to 43years of age. Microphthalmia was the most common congenital ocular abnormality (95.2%). A decrease in anthropometric measurements was observed, including palpebral fissure length (78/103 patients [76.5%]), microcornea (48/103 patients [46.6%]), and ptosis (31/103 patients [30.1%]). We identified a new ophthalmic condition in 15 patients with FA, that is, epiretinal tissue on the optic disc. The genetic subtype was identified in 78 patients (79.6%), the FA-A subtype was most prevalent (50%). The most common acquired ocular manifestation (non-graft-versus-host disease [GVHD] related) in patients who did not undergo HSCT (n=44) was limbal neovascularization (13.6%), whereas in patients who underwent HSCT (n=62), the GVHD-related manifestation was ocular GVHD (51.6%). The most frequent symptom of ocular GVHD was keratoconjunctivitis sicca (29%). Several ocular manifestations were identified in patients with FA.

Evolution of ocular defects in infant macaques following in utero Zika virus infection.

Congenital Zika syndrome (CZS) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. Rhesus macaques are superior to rodents as models of CZS because they are natural hosts of the virus and share similar immune and ocular characteristics, including blood–retinal barrier characteristics and the unique presence of a macula. Using a previously described model of CZS, we infected pregnant rhesus macaques with Zika virus (ZIKV) during the late first trimester and characterized postnatal ocular development and evolution of ocular defects in 2 infant macaques over 2 years. We found that one of them exhibited colobomatous chorioretinal atrophic lesions with macular and vascular dragging as well as retinal thinning caused by loss of retinal ganglion neuron and photoreceptor layers. Despite these congenital ocular malformations, axial elongation and retinal development in these infants progressed at normal rates compared with healthy animals. The ZIKV-exposed infants displayed a rapid loss of ZIKV-specific antibodies, suggesting the absence of viral replication after birth, and did not show any behavioral or neurological defects postnatally. Our findings suggest that ZIKV infection during early pregnancy can impact fetal retinal development and cause congenital ocular anomalies but does not appear to affect postnatal ocular growth.

Nf2 fine-tunes proliferation and tissue alignment during closure of the optic fissure in the embryonic mouse eye.

Uveal coloboma represents one of the most common congenital ocular malformations accounting for up to 10% of childhood blindness (~1 in 5000 live birth). Coloboma originates from defective fusion of the optic fissure (OF), a transient gap that forms during eye morphogenesis by asymmetric, ventral invagination. Genetic heterogeneity combined with the activity of developmentally regulated genes suggests multiple mechanisms regulating OF closure. The tumor suppressor and FERM domain protein Neurofibromin 2 (NF2) controls diverse processes in cancer, development and regeneration, via Hippo pathway and cytoskeleton regulation. In humans, NF2 mutations can cause ocular abnormalities, including coloboma, however, its actual role in OF closure is unknown. Using conditional inactivation in the embryonic mouse eye, our data indicate that loss of Nf2 function results in a novel underlying cause for coloboma. In particular, mutant eyes show substantially increased retinal pigmented epithelium (RPE) proliferation in the fissure region with concomitant acquisition of RPE cell fate. Cells lining the OF margin can maintain RPE fate ectopically and fail to transition from neuroepithelial to cuboidal shape. In the dorsal RPE of the optic cup, Nf2 inactivation leads to a robust increase in cell number, with local disorganization of the cytoskeleton components F-actin and pMLC2. We propose that RPE hyperproliferation is the primary cause for the observed defects causing insufficient alignment of the OF margins in Nf2 mutants and failure to fuse properly, resulting in persistent coloboma. Our findings indicate that limiting proliferation particularly in the RPE layer is a critical mechanism during OF closure.

Congenital ocular malformations in dogs and cats: 123 cases.

Provide epidemiological data regarding the prevalence of congenital ocular malformations in dogs and cats. A population of 32974 dogs and 13977 cats that presented for consultation at the veterinary teaching hospital. Medical records from 2011 to 2018 were reviewed. A retrospective and prospective epidemiological clinical study addressing congenital ocular malformations was conducted. Signalment, medical history, reason for presentation, clinical findings, vision impairment, and treatment options were analyzed. From the total of cases analyzed, 103 dogs (0.3%) and 20 cats (0.1%) met the inclusion criteria. The majority of dogs were mixed breed, the most common breed being the French Bulldog, while the majority of cats were European domestic shorthair. The median age of diagnosis was 12months for dogs and 6months for cats. Sex predisposition was not found. The most frequently identified abnormalities were as follows: congenital cataract (dogs: 31.1%; cats: 30.0%), microphthalmia (dogs: 35.0%, cats: 25.0%), and persistent pupillary membrane (dogs: 27.2%, cats: 40.0%). Some of the concurrently observed malformations were significantly associated. A statistically significant association was found between ocular dermoids and the French Bulldog breed (P<.001). Even though congenital ocular malformations are uncommon, knowledge about their prevalence is important, since they can cause vision impairment or even blindness. Moreover, some human ocular disease phenotypes are similar to the ones presented by dogs and cats, so they can be used as models to investigate pathophysiology and therapeutic approaches.

CAUSES OF VISUAL HANDICAP AMONGST PATIENTS ATTENDING OUTPATIENT DEPARTMENT OF A TERTIARY CARE CENTER FOR VISUAL HANDICAP CERTIFICATE

PURPOSE- To analyse various ocular diseases leading to permanent visual handicap in a district based on visual handicap certification issued by ophthalmologist at tertiary care center after verification of the domicile of the person. METHOD – This is a retrospective analysis of patients attending outpatient department of tertiary care center for visual handicap certification. It was done over the period of one year with total recruitment of 311 patients. All patients were examined for best corrected visual acuity according to Snellen’s chart, anterior and posterior segment examination. Ultrasonography and/or Optical Coherence Tomography and/or electroretinography / visual evoked potential was done in selected cases. After diagnosis, percentage of blindness was determined according to the categories of visual disability and blindness certificate was issued. RESULT- Maximum of the certified visually disabled individuals are of 21- 30 years (73 patients, 23.47%). 212 patients were males and 99 were females. Visual disability of 100% was seen in 258 cases. Retinitis Pigmentosa was the most common cause seen in 67(21.54%) cases. Other major causes include congenital ocular malformation(16.40%) optic atrophy(13.83%), phthisis bulbi (8.68%), corneal opacities(8.36%), glaucoma(6.75%). CONCLUSION- The burden of the blindness can be decreased by public educationand genetic counselling regarding common and preventable causes of blindness, as early diagnosis, treatment and visual rehabilitation can help to improve visual outcome and ultimately visual handicap in the society for the better future.

High-throughput custom capture sequencing identifies novel mutations in coloboma-associated genes: Mutation in DNA-binding domain of retinoic acid receptor beta affects nuclear localization causing ocular coloboma.

Uveal coloboma is a potentially blinding congenital ocular malformation caused by the failure of optic fissure closure during the fifth week of human gestation. We performed custom capture high‐throughput screening of 38 known coloboma‐associated genes in 66 families. Suspected causative novel variants were identified in TFAP2A and CHD7, as well as two previously reported variants of uncertain significance in RARB and BMP7. The variant in RARB, unlike previously reported disease mutations in the ligand‐binding domain, was a missense change in the highly conserved DNA‐binding domain predicted to affect the protein's DNA‐binding ability. In vitro studies revealed lower steady‐state protein levels, reduced transcriptional activity, and incomplete nuclear localization of the mutant RARB protein compared with wild‐type. Zebrafish studies showed that human RARB messenger RNA partially reduced the ocular phenotype caused by morpholino knockdown of rarga gene, a zebrafish homolog of human RARB. Our study indicates that sequence alterations in known coloboma genes account for a small percentage of coloboma cases and that mutations in the RARB DNA‐binding domain could result in human disease.

Pediatric retina imaging in aniridia

AbstractAniridia is a congenital complex ocular malformation characterized by complete or partial iris hypoplasia and foveal hypoplasia, resulting in nystagmus and low visual acuity from early infancy. In the majority of cases, aniridia is caused by the loss of function of one functional copy (haploinsufficiency) of the PAX6 protein resulting from mutations in PAX6 gene or chromosomal rearrangement at the 11p13 locus. High‐resolution foveal imaging by spectral‐domain optical coherence tomography (SD‐OCT) has improved over recent years the evaluation of foveal architecture analyze. We have analyzed foveal anomalies on SD‐OCT in a large cohort (89 patients) of aniridia patients. We have shown that the grade of foveal hypoplasia is correlated to visual acuity. We have also shown that foveal hypoplasia is a constant finding in PAX6 aniridia patients, although iris defects could vary from complete aniridia to slight iris defects, even in the same family. Foveal imaging and grading by SD‐OCT could offer a non‐invasive tool to determine the visual potential of aniridia eyes and indicate further investigations or treatments. Additionally, SD‐OCT could contribute in the diagnosis of congenital aniridia by detecting foveal hypoplasia as the first sign of the disease.

Overlapping Phenotypes in Congenital Ocular Malformations and the Importance of Molecular Testing

Overlapping Phenotypes in Congenital Ocular Malformations and the Importance of Molecular Testing

Aniridia due to a novel microdeletion affecting $$\textit{PAX6}$$ PAX 6 regulatory enhancers: case report and review of the literature

Aniridia is a rare congenital ocular malformation that follows an autosomal dominant mode of inheritance. Most patients carry pathogenic point mutations in the paired box 6 gene (PAX6), but some carry deletions involving the 11p13 region, encompassing partly or completely PAX6 or the region downstream. We identified a novel deletion, ~564 kb in size located about 46.5 kb downstream of PAX6 in a family with bilateral aniridia and foveal hypoplasia using array-CGH and multiplex ligation-dependent probe amplification. We also reviewall of the reported deletions downstream of PAX6 in patients with aniridia and/or other congenital malformations and define the overlapping region that leads to aniridia when deleted.

Children with optic nerve hypoplasia face a high risk of neurodevelopmental disorders

Optic nerve hypoplasia (ONH) is a congenital ocular malformation that has been associated with neurodevelopmental disorders, but the prevalence in unilateral disease and less severe visual impairment is unknown. We studied intellectual disability and autism spectrum disorders (ASDs) in patients with ONH. This was a population-based cross-sectional cohort study of 65 patients (33 female) with ONH below 20 years of age, living in Stockholm in December 2009, with data analysed in January 2016. Of these 35 were bilateral and 30 were unilateral. Neurodevelopmental disorders were diagnosed or confirmed by neurological assessments, the Five to Fifteen parent questionnaire and reviewing previous neuropsychological investigations or conducting neuropsychological tests. Bilateral ONH patients had lower mean full scale intelligence quotient scores than unilateral patients (84.4 and 99.4, respectively, p = 0.049). We assessed intellectual disability in 55 eligible patients, and it was more common in patients with bilateral ONH (18 of 32, 56%) than unilateral ONH (two of 23, 9%, p < 0.001). ASDs were diagnosed in seven of 42 (17%) patients. Children with bilateral ONH had a high risk of neurodevelopmental disorders, especially intellectual disability. The risk was lower in unilateral ONH, but the levels of neurodevelopmental disorders warrant screening of both groups.

A study to evaluate the cause of blindness/low vision among certified visually disabled individuals in Mandya district of Karnataka

Aim: To identify the demographic characteristics, degree and cause of visual disability among certified visually disabled individuals in Mandya district, Karnataka, India in patients attending Ophthalmology OPD. Materials and Methods: Retrospective record based observational study was carried out in teaching Hospital of Mandya district. Data was collected from visual disability certificates of patients who attended our OPD during the period May 2013 to May 2016. The cause of the visual loss was ascertained. Information from the history, clinical examination and investigations was compiled. Results: In our study, a total of 152 patients were enrolled out of 170 cases. Children and young adults up to age of 30 years constituted around (48, 31.57%) of cases. Among certified visually disabled individuals there were more males (105, 69.08%) compared to females (47, 30.92%). Amount of visual disability percentage of 100%, 75% and 40% was seen in 102(67.10%), 36(23.68%) and 14(9.21%) people respectively. Congenital ocular malformations (32, 21.05%), Retinitis pigmentosa (27, 17.76%) and Optic atrophy (21, 13.81%) were responsible for more than 50% of the cases. Conclusion: Children and young adults constitute around one third of disabled individuals. Men are more common beneficiaries when compared to women showing gender bias. Congenital ocular malformation and Retinitis pigmentosa were the most common causes of certified visual disability. Keywords: Certification, Congenital Ocular malformation, Retinitis pigmentosa, Visually disabled, Optic atrophy

Evaluation of Ocular Side Effects in the Patients on Topiramate Therapy for Control of Migrainous Headache.

Topiramate, a sulfa-derivative monosaccharide, is an antiepileptic drug which is administered in the control of migraine. It is reported to cause various ocular side effects such as visual field defect and myopic shift. To investigate the alterations in refractive error, properties of the cornea and changes in the anterior chamber in patients that receive Topiramate for migraine control. This is a hospital-based, non-interventional, observational study that is conducted at Imam Hossein Hospital, affiliated to Shahid Beheshti University of Medical Sciences, Department of Neurology, in collaboration with the department of Ophthalmology. Thirty three consecutive patients with the diagnosis of migraine that were candidate for Topiramate therapy were recruited. Patients with history of ocular trauma or surgery, keratoconus, glaucoma, congenital ocular malformations and any history of unexplained visual loss were excluded. After thorough ophthalmic examination, all the patients underwent central corneal thickness (CCT) measurement, and Pentacam imaging (Scheimpflug camera) at the baseline. Various parameters were extracted and used for analysis. Anterior chamber volume (ACV), anterior chamber depth (ACD), and anterior chamber angle (ACA) measurement was performed. These measurements were repeated on day 30(th) and 90(th) after the initiation of Topiramate therapy. According to the normality tests, parameters with normal distribution were analysed using the repeated measures test and the remaining parameters (with non-normal distribution) were analysed using the non-parametric k-sample test. A p-value< 0.05 was considered statistically significant, according to Bonferroni post hoc correction. There were 66 eyes of 33 patients under the diagnosis of migrainous headache, that Topiramate was initiated for headache control, included in the study. The mean value of refractive error had a statistically significant myopic change, from -0.23 diopters (D) at the baseline to -0.61 D at the 90(th) day of follow-up period (p-value < 0.001). Mean CCT was 531.43 μm at the baseline and increased to 534.72 μm at the 30(th) day, and 537.51 μm at the 90(th) day after the administration of Topiramate (p-value=0.001). Mean value of other parameters, ACV, ACD, and ACA, did not reveal statistically significant change. Myopic shift and gradually increasing CCT in the patients after Topiramate administration should be considered before any refractive surgery. We found no gradual change in the anterior chamber and angle parameters in our patients in the 90 days of follow up. More studies with a longer duration of follow-up are needed to elucidate dose-dependent ocular manifestations.

Validation of the existing modified screening criteria for detection of all cases of Retinopathy of Prematurity in preterm babies – 11 year study from a governorate referral hospital in Oman

PurposeTo study appropriateness of our modified screening criteria for detection of all cases of Retinopathy of Prematurity (ROP) among preterm babies. MethodRetrospective observational cohort study among preterm neonates who underwent ROP screening as per set protocol for 11years at Nizwa Hospital, Al Dhakilya Governorate, Oman. We screened all babies with gestational age ⩽32weeks or BW⩽1500g. Preterm babies >32weeks of GA or BW>1500g with unstable clinical course believed to be at high risk by the attending neonatologist also were screened. ResultsDuring the study period 528 babies were screened for ROP of which 76 babies were excluded due to death, associated congenital ocular malformation and loss for follow-up either due to transfer to other institution or defaulting. Thus 452 babies were included in the final analysis. Incidence of ROP was 46.4% of which 27.9% had mild ROP, 11.3% had severe ROP which regressed and 7.3% had severe ROP who were treated. The incidence of ROP among infants with GA<26wks, 26–28wks, 29–30wks, 31–32wks and above 32weeks was 100.0%, 80.0%, 59.3%, 34.4% and 19.4% respectively.56 babies of this cohort belonged to Extended (modified) criteria group. Among these 12 babies had ROP out of which 9 had mild ROP and 3 had severe ROP. Among cases with severe ROP, two cases regressed spontaneously and one case needed treatment.Multivariate analysis using stepwise regression model showed statistically significant association of GA and BW to development of ROP.We would have missed few babies with ROP if we had followed other criteria. ConclusionOur modified screening criteria seem to be appropriate as no infant with severe ROP was missed during the study period. Incidence of severe ROP among babies in the extended criteria group (5.4%) is low but significant compared to lower gestational age. We plan to formulate a scoring system following all risk factor analysis to enable us to optimize the number of infants screened. Detection of all babies with ROP is important as they need long-term follow-up for the timely detection and management of associated ocular comorbidities.

Genetics of strabismus and lid diseases.

The prevalence of congenital ocular malformations has been described to vary from 0.04 to 6.8 per 10,000 live births. The nuclear mutations identified in chronic progressive external ophthalmoplegia harbor multiple mtDNA deletions that include POLG mutations, PEO1 mutations, OPA1 mutations and RRM2B mutations. In Kearns-Sayre syndrome, the spontaneous mitochondrial deletions vary from 1.3 to 8.0 kb subunits of the oxidative phosphorylation enzymes and several t-RNA genes are affected. Oculopharyngeal muscle dystrophy is both autosomal dominant and recessive form. Congenital fibrosis of extraocular muscles (CFEOM) 1 has mutations in KIF21A on chromosome 12 with TUBB3 mutation also being seen. CFEOM 2 is an autosomal recessive, genetically distinct entity with homozygous mutations in PHOX2A. CFEOM 3 is autosomal dominant heterozygous missense mutations in TUBB3. Most cases of Mobius syndrome are sporadic with familial cases being autosomal dominant, autosomal recessive or X-linked recessive inheritance. Genetic testing has shown abnormalities involving chromosome 1 and 13. Presynaptic congenital myasthenic syndrome is caused by ChAT (choline acetyltransferase) mutation. Two loci have been found for myotonic dystrophy (DM). DM1, which is associated with trinucleotide expansion on chromosome 19q13.3 and DM2 which is associated with CCTG tetranucleotide expansion at 3q21. Blepharophimosis is caused by mutations in the FOXL2 gene 49 located at chromosome 3q23. Lymphedema-distichiasis is an autosomal dominant disorder caused by mutations in the FOXC2 gene.