Two New Variants in FYCO1 Are Responsible for Autosomal Recessive Congenital Cataract in Iranian Population.

The purpose of this experimental study was to investigate the genetic etiology of congenital cataract (CC) manifesting an autosomal recessive pattern of inheritance in four Iranian families. Affected individuals and their normal first-degree relatives in each family were included in the present study. The genomic DNA of the blood samples was extracted from all participants, and one affected member belonging to each family was subjected to Whole Exome Sequencing (WES). Using bidirectional Sanger sequencing, the identified variants were validated by co-segregation analysis. Two different mutations were detected in the FYCO1 gene encoding FYVE and coiled-coil domain-containing protein. A previously reported missense mutation, c.265C>T (p.Arg89Cys), was found in one Iranian family for the first time, and a combination of two variants in a single codon, c.[265C>T;267C>A] (p.Arg89X), was identified in the three other families. On the other hand, accompanying the c.265C>T mutation, the presence of the c.267C>A polymorphism leads to a premature stop codon. In-Silico Analysis of FYCO1 protein demonstrated that RUN domain will be interrupted so that the large part of functional protein will be eliminated due to this novel variant. FYCO1 has been proved to be involved in human lens development and transparency. Its mutations, therefore, result in CC. Herein, we reported the first autosomal recessive CC patients with c.265C>T (p.Arg89Cys) or c.[265C>T;267C>A] variant in Iranian population for the FYCO1 gene. FYCO1 mutations could be tracked for preventive objectives or even be targeted as therapeutic candidates via treatment approaches in the future.

KIF21A Gene c.2860C>T Mutation in CFEOM1A: The First Report from Iran.

Congenital Fibrosis of the Extra Ocular Muscles1 (CFEOM1) is an autosomal dominant condition, caused by mutation in the KIF21A and TUBB3. It is characterized by congenital non-progressive restrictive ophthalmoplegia and ptosis. Mutational analysis of the known genes in such rare diseases by Sanger sequencing not only prevents wasting the time and expenses but also speeds diagnosis process, genetic counseling, and the possibility of prenatal diagnosis. Here, for the first time, association of pathogenic variant c.2860C>T in KIF21A gene in an Iranian family with positive history of CFEO-M1A was reported.

Expanding the clinical phenotype of IARS2-related mitochondrial disease.

BACKGROUND: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. METHODS: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. RESULTS: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. CONCLUSIONS: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia.

Expression of Pluripotency Markers, SOX2 and OCT4, in Pterygium Development.

Pterygium is a common ocular surface disease characterized by the abnormal epithelial proliferation, matrix remodeling, vascularization and the migration of the lesion. Although the etiology of pterygium is elusive, recent studies have focused on the role of limbal stem cells (LSCs) damage and effects of UVB. This study aimed to determine the expression levels of pluripotent markers of SOX2 and OCT4 in primary pterygium and normal conjunctiva. Using real time polymerase chain reaction (PCR), the SOX2 and OCT4 expressions were compared in primary pterygium and normal conjunctiva. This study assessed the correlation between SOX2 mRNA expression and OCT4 mRNA expression, as well as the association between the clinicopathological indices and both gene expression levels. The relative mRNA expression levels of OCT4 genes in primary pterygium were significantly reduced compared to the normal conjunctiva tissues. The association between OCT4 gene expression and the clinicopathological indices reported significant laterality (P = .004) and marginal growth activity indices (P = .063). The univariate correlation between the SOX2 and OCT4 expressions was statistically significant (P = .001). The present study emphasized the downregulation of pluripotent marker OCT4 genes in the pterygium. It is speculated that these results may predict a new avenue for exploring the role of stem cell deficiency in the development of pterygium.

Unrestricted somatic stem cells, as a novel feeder layer: Ex vivo culture of human limbal stem cells.

Ex vivo culture of limbal stem cells (LSCs) is a current promising approach for reconstruction of the ocular surface. In this context, 3T3 feeder layer cells (mouse embryo fibroblast) are generally utilized to maintain and expand LSCs. The aim of this study is to develop a novel culture method (animal-derived products free) to expand LSCs, using umbilical cord derived human unrestricted somatic stem cells (hUSSCs) instead of 3T3 cell with an emphasis on maintaining of the Stemness in LSCs. Using flow-cytometer, isolated hUSSCs were characterized for CD105, CD90, CD166, CD34, CD45, CD31 cell surface markers and their differentiation capability into adipogenic as well as osteogenic lineages were evaluated. In addition to colony-forming efficiency (CFE), epithelial lineage differentiation and karyotyping, LSC properties were evaluated for ABCG2, ΔNP63-α, CK19, CK3, and CK12 mRNA and protein expressions using quantitative RT-PCR (qRT-PCR) and immunocytochemistry, when these cells were co-cultured with hUSSCs (in comparison with 3T3 feeder layer). LSCs, co-cultured with hUSSCs, showed normal karyotype (46, XX), while they could efficiently form colony (86 ± 3) and display up-regulation of the genes associated with stemness and down-regulation of corneal epithelial differentiation genes. Consistent with 3T3 feeder cells, hUSSCs with spindle-shaped morphology and quick splitting up properties had ability to preserve the stem like-cell phenotype of LSCs. These findings were confirmed by qRT-PCR and flow-cytometer. Findings of present study suggest hUSSCs as a promising alternative method for 3T3 feeder layer cells, to preserve growth and stemness of LSCs ex vivo culture.

Severe Rosacea: A Case Report.

PURPOSE: To describe a case of severe rosacea with ocular involvement. CASE REPORT: A 28-year-old female patient presented with extensive facial and ocular eruptions. She had a history of treatment with oral prednisolone due to the clinical diagnosis of lupus erythematosus (LE), which had resulted in transient improvement of the lesions, but was followed by exacerbation of the lesions. With the clinical diagnosis of severe oculofacial rosacea, she was successfully treated with oral doxycycline, steroid eye drops, and ocular lubricants. Histopathological features of skin biopsy were consistent with rosacea in the context of infection with Demodexfolliculorum. After four years, a relapse of the oculofacial lesions occurred, for which retreatment with oral tetracycline, steroid eye drops, and ocular lubricants was administered. CONCLUSION: Rosacea can be extremely severe and disfiguring, and it can be misdiagnosed as the pathognomonic butterfly rash of LE. Demodex carriage in rosacea is consistent and may play a significant role in the severe forms.

Current and Upcoming Therapies for Ocular Surface Chemical Injuries.

Chemical injuries frequently result in vision loss, disfigurement, and challenging ocular surface complications. Acute interventions are directed at decreasing the extent of the injury, suppressing inflammation, and promoting ocular surface re-epithelialization. Chronically, management involves controlling inflammation along with rehabilitation and reconstruction of the ocular surface. Future therapies aimed at inhibiting neovascularization and promoting ocular surface regeneration should provide more effective treatment options for the management of ocular chemical injuries.

The Relationship Between Breastfeeding and Measurements of Refraction and Visual Acuity in Primary School Children.

BACKGROUND: Nutrition has been implicated in the development of some refractive errors. This study aims to investigate the relationship between refractive errors, visual acuity (VA), and Breastfeeding. METHODOLOGY: In this cross-sectional study, cluster sampling was used to select 400 children aged 1-5. Fieldwork for the main study took place from September 2005 to May 2006 in two public schools of Sabzevar, Iran. Breastfeeding was defined as 6 months or more feeding. A significant refractive error was defined as at least -0.50 diopters (D) for myopia, +0.50D for hyperopia, and -0.50D for astigmatism. In addition, refractive error was calculated by converting it to spherical equivalent (SE). Statistical analysis used includes Descriptive statistics; Spearman correlation coefficients; one-way ANOVA; independent sample t-test; and Pearson chi-square test. RESULTS: Finally, 367 children were selected: 156 boys (42.5%) and 211 girls (57.5%). Three hundred eleven subjects (85%) had Breastfeeding. According to SE in right eye, 25.5% and 5.2% of the subjects were hyperopic and myopic, respectively, in the breastfed group, compared to 26.8% and 5.4% in the non-Breastfeeding group. In addition, hyperopia and myopia were less observable in breastfeeders than the other group for left eye. Mean VA and refractive error were different according to feeding type, but this study did not show statistically significant differences between the two groups; however, for exact judgment about these findings, more studies are suggested with a larger sample size. CONCLUSION: In conclusions based on the results, there was no significant relationship between kind of feeding during the first 6 months of infancy and VA and refractive errors.

Sensitivity and specificity of posterior and anterior corneal elevation measured by orbscan in diagnosis of clinical and subclinical keratoconus.

PURPOSE: To determine the sensitivity and specificity of anterior and posterior corneal elevation parameters as determined by Orbscan II (Bausch and Lomb, Rochester, NY, USA) in discriminating between (sub) clinical keratoconus (KCN) and normal corneas. METHODS: This prospective case-control study included 28 eyes with subclinical KCN, 65 with clinical KCN and 141 normal corneas. Anterior and posterior corneal elevation was measured and compared in the central 5-mm corneal zone using Orbscan II. RESULTS: Receiver operating curves (ROC) curve analyses for posterior corneal elevation showed predictive accuracy in both KCN and subclinical KCN with an area under the curve (AUC) of 0.97 and 0.69, respectively while optimal cutoff points were 51 µm for KCN and 35 µm for subclinical KCN. These values were associated with sensitivity and specificity of 89.23% and 98.58%, respectively, for KCN; and 50.00% and 88.65% for subclinical KCN. ROC curve analyses for anterior corneal elevation showed predictive accuracy in both KCN and subclinical KCN with AUC of 0.97 and 0.69, respectively while optimal cutoff points were 19 µm for KCN and 16 µm for subclinical KCN. These values were associated with sensitivity and specificity of 93.85% and 97.16%, respectively, for KCN; and 60.71% and 87.94% for subclinical KCN. CONCLUSION: Anterior and posterior corneal elevation data obtained by Orbscan II can well discriminate between KCN and normal corneas, however the reliability of their indices is lower in differentiating subclinical KCN from normal cases.

Optical correction of aphakia in children.

There are several reasons for which the correction of aphakia differs between children and adults. First, a child's eye is still growing during the first few years of life and during early childhood, the refractive elements of the eye undergo radical changes. Second, the immature visual system in young children puts them at risk of developing amblyopia if visual input is defocused or unequal between the two eyes. Third, the incidence of many complications, in which certain risks are acceptable in adults, is unacceptable in children. The optical correction of aphakia in children has changed dramatically however, accurate optical rehabilitation and postoperative supervision in pediatric cases is more difficult than adults. Treatment and optical rehabilitation in pediatric aphakic patients remains a challenge for ophthalmologists. The aim of this review is to cover issues regarding optical correction of pediatric aphakia in children; kinds of optical correction , indications, timing of intraocular lens (IOL) implantation, types of IOLs, site of implantation, IOL power calculations and selection, complications of IOL implantation in pediatric patients and finally to determine the preferred choice of optical correction. However treatment of pediatric aphakia is one step on the long road to visual rehabilitation, not the end of the journey.