Congenital pterygium with anterior segment dysgenesis: rare ocular manifestation in Rubinstein-Taybi syndrome.

Pterygium is a benign, wing-shaped fibrovascular overgrowth of subconjunctival tissue that can encroach over the cornea. This condition usually occurs in individuals aged 20-40 years but is rarely seen in children. We report a case of an infant with Rubenstein-Taybi syndrome presenting with nebulo-macular corneal opacity and congenital pterygium. On examination under anaesthesia, bilateral infero-nasal nebulo-macular corneal opacity (6 × 5 mm) with a whitish pink tissue originating from nasal bulbar conjunctiva was noticed. The probe test was negative for this tissue. To the best of our knowledge, only two other cases of congenital pterygium have been reported in the literature. The presence of this anomaly supports the hypothesis of genetic factors having a role in the development of pterygium.

Descemet stripping automated endothelial keratoplasty via a frown incision.

PURPOSE: To assess the outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) via a sclerocorneal frown incision. STUDY DESIGN: Retrospective comparative study. METHODS: The outcomes of Descement stripping endothelial keratoplasty (DSAEK) were retrospectively compared between 36 patients (36 eyes) who underwent surgery via a 3.8-mm frown incision (frown incision group) and 20 patients (20 eyes) who underwent surgery via a 4.6-mm straight incision (straight incision group). In all patients, an NS Endo-Inserter was used as the graft inserter and the incision for a frown incision was via the superior sclerocorneal site and for the straight incision via the temporal cornea. DSAEK was performed by the standard technique, except for the incision. At 1 year after surgery, the two groups were compared with respect to the visual acuity, decrease of corneal endothelial cell density, the severity of corneal astigmatism (diopters), the number of sutures for wound closure, and intraoperative/postoperative complications. RESULTS: There was no significant difference between the two groups in terms of postoperative visual acuity, corneal astigmatism, and intraoperative/postoperative complications one year after surgery. On the other hand, the number of sutures required for wound closure was 1.13 ± 0.42 in the frown incision group, whereas in the straight incision group, it was 3.20 ± 0.40, showing a significant difference (P<0.001). In addition, there was no decreased corneal endothelial cell density associated with the reduction in incision width. CONCLUSIONS: A sclerocorneal frown incision is useful for performing DSAEK with an NS Endo-Inserter as it does not affect endothelial cell loss despite its short incision width.

[PETERS ANOMALY AND PETERS PLUS SYNDROME].

INTRODUCTION: Peters anomaly is characterized by a defect in the development of the anterior segment of the eye during fetal development (Anterior segment dysgenesis). This anomaly presents a broad clinical presentation ranging from minimal peripheral corneal opacity to extensive adhesions of the iris and lens with dense central corneal opacity that impairs vision. Peters Plus Syndrome is a recessive autosomal syndrome manifested by Peters anomaly, along with systemic disorders such as brachydactyly (short fingers and toes), short stature, a developmental delay, dysmorphic facial features, and may accompanied with heart and genitourinary malformations. The most common sign of Peters' anomaly is corneal opacity that appears at birth. This opacity can cause blockage of the central visual axis and cause the development of a deprivational amblyopia. In addition, the patient may suffer from glaucoma due to malformations in the angle structures as well as a shallow anterior chamber. Treatments are aimed at clearing the central visual axis as soon as possible in order to allow the visual system to mature and to avoid the development of amblyopia. Full-thickness corneal transplantation combined with Cataract surgery if necessary is the current standard of care. Optical iridoplasty is a milder surgical alternative in cases where the corneal opacity is not significant.

A lower birth weight percentile is associated with central corneal thickness thinning: Results from the Gutenberg Prematurity Eye Study (GPES)

Purpose: Prematurity, prenatal growth restriction, and retinopathy of prematurity (ROP) are associated with altered ocular geometry, such as a steeper corneal shape in childhood, but it is unclear whether perinatal history affects corneal thickness development, so this study investigated whether corneal thickness in adulthood is affected by perinatal history. Marterials and Methods: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. The corneal thickness was measured by Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany), and the relationship between perinatal parameters respective birth weight percentile and corneal thickness at different locations was assessed using uni- and multivariable linear regression models. Covariates included age, sex, mean corneal radius, white-to-white distance, gestational age, birth weight percentile, ROP occurrence, and treatment. The main outcome measures were corneal thickness at the apex, the pupil center, and the corneal periphery. Results: The corneal thickness was measured in 390 participants (754 eyes, mean age 29.7+/-8.7 years, 224 females). In multivariable analyses, a lower birth weight percentile was associated with a lower corneal thickness at the apex (B = 0.20, p = 0.003) and the pupil (B = 0.19, p = 0.007). These effects diminished towards the corneal periphery and were not observed beyond the 4-mm diameter circle around the thinnest corneal position. Neither gestational age, ROP occurrence, or ROP treatment affected the corneal thickness. Conclusion: A lower birth weight percentile in subjects born preterm as a proxy for restricted fetal growth is associated with corneal thickness thinning in adults aged 18 to 52 years, indicating that corneal thickness development, particularly in the corneal center, may originate in the fetal stage. (AU)

Ocular Manifestations of Peters Plus-Like Syndrome in 8q21.11 Microdeletion Syndrome.

PURPOSE: The aim of this study was to report a case of Peters plus-like syndrome, which revealed to have an 8q21.11 microdeletion by copy number variation analysis using exome data. METHODS: A 6-month-old Japanese boy presented with bilateral corneal opacity since birth. The right eye maintained central corneal transparency with slightly inferior nasal and superior peripheral corneal opacities. The entire cornea was opacified in the left eye, particularly in the superior quadrants with vascularization, suggesting Peters anomaly. Identification of intraocular structures in the left eye was difficult; however, hypoplasia of the circumferential anterior iris stroma appeared bilaterally present, and no abnormalities were present in the posterior segment on funduscopic examination of the right eye and ultrasonography in the left eye. He had several facial malformations in addition to corneal opacity, but no other external abnormalities. General examination, including biochemical tests of blood and urine, physiological and imaging tests including abdominal echo, auditory brain stem response, brain computed tomography, and magnetic resonance imaging, showed no abnormalities. However, the patient showed intellectual disability and delayed motor development. RESULTS: Although his karyotype was normal, copy number variation analysis using exome data and subsequent quantitative polymerase chain reaction identified a de novo 4.6-Mb deletion at 8q21.11q21.13; thus, the patient was diagnosed with 8q21.11 microdeletion syndrome. CONCLUSIONS: We identified a de novo 4.6-Mb deletion at 8q21.11q21.13 in a patient with ophthalmic anterior segment dysgenesis and systemic complications, clinically diagnosed as Peters plus-like syndrome. Clinically, the 8q21.11 microdeletion syndrome shows a phenotype similar to that of Peters plus syndrome, and a genetic diagnosis is required.

Isolated traumatic aniridia with full and partial iris expulsion in pseudophakic eyes.

BACKGROUND: Total aniridia after ocular trauma without disruption of the intraocular lens (IOL) has been reported in patients with a history of small-incisional cataract surgery. We report one case each of total and partial aniridia after accidental falls experienced by two elderly Japanese women. CASE PRESENTATIONS: Case 1. A 76-year-old woman with a history of small-incisional cataract surgery more than 10 years previously fell onto concrete and had a contusion that affected the left side of her face. At the initial visit, the best-corrected visual acuity (BCVA) was hand motions and the intraocular pressure (IOP) was 38 mmHg in her left eye (OS). A blood clot was present in the well-formed anterior chamber and expulsed iris tissue was seen beneath the conjunctiva. Exploratory surgery showed no scleral laceration other than the previous sclerocorneal tunnel. After hyphema removal, total aniridia and an intact in-the-bag fixed IOL were seen. By 4 months, the BCVA was 1.2 and the IOP was 13 mmHg OS. CASE 2: An 88-year-old woman with a history of small-incisional cataract surgery more than 10 years previously had a fall that resulted in right-sided zygomatic and maxillary bone fractures. The BCVA was light perception and the IOP was 29 mmHg in her right eye (OD). Exploratory surgery showed no scleral laceration and the previous sclerocorneal tunnel was found; iris strand prolapsing from the sclerocorneal tunnel was seen. After hyphema removal, partial iris loss and an intact lens position were seen. By 1 week postoperatively, the BCVA was 0.05 OD and the IOP was 12 mmHg OD. CONCLUSIONS: It has been postulated that previously created small-incision tunnels can function as release valves during blunt trauma by preventing further global rupture and limiting IOL prolapse or retinal injury. Our cases suggested this can happen even long periods after cataract surgery. The case with partial aniridia demonstrated the process of the expulsive aniridia, and its findings do not contradict the postulated mechanisms.

A critical role of calcineurin in stress responses, hyphal formation, and virulence of the pathogenic fungus Trichosporon asahii.

Trichosporon asahii is a conditional pathogenic fungus that causes severe and sometimes fatal infections in immunocompromised patients. While calcineurin, an essential component of a calcium-dependent signaling pathway, is known to regulate stress resistance and virulence of some pathogenic fungi, its role in T. asahii has not been investigated. Here, we demonstrated that calcineurin gene-deficient T. asahii mutants are sensitive to high temperature as well as cell-membrane and cell-wall stress, and exhibit decreased hyphal formation and virulence against silkworms. Growth of T. asahii mutants deficient in genes encoding subunits of calcineurin, cna1 and cnb1, was delayed at 40 °C. The cna1 and cnb1 gene-deficient mutants also showed sensitivity to sodium dodecyl sulfate, Congo red, dithiothreitol, and tunicamycin. On the other hand, these mutants exhibited no sensitivity to caffeine, sorbitol, monensin, CaCl2, LiCl, NaCl, amphotericin B, fluconazole, or voriconazole. The ratio of hyphal formation in the cna1 and cnb1 gene-deficient mutants was decreased. Moreover, the virulence of the cna1 and cnb1 gene-deficient mutants against silkworms was attenuated. These phenotypes were restored by re-introducing each respective gene into the gene-deficient mutants. Our findings suggest that calcineurin has a role in regulating the cellular stress response and virulence of T. asahii.

Effect of depth of the sclerocorneal incision on postoperative corneal astigmatism in manual small-incision cataract surgery.

Purpose: To determine the effect of depth of scleral tunnel incision measured by anterior segment OCT on postoperative corneal astigmatism by comparing the change of magnitude of corneal astigmatism between superficial and deep sclerocorneal tunnel incision in manual small-incision cataract surgery (SICS). Methods: Depths of sclerocorneal incision of 72 eyes of patients undergoing uncomplicated manual SICS and attending regular follow-up schedule were assessed with anterior segment OCT at 6-week post-op follow-up. Results: The overall mean ± standard deviation (SD) change of astigmatism for superficial incision, that is, ≤399 µm, was 0.44 ± 0.30 and that for deeper, that is, ≥400 µm, was 0.13 ± 0.48 and the change was significantly higher in ≤399 µm group than in ≥400 µm group (P = 0.003). In both superior and temporal incision locations, the mean ± SD change of astigmatism for ≤399 µm incision was 0.48 ± 0.29 and 0.40 ± 0.30, respectively, and that for ≥400 µm was 0.03 ± 0.34 and 0.23 ± 0.57, respectively. The change of astigmatism was significantly higher in ≤399 µm incision group overall (P = 0.003) and also higher in both superior and temporal incision location groups (P = 0.001 and P = 0.479, respectively). Conclusion: The depth of sclerocorneal incision had a statistically significant effect on the change of astigmatism following manual SICS, with superficial incision (≤399 µm) causing a higher change than deeper incision (≥ 400 µm).

Sodium hydrosulfide reverses ß2-microglobulin-induced depressive-like behaviors of male Sprague-Dawley rats: Involving improvement of synaptic plasticity and enhancement of Warburg effect in hippocampus.

BACKGROUND: Our previous works demonstrated that ß2-microglobulin (ß2m), a systemic pro-aging factor, induce depressive-like behaviors. Hydrogen sulfide (H2S) is identified as a potential target for treatment of depression. The aim of the present work is to explore whether H2S antagonizes ß2m-induced depressive-like behaviors and the underlying mechanisms. METHODS: The depressive-like behaviors were detected using the novelty suppressed feeding test (NSFT), tail suspension test (TST), forced swimming test (FST) and open field test (OFT). The expressions of Warburg-related proteins, including hexokinase II (HK II), pyruvate kinase M2 (PKM2), Lactate dehydrogenase A (LDHA), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase 1(PDK1), and synaptic plasticity-related proteins, including postsynaptic density protein 95 (PSD95) and synaptophysin1 (SYN1), were determined by western blotting. RESULT: we found that NaHS (the donor of H2S) attenuated the depressive-like behaviors in the ß2m-exposed rats, as judged by NSFT, TST, FST, and OFT. We also demonstrated that NaHS enhanced the synaptic plasticity, as evidenced by the upregulations of PSD95 and SYN1 expressions in the hippocampus of ß2m-exposed rats. Furthermore, NaHS improved the Warburg effect in the hippocampus of ß2m-exposed rats, as evidenced by the upregulations of HK II, PKM2, LDHA and PDK1 expressions, and the downregulation of PDH expression. CONCLUSION: H2S prevents ß2m-induced depressive-like behaviors, which is involved in improvement of hippocampal synaptic plasticity as a result of enhancement of hippocampal Warburg effect.

Ocular Phenotype of Peters-Plus Syndrome.

PURPOSE: Peters-plus syndrome is a rare, autosomal recessive congenital disorder of glycosylation caused by mutations in the gene B3GLCT. A detailed description of the ocular findings is currently lacking in the scientific literature. We report a case series of Peters-plus syndrome with deep ocular phenotyping using anterior segment optical coherence tomography and ultrasound biomicroscopy. Where available, we describe the histology of host corneal buttons. METHODS: A retrospective chart review of patients with Peters-plus syndrome was conducted under the care of the senior author between January 2000 and June 2019. Demographic and clinical data including ocular and systemic features, ophthalmic imaging, and molecular diagnostic reports were collected. RESULTS: Four cases of Peters-plus syndrome were identified. Three patients were male and 1 was female. Five of the 8 eyes had an avascular paracentral ring opacity with relative central clearing. The paracentral opacity is due to iridocorneal adhesion and the relative central clearing associated with posterior stromal thinning. One eye had persistent fetal vasculature and microphthalmia, which has not previously been reported. One eye from each of 2 patients had a significantly different phenotype with a large vascularized central corneal opacity. CONCLUSIONS: The most common ocular phenotype seen in Peters-plus syndrome is an avascular paracentral ring opacity with relative central clearing. A different phenotype with a large vascularized corneal opacity may also be observed.

Corneal biomechanical parameters in keratoconus eyes with abnormal elevation on the back corneal surface only versus both back and front surfaces.

Corneal biomechanical parameters were compared in 100 keratoconus eyes with abnormal elevation on the back corneal surface only (group 1), versus both the back and front surfaces (group 2). Scheimpflug tomography with Pentacam HR, corneal biomechanical assessments using Corvis ST and Ocular Response Analyzer (ORA) and corneal epithelium thickness maps using anterior segment optical coherence tomography were assessed. There were no significant differences in the IOP measured using Corvis ST and ORA, age or sex between the two groups. Statistically significant differences were found in all corneal shape parameters and all new parameters of Corvis ST: corneal stiffness parameter at first applanation (SP-A1), integrated inverse radius (IR) and deformation amplitude ratio (DAR)) between groups (p < 0.001). The classic parameters of ORA including corneal hysteresis (CH) and corneal resistance factor (CRF) were about 1.00 mmHg higher in group 1 (p < 0.001). In conclusion, keratoconus eyes with abnormal elevation limited to the back corneal surface have lower grade, stiffer corneal biomechanical parameters and less asymmetric shape. This is consistent with progressive biomechanical weakening from the first detectable back surface elevation to manifestation on the front surface as the severity overwhelms the ability of the epithelium to compensate.

High-Throughput miRFluR Platform Identifies miRNA Regulating B3GLCT That Predict Peters' Plus Syndrome Phenotype, Supporting the miRNA Proxy Hypothesis.

MicroRNAs (miRNAs, miRs) finely tune protein expression and target networks of hundreds to thousands of genes that control specific biological processes. They are critical regulators of glycosylation, one of the most diverse and abundant post-translational modifications. In recent work, miRs have been shown to predict the biological functions of glycosylation enzymes, leading to the "miRNA proxy hypothesis" which states, "if a miR drives a specific biological phenotype..., the targets of that miR will drive the same biological phenotype." Testing of this powerful hypothesis is hampered by our lack of knowledge about miR targets. Target prediction suffers from low accuracy and a high false prediction rate. Herein, we develop a high-throughput experimental platform to analyze miR-target interactions, miRFluR. We utilize this system to analyze the interactions of the entire human miRome with beta-3-glucosyltransferase (B3GLCT), a glycosylation enzyme whose loss underpins the congenital disorder Peters' Plus Syndrome. Although this enzyme is predicted by multiple algorithms to be highly targeted by miRs, we identify only 27 miRs that downregulate B3GLCT, a >96% false positive rate for prediction. Functional enrichment analysis of these validated miRs predicts phenotypes associated with Peters' Plus Syndrome, although B3GLCT is not in their known target network. Thus, biological phenotypes driven by B3GLCT may be driven by the target networks of miRs that regulate this enzyme, providing additional evidence for the miRNA proxy hypothesis.

Peters plus syndrome mutations affect the function and stability of human ß1,3-glucosyltransferase.

Peters Plus Syndrome (PTRPLS OMIM #261540) is a severe congenital disorder of glycosylation where patients have multiple structural anomalies, including Peters anomaly of the eye (anterior segment dysgenesis), disproportionate short stature, brachydactyly, dysmorphic facial features, developmental delay, and variable additional abnormalities. PTRPLS patients and some Peters Plus-like (PTRPLS-like) patients (who only have a subset of PTRPLS phenotypes) have mutations in the gene encoding ß1,3-glucosyltransferase (B3GLCT). B3GLCT catalyzes the transfer of glucose to O-linked fucose on thrombospondin type-1 repeats. Most B3GLCT substrate proteins belong to the ADAMTS superfamily and play critical roles in extracellular matrix. We sought to determine whether the PTRPLS or PTRPLS-like mutations abrogated B3GLCT activity. B3GLCT has two putative active sites, one in the N-terminal region and the other in the C-terminal glycosyltransferase domain. Using sequence analysis and in vitro activity assays, we demonstrated that the C-terminal domain catalyzes transfer of glucose to O-linked fucose. We also generated a homology model of B3GLCT and identified D421 as the catalytic base. PTRPLS and PTRPLS-like mutations were individually introduced into B3GLCT, and the mutated enzymes were evaluated using in vitro enzyme assays and cell-based functional assays. Our results demonstrated that PTRPLS mutations caused loss of B3GLCT enzymatic activity and/or significantly reduced protein stability. In contrast, B3GLCT with PTRPLS-like mutations retained enzymatic activity, although some showed a minor destabilizing effect. Overall, our data supports the hypothesis that loss of glucose from B3GLCT substrate proteins is responsible for the defects observed in PTRPLS patients, but not for those observed in PTRPLS-like patients.

From cataract to syndrome diagnosis: Revaluation of Warburg-Micro syndrome Type 1 patients.

Warburg-Micro syndrome (WARBM) is a rare autosomal recessively inherited neuro-ophthalmologic syndrome. Although WARBM shows genetic heterogeneity, the pathogenic variants in RAB3GAP1 were the most common cause of WARBM. In this study, we aimed to evaluate the detailed clinical and dysmorphic features of seven WARBM1 patients and overview the variant spectrum of RAB3GAP1 in comparison with the literature who were referred due to congenital cataracts. A previously reported homozygous variant (c.2187_2188delGAinsCT) was identified in three of these patients, while the other four had three novel variants (c.251_258delAGAA, c.2606+1G>A, and c.2861_2862dupGC). Congenital cataract and corpus callosum hypo/agenesia are pathognomonic for WARBM, which could be distinguished from other similar syndromes with additional typical dysmorphic facial features. Although there is no known phenotype and genotype correlation in any type of WARBM, RAB3GAP1 gene analysis should be previously requested as the first step of genetic diagnosis in clinically suspicious patients when it is not possible to request a multi-gene panel.

Novel manifestations of Warburg micro syndrome type 1 caused by a new splicing variant of RAB3GAP1: a case report.

BACKGROUND: The present study aimed to determine the underlying genetic factors causing the possible Warburg micro syndrome (WARBM) phenotype in two Iranian patients. CASE PRESENTATION: A 5-year-old female and a 4.5-year-old male were referred due to microcephaly, global developmental delay, and dysmorphic features. After doing neuroimaging and clinical examinations, due to the heterogeneity of neurodevelopmental disorders, we subjected 7 family members to whole-exome sequencing. Three candidate variants were confirmed by Sanger sequencing and allele frequency of each variant was also determined in 300 healthy ethnically matched people using the tetra-primer amplification refractory mutation system-PCR and PCR-restriction fragment length polymorphism. To show the splicing effects, reverse transcription-PCR (RT-PCR) and RT-qPCR were performed, followed by Sanger sequencing. A novel homozygous variant-NM_012233.2: c.151-5 T > G; p.(Gly51IlefsTer15)-in the RAB3GAP1 gene was identified as the most likely disease-causing variant. RT-PCR/RT-qPCR showed that this variant can activate a cryptic site of splicing in intron 3, changing the splicing and gene expression processes. We also identified some novel manifestations in association with WARBM type 1 to touch upon abnormal philtrum, prominent antitragus, downturned corners of the mouth, malaligned teeth, scrotal hypoplasia, low anterior hairline, hypertrichosis of upper back, spastic diplegia to quadriplegia, and cerebral white matter signal changes. CONCLUSIONS: Due to the common phenotypes between WARBMs and Martsolf syndrome (MIM: 212720), we suggest using the "RABopathies" term that can in turn cover a broad range of manifestations. This study can per se increase the genotype-phenotype spectrum of WARBM type 1.

A novel mutation in RAB3GAP1 gene in Chinese patient causing the Warburg micro syndrome: A case report.

RATIONALE: Warburg Micro syndrome is a rare, autosomal recessive disorder characterized by multiple organ abnormalities involving the ocular, nervous, and genital systems. This case report describes a novel mutation in the RAB3GAP1 gene associated with Warburg Micro syndrome. PATIENT CONCERNS: A 6-month-old female infant with bilateral congenital cataracts and developmental delay was referred to our department for further assessment. She presented with facial dysmorphic features, including a prominent forehead, microphthalmia, wide nasal bridge, relatively narrow mouth, large anteverted ears, and micrognathia. DIAGNOSES: The patient was diagnosed with Warburg Micro syndrome based on clinical manifestations, as well as a novel homozygous mutation in RAB3GAP1: c.75-2A>C. Both parents were identified as heterozygotic carriers of this mutation. INTERVENTIONS: Bilateral cataract extraction and anterior vitrectomy were performed at age 6 months, followed by physical rehabilitation. Convex lenses were used to protect the eyes postoperatively until intraocular lens implantation. OUTCOMES: Although the patient received physical rehabilitation, she suffered global developmental delay. LESSONS: The c.75-2A>C mutation in RAB3GAP1 expands the spectrum of known mutations in this gene, and it may be associated with Warburg Micro syndrome. Genetic counselors may wish to take this finding into consideration, especially given the poor prognosis associated with the disease.

The Warburg Micro Syndrome-associated Rab3GAP-Rab18 module promotes autolysosome maturation through the Vps34 Complex I.

Warburg micro syndrome (WMS) is a hereditary autosomal neuromuscular disorder in humans caused by mutations in Rab18, Rab3GAP1, or Rab3GAP2 genes. Rab3GAP1/2 forms a heterodimeric complex, which acts as a guanosine nucleotide exchange factor and activates Rab18. Although the genetic causes of WMS are known, it is still unclear whether loss of the Rab3GAP-Rab18 module affects neuronal or muscle cell physiology or both, and how. In this work, we characterize a Rab3GAP2 mutant Drosophila line to establish a novel animal model for WMS. Similarly to symptoms of WMS, loss of Rab3GAP2 leads to highly decreased motility in Drosophila that becomes more serious with age. We demonstrate that these mutant flies are defective for autophagic degradation in multiple tissues including fat cells and muscles. Loss of Rab3GAP-Rab18 module members leads to perturbed autolysosome morphology due to destabilization of Rab7-positive autophagosomal and late endosomal compartments and perturbation of lysosomal biosynthetic transport. Importantly, overexpression of UVRAG or loss of Atg14, two alternative subunits of the Vps34/PI3K (vacuole protein sorting 34/phosphatidylinositol 3-kinase) complexes in fat cells, mimics the autophagic phenotype of Rab3GAP-Rab18 module loss. We find that GTP-bound Rab18 binds to Atg6/Beclin1, a permanent subunit of Vps34 complexes. Finally, we show that Rab3GAP2 and Rab18 are present on autophagosomal and autolysosomal membranes and colocalize with Vps34 Complex I subunits. Our data suggest that the Rab3GAP-Rab18 module regulates autolysosomal maturation through its interaction with the Vps34 Complex I, and perturbed autophagy due to loss of the Rab3GAP-Rab18 module may contribute to the development of WMS.

Clinical spectrum of non-syndromic microphthalmos, anophthalmos and coloboma in the paediatric population: a multicentric study from North India.

AIMS: To describe the clinical features, visual acuity and causes of ocular morbidity in children (0-18 years) with microphthalmos, anophthalmos, and coloboma (MAC) from North India. METHODS: A retrospective study conducted between October 2017 and September 2018 in three tertiary eye institutes, part of the Bodhya Eye Consortium with consensus led common pro formas. Children with complete clinical data and without syndromic/systemic involvement were included. The clinical phenotype was divided into isolated ocular coloboma (CB), coloboma with microcornea (CBMC), colobomatous microphthalmos (CBMO), non-colobomatous microphthalmos (MO) and anophthalmos (AO). RESULTS: A total of 532 children with MAC were examined. Seventeen records were excluded due to incomplete data (0.2%). 515 children (845 eyes) were included: 54.4% males and 45.6% females. MAC was unilateral in 36% and bilateral in 64%. CB, CBMC, CBMO, MO and AO were seen in 26.4%, 31%, 22%, 8% and 12.5% of eyes, respectively. Nystagmus was found in 40%, strabismus in 23%, cataract in 18.7% and retinal detachment in 15%. Best-corrected visual acuity (BCVA) of <3/60 was seen in 62.4% eyes. Blindness (BCVA <3/60 in better eye) was seen in 42.8% of bilateral patients. Those with microcornea or microphthalmos with coloboma had worse BCVA (p<0.001). There were regional differences in the type of MAC phenotype presenting to the three institutes. CONCLUSION: The MAC group of disorders cause significant ocular morbidity. The presence of microcornea or microphthalmos with coloboma predicts worse BCVA. The variation of the MAC phenotype with the district of origin of the patient raises questions of aetiology and is subject to further studies.