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.

High Clinical Exome Sequencing Diagnostic Rates and Novel Phenotypic Expansions for Nonisolated Microphthalmia, Anophthalmia, and Coloboma.

Purpose: A molecular diagnosis is only made in a subset of individuals with nonisolated microphthalmia, anophthalmia, and coloboma (MAC). This may be due to underutilization of clinical (whole) exome sequencing (cES) and an incomplete understanding of the genes that cause MAC. The purpose of this study is to determine the efficacy of cES in cases of nonisolated MAC and to identify new MAC phenotypic expansions. Methods: We determined the efficacy of cES in 189 individuals with nonisolated MAC. We then used cES data, a validated machine learning algorithm, and previously published expression data, case reports, and animal models to determine which candidate genes were most likely to contribute to the development of MAC. Results: We found the efficacy of cES in nonisolated MAC to be between 32.3% (61/189) and 48.1% (91/189). Most genes affected in our cohort were not among genes currently screened in clinically available ophthalmologic gene panels. A subset of the genes implicated in our cohort had not been clearly associated with MAC. Our analyses revealed sufficient evidence to support low-penetrance MAC phenotypic expansions involving nine of these human disease genes. Conclusions: We conclude that cES is an effective means of identifying a molecular diagnosis in individuals with nonisolated MAC and may identify putatively damaging variants that would be missed if only a clinically available ophthalmologic gene panel was obtained. Our data also suggest that deleterious variants in BRCA2, BRIP1, KAT6A, KAT6B, NSF, RAC1, SMARCA4, SMC1A, and TUBA1A can contribute to the development of MAC.

Stepwise self-inflating hydrogel expansion for congenital anophthalmia and blind microphthalmia: Over 15 years' experience in China.

BACKGROUND: Self-inflating hydrogel expanders have been used to treat anophthalmia and blind microphthalmia. This study aimed to investigate the long-term outcomes of treatment with self-inflating hydrogel expanders for congenital anophthalmia and blind microphthalmia. METHODS: In this retrospective study, the medical records of 161 patients with anophthalmia and blind microphthalmia who underwent hydrogel expansion were reviewed. We measured the palpebral fissure height (PFH), palpebral fissure length (PFL), and distance between the inner canthal and mid-nasal line (ICMN) before and after surgery. Cox regression analysis was conducted to determine which variables were related to the implantation of spherical expanders following hemispherical expander implantation. RESULTS: After treatment, the PFH and PFL increased significantly (p < 0.001). Complications including expander migration and extrusion occurred in 15 cases. Five patients needed enucleation or further dermis fat graft implantation because of insufficient expansion. The necessity for further spherical expansion was substantially related to a relative axial length (rAL) <0.5 (p = 0.007). CONCLUSION: Self-inflating hydrogel expansion can significantly increase the lid fissure. The occurrence of complications is rare, and surgical intervention can effectively address them. Abnormal eyes with a rAL of less than 0.5 demonstrate a higher possibility of needing additional orbital expansion.

Primary orbital rhabdoid tumour masquerading as atypical persistent foetal vasculature.

We present a case of primary rhabdoid tumour of the orbit. Presenting features at birth included congenital ptosis, conjunctival injection, hyphaema and microphthalmia. The unique presentation caused a late diagnosis following the development of rapid proptosis 6 months later. We suggest that orbital rhabdoid tumour be considered in the differential diagnoses of patients presenting with atypical persistent foetal vasculature features.

Generation of the induced pluripotent stem cell line IOCVi001-A from a patient with the MFRP-related retinitis pigmentosa-nanophthalmos syndrome.

Retinitis pigmentosa (RP) is the most common retinal degeneration in humans and is characterized by the progressive degeneration of rods and cones and retinal pigment epithelium. We generated the IOCVi001-A induced pluripotent stem cell (iPSC) line from dermal fibroblast of a patient with a homozygous c.498_499insC (p.(Asn167Glnfs⁎34) variant in the Membrane-type frizzled related protein (MFRP) gene, a genetic defect causing a syndrome characterized by RP and small eye size (nanophthalmos). IOCVi001-A displayed normal stemness, expressed pluripotent stem cell markers and displayed a normal karyotype. This iPSC line can be used for in vitro disease modeling for complex forms of RP.

Orbital administration of fillers for optimization of symmetry in patients with microphthalmos or acquired anophthalmic sockets: A review.

The treatment of facial asymmetry in patients with microphthalmos or acquired anophthalmic sockets usually requires aggressive reconstructive surgeries. In recent years, studies have been published on the use of fillers to optimize orbital tissue symmetry, as minimally invasive techniques. For this reason, we performed a systematic review of the literature published to date on the use of fillers for the treatment of volume loss in acquired anophthalmic or microphthalmic cavities. Fourteen articles were reviewed in which the material used, the injection technique, the anatomical study of the patients before the procedure and the presence of associated complications were analyzed. Various materials have been used as fillers, including autologous fat, calcium hydroxyapatite, collagen, hyaluronic acid, or polyacrylamide gel. Standard peribulbar and retrobulbar injection techniques were applied, with few associated complications, the most serious being the development of vasovagal symptoms. Patient follow-up is usually limited in most studies to 12 months. In Conclusion, the use of fillers seems to be a safe practice, with good results and few complications, although studies with longer follow-up times than those published to date would be required.

Clinical update in nanophthalmos: Features, diseases and complications associated.

Nanophthalmos is a rare congenital condition of the eyeball that is characterised by a smaller size of the anterior and posterior segments without associated ocular malformations. Typical features that have traditionally been described in these eyes are short axial length, thickened sclera, cornea with a smaller diameter, narrow anterior chamber, and an increased lens to globe volume ratio. However, at present, there is still a lack of recognised diagnostic criteria for nanophthalmos and a classification of its severity. Its clinical relevance stems from the increased risk of multiple ocular conditions, such as high hyperopia, amblyopia, angle-closure glaucoma, retinal detachment, and cataracts. Likewise, in relation to surgery in these eyes, there are particularities in cataract and glaucoma surgery and with a greater risk of associated intra- and postoperative complications. In this way, the treatment of nanophthalmos focuses on controlling the associated eye conditions and reducing and controlling surgical complications. This review aims to update what has been published in recent years regarding nanophthalmos.

A unique case of bilateral nanophthalmos and pigmentary retinal abnormality with unilateral angle closure glaucoma and optic disc pit.

BACKGROUND: Microophthalmos or 'dwarf eye' is characterized by an axial length 2 standard deviation less than age-matched controls. It is classified into nanophthalmos, relative anterior microphthalmos, and posterior microphthalmos based on the anterior segment: posterior segment ratio. Nanophthalmos can occur in association with optic disc drusen, foveoschisis, and retinitis pigmentosa, as an autosomal recessive syndrome linked to mutations in the MFRP gene. We report a case of bilateral nanophthalmos and pigmentary retinopathy with angle closure glaucoma and optic disc pit in one eye. We believe this to be the first case presenting with optic disc pit in association with nanophthalmos. CASE PRESENTATION: A 56-year-old female presented with bilateral small eyes, high hypermetropia, shallow anterior chamber depth, increased lens thickness, mid-peripheral retinal flecks, and macular edema. She also had high intraocular pressure in the right eye, with a disc cupping of 0.9 with an Optic disc pit. The macular edema in the right eye was found to occur in association with the Optic disc pit, whereas, in the left eye, it was associated with intra-retinal hemorrhages and diagnosed as macular branch retinal vein occlusion secondary to hypertension. She was started on anti-glaucoma medications in both eyes and planned for Anti-VEGF injection in the left eye. CONCLUSION: This case report is unique as it reports an association of Nanophthalmos with Optic Disc pit, with an associated angle closure glaucoma in the same eye, an association which has never been previously reported in the literature.

Multimodal prenatal and postnatal imaging of microphthalmia with cyst.

Congenital ocular anomalies may be detected on prenatal imaging using fetal ultrasound and magnetic resonance imaging (MRI), although standard prenatal ultrasound for fetal physical development does not currently include ocular and orbital evaluation. We present the case of a male infant born at 39 weeks' gestation with microphthalmia with cyst that was characterized using serial multimodal imaging, including fetal ultrasound and MRI, B-scan ultrasonography, ultrasound biomicroscopy, and postnatal MRI. Multiple prenatal and postnatal imaging modalities yielded comparable evaluations of the ocular and orbital pathology, validating the prenatal assessments.

Clinical Characterization of Congenital Anophthalmic and Microphthalmic Cavities in Inidviduals With Craniofacial Anomalies.

OBJECTIVE: Measure the frequency of anophthalmic and microphthalmic patients with craniofacial anomalies (FCAs). DESIGN: Descriptive, cross-sectional, retrospective study. SETTING: Hospital for Rehabilitation of Craniofacial Anomalies of the University of São Paulo (HRAC-USP). The medical records of patients treated at HRAC from 2000 to 2012 with a diagnosis of congenital anophthalmia or microphthalmia were examined. Patients were excluded for secondary anophthalmia, incomplete medical records, or information that could not be accessed. OUTCOME MEASURES: Frequency of anophthalmia and microphthalmia; the proportions and diagnoses of associated FCAs; impairment of ocular appendages; extracranial or facial anomalies; genetic alterations; and surgical approach. RESULTS: A total of 56 patients had anophthalmia (52.3%), 35 had microphthalmia (32.7%), and 16 patients had both (15%). Individuals with FCAs associated with microphthalmia, anophthalmia, or both totaled 74, corresponding to 69.2%. Anophthalmia was more likely than microphthalmia to be accompanied by FCAs, at 76.4% of patients ( P < 0.05). Cleft lip and palate were the main malformations associated with anophthalmia (23.64%), with microphthalmia (45%), and with both (44.44%). Reconstructive surgery was done in 63.6% of cases. The ocular attachments were compromised in 71% of cases. Extracraniofacial malformations were found in 9.3% of patients. Only 7 records contained karyotypes, and no changes directly related to anophthalmia or microphthalmia were found. CONCLUSION: Anophthalmia is more frequent than microphthalmia and is more often accompanied by FCA. Cleft lip and cleft palate are the most frequent concomitant malformations.

Emerging roles of the MiT/TFE factors in cancer.

The microphthalmia/transcription factor E (MiT/TFE) transcription factors (TFs; TFEB, TFE3, MITF, and TFEC) play a central role in cellular catabolism and quality control and are subject to extensive layers of regulation that influence their localization, stability, and activity. Recent studies have highlighted a broader role for these TFs in driving diverse stress-adaptation pathways, which manifest in a context- and tissue-dependent manner. Several human cancers upregulate the MiT/TFE factors to survive extreme fluctuations in nutrients, energy, and pharmacological challenges. Emerging data suggest that reduced activity of the MiT/TFE factors can also promote tumorigenesis. Here, we outline recent findings relating to novel mechanisms of regulation and activity of MiT/TFE proteins across some of the most aggressive human cancers.

Bilateral cryptophthalmos with overlapping features of Manitoba oculo-tricho-anal (MOTA) syndrome and Fraser syndrome 2.

A male baby with bilateral cryptophthalmos without eyebrows, distorted anterior hairline, bifid nasal tip, low-set ears, hypertelorism and low anorectal anomaly who was phenotypically diagnosed with Manitoba oculo-tricho-anal syndrome (mutation in FREM1 gene) had an overlapping genotypic diagnosis of autosomal recessive Fraser syndrome 2 because of the presence of a closely related mutation in FREM2 This heterozygous variant was likely to be sporadic. Another mutation was identified in the CEP85L gene indicating lissencephaly 10. This genetic condition has abnormal gyri pattern in the occiput area. This form of lissencephaly is characterised by phenotypic heterogeneity whereby some patients have only mild mental retardation, while others have a very complex clinical picture.In conclusion, this rare condition with the overlap of genetics between several conditions highlights the need for genetic testing even in an low middle income country (LMIC).

ALDH1A3-related congenital microphthalmia-8 due to a novel frameshift variant.

Microphthalmia (MCOP) is a group of rare developmental malformations of eye with often reduced size of the eyeball, leading to blindness. Affecting about 1 in 7000 live births, MCOP can occur due to either environmental or genetic factors. Isolated microphthalmia-8 (MCOP8) has been proved to be caused by autosomal recessive mutations of the ALDH1A3 gene (MIM*600463) encoding aldehyde dehydrogenase 1 family, member A3. Herein, we report an 8-year-old boy with vision problems since birth from a first-cousin consanguineous parents. The main symptoms of the patient included severe bilateral microphthalmia, cyst in the left eye and blindness. The child developed behavioral disorders at the age of 7. It should be noted that there is no family history of the disease. To identify the genetic factor underlying the pathogenesis in this case Whole Exome Sequencing (WES) was performed and followed by Sanger sequencing. A novel pathogenic variant, c.1441delA (p.M482Cfs*8), in the ALDH1A3 gene was detected by WES in the proband. Further prenatal diagnosis is highly suggested to the family for the future pregnancies.

Microphthalmia-Associated Transcription Factor: A Differentiation Marker in Uveal Melanoma.

Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development. In cutaneous melanoma, MITF loss has been linked to an increased expression of stem cell markers, a shift in epithelial-to-mesenchymal transition (EMT)-related factors, and increased inflammation. We explored the role of MITF in Uveal Melanoma (UM) using a cohort of 64 patients enucleated at the Leiden University Medical Center. We analysed the relation between MITF expression and clinical, histopathological and genetic features of UM, as well as survival. We performed differential gene expression and gene set enrichment analysis using mRNA microarray data, comparing MITF-low with MITF-high UM. MITF expression was lower in heavily pigmented UM than in lightly pigmented UM (p = 0.003), which we confirmed by immunohistochemistry. Furthermore, MITF was significantly lower in UM with monosomy 3/BAP1 loss than in those with disomy 3/no BAP1 loss (p < 0.001) and with 8q gain/amplification 8q (p = 0.02). Spearman correlation analysis showed that a low MITF expression was associated with an increase in inflammatory markers, hallmark pathways involved in inflammation, and epithelial-mesenchymal transition. Similar to the situation in cutaneous melanoma, we propose that MITF loss in UM is related to de-differentiation to a less favourable EMT profile and inflammation.

[Macrophthalmos mimics microphthalmos in an 8-month-old Great Swiss Mountain Dog]. / Makrophthalmus imitiert Mikrophthalmus bei einem 8 Monate alten Großen Schweizer Sennenhund.

An 8-month-old Great Swiss Mountain dog was presented with a suspected right-sided microphthalmos, malformed and blind globe which was present since birth. On magnetic resonance imaging an ellipsoid macrophthalmos with absence of the normal retrobulbar tissue was detected. Histology revealed a dysplastic uvea with unilateral cyst formation associated with mild lymphohistiocytic inflammation. The ciliary body covered the posterior side of the lens unilaterally and showed focal metaplastic bone formation. Slight cataract formation as well as diffuse panretinal atrophy and intravitreal retinal detachment was evident. Preoperative diagnostic imaging procedure is recommended in eyes that clinically demonstrate as microphthalmos and are planned to be enucleated. As described in this case report the bulbus may be macrophthalmic which potentially complicates the enucleation. The performance of such a procedure at a site with ophthalmologic and soft tissue expertise is advisable. To the authors' knowledge this is the first report of a macrophthalmos with multiple ocular defects in a dog.

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.

Progressive scoliosis associated with microphthalmia with limb anomalies: A case report.

RATIONALE: Microphthalmia with limb anomalies is a rare, autosomal recessive, multiple congenital anomaly syndrome. Patients with this syndrome particularly present with monocular or bilateral anophthalmia/microphthalmia and distal limb anomalies. However, details regarding associated spinal deformities have not been fully elucidated. PATIENT CONCERNS: A 12-year-old girl initially presented with progressive scoliosis, who was previously diagnosed with microphthalmia with limb anomalies. However, 4 years after the initial visit, the scoliosis deformity gradually progressed. The patient and family requested the surgical treatment to preserve standing/sitting balance. DIAGNOSES: She was diagnosed with microphthalmia with limb anomalies and progressive scoliosis. INTERVENTIONS: A posterior corrective fusion surgery (including a pelvic fusion) was performed to prevent future standing/sitting imbalance. OUTCOMES: Significant improvement of spinal deformity was observed, with no adverse events. LESSONS: This report demonstrated a case of progressive scoliosis associated with microphthalmia with limb anomalies. A posterior corrective spinal fusion was effective to preserve standing/sitting balance. To the best of our knowledge, this is the first report of surgical treatment of progressive scoliosis associated with microphthalmia with limb anomalies.

[Outcomes of surgical treatment of congenital cataract with microphthalmia in infancy].

Objective: To examine the outcomes of surgical treatment for infants with congenital cataract and microphthalmia (CATM). Methods: It was a retrospective case series study. Data of 28 (55 eyes) CATM children who underwent cataract surgery at the Qingdao Eye Hospital of Shandong First Medical University and were followed up for more than 5 years between January 2010 and December 2014 under the age of 6 months. There were 15 male and 13 female children. The age at the time of surgery was (3.2±1.3) months, and the follow-up time was (8.2±1.7) years. The data included the basic information of the children, the ocular biological parameters before and after surgery and intraocular lens (IOL) implantation, and the occurrence of complications. Paired t-tests or Wilcoxon signed rank tests were used to compare groups, and logistic regression analysis was used to identify factors related to IOL implantation, secondary glaucoma, and visual axis opacification (VAO). Results: The mean preoperative axial length was (16.6±1.0) mm, and the mean horizontal corneal diameter was (9.5±0.9) mm. The axial growth rate within 2 years after the first stage of surgery was (1.4±0.8) mm/year. None of the children had an IOL implanted before the age of 2. Sixty percent of the eyes (33/55) received IOL implantation within 2 to 4 years after the first stage of surgery, while the remaining 40% (22/55) did not receive IOL implantation at the last follow-up. The axial growth rate was (0.9±0.7) mm/year within two years after the second stage of surgery. Postoperative secondary glaucoma occurred in 7 eyes (12.7%), and VAO occurred in 15 eyes (27.3%). IOL implantation was associated with preoperative axial length (OR=0.072, P<0.001) and age at the first stage of surgery (OR=7.270, P<0.001), but not with preoperative corneal diameter (P=0.735). The incidence of VAO was associated with preoperative corneal diameter (OR=4.124, P=0.011), but not with age at the first stage of surgery (P=0.489) or preoperative axial length (P=0.489). No factors related to the occurrence of secondary glaucoma were found. The best corrected visual acuity at the last follow-up after IOL implantation was (0.37±0.28) logMAR, which was better than that of children without IOL implantation (0.67±0.19) logMAR (U=49.50, P=0.003). Conclusions: Children with CATM can obtain the opportunity for IOL implantation through early surgery and ultimately achieve good visual outcomes. Properly selecting the timing for implanting IOL can keep the incidence of secondary glaucoma at an acceptable level.