OBJECTIVE: A horizontal corneal diameter greater than 2 standard deviations from the mean (9.8 mm) or greater than 11 mm in term infants defines megalocornea (herein referred to as a large clear cornea). The aim of the current study was to report on the incidence and clinical characteristics of children presenting with large clear cornea that do not suffer glaucoma.
METHODS: A retrospective chart review of children presenting with large clear cornea to the pediatric ophthalmology unit of the ophthalmology department of Alexandria Main University Hospital in the period from March 2011 to December 2020 was conducted. A large clear cornea was defined as a horizontal white-to-white corneal diameter (as measured by calipers) greater than 12 mm. Glaucoma was diagnosed according to the childhood glaucoma research network (CGRN) criteria and the axial length was used to filter out eyes with large clear corneas due to congenital high myopia.
RESULTS: Out of 120 eyes of 91 (58 males) children a total of 76 eyes of 67 (41 males) children were diagnosed with glaucoma and 44 eyes of 24 (17 males) children (36.7%) did not suffer glaucoma. Out of these, 30 eyes were classified as myopia and 14 eyes as congenital megalocornea.
CONCLUSIONS: More than one third of eyes presenting with large clear corneas may not have glaucoma, and almost two thirds of these eyes (that are not suffering from glaucoma) demonstrate axial myopia.

Hyperphosphatasia with mental retardation syndrome 4 (HPMRS4) is a rare autosomal recessive disorder caused by glycosylphosphatidylinositol (GPI) deficiency. GPI deficiency results from a mutation in one of six known genes. Mutation in post-GPI attachment to protein phospholipase 3 gene (PGAP3) is linked to HPMRS4. Patients usually present with dysmorphic features, developmental delay, central hypotonia, and seizure. However, in our case, we report a novel homozygous missense mutation of PGAP3 gene in a female child who presented with megalocornea, which is an unusual clinical presentation for HPMRS4. Megalocornea, in her first days of life, led to a misdiagnosis of primary congenital glaucoma. Later, other common clinical features of HPMRS4 became apparent.

UNASSIGNED: Primary congenital glaucoma is potentially blinding condition characterized by elevated intraocular pressure and optic disc cupping. It is typically bilateral and usually manifest in the first year of life. Spontaneously arrested primary congenital glaucoma can occur, but it is very rare.
UNASSIGNED: A 32-year-old male patient from North Shewa presented to the department of ophthalmology, Menelik II Hospital with deterioration of vision. On examination he had large corneas with horizontal diameter of 14 mm, increased axial length, faint corneal stromal opacity and Haab\'s striae of both eyes. Anterior chamber angles were wide open. His intraocular pressure, optic nerve head appearance and visual field in both eyes were normal. He had subluxated dense cataract of the right eye.
UNASSIGNED: Late presentation with sequelae of primary congenital glaucoma without optic neuropathy is possible. Regular follow-up of spontaneously arrested congenital glaucoma and scleral fixation of intraocular lens is recommended.

UNASSIGNED: The aim of this study was to examine the biometric ocular manifestations and structural ocular features of anterior megalophthalmos (AM).
UNASSIGNED: Fifteen patients with AM (30 eyes) from the Eye & ENT Hospital of Fudan University were included. The age-matched control group consisted of 30 participants (30 eyes) who underwent Pentacam HR and IOLMaster 700 measurements for one normal eye. Data on demographics, biometric manifestations, and genotypes were carefully compared.
UNASSIGNED: A total of 15 patients with AM and 30 control patients were enrolled. There were no differences in age (37.27 ± 19.1 vs. 31.43 ± 19.69 years, P = 0.249) between these two groups. AM eyes were characterized by premature cataracts (11/30, 36.67%) and zonular weakness with lens subluxation (22/30, 73.33%) compared with the control group. Notably, 20 of the 30 AM eyes (66.67%) had significant posterior iris bowing, and 16 of the 30 AM eyes (53.33%) showed an enlarged ciliary ring on ultrasound biomicroscopy (UBM). Mean corneal curvature was lower in the AM eyes (42.01 ± 2.06 D vs. 43.14 ± 1.38 D, P = 0.023). There was no significant difference in corneal pachymetry and central endothelial cell count between the AM and control groups. Significant differences were found in terms of the anterior chamber and white-to-white (WTW) among the Pentacam HR and IOLMaster 700 in patients with AM (P < 0.05). The difference was 0.53 ± 0.48 mm and 0.36 ± 0.14 mm, respectively (P < 0.001).
UNASSIGNED: The results of this cohort study conclude the biometric and structural ocular manifestations in Chinese cohorts. Posterior iris bowing (66.67%) and lens subluxation (73.33%) are the most characteristic findings in patients with AM with anatomical abnormalities of megalocornea and a deep anterior chamber, although corneal biometric manifestations of AM included flatter cornea and lower total corneal astigmatism. The knowledge of ocular manifestations of AM is important for diagnosis and preparation for the operation in advance to avoid intraoperative and postoperative complications. Significant differences were found in the anterior chamber and WTW values between the Pentacam HR and IOLMaster 700. Thus, we suggest that various examinations should be carefully considered before determining an AM diagnosis.

UNASSIGNED: X-linked megalocornea (XMC) is a rare anterior segment malformation characterized by a nonprogressive enlargement of the cornea to 13 mm or greater in the setting of normal intraocular pressure. XMC is caused by mutations in the CHRDL1 gene and it is inherited as an X-linked recessive trait affecting only males. Here, we describe the results of phenotypic and genetic assessment in a novel XMC pedigree.
UNASSIGNED: Three subjects (a father and his two daughters) underwent a complete clinical and imaging ocular examination including biomicroscopy, fundoscopy, tonometry, visual acuity, Pentacam Scheimpflug imaging, anterior segment Swept Source OCT, and ultrabiomicroscopy. Genetic analysis was performed through whole exome sequencing in 3 family members. Candidate variants were validated by sanger sequencing.
UNASSIGNED: The affected father exhibited megalocornea, very deep anterior chambers, retrocorneal pigmentation, iris atrophy, queer iris configuration, extremely open iridocorneal angles, and cataracts. Notably, both daughters showed queer iris configuration and abnormally widely open iridocorneal angles in both eyes. Genetic analysis identified a novel hemizygous c.207+1G>A splicing variant in CHRDL1 in the affected father. Both mildly affected daughters were heterozygous for the pathogenic variant.
UNASSIGNED: Here, we report an additional XMC family due to a novel mutation in the CHRDL1 gene. Mild anterior segment anomalies were observed in two heterozygous carriers demonstrating for the first time a CHRDL1-linked phenotype in females. A detailed comparison of the clinical and genetic features of this pedigree with those observed in previously published XMC cases is also presented.

OBJECTIVE: The aim of the study was to describe the phenotype and molecular genetic causes of X-linked megalocornea (MGC1). We recruited four British, one New Zealand, one Vietnamese and four Czech families.
METHODS: All probands and three female carriers underwent ocular examination and Sanger sequencing of the CHRDL1 gene. Two of the probands also had magnetic resonance imaging (MRI) of the brain.
RESULTS: We identified nine pathogenic or likely pathogenic and one variant of uncertain significance in CHRDL1, of which eight are novel. Three probands had ocular findings that have not previously been associated with MGC1, namely pigmentary glaucoma, unilateral posterior corneal vesicles, unilateral keratoconus and unilateral Fuchs heterochromic iridocyclitis. The corneal diameters of the three heterozygous carriers were normal, but two had abnormally thin corneas, and one of these was also diagnosed with unilateral keratoconus. Brain MRI identified arachnoid cysts in both probands, one also had a neuroepithelial cyst, while the second had a midsagittal neurodevelopmental abnormality (cavum septum pellucidum et vergae).
CONCLUSIONS: The study expands the spectrum of pathogenic variants and the ocular and brain abnormalities that have been identified in individuals with MGC1. Reduced corneal thickness may represent a mild phenotypic feature in some heterozygous female carriers of CHRDL1 pathogenic variants.

Megalocornea and anterior megalophthalmos (megalocornea spectrum) disorders are typically defined by corneal diameter > 12.5 mm in the absence of elevated intraocular pressure. Clinical features overlap with keratoglobus but are distinct from buphthalmos and severe (globus) keratoconus. Megalocornea spectrum disorders and keratoglobus are primarily congenital disorders, often with syndromic associations; both can present with large and thin corneas, creating difficulty in diagnosis, however, only keratoglobus is typically progressive. Molecular genetics provide significant insight into underlying aetiologies. Nonetheless, careful clinical assessment remains intrinsic to diagnosis. Surgical management can be challenging due to the enlarged ciliary ring and weakened zonules in megalocornea spectrum disorders and the extreme corneal thinning of keratoglobus. In this review, the established literature on measurement of corneal diameter, diagnosis of megalocornea, anterior megalophthalmos and keratoglobus, differentiation from severe keratoconus, recent molecular genetics research and key surgical modalities in the management of these rare disorders are outlined and discussed.

Neonatal diabetes with congenital hypothyroidism (NDH) syndrome is a rare condition caused by homozygous or compound heterozygous mutations in the GLI-similar 3 coding gene GLIS3. Almost 20 patients have been reported to date, with significant phenotypic variability.
We describe a boy with a homozygous deletion (exons 5-9) in the GLIS3 gene, who presents novel clinical aspects not reported previously. In addition to neonatal diabetes, congenital hypothyroidism and other known multi-organ manifestations such as cholestasis and renal cysts, he suffered from hyporegenerative anemia during the first four months of life and presents megalocornea in the absence of elevated intraocular pressure. Compensation of partial exocrine pancreatic insufficiency and deficiencies in antioxidative vitamins seemed to have exerted marked beneficial impact on several disease symptoms including cholestasis and TSH resistance, although a causal relation is difficult to prove. Considering reports on persistent fetal hemoglobin detected in a few children with GLIS3 mutations, the transient anemia seen in our patient may represent a further symptom associated with either the GLIS3 defect itself or, secondarily, micronutrient deficiency related to exocrine pancreatic deficiency or cholestasis.
Our report expands the phenotypic spectrum of patients with GLIS3 mutations and adds important information on the clinical course, highlighting the possible beneficial effects of pancreatic enzyme and antioxidative vitamin substitutions on characteristic NDH syndrome manifestations such as TSH resistance and cholestasis. We recommend to carefully screen infants with GLIS3 mutations for subtle biochemical signs of partial exocrine pancreatic deficiency or to discuss exploratory administration of pancreatic enzymes and antioxidative vitamins, even in case of good weight gain and fecal elastase concentrations in the low-to-normal range.

We present a male infant with alveolar capillary dysplasia without misalignment of pulmonary veins, hyperinflammation, megalocornea and macrosomia/macrocephaly at birth. Whole-exome sequencing revealed a homozygous 2bp-insertion in the latent transforming growth factor-beta binding protein 2 (LTBP2) (c.278_279dup, p.(Ser94Glyfs*187)). So far, LTBP2-variants have been frequently reported with an eye-restricted phenotype including primary congenital glaucoma and megalocornea/microspherphakia and ectopia lentis with/without secondary glaucoma. Hitherto reported systemic phenotypes showed, among others, features as tall stature, finger anomalies, high-arched palate and cardiovascular anomalies. The main pathophysiological finding of our patient was an alveolar capillary dysplasia (with pulmonary arterial hypertension and right ventricular impairment but without misalignment of pulmonary veins) resulting in almost continuous oxygen demand and prolonged dependence on mechanical ventilation. He died of respiratory failure at the age of seven months. This patient may extend the LTBP2-related phenotype with resulting diagnostic implications.

The article presents a clinical case of bilateral cataract surgery on megalocornea eyes of a 20-year-old male. The Haigis formula has demonstrated the greatest potential accuracy for IOL calculation in such eyes, while the use of other formulas was associated with a higher risk of significant hyperopic refractive error. An unusually high level of pseudoaccommodation was obtained in both eyes.
В статье представлен клинический случай двусторонней хирургии катаракты на глазах с мегалокорнеа у молодого человека 20 лет. Выявлено, что наибольшей потенциальной точностью для расчета оптической силы интраокулярной линзы при мегалокорнеа обладает формула Haigis. При расчете по другим формулам велик риск значительной рефракционной ошибки в сторону гиперметропии. На обоих артифакичных глазах получен необычно высокий уровень псевдоаккомодации.