Novel disease-causing variants and phenotypic features of X-linked megalocornea.

PURPOSE: 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). CONCLUSION: 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.

Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN) in 10 Czech Gypsy children--frequent and underestimated cause of disability among Czech Gypsies.

BACKGROUND: Congenital Cataract Facial Dysmorphism and demyelinating Neuropathy (CCFDN, OMIM 604468) is an autosomal recessive multi-system disorder which was first described in Bulgarian Gypsies in 1999. It is caused by the homozygous founder mutation c.863 + 389C > T in the CTDP1 gene. The syndrome has been described exclusively in patients of Gypsy ancestry. The prevalence of this disorder in the Gypsy population in the Czech Republic and Central Europe is not known and is probably underestimated and under-diagnosed. METHODS: We clinically diagnosed and assessed 10 CCFDN children living in the Czech Republic. All patients are children of different ages, all of Gypsy origin born in the Czech Republic. Molecular genetic testing for the founder CTDP1 gene mutation was performed. RESULTS: All patients are homozygous for the c.863 + 389C > T mutation in the CTDP1 gene. All patients presented a bilateral congenital cataract and microphthalmos and had early cataract surgery. Correct diagnosis was not made until the age of two. All patients had variably delayed motor milestones. Gait is characteristically paleocerebellar in all the patients. Mental retardation was variable and usually mild. CONCLUSIONS: Clinical diagnosis of CCFDN should be easy for an informed pediatrician or neurologist by the obligate signalling trias of congenital bilateral cataract, developmental delay and later demyelinating neuropathy. Our data indicate a probably high prevalence of CCFDN in the Czech Gypsy ethnic subpopulation.

Corneal changes assessed using confocal microscopy in patients with unilateral buphthalmos.

PURPOSE: To compare corneal structures in buphthalmic eyes and healthy eyes in patients with unilateral congenital glaucoma using a corneal confocal microscope. METHODS: Ten patients with unilateral buphthalmos (mean ± SD age, 14.85 ± 5.12 years) were examined using corneal confocal microscopy. The cell density and cell area of endothelial cells and superficial and basal epithelial cells and the number of keratocytes were evaluated. RESULTS: There was no significant difference between the cell density of superficial epithelial cells in buphthalmic eyes relative to healthy eyes (P = 0.1944). The cell density of basal epithelial cells was significantly higher (P = 0.0234) and the cell area was significantly smaller (P = 0.0181) in buphthalmic eyes relative to healthy eyes. There was no difference between the number of keratocytes in buphthalmic eyes and healthy eyes in the anterior stroma (P = 0.273) or in the posterior stroma (P = 0.0799). The cell density of endothelial cells was significantly lower and the cell area was significantly larger in buphthalmic eyes relative to healthy eyes (P = 0.0009). CONCLUSIONS: We demonstrated a lower cell density of endothelial cells in buphthalmic eyes. We found no differences in keratocyte density between the buphthalmic eyes and healthy eyes. The cell density of basal epithelial cells was higher in buphthalmic eyes. These differences could be due to buphthalmos or due to the previous surgical and medical therapies. Monitoring of these changes could help to contribute to accurate assessments regarding future ocular surgical procedures.

The retinal nerve fibre layer thickness in glaucomatous hydrophthalmic eyes assessed by scanning laser polarimetry with variable corneal compensation in comparison with age-matched healthy children.

PURPOSE: To compare the thickness of the retinal nerve fibre layer (RNFL) in hydrophthalmic glaucomatous eyes in children with age-matched healthy controls using scanning laser polarimetry with variable corneal compensation (GDxVCC). METHODS: Twenty hydrophthalmic eyes of 20 patients with the mean age of 10.64 ± 3.02 years being treated for congenital or infantile glaucoma were included in the analysis. Evaluation of RNFL thickness measured by GDxVCC in standard Temporal-Superior-Nasal-Inferior-Temporal (TSNIT) parameters was performed. The results were compared to TSNIT values of an age-matched control group of 120 healthy children published recently as referential values. The correlation between horizontal corneal diameter and RNFL thickness in hydrophthalmic eyes was also investigated. RESULTS: The mean ± SD values in TSNIT Average, Superior Average, Inferior Average and TSNIT SD in hydrophthalmic eyes were 52.3 ± 11.4, 59.7 ± 17.1, 62.0 ± 15.6 and 20.0 ± 7.8 µm, respectively. All these values were significantly lower compared to referential TSNIT parameters of age-matched healthy eyes (p = 0.021, p = 0.001, p = 0.003 and p = 0.018, respectively). A substantial number of hydrophthalmic eyes laid below the level of 5% probability of normality in respective TSNIT parameters: 30% of the eyes in TSNIT average, 50% of the eyes in superior average, 30% of the eyes in inferior average and 45% of the eyes in TSNIT SD. No significant correlation between enlarged corneal diameter and RNFL thickness was found. CONCLUSIONS: The mean values of all standard TSNIT parameters assessed using GDxVCC in hydrophthalmic glaucomatous eyes in children were significantly lower in comparison with referential values of healthy age-matched children.

Central corneal thickness in microphthalmic eyes with or without history of congenital cataract surgery.

PURPOSE: To determine the central corneal thickness (CCT) in microphthalmic aphakic or pseudophakic eyes as well as in microphthalmic eyes without any history of eye surgery. METHODS: Thirty-two patients with a mean age of 6.41±5.24 years after congenital cataract surgery with absolute microcornea, i.e., horizontal corneal diameter (HCD)<10 mm, or relative microcornea, i.e., HCD 10-11 mm but in the affected eye at least 0.5 mm smaller compared to the fellow eye, formed group A. Thirteen patients of mean age 0.94±1.22 years with absolute or relative microcornea plus another developmental anomaly of an eye without any history of eye surgery formed group B. The patients with corneal edema or scars were excluded. The control group consisted of 124 healthy school-aged children. Horizontal corneal diameter was measured with caliper and CCT with an ultrasound pachymeter. In infants, these measurements were performed under general anesthesia. RESULTS: In 48 eyes in group A and in 16 eyes in group B, the mean CCT was 635.13±65.35 µm and 642.31±93.07 µm, respectively, which was significantly greater (p<0.0001 and p=0.0018) in comparison with the mean CCT (553.58±33.12 µm) in the control group. Regression curve demonstrated the significant increase of CCT values along with the decrease of HCD in microphthalmic eyes. CONCLUSIONS: Small corneas in microphthalmic eyes either with or without congenital cataract surgery have significantly higher CCT. The results demonstrate significant negative correlation between horizontal corneal diameter and CCT.

The occurrence and features of the atypical birefringence pattern in scanning laser polarimetry using GD × VCC in healthy children and its impact on the retinal nerve fiber layer thickness values.

PURPOSE: To investigate the occurrence and features of the atypical birefringence pattern (ABP) images in scanning laser polarimetry with variable corneal compensation (GD×VCC) in healthy children and to assess their impact on the values of the retinal nerve fiber layer (RNFL) thickness. METHODS: GD×VCC scans in 120 healthy white school-aged children with mean age ± standard deviation (SD) 12.85 ± 3.0 years were evaluated using typical scan score (TSS) calculation and by subjective grading of the scans. Statistical analysis including the impact of ABP on the RNFL thickness in GD × VCC Temporal-Superior-Nasal-Inferior-Temporal (TSNIT) parameters was done. RESULTS: The ABP was found in 18 out of 120 patients (15%) at cut-off value of TSS <80. Subjective evaluation of the scans raised the frequency of ABP to 20% of patients. The mean ± SD values of TSNIT Average, Superior Average, and Inferior Average in 26 eyes with ABP versus 214 eyes with normal birefringence pattern were 66.99 ± 7.29 µm versus 58.00 ± 6.22 µm (P = 7.2E to -11), 78.43 ± 9.27 µm versus 72.33 ± 8.72 µm (P = 0.001) and 80.87 ± 12.01 µm versus 70.00 ± 10.20 µm (P = 0.000001), respectively. The same comparison in TSNIT SD showed minimal difference and was 25.42 ± 5.84 µm versus 26.41 ± 4.81 µm (P = 0.41). CONCLUSIONS: The occurrence of ABP in children is not rare and may significantly distort the measured values of the RNFL thickness in TSNIT parameters using GD × VCC.

[Two types of CMV ocular complications in patients with HIV infection]. / Dva typy cytomegalovirového postizení oka u pacientu s HIV infekcí.

CMV retinitis is the most serious ocular complication of AIDS. Introduction of the combination antiretroviral therapy markedly reduced the occurrence of CMV retinitis, on the other hand it brought a new ocular complication - CMV uveitis. CMV uveitis is an immunopathological inflammatory reaction associated with the immune reconstitution inflammatory syndrome, which is a side effect of successfully initiated cART. These two forms of CMV ocular complications differ in pathogenesis, symptomatology and therapy. The CMV retinitis is treated with anti-CMV virostatics whereas the therapy of CMV uveitis is based on attenuation of the inflammatory reaction by administration of corticosteroids. The optimal prevention of both complications is an early initiation of cART before the CD4+ T lymphocytes drop below 200/microl.

Retinal nerve fiber layer assessment in healthy children using scanning laser polarimetry with variable corneal compensation.

PURPOSE: To assess the normative data of the retinal nerve fiber layer (RNFL) thickness in healthy children using the scanning laser polarimeter with variable corneal compensation (GDxVCC). METHODS: Of the 186 enrolled white school-aged children, 120 subjects of the mean 12.85 +/- 3.0 years (age +/- SD) fulfilled inclusion criteria. After complete ophthalmic examination, including GDxVCC, 240 normal eyes were analyzed. Evaluation of RNFL thickness in GDxVCC temporal-superior-nasal-inferior-temporal (TSNIT) parameters was performed, and probability of normality was calculated. The influence of sex and age was investigated. RESULTS: The mean +/- SD values in TSNIT Average, Superior Average, Inferior Average, and TSNIT SD were 58.98 +/- 6.92 microm, 72.99 +/- 8.97 microm, 71.18 +/- 10.92 microm, and 26.30 +/- 4.92 microm. The values of 5% probability of normality in the same order were 47.6 microm, 58.2 microm, 53.2 microm, and 18.2 microm. The mean values of Inferior Average and TSNIT SD were greater in left eyes by 1.84 +/- 6.6 microm (p = 0.003) and by 3.04 +/- 3.8 microm (p < 0.00005), respectively. No correlation to sex and age was found. CONCLUSIONS: RNFL thickness assessed using GDxVCC was greater in children compared with previous published data in healthy adults. The values of Inferior Average and TSNIT SD were significantly greater in left eyes.

Results of the modified trabeculotomy in the treatment of primary congenital glaucoma.

PURPOSE: To evaluate the effect of trabeculotomy employing probes with curvatures more closely corresponding to variable course of Schlemm's canal. METHODS: Forty-six children with primary congenital glaucoma who underwent trabeculotomy with newly designed probes between 1990 and 1998 were evaluated retrospectively. One set of the newly designed instruments consists of 3 pairs of trabeculotomy probes, the curvatures of which correspond to corneal diameters of 10, 12, and 14 mm. The criteria for surgical success were intraocular pressure (IOP) below 21 mmHg and simultaneous absence of cup to disc (C/D) ratio progression and of disproportional enlargement of the cornea. RESULTS: Forty-six children who underwent surgery over the course of 7 years were evaluated in a follow-up period from 7 to 83 months (38.4 +/- 22.5 months). A total of 102 trabeculotomies were performed in a total of 78 eyes, with the following complications: 8 large intraoperative hemorrhages, 3 small iris prolapses, 2 small descemetolyses, and 1 short iridodialysis. Postoperatively, glaucoma was successfully controlled in 68 eyes (87%), IOP fell in average from 30.81 +/- 6.55 mmHg to 16.32 +/- 5.13 mmHg (P <.00005). Visual acuity was better than 0.4 in 50 eyes and worse than 0.1 in 5 eyes at the end of the study. CONCLUSION: The probing of the Schlemm's canal was feasible in all procedures and the number of complications was low. The success rate of surgery was high. Adaptation of the trabeculotomy probes to the Schlemm's canal curvature seems to make probing easier and safer.