Ocular Features in 16 Brazilian Patients with Williams-Beuren Syndrome

Objectives: Williams-Beuren Syndrome (WBS) is a multisystem disorder caused by the deletion of contiguous genes on chromosome 7q11.23. Ophthalmologic abnormalities and deficits in visual motor integration are important features of WBS. Here we describe our experience with Brazilian WBS patients and their ophthalmologic features.

Methods: Sixteen patients with confirmed WBS went through thorough ophthalmologic examination.

Results: The most frequent ocular findings in our group of patients were stellate iris pattern (81.2%), hyperopic astigmatism (50%), hyperopia (37.5%), tortuosity of retinal vessel (37.5%) and strabismus (18.7%).

Conclusions: This is the second report of ophthalmologic abnormalities in a group of Brazilian individuals with WBS. It is extremely valuable that specific populations are studied so that clinical diagnosis can be refined and management of patients can be driven to the most common presentations of the disease.     

A Case of Unusual Coexistence of Keratoconus and Optic Disc Pit

Abstract

Purpose: To report a case of unusual coexistence of keratoconus and optic disc pit. Methods: A 29-year-old male patient followed up because of the left established and right subclinical keratoconus presented with blurred vision on the left eye that occurred within days. In addition to a comprehensive ophthalmic examination, computerized corneal topography (CT), corneal pachymetry, and optical coherence tomography (OCT) examination were performed. Results: The corneal CT showed a mild keratoconus pattern, with a minimum corneal pachymetry of 472 in the right eye and moderate keratoconus pattern with a minimum pachymetry of 435 micron in the left eye. The OCT scans showed the presence of the optic disc pit and related maculopathy. Conclusions: This is the second report of the coexistence of keratoconus and optic disc pit in the literature. The association of these two entities is therefore less likely to be accidental. Further histopathological studies will be necessary to explain this relationship between two entities.     

Sturge-Weber Syndrome Associated with Early Diffuse Choroidal Hemangiaoma： A Case Report

Purpose:To report indocyanine green angiography (ICGA) findings in one patient of diffuse choroidal hemangioma associated with Struge-Weber syndrome. Methods: Color fundus photography, fluorescein angiography (FA) and ICGA were performed in a patient with diffuse choroidal hemangioma associated with Sturge-Weber syndrome, Results: Three findings were unveiled by ICGA : rapid filling of diffuse choroidal hemangio‘s vascular network in the early stages; diffuse hyperfluorescence visual up to the late phase; no “wash-out“ phenomenon was observed in the late phase. Conclusion:Indocyanine green angiography can provide information that is not detected by clinical or fluorescence angiographic examination in the patient with Sturge-Weber syndrome. ICGA may be important and sensitive in detecting the diffuse choroidal hamangioma associated with Sturge-Weber syndrome. Eye Science 2004:20:168-170     

表面角膜镜片术治疗圆锥角膜的初步评价

采用自制冷冻车床加工切削角膜成为平镜治疗５例角膜中央无瘢痕形成的圆锥角膜，平均随访０．５－１年，全部透明成功，角膜曲率明显减少，裸眼视力提高，矫正视力０．２、０．４和０．８各１例，０．６的２例，该５例例为初步尝试。认为表面阄片术为治疗圆锥角膜提供了一种理想、安全、有效的手术方法。     

Keratoconus: A biomechanical perspective on loss of corneal stiffness

Keratoconus (KC) is progressive disease of corneal thinning, steepening and collagen degradation. Biomechanics of the cornea is maintained by the intricate collagen network, which is responsible for its unique shape and function. With the disruption of this collagen network, the cornea loses its shape and function, resulting in progressive visual degradation. While KC is essentially a stromal disease, there is evidence that the epithelium undergoes significant thinning similar to the stroma. Several topographical approaches have been developed to detect KC early. However, it is now hypothesized that biomechanical destabilization of the cornea may precede topographic evidence of KC. Biomechanics of KC has been investigated only to a limited extent due to lack of in vivo measurement techniques and/or devices. In this review, we focus on recent work performed to characterize the biomechanical characteristics of KC.     

A Case of 22q11.2 Deletion Syndrome with Right Microphthalmia and Left Corneal Staphyloma

Abstract

Background: A microdeletion in the chromosome 22q11.2 (DiGeorge or velocardiofacial syndrome) is the most common human deletion syndrome. Patients with 22q11.2 deletion may have a wide range of ocular findings but severe ocular involvement is uncommon. Here, we describe a 2-year-old boy who had growth retardation, developmental delay, right renal agenesis, ventricular septal defect and severe bilateral ocular anomalies.

Materials and methods: The systemic and ocular findings and cranial magnetic resonance imaging study results were reviewed. Fluorescence in situ hybridization analysis was performed on his peripheral blood.

Results: The patient presented with the oculodigital sign. On examination, he had severe right microphthalmia with no light perception and his left eye could not fix and follow. The left eye had anterior segment dysgenesis, mild sclerocornea, corneal staphyloma and congenital aphakia. Systemic findings included growth deficiency, microcephaly, micrognathia, ventricular septal defect, atrial septal defect and right renal agenesis. Fluorescence in situ hybridization analysis of this patient was significant for a heterozygous deletion covering DiGeorge critical region 2 and spanning a 250?kb region in the 22q11.2 locus.

Conclusion: The 22q11.2 deletion syndrome may be associated with severe bilateral ocular malformations including microphthalmia, sclerocornea, corneal staphyloma, anterior segment dysgenesis and congenital aphakia. Corneal staphyloma might have resulted from the oculodigital phenomenon or increased intraocular pressure.     

A Patient with Keratoconus,Nanophthalmos, Lipodermoids,and Pigmentary Retinopathy

A 44-year-old male with no pertinent history other than poor vision for more than 25 years was examined. Best corrected visual acuity was 20/80 OD [MR: +14.25 +1.00?×?15°] and 20/200 OS [MR: +15.00 +1.50?×?175°]. Significant limitation in ocular movements and the presence of an orbital lipodermoid in the infero-temporal aspect of each eye were noted. Forced duction test was positive for the same directions of limitation indicating possible extraocular muscle fibrosis. Ophthalmoscopy was remarkable for the presence of peripheral bony spicules. Corneal topography was compatible with keratoconus (K_max?=?55.04D OD and 52.87D OS). A-scan revealed axial lengths of 16.96?mm OD and 16.32?mm OS, compatible with a diagnosis of nanophthalmos. OCT revealed diffuse macular thickening for both eyes with foveal thickness of 350?µm OD and 353?µm OS. Over the next 12 years the patient had stable visual acuity, manifest refractions and anterior segment examination. Ophthalmoscopy revealed only minimal progression of pigmentary changes. We report the first case of these simultaneous multiple findings which may refer to a possible syndromic association of congenital or early childhood onset.     

Polymorphism Analysis of VSX1 and SOD1 Genes in Greek Patients with Keratoconus

Background: A number of mutations in the VSX1 and SOD1 genes have been reported to be associated with keratoconus (KC), however the results from different studies are controversial. In this study, we conducted the genotyping of common polymorphisms [VSX1: D144E, H244R, R166W, G160D; SOD1: intronic 7-base deletion (c.169?+?50delTAAACAG)], in a case–control sample panel of the Greek population.

Materials and methods: A case–control panel, with 33 KC patients and 78 healthy controls, were surveyed. DNA from each individual was tested for the VSX1: D144E, H244R, R166W, G160D and SOD1: intronic 7-base deletion (c.169?+?50delTAAACAG) polymorphisms by direct sequencing.

Results: We observed no polymorphisms of the VSX1 gene in the case–control panel. Concerning the SOD1 intronic 7-base deletion (c.169?+?50delTAAACAG), our findings suggest that heterozygous carriers are over-represented among KC cases compared to healthy controls (p?=?0.002).

Conclusions: We cannot confirm the previously reported association of the polymorphism in the VSX1 gene with KC. Our results suggest a possible causative role of SOD1 in the pathogenesis of KC. Further studies are required to identify other important genetic factors involved in the pathogenesis and progression of KC.     

Scleritis Associated with SAPHO Syndrome: A Case Report

A 31-year-old woman developed bilateral painful red eyes. A slit-lamp examination revealed anterior diffuse scleritis. She had been diagnosed with palmoplantar pustulosis 2 years before. Further evaluation revealed hyperostosis of the sacroiliac joint and inflammation of the bilateral sternoclavicular joints and right sternocostal joint. Ultimately, she was diagnosed with SAPHO syndrome by rheumatologists after excluding other causative diseases. Scleritis associated with SAPHO syndrome is relatively uncommon. An identification of any systemic symptoms and early consultation with rheumatologists are key to making an early and correct diagnosis.     

应用Corvis ST新参数分析圆锥角膜生物力学特性

目的：:应用可视化角膜生物力学分析仪（Corvis ST）新参数分析临床期圆锥角膜、亚临床期圆锥角膜及正常角膜的生物力学特性,评价其在圆锥角膜诊断中的价值。方法：:病例对照研究。选取2019年1月至2021年1月在襄阳爱尔眼科医院就诊的圆锥角膜患者68例（68眼）,其中亚临床期圆锥角膜（SKC）28例（28眼）为SKC...     

The Effect of Corneal Epithelium on Corneal Curvature in Patients with Keratoconus

Abstract

Objective: To investigate the effects of corneal epithelium on corneal curvature in patients with keratoconus. Design: This is a prospective, nonrandomized study. Participants: Fifty-nine eyes of 47 patients diagnosed as keratoconus and for whom corneal collagen crosslinking (CXL) was recruited in this study. Methods: This study is a single-center clinical trial. Pregnancy, lactation, connective tissue disease, corneal thickness below 350?μm, severe dry eyes, or scar of corneal surgery were exclusion criteria. Before and during CXL procedure after removing the corneal epithelium, maximum values of corneal apical curvature, simulated keratometry 1 (Sim-K1), simulated keratometry 2 (Sim-K2), temporal and inferior curvature values, all of which are 1.5?mm from the corneal center, were calculated. These values before and after removal of epithelium were compared statistically. Results: Mean age of patients was 23.30?±?5.5 (12–38) years. Twenty-eight (59%) were male while 19 (41%) were female. Mean values measured before and after removing the corneal epithelium were: apical curvature; 59.19?±?7.2 (47.06–82.40) diopter (D) and 61.70?±?8.8 (49.19–92.66) D (p?=?0.001), SimK1; 47.57?±?4.3 (39.14–64.57) D and 48.23?±?4.3 (41.89–66.70) D (p?=?0.001), SimK2; 52.04?±?5.3 (43.56–69.34) D and 53.34?±?5.6 (43.73–70.89) D (p?=?0.001), inferior curvature; 53,85?±?5.2 (43.47–76.56) D and 55.05?±?5.8 (44.56–81.93) D (p?=?0.002), temporal curvature 49.49?±?5.1 (41.50–71.03) D and 51.53?±?5.4 (41.58–73.34) D (p?=?0.001), respectively. Conclusions: In keratoconus patients during CXL treatment, after removing the corneal epithelium, more steepness is detected in the curvature of the steeper area of the cornea. When evaluating patients with keratoconus, the masking effect of corneal epithelium on values of curvature should be taken into consideration.     

Insufficient Dose of ERCC8 Protein Caused by a Frameshift Mutation Is Associated With Keratoconus With Congenital Cataracts

PurposeThe purpose of this study was to identify a new candidate gene for keratoconus and congenital cataracts and further investigate its underlying pathogenic mechanisms.MethodsThis study, using a Chinese family with keratoconus and congenital cataracts, 262 patients with sporadic keratoconus, and 20 patients with sporadic congenital cataract as subjects, used clinical and genetic analysis and in vitro cell experiments to detect genetic mutations and further investigate the underlying pathogenic mechanisms.ResultsWe found that a novel frameshift mutation of ERCC8 (NM_000082.3: c.394-398del, p. L132Nfs*6) is responsible for familial keratoconus with congenital cataracts. This mutation showed co-segregation with the phenotype in the family. This was revealed in another patient with sporadic keratoconus, absent in the 210 unrelated health controls, and considered to be “disease-causing.” ERCC8 was expressed both in the cornea and lens. Through an in vitro cell experiment, we further demonstrated that the mutant proteins of ERCC8 were degraded and could lead to an insufficient dose of the ERCC8 protein. An insufficient dose reduced the DNA damage repair ability of human corneal fibroblast (HTK) and lens epithelial cells (HLEC) treated with hydrogen peroxide, leading to both cells showing higher DNA damage levels. In addition, it decreased cell viability, resulting in decreased collagen expression in HTK and increased apoptosis in HLEC via aberrant activation of the unfolded protein response. All these results suggested that ERCC8 plays an important role in the normal function of corneal stromal and lens epithelial cells.ConclusionsOur study showed that ERCC8 is a new gene associated with keratoconus and congenital cataracts.  Chinese Abstract     

基于双通道技术的视觉质量分析系统在评估轻度圆锥角膜视觉质量中的应用

探讨视觉质量分析系统（OQAS）测量圆锥角膜眼与正常角膜眼之间视觉质量的差异。方法：横断面研究。选取正常角膜屈光不正患者32例（32眼）作为对照组,圆锥角膜患者27例（27眼）作为圆锥角膜组。采用OQAS测量每组在3、4、5 mm的人工瞳孔直径下的视觉质量参数调制传递函数截止频率（MTFcutoff）、Strehl比、不同对比度下的OQAS值（OV-100、OV-20、OV-9）,组间差异采用独立样本t检验或Mann-Whitney U检验,组内差异采用重复测量资料方差分析及Bonferroni校正。结果：圆锥角膜组在人工瞳孔分别为3、4、5 mm时的MTFcutoff、Strehl比、OV-100、OV-20、OV-9均低于对照组（3 mm：t=6.658、6.695、6.660、6.493、6.778;4 mm：t=7.106、6.567、7.109、6.802、6.788; 5 mm：t=6.148、7.254、6.158、6.446、7.210;P均<0.001）。对照组及圆锥角膜组内MTFcutoff、Strehl比、 OV-100、OV-20、OV-9 在不同人工瞳孔大小的组内比较差异有统计学意义（对照组：F=42.205、 28.335、42.559、32.621、30.372;圆锥角膜组：F=15.732、11.533、15.625、13.870、10.495;均 P<0.001）。结论：双通道OQAS测量结果表明圆锥角膜的视觉质量较正常眼明显下降,圆锥角膜及正常眼的视觉质量均随着瞳孔增大而下降。     

Case report of a PRDM5 linked brittle cornea syndrome type 2 in association with a novel SLC6A5 mutation

A 3-year-old girl presenting with blue sclera, hyperlaxity and developmental dysplasia of hip was found to have bilateral corneal thinning with astigmatism and keratoconus. By clinical exome sequencing, a frameshift mutation c.713_716 del TTTG p.(Val238Alafs*35) in PRDM5 gene causing brittle cornea syndrome 2 and a novel frameshift mutation c.401dup p.(Ser135Glufs*53) in SLC6A5 gene causing Hyperekplexia 3 were identified. No features of hyperekplexia were identified in proband. The novel homozygous mutation of SLC6A5 gene in the proband was presently asymptomatic but they were apprised of the possibility of developing neurological symptoms in the later years.     

Polymorphism Analysis of COL4A3 and COL4A4 Genes in Greek Patients with Keratoconus

Abstract

Background: In this study, we conducted the genotyping of D326Y in COL4A3 and M1327V, as well as F1644F in COL4A4 polymorphisms, in a case–control sample panel of Greek origin population.

Materials and Methods: A case–control panel, with 45 keratoconus (KC) patients and 78 healthy controls, were surveyed. DNA from each individual was tested for the D326Y in COL4A3 and M1327V, as well as F1644F in COL4A4 polymorphisms by direct sequencing.

Results: When analyzing the Hardy-Weinberg equilibrium, we observed no significant deviation from expected numbers in both KC patients and controls. The genotype frequencies in the polymorphisms tested were not found to be significantly associated with KC development risk. The M1327V AA and F1644F TT genotypes were significantly over-represented in healthy individuals.

Conclusions: We could hypothesize that mutations in COL4A3 and COL4A4 genes are not involved in KC risk in Greek population. Nevertheless, the M1327V AA and F1644F TT genotypes were significantly over-represented in healthy individuals, suggesting a protective role of these genotypes in KC development risk in our population.     

A Case of Susac Syndrome

The purpose of this article is to report on the first known Korean case of Susac syndrome. An 18-year-old female came to our clinic reporting blurred vision of the left eye for 2 days. She also complained of decreased hearing with tinnitus of the right ear and mild headache. She was previously healthy and had no remarkable medical history. Best-corrected visual acuity was 20 / 50 in the left eye and 20 / 20 in the right eye. An axiomatic triad of ocular, cochlear, and neurologic involvement was observed in the patient. Fluorescein angiography showed branched retinal arterial occlusions in the left eye. A sudden right sensorineural hearing loss was observed on audimetry. Magnetic resonance images showed a hyperintense lesion in the white matter around the corpus callosum. The patient was treated with high doses of systemic corticosteroids, and no neuropsychological sequelae were observed. This is the first case report of Susac syndrome in Korea. In cases of retinal arterial occlusion with hearing loss or neuropsychological symptoms, Susac syndrome should be suspected.     

Juxtafoveolar Telangiectasis Associated with Crest Syndrome

Purpose: To report a case of CREST syndrome associated with juxtafoveolar telangiectasias (JT). Design: Case report. Methods: Observational case report. Results: A 64-year-old woman affected with CREST syndrome developed bilateral visual loss. Capillary dilatation and permeability changes in the outer retina were noticed during an angiographic study. Optical coherence tomography (OCT) showed thickening with loss of the foveal depression and inner lamellar cyst. The patient was diagnosed as stage 3, group 2A JT associated with CREST syndrome. Conclusions: Finding JT in association with CREST syndrome suggests a common pathophysiologic process.     

Papilledema Associated with Dialysis Disequilibrium Syndrome

The purpose of this paper is to report a case of dialysis disequilibrium syndrome as an unusual cause of papilledema. A 38-year-old woman with type 1 diabetes mellitus presented with decreased visual acuity and bilateral optic nerve swelling associated with systemic signs and symptoms of dialysis disequilibrium syndrome. Repeated lumbar punctures revealed elevated intracranial pressures. She was placed on acetazolamide with some improvement in symptoms. After renal transplantation, the patient had complete resolution of headaches, nausea and the papilledema. Our conclusion is that patients with visual disturbance and focal neurological symptoms during and after hemodialysis should be suspected of having dialysis disequilibrium syndrome (DDS). DDS is thought to occur as a result of a rapid reduction in plasma osmolality during dialysis. As the shift of urea from cerebral spinal fluid (CSF) is delayed, the relative increase in CSF osmolality draws fluid into the brain. The ensuing cerebral edema is responsible for the characteristic neurological symptoms. We report the association of papilledema with this syndrome, and caution as to the possible concurrent risk of permanent visual impairment.     

A Case of 22q11.2 Deletion Syndrome with Peters Anomaly,Congenital Glaucoma,and Heterozygous Mutation in CYP1B1

We read with interest the recent publication by Tarlan and colleagues1 Tarlan B, Kiratli H, Kilic E, et al. A case of 22q11.2 deletion syndrome with right microphthalmia and left corneal staphyloma. Ophthalmic Genet 2013; [Epub ahead of print][PubMed], [Web of Science ®] , [Google Scholar] describing a patient with 22q11.2 deletion syndrome and ocular features of right microphthalmia and left anterior segment dysgenesis. While anterior segment dysgenesis disorders are occasionally reported with 22q11.2 deletions,2–5 Casteels I, Devriendt K. Unilateral Peters’ anomaly in a patient with DiGeorge syndrome. J Pediatr Ophthalmol Strabismus 2005;42:311–313 Binenbaum G, McDonald-McGinn DM, Zackai EH, et al. Sclerocornea associated with the chromosome 22q11.2 deletion syndrome. Am J Med Genet A 2008;146:904–909 Casteels I, Casaer P, Gewillig M, et al. Ocular findings in children with a microdeletion in chromosome 22q11.2. Eur J Pediatr 2008;167:751–755 Erdogan MK, Utine GE, Alanay Y, Aktas D. Unilateral Peters’ anomaly in an infant with 22q11.2 deletion syndrome. Clin Dysmorphol 2008;17:289–290  this remains a rare association. We report here an 8-year-old patient with 22q11.2 deletion syndrome and bilateral Peters anomaly with congenital glaucoma; in addition, our patient was found to have a single heterozygous mutation in CYP1B1, c.83C?>?T, p.(Ser28Trp).     

High Myopia Associated with Triple X Syndrome

We report our findings in a 3-year-old girl who was suspected of having triple X syndrome because she was taller than +4.35 standard deviations for her age. She also had high myopia. Optical coherence tomography (OCT) showed that her retinas were thin, the lenses were subluxated, and the axial length was elongated. Our findings indicate that for a female child with tall stature, there should be thorough evaluations for endocrinological disorders, overgrowth syndromes, connective tissue disorders, and genetic disorders. If there are also behavioral issues, this may lead to consideration of 47 XXX in a female or 47 XXY in a male infant. The 47 XXX syndrome is a potential and neglected cause for tall stature and requires a high index of suspicion.