Zonula Research Articles

Miyake-Apple view of inner side of sclerotomy during microincision vitrectomy surgery

To examine the inner surface of the sclerotomy during microincision vitrectomy surgery by Miyake-Apple view. The anterior half of porcine eyes was attached to a transparent acrylic plate with cyanoacrylate glue. Then, either a 23-gauge or a 25-gauge trocar-cannula was inserted through the sclera obliquely. The inner surface of the entrance site was observed posteriorly by Miyake-Apple view. These images were compared with the endoscopic view of two patients who underwent vitreous surgery for an epiretinal membrane. When the trocar-cannula was inserted obliquely, the Miyake-Apple view showed that the ciliary epithelium at the sclerotomy site was stretched. When the trocar-cannula was inserted vertically, the ciliary epithelium was folded, and the folds remained even after the trocar was removed. Vitreous strands were seen incarcerated into the sclerotomy site. In human eyes, a folding of the ciliary epithelium was not clearly seen with the endoscopic view but the incarcerated vitreous was seen. The Miyake-Apple view provided a precise, in vivo, observation of the inner surface of the entry site. It disclosed the morphological stress on the ciliary epithelium by the sclerotomy.

Late capsular bag contraction and intraocular lens subluxation in retinitis pigmentosa: a case report

IntroductionRetinitis pigmentosa is clinically characterized by loss of predominantly rod photoreceptor function as well as loss of peripheral vision. The classic clinical triad is considered to be the presence of bone spicule pigmentation in the peripheral retina, arteriolar attenuation, and waxy disc pallor. Cataracts, most commonly of the posterior subcapsular type, are often found in all forms of retinitis pigmentosa. Ectopia lentis and lens dislocation are known risk factors for those with retinitis pigmentosa, presumably secondary to zonular fiber weakness and vitreous degeneration. The post-operative complication of lens dislocation following cataract extraction in patients with retinitis pigmentosa has also been documented.Case presentationWe report a case of severe capsular bag contraction with intraocular lens subluxation following cataract extraction in a 58-year-old Hispanic woman with retinitis pigmentosa.ConclusionPatients with retinitis pigmentosa undergoing cataract surgery should be notified of this potentially late complication of surgery.

Biological characterization of cultured rabbit corneal endothelial cells

Background How to harvest the purified corneal endothelial seed cells is very important for the corneal tissue engineering technology. Herein,to establish a good culture method and effective identification method of corneal endothelial cells ( CECs) is the key. Objective Present study wag to establish the cultivating and identifying approach of the rabbit CECs and detect the biological characteristics of passaged cells. Methods Rabbits CECs were isolated from Descemet's membrane peeled off completely in 30 New Zealand white rabbits and then digested with 0. 25% trypsin-0. 02% EDTA and primarily cultured in CECs medium containing 15% fetal bovine serum. The growth situate and cellular morphology of rabbit CECs were observed under the inverted phase-contrast microscope following the alizarin red staining. Rabbit CECs were identified by cellular morphology as well as in gene and protein level, including the detection of expressions of collagen type IV α2(COL4A2) ,vascular endothelial growth factor receptor 2 ( FLK1 ) , Na+-K+ ATPase alpha 1 subunit ( ATP1 A1 ) , aquaporin 1 ( AQP1 ) , voltage-dependent anion channels ( VDACs) by reverse transcription-polymerase chain reaction ( RT-PCR ). The expression and distribution of neurone specific enolase ( NSE) , Na+-K+ ATPase, zonula occludens-1 ( ZO-1 ) were also detected by immunocytochemistry under the fluorescence microscope. The proliferation activity of the passage cells was dynamically observed by MTT assay,and Na+-K+ ATPase activity of different generations cells was detected by ATPase kit. Results Majority of the primarily cultured cells adhered in 24 hours, infused in 2-3 days with the hexagon shape in appearance. The morphology of the cells was very varied with passage. Alizarin red staining showed a well- defined and well-lined cellular morphology similar to the corneal cells in vivo. Target genes of C0L4A2, FLK1, ATPIAI ,AQPI and VDACs were positively expressed in the cells. However,the expression of CK12 was absent in the cells. NSE, Na+-K+ ATPase, ZO-1 positive cells were respectively observed under the laser confocal scanning microscopy. MTT results showed a gradually low growth curve with the passage. Quantitative results also revealed that the Na+-K+ ATPase activity was gradually declined in different generations of cells ( F = 77. 174, P = 0. 000 ). Conclusion The enzyme digestion is a better approach of isolating and culturing comeal endothelial cells. Cultured cells can be identified by cells staining, gene expression and protein level. Earlier generation of CECs are ideal seed cells for cornea tissue engineering. Key words: Corneal endothelial cell; Cellular culture; Cellular identification; Tissue engineering; Na+-K+ ATPase

Occurrence of capsular delamination in the dislocated in-the-bag intraocular lens

To examine the lens capsules of dislocated in-the-bag IOLs. Retrospective case series. Nineteen dislocated IOLs encased in capsules (in-the-bag IOLs) from 19 patients were included. The clinical characteristics of the 19 patients were reviewed. The explanted in-the- bag IOLs were examined by scanning electron microscopy. Associated clinical conditions included pseudoexfoliation (PEX) in seven eyes, high myopia in three eyes, previous history of trauma in two eyes, previous vitreoretinal surgery in two eyes, retinitis pigmentosa in one eye and uveitis in one eye. PEX specimens showed capsular contraction, shrinkage of the diameter of the capsular bag and dehiscence of zonular fibers. The remaining 12 specimens exhibited slight capsular contraction that lacked shrinkage of the bag and exhibited capsular delamination at the equatorial region, in which the zonular fibers had completely disappeared. Capsular delamination as well as dehiscence of zonular fibers may be involved in the dislocation of in-the-bag IOLs.

Molecular characterization and structure determination of human ADAMTSL4

The thrombospondin type 1 repeat (TSR) is an ancient extracellular protein domain that is commonly found in invertebrate and vertebrate proteins. The ADAMTSL4 protein, also known as TSRC1, belongs to the TSR superfamily and has multiple thrombospondin repeats, most of which are clustered at the C-terminus. It has been reported that some TSP1 domain-containing proteins, e.g. thrombospondin 1 and thrombospondin 2, could induce apoptosis of endothelial cells but it is not clear how these proteins operate in death pathways. Our recent work shows that mutations in ADAMTSL4 are responsible for autosomal-recessive isolated ectopia lentis, i.e. abnormal positioning of the lens of the eye and affect the development of the zonular fiber. However, little is known about the function of ADAMTSL4. To shed more light on the function of the ADMTSL4 and its roles in different tissues we extended our work to carry out molecular characterization of this gene and its variants. We have obtained cDNA clones encoding the full ADAMTSL4 protein and its truncated isoform. Both are subcloned into the pET28a vector for expression in E. coli. In anticipation of possible expression challenges in this host, e.g. formation of inclusion bodies or lack of expression, we subcloned each fragment into the yeast vector, pYES2. The gene in both cases has been fused in frame with a region encoding an N-terminal His-Tag to facilitate the purification of the recombinant protein. DNA analysis indicates that each fragment has been correctly cloned into the pYES2 vector. Each construct was transformed into Saccharomyces cerevisiae for protein expression. Our preliminary analysis indicates that one of the genes is expressed in S. cerevisiae but at a very low level. Work to optimize the expression of ADAMTSL4 in yeast as well as in E. coli is in progress. We also extracted the seven domains of the ADAMTSL4 using PCR. Each domain was subcloned into the E. coli overexpression vector, pET28a. Expression studies of all the constructs have shown that the seven domains have been successfully overexpressed in E. coli. The overexpression was confirmed using Western blot techniques. The recombinant protein of each domain is purified for NMR and x-ray studies.

Intracapsular Organization of Ciliary Zonules in Monkey Eyes

Ciliary zonules are responsible for changing the curvature of a lens in the dioptric focus of an eye. Present established theory is based on the relaxation of zonular superficial fasciculi affixed to the capsular surface, thereby inducing the change of anterior- and posterior lens curvature causing spontaneous liquid movement of lens material. To achieve precise focusing at any distance, a more active functional organization should exist. The present studies were performed to determine not only the surface attachment but also the intracapsular affix of zonules on monkey eyes. In addition, the development of focusing in newborn and presbyopia is analyzed. Histology was prepared by conventional and molecular immunofluorescence stainings on the compositions of zonules with fibrillin-1 (FBN 1) and lens capsule with collagen IV (COL IV), and in situ hybridization (ISH) analyses on frozen sections. Superficial circumferential attachments of zonule were found radially oriented between ciliary processes and anterior/posterior lens capsules forming a triangular figure. Two functional intralayer integrations were found above them; anterior-posterior crossed fibers over the equator and radial fibers distributed toward the anterior or posterior polar areas. These fibers were bound tightly to the deep layer connective tissues close to the lens epithelium. Fine zonular fibers were aggregated, gradually forming bundles and bifurcated again on the way to the capsule. The lateral striped staining pattern in bundles suggested their elastic nature. Response of α-helixes of collagen IV immunostaining was more positive on α-1,2,4 than α-3,5,6 on anterior- and posterior lens capsules. Newborn eyes revealed not fascicular but fine membranous zonules on the lens surface and small ciliary processes. ISH analysis revealed high synthetic expression of FBN 1 mRNA in cytoplasm of nonpigmented epithelial cells of ciliary processes. The synthetic expression of FBN 1 declined with aging. According to the mechanism of accommodation, active dynamic movement of anterior or posterior capsules play the main role of changing the lens configuration by two intralayer zonular integrations, including anterior-posterior crossed fibers over the equator and radial fibers toward anterior or posterior polar areas acting with coordinated contraction of circular or longitudinal ciliary muscles. The developmental change on focusing is brought about by synthesis of FBN 1 in the newborn eye.

A homozygous mutation in LTBP2 causes isolated microspherophakia

Microspherophakia is an autosomal-recessive congenital disorder characterized by small spherical lens. It may be isolated or occur as part of a hereditary systemic disorder, such as Marfan syndrome, autosomal dominant and recessive forms of Weill-Marchesani syndrome, autosomal dominant glaucoma-lens ectopia-microspherophakia-stiffness-shortness syndrome, autosomal dominant microspherophakia with hernia, and microspherophakia-metaphyseal dysplasia. The purpose of this study was to map and identify the gene for isolated microspherophakia in two consanguineous Indian families. Using a whole-genome linkage scan in one family, we identified a likely locus for microspherophakia (MSP1) on chromosome 14q24.1-q32.12 between markers D14S588 and D14S1050 in a physical distance of 22.76Mb. The maximum multi-point lod score was 2.91 between markers D14S1020 and D14S606. The MSP1 candidate region harbors 110 reference genes. DNA sequence analysis of one of the genes, LTBP2, detected a homozygous duplication (insertion) mutation, c.5446dupC, in the last exon (exon 36) in affected family members. This homozygous mutation is predicted to elongate the LTBP2 protein by replacing the last 6 amino acids with 27 novel amino acids. Microspherophakia in the second family did not map to this locus, suggesting genetic heterogeneity. The present study suggests a role for LTBP2 in the structural stability of ciliary zonules, and growth and development of lens.

A fibrous membrane suspends the multifocal lens in the eyes of lampreys and African lungfishes

The sharpness and thus information content of the retinal image in the eye depends on the optical quality of the lens and its accurate positioning in the eye. Multifocal lenses create well-focused color images and are present in the eyes of all vertebrate groups studied to date (mammals, reptiles including birds, amphibians, and ray-finned fishes) and occur even in lampreys, i.e., the most basal vertebrates with well-developed eyes. Results from photoretinoscopy obtained in this study indicate that the Dipnoi (lungfishes), i.e., the closest piscine relatives to tetrapods, also possess multifocal lenses. Suspension of the lens is complex and sophisticated in teleosts (bony fishes) and tetrapods. We studied lens suspension using light and electron microscopy in one species of lamprey (Lampetra fluviatilis) and two species of African lungfish (Protopterus aethiopicus aethiopicus and Protopterus annectens annectens). A fibrous and highly transparent membrane suspends the lens in both of these phylogenetically widely separated vertebrate groups. The membrane attaches to the lens approximately along the lens equator, from where it extends to the ora retinalis. The material forming the membrane is similar in ultrastructure to microfibrils in the zonule fibers of tetrapods. The membrane, possibly in conjunction with the cornea, iris, and vitreous body, seems suitable for keeping the lens in the correct position for well-focused imaging. Suspension of the lens by a multitude of zonule fibers in tetrapods may have evolved from a suspensory membrane similar to that in extant African lungfishes, a structure that seems to have appeared first in the lamprey-like ancestors of allextant vertebrates.

Diagnostic significance of tight junction associated proteins in meningeal neoplasms

Objective To investigate the expression pattern and value of differential diagnosis of tight junction associated proteins in meningioma, hemangiopericytoma (HPC) and solitary fibrous tumor (SFT). Methods Clinicopathologic and immunohistochemical features of 77 meningiomas, in which including 57 WHO Ⅰmeningiomas composed of 10 fibrous (fibroblastic), 10 meningiothelial, 10 transitional (mixed), 10 angiomatous, 10 psammomatous, and 7 microcystic meningiomas, 10 WHO Ⅱ and 10 WHO Ⅲ meningiomas and 10 HPC and 3 SFT were analyzed. Results Eighty ⁃ five point seventy ⁃ one percent positive epithelial membrance antigen (EMA) immunostain was found in meningiomas (66/77), in which the positive rate of WHO Ⅰ meningiomas was 87.72% (50/57), meningiothelial type was the highest (100%), angiomatous and transitional type were the lowest (80%, for all), WHO Ⅱ and WHO Ⅲ meningioma was 90% (9/10) and 70% (7/10), respectively, and negative for HPC and SFT. The immunoreactivity of CD34, Bcl⁃2, S⁃100 protein (S⁃100) was expressed in some different degree in the above meningeal neoplasms. Except for one HPC showed a special performance of negative⁃stained in tumor cells at the central region around the blood vessel and positive⁃stained in tumor cells at the surrounding region, the rest was positive staining for vimentin (Vim). Except for one WHO Ⅲ meningioma was negative, the others were positive for CD99 staining. Ki⁃67 proliferation index increased with the grade in meningiomas and lower in SFT, but higher in HPC. Immunoreactivities of the tight junction associated protein Claudin⁃1, ⁃3, ⁃4 and ⁃7 were 44.16%-57.14% in meningiomas, in which WHO Ⅰmeningiothelial type was the highest, however, negative for HPC and SFT. Zonula occludens⁃1 (ZO⁃1) was highly positive⁃stained in meningiomas, HPC and SFT. Conclusion Positive ⁃ immunostaining of tight junction associated protein Claudin ⁃ 1, ⁃ 3, ⁃ 4 and ⁃ 7 in meningiomas and negative in HPC and SFT suggest that these claudin proteins could be serve as specific markers in the diagnosis and differential diagnosis of meningeal neoplasms. DOI：10.3969/j.issn.1672-6731.2010.02.021

Impact of iris pigment and pupil size in ultraviolet radiation cataract in rat

To investigate the effect of iris pigment and pupil size in ultraviolet radiation (UVR)-induced cataract. Brown-Norway rats (pigmented) and Fischer-344 rats (non-pigmented) were unilaterally exposed in vivo to 5 kJ/m(2) UVR. Each strain was split into two groups, each receiving either mydriatic (tropicamide) or miotic (pilocarpine) eye-drops. One week after exposure, the degree of ocular inflammation and damage in the anterior segment was determined. The lenses were extracted, photographed and the degree of forward light scattering (cataract) was quantified. The cataract types differed between the two strains. All Fischer rats developed macroscopically identifiable UVR cataract while only 41% of Brown-Norway rats did so. All groups except the miotic Brown-Norway developed significant light scattering. The Fischer rats developed 3-4-fold more lens light scattering than the Brown-Norway rats. The miotic Fischer group exhibited significantly more light scattering than the mydriatic Fischer group. There was no significant difference in light scattering between the two Brown-Norway groups. There was a correlation between ocular inflammation and degree of light scattering, with Brown-Norway rats exhibiting less inflammation and lens light scattering. Pigmented rats develop less UVR cataract and less ocular inflammation than non-pigmented rats. Pupil size plays a smaller role in UVR cataract development in pigmented rats than in non-pigmented. The role of UVR-induced ocular inflammation in cataract development is still ambiguous.

Confirmation of ADAMTSL4 mutations for autosomal recessive isolated bilateral Ectopia Lentis

Ectopia lentis (EL) is a zonular disease where alteration of the zonular fibers leads progressively to lens dislocation. It is most often associated with systemic diseases such as Marfan syndrome, Weill-Marchesani syndrome or homocystinuria. Isolated non syndromic ectopia lentis (IEL) is reported in families with autosomal inheritance, with dominant forms being more common than recessive. LTBP2 truncating mutations have been described as a cause of autosomal recessive ectopia lentis as a primary or secondary feature in patients showing ocular (eg, glaucoma) or extraocular manifestations (eg, Marfanoid habitus). Recently, ADAMTSL4 has been shown to be responsible for isolated autosomal recessive ectopia lentis in an inbred family. Herein we show a consanguineous family that carries a novel homozygous splice mutation IVS4-1G>A/IVS4-1G>A in ADAMTSL4 responsible for isolated autosomal recessive EL, thus confirming the involvement of this gene in this condition and underlining the major role of ADAMTS proteases in zonular fibers homeostasis.

Anterior-segment imaging for assessment of glaucoma

This article summarizes the physics, technology and clinical application of ultrasound biomicroscopy (UBM) and optical coherence tomography (OCT) for assessment of the anterior segment in glaucoma. UBM systems use frequencies ranging from approximately 35 to 80 MHz, as compared with typical 10-MHz systems used for general-purpose ophthalmic imaging. OCT systems use low-coherence, near-infrared light to provide detailed images of anterior segment structures at resolutions exceeding that of UBM. Both technologies allow visualization of the iridocorneal angle and, thus, can contribute to the diagnosis and management of glaucoma. OCT systems are advantageous, being noncontact proceedures and providing finer resolution than UBM, but UBM systems are superior for the visualization of retroiridal structures, including the ciliary body, posterior chamber and zonules, which can provide crucial diagnostic information for the assessment of glaucoma.

Role of ultrasound and biomicroscopy in evaluation of anterior segment anatomy in congenital and developmental cataract cases

To investigate the role of ultrasound biomicroscopy (UBM) in the evaluation of anterior segment anatomy in cases of congenital and developmental cataract. Alexandria Main University Hospital, Ophthalmology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt. In this cross-sectional nonrandomized unmasked study, ultrasound biomicroscopy (UBM) was used to evaluate the anterior segment anatomy of 32 eyes of 21 children with congenital and developmental cataract. The parents were questioned for details of the children's history. An initial office examination was done to detect visual function, pupil color, lens morphology, corneal clarity, and presence of gross anterior segment anomaly. If the fundus was visible, it was examined in cooperative children after mydriasis. Under general anesthesia, each child was examined by UBM. The parameters detected by UBM included anterior chamber depth, lens thickness, zonular fiber length, ciliary process length, anterior chamber angle, and lens morphology. A-scan biometry was also performed to detect anterior chamber biometric characteristics. Ultrasound biomicroscopy is a valuable tool for evaluating childhood cataracts and associated ocular anomalies as well as anterior segment biometric characteristics.

Observation on retinal ultrastructures of the human fetus at the gestational age of 9 months

Objective To observe the retinal ultrastructure of the human fetal at the age of 9 months, and to investigate the clinical significance of the observation on retinal neuron development during the prenatal period. Methods Four human fetal eyes of 2 fetus at the gestational age of 9 months, including 1 at 35 and the other at 36 weeks, were obtained after termination of pregnancy due to trauma. The gestational ages of the fetus were estimated according to both last menstrual period (LMP) of the pregnant women and the weight/crown-heel length of fetus at the delivery. From each eyeball, 4 pieces of retina at the posterior pole were obtained and observed after specimens handling according to the procedure of routine electron microscopy. Eight pieces of retina which were randomly selected from total of 16 pieces of retina in each group were processed and observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Permissions from pregnant women and family members were guaranteed. Results At the gestational age of 9 months, the outer nuclear layer of fetal retina contained 5 to 6 layers of photoreceptor cells (PRC), and spherical-like membrane structures were found outside of the outer limiting membrane (OLM). Among many tight-aligned inner segments of PRCs there was zonula adherens of OLM, mitochondrias at inner side of OLM, and cilium at outer side of OLM. Outer segment of PRCs were short and contained a few irregularly arranged disc membrane. Some PRC had a multi-shaped nucleus in which equal amount of euehromatin and heteroehromatin. There were only few and thin axon branches from photoreceptor cells, and very few axons contacted with inner nuclear layer (INL) and no typical synapse was found. The INL contained 4 to 5 layers of cell bodies, in which many cellular nuclear had uneven density of euchromatin and heterochromatin; some were lobulated nucleus with clear karyotheca. In inner plexiform layer (IPL), the nerve cells had small branches, and only little connection among the synapses and few synapse structures were found. Although not many retinal ganglion cells (RGC) existed, RGC had both intact cell membrane and some rough endoplasmic reticulum (RER). The karyotheca of RGC had double-layers structures, and the nucleus was mainly consisted of euchromatin. Internal limiting membrane (ILM) had double-layer membrane structures, and the well-arranged nerve fiber layer was located at the outer side of ILM, with some micropores on the surface. Conclusions At the gestational age of 9 months, all layers of the human retinal has been formed, but some cell structure and cell connections are not yet mature, suggesting that at this time of period, human retina is still at an important stage of developing and remodeling. Key words: Retina/growth & development; Retina/ultrastructure; Microscopy; electron; transmission

Biomimetic variable-focus lens system controlled by winding-type SMA actuator

Inspired by the biomechanics of the human eye, which includes a crystalline lens, ciliary muscles, and zonular fibers, the proposed variablefocus lens system consists of a PDMS lens, winding-type SMA actuator, and load arms. The PDMS lens is encircled and stretched by the load arms joined to an outer ring that is rotated by the winding-type SMA actuator, thereby changing the focal length of the lens. In contrast to other single tunable-focus lenses, the proposed system uses a gel-type PDMS lens, which is insensitive to gravity and external vibration, and can be made into a biconvex or aspheric shape. The design of the proposed system is described in detail, and experimental results demonstrate the validity of the proposed system.

Beitrag zur vergleichenden Ophthalmo-Morphologie: Das Bachforellenauge

The aim of this study was to assess similarities and differences between the trout eye and the human eye. Gross and microscopic examinations of the formalin-fixed eyes of each five trout and human eyes (donor eyes not suitable for keratoplastic) were carried out. Compared to the human eye, the trout showed a flattening of the anterior-posterior axis, and cartilage-stabilized sclera. The peripheral cornea was much thicker than the central, had a multilayered thick epithelium, a distinct Bowman layer, and an implied Descement membrane. A ring-shaped ligament filled up the angle of the anterior chamber and linked the iris to the cornea. The lens showed a spherical aspect with a thick capsule and missing zonular fibres, however, a suspensory ligament of a superior part of the lens was present. Ventrally, at the end of the falciform process, a small, pigmented structure was in contact with the lens. The retina was similarly differentiated, but the choroid showed special structures like choroidal gland, falciform process and the argentea compared to the human eye. Great variations between the ocular anatomy of the trout and the human exist. However, the retina of the trout is fully differentiated and remarkably similar to that of human eyes.

Effect of Anterior Zonule Transection on the Change in Lens Diameter and Power in Cynomolgus Monkeys during Simulated Accommodation

To quantify the role of anterior zonular tension on the optomechanical lens response during simulation of accommodation in primates. Postmortem cynomolgus monkey eyes (n = 14; age range, 3.0-11.5 years) were dissected leaving intact the lens, zonules, ciliary body, hyaloid membrane, anterior vitreous, and a scleral rim. The lens was mounted in a lens-stretching system and stretched radially in step-wise fashion. The load, and the lens diameter and power were measured at each step and the diameter- and power-load relationships were quantified. The anterior zonular fibers were then transected, and the experiment was repeated. The equatorial lens diameter and lens optical power before and after zonular transection were compared. Stretching increased the lens diameter by 0.25 +/- 0.09 mm (median +/- interquartile range) before and 0.25 +/- 0.19 mm after zonular transection. Stretching decreased the lens power by 13.0 +/- 6.5 D before and 10.6 +/- 8.0 D after zonular transection. The load required to change the diameter of the lens by 1 mm decreased from 18.8 +/- 10.7 g before to 15.0 +/- 7.8 g after zonular transection. The absolute change in power per gram of loading decreased from 2.5 +/- 1.1 before to 2.0 +/- 1.2 D after zonular transection. The cynomolgus monkey lens retains a significant fraction of its accommodative ability after transection of the anterior zonules in simulated accommodation experiments.

A Homozygous Mutation in ADAMTSL4 Causes Autosomal-Recessive Isolated Ectopia Lentis

Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T-->G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay. We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers.

Diagnosis and management of traumatic cyclodialysis cleft

A 48-year-old man presented with hyphema, iridocyclitis, iridophacodonesis, and maculopathy after a contusive trauma. Ultrasound biomicroscopy identified a 90-degree cyclodialysis cleft with severe damage of the zonular fibers. Echographic B-scan examination revealed intravitreal hemorrhage and a 360-degree choroidal detachment. One month later, phacoemulsification was performed and a single-piece poly(methyl methacrylate) intraocular lens was inserted into the ciliary sulcus, with the haptic rotated toward the cyclodialysis cleft area. Postoperatively, the visual acuity improved and the intraocular pressure returned to normal. Ultrasound biomicroscopy showed closure of the cleft by reattachment of the ciliary body to the scleral spur. Optical coherence tomography revealed complete resolution of the macular and choroidal folds. Ultrasound biomicroscopy is a useful method for appropriate management of traumatic cyclodialysis cleft. In cases of small cyclodialysis clefts, with the surgical method we describe, the lens haptics apply directional force toward the sclera, fostering adherence of the ciliary body fibers.

Use of High-Resolution Microscopy Coil MRI for Depicting Orbital Anatomy

Objective: High-resolution MRI (HR-MRI) is a powerful non-invasive tool that provides images of higher spatial resolution and enables visualization of tissues previously unidentified with conventional techniques. The utilization of HR-MRI in the eye and orbit is essential due to the minute structure with great tissue diversity. The purpose of this study is to investigate the use of a novel surface coil and to explore the potential of this approach to depict normal anatomy. Methods: MR images were acquired using a commonly available 1.5T scanner. Ten normal volunteers were imaged using a surface microscopy coil of 47 mm inner diameter. T1- and T2-weighting and fat suppression techniques were used. HR-MR images were compared with conventional head coil MR images. Results: Overall exquisite anatomic detail of the eye and orbit is revealed. The in-plane resolution was 312 μ m and the displayed pixel dimension 156 μ m. Previously unobserved distinction of the globe layers and muscle groups is possible. To our best knowledge, our group was the first to demonstrate Tenon's capsule and the tarsal plate with MRI. The ciliary body and zonules of the lens are clearly visible. The superior muscle group is illustrated, being apparently divided into its components, namely the superior rectus and the levator palpebrae superioris muscles. Finally, the retrobulbar fat and parts of its connective tissue are depicted. Conclusion: High-resolution microscopy coil MRI improves the image resolution dramatically and enables a detailed tissue depiction of the orbital and globe structures. Therefore, its introduction in routine clinical use can facilitate diagnosis and pre-operative planning in challenging cases.